Clay-based Hemostatic Agents and Devices for the Delivery Thereof

ES 2 394 232 T3

DESCRIPTION

Clay-based hemostatic agents and devices for their delivery

TECHNICAL SCOPE

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

BACKGROUND OF THE INVENTION

Blood is a liquid tissue comprising erythrocytes, leukocytes, blood cells, and thrombocytes dispersed in a liquid phase. Said liquid phase is plasma, which comprises acids, lipids, solubilized electrolytes and proteins. Proteins are suspended in the liquid phase and can be separated from it by various methods such as filtration, centrifugation, electrophoresis, and immunochemical techniques. One of the proteins 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.

In a wide variety of circumstances, animals, including humans, can be injured. Bleeding often occurs from wounds. In some circumstances, the injury and bleeding are minor, and all that is required are normal clotting functions and basic first aid. However, unfortunately in other circumstances considerable bleeding can occur. In these situations, specialized equipment and supplies are often required, as well as personnel with adequate training to administer the necessary care. If such care cannot be administered, significant blood loss can occur. When the bleeding is severe, sometimes the immediate availability of equipment and trained personnel is not enough to contain the loss of blood in time.

Furthermore, serious injuries often occur in remote locations or in situations, such as on a battlefield, where there is no possibility of immediate adequate medical assistance. In these cases, it is important to stop the bleeding, even in the slightest wounds, long enough to allow the injured person or animal to receive medical assistance.

In order to solve the problems described above, materials have been developed to control excessive bleeding in situations where conventional care is not available or cannot provide optimal results. Although these materials have been shown to be relatively useful, they are sometimes not effective enough in traumatic wounds and are often expensive. Also, such materials are sometimes not helpful in certain situations and can be difficult to apply and remove from a wound.

In addition, or alternatively, already developed materials can cause adverse side effects. For example, one type of prior art blood clotting material is typically a powdery substance or fine particles in which the surface area of ​​the material tends to exotherm when it comes into contact with blood. An excess amount of material is often applied to the wound, which can exacerbate the exothermic effects. Depending on the specific qualities of the material, the resulting exotherm may be sufficient to cause discomfort or even burns to the patient. Although some prior art patents specifically describe such a resulting exotherm as an intended feature that can provide coagulant effects similar to cauterization, there is a possibility that tissue in the wound area and surrounding part will suffer adverse effects.

In addition, to remove such materials from the wound, it is often necessary to irrigate the wound. If an amount of material is administered that causes discomfort or burns, the wound may need immediate water flushing. In cases where the injured person or animal has not yet been transported to a facility capable of providing such necessary irrigation, unwanted effects or over-treatment of the wound may arise.

Bleeding can also be a problem during surgery. In addition to suturing or stapling an incision or area of ​​internal bleeding, bleeding is usually controlled by a sponge or other materials used to exert pressure against the area of ​​bleeding and / or absorb blood. However, when bleeding becomes excessive, these measures may not be enough to stop it. In addition, any bleeding control material with highly exothermic properties may damage the surrounding tissue in the bleeding site and may not have been configured for easy removal after use.

WO 2006/088912 discloses a device for stimulating hemostasis comprising clay minerals. WO 2005/030279 discloses absorbent materials with nanocomposites. The

ES 2 394 232 T3 document EP 1810697 discloses a kit for stimulating blood clotting comprising a zeolite.

According to all the aforementioned, the present invention has the general objective of providing a hemostatic agent that overcomes or improves the drawbacks associated with the prior state of the art. Another objective of the present invention is to provide devices that can apply said hemostatic agents.

SUMMARY OF THE INVENTION

According to one aspect, the present invention relates to a device that stimulates blood clotting, and therefore controls bleeding.

The present invention relates to a hemostatic device capable of providing a hemostatic effect on a bleeding wound to control blood loss from said wound. Said device comprises a gauze substrate, a clay material arranged on said gauze substrate and a polyol also arranged on said substrate to bond the clay material. The polyol is selected from a group comprising glycerol, propylene glycol, triacetin, sorbitol, xylitol, maltol, polydextrose, and combinations thereof. When the device is applied to the bleeding wound, at least a part of the clay material comes into contact with the blood to cause the hemostatic effect.

