Clay-based Hemostatic Agents and Devices for the Delivery Thereof

1/25 "DEVICE CAPABLE OF PROVIDING HEMOSTATIC EFFECT

IN HEMORRHAGE INJURY”

DESCRIPTIVE REPORT

TECHNICAL FIELD

1. The present invention relates generally to agents and devices for promoting hemostasis, and more particularly to clay-based hemostatic agents and devices incorporating such agents for delivery thereof to bleeding wounds.

BACKGROUND OF THE INVENTION

two. 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, solubilized electrolytes and proteins. Proteins are suspended in the liquid phase and can be separated from 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, fibrinogen reacts with water and thrombin (an enzyme) to form fibrin, which is insoluble in blood and polymerizes to form clots.

3. In a wide variety of circumstances, animals, including humans, can be injured. Bleeding is often associated with these injuries. In some circumstances, the wound and bleeding are minor and normal blood clotting goes beyond the application of simple first aid and is all that is required. Unfortunately, however, in other circumstances, substantial bleeding can occur. These situations normally require specialized equipment and materials, as well as

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2/25 also trained personnel to administer appropriate help. If this help is not readily available, excessive blood loss can result. When hemorrhage is severe, sometimes the immediate availability of equipment and trained personnel is still insufficient to stop the flow of blood in a timely manner.

4. In addition, severe injuries can often be inflicted in remote areas or in situations, such as a battlefield, where adequate medical help is not immediately available. In these instances, it is important to stop bleeding, even in less severe injuries, for a time sufficient to allow the injured person or animal to receive medical attention.

5. In an effort to solve the problems described above, materials have been developed to control excessive bleeding in situations where conventional help is unavailable or less than optimally effective. While these materials have been shown to have some success, they are sometimes not effective enough for traumatic injuries and tend to be expensive. In addition, these materials are sometimes ineffective in some situations and can be difficult to apply as well as remove from a wound.

6. Additionally or alternatively, previously developed materials may produce undesirable side effects. For example, one type of prior art blood clotting material is generally a powder or fine particulate where the surface area of ​​the material often produces an exothermic reaction upon application of the material to the blood. Too often, excess material is unnecessarily poured over a wound, which can exacerbate exothermic effects. Depending on the specific attributes of the material, the resulting exothermy can cause discomfort or even burn the patient. Although some prior art patents specifically cite the resulting exotherm as a desirable feature that can provide

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3/25 clotting to the wound that are similar to cauterization, there is a possibility that tissue at and around the wound site may be undesirably impacted.

7. In addition, to remove these materials from wounds, irrigation of the wound is often required. If an amount of material is administered that causes discomfort or burns, the wound may require immediate washing. In instances where an injured person or animal has not yet been transported to a facility capable of providing the necessary irrigation, undesirable effects or over-treatment of the wound may result.

8. Bleeding can also be a problem during surgical procedures. In addition to suturing or stapling an incision or internal bleeding area, bleeding is often controlled using a sponge or other material used to exert pressure against the bleeding site and/or absorb blood. However, when bleeding becomes excessive, these measures may not be enough to stop the flow of blood. In addition, any highly exothermic bleed control material can damage the tissue surrounding the bleed site and may not be configured for easy removal after use.

9. Based on the foregoing, it is a general objective of the present invention to provide a hemostatic agent that overcomes or improves upon the drawbacks associated with the prior art. It is also a general objective of the present invention to provide devices capable of delivering such hemostatic agents.

SUMMARY OF THE INVENTION

10. In one aspect, the present invention resides in a device for promoting clotting, thereby controlling bleeding. The device comprises a particulate clay material and a receptacle for containing the clay material. Fur

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At least a portion of the receptacle is defined by a mesh having openings therein such that, when the device is applied to a bleeding site, clay particles come into contact with blood through the opening.

11. In another aspect, the present invention resides in another device capable of providing a hemostatic effect on a bleeding wound to control blood flow from the wound. The device comprises a gauze substrate and a clay material disposed on the gauze substrate. After application of the device to the bleeding wound, at least a part of the clay material comes into contact with the blood in order to bring about the hemostatic effect.

12. In another aspect, the present invention resides in a gauze bandage that can be applied to a bleeding wound to promote clotting, thereby controlling bleeding. The gauze bandage comprises a substrate, a mesh mounted on the substrate and particles of a clay material retained in the mesh. The mesh is defined by a plurality of members arranged to define openings that allow blood to flow into the mesh and clay material, thereby producing a clotting effect.

