JP6527266B2 - Hemostatic device and method - Google Patents

Description

  The present invention relates generally to hemostatic products, and in particular to a novel hemostatic device comprising potassium ferrate and a cation exchange resin that performs surprisingly improved performance when applied to hemorrhaging or exuding wounds.

  Hemostatic powders are well known. Thompson et al., U.S. Pat. Nos. 4,545,974 and 4,551,326 disclose methods of making potassium ferrate and similar high oxidation state iron oxide compounds. No. 8,187,347 by Patterson et al. And U.S. Pat. No. 6,521,265 by Patterson et al. Disclose mixing potassium ferrate with an anhydrous strongly acidic cation exchange resin to stop bleeding. These patents are incorporated herein by reference in their entirety. Kuo et al. (J. Vase Interv. Radiol. 19: 1 72-79 2008) is the market leader in hemostasis pads for the time to hemostasis (TTH), which is the disclosure of benefit of a ferrate / ferrate mixture. The advantage of shortening from 4 minutes by D-stat to 4 minutes is disclosed. Michelson (The American Journal of Cosmetic Surgery 25-3 2008) shows that a ferrate / resin mixture is excellent for wound healing. Michelson showed that the patient's open-arms wound on cosmetic treatment was completely closed. After 16 weeks, the patient healed without scarring.

  Cook et al., In U.S. Pat. No. 2,923,664, disclose a hemostatic plate formed by wet granulation and compression of a mixture of cellulose glycolate ether and its sodium salt. U.S. Pat. No. 3,368,911 to Kuntz et al. Discloses a hemostatic sponge prepared by freeze-drying acid swollen collagen fibers. Pawelchak et al., In U.S. Pat. No. 4,292,972, disclose a lyophilized hydrocolloid foam having hemostatic properties. Although the prior art exemplifies a hemostatic plate or sponge, the comparison with the powder or granulation used as the raw material of a plate is hardly performed.

  There has been an unmet need to provide another means of delivering a hemostatic material to the wound that can avoid the complications associated with the use, application and delivery of free particulate powder to the wound site. . Solid devices, preferably plates, formed from free hemostatic powder, are very dense due to the high compression forces during plate preparation. By compacting the loose powder into a solid, it is of course possible to form less complex product applications, but the surface area is reduced as a result of the compression correction. Therefore, the free hemostatic powder itself is more effective for immediate action as compared with the solid flat plate of such a material.

  The related art described above and the limitations associated therewith are intended to be illustrative and not exclusive. Other limitations of the related art will also become apparent to one of ordinary skill in the art through an examination of the readings and drawings of this specification.

  The present invention is a novel hemostatic device, preferably prepared from a powder or powdery mixture comprising an effective amount of insoluble cation exchange material, preferably in combination with an anhydrous ferrate compound (product name STATSEAL by Biolife, LLC) Marketed) and methods of stopping blood flow from bleeding wounds. According to such a method, the plate is wound for a time sufficient to coagulate the blood and substantially stop further blood from the wound by pressing the device in the form of a solid plate against the wound. Apply to

Agglomerate Size enlargement or aggregation is any process by which small particles assemble to form a larger, relatively persistent mass, and within that mass It is still possible to identify the original particles. Its applications include, for example, the formation of useful shapes (bricks, tiles etc) and the formation of irregular pellets or spheres for the industrial beneficiation of finely divided materials.

The granulation process has numerous benefits and various granulation methods and applications are available. One of them is pressure compaction. Devices used for pressure compaction include, for example, piston or molding presses, tablet presses, roll presses, pellet mills, and screw extruders, which provide various granulation methods and applications. The binding mechanism of aggregates is divided into five main groups: (1) solid bridges; (2) mobile liquid binding; (3) immobile liquid bridges. (4) intermolecular and electrostatic force; (5) mechanical interlocking. Robert H. Perry, ed. Et al., ( Perry's Chemical Engineers' Handbook , 6 ^th ed., 8-60-8-61 1984).

  The STATSEAL hemostatic device of the present disclosure, made by pressure compaction, preferably from a powdery mixture of potassium ferrate / strong acid cation exchange resin, comprises a stain associated with the application of loose powder. Provides improved delivery and control of application on the wound site without development. In topical application to a hemorrhagic wound, for example, high density filling in a flat plate is expected to have a slower action on hemostasis because the surface area is reduced as compared to the case where the same mixture is in the form of free powder. Surprisingly, it turned out that the fact is the reverse. Compared to the powder, the hemostasis plate adhered more strongly to the bleeding wound and hemostasis occurred more quickly. Once the sealant is formed, most of the unused plate will be easily peeled off from the sealant, or the unused portion of the plate left in place will stop further bleeding and prevent antimicrobial protection and healing. Provide a reservoir for hemostatic dressings for the provided sustained and long-term ability.

  The solid hemostatic plate can be applied to a wound that is bleeding or to a site at which bleeding may occur in the future. The solid hemostatic agent also seals the part where exudative fluid exudes and forms a sealant by combination with blood or exudate, thereby keeping the wound site dry and preventing maceration, while wounding It may be used to prevent the drying of

Mechanism of action A preferred 1: 7 ferric salt: hydrogen resin blend powder aids pressure and forms a nothing-in / nothing-out sealant with blood in a known process.
a. External semi- or non-occlusive vertical pressure is important to achieve hemostasis. Without pressure, consistent hemostasis is not achieved.
b. Types of physical elements include, for example, particle size, density, hardness, thickness, shape, dryness, and proportions of components.

  2. Compressing the preferred 1: 7 ferrate: hydrogen resin blend powder at at least about 8 Kpsi (about 55.158 MPa) forms a high density solid device. The high density solid device, preferably a flat plate, withstands considerable manual pressure, such pressure providing a very strong and even force to compress the wound surface. On the other hand, similar pressures are not easily applied to loose powders which are unevenly distributed throughout the wound bed and relatively thin. Even if some areas have a thicker powder coating compared to other areas, there may be no coverage in other areas. The non-uniform coverage of the wound site with this free powder results in a low net pressure as compared to the uniform high net pressure achievable with the use of flats. Also, the uniform surface of the solid plate more evenly displaces the underlying blood to form a more uniform sealant, allowing for blood retention that may occur with the application of uneven free powder. Reduce sex. As a result, the plate adheres more quickly to the bleeding wound and hemostasis is achieved earlier than the powder.

