Title of Invention


Abstract The present invention relates to a hemostatic agent adapted to be applied directly onto a bleeding wound comprising: an effective amount of a yacid salt combined with an effective amount of an i change material, said oxyacid salt combining with blood clotting at the wound, said cation exchange mat forming a , protective cover over the wound as blood is thereby clotted.
This invention relates generally to topically applied agents for promoting blood dotting to anrest blood flow from an open wound, and more particularly to a method of applying an anhydrous hemostatic agent which may be mixed with an aqueous media just prior to its application directly over an open bleeding wound or a wound from which body fluid is flowing to accelerate flowing blood and body fluid clotting and enhance healing. PRIOR ART
In addition to conventional bandages, adhesive means, compresses and the like which are applied with pressure directly against a bleeding open wound, considerable effort has been directed toward the development of chemical agents in various forms which accelerate or enhance the coagulation of blood flowing from an open wound to anrest blood flow. Many of these agents are in the "dotting cascade", i.e., fibrinogen, thrombin. Factor Vlll and the like. Others are based upon the use of collagens. Edwardson, in U.S. patents 5.763,411. 5.804,428. and 5,962.026. for example, teaches the use of fibrin in conjunction with a solid support in the '411 patent, and as an enzyme free sealant in the '428 patent, and as a solid hemostatic agent substantially free of catalytic enzymes.
Three U.S. Patents invented by Martin. U.S. 5,692.302, 5,874,479 and 5.981,606. are generally directed to the use of pyruvate in combination with fatty acids and an anti-oxidant as a therapeutic wound healing hemostatic agent
Stilwell, in U.S. Patent 5,484.913 teaches the use of caldum-modified .oxidized cellulose to promote faster hemostasis. In U.S. Patent 5,474,782. Winter, et al. teaches a wound healing hemostatic agent or its salt present in a phannaceutically acceptable carrier, the preferred embodiment being a salt of sodium. Winter provides a wound dressing with a taspine compound for promoting healing rather than dotting.
In U.S. Patent 2,163.588. Cornish teaches a wound pad having very fine fibers carrying a viscous agent and a septic for arresting and clotting blood flow. Eberl, et al., in U.S. Patent 2,688,586, teaches an improved hemostatic surgical dressing with alginic add as a dotting agent Masd. et at In U.S. Patents 2,772,999

and 2.773.000 also teaches hemostatic surgical dressing including a pad and free acid cellulose glycolic add.
A patent for another hemostatic wound dressing is taught by Shelley in U.S. patent 3,206.361 having an active agent in the form of methylaminoacetocatechol hydrochloride. Likewise. Anderson, in U.S. Patent 3,328,259, another wound dressing containing a film of cellulose glycolic acid ether is provided as the hemostatic agent
The hemostatic agent taught by SugitachI, et al. as disclosed in U.S. Patent 4,265.233 is blood coagulation Factor VIII plus either fibrin or thrombin. A ready-to-use bandage is taught by Altshuler in U.S. Patent 4.363,319 which also contains tiirombin as an active agent, the bandage all of which is contained within a sealed package.
Invented by Lindner, et al., a wound pad which is impregnated with tissue-compatible protein such as collagen and lyophilized Factor Xlll, thrombin and fibrinogen, are taught In U.S. Patent No. 4.600,574. The use of collagen as a hemostatic agent within a pad that has been freeze dried is taught by Sawyer in U.S. Patent 4.606,910.
In U.S. Patent 4,616,644, Saferstein, et al. teaches the use of an adhesive bandage with high molecular weight polyethylene oxide applied to the surface of the perforated plastic film wound release cover of the bandage to arrest blood flow from minor cuts. Yet another hemostatic agent including a canler in the shape of a flake or fiber having thrombin and Factor Xlll affixed thereto is taught by Sakamoto in U.S. Patent 4.655.211. The use of an ultra-pure, clean thrombin solution as a hemostatic agent is taught in U.S. Patent 5,525.498 invented by Boctor. Two recent patents invented by Pruss. et al., U.S. 5,643,596 and 5.645,849 both teach the use of hemostatic dressings which incorporate thrombin and epsilon aminocaproic acid (EACA) and calcium chloride on gelatin.
An absorbable spun cotton-like topical hemostat is taught by Shimuzu, et al. in U.S. Patent 5.679.372. This disclosure is directed to an absorbable dressing made of acetocollagen fibers which are innately adhesive to a bleeding surface. In a patent to Bell, et al. U.S. 5,800,372, a dressing made of microfibrillar collagen and a superabsoribant polymer provides both blood absorption and dotting inducement

