WO2007033135A2

WO2007033135A2 - Process for manufacturing hemostatic agents and their uses

Info

Publication number: WO2007033135A2
Application number: PCT/US2006/035417
Authority: WO
Inventors: Robert E. Moore
Original assignee: Imed Scientific Corporation
Priority date: 2005-09-13
Filing date: 2006-09-13
Publication date: 2007-03-22
Also published as: WO2007033135A3

Abstract

Disclosed herein is a composition and method for applying a hemostatic agent in a granular form that incorporates easy application and removal. In a first illustrative embodiment the hemostatic agent is a synthesized manganese oxide having a selected crystalline structure. The manganese oxide when attached to or encased with materials will effectively adsorb water from flowing body fluid and concentrate the cellular matter to initiate the clotting process. Additionally disclosed is a process for making molecular sieve in paper-like and rubber-like forms. These forms allowed more efficient use of molecular sieve in a variety of industrial applications.

Description

PROCESS FOR MANUFACTURING HEMOSTATIC AGENTS AND THEIR USES

CROSS REFERENCE TO RELATED APPLICATIONS This Patent Application claims priority from U.S. Provisional Patent Application

Serial No. 60/716,784, filed on September 13, 2005 and U.S. Provisional Patent Application Serial No. 60/724,030, filed on October 6, 2005, the contents of which are incorporated herein by reference in their entirety.

BACKGROUND

1. Technical Field

The present disclosure relates generally to the process of manufacturing molecular sieve in paper-like and rubber-like forms, and more particularly, to the process of manufacturing sieve materials for us as hemostatic agents and for other industrial uses.

2. Description of the Related Art

As is well known, many medical procedures involve body fluid loss, including but not limited to blood. Conservation of body fluids and constituents thereof is crucial to medical procedure success rate and to promote rapid healing and reduce the risk of infection.

Body fluid loss and conservation of that body fluid arise under a variety of situations. One situation occurs with acute trauma. Generally, acute trauma is the result of a serious accident or a battlefield injury. When this occurs, the patient can be in a life- threatening situation from exsanguination, among other things. Stopping blood loss and conserving blood components becomes a priority and failure to do so can result in death. An agent that stops bleeding and fluid loss quickly and efficiently represents a valuable tool for medical professionals and first responders.

Another situation under which the patient can experience body fluid loss is during surgery. Surgical procedures are almost always undertaken in the tightly controlled environment of the surgical suite. There are, however, still situations that are problematic. Surgeries on the liver, spleen, and bone can result in extreme blood loss even under the best conditions. Efforts are made to keep surgical time, including time under anesthesia, to a minimum. Additionally, minimizing blood loss and the subsequent need for transfusions is critical to the success rate of surgery.

Other situations where body fluid loss arises include, but are not limited to, burns, scratches, abrasions, minor cuts, and other common injuries. In particular, burns are a common injury that are difficult to treat because of the large area of the body usually involved, pain, the high risk of infection, and the general nature of the healing process. To control burns it is important to minimize fluid, electrolyte, and protein loss to promote rapid healing without infection.

Controlling fluid loss has been approached using various hemostatic agents and application methods. Previous solutions can be grouped into a few general classes; however, many incorporate a common approach, which is to trigger the clotting cascade by concentrating the natural cellular promoters of clot formation.

A large group of products addressing fluid loss are hemostatic agents derived from collagen. In the natural clotting process, platelets adhere to collagen and are then activated. Hemostatic products such as University of Arizona's MedStat-F™, Davol, Inc.'s Avitene©, Pharmacia and Upjohn's Gelfoam®, and Integra NeuroScience's Helistat® are all based on collagen. These are animal source collagen products and must be treated accordingly to ensure that they are non-pyrogenic and non-immunogenic. Unfortunately, animal based products require expensive collection and processing procedures to minimize immunogenicity and pyrogenicity. Nycomed Austric GmbH's TachoComb® is also a collagen product coated with fibrinogen, thrombin, and aprotinin. These are naturally occurring clotting agents, however, and unfortunately they can be very expensive and not practical for wide spread use. Furthermore, as they are naturally occurring the quality of the product may vary from lot to lot.