13. In another aspect, the present invention resides in a hemostatic sponge that can be applied to a bleeding wound to clot blood and control bleeding. Such a sponge comprises a substrate, a hemostatic material disposed on a first surface of the substrate and a release agent disposed on a second surface of the substrate. The release agent is disposed on the wound contact surface of the substrate so as to inhibit the sponge from adhering to the wound tissue after clot formation. When treating a bleeding wound, the application of the hemostatic sponge causes at least a part of the hemostatic material to come into contact with the

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5/25 blood through the releasing agent and through the substrate.

14. In yet another aspect, the present invention resides in other forms of hemostatic sponges. In such forms, the hemostatic sponge may comprise a film and a hemostatic material incorporated into the film; a substrate, a hemostatic material disposed on the substrate and a film disposed on the hemostatic material; or a hemostatic material sandwiched between two substrates.

15. In yet another aspect, the present invention resides in a hemostatic device for promoting clotting, thereby controlling bleeding. The device has a gauze substrate, a clay material disposed on the gauze substrate and also a polyol such as glycerol or the like disposed on the gauze substrate to bind the clay material. When the device is used to treat a bleeding wound, at least some of the clay material comes into contact with blood emanating from the wound to cause clotting.

16. In yet another aspect, the present invention resides in a gauze bandage that can be applied to a bleeding wound to promote clotting, thereby controlling bleeding. The gauze bandage has a flexible substrate and a gauze substrate mounted on top of it. The gauze substrate includes a clay material and a polyol. When the gauze bandage is used to treat a bleeding wound, applying the gauze bandage causes at least some of the clay material to come into contact with the blood emanating from the wound.

17. In yet another aspect, the present invention resides in hemostatic sponges. One type of sponge has a gauze substrate and a dispersion of hemostatic material and a polyol on a first surface of the substrate. When this sponge is used to treat a bleeding wound, application of the sponge causes at least some of the hemostatic material to come into contact with blood. Another type of sponge has first and second

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6/25 substrates. A hemostatic material is dispersed in the polyol and applied to the first substrate and the second substrate is placed over the hemostatic material dispersed in the polyol. When this sponge is used to treat a bleeding wound, application of the sponge causes at least some of the hemostatic material to come into contact with blood through at least one of the substrates.

18. An advantage of the present invention is that, unlike other materials, such as, for example, zeolites, the clay component does not produce any exothermic reaction with blood. Eliminating heat generation at a wound site is useful in minimizing additional discomfort and/or harm to a patient and may be especially useful in treating certain patients such as pediatric or geriatric patients or when the wound being treated is in an area particularly sensitive or delicate.

19. Another advantage is that the clay can be finely divided and deposited on a multitude of surfaces, thus facilitating its use as a component in a variety of blood control devices. In particular, the clay may be used in particulate form (e.g. retained in a mesh or film) or may be used in powder form (e.g. deposited on a fibrous substrate to form a gauze or sponge). In either embodiment, the clay's effectiveness in promoting hemostasis at a wound site is improved over similar agents that can be used in only one form (e.g., as particles of a particular size) to limit undesirable side effects such as exothermic reactions. excessive.

20. Yet another advantage of the present invention is that the devices and agents of the present invention are easily applied to open wounds. Particularly, when the hemostatic agent is retained in a mesh or similar device or when it is incorporated into a woven structure to form a gauze, the device can be readily removed from a sterile package and

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7/25 placed or held directly on points from which blood emanates in order to cause clotting.

21. An advantage of using a polyol such as glycerol together with clay (or any other hemostatic agent) is that dust often associated with clay (or other hemostatic agent) is suppressed. Because of its low volatility, glycerol, for example, does not readily evaporate. As it does not readily evaporate, the generation of clay dust when clay is dispersed in glycerol is mitigated. Mitigating or suppressing dust means more hemostatic material is available for blood clotting purposes. Another advantage of using a polyol in conjunction with clay (or other hemostatic agents) is that the unwanted adhesion of the sponge to the wound is reduced. Consequently, the sponge or other device can be easily removed from a wound without breaking a newly formed blood clot.

BRIEF DESCRIPTION OF THE DRAWINGS

22. Figure 1 is a schematic representation of a mesh structure of a blood clotting device of the present invention.

23. Figure 2 is a side view of the blood clotting device of Figure 1 illustrating the retention of clay particles in the mesh structure.