One embodiment of the present method utilizes an improved ion exchange resin, preferably in the form of a styrene divinylbenzene copolymer which has been sulfonated. The collective teaching of making this prior art resin is to be found In an earlier patent to co-inventor, Patterson, U.S. 4.291,980 which was based at least in part on the production of spherical beads comprised of copolymer styrene and divinylbenzene as taught in U.S. Patents 2.366.007 and 3.463.320. This collective teaching is incorporated herein by reference. An improvement better adapting this resin to the present invention is in the fonn of substantially reduced cross-linking down to about 0.25%.
Another primary aspect of the present method incorporates an oxyacid salt, preferably potassium ferrate (2K2Fe04), The teaching of a process for producing alkali metal ferrates is taught by another co-inventor, Thompson, in U.S. Patent 4.545.974. This teaching is also incorporated herein by reference. See also U.S. Patent 6.187,347 by co-inventors herein.
It is submitted that the above-referenced prior art, either taken individually or collectively in any combination thereof fail to teach an enhanced hemostatic agent, method or canier for a flowing blood or body fluid clotting agent which includes an admixture of a salt ferrate which produces a trivalent Fe*** ion which reacts with the blood to accelerate coagulation and clotting of the blood. Moreover, the utilization of an enhanced insoluble cation exchange material, e.g. a sulfonated Ion exchange resin, in combination with the salt ferrate to form the enhanced hemostatic agent, additionally produces a protective matrix covering over the wound and also supplies an oxidative capacity which acts as an antibacterial, antiviral and antifungal agent Further, the presence of selected salts neutralize hydroxide radicals as dotting occurs so as to eliminate any substantial stinging sensation.
The "protective matrix" is formed by the interaction of the components of the invention with the liquid and solid components of the blood and tissue assodated with the wound or trauma. The term dot and/or dotting indudes both or either the product of the natural blood dotting cascade and the protedive matrix formed by the invention. A "wound" indudes all traumas resulting in the egress of blood, plasma and/or lymph from blood vessels and/or tissues, espedally tiirough tiie skin. *'Body fluids indude complete blood (red blood cells, white blood cells, platelets and

piasma alone, lymph alone (including suspended cells) and other body fluids, excluding urine, saliva and vaginal fluid. "Blood" refers to complete blood. plasma and/or lymph. Bleeding refers to the egress of bodily fluids including blood, plasma and/or lymph. A "hemostatic agent" refers to natural and/or artificial material which brings about stoppage of blood loss.
Neither does prior art teach another broad aspect of this invention which includes a flowing blood or body fluid clotting (hemostatic) agent which includes an admixture of an oxacid salt, in combination with a cation exchange resin, an organic acid or an acidic inorganic salt, which reacts with the blood or protein in blood to accelerate coagulation and dotting of the blood. The utilization of the insoluble cation exchange material, in combination with the oxacid salt, also produces a protective matrix covering over the wound and also supplying oxidative capacity which acts as an antibacterial, antiviral and antifungal agent in yet another aspect the presence of a selected hydrophilic proton donor neutralizes hydroxide radicals as clotting occurs so as to eliminate any substantial stinging sensation.
This invention is directed to a method, canier and enhanced hemostatic agent for arresting the flow of blood and other body fluid from an open wound and for promoting wound healing. In the method, the substantially anhydrous hemodstatic agent of a salt ferrate and an enhanced cation exchange resin is provided for unique use which will hydrate in the presence of blood or other proteirvoontaining body fluids. Fe*** is produced, thereby promoting dotting of the blood and otiier body fluids when applied to the open wound for a time suffident to promptly arrest substantial further flow of bodily fluids from tiie wound. The anhydrous hemostatic agent indudes a monovalent divalent or bivalent salt ferrate (M2 Fe O4. M Fe O4 or M2 (Fe 04)3 taken from the cationic group consisting of H, U, Na, K, Rb, Cs and Fr. However, to decrease or elirninate stinging sensation, the compound may be formed having a salt taken from Uie cationic group consisting of Be, Mg, Ca, Sr, Ba, Ra, Ti, V. Cr, Mn, Fe, Co, Ni. Cu, Zn. Ga, Ge, Zr. Nb. Mo. Tc, Ru, Rh, Pd. Ag, Cd, In. Sn, Hf. Ta. W. Re. Os, Ir. Pt Au, Hg. TI, Pb, Bi, Al, As. NH4, and N(C4H9)4. One prefenred hemostatic agent Indudes the substantially anhydrous salt ferrate compound and an enhanced sulfonated Ion exchange resin as an admixture which will rapidly hydrate in the presence of blood or other aqueous media to produce Fe***, thereby