According to another aspect, the present invention relates to a bandage that can be applied to a bleeding wound to stimulate blood clotting, thereby controlling bleeding. Said dressing comprises a flexible substrate, a gauze substrate attached to said flexible substrate, a clay material provided on the gauze substrate and a polyol also provided on said gauze substrate to bind the clay material. The polyol is selected from a group comprising glycerol, propylene glycol, triacetin, sorbitol, xylitol, maltol, polydextrose, and combinations thereof. When the bandage is applied when treating a bleeding wound, at least some of the clay material comes into contact with the blood.

According to another aspect, the present invention relates to a hemostatic device for stimulating blood clotting, thereby controlling bleeding. Said device comprises a gauze substrate, a clay material arranged on the gauze substrate and also a polyol such as glycerol or the like, arranged on the gauze substrate to bind the clay material, When the device is used to treat a bleeding wound , at least a part of the clay material comes into contact with the blood flowing from the wound to cause clotting.

According to another aspect, the present invention relates to a bandage that can be applied to a bleeding wound to stimulate blood clotting, thereby controlling bleeding. Said bandage comprises a flexible substrate and a gauze substrate fixed thereon. The gauze substrate comprises a clay material and a polyol. When the dressing is used to treat a bleeding wound, the application of the dressing to the wound causes at least a portion of the clay material to come into contact with the blood flowing from the wound.

According to yet another aspect, the present invention relates to hemostatic sponges. One type of sponge comprises a gauze substrate and a dispersion of hemostatic clay material and a polyol, on a first surface of the substrate. When the sponge is used to treat a bleeding wound, the application of the sponge causes at least a part of the hemostatic material to come into contact with the blood. Another type of sponge comprises first and second substrates. A hemostatic material is dispersed in the polyol and applied to the first substrate, and the second substrate is disposed on the hemostatic material dispersed in the polyol. When this sponge is used to treat a bleeding wound, the application of said sponge causes at least a part of the hemostatic material to come into contact with the blood through at least one of the substrates.

An advantage of the present invention is that, unlike other materials such as zeolites, the clay component does not exotherm with blood. Eliminating the generation of heat in a wound is useful to minimize additional discomfort and / or injury to the patient, and can be particularly useful in the treatment of certain patients such as pediatric or geriatric patients, or when the wound is in a particularly sensitive or delicate area.

Another advantage is that clay can be divided into very fine particles and deposited on a wide variety of surfaces, thus facilitating its use as a component in various bleeding control devices. In particular, the clay can be used in particulate form (eg, retained in a mesh or film), or in powder form (eg, deposited on a fibrous substrate to form a gauze or sponge). In either embodiment, the efficacy of clay in stimulating hemostasis in a wound is better than other agents that can only be used in one state (eg as particles of a particular size) to limit the effects. adverse side effects such as excessively exothermic reactions.

Yet another advantage of the present invention is that the devices and agents of said invention are easily applied to open wounds. Especially when the hemostatic agent is trapped in a mesh

ES 2 394 232 T3 or similar device, or when incorporated into a woven structure to form a gauze, the device can be easily removed from a sterile wrapping, and can be placed or clamped directly over the sites of blood loss to induce clotting .

An advantage of combining the use of a polyol such as glycerol with clay (or any other hemostatic agent) is that the dust that often accompanies clay (or other hemostatic agent) is removed. Due to its low volatility, glycerol, for example, does not evaporate easily. For this reason the generation of clay dust is mitigated when it is dispersed in the glycerol. Mitigating or suppressing dust means that there is more hemostatic material for blood clotting purposes.

Another advantage of using a polyol in combination with clay (or other hemostatic agent) is that unintended adhesion of the sponge to the wound is reduced. Thus, the sponge, or other device, can be easily removed from a wound without breaking up the newly formed clot.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic representation of a mesh structure of a blood coagulation device of the present invention.

Fig. 2 is a side view of the blood coagulation device of Fig. 1 illustrating the retention of clay particles in the mesh structure.

Fig. 3 is a perspective view of a blood coagulation device incorporating a clay material into a gauze.