  3. When a sealant is formed from the interaction between the blood and the surface of the flat plate in contact with the wound, the sealant remains intact to protect the wound and of the unused solid hemostatic material Separates easily from the rest. If this unused residue remains attached, the large reservoir of hemostatic material provides a lasting and long-term ability to stop further bleeding, and also promotes antimicrobial protection and consequently healing. Be done. The degree of sustained and long-term ability can be designed according to the size, shape, density, grain size and thickness of the plate.

  4. The solid hemostatic device can be made to be applied to all possible surfaces, such as horizontal, vertical and inclined surfaces.

  5. The solids may be compression molded into different shapes or machined into different shapes after plate formation. Machining may be done with a blade or a laser, or larger plates may be scored and machined so that they can be split into smaller shapes for application.

  6. The solid may be an extruded solid material, or a continuous ribbon thereof, and any form of mechanical compression may be used.

  7. The solids may be attached to gauze bandages, swabs, surgical or dental instruments, vacuum devices, and magnets when the powder is mixed with a suitable material such as magnetite. The device attached to the solid hemostatic agent may be straight or curved, and may be rigid or flexible.

  8. The solid hemostatic agent may be a single uniform powder compressed into a flat plate, or the powder may form a layer.

  9. The antimicrobial agent may be added to the powder as a dry powder, may be absorbed by the resin, or may be added after the plate has been formed.

  10. The solids may be attached to compression aids, such as balloons, compression foams, mechanical clamps, and compression bandages.

  11. Additives such as fibrous materials may be used to increase the strength of the table so that it is thin, flexible, moldable during application, or has an improved cosmetic appearance.

  12. The plate may be attached to a backing, the backing may include an antimicrobial agent, and may include an adhesive to hold the plate in place and protect the plate. Or as a cosmetic function.

  13. The plate may be applied to the bleeding wound after pretreatment.

  The following embodiments and aspects thereof are described and described in connection with systems, tools, and methods intended to be exemplary and exemplary, not limiting in scope. In various embodiments, while one or more of the above problems are mitigated or eliminated, other embodiments are directed to other improvements. In addition to the illustrative aspects and embodiments described above, further aspects and embodiments will become apparent by reference to the drawings and by study of the following description.

FIG. 1 is a perspective view of a flat plate embodiment of the present invention. FIG. 2 is a top view of FIG. FIG. 3 is a side view of FIG. FIG. 3A is a perspective view of a two-piece flat plate embodiment of the present invention. FIG. 4 is a perspective view of the alternative embodiment of FIG. 1 with the addition of a reinforced foam backing. FIG. 5 is a reverse perspective view of FIG. 6 is a cross-sectional view in the direction of arrow 6-6 in FIG. Same as above. 7 to 10 show I.I. V. FIG. 7 is a perspective view showing the catheter removed and the embodiment of FIG. 1 deployed on the patient's arm. Same as above. Same as above. Same as above. FIG. 11 is a perspective view of another two-piece embodiment. FIG. 12 is a top view of FIG. 13 is a cross-sectional view in the direction of arrow 13-13 of FIG. FIG. 13A is a cross-sectional view similar to FIG. 13 with the addition of a reinforced foam backing. 14 and 15 are perspective views of other one-piece flat plate embodiments. Same as above. 16 is a cross-sectional view in the direction of arrows 16-16 of FIG. 17-24 are perspective and corresponding cross-sectional views of the hollow feature configuration of the present invention. Same as above. Same as above. Same as above. Same as above. Same as above. Same as above. Same as above. 25-27C are perspective views of other configurations of one or multi-piece embodiments adhered to adhesive bandages. Same as above. Same as above. Same as above. Same as above. Figures 28-33A are perspective views of other configurations of solid one-piece embodiments adhered to a delivery member. Same as above. Same as above. Same as above. Same as above. Same as above. Same as above. FIG. 34 is a perspective view of another one-piece embodiment. 35 is a cross-sectional view in the direction of arrows 35-35 of FIG. FIG. 36 is a perspective view of another one-piece embodiment. 37 is a cross-sectional view in the direction of arrows 37-37 of FIG. 37A-37E are cross-sectional views of the alternate embodiment of FIG. Same as above. Same as above. Same as above. Same as above. Figures 38A and 38B are top views of smaller pellets of the present invention. Same as above. FIG. 39 is a perspective view of another one-piece flat plate embodiment. 40 is a cross-sectional view in the direction of arrows 40-40 of FIG. 41 shows the I.I. inserted through the central opening. V. FIG. 40 is a perspective view of the embodiment of FIG. 39 packaged with a cannula. FIG. 42 is a perspective view of the granules of FIG. 38B affixed to the surface of a flexible waxy form for atypical wounds. FIG. 43 is a perspective view of the granules of FIG. 38B affixed to a length of cord, string or rope. Same as above. FIG. 44 is a perspective view of a hollow wafer embodiment containing a foam inner core. 45 is a cross-sectional view in the direction of arrows 45-45 of FIG. FIG. 46 is a three independent chart showing the percentage ratio of whole beads to bead fragments required to form the hemostatic device of the present invention. FIG. 47 illustrates the effect of thickness in forming the hemostatic device of the present invention. FIG. 48 is a graph showing the relationship between the hemostatic material density and the formation pressure. FIG. 49 is a schematic diagram of a laboratory test designed to evaluate the ability of a solid hemostatic device and its powder form to adhere to the blood surface. FIG. 50 is a schematic view of a laboratory test different from the test shown in FIG. 49, for evaluating the blood adhesion properties of the hemostatic plate hemostatic material and the free powder hemostatic material. In this test, higher static pressure is achieved using a syringe. FIG. 51 is a graph showing the relationship between the rate of collapse of the hemostatic device and the formation pressure. 52 is a scanning electron microscope (SEM) photograph of the hemostasis device of FIG. 11 positioned near an endovascular access cannula. FIG. 53 is an enlarged view of the area 53 of FIG. FIG. 54 is a SEM side view of a hemostatic device applied over a bleeding wound.