24. Figure 3 is a perspective view of a blood clotting device that incorporates a clay material in a gauze.

25. Figure 4 is a perspective view of a blood clotting device that incorporates a clay material in a cloth.

26. Figure 5A is a perspective view of a gauze bandage incorporating clay particles in a mesh container for application to a bleeding wound.

27. Figure 5B is a perspective view of a gauze bandage

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8/25 which incorporates the hemostatic material and a polyol in a gauze substrate for application to a bleeding wound.

28. Figure 6 is a schematic representation of a sponge having hemostatic capabilities.

29. Figure 7 is a schematic representation of another embodiment of a sponge having hemostatic capabilities.

30. Figure 8 is a schematic representation of another embodiment of a sponge having hemostatic capabilities.

31. Figure 9 is a schematic representation of another embodiment of a sponge having hemostatic capabilities.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES

32. Disclosed herein are hemostatic devices and hemostatic agents that are applicable to bleeding wounds to promote hemostasis. Hemostatic agents generally include clay or other silica-based materials which, when brought into contact with a bleeding wound, can minimize or stop the flow of blood by absorbing at least parts of the liquid phases of the blood, thereby facilitating the clotting. The present invention is not limited to clay, however, as other materials such as bioactive glasses, biological hemostats, molecular sieve materials, diatomaceous earth, combinations of the aforementioned and the like are within the scope of the present invention and can be used in together with clay or separately as a hemostatic agent.

33. As used herein, the term "clay" refers to a crystalline form of hydrated aluminum silicate. Clay crystals are irregularly formed and insoluble in water. Combining some types of clay with water can produce a dough having some degree of plasticity. Depending on the type of clay, its combination with water can produce a colloidal gel having properties

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9/25 thixotropic.

34. In a preferred embodiment of the present invention, the clay material is kaolin, which includes the mineral "kaolinite". Although the term "kaolin" is used hereinafter to describe the present invention, it should be understood that kaolinite may also be used in conjunction with or in place of kaolin. The present invention is also not limited as it relates to kaolin or kaolinite, however, like other materials, they are within the scope of the present invention. Such materials include, but are not limited to, attapulgite, bentonite, combinations of the foregoing, combinations of the foregoing with kaolin and/or diatomaceous earth, and the like.

35. As used herein, the term "kaolin" refers to a soft, earthy aluminosilicate clay (and more specifically, a dioctahedral phyllosilicate clay) having the chemical formula Al2Si2O5(OH)4. Kaolin is a naturally occurring layered silicate mineral having alternating tetrahedral sheets and octahedral alumina octahedral sheets bonded via the oxygen atoms of hydroxy groups. Kaolin comprises about 50% alumina, about 50% silica and traces of impurities.

36. Most 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, Florida. Edgar's plastic kaolin has desirable plasticity characteristics, is capable of being melted and, when mixed with water, produces a thixotropic paste.

37. The kaolin material of the present invention may be blended or otherwise used in conjunction with other materials to provide additional improved clotting functions and/or effectiveness. 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.

38. Various materials can be mixed, combined or

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10/25 incorporated into the kaolin to maintain an antiseptic environment at the wound site or to provide functions that are supplementary to the clotting functions of the clay. Exemplary materials that may be used include, but are not limited to, pharmaceutically active compositions such as antibiotics, antifungal agents, antimicrobial agents, anti-inflammatory agents, analgesics, antihistamines (e.g., cimetidine, chlorpheniramine maleate, diphenhydramine chloride and promethazine chloride ), compounds containing silver or copper ions, combinations of the aforementioned and the like. Other materials that can be incorporated to provide additional hemostatic functions include ascorbic acid, tranexamic acid, rutin and thrombin. Botanical agents may also be added having desirable effects at the wound site.

39. For use in the present invention, the kaolin (or other clay or diatomaceous earth material) is preferably in particulate form. As used herein, "particles" include beads, pellets, granules, bars or any other surface morphology or combination of surface morphologies. Regardless of surface morphology, the particles are from about 0.2 mm (millimeters) to about 10 mm, preferably from about 0.5 mm to about 5 mm and more preferably about 1 mm to more or less than 2 mm in effective diameter. The present invention is not limited in this regard, however, and other particle sizes (e.g., less than about 0.2 mm) are also within the scope of the present invention. The particle size of kaolin (or other clay material or diatomaceous earth) can be so small that it is considered dust. If the particle size is considered to be dust, the dust may be impalpable (i.e., undetectable to the touch).