Another group of hemostatic agents are a variety of molecular sieves. These materials adsorb water and concentrate the cellular material, thus initiating the clotting process. Z-Medica's QuickClot™, a zeolite, is one of these products. Molecular sieves absorb water through the process of hydration. Unfortunately, hydration is an exothermic reaction which can create large amounts of heat. Significant heat caused by hydration can lead to tissue damage causing short and long term side effects. Most of the approaches and products mentioned above are in powder or granular form and are applied by sprinkling or dusting the wound. These application methods make accurate and precise application of the products difficult. Moreover, some of these products are non-biodegradable and must be removed from the body. Removal of powders and granules is difficult to achieve quickly and efficiently. This can become a problem in emergency rooms and aid stations where it may be necessary to treat many patients promptly and efficiently, Removal of non-biodegradable products is necessary to minimize the potential for granulomas, adhesions, and increased infection rates. Unfortunately, non-biodegradeable products have a potential for long-term complications if they remain in the wound.

Therefore, it would be desirable to overcome the disadvantages and drawbacks of the prior art with product or products that utilizes chemical hemostatic agents in forms that are easily applied to specific areas with accuracy and precision. Additionally, it would be desirable to apply a hemostatic agent that can be removed completely from the site of injury quickly and efficiently. It would be of a substantial advantage to the art to utilize an application method that allows large areas of injury to be easily covered by a hemostatic agent. It would also be advantageous to apply a hemostatic agent that does not create tissue damage during use.

SUMMARY

Accordingly, to overcome the disadvantages and drawbacks of the prior art, an application of chemical hemostatic agents is provided that utilizes chemical hemostatic agents in forms that can be accurately applied, quickly initiate clotting action, are easily removed if necessary and do not cause any permanent tissue damage.

According to an aspect of the current disclosure, the method of application utilizes synthesized manganese oxide as an effective chemical hemostat. The manganese oxide is synthesized according to U.S. patents 6,503,476, 6,486,357, 5,702,674, and 5,635,155, which are incorporated by reference in their entirety. Manganese oxide synthesized by the above referenced patents and contemplated by the current disclosure advantageously self-assembles into helices, rings, and strands forming an advantageous porous crystalline structure. The current disclosure also contemplates manganese oxide as an octahedral molecular sieve. The molecular sieve can by synthesized to produce manganese oxide hydrates of various structures, including, but not limited to, pyrolusite, nsutite, romanechite, todorokite, and hollandite. These synthesized forms of manganese oxide offer greater purity and crystallinity and porosity than various naturally occurring minerals.

Desirably, the hydration of manganese oxide of these forms and application thereof creates insignificant heat. Therefore, no considerable thermal tissue damage occurs with application according to the current disclosure. The present disclosure provides, among other things, a method for applying synthesized manganese oxide in a granular form that incorporates easy application and removal of the inorganic product. The structure of the granular material allows for controlled release of medicaments and can be engineered to specific pore size to selectively allow the passage of biomolecules in either direction. According to another aspect of the current disclosure, the synthesized manganese oxide is attached to or encased in a material including, but not limited to, Teflon®, silk, cotton, rayon, Tefla™, gauze, paper, or other fabrics that will readily conform to the contours of the body. Desirably, the manganese oxide when attached to or encased with materials will effectively adsorb water from flowing body fluid and concentrate the cellular matter to initiate the clotting process. Synthesized manganese oxide in combination with the binding and encasing materials according to the invention is easily applied and removed.

According to yet another aspect of the current disclosure, the synthesized manganese oxide is incorporated into a paper like material that will readily conform to the contours of the body. Desirably, the synthesized manganese oxide when incorporated into a paper like material will effectively adsorb water from flowing body fluid and concentrate the cellular matter to initiate the clotting process. Synthesized manganese oxide in combination with the paper like material according to the invention is easily applied and removed. According to further aspect of the current disclosure, a block polymer is utilized in the method of application. The polymer can be used as a support for the synthesized manganese oxide and or for additional haemostatic agents to increase the overall efficiency of the final product. The block polymer in itself is a hemostatic agent and in a first illustrative embodiment is comprised of alpha hydroxyacids, alcohols, and glycols. These block polymers according to the invention can be engineered for biodegradability and molecular characteristics beneficial to specific applications, i.e., to allow for various surgical or healing requirements. The block polymers may be formed into sheets, strips, foam, sponges, gels, or other various particle forms. The polymer in these forms is biologically absorbable and non-reactive. Most desirably, the product, when formed in large, thin sheets is strong and pliable materials that may be used to protect large area wounds including, but not limited to bums. The large area polymeric sheets allow for the passage of water and air, but are advantageously not bacterial. This embodiment of the current disclosure will minimize fluid loss and reduce the incidence of infection while allowing for easy application to a specific injury site.