  Generally speaking, the hemostatic powder composition used to form the hemostatic device of the present disclosure sold under the trademark STATSEAL by Biolife, LLC (as Assignee) preferably has an effective amount of insoluble cation exchange material. , Preferably in combination with an effective amount of an anhydrous ferrate compound. Preferably, the hemostatic powder comprises a mixture of cation exchange resin in hydrogen form (hereinafter abbreviated as hydrogen resin) and potassium ferrate. The hemostatic powder can be converted to a flat plate by any known compression method, and can be converted to any size, shape, thickness and configuration. Optionally, other materials may be incorporated into the hemostatic powder to enhance performance, such as antimicrobial agents, zinc oxide, binders and excipients to aid in plate formation, magnesium stearate, sodium carboxymethylcellulose Hydroxymethyl cellulose, polyvinyl pyrrolidone, medical grade fibers to increase strength, and natural and synthetic rubbers.

STATSEAL solid hemostatic devices (also referred to as flats, discs, and wafers) are used to control bleeding associated with minor injuries, for example, to control mild external bleeding and bleeding from sutures and / or surgical procedures. Intended for use as a topical coating. The STATSEAL device preferably consists of two main components: 1 part by weight potassium ferrate and 7 parts by weight hydrophilic polymer. Potassium ferrate is an oxyacid by-product in the reaction of ferric acid (H ₂ FeO ₄ ) with potassium hydroxide (KOH). Potassium fusion ferrate (potassium fusion ferrate) is produced by thermal combination of iron oxide (Fe ₂ O ₃ ) and potassium nitrate (KNO ₃ ). Potassium ferrate readily decomposes in water to form Fe ₂ O ₃ and KOH as follows:
2K ₂ FeO ₄ + 2H ₂ O → Fe ₂ O ₃ + 4 KOH + 1.5 O ₂ (g)
General

  The hydrophilic polymer is a strong acid cation exchange resin in hydrogen form formed of a sulfonated copolymer of styrene and divinyl benzene (2%). The polymer used in the STATSEAL instrument (PUROLITE C-122 (H); CAS No., 069011-20-7) is purchased completely hydrated and is simply heat dried to less than 3% moisture It is used for mixing with potassium ferrate.

The STATSEAL hemostatic device achieves its intended purpose of action (hemostasis) by creating a physical barrier or seal against blood flow. This product establishes an environment where natural clots are built and formed under the physical sealant formed by STATSEAL. The hemostatic effect of the device is exerted by two simultaneous mechanisms of action:
The aforementioned iron-based oxyacid salts, which promote clotting, coagulate blood proteins.
The hydrophilic polymer rapidly dehydrates the blood and absorbs exudates.
The reaction of the hydrophilic polymer with the oxy acid salt is as described below:
Resin-H + K ₂ FeO ₄ → Resin-K + Fe ₂ O ₃ + H ₂ O + O ₂
blood

  As soon as the device comes in contact with the blood, the formation of the sealing agent is initiated. The polymer rapidly absorbs the liquid portion of blood while depositing blood cells thereunder. The polymer swells upon absorbing the liquid. The blood cells are rapidly deposited under the plate to form a sealant. This sealant stops bleeding and also prevents further absorption of the liquid by the polymer in the plate. The swollen wet polymer allows the portion of the solid hemostatic agent in contact with the blood to delaminate from the remaining dry material. The remaining dry plate may be removed or held in place with the dressing. Only a small fraction of the flat material remains attached to the blood or sealant surface. As the wound heals under the sealant, the remaining material drops out of the wound site.

Amazing results

  The solid hemostatic device was expected to take much longer than the free powder to achieve hemostasis in bleeding wounds due to the reduced surface area, high density and hardness. Surprisingly, hemostasis was achieved in a shorter time as compared to the free powder case. Furthermore, adhesion to the bleeding wound site occurred more quickly on the proximal side of the plate as compared to the free powder. This unexpected finding is explained as follows. When the solid hemostatic plate is applied to a bleeding wound, the manual pressure applied to the distal side of the plate exerts a very strong and even force on the wound surface. However, in the case of free powders which are unevenly distributed, relatively thin in some areas of the wound bed, and possibly in the absence of powder coverage in some areas, similar pressures are not easily applied. , Resulting in low net pressure. Thus, compared to free powder, the plate adheres more quickly to the bleeding wound and hemostasis is achieved earlier.

  Another surprising finding in the plate is that the formed sealant separates quickly from the unused portion of the plate. As discussed above, the sealant is easily formed by the interaction of blood with the surface of the plate in contact with the wound. It is unexpected that such a quick separation occurs between the used and unused parts of the plate. Also in this plate separation process, the sealing agent protects the wound without loss. This leaves a large reservoir of unreacted solid hemostatic material, thereby providing a sustained and long-term ability to stop further bleeding, providing antimicrobial protection, and consequently healing.

  The degree of continuous and long-term action can be designed according to the size, shape and thickness of the plate. The foregoing examples of flat plate sizes, shapes, and thicknesses, and the limitations associated therewith, are intended to be illustrative and not limiting. Furthermore, the hemostatic device can be made to be applied to all conceivable surfaces, such as horizontal, vertical and inclined surfaces. The particle size of the hemostatic powder partially determines the integrity of the device, in particular in the absence of a binder. The preferred particle size range is 80 microns to 500 microns, more preferably 150 to 300 microns. Below 80 microns, the sealant is thin and weak, while above 500 microns the sealant is nonuniform, too thick, with weak spots.

  Any form of insoluble cation exchanger can be selected as a component of the hemostatic plate. Preferably, the cation exchanger is a cation exchange resin crosslinked in the range of 0.25% to 15%. Cation exchange resins in hydrogen form are preferred over those in other cation forms.

Details of the embodiment

  Hereinafter, reference will be made to the drawings. First, in FIGS. 1-3, one embodiment of the present invention is indicated generally by the numeral 10. The present embodiment includes a circular body 12 formed of a hemostatic material. The contents and physical properties are shown below. The body 12, sometimes referred to as a wafer body, disc or plate, includes an elongated cannula access slot 14, which is formed radially inward from the periphery of the body 12 to the center, and has a slot proximal end Let 16 be the end point. As shown in FIGS. V. A rounded slot entry angle 18 is provided to form the entry end of the cannula access slot 14 to facilitate mounting around the cannula.