40. Clay particles can be produced by any of a number of methods. Such methods include mixing, extrusion, spheronization and the like. Equipment that can be used for mixing, extrusion or spheronization of clay is available at

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11/25 from Caleva Process Solutions Ltd. in Dorset, UK. Other methods include the use of fluid bed equipment or pelleting. Fluid beds for producing clay particles are available from Glatt Air Technologies in Ramsey, New Jersey. Disc pelletizers for the production of clay particles are available from Feeco International, Inc., in Green Bay, Wisconsin. 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 particulate clay are within the scope of the present invention.

41. The EPK used in the present invention is particulate, dried and heated to about 600 degrees C. In order to get a properly homogeneous mixture of EPK to form the particles, a relatively high torque is applied to a mass of EPK using equipment. appropriate mixing. Prior to shearing, the water content of the clay is measured and adjusted to be plus or minus 20% by weight to give a sufficiently workable mixture for subsequent extrusion and handling.

42. During heating of the EPK to approximately 600 degrees C, the material is vitrified. The vitrification is carried out 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 crystal structure is broken down to an amorphous composition. The amorphous nature of EPK allows it to maintain its structural integrity when subsequently wetted. As a result, EPK retains its structural integrity when wet during use, for example when applied to blood. The present invention is not limited to the use of vitrified clays, however, as clay material that has not been vitrified is still within the scope of the present invention. In particular, unglazed clay can still be applied to a wound of

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12/25 bleeding to provide hemostasis.

43. Clay's cellular clotting mechanism is believed to activate certain contact factors when applied to blood. More specifically, kaolin (particularly, EPK) is believed to initiate mechanisms by which water in the blood is absorbed to facilitate clotting functions.

44. Referring now to Figure 1, an embodiment of a hemostatic device in which kaolin is incorporated in particulate form is shown. The device is a permeable bag that allows liquid to enter to contact the kaolin particles trapped therein. The hermetically sealed package (not shown) provides a sterile environment to store the hemostatic device until it can be used. The device, which is generally shown at 10 and is hereinafter called "bag 10", comprises a screen or mesh 12 and the particulate kaolin 14 retained therein by the screen or mesh. Mesh 12 is closed on all sides and defines openings which are capable of retaining particulate kaolin 14 therein, while allowing liquid to flow therethrough. As illustrated, the mesh 12 is shown to be flat and, by way of example, only a few particles of particulate kaolin 14 are shown. The particulate kaolin 14 can be mixed with particles of other types of clay, diatomaceous earth and the like in a to form a homogeneous mixture.

45. The mesh 12 is defined by interconnecting filaments, filaments or strips of material. The filaments, or strips, may be interconnected in any one or a combination of ways, including, but not limited to, being gauze-woven, interwoven, massively formed, and the like. Preferably, the interconnection is such that the mesh can flex while substantially maintaining the dimensions of the opening so defined. The material from which the filaments or strips are made may be a polymer (e.g. synthetic fiber, polyethylene, polypropylene, polyester or the like),

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13/25 metal, fiberglass or an organic substance (eg cotton, wool, silk or the like).

46. Referring now to Figure 2, the openings defined by mesh 12 are sized to retain particulate kaolin 14 but allow blood to flow therethrough. As the mesh 12 can be pulled tightly around the particulate kaolin 14, the particles can extend through the opening for a distance d. If the particles extend through the openings, they will directly contact the tissue against which the pouch 10 is applied. In this way, the blood emanating from the tissue immediately contacts the particulate kaolin 14 and the aqueous phase thereof is mixed into the kaolin, thus facilitating blood clotting. However, it is not a requirement of the present invention that the particles protrude through the mesh.

47. To apply the pouch 10 to a bleeding wound, the pouch is removed from the package and placed on the bleeding wound. The particulate kaolin 14 in the mesh 12 contacts the wound tissue and/or the blood emanating from the wound and at least a part of the liquid blood phase is adsorbed by the clay material, thus promoting clotting. The flexibility of mesh 12 allows the mesh to conform to the shape of the bleeding wound and retain that shape after application.