In another application of the current disclosure, the block polymers may be in a soft and pliable form. The pliable polymers can be used to form a plug that can be utilized during catheterization procedures to eliminate excessive bleeding from a puncture site. Due to the absorbable and hemostatic nature of the polymer, it can be produced to be used in dental extractions to reduce the incidence of dry socket.

According to further aspect of the current disclosure, a hemostatic ointment is utilized in the method of application. The hemostatic ointment is comprised of silver and calcium compounds incorporated into a starch based hemostatic agent such as but not limited to amylopectin phosphate, 2-hydroxyproply ether. This hemostatic ointment according to the invention can be engineered for biodegradability and molecular characteristics beneficial to specific applications, i.e., to allow for various surgical or healing requirements. Along with use as a hemostatic agent for humans, it also has application within veterinary application.

According to further aspect of the current disclosure, a hemostatic dry aerosol is utilized in the method of application. The hemostatic dry aerosol is comprised of silver and calcium compounds incorporated into a starch based hemostatic agent such as but not limited to amylopectin phosphate, 2-hydroxyproply ether. This dry aerosol formulation is incorporated with dry flow agents known in the art to allow for ease of application. This hemostatic dry aerosol according to the invention can be engineered for b molecular characteristics beneficial to specific applications, i.e., to allow for various surgical or healing requirements. Along with use as a hemostatic agent for humans, it also has application within veterinary applications.

According to further aspect of the current disclosure, a hemostatic bandage is utilized in the method of application. The hemostatic bandage is comprised of a natural or polymeric fabric sheet having a layer of silver and calcium compounds incorporated into a starch based hemostatic agent such as but not limited to amylopectin phosphate, 2- hydroxyproply ether. This hemostatic bandage according to the invention can be engineered for biodegradability and molecular characteristics beneficial to specific applications, i.e., to allow for various surgical or healing requirements. Along with use as a hemostatic agent for humans, it also has application within the veterinary practice.

According to yet another aspect of the current disclosure, a physiologically degradable hemostatic bandage is utilized in the method of application. The physiologically degradable hemostatic bandage is comprised of a polymeric sheet encasing hemostatic compounds such as silver and calcium compounds incorporated into a starch based hemostatic agent such as but not limited to amylopectin phosphate, 2- hydroxyproply ether. This physiologically degradable hemostatic bandage according to the invention can be engineered for biodegradability and molecular characteristics beneficial to specific applications, i.e., to allow for various surgical or healing requirements. In particular, according to the invention, a polymeric sheet is wrapped around the hemostatic material. Along with use as a hemostatic agent for humans, it also has application within the veterinary practice.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS Detailed embodiments of the present invention are disclosed herein, however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which may be embodied in various forms. Therefore, specific functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed embodiment.

A chemical composition alone or incased in a fibrous article and method for the enhancement of clotting in wounds and surgical incisions according to the invention is described. According to a first illustrative embodiment a hemostatic agent comprised substantially of synthesized manganese oxide is used as effective chemical hemostat. The manganese oxide is synthesized according to U.S. patents 6,503,476, 6,486,357, 5,702,674, and 5,635,155, which are incorporated by reference in their entirety. Manganese oxide synthesized by the above referenced patents and contemplated by the current disclosure advantageously self-assembles into helices, rings, and strands without any imposed concentration gradient. The assembled physical structure of the synthetic manganese oxide has been advantageously found to have desirable hemostatic properties. According to the disclosure the synthesized manganese oxide is dialyzed against a strong Ca solution to increase its calcium content. Without being bound to any particular theory it is thought that the increased calcium content increases the hemostatic properties of the synthesized manganese oxide.