  As seen in FIG. 7, the hemostatic device 10 is oriented in the direction of arrow A such that the catheter, needle or cannula access slot 14 slides around the catheter and is located on the skin of the arm at the wound site W It is possible. The skin-contacting surface 15 of the hemostatic device 10 is pressed against the skin in the direction of arrow C in FIG. 8 for a sufficient time for the hemostatic material of the device 10 to interact with blood and exudate from the wound site W, Thereafter, the catheter is removed in the direction of arrow B. A clear dressing is applied to the hemostasis device 10 in the position shown on the skin of the arm in FIG. 9, which covers and holds the hemostasis device 10 in position on the wound.

  Another embodiment of a hemostatic device is shown in FIG. The present embodiment includes a body segment 25 through which the central cannula access hole 19 passes. The body segment 25 includes a segment opening 21. After placing the cannula through the slot access cannula access hole 19, the rod-like body 17 may be inserted into the segment opening 21 in the direction of the arrow. An access hole segment 23 completes the cannula access hole 19 which will surround the cannula when properly installed.

  Another embodiment of the invention is shown at 20 in FIGS. This embodiment includes the hemostatic device 10 of FIG. 1, which is adhered to a matingly shaped layer of a rigid backing 24 covering one side of the body 12. The proximal surface of the body 12 defines a skin contact surface 15.

  A further embodiment of the invention is shown in FIG. 6A. The present embodiment includes a hemostatic device 10 formed of the aforementioned body 12 which, as described below, comprises a hemostatic material 13 that has been compressed and brought together. A foam backing 22 is provided, which includes an edge 22a. The edge 22a completely encloses the peripheral edge of the body 12 which would otherwise be exposed but does not cover the skin contact surface 15.

  One preferred embodiment of the present invention is generally designated by the numeral 30 in FIGS. The present embodiment is formed from a hemostatic half body portion 32 that can be joined together along the proximal coupling end 34. A centrally located catheter access half hole 36 is formed in the proximal end 34 and the half hole 36 encloses the catheter when the skin contacting surface 35 or 37 is placed on the skin and around the catheter. Be Rounded corners 38 are provided to reduce damage to the body. Preferred dimensions for each of the half body portions 32 of this embodiment 30 are: l = 0.82 inch, w = 0.44 inch, t = 0.13 inch. .330 cm), slot diameter = 0.12 inches (about 0.305 cm).

  FIG. 13A shows another embodiment of the present invention. This embodiment includes the hemostatic device 30 of FIG. 11 and a reinforced foam backing 39 adhered to one surface 35 of each of the half body portions 32, but the skin contact surface 37 is to the skin when worn Because of the adhesion of

  Another embodiment of a hemostasis device is shown at 40 in FIG. This embodiment includes the half body portions 42 connected along the fold line 44 and joined by the groove thickness 46 of the hemostatic material. The purpose of this embodiment 40 is to provide better skin surface contact in the area of a curved skin surface by facilitating the tear along the fold line 44 of the half body portion 42 and making it easier to tear. It is.

  In FIGS. 15 and 16 a hemostatic device 50 is provided which is formed from a body 52 having a flat skin contact surface 52 and a convex skin contact surface 56.

  Figures 17-24 illustrate a series of recessed configurations of the present invention. These hemostatic assemblies 60 and 70 provide concave curved skin contact surfaces 66 and 76, respectively, which are formed from a cup or thimble hemostatic body 62 or 72, respectively. To provide strength to these hemostatic assemblies 60 and 70, respectively, a rigid or semi-rigid backing 64 or 74 having smooth protective outer surfaces 68 or 78, respectively, is provided. One specific embodiment is the use of a bleeding finger tip or overcutting of the dog's toenail.

  In FIGS. 21-24, convex or spherical outer skin contact surfaces 66 'and 76' of cup-shaped or thimble-shaped hemostatic bodies 60 'and 70', respectively, are provided. The hemostasis bodies 62 'and 72' are supported on their inner surfaces by adhesion to a rigid or semi-rigid mating outer backing 64 'or 74', respectively.

  25-27C, a series of hemostatic bandages 80, 80 ', 90, and 90' are shown. Each of these hemostatic bandages comprises an elongated strip of flexible adhesive carrier 82 having an adhesive surface 86. In the embodiment 80, a circular flat body 84 formed of the hemostatic material 85 and having a skin contact surface 88 is centrally located on the adhesive carrier 82 and adhered. The hemostatic bandage 90 comprises a rectangular main body 94 which is formed as described below from the compressed and assembled hemostatic material 95 and which has a skin contacting surface 98.

  With respect to the hemostatic bandage 90 'of FIG. 27A, an array 94' of thin, compact hemostasis bodies is attached to the adhesive surface 86. The hemostatic bodies are each formed of a hemostatic material 95 'and have a skin contact surface 98'. This embodiment 90 'is such that the skin contact surface 98' is flexible on the irregular or curved shaped skin surface. Similarly, the embodiment 80 'in FIG. 27B includes a body array 92 comprised of a thin compact hexagonal shaped hemostasis body. The hemostatic bodies are each formed of a hemostatic material 97 and have a skin contact surface 96. This body array 92 provides another ability to conform to curved and irregular skin surfaces.

  In FIG. 27C, embodiment 80 ′ ′ provides adhesive carrier 82 ′ ′, which is spaced apart transverse tear lines or cuts 98 for easy adjustment of its length. An array of closely spaced very compact hemostasis bodies 84 'adhered to the adhesive surface 86' and extending longitudinally along said flexible adhesive carrier 82 'may be a long wound, for example a suture. It can be placed on the wound The individual hemostatic body provides extremely flexible application on rough skin surfaces.

  The multiple hemostatic devices 100, 110, 120, 130, 140, 150, and 150 'are shown side by side in FIGS. 28-33A. Each device has a solid hemostatic body 102, 112, 122, 132, 142, 152 and 152 'having a unique configuration, which hemostatic body 106 is in contact with the skin 106, 116, 126, 136, 146, 156 , And 156 'and attached to the elongated handle 104, 114, 124, 134, 144, 154, and 154'. Each of the above solid hemostatic body configurations may be applied to address bleeding wounds at various body sites. The flexible strap-like handle 144 of embodiment 140 provides a further indication for replacement and retrieval of the hemostasis body 142, the curved handle 154 'of the irregular irregular hemostasis body 152' with relief. Easy to operate and adjust position.