Fig. 4 is a perspective view of a blood coagulation device incorporating a clay material into a fabric.

Fig. 5A is a perspective view of a bandage incorporating the clay particles into a mesh container for application to a bleeding wound.

Fig. 5B is a perspective view of a bandage incorporating hemostatic material and a polyol to a gauze substrate for application to a bleeding wound.

Fig. 6 is a schematic representation of a sponge with hemostatic capabilities.

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hemostatic.

DETAILED DESCRIPTION OF THE PREFERRED FORMS OF EMBODIMENT

The following discloses hemostatic agents and devices that can be applied to bleeding wounds to promote hemostasis. Haemostatic agents typically comprise clay or other silica-based materials that, when in contact with a bleeding wound, can minimize or stop blood flow by absorbing at least part of the liquid phases of the blood, thereby facilitating its coagulation. However, the present invention is not limited to clay, as there are other materials such as bioactive crystals, biological hemostats, molecular filter materials, diatomite, combinations of the above, and the like, which are within the scope of the present invention. and they can be used together with the clay or separately as a hemostatic agent.

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

In a preferred embodiment of the present invention, the clay material is kaolin, which comprises the mineral kaolinite. Although the term kaolin will be used hereinafter to describe the present invention, it should be noted that kaolinite can also be used in conjunction with, or in place of kaolin. The present invention is also not limited with respect to kaolin and kaolinite, however, as there are other materials that are within the scope of the present invention. Such materials include, without being limited thereto, attapulgite, bentonite, combinations thereof, combinations thereof with kaolin and / or diatomite, and the like.

As used herein, the term kaolin refers to a soft and earthy aluminum silicate clay (and more specifically to a dioctahedral phyllosilicate clay) with the chemical formula Al2SÍ2Os (OH) 4. Kaolin is a layered silicate mineral of natural origin, which alternates tetrahedral and octahedral layers of alumina octahedron, linked by the oxygen atoms of the hydroxyl groups. Kaolin comprises approximately 50% alumina, 50% silica, and trace impurities.

ES 2 394 232 T3

Most preferably, the clay will be Edgar's Plastic Kaolin (CPE), a water washed kaolin clay that is mined and processed in and around Edgar, Florida (USA). Edgar's plastic kaolin has desirable plasticity characteristics, is moldable, and when mixed with water produces a thixotropic pasty medium.

The kaolin material of the present invention can be mixed or used in conjunction with other materials to provide additional coagulation functions and / or improved efficacy. Said materials include, but are not limited to, magnesium sulfate, sodium metaphosphate, calcium chloride, dextrin, combinations of the foregoing materials, and hydrates of such materials.

Various materials can be mixed, associated or incorporated into the kaolin to maintain an antiseptic environment in the wound or to offer functions complementary to the coagulant functions of the clay. Some examples of materials that can be used, without being limited thereto, are pharmaceutically active principles such as antibiotics, fungicides, antimicrobials, anti-inflammatories, analgesics, antihistamines (eg. cimetidine, chlorphenamine maleate, diphenhydramine hydrochloride, and promethazine hydrochloride), compounds containing silver or copper ions, combinations of the foregoing, and the like. Other materials that can be incorporated to provide additional hemostatic functions are for example ascorbic acid, tranexamic acid, rutin, and thrombin. Vegetable agents can also be added with advantageous effects in the wound area.

For use in the present invention, kaolin (or other clay or diatomite material) is preferably in particulate form. In the context of the present document, the term "particulate" encompasses beads, balls, granules, rods or any other surface morphology or combination of surface morphologies. Regardless of surface morphology, the particles typically measure between about 0.2mm (millimeters) and 10mm, preferably about 0.5mm to 5mm, and more preferably about 1mm to 2mm, in effective diameter. However, the present invention is not limited in this regard, and other particle sizes (eg less than 0.2 mm) are also within its scope. The particle size of kaolin (or other clay or diatomaceous material) can be small enough to be considered a powder. If the particle size is considered to be powder, such powder may be impalpable (ie not detectable to the touch).