Without being bound to any particular theory, it is thought that assembled physical structure with its porous nature acts as molecular sieve. It is contemplated within the scope of the invention that various molecular sieves can by synthesized to produce manganese oxide hydrates of various structures, including, but not limited to, pyrolusite, nsutite, romanechite, todorokite, and hollandite. These synthesized forms of manganese oxide offer greater purity and crystallinity than various naturally occurring mineral and the crystalline structure with its porous nature offers a hemostatic agent having no exothermic properties upon hydration.

The synthesized forms of manganese oxide according to the invention may be directly applied to wound surfaces or held in place by pressure. It is contemplated within the scope of the disclosure that these synthesized forms of manganese oxide may be free flowing or be supported on or in a containment system. For example, the synthesized forms of manganese oxide may be adhered to the surface of a sheet or film which is applied (e.g., contacted, wrapped, adhered, secured, affixed or otherwise place into a position where blood on the wound area will be absorbed or adsorbed by the synthesized forms of manganese oxide) to areas of a wound or surgical incision.

The synthesized forms of manganese oxide according to the invention may also be provided interspersed with fibers, filaments or other particles in a self-supporting structure, entangled within the fibrous elements of a net, web, fabric or sheet, embedded in a sheet or film (with the manganese oxide enable in a manner for the adsorption or absorption of blood in contact with the wound), a packet of material, with the manganese oxide free-flowing within the confines of the packet. It is contemplated within the scope of the disclosure that the synthesized manganese oxide may be in various physical crystalline structures as produced by the methods in the patents referenced above. It is also contemplated within the scope of the disclosure that the synthesized forms of manganese oxide may be combined with other hemostatic materials such as, but not limited to, porous particulates as described in U.S. Patent No. 6,060,461 to Drake, the teachings of which are incorporated in its entirety by reference.

The manganese oxide according to the invention may also be provided as part of a patch system, with a fibrous network associated with the manganese oxide providing a high level of structural integrity and strength to the applied assembly over the wound or surgical incision, even before clotting has occurred. This would be particularly appropriate where the assembly was being used as a stitch replacement or true wound closure system rather than only promoting clotting. It is contemplated within the scope of the disclosure that the porous particles may easily be associated with or carry additional, but optional, clotting or wound treating materials or ingredients. It is further contemplated that it would be desirable to provide the synthesized manganese oxide with anti-microbials, antifungal agents, topical pain reducing medication, pharmaceutical additives, anti-inflammatants, mixtures thereof and the like. Anti -microbial additives utilized as pharmacological additives within the present disclosure include the biguanides, especially chlorhexidine and its salts, including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate, silver and its salts, including silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such as tobramycin and gentamicin, rifampician, bacitracin, neomycin, chloramphenical, miconazole, tolnaftate, quinolones such as oxolinic acid, norfloxacin, nalidix acid, pefloxacin, enoxacin and ciprofloxacin, penicillins such as ampicillin, amoxicillin and piracil, cephalosporins, vancomycin, and combinations of any of the above anti-microbials.

Additionally, organic compounds derived from plants and herbs having desirable pharmacological properties can be utilized as pharmacological additives. Extracts of plants and herbs have been known to possess anti-microbial activity and their use has been shown to be safe for human and animal consumption. Extracts of such plants, known as phytochemicals, may be utilized for their anti-microbial properties. Some of these extracts, such as grapefruit seed extract, Tea Tree Oil and Myrtle Oil and others can be incorporated into the hemostatic composition and their anti-microbial properties released to the surrounding tissue in an efficacious manner.

In some illustrative embodiments of the present disclosure colorants, emulsifiers, surfactants, pharmaceutical fillers and excipents and color stabilizers that are well known within the art may be added to the hemostatic composition. According to another aspect of the current disclosure, a block polymer is utilized in the method of application. The block polymer according to the disclosure has hemostatic properties and can be used as a support or substrate for additional hemostatic agents to increase the overall efficiency of the final product. In a first illustrative embodiment according to the invention the block polymer is used as a substrate to support the synthesized manganese oxide. It is contemplated within the scope of the invention that the block polymer can be used to support other hemostatic agents known in the art.