  Still another hemostatic device 160 is shown in FIGS. The hemostatic device 160 is formed from a body 162 having outwardly curved curved skin contact surfaces 164 and 166. The surfaces 164 and 166 may be identical or may be of different curvatures to enhance versatility in the application of the present embodiment 160. The body 162 is formed from a hemostatic material 163 as described below.

  Another integrated embodiment of the present invention is shown generally at 170 in FIGS. This embodiment has the reinforcing fibers mixed with the hemostatic material 176 before the body 172 is compression molded. Opposite skin contact surfaces 174 are provided. In FIG. 37A, the reinforced hemostatic material 176 of the body 172 is further reinforced by the screen backing 177 adhered to one of the skin contact surfaces 174. In FIG. 37B, the body 172 is reinforced with a thicker reinforced foam backing 178, while in FIG. 37C the body 180 is formed with the mesh material mixed with the hemostatic material 184. In FIG. 37D, a hemostatic body 186 is formed utilizing a rigid or semi-rigid hemostatic powder 190 filled with a very open foam. Then, in FIG. 37E, various additives may be mixed with the hemostatic material 196 to form the hemostatic main body 192 having the skin contact surface 194. The additive 196 incorporated into the hemostatic material may be of various forms, such as, for example, binding additives, lubricants, and antimicrobials.

  In Figures 38A and 38B, arrays 200 and 204 of compact solid hemostatic bodies 202 and 206 compacted with powdered hydrostatic material are provided, but despite their small size, the free particles Reduce the soiling associated with the hydrostatic powder material. The hemostasis bodies 202 and 206 may be of similar shape and size to the KITTY LITTER, again reducing the contamination associated with the powdered hemostatic material used to compact these hemostasis bodies 202 and 206. .

  In Figures 39, 40 and 41, a true circular flat hemostatic device 210 formed from an annular hemostatic body 212 is provided. A central hole 214 is formed therethrough, the central hole 214 having a dimension through which a cannula of a catheter slidably inserted therein passes. It may be packaged as shown in FIG.

  FIG. 42 shows a hemostasis assembly 220 formed by attaching a plurality of small irregularly shaped solid hemostatic body 226 to a soft, resilient, inert carrier 222 having an adhesive surface 224. This embodiment 220 encourages the pressure of the hemostasis body 226 to be applied to various irregularly shaped skin surfaces. In FIG. 43, one embodiment 230 of the irregularly shaped hemostasis body 234 is shown running along the length of a thread or wire 232. And, in FIG. 43A, a plurality of these hemostatic assemblies 230 may be interwoven to form hemostatic mat 236.

  In FIGS. 44 and 45, a hollow hemostatic body 242 containing a foam insert 244 forms the hemostatic assembly 240 to reduce the volume of compressed hemostatic material.

Example 1
Forming Pressure The hemostatic composition for the powder is preferably a 1: 7 ratio by weight of iron salt: hydrogen resin mixture, but this ratio has a range of 1: 3 to 1:12. The hydrogen resin is preferably a 2% cross-linked sulfonated poly (styrene) resin in hydrogen form. The hydrogen resin may be available as insoluble intact beads in the range of 500 microns, or may be ground into much finer pieces of average size of 80 microns to 200 microns. The formation of the device is partly based on the ratio of broken resin to intact beads. The cross-linked hydrogen ion exchange resin does not melt due to the increase in temperature, nor does it cause a cold flow due to pressure. Therefore, it is impossible to mold only the intact resin beads themselves into a flat plate by pressure.

  As seen in row 3 of FIG. 46, at 45 kpsi (about 310.264 MPa), intact beads do not bond together to form a solid. As shown in the third row of FIG. 46, the mixture of intact beads and fragments (61-89%: 39-11%) will bind to each other. As shown in the first row, a sufficient fraction of fragments to intact beads (40 to 100%: 0 to 60%) fills the interstices generated when the intact beads are stacked, and mechanically mechanicalizes the material. It is necessary to form a useable solid by allowing sufficient interaction to bind tabularly.

  All or part of the fragments may be a resin alone or may be substituted with other additives to fill the gaps between the intact resin beads. The additives are potassium ferrate (preferred), a binder (stearate, wax), a solid lubricant, an antimicrobial agent, to increase the packing density and the contact surface to form a strong flat plate. It may be a combination of one or more of other amorphous solid materials (calcium carbonate) and other non-spherical absorbent materials that do not have the same size as the resin.

Example 2
Minimal Thickness As seen in FIG. 47, a hemostatic powder, which is preferably a 1: 7 potassium ferrate: hydrogen resin, was prepared into a plate-like solid using a laboratory press. A flat plate pre-plating test of about 0.5 mm to 30 mm established a minimum thickness of about 0.5 mm for compressing the hemostatic powder into a solid device. The picture in FIG. 47 shows that a thickness of at least 0.5 mm is required to produce a fully usable flat plate. The material was milled to <250 pm. However, changes in milling size can affect the minimum thickness of powder needed to form a complete plate. Based on ease of handling or use, thin (0.53 mm) 20 mm diameter flat plates (# 3) made at 45 K psi (about 310.264 MPa) are thin flat plates at a forming pressure of 29 K psi (about 199.948 MPa) It had stronger binding than that. In Test # 1, 29 Kpsi (about 199.948 MPa) was insufficient to form a 0.426 mm thick flat plate, but in Test # 2, a brittle unstable flat plate of 0.535 mm thick was formed.

  Three tests evaluated the available hemostatic devices at the time of application: density test, formation test, and fragility test.

Example 3
Density Test In FIG. 48, a plate density test was used to determine the relationship between solid density (ml / g) and forming pressure (psi) in the range of 8 K (about 55.158 MPa) to 45 K psi (about 310.264 MPa) . Above 45 Kpsi (approx. 310.264 MPa) the increase in density with pressing pressure appears to be flat. The pressure of 45 Kpsi (about 310.264 MPa) is the maximum rated pressure of the 20 mm round table die used in the test to determine the amount of force required to form a solid plate. The integrity of the plate was determined by measuring the harness and wetting rate. In addition, manual fracture of multiple plates was also performed to select appropriate plate parameters.