48. Referring now to Figure 3, another embodiment of a hemostatic device of the present invention is a kaolin gauze, which is generally shown at 20 and is hereinafter called "gauze 20". The kaolin is coated onto a gauze substrate using any suitable method to yield the gauze 20. An exemplary method of coating kaolin onto the gauze substrate is to submerge the substrate in a kaolin/water slurry. The kaolin material used for the slurry is preferably finely ground kaolin powder, although the present invention is not limited in this regard, as kaolin particles, flakes, chips, beads, bars, granules or the like

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14/25 may be alternatively or additionally used. The gauze substrate can be any suitable fibrous material, woven or non-woven, including, but not limited to, cotton, silk, wool, plastic, cellulose, rayon, polyester, combinations of the aforementioned and the like. The present invention is not limited to woven or non-woven fibrous materials such as gauze substrates, however, as fleters and the like are also within the scope of the present invention.

49. The gauze 20 of the present invention is not limited to kaolin, however, as other clays such as attapulgite, bentonite and combinations thereof can be used in place of or in addition to kaolin. In addition, other silica-based materials such as bioactive glasses, diatomaceous earth, combinations of the aforementioned and the like may also be used in addition to or in place of any of the foregoing clay materials.

50. Once the kaolin is dried on the gauze substrate to form the gauze 20, the gauze is flexible enough to allow it to be folded, rolled or otherwise manipulated for packaging.

51. The flexibility of the gauze substrate 20 allows the gauze to take the shape of the bleeding wound and retain the shape of the bleeding wound after application.

52. One way to deposit the kaolin (or other clay) coating onto the gauze substrate includes heating the kaolin/water slurry. Preferably, the slurry is heated to boiling, as higher temperatures tend to facilitate the adhesion of the kaolin to the substrate. The present invention is not limited in this regard, however, as the pulp can be heated to a lower temperature, depending on the desired characteristics of the kaolin coating. Boiling the slurry also provides an effective form of agitation that evenly disperses the kaolin in the liquid phase.

53. The substrate is then submerged in the boiling slurry for a sufficient amount of time to cause the kaolin to settle.

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15/25 on the substrate. Given the rheology of wet kaolin and the material from which the gauze or substrate is made, kaolin may adhere as a film directly to substrate surfaces or it may agglomerate in the interstices of the filaments as well as along the edges. the filaments themselves, thereby becoming trapped in the fiber matrix.

54. Another way of depositing the kaolin coating on the substrate includes applying the kaolin in paste form onto one side of the gauze substrate using a spray technique, a slit matrix technique or a combination thereof. When using either technique, the amount of paste applied to the gauze substrate is limited to avoid or at least minimize saturation of the substrate. Preferably, a colloidal form of the kaolin (or other clay) is used to provide a stable suspension of the material with appropriate viscosity for application using the slit matrix technique.

55. Once sprayed or applied using the slit matrix technique, the coated gauze substrate is then rolled or scraped to further embed the kaolin into the substrate material. The gauze substrate is then dried.

56. In some embodiments, the kaolin may be attached to the gauze substrate using a binder. In embodiments where a binder is used, the binder material is compatible with the biological gauze. Preferred binders include polyols, chitosan and polyvinyl alcohol, all of which have adhesive qualities and are compatible with biological gauze. At least chitosan exhibits hemostatic properties.

57. An exemplary method for producing this device may comprise the steps of unrolling the gauze from a roller, submerging the gauze in a slurry of hemostatic material and water, applying pressure to the gauze by rolling the wet gauze under high pressure to incorporate the hemostatic material into the gauze material, dry the wet, rolled gauze, and remove dust from the gauze (e.g., via scratching with air knives or air nozzles, by using energy

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16/25 electrostatic, forming a vacuum or brushing with brushes in direct contact). Following dust removal from the gauze, the back of the gauze can be rolled back over a roller or can be cut into sheets for individual packaging.

58. One or more variables can be manipulated to optimize the amount and integrity of kaolin retained in the gauze. These variables include, but are not limited to, slurry temperature, immersion time, slurry stirring method, and liquid (slurry) type. Raising the paste temperature, as indicated above, helps retain the kaolin in the gauze. Agitation can be effected by forcing air or other gas through nozzles, stirring, bubbling, boiling or by ultrasonic vibration.

59. The liquid used for the paste can also be something other than water. For example, the liquid may be an aqueous solution of ammonia. Aqueous ammonia has been found to induce swelling in certain fibrous materials, such as the materials typically used to make gauze.

60. In embodiments where a polyol is used in the gauze 20, the polyol may be glycerol (also known as glycerin, glyceritol, glycyl alcohol and by its chemical name propane-1,2,3 triol). Glycerol is a slippery, hygroscopic, water-soluble liquid that is compatible with biological gauze. The kaolin is dispersed in the glycerol to form a dispersion or otherwise mixed with the glycerol and deposited onto the gauze substrate using any suitable method. Suitable methods for depositing the kaolin/glycerol dispersion onto the gauze substrate include, but are not limited to, spraying the dispersion, soaking the gauze substrate in the dispersion, application via slit matrix techniques, physical means such as brushing or rolling. dispersion on gauze and the like.