promoting clotting. The resin produces a protective matrix coating over the wound for protection and promotes healing. Oxidative capadty produced during the reaction substantially reduces the level of bacteria, vims and fungus at the wound.
Another broad aspect of this invention is directed to a substantially anhydrous admixture of an oxyacid salt and a hydrophilic proton donor which will hydrate in the presence of blood and body fluid to provide protons which neutralize hydroxides and promote blood dotting. The preferred oxyadd salts are alkali and alkaline earth salts of transition metals and halogen oxyacids with oxidizing capabilities suffident to promote blood dotting. A variation indudes the compound containing an oxyadd salt plus a non-ionic hydrophilic polymer such as carboxy methylceilulose, polyvinyl alcohol, an alginate, starch, sugar and all soluble gums. Still another embodiment indudes the compound fonmed of an oxyadd salt in combination wiUi a hydrophilic proton donor and a solid de^ccant which promotes dot fonnation. The enhanced -cation exchange material or an admixture of an alkali metal oxyadd salt plus addic inorganic salt produces a scab or protedive coating over the wound for protection and enhanced healing.
It is therefore an objed of this invention to provide a method of utilizing a salt ferrate as a dotting agent for an'esting blood flow from an open surface wound.
It is another objed of this invention to provide a method of arresting blood and body fluid flow utilizing a salt fenrate hemostatic agent which is substantially sting-free when applied onto an open wound.
it is still another objed of this invention to provide an anhydrous hemostatic agent utilizing a salt ferrate combined with an enhanced insoluble cation exchange material which may be mixed with an aqueous media just prior to use for anresting blood flow from an open skin wound.
Still another objed of this invention is to provide a method for preparing a localized rapid forming protective coating or covering that has antibacterial, antifungal and antiviral properties.
It is therefore an object of this invention to provide a method of utilizing an oxyadd salt as a blood clotting agent for arresting blood flow from an open surface wound.

It is another object of this invention to provide a method of arresting blood and body fluid flow utilizing an oxyacid salt hemostatic agent which is substantially sting-free when applied onto an open wound.
It is still another object of this invention to provide a composition utilizing an oxyacid salt combined with an enhanced insoluble cation exchange material or an organic acidic or an inorganic salt to anrest blood flow from an open skin wound.
Another object of this invention is to provide a composition of an oxyadd salt and an insoluble cation exchange material which, in addition to promoting blood dotting to arrest blood flow from an open wound, also provides antiseptic and a protective matrix over the wound.
It is a yet further object of this invention to enhance the fluid uptake capadty of resin mixed with a salt ferrate by use of a lower cross-linked resin and/or appropriate treatment of the resin.
In accordance with these and other objects which will become apparent hereinafter, the instant invention will now be described.
Figure 1 is a schematic flow diagram of material hemostatic agent additives and delivery modes for spedfic applications of the invention.
Figure 2 depicts a prefenred delivery mode of the invention in the form of individual sealed ampules.
Figure 3 depicts the enhanced moisture uptake of resin as a result of boiling treatment in hydrogen peroxide (H2O2) prior to admixture with a salt fenrate. MECHANISM OF BLOOD COAGULATION
The following is offered as a brief explanation of one possible alternative mechanism which would explain the effectiveness of the present invention as described herebelow in full detail. ALTERNATE THEORY MECHANISM OF HEMOSTASIS
Blood contains both a solid and a liquid component. The liquid component is called plasma and contains a very broad variety of proteins. Among them are albumin, immunoglobulin and an assortment of proteins which participate in blood dotting. The solid components of the blood include red