Test on a single LANE STOKES disc press, a laboratory press, using 1/8 inch thick 20 mm round dies (0.487 in ² (about 3.142 cm ² )) When I did it, the following was shown.
Below 8 K psi (about 55.158 MPa), the flat plate is too brittle and difficult to handle, and often breaks when removed from the die.
Between 12 Kpsi (about 82.737 MPa) and 15 Kpsi (about 103.421 MPa), the flat plate can be handled but is easily broken.

  The flat plate is satisfactory between 20 L and 33 K psi (about 227.527 MPa). A further evaluation was performed at 29 Kpsi (about 199.948 MPa).

Example 4
Vulnerability Test This Flat Plate Vulnerability Test is based on the following FDA Guidelines for Flat Plates.
Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions: Annex 9 Disc Friability General Chapter
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM176888.pdf

  For fragility, determine the mass loss during the tumbling test. The plate is dropped 100 times from a specific height and measurements are made to determine how much mass has been lost. According to the USP, the average loss should be less than 1% of the plate, unless otherwise specified by dosier.

  The USP test ensures that the plates packed in bottles with a number of other plates do not lose weight prior to ingestion by the patient. Loss of mass reduces the amount of drug taken. In the case of a hemostatic plate applied topically, there is no drug prescribed, and more importantly, the plate is packaged in individual units and protected to ensure that the plate is intact upon arrival Will be done. The risk of any breakage will be mitigated by the packaging.

  The modified plate fragility test was designed to pour the plate from the beaker through a 2 inch (5.08 cm) PVC tube into the receiving beaker. The height from the top of the PVC to the face of the receiving beaker was 150 mm (based on USP vulnerability protocol). The plate fragility test showed that the average loss was 2.5%. The amount of loss is acceptable. This is because the plate is applied externally / topically to the wound surface, and the unitized, protected packaging reduces damage.

Example 5
Adhesion Test A 20 mm plate and free powder prepared from the same composition of 1: 7 potassium ferrate: hydrogen resin was tested for its ability to achieve adhesion to the bleeding surface. The blood sealant test was adopted as follows.
1.0.10 mL of EDTA stabilized pig blood was placed in a 1 inch (2.54 cm) diameter circle drawn in a plastic boat and spread evenly.
2. The test material was poured or placed on the uniformly spread blood.
3. Moderate manual pressure was applied on the test material for 90 seconds.
4. The blood sealant formed by the action of the blood and the test material was tested for its adhesion and strength by scraping with a spatula.

  As a result, the free powder produced a non-uniform blood sealant exhibiting moderate adhesion, and when scraped, provided moderate strength with respect to the lifted sealant. The excess portion of unused free powder was exposed to the atmosphere, inactivated, and largely lost the ability for further use. On the other hand, the above-mentioned 20 mm diameter flat plate is broken into two parts, and the first part shows a blood sealant that is thicker and exhibits excellent adhesion and strength, and the second part is unused And had a substantial portion of the intact plate. The second part of the used flat plate remains as a reservoir for stopping absorption of bleeding and exudates.

Example 6
Comparison of powder and solid plate in hemostasis As shown in FIG. 49, regarding the hemostatic effect of 20 mm diameter flat plate and free powder prepared from the same composition of 1: 7 potassium ferrate: hydrogen resin, low pressure gravity flow system It was used and tested. As a result, for the low pressure gravity flow system, there was no impact on hemostasis when comparing the mechanical compression of the powder with the use of the free powder itself. In the following example, it was clearly shown that in the high air pressure test, the plate has a surprisingly excellent performance as compared to the free powder.

Fill a 60 ml syringe with about 25 ml of blood. The test block is formed from a 1.5 inch (3.81 cm) clear acrylic block. An inlet hole designed to fit a fitting with a suspension that connects to a 1/4 inch (0.635 cm) flexible vinyl tube, and an 1/8 inch (about 0.318 cm) diameter outlet hole Assume. The syringe is raised 30 cm above the top of the test block to produce a pressure of 30 cm H ₂ O equivalent to 20 mm Hg (mercury) (about 2.666 kPa).

  Open the valve and put the blood on the surface. The valve was closed and blood was spread to about 0.5 inch (about 1.27 cm) from the outlet. The test material was placed on the blood covering the outlet hole. The contact pressure was maintained at 100 grams mass for 60 seconds. After 60 seconds, the 100 gram mass was removed and the valve was opened for 30 seconds. If blood did not exit the outlet hole, sealing of the outlet hole would have occurred and the test sample passed the test.

As shown in Table 1 below, powder (N = 5) and tablet (Tablet) (N = 10) passed all tests.

Example 7
Sealed Test Powders vs. Solid Plates The hemostatic effect of 20 mm diameter plates and free powder prepared from the same composition of 1: 7 potassium ferrate: hydrogen resin was tested using a high pressure system. The details of the study design and experiments are described below. An outline of the apparatus is shown in FIG. In the hemostatic effect during the hyperbaric test, the results showed that the plate was unexpectedly superior to the free powder. Compared to the unanticipated free powder, the plate produces a significantly stronger seal that can stop bleeding at higher pressures. This surprising finding means that the uniform surface of the plate allows an extremely large manual pressure to be exerted on the blood as compared to the free powder which provides an uneven and irreproducible force on the blood. Do. Furthermore, the compact nature of the plate in contact with blood, and the large reservoir of the composition concentrated in the plate, are significantly superior to rapid dehydration and the low density free powder. Enable bonding. The very large surface area of the free powder will lead to the expectation that the powder will work significantly better than the plate which is only in small surface contact with the blood.

  In this test, a test block is produced from a 1.5 inch (3.81 cm) clear acrylic block. The test block is 1/8 inch (about 0.318 cm) with an inlet hole designed to mate with a hanging joint that connects to a 1/4 inch (0.635 cm) flexible vinyl tube. And an outlet hole of a diameter. The first step is to pull back the piston of the syringe, turn on the pressure gauge, and set the pressure gauge to record the maximum value. Push the piston of the syringe and apply pressure to the above system until the blood sealant breaks down. The pressure gauge records the maximum pressure generated just prior to the failure of the sealant. The next blood is placed around the 1/8 inch exit hole. Thereafter, a flat plate is placed on the blood. Care is taken that the blood completely surrounds the hole and that the plate completely covers the hole. Using a gloved finger, apply slight manual pressure to the flat plate. The pressure pushes liquid blood from under the flat plate. After freezing the plate for about 15 seconds, push the piston.