61. The present invention is not limited to the use of glycerol, however, as other glycerol-based compounds including glycerol alcohols (e.g. propylene glycol), esterified fatty acids

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17/25 based on glycerol (e.g. glyceryl triacetates) and other materials having wetting and similar properties (as well as combinations of the aforementioned) are within the scope of the present invention. Furthermore, other polyols such as sorbitol, xylitol, maltol, combinations of the aforementioned and the like as well as polymeric polyols (e.g. polydextrose) are also within the scope of the present invention.

62. Referring now to Figure 4, another embodiment of a hemostatic device of the present invention is a cloth having hemostatic properties, shown generally at 20 and which is hereinafter referred to as "cloth 30". The cloth 30 is a fabric which may be defined by woven or non-woven filaments or a felt or the like into which a biological hemostatic material is infused or impregnated. Hemostatic materials that can be infused or impregnated into the cloth fabric 30 include, but are not limited to, clays (such as kaolin) in particulate form 32, other silica-based material (such as diatomaceous earth, combinations thereof, or the like) , chitosan, combinations of the aforementioned and the like. In embodiments where such materials are infused or impregnated into a cloth, the material is preferably incorporated into the cloth in a hydrated and subsequently dry state.

63. In gauze or cloth embodiments, the gauze or cloth material may be crossed with a polysaccharide or similar material.

64. Referring now to Figure 5A, another embodiment of the present invention is a gauze bandage, shown at 50, comprising particulate kaolin 14 (or some other clay or diatomaceous earth material) retained in mesh 12 and mounted on a flexible substrate 52 that can be applied to a wound (eg, using a pressure sensitive adhesive to adhere the gauze bandage 50 to the wearer's skin). Mesh 12 is sewn, glued or otherwise mounted on substrate 52 to form gauze bandage 50.

65. Substrate 52 is a plastic or cloth member that is

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18/25 conductive to be trapped in the skin of an injured person or animal on or near a bleeding wound. An adhesive 54 is disposed on a surface of the substrate 52 which attaches to the skin of the injured person or animal. Particularly, if the substrate 52 is a non-breathable plastics material, the substrate may include holes 56 to allow moisture evaporating from the skin surface to dissipate.

66. Referring now to Figure 5B, another embodiment of the gauze bandage is shown at 150. The gauze bandage 150 comprises particulate kaolin (or some other clay or diatomaceous earth material capable of imparting a hemostatic function) dispersed in glycerol and applied to a gauze substrate 112. The gauze substrate 112 is mounted on a flexible substrate 152 that can be applied to a wound (e.g., using a pressure sensitive adhesive 154 disposed over substantially the entire skin contacting surface of the flexible substrate 152 to adhere the gauze bandage 150 to the user's skin). The gauze substrate 112 is baked, glued or otherwise mounted to the substrate 152, which may be a plastic or cloth member which may include holes 156. A release agent (e.g., polyvinyl alcohol, glycerol, carboxymethyl cellulose or the like) can be disposed over the kaolin/glycerol dispersion on the gauze substrate 112.

67. Referring now to Figure 6, another embodiment of the present invention is a sponge, shown at 60, which comprises a substrate 62, particulate kaolin 14 (or some other clay or diatomaceous earth material) disposed on one face of the substrate 62 and a release agent 64 disposed on an opposite face of the substrate. The sponge 60 allows sufficient contact of the particulate kaolin 14 with blood emanating from a wound and through the release agent 64 and substrate 62, while minimizing adhesion of the sponge to the wound gauze. Sponge 60 is also compatible with living tissue.

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19/25

68. Substrate 62 is an absorbent gauze material that defines a matrix. The present invention is not limited thereto, however, as other materials such as rayon/polyester cellulose blends and the like are also within the scope of the present invention. Other materials from which substrate 62 can be made include woven textile material, non-woven textile material, paper (e.g., kraft paper and the like), and cellulose material (e.g., cotton in the form of balls, cotton swabs, and the like). Any material from which the substrate 62 can be made can have an elastic quality. When elastic materials are used as the substrate 62, the sponge 60 becomes both a hemostatic device and a pressure gauze bandage, particularly in embodiments where a surface cohesive agent or mechanical fastener is added to secure the sponge in place over an injury.