blood cells (erythrocytes), white blood cells (leucocytes), and platelets. Of
these, only platelets participate directly in blood dotting.
When blood clots, depending upon the immediate cause, the proteins in
the plasma which are involved (which are proteolytic enzymes) act in a chain
reaction (i.e. protein #1 activates protein #2 which activates, in turn, protein #3.
etc.). This is called the cascade mechanism of blood clotting. Simplifying the
process, the last three steps are as follows:
Irritation and disruption of platelets cause the release of Prothromboplastin. Calcium ions (CA**), which are normally present in the plasma, cause the conversion of inactive Prothromboplastin into the active proteolytic enzyme, Thromboplastin. Thromboplastin, in the presence of calcium ions (Ca++) causes the activation of Prothrombin into Thrombin. Thrombin (also a proteolytic enzyme) acts upon Fibrinogen (present in great quantity in the -plasma) to remove a portion of that protein, thus converting it to Fibrin, which then actively polymerizes with itself. A simple diagram of this clotting process is

adjacent to the wound, but aiso to themselves. This "self-sticking" forms a molecular web which expands and becomes stronger as more and more Fibrin strands become enmeshed across the wound. As blood continues to flow from the wound, the solid components of the blood become enmeshed, trapped and stuck upon the Fibrin "web", thus eventually blocking the egress of blood from the wound...forming a clot.
The clot naturally falls off when the damaged tissues underneath the clot (the callus of dedifferentiated wound tissue) becomes reorganized into repaired tissue.
The invention includes a non-drug, non-biological powder that covers a wound to control bleeding and fluid loss, absorbs wound exudate and protects against abrasion, friction, desiccation and contamination. This powder is composed of a uniform admixture of a hydrophilic polymer and an inorganic Ferrate ionic material. In one delivery mode, the granules/powder are used by sprinkling directly onto the wound site or in the nose by using a moist cotton/Dacron applicator containing the admixture. The admixture and its constituents are applied topically and is not metabolized by the body.
The mechanism of this invention is independent of the normal clotting mechanism, the clotting cascade. The invention creates a synthetic plug or barrier by providing its owrr means of binding with the skin, wound tissue and blood components. The invention provides for linking trivalent ions with tissue and blood components to the resin, rapidly forming a matrix regardless of anticoagulant usage. Being independent of the normal blood clotting mechanism, it may be functional for use by persons using anti-coagulants which interfere with, and prevent coagulation and by persons afflicted with genetic defects in the blood clotting mechanism such as hemophilia. It should be noted that normal blood clotting (unless inhibited by patient therapies or prevented by genetic defects) can and does occur beneath, and simultaneously with, the invention's artificial matrix/clot formation.

A possible secondary mechanism may be that the trivalent ferric ions irritate platelets to release not only Prothromboplastin. but also biologicals involved with wound healing, thereby promoting the reconstruction/regeneration of the damaged tissue. Other possibilities include the chemical stimulus by trivalent Ferrate ions of the precursors to active coagulation components.
The trivalent fem'c ionic component of the invention may bind to the skin and the tissues exposed by the open wound. As red and white blood cells and platelets are canied out of the wound in the plasma, they bind with the fem'c ions and the resin to form a water-resistant barrier, an artificial clot to the escaping blood. The tissue exudates and plasma (the lymph and the liquid component of the blood, which is mostly water), are absorbed by the resin polymer. This absorption of fluid by the resin polymer causes It to swell vigorously. This swelling, in turn, occludes the wound site, thus controlling/stopping the flow of-blood.
The protective matrix of the fenic ions, the water-swollen resin, natural solid blood components (fibrin plus the red cells, white cells and platelets) combine to cause the rapid formation of a protective matrix. In accomplishing this, the invention helps promote healing, protects against infection and minimizes the pain and discomfort to the wound area.
All polyvalent cations can induce the natural blood clotting cascade. It is known that the decomposition of potassium ferrate produces the finest particles of iron oxide (Fe2O3) available. (See U.S. Patent 4,545,974). Upon addition to water. K2Fe04 becomes Fe*** in the form of FeOOH, which upon drying, yields Fe2 O3. The FeOOH (or Fe2 O3 H2O) is a solid in suspension and this ultra-fine material seems to be an ideal irritant for platelet membranes, thereby releasing the prothromboplastin that is needed to initialize the natural clotting cascade. It is possible that they may tend to rupture the platelets themselves, thereby causing a massive release of clotting factors as does the rough surface of a wound achieve the same end.
The Fe*** ion is an example of a polyvalent cation that will induce coagulation of blood. Trivalent ions, by lowering the zeta potential of a particle in solution, allow the particles (platelets) to aggregate more easily. Platelets are