According to the invention, the block polymer hemostatic agent is comprised of alpha hydroxyacids, alcohols, and glycols. These block polymers according to the invention can be engineered for biodegradability and molecular characteristics beneficial to specific applications, i.e., to allow for various surgical or healing requirements.

In one illustrative embodiment the block polymer is synthesized according to a synthesis adopted from the literature (Biomaterials Volume 26, Issue 36, December 2005, Pages 7555-7563; Synthesis of degradable poly (1-lactide-co-ethylene glycol) porous tubes by liquid-liquid centrifugal casting for use as nerve guidance channels; Alex Goraltchouka, Thomas Freiera, and Molly S. Shoicheta,), the contents of which are incorporated by reference in their entirety. In a first illustrative embodiment the following synthesis is used to create the block polymer according to the invention:

In further hemostatic block polymers according to the invention, materials such as but not limited to, poly (lactic acid), poly(glycolic acid), poly(caprolactone), polyethylene glycol of molecular weights 200 to 6000, hydroxyvalerate, and B-malonic acid can be used.

In one illustrative embodiment, the formation of a hemostatic block polymer film according to the disclosure is done by casting a solution (methylene chloride) on flat glass plates and drying the solution. Sponges and gels are formed in a similar manner except the drying is done under vacuum and usually includes a water soluble salt or other compound. When the product has been dried of the organic solvent, it is washed with water and the salt is dissolved. This leaves pores, channels, and voids that can be used for channeling water away from the wound. In all these cases the flexibility of the final product is dependent upon the polyethylene glycol molecular weight and concentration in the polymer.

In a further illustrative embodiment according to the disclosure a hemostatic block polymer is formed of about 45% poly(lactic acid), about 45% poly(glycolic acid) and about 10% polyethylene glycol Mw 6000. This particular block polymer forms a porous film according to the disclosure. This block polymer formed as a film can be used as a substrate for at least one additional clotting agent in or on top of the film. It is contemplated within the scope of the disclosure that at least one additional clotting agent can be pressed into the surface of the film or it can be suspended into the solution and dried within the film. It is further contemplated within the scope of the disclosure that formation of a block polymer film having a porous makeup forming a sponge like material, can have synthesized manganese oxide incorporated in the sponge like material.

The block polymers according to the disclosure may be formed into sheets, strips, foam, sponges, or other various particle forms. Desirably, the block polymer in these forms is biologically absorbable and non-reactive. According to the invention the block polymer, when formed in large, thin sheets is strong and pliable that may be used to protect large area wounds including, but not limited to burns. The large area polymeric sheets allow for the passage of water and air, but are advantageously not bacterial. The block polymer according to the invention will minimize fluid loss and reduce the incidence of infection while allowing for easy application to a specific injury site.

In a further illustrative embodiment synthesized manganese oxide according to the disclosure is incorporated in a paper like form by suspending the synthesized manganese oxide with other materials in solution and then drying the material at a controlled temperature. The temperature at which the drying is done determines the ultimate physical characteristics of the finished paper product. Additional materials in this process are any material known in the art that can add strength and increase thickness, such as but not limited to cellulosics or the like.

It is contemplated within the scope of the disclosure that fibers, such as wool, cotton, wood pulp, synthetic fabrics, metals and cellulosics or the like can be added to increase strength and performance characteristics of the paper like material.

It is also contemplated within the scope of the disclosure that it is possible to form this manganese oxide like paper on substrates known in the art such as gauze, screens, webs, and any sort of support. The use of a substrate will give a convenient form, shape and or geometry to the manganese oxide like paper for applications to varying wound or incision sites.

It is further contemplated within the scope of the disclosure that since the manganese oxide is susceptible to magnetic fields, that forming the paper in the presence of an electromagnetic field will align the manganese fibers to enhance the character of the material for this use and other applications that require fibers in a specific orientation.