69. The hemostatic agent used in sponge 60 is not limited to particulate kaolin 14. Other materials such as attapulgite, bentonite, combinations of the aforementioned or a combination of the foregoing with kaolin may be used. The present invention is also not limited to clays, as other materials such as bioactive glass, biological hemostatics, diatomaceous earth, combinations thereof, combinations thereof with clay are also within the scope of the present invention.

70. The particulate kaolin 14 may be bonded to the substrate 62 via coulombic forces, impregnating or otherwise incorporating the clay or other hemostatic material directly into the substrate material, using a binder, trapping the hemostatic material within the matrix, or the like.

71. When a binder is used to bond the particulate kaolin 14 to the substrate 62, the binder material can provide additional functionality to the sponge 60. Materials from which the binder can be made include, but are not limited to, chitosan, polyvinyl alcohol, guar gum, gelatinized starches, polysaccharides, cellulose,

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20/25 calcium and the like, as well as combinations of the aforementioned.

72. In embodiments where particulate kaolin 14 is directly incorporated into substrate 62, particulate kaolin may be added during substrate fabrication. If the substrate is a non-woven gauze material containing rayon and polyester, then the particulate kaolin 14 can be incorporated into or on top of the rayon and polyester fibers. For example, the particulate kaolin 14 can be in powder form and applied to molten polyester and the polyester fibers can be taken from the molten polyester/hemostatic material. If the substrate is a woven gauze (eg cotton), kaolin 14 in powder form can be incorporated into the cotton yarns during yarn formation.

73. Particulate kaolin 14 may also be dispersed in glycerol and applied to substrate 62 via a spray technique, a slit matrix technique, embedding, brushing, rolling, or the like.

74. The release agent 64 is a material that is disposed on the side of the substrate that contacts the wound 62 to facilitate easy removal of the sponge 60 from the gauze fabric after blood clots have formed. The release agent 64 may be a continuous film or it may be discontinuous over the surface of the substrate. One material that can be used as a release agent is polyvinyl alcohol, which is a biocompatible material that can be formed into a thin film and does not significantly affect the absorbency and liquid permeability of sponge 60. Another material that can be used as a release agent. release 64 is glycerol, which can be applied in addition to particulate kaolin 14 dispersed in glycerol. When applied as release agent 64, glycerol forms a film over the particulate kaolin 14 dispersion in glycerol. Other materials that can be used as release agents include, but are not limited to, carboxymethyl cellulose. In any configuration of sponge 60, release agent 64 can be directly applied to the wound contact surface of substrate 62.

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75. In the alternative, release agent 64 can be applied to the non-wound contacting surface of substrate 62 as a clay slurry and release agent. In this embodiment, the concentration of the polyvinyl alcohol or glycerol is such that at least some of the alcohol component thereof leaks to the wound contact surface of substrate 62, while the clay material remains on or near the surface of the clay. non-injury contact. In any embodiment, polyvinyl alcohol or glycerol not only serves as a release agent, but as an agent that suppresses particulate kaolin dust 14.

76. Other materials that can be used as release agents that are within the scope of the present invention include, but are not limited to, silicone and gelatinized starches. As with polyvinyl alcohol and glycerol, either can be applied in film form.

77. The sponge 60 may further include a component that imparts a radiopaque characteristic to the sponge. In this embodiment, the barium sulfate can be incorporated into a paste that includes the particulate kaolin 14 and applied to the substrate 62.

78. The sponge 60 may further include water or alcohol, thereby allowing the sponge to be used as a wipe.

79. Referring now to Figure 7, another embodiment of a sponge is generally shown at 160. The sponge 160 comprises a film 162 in which the particulate kaolin 14 is dispersed. The physical integrity of the sponge 160 is maintained by the film 162. Preferably, the material from which the film 162 is made is polyvinyl alcohol. In making the sponge 160, the particulate kaolin 14 is dispersed in polyvinyl alcohol, which is then formed into a sheet. Sponge 160 is especially useful when incorporated into a gauze bandage.

80. Referring now to Figure 8, another embodiment of a sponge is generally shown at 260. The sponge 260 comprises a substrate 262, particulate kaolin 14 disposed on the substrate, and a film 266

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22/25 placed on the hemostatic material. Particulate kaolin 14 is a disconnected blood clotting agent (no binder) and is preferably disposed on substrate 262 in strips to facilitate folding of sponge 260. Film 266 is polyvinyl alcohol, glycerol or the like and is applied both to contain particulate kaolin 14 how to minimize dust generation. After application to a bleeding wound, blood from the wound is soaked in substrate 262 and contacts particulate kaolin 14.