cytoplasm found in the blood of mammals. After a wound is received they begin to aggregate and stick around the wound area, causing the aggregation and sticking of another cytoplasmic component, the thrombocycte. During this aggregation process, certain phospholipids from the membrane of the platelets contribute to the overall clotting process, combined with the inactive plasma enzyme. Factor XII. Mechanical abrasion of the platelet membranes is important in freeing the phospholipid component from the platelets. RANGE OF USEFUL SALT FERRATES

One of the important results is the production of the trivalent Fe*""* ion which appears to be the beneficial clotting agent provided in this aspect of this invention. Moreover, it has been determined that the present invention acts on all body fluids containing protein, such as that which flows from an open skin blister or bum.
A broadening of this aspect of the inventive compound would be to substitute the potassium salt with others which possess the same cation properties as does the potassium cation. Those salt elements which will substitute for the potassium cation are shown in Tables I and II herebelow.

H Hydrogen
Li Lithium
Na Sodium
K Potassium
Rb Rubidium
Cs Cesium
Fr Francium
Be Beryllium Mg Magnesium Ca Calcium
Sr Strontium Ba Barium Ra Radium
Ti Titanium V Vanadium Cr Chromium
Mn Manganese Fe Iron Co Cobalt
Ni Nickel Cu Copper Zn Zinc
Ga Gallium Ge Geranium Zr Zirconium
Nb Niobium Mo Molybdenum Tc Technetium
Ru Ruthenium Rh Rhodium Pd Palladium
Ag Silver Cd Cadmium In Indium
Sn Tin Hf Hafnium Ta Tantalum
W Tungsten Re Rhenium Os Osmium
Ir Iridium Pt Platinum Au Gold
Hg Mercury Tl Thallium Pb Lead
Bi Bismuth A! Aluminum As Arsenic
NH4 Cation N(C4 H9)4 Cation
In addition to the above salts in the cation form, all zeolites, sulfonated coal, and natural occurring membranes such as protein membranes will also act in compound form with ferrate to release the trivalent Fe*** ion to effect blood and body fluid coagulation.

In utilizing the K2 Fe O4 as above described to arrest blood flow from a bleeding wound, equation 1 shows the presence of hydroxide (OH)"" radicals which are produced. The hydroxide (OH)'radicals remain present in equation 3 and cause stinging at the wound site. Moreover, all of the cation salts of Table I produce the same result, i.e. stinging caused by the presence of the hydroxide ion.
All of the cation salts listed in Table 11. however, produce a slightly altered chemical reaction which neutralizes all of the hydroxide ions produced. For example, using a calcium cation salt to replace the potassium cation causes the following chemical reaction with water in blood:

As can be observed from Equation 4, no hydroxide ions are produced. Rather, all are neutralized and combined with calcium as shown in the equation. As provided by the above compounds, a method of arresting blood and
body fluid flow from an open skin wound is provided. An effective amount of any of the above salt ferrates, and preferably potassium ferrate in powder form, is applied directly onto the wound to interact with flowing blood or body fluid to
accelerate its clotting.
Although the above methodology and utilization of a salt ferrate greatly enhances blood clotting, the wound nonetheless remains opened and generally unprotected unless the salt ferrate is combined with a carrier such as a finger bandage, swab or the like which has been impregnated or coated with a dry powder taken from of one of the above chosen salt ferrate hemostatic agents.
By the addition of an ion exchange resin R with the salt ferrate, an additional benefit of protective matrix formation or depositing of a substance produced by the reaction with water in the blood is accomplished over the open wound. Details of the hemostatic agent and method of produdng the preferred ion exchange resin R in the form of styrene divinylbenzene are disclosed in the previously referenced patents and are herein Incorporated by reference- As described in formulas herebelow, the resin R may be shown in its chemical form

or generally designated by the symbol "R" for simplicity. The ion exchange resin R is sulfonated as is shown in chemical terms in each chemical equation herebelow.