Clay particles can be produced by various methods. Said methods comprise mixing, extrusion, spherisation or the like. Equipment used for clay mixing, extrusion or spherisation processes is available from Caleva Process Solutions Ltd. of Dorset, UK. Other methods are for example the use of a fluid bed or granulation equipment. Fluid beds for the production of clay particles can be found at Glatt Air Technologies of Ramsey, NJ (USA). Disc granulators for the production of clay particles can be found from Feeco International, Inc. in Green Bay, Wisconsin (USA). Preferably, the clay is extruded by a suitable granulating device. However, the present invention is not limited in this regard, as there are other devices and methods for the production of clay particles within the scope of the present invention.

The CPE used in the present invention is particulate, dried, and baked to about 600 ° C. To achieve a homogeneous mixture of CPE to form the particles, a relatively high shear stress is applied to a mass of CPE using suitable mixing equipment. Before shearing, the water content of the clay is measured and adjusted up to 20% by weight to provide a mix sufficiently moldable for extrusion and subsequent handling.

During CPE firing to approximately 600 ° C, the material vitrifies. Vitrification is obtained by repeated cycles of melting and cooling, so that the CPE (or other clay material) can become a glassy substance. As the number of cycles increases, the crystalline structure decomposes to an amorphous composition. The amorphous nature of CPE allows it to maintain its structural integrity when subsequently wet. As a result, CPE maintains its structural integrity when wet with 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 also within the scope of the present invention. Specifically, unverified clay can also be applied to a bleeding wound to provide hemostasis.

The cellular coagulation mechanism of clay is believed to activate certain contact factors when applied to the blood. More specifically, kaolin (specifically CPE) is believed to initiate mechanisms by which water from the blood is absorbed to facilitate coagulation functions.

Referring to Fig. 1, a hemostatic device is depicted into which kaolin in particulate form is incorporated. Said device is a permeable bag that allows the liquid to come into contact with the kaolin particles retained inside. The sealed package (not shown) provides a sterile environment to store the hemostatic device until use. The device, which is represented in a general way indicated with the numerical reference 10 and hereinafter will be known as bag 10, comprises a screen or mesh 12 and the

ES 2 394 232 T3 kaolin 14 in particulate form retained inside by said screen or mesh. The mesh 12 is closed on all sides and defines openings capable of retaining the kaolin 14 in particulate form while allowing the entry of liquids. As illustrated, mesh 12 is shown flattened and, by way of example, only some kaolin 14 particles are shown. The particulate kaolin 14 can be mixed with particles of other types of clay, diatomaceous earth or the like to form a homogeneous mixture.

Mesh 12 is defined by strands, filaments, or strips of interconnected material. Said strands, filaments or strips can be interconnected by any type of combination comprising, but not limited to, being woven into a gauze, being interwoven, being integrally formed, or the like. Preferably, the interconnection is made such that the mesh can flex while essentially maintaining the dimensions of the defined openings. The material from which the threads, filaments or strips are made can be a polymer (eg nylon, polyethylene, polypropylene, polyester or the like), metal, fiberglass or an organic substance (eg cotton, wool, silk or similar).

Referring to Fig. 2, the size of the openings defined by mesh 12 is adequate to retain kaolin 14 in particulate form while allowing blood to pass therethrough. Because the mesh 12 can be stretched around the kaolin particles 14, the kaolin particles can extend through the openings a distance d. If the particles spread through the openings, they will come into direct contact with the tissue to which the bag 10 is applied. Therefore, the blood emanating from said tissue will immediately come into contact with the kaolin particles 14, and the phase Water from the blood binds to kaolin, thereby facilitating blood clotting. However, it is not a requirement of the present invention that the particles protrude through the mesh.

To apply the bag 10 to a bleeding wound, the bag is removed from the wrapper and placed over the bleeding wound. The kaolin particles 14 within the mesh 12 come into contact with the wound tissue and / or the blood emanating from it, and at least a part of the liquid phase of the blood is absorbed by the clay material, stimulating thus coagulation. The flexibility of the mesh 12 allows the mesh to conform to the shape of the bleeding wound and to maintain that shape when applied.