Example I In an illustrative embodiment according to the disclosure, potassium sulfate, potassium persulfate and manganese sulfate monohydrate are combined in a stoichiometric ratio of 3:3:2 and dissolved in distilled, deionized water (DDW). This mixture is sealed in a Teflon®' stainless steel vessel and heated to about 250 C for about 4 days. This paper like method is partially disclosed in the journal article entitled "Spontaneous Formation of Inorganic Paper-Like Materials" Yuan et al. ( Advanced Materials DOl: 10.1002/adma.200400659) ("Yuan"), the contents of which are incorporated by reference in its entirety. The resulting product is a rigid, solid material that is then suspended in DDW and stirred for 12 to 14 hours producing a slurry. The slurry material is dialyzed against a strong Ca solution to increase its calcium content. The dialyzed slurry is poured onto a glass plate or other appropriate substrate and heated to about 85 C for about 24 hours. After drying the resultant paper like material is removed and ready for use in applications.

Example II. In a further illustrative embodiment according to the disclosure a process and composition of material that allows the efficient and cost effective production of inorganic sieve materials for use in multiple applications is contemplated. In this further illustrative embodiment , manganese oxide can be compounded with a starch or starch like material to form a rubber-like material that can be extruded through a die to generate uniform particles. It is contemplated within the scope of the invention that molecular sieve other than manganese oxide can be used. It is also contemplated within the scope of the invention that the starch can be from plant sources or the starch can be a synthesized starch like material or the like. The generated uniform particles are then thermally rearranged, as set forth in the synthesis shown in Example I. The thermal rearrangement is achieved by placing the uniform particles in a sealed Teflon®, stainless steel vessel and heated to about 250 C for about 4 days as described in Yuan. The resultant octahedral molecular sieve can be used in various applications.

Materials that can be compounded with the molecular sieve to form the rubber-like material include such classes of compounds such as starches, sugars, plasticizers, polyvinyl alcohols, long chain alcohols, mannitol, microcrystalline starch, salts of steric acid, dicalcium phosphate, binding agents or the like. It is contemplated within the scope of the disclosure that it is possible to generate large sheets of molecular sieve material by compounding the molecular sieve with these binding agents at the gel stage of the synthesis. The gel can be extruded or rolled to fit the shape and size required by various applications. The extruded or rolled material is then thermally rearranged by heating to about 250 C for about 4 days to form the finished compound as described in Yuan.

It is further contemplated within the scope of the disclosure that it is possible to dope these resulting compounds with pharmaceutical compounds such as but not limited to antibacterial salts, if the application is medical. In one illustrative embodiment antibacterial salts such as silver in its various salt forms are used to dope the resulting compounds.

Example III.

In a further illustrative embodiment according to the disclosure a process and composition of material that allows the efficient and cost effective production of a hemostatic paste for use in multiple applications is contemplated. In this further illustrative embodiment , a starch or starch like material is incorporated into an ointment or cream base known in the art with an antimicrobial such as soluble silver salts in a concentration of about 100 ppm to about 10000 ppm. Various salt forms of calcium are incorporated to accelerate the clotting process. Optionally an emollient known in the art including but not limited to Glycerol is incorporated into the hemostatic paste according to the disclosure. In one illustrative embodiment a hemostatic paste is formed of the following components: Amylpectin phosphate, 2-hydroxyproply ether 0.1% to 90% w/v Silver citrate 0.01 % to 90% w/v

Calcium citrate 0.01 % to 90% w/v

Glycerol 0.1% to 90% w/v

Example IV.

In a further illustrative embodiment according to the disclosure a process and composition of material that allows the efficient and cost effective production of a hemostatic aerosol for use in multiple applications is contemplated. In this further illustrative embodiment , a starch, starch like material or hydrophilic polymer is finely ground and incorporated in its dry form with an antimicrobial such as soluble silver salts in a concentration of about 100 ppm to about 10000 ppm. Various salt forms of calcium are incorporated to accelerate the clotting process. Dry flow compositions known in the art are incorporate allowing the above powder to be dispensed in an aerosol form. In one illustrative embodiment the hemostatic aerosol is formed of the following components: Amylpectin phosphate, 2-hydroxyproply ether 0.1 % to 90% w/v Silver citrate 0.01% to 90% w/v

Calcium citrate 0.01 % to 90% w/v

Glycerol 0.1% to 90% w/v Flow agent 0.1% to 90% w/v

Example V.