81. Referring now to Figure 9, another embodiment of a sponge is generally shown at 360. The sponge 360 ​​comprises particulate kaolin 14 sandwiched between two substrates 362. The substrates 362 may be joined in any appropriate manner, such as heat sealing across selectively absent areas of particulate kaolin 14, using an adhesive or binder in selected areas, applying a material retention film (such as polyvinyl alcohol) over the whole sponge 360 ​​or a combination of any of the above. Particulate kaolin 14 can also be used in conjunction with glycerol, for example being dispersed in glycerol and applied to sponge 360.

82. The sponge 60 (as well as the sponges shown at 160, 260 and 360) can be folded and used in a variety of ways. The sponge 60 can be folded in such a way that the surfaces on which the particulate kaolin 14 is disposed are on the inside surfaces of the folded sponge, to minimize problems of dusting and separation of hemostatic material from the substrate 62. Sponge 60 (and sponges 160, 260 and 360) can also be folded into a pleated shape or configuration to produce several distinct pleats joined along the edges. By configuring the sponge 60 in this way, the compliance and absorbency requirements of different applications can be addressed. The sponge 60 can also be cut or formed into long strips to wrap around the wounds of an injured person or animal or to

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23/25 incorporation in cylinders or swabs. The sponge 60 can also be cut, trimmed, milled or otherwise formed into small pieces for applications such as stuffing into mesh containers.

83. Example 1 - The effect of slurry temperature on the ability of cotton gauze to retain kaolin clay.

84. The temperatures of the kaolin/water pastes were varied to assess the ability of the cotton gauze to retain kaolin clay. Water and EPK slurries were prepared in which kaolin was 40% of the total weight of the slurry. Three sponges were made (one from each piece of gauze) by submerging the cotton gauzes in the pastes of varying temperatures, rolling the wet sponges under pressure and drying. The Table below indicates the parameters for each folder and the results obtained.

<td>Sample</td><td>Paste Temperature (degrees C)</td><td>stirring method</td><td>Departure gauze weight (grams)</td><td>Ulter weight (% by weight) of the gauze (grams)</td><td>% in kaolin</td>

<td> 1</td><td> 22</td><td>Shake for 1 minute</td><td> 3,139</td><td> 5,59</td><td> 44</td>

<td> 2</td><td> 90</td><td>Shake for 1 minute</td><td> 3,064</td><td> 5,868</td><td> 48</td>

<td> 3</td><td> 100</td><td>Boil for 1 minute</td><td> 3,085</td><td> 6,481</td><td> 52</td>

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85. The gauze ulterior weight is the weight of the gauze after rolling and drying.

It was noted that the elevated temperature of the slurry increased the amount of kaolin retained. One theory for this is that the cotton fiber structure of the gauze is loosened and swollen by its immersion in the hot liquid.

86. Example 2 - Application of dry kaolin to dry cotton gauze to form a hemostatic device.

87. Dry kaolin was applied to a dry cotton gauze. The gauze was then rolled. The amount of kaolin retained in the gauze was visible and significantly less than the amount of kaolin retained in the gauze of Sample 3 (Example 1). This sample, however, accelerated the clot time in sheep whole blood by 70% over the unaccelerated blood clot time.

88. Example 3 - Reduction of kaolin powder using glycerol

89. A slurry of 50 grams (g) of water, 20 g of glycerol and 15 g of kaolin powder was prepared and used to fill a gauze sponge (Kendall Curity 2733). The filled gauze sponge was dried. The sponge was held and drained with a pencil onto a clean glass surface. A visual determination indicated that no readily discernible dust was removed from the sponge as a result of draining.

90. A second sponge without glycerol was prepared and dried. The second sponge was held and drained with a pencil onto a clean glass surface. A visual determination indicated that a substantial amount of kaolin powder was removed from the second sponge as a result of the casting.

91. While this invention has been shown and described with respect to detailed embodiments thereof, it will be understood by those of skill in the art that various changes may be made and equivalents may replace elements thereof without departing from the scope of the invention. Furthermore, 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 is not limited to the particular embodiments

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25/25 described in the above detailed description, but that the invention includes all embodiments that fall within the scope of the appended Claims.

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