With reference to Fig. 3, another embodiment of a hemostatic device of the present invention is a kaolin gauze, which is represented in a general way indicated with the numerical reference 20 and which will be known hereinafter as gauze 20. It is applied a layer of kaolin on the gauze substrate using any suitable method to obtain the gauze 20. An example of a method of applying a kaolin layer on the gauze substrate is to immerse the substrate in a paste material of kaolin and water. The kaolin material used for said pasty material is preferably kaolin ground to a fine powder, although the present invention is not limited in this regard, since particles, flakes, chips, beads, rods, granules or the like, of alternative or additional mode. The gauze substrate can be any suitable fibrous material, woven or non-woven, comprising, but not limited to, cotton, silk, wool, plastic, cellulose, rayon, polyester, combinations of the foregoing, or the like. However, the present invention is not limited to woven or non-woven fibrous materials to form the gauze substrate, as felts or the like are also within its scope.

However, the gauze 20 of the present invention is not limited to kaolin, as other clays such as attapulgite, bentonite or combinations thereof may be used, in combination or as a substitute for kaolin. In addition, other silica-based materials such as bioactive glasses, diatomaceous earth, combinations of the above or the like, can also be used in combination or as substitutes for the above-mentioned clay materials.

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

The flexibility of the gauze substrate 20 allows the gauze to conform to the shape of the bleeding wound and maintain that shape when applied to the wound.

One way to deposit the kaolin (or other clay) layer on the gauze substrate is by heating the pasty kaolin material and water. Preferably, said pasty material is heated to boiling because higher temperatures tend to facilitate the adhesion of kaolin to the substrate. However, the present invention is not limited in this regard, as the pasty material can be heated to lower temperatures according to the intended characteristics of the kaolin layer. Boiling the pasty material is also an effective form of stirring that disperses the kaolin evenly in the liquid phase.

The substrate is then immersed in the boiling pasty material for a time sufficient for the kaolin to settle on the substrate. Given the rheology of the moistened kaolin and the material from which the substrate or gauze is made, the kaolin can adhere as a film directly to the surfaces of the substrate, or it can agglomerate in the interstices of the strands and also along them. strands, then being trapped in the fibrous matrix.

ES 2 394 232 T3

Another way of depositing the kaolin layer on the substrate comprises applying the kaolin in the form of a pasty material to one side of the gauze substrate by a spray technique, a wide slot nozzle coating technique, or a combination thereof. By using either technique, the amount of pasty material 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 a suitable viscosity for application with the wide slot nozzle coating technique.

Once sprayed or applied by the wide slot nozzle coating technique, the coated gauze substrate is rolled or scraped to further embed the kaolin into the substrate material. Subsequently, the gauze substrate is dried.

The kaolin is attached to the gauze substrate by a binder. The material of this product is compatible with biological tissue. The binder is a polyol that is selected from the group comprising glycerol, propylene glycol, triacetin, sorbitol, xylitol, maltol, polydextrose, and combinations thereof. Polyols have adhesive qualities and are compatible with biological tissue.

An example of a method for the production of this device may comprise the steps of unrolling the gauze from a roll, dipping the gauze into a pasty material of hemostatic material and water, applying pressure to the gauze by rolling the wet gauze under elevated pressure to Incorporate the hemostatic material into the gauze material, dry the rolled wet gauze and remove the dust from the gauze (eg. using metering air jets or air nozzles, using electrostatic energy, vacuuming or brushing with direct contact brushes). After removing the dust from the gauze, the gauze can be re-rolled, or cut into pieces for individual packaging.

One or more variables can be manipulated to optimize the amount and integrity of kaolin retained in the gauze. Said variables include, but are not limited to, the temperature of the pasty material, the immersion time, the method of stirring the pasty material, and the type of liquid (of the pasty material). Increasing the temperature of the pasty material, as noted above, aids in retention of the kaolin in the gauze. Agitation can be affected by forcing air or other gas through the nozzles, stirring, creating bubbles, boiling, or applying ultrasonic vibrations.

The liquid used for the pasty material can also be other than water. For example, the liquid can be an aqueous solution of ammonia. Aqueous ammonia is known to cause certain fibrous materials to swell, such as materials commonly used to produce gauze.