In a further illustrative embodiment according to the disclosure a process and composition of material that allows the efficient and cost effective production of a hemostatic containment package to hold hemostatic material for use in multiple applications is contemplated. In this further illustrative embodiment, a starch or starch like material or hydrophilic polymer finely ground and incorporated with an antimicrobial such as soluble silver salts in a concentration of about 100 ppm to about 10000 ppm. Various salt forms of calcium are incorporated to accelerate the clotting process. The hemostatic containment package is formed in a manner allowing hemostatic agents to be placed within.

In one illustrative embodiment the hemostatic containment package is formed of a natural fiber fabric that is hydrophilic and adsorbent. If the selected material is hydrophobic in nature treatment with a surfactant will allow the fabric to become somewhat adsorbent. In one illustrative embodiment a cloth type containment package is treated with a solution of a silver salt and calcium salt along with a surfactant. The treated containment package is allowed to dry and a starch like hemostatic product is added to the treated containment package. It is contemplated within the scope of the disclosure that other hemostatic agents can be used or optionally mixed with the starch or starch like product. In a first illustrative embodiment the components of the containment package contain the following components: Amylpectin phosphate, 2-hydroxyproply ether 0.1% to 90% w/v

Silver citrate 0.01 % to 90% w/v

Calcium citrate 0.01 % to 90% w/v

Example VI. In a further illustrative embodiment according to the disclosure a process and composition of material that allows the efficient and cost effective production of a hemostatic bandage for use in multiple applications is contemplated. In this further illustrative embodiment, a starch or starch like material or hydrophilic polymer is finely ground and incorporated with an antimicrobial such as soluble silver salts in a concentration of about 100 ppm to about 10000 ppm. Various salt forms of calcium are incorporated to accelerate the clotting process. Binding compositions known in the art are also incorporated allowing the above mixture to be adhered to a natural or polymeric fabric. In one illustrative embodiment the hemostatic bandage is formed of a natural fiber with the following components of a mixture adhered to it: Amylpectin phosphate, 2-hydroxyproply ether 0.1% to 90% w/v

Silver citrate 0.01 % to 90% w/v

Calcium citrate 0.01 % to 90% w/v

Example VII. In a further illustrative embodiment according to the disclosure a process and composition of material that allows the efficient and cost effective production of a physiologically degradable hemostatic bandage for use in multiple applications is contemplated. In this further illustrative embodiment , a starch or starch like material is finely ground and incorporated with an antimicrobial such as soluble silver salts in a concentration of about 100 ppm to about 10000 ppm.. Various salt forms of calcium are further incorporated to accelerate the clotting process. Binding compositions known in the art are incorporated allowing the above mixture to be adhered or embedded into a physiologically degradable polymeric sheet. In another embodiment according to the disclosure the physiologically degradable polymeric sheet is formed into a thin sheet and wrapped around hemostatic material. In a further illustrative embodiment the physiologically degradable polymeric sheet is embedded with a hemostatic material and formed into thin strips that can be placed within a wound having various contours. In one illustrative embodiment the physiologically degradable polymeric sheet has the following mixture of components adhered to it:

Amylpectin phosphate, 2-hydroxyproply ether 0.1% to 90% w/v Silver citrate 0.01% to 90% w/v ^' Calcium citrate 0.01 % to 90% w/v

Although the illustrative embodiments within the disclosure disclose the use of molecular sieve in either paper-like or rubber-like forms for medical uses as hemostatic agents, it will also be appreciated by those skilled in the art that the molecular sieves according to the disclosure can be used as reaction catalysts. Likewise, it will be appreciated by those skilled in the art that the molecular sieve according to the disclosure can be used in petroleum refining. Similarly, those skilled in the art will appreciate that the molecular sieve according to the invention may be used in drug delivery systems. It will further be appreciated by those skilled in the art that the molecular sieve according to the disclosure can be used in applications such as air filtration, liquid filtration and as liquid purifiers.

While the invention has been described with reference to illustrative embodiments, it will be understood by those skilled in the art that various other changes, omissions and/or additions may be made and substantial equivalents may be substituted for elements thereof without departing from the spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A method for making a paper-like molecular sieve comprising the steps of preparing a synthesized manganese oxide having a selected porous crystalline structure, mixing said synthesized manganese oxide with a fibrous material thereby forming a slurry, drying said slurry into a film, and heating said film with a selected temperature and time.