  During the first attempt, the maximum reading of the pressure gauge reached 408 mm Hg (about 54.396 kPa) and the tube was removed from the syringe. A zip tie was used to prevent further removal and a pressure of 500 mm Hg (about 66.661 kPa) was set at the end.

  The plate was tested 15 times, all consistently reaching an end point of 500 mm Hg (about 66.661 kPa) without failure of the sealant. On the other hand, the free powder only reached an end point of 100 mmHg (about 13.332 kPa), showing excellent performance beyond the expectation of the plate.

  The relatively liberated powder reached an average holding pressure of 310 mm Hg (about 41.330 kPa) in the same test. A small foil disk was used to prevent the powder from clogging the holder during the free powder test and blocking the holder. The powder also needed 75 g mass to maintain the integrity of the sealant. Surprisingly, the solid was better preformed than the free powder without the addition of a mass to hold the solid placed on the simulated wound.

Example 8
Oxygen formation Potassium ferrate decomposes when wet. During decomposition, potassium ferrate released oxygen gas:
2K ₂ FeO ₄ + 2H ₂ O → Fe ₂ O ₃ + 4 KOH + 1.5 O ₂ (g)

  The test is designed to measure the amount of oxygen produced upon wetting with a mass of PRO QR powder and a powder of similar mass compressed into a flat plate. For this test, 45 K psi (about 310.264 MPa) was applied to 2-3 grams of powder in a 20 mm diameter flat die using a laboratory press. During processing, 29 Kpsi (about 199.948 MPa) will typically be required to produce a 20 mm diameter flat plate. In this test, excessive force is used to further enhance the possibility of decomposition of potassium ferrate by mechanical compaction of the powder.

  This test led to the conclusion that when wet the powder released 3.90 ml oxygen gas per gram and the compressed powder of the powder would release 4.05 ml oxygen gas per gram . The difference in the recovered oxygen between the powder and the flat plate is 3.77% in proportion. This difference is within the 5% coefficient of variation used to show good analytical testing. Thus, it can be concluded that the results are nearly identical and that no decomposition of potassium ferrate by compacting the powder into flats occurs.

  In this experiment, the powder or plate sample is placed in a small dry bottle. The bottle is sealed, providing a closed system in which any gas produced is forced out through a small tube. The outlet of the outlet tube is arranged so that air bubbles enter into a filled (water filled) measuring cylinder which is partially submerged and inverted. When air bubbles enter the measuring cylinder, they replace the same volume of water. Thereby, the generated gas can be measured.

  When the powder or plate gets wet, the potassium ferrate decomposes to release oxygen. The test material is placed in a dry bottle of the closed system. Water is injected into the bottle using a syringe. In this test, 15 ml of water was injected each time. This volume of water was taken into account in the calculation. The measuring cylinder was also replaced with a 50 ml burette for more accurate reading of the results. The starting point of the gas measurement was the displacement point generated by injecting 15 ml of water into the closed bottle of the closed system.

Example 9
Disc Collapse Test This test is designed to measure the time it takes for the hemostasis plate to physically break down into constituent material in water. The flat plate is formed by manually compressing a powder composed of a hydrophilic polymer which swells when it absorbs water, and potassium ferrate. The wetting and swelling of the polymer causes the flat plate to collapse. The wetting rate depends on the pressure at which the plate is pressed.

  In this experiment, water is allowed to flow across the flat plate in the tube. The flat plate is supported in a 2.9 cm diameter tube using a sieve with an opening of about 2 mm. Raise the siphon break and keep the water level 2 inches (5.08 cm) to 3 inches (7.62 cm) above the sieve. The flow rate in this test was 562 ml / min. The end point was when no material was present on the sieve.

  Turn on the pump. Drop the disc into the tube while flushing with water and start the stopwatch. The disc is observed and time is recorded when no material is present on the screen.

  Nine flat plates were produced on a laboratory press with 20 mm dies at various amounts of force. Machine-made samples were made on a Stokes single-lane flat plate press. The machine produced a sample with an average weight of 1500 mg for the laboratory press. Fifteen samples were produced on the Stokes single lane disc press. Average mass 750 mg. All plates tested had a similar thickness of approximately 1/8 inch (about 3.175 mm).

  The disintegration rate should be linear to the pressure applied to the plate in the range of 8 Kpsi (about 55.158MPa) (disruption time: 40 seconds) to 45 Kpsi (about 310.264 MPa) (disintegration time: 180 seconds) , 20 mm diameter circular flat plate is shown. Thus, the rate of wetting or disintegration is related to the density of the particles and the capillary action that wets the "next" layer of material, with a minimum preferred disintegration time of 40 seconds being 8 Kpsi (about 55.158 MPa). Is achieved by the formation pressure of

  While numerous illustrative aspects and embodiments have been described above, one of ordinary skill in the art would recognize certain modifications, variations, additions, and combinations thereof. Accordingly, the appended claims and the following claims are intended to cover all modifications, variations, additions, and combinations thereof within the true spirit and scope of the present invention.