A polyol is used in the gauze 20, which can be glycerol (also known as glycerin, glyceritol, glycyl alcohol, and by its chemical name 1,2,3-propanetriol). Glycerol is a lubricious, hygroscopic and water-soluble liquid, compatible with biological tissue. The kaolin is dispersed in the glycerol to form a dispersion, or is otherwise mixed with the glycerol, and deposited on the gauze substrate by any appropriate method. Appropriate 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, applying by the wide slot nozzle coating technique, physical means such as brushing or rolling the dispersion on the gauze, or the like.

Besides glycerol, other polyols may also be present. These include other glycerol-based compounds, such as glycerol alcohols (eg propylene glycol), esterified glycerol-based fatty acids (eg triacetins), and other materials with wetting and similar properties (as well as combinations of the above) and other polyols such as sorbitol, xylitol, maltol, combinations of the above and the like, and also polymeric polyols (eg. polydextrose).

With reference to Fig. 4, a hemostatic device formed by a fabric with hemostatic properties is represented, generally indicated with the numerical reference 20, and which will be known hereinafter as fabric 30. The fabric 30 is a fabric that can be formed by woven or non-woven strands, a felt or the like, into which a biological hemostatic material is impregnated or infused. The hemostatic materials that can be infused or impregnated into the fabric of the fabric 30 include, but are not limited to, clays (such as kaolin) in particulate form 32, other silica-based materials (such as diatomite, combinations thereof , or similar), chitosan, combinations of the above, or similar. In embodiments where such materials are infused or impregnated into a fabric, the material is preferably incorporated into the fabric in a hydrated state and subsequently dried.

In both the gauze and cloth embodiments, the gauze or cloth material may be interwoven with a polysaccharide or similar material.

Referring to Fig. 5A, a bandage is depicted, indicated at 50, comprising kaolin 14 (or other clay or diatomaceous material) particles retained on mesh 12 and fixed on a flexible substrate 52 that can be applied to a wound (for example, using a pressure-sensitive adhesive to adhere

ES 2 394 232 T3 said bandage 50 to the skin of the injured person). Mesh 12 is sewn, glued, or otherwise affixed to substrate 52 to form bandage 50.

The substrate 52 is an integral part of a plastic or fabric suitable for being attached to the skin of an injured person or animal, on or near a bleeding wound. An adhesive 54 is disposed on the substrate 52 that comes into contact with the skin of the injured person or animal. Specifically, if the substrate 52 is a non-breathable plastic material, said substrate may comprise holes 56 to allow dissipation of moisture that evaporates from the surface of the skin.

With reference to Fig. 5B, the bandage is indicated with the numerical reference 150. Said bandage 150 comprises particles of kaolin (or other clay or diatomite material, capable of performing a hemostatic function) dispersed in glycerol and applied to a gauze substrate. 1 12. Said gauze substrate 1 12 is attached to a flexible substrate 152 that can be applied to a wound (for example, by a pressure sensitive adhesive 154 disposed over essentially the entire skin-contacting surface of the flexible substrate 152 to adhere the bandage 150 to the skin of the injured person). The gauze substrate 1 12 is sewn, glued, or otherwise attached to the substrate 152, which may be an integral part of plastic or fabric and may comprise holes 156. A release agent (eg, polyvinyl alcohol, glycerol, carmellose, or the like) may be disposed on the kaolin / glycerol dispersion in the gauze substrate 112.

Referring to Fig. 6, a sponge is represented, indicated with the numerical reference 60, comprising a substrate 62, with kaolin 14 (or other clay or diatomaceous material) particles disposed on one face of the substrate 62, and an agent releaser 64 arranged on the opposite face of said substrate. Sponge 60 allows sufficient contact of kaolin particles 14 with blood emanating from a wound, and through release agent 64 and substrate 62, while minimizing adhesion of the sponge to wound tissue. Sponge 60 is also compatible with living tissue.

Substrate 62 is an absorbent gauze material that defines a matrix. However, the present invention is not so limited as other materials such as rayon / polyester cellulose blends and the like are also within the scope of the present invention. The substrate 62 can be made from other materials such as woven fabric, nonwoven fabric, paper (eg brown paper or the like), and cellulose material (eg. cotton balls, swabs or similar). Any material that can be used to make substrate 62 must possess elasticity. When elastic materials are used as the substrate 62, the sponge 60 serves as a hemostatic device and compression bandage, especially in embodiments where a surface cohesive agent or mechanical fastener is added to hold the sponge on. the wound.