2. The method according to claim 1 wherein said crystalline structure is selected from the group consisting of helices, rings, and strands.

3. The method according to claim 1 wherein said synthesized manganese oxide is manganese oxide hydrates of various structures selected from the group consisting of pyrolusite, nsutite, romanechite, todorokite, and hollandite.

4. The method according to claim 1 comprising the additional step of dialyzing said slurry against a strong Ca solution to increase its calcium content.

5. The method according to claim 4 wherein said film is form onto a fibrous element which is a self-supporting structure.

6. The method according to claim 1 wherein said fibrous material is selected from the group consisting of wool, cotton, wood pulp, synthetic fabrics, metals and cellulosics or the like..

7. The method of claim 5 wherein said fibrous element is a net, web, fabric or sheet.

8. The method according to claim 1 wherein said synthesized manganese oxide in a paper-like form is doped with at least one other composition selected from the group consisting of antibiotics, antifungal agents, analgesics, anti-inflammatory agents and mixtures thereof.

9, The method according to claim 1 wherein said synthesized manganese oxide in a paper-like form is in combination with at least one other hemostatic agent.

10. A method for making a rubber-like molecular sieve comprising the steps of preparing a synthesized manganese oxide having a selected porous crystalline structure, mixing said synthesized manganese oxide with a starch-like material thereby forming uniformed particles, forming said particles into a selected shape, and heating said selected shape with a selected temperature and time.

11. The method according to claim 10 wherein said starch-like material is selected form the group consisting of starches, sugars, plasticizers, polyvinyl alcohols, long chain alcohols, mannitol, microcrystalline starch, salts of steric acid, dicalcium phosphate, binding agents and mixtures thereof.

12. The method according to claim 10 wherein said synthesized manganese oxide in a rubber-like form is doped with at least one other composition selected from the group consisting of antibiotics, antifungal agents, analgesics, anti-inflammatory agents and mixtures thereof.

13. The method according to claim 10 wherein said selected temperature is from about 10° C. to about 500⁰C.

14. The method according to claim 10 wherein said selected time is from about 1 hours to about 200 hours.

15. The method according to claim 10 wherein said use of rubber-like molecular sieve is selected from the group consisting of hemostatic agent, petroleum refining, air filtration, liquid filtration and drug delivery.

16. The method according to claim 1 wherein said use of paper-like molecular sieve is selected from the group consisting of hemostatic agent, petroleum refining, air filtration, liquid filtration and drug delivery.

17. The method according to claim 10 comprising the additional step of dialyzing said uniform particles against a strong Ca solution to increase its calcium content.

18. A method for making a rubber-like molecular sieve comprising the steps of preparing a molecular sieve, mixing said molecular sieve with a starch-like material thereby forming uniformed particles, forming said particles into a selected shape, and heating said selected shape with a selected temperature and time.

19. A method for making a paper-like molecular sieve comprising the steps of preparing a molecular sieve, mixing said molecular sieve with a fibrous material thereby forming a slurry, drying said slurry into a film, and heating said film with a selected temperature and time.

20. A method for making a hemostatic paste comprising the steps of providing a starch or starch like material said starch or starch like material being ground into a fine powder, providing a soluble silver salt, providing a calcium salt mixing said starch or starch like material with said soluble silver salt and said calcium salt forming a hemostatic mixture, and incorporating said hemostatic mixture into an emollient base.

21. A method for making a hemostatic aerosol comprising the steps of providing a starch or starch like material said starch or starch like material being ground into a fine powder, providing a soluble silver salt, providing a calcium salt mixing said starch or starch like material with said soluble silver salt and said calcium salt forming a dry hemostatic mixture, and incorporating said hemostatic mixture into a dry flow composition.

22. A method for making a hemostatic containment package comprising the steps of providing a starch or starch like material said starch or starch like material being ground into a fine powder, providing a soluble silver salt, providing a calcium salt mixing said starch or starch like material with said soluble silver salt and said calcium salt forming a hemostatic mixture, and incorporating said hemostatic mixture into a fibrous containment pouch.