10. Hemostatic device 11. Hemostatic device 12. Hemostasis body 13. Hemostatic material 14. Canal access slot 15. Skin contact surface 16. Slot proximal end 17. Body segment 18. Slot entry corner 19. Cannula Access Hole 20. Hemostasis assembly 21. Segment opening 22. Foam backing 22a. End 23. Access hole segments 24. Rigid back 25. Body segment 26. Canal access slot 30. Hemostatic device 32. Half body portion 34. Fitting end 35. Skin contact surface 36. Catheter access hole forming half 37. Skin contact surface 38. Slot entrance corners 39. Foam backing 40. Hemostatic device 42. Half body portion 44. Folding line 45. Skin contact surface 48. Groove thickness 48. Skin contact surface 50. Hemostatic device 52. Hemostasis body 54. Smooth skin contact surface 56. Convex skin contact surface 58. Hemostatic material 60. Hemostasis assembly 62. Hemostasis body 63. Hemostatic material 64. Rigid outer backing 66. Skin contact surface 68. Outer surface 70. Hemostasis assembly 72. Hemostasis body 73. Hemostatic material 74. Rigid outer backing 76. Skin contact surface 78. Outer surface 80, 80 ', 80 ". Hemostatic bandage 82, 82'. Adhesive carrier 84, 84". Hemostasis body 85, hemostatic material 86, 86 '. Adhesive surface 88. Skin contact surface 90, 90 '. Hemostatic bandage 92. Main body array 94. Hemostasis body 94 '. Body array 95.95 '. Hemostatic material 96. Skin contact surface 97. Hemostatic material 98.98 '. Skin contact surface 99. Curves 100, 110, 12Q, 130, 140, 150, 150 '. Hemostatic devices 102, 112, 122, 132, 142, 152, 152 '. Hemostasis body 104, 114, 124, 134, 154, 154 '. The handle 106, 116, 126, 136, 146, 156, 156 '. Skin contact surface 108. Blunt end surface 118. Curved body end 144. Flexible cord handle 148. Curved body end 158. Curved body end 160. Hemostatic device 162. Hemostasis body 163. Hemostatic material 164.166. Convex skin contact surface 170. Hemostatic device 172. Hemostasis body 74. Skin contact surface 176. Fiber filled hemostatic material 177. Rigid backing 178. Foam backing 180. Hemostasis body 182. Skin contact surface 184. Hemostatic material 186. Hemostasis body 188. Skin contact surface 190. Additional hemostatic material 192. Hemostasis body 194. Skin contact surface 196. Hemostatic material 200. Array 202. Hemostasis body 204. Array 206. Hemostasis body 210. Hemostatic device 212. Hemostasis body 214. Cannula Access Hole 216. Hemostatic material 220. Hemostasis assembly 222. Inert carrier 224. Adhesive side 226. Irregular hemostasis body 230. Hemostasis assembly 232. String or wire 234. Irregular hemostasis body 236. Hemostatic mat 240. Hemostasis assembly 242. Hollow hemostasis body 244. Foam insert

Claims (6)

A solid hemostatic plate used in a method of stopping blood flow from a bleeding wound,
The solid hemostatic plate defines a proximal portion and a distal portion and is formed by compressing an insoluble cation exchanger and a powder of ferrate, and prior to compression, the insoluble cation exchanger is formed of beads. becomes, at least 40% of the beads will be crushed, prior to SL method,
Applying the proximal portion directly to the bleeding wound and applying pressure to the distal portion of the hemostatic plate, in any orientation of the bleeding wound;
Promoting the blood coagulation in the wound by the ferric salt in the proximal part;
To seal the bleeding wound in the cation exchange of the proximal portion, to form a sealant on the wound, wherein said distal portion is separated from the proximal portion, the proximal portion A solid hemostatic plate comprising the insoluble cation exchanger and the ferrous salt forming a reservoir for sustained and long-term protection against further bleeding and exudation. A hemostasis device adapted to be applied directly to a bleeding wound, wherein
Including a solid hemostatic plate defining a proximal portion and a distal portion;
The solid hemostatic plate is formed by compressing powder of insoluble cation exchanger and ferrate, and prior to compression, the insoluble cation exchanger consists of beads and at least 40% of the beads are crushed. ,
The proximal portion is applied directly to the bleeding wound and pressure is applied to the distal portion,
The proximal portion forms a sealing agent for sealing the bleeding wound on the wound by promoting blood coagulation in the bleeding wound;
A hemostatic device, wherein said distal portion peels off from said proximal portion , said proximal portion forming a reservoir for continuous and long-term protection against further bleeding and exudation.   The hemostatic device according to claim 2, further comprising a reinforcing backing layer adhered to and covering one surface of the solid hemostatic plate. A hemostasis device adapted to be applied directly to a bleeding wound, wherein
Including a solid hemostatic plate defining a proximal portion and a distal portion;
The hemostasis plate is formed by compressing powder of insoluble cation exchanger and iron salt, and prior to compression, the insoluble cation exchanger consists of beads and at least 40% of the beads are broken up,
In either direction of the bleeding wound, the proximal portion is applied directly to the bleeding wound and pressure is applied to the distal portion of the hemostasis plate,
The ferric salt in the proximal part promotes blood coagulation in the wound, and the cation exchanger in the proximal part forms a sealing agent on the wound for sealing the bleeding wound. ,
The distal portion peels off from the proximal portion, and the insoluble cation exchanger and the ferrate in the proximal portion hold a reservoir for sustained and long-term protection against further bleeding and exudation. Hemostatic device to form. A hemostasis device for preventing bleeding from a catheter wound caused by the presence of a catheter in the wound, comprising:
Including a solid hemostatic plate defining a proximal portion and a distal portion;
The hemostatic plate is formed by compressing powder of insoluble cation exchanger and ferrate , and prior to compression, the insoluble cation exchanger consists of beads, and at least 40% of the beads are crushed ;
The flat plate has two separate halves which, when fitted along the mating end, define a catheter access hole for receiving a catheter,
The proximal portion forms a sealing agent on the catheter wound for sealing bleeding of the catheter wound by promoting blood coagulation in the catheter wound;
A hemostatic device, wherein the distal portion peels off the proximal portion, and the proximal portion forms a reservoir for continuous and long-term protection against further bleeding and exudation of the catheter wound. A solid hemostatic plate used in a method of stopping blood flow from a bleeding wound,
The solid hemostatic plate has a skin-contacting surface and a distal side, and is formed by compressing powder of insoluble cation exchanger and ferrate, and prior to compression, the insoluble cation exchanger consists of beads, At least 40% of the beads are crushed;
The method is
By applying the skin contact surface directly to the bleeding wound and applying pressure to the distal side of the plate, the skin contact surface promotes blood coagulation and forms a sealing agent on the bleeding wound ,
After formation of the sealant, a portion of the unused portion of the plate is separated from the sealant, and the remaining portion of the unused portion of the plate is for continuous and long-term protection against further bleeding and exudation. Solid hemostatic plate, including forming a reservoir.