The hemostatic agent used for sponge 60 is not limited to kaolin 14 particles. Other materials such as attapulgite, bentonite, combinations thereof, or a combination of the above with kaolin may be used. The present invention is also not limited to clays, since other materials such as bioactive glass, biological hemostats, diatomaceous earth, combinations thereof, and combinations of the above with clay are also within the scope of the present invention.

Kaolin particles 14 may be attached to substrate 62 by a binder.

If a binder is used to bond kaolin particles 14 to substrate 62, said binder can provide additional functionality to sponge 60. The binder is a polyol selected from a group consisting of glycerol, propylene glycol, triacetin, sorbitol, xylitol, maltol, polydextrose, and combinations thereof.

In embodiments where the kaolin particles 14 are directly incorporated into the substrate 62, the kaolin particles can be added during the making of the substrate. If said substrate is a nonwoven gauze material containing rayon and polyester, the kaolin particles 14 can be incorporated into or on the rayon or polyester fibers. For example, kaolin particles 14 can be added in powder form to molten polyester, and polyester fibers can be made from the liquid polyester / hemostatic material blend. If the substrate is a woven gauze (eg cotton), kaolin powder 14 can be incorporated into the cotton yarns during the formation of the cotton yarns.

The kaolin particles 14 can form a dispersion with glycerol, and said dispersion can be applied to the substrate 62 by a spray technique, a wide slot nozzle coating technique, or by dipping, brushing, rolling or the like.

Release agent 64 is a material disposed on the side of substrate 62 that contacts the wound, to facilitate removal of sponge 60 from wound tissue after clot formation. Release agent 64 may be a continuous film or it may be discontinuous on the surface of the substrate. One of the materials that can be used as a release agent is polyvinyl alcohol, a biocompatible material that can be made in the form of a thin film and does not significantly affect the absorbency and permeability of the sponge 60. Another material that can be used as a release agent 64 is glycerol, which can be applied together with the particles of

ES 2 394 232 T3 kaolin 14 dispersed in glycerol. When used as a release agent 64, glycerol forms a film on the dispersion of kaolin particles 14 in glycerol. Another material that can be used as a releasing agent, without being limited thereto, is carmellose. In any configuration of sponge 60, release agent 64 can be applied directly to the surface of substrate 62 that contacts the wound.

Alternatively, the release agent 64 may be applied to the surface of the substrate 62 that does not come in contact with the wound, in the form of a pasty material composed of clay and the release agent. In such an embodiment, the concentration of polyvinyl alcohol is sufficient so that at least part of the alcoholic component of the same leaks towards the surface of the substrate 62 that is in contact with the wound, while the clay material remains on the surface that it is not in contact with or near the wound. In either embodiment, the polyvinyl alcohol or glycerol not only acts as a release agent, but also as a dust removal agent for the kaolin 14 particles.

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

Sponge 60 may further comprise a component that gives it a radiopaque characteristic. In such an embodiment, barium sulfate can be incorporated into a pasty material comprising kaolin particles 14 and subsequently applied to substrate 62.

Sponge 60 may further comprise water or alcohol, thus allowing its use as a cleaning sponge.

With reference to Fig. 7, a sponge generally indicated with the numerical reference 160 is represented. Said sponge 160 comprises a film 162 in which kaolin particles 14 are dispersed. Said film 162 maintains the physical integrity of the sponge 160. Preferably , the material from which the film 162 is made is polyvinyl alcohol. In making sponge 160, kaolin particles 14 are dispersed in polyvinyl alcohol, which subsequently forms a sheet. Sponge 160 is particularly useful when incorporated into a bandage.

Referring to Fig. 8, a comparative embodiment of a sponge is depicted, generally indicated by the reference numeral 260. The sponge 260 comprises a substrate 262, kaolin particles 14 disposed on the substrate, and a film 266 disposed on the substrate. hemostatic material. The kaolin particles 14 are an unfixed coagulating agent (without binder) and are preferably arranged on the substrate 262 in strips to facilitate folding of the sponge 260. Film 266 is made of polyvinyl alcohol, glycerol, or the like, and is applied both to contain the kaolin 14 particles and to minimize the generation of dust. When applied to a bleeding wound, the blood from the wound is incorporated into the substrate 262 and comes into contact with the kaolin particles 14.

Referring to Fig. 9, a sponge generally indicated by the reference numeral 360 is shown. Said sponge 360 ​​comprises kaolin particles 14 between two layers of substrate 362. Said substrate layers 362 can be joined in any suitable way, such as, for example, by heat sealing in areas with selective absence of kaolin particles 14, using an adhesive or binder in specific areas, applying a film or containment material (such as polyvinyl alcohol) throughout the 360 ​​sponge, or by a combination of any of the above. The kaolin particles 14 can also be used in conjunction with glycerol, e.g. eg, dispersing them in glycerol and applying them to sponge 360.

Sponge 60 (as well as sponges 160, 260, and 360) can be folded and used in a variety of ways. The sponge 60 can be bent so that the surfaces containing kaolin particles 14 are on the inside of the bent sponge, to minimize problems of dusting and shedding of hemostatic material from substrate 62. The sponge 60 (as well as the sponges 160, 260, and 360) can also be folded into various pleats or so as to obtain various marked and edge-joined pleats. By configuring the sponge 60 in this manner, the compliance and absorbency requirements of its various applications can be met. The sponge 60 can also be cut or made into elongated strips to wrap the wounds of a person or animal, or to be incorporated into cylinders or swabs. The sponge 60 can also be cut, torn, ground, or divided into small pieces in some other way, for applications such as filling mesh containers.

Comparative Example 1 - Effect of the temperature of the pasty material on the kaolin retention capacity of cotton gauze

The temperatures of the water / kaolin pasty materials were varied to study the ability of the cotton gauze to retain kaolin clay. Water-paste and CPE materials were prepared in which kaolin was 40% of the total weight of the clay. Three sponges (one from each piece of gauze) were made by dipping the cotton gauze into the muds at various temperatures, rolling the wet sponges under pressure, and subsequently drying them. The following Table indicates the parameters for each pasty material and the results obtained.

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<td>Sample</td><td>Temp. pasty material (° C)</td><td>Stirring method</td><td>Gauze starting weight (grams)</td><td>Gauze final weight (grams)</td><td>% kaolin (% weight)</td>

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

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

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

The final weight of the gauze is the weight of the gauze after rolling and drying. The elevated temperature of the pasty material was observed to increase the amount of kaolin retained. One theory to explain this result is that the fibrous structure of the gauze cotton loosens and swells due to immersion in hot liquid.

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

Dried kaolin was applied to a dry cotton gauze. Subsequently, the gauze was rolled up. 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). However, this sample accelerated the clotting time in whole sheep blood by 70% greater than the unaccelerated clotting time.

Example 3 - Kaolin powder reduction using glycerol

A pasty material was prepared with 50 grams (g) of water, 20 g of glycerol and 15 g of kaolin powder, and used to saturate a gauze sponge (Kendall Curity 2733). Subsequently, the saturated gauze sponge was dried. Said sponge was held and tapped with a pencil on a clean glass surface. A visual determination indicated that no noticeable amount of dust was released as a result of strokes with the pencil.

A second sponge without glycerol was prepared and dried. Said second sponge was held and tapped with a pencil on a clean glass surface. A visual determination indicated that a noticeable amount of kaolin powder was released from the second sponge as a result of strokes with the pencil.

Although the present invention has been shown and described in accordance with the detailed embodiments thereof, it is the objective that the present invention is not limited to these particular embodiments disclosed in the detailed description made above, but rather that the present invention is The present invention encompasses all embodiments that are within the scope of the appended claims.

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REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is presented solely for the convenience of the reader. It is not part of the European patent document. Although the references have been carefully compiled, errors or omissions cannot be excluded and the EPO declines all responsibility in this regard.

Patent documents cited in the description WO 2006088912 A EP 1810697 A WO 2005030279 A