linking of the resin R should be below 4.0 and as low as 0.25% and hygroscopic. The weight ratio should favor the dry ion exchange resin R by at least 4 to 1 of dry salt ferrate. The ion exchange resin R is preferably a cation exchange resin.
In another embodiment, a small amount of divalent calcium Ca++ may be added as an additional coagulant Heparins, EDTA (Ethylene Dismine Tetracacitic Acid), potassium oxalate, and warfarins are anticoagulants and are ionic in nature and remove Caldum Ca++ and trivalent ion Fe+++ by chelation to inhibit the natural dotting cascade. By supplying excess of polyvalent ions, the above anticoagulants

By combining even a trace amount of the above-described sulfonated resin (RSO3) as an admixture with potassium ferrate (KzFeOO, the following benefits are derived:
1. The trivalent Fe*** + 3 RSO3 produces a protective matrix and blood
flow stoppage;
2. The oxidizing capadty produced by the reaction serves as an
antibacterial, antiviral and antifungal agent;
3. The dotting with resin R produces a protective matrix that acts as a
protective coating for the wound;
4. Resin (RSO3) in this admixture neutralizes hydroxyl ions to prevent

Anhydrous Powder Preparation
A fenrate - ion exchange resin admixture (moisture free) was prepared for
direct application to a bleeding injury. The cation exchange resin R was prepared
in the washed hydrogen form, and then dried at 110° for 24 hours and powdered in
grinder to about 100 mesh.
This hemostatic agent was then applied directly to a fresh bleeding finger wound produced by a skin lancet having a penetration of 1.6 - 2.2 mm. The subject was 77 years old. skin condition non-flexible. Wound blood flow was at a rate of 0.206g/30 seconds or .0412g per minute to .0606g per minute.
When a single penetration of the skin was made and blood flow started at 0.0412 to 0.0605 g per minute, application of 5 sec. of the above resin - fenrate hemostatic agent directly to the wound dropped blood to zero as determined with a -blot pickup of 0.0020g within 1.0 minute. The resin- ferrate applied was on the order of 0.0175 - 0.0170 grams, forming a hard protecting sterilized coating over the penetration injury by the time that blood flow from the wound was stopped. DOSAGE ECONOMY
Pretreatment Blood Flow 0305g blood/30 sec. (.0605g/min)
After treatment Blood Row 0010g blood/30 sec. {.0028g/min
Dosage 0174g of anhydrous fenrate and resin admixture was used to treat
At this dosage, a 30g quantity of the hemostatic agent will provide approximately 1724 separate treatments.
METHOD OF PREPARATION Just Prior to Use The above-described anhydrous compound is preferably in the form of a combination of potassium ferrate (K2Fe04) and the acid form of low cross-linked ion exchange resin particles. Both of the materials are in powder form and are stored together in an anhydrous form (no water). They have been previously applied directly to body fluids, i.e. blood, in the dry form (powder). Using thiis technique, this dry compound is difficult for control as to location of application and stability on a wound.

Certain chemical reactions slow down the blood clotting action and the production of benefidal oxidizing capacity. By controlling the neutralization of potassium hydroxide (KOH) by the add resin, the mixing time and application time can be controlled. An aqueous media is used to mix the K2Fe04 and RSO3H. Thereafter, the mixture is spread on the wound to dot the blood and stop the bleeding. Mix time and spreading time total is about five minutes working time. The amount of aqueous media is just suflident to fonm a spreadable paste when combined with the fen-ate (VI) salt and resin. The lower the percentage of cross-linking of the resin, and the more resin used, the greater the amount of aqueous media needed.
The aqueous media that have been shown to provide the beneficial results of the present invention are:
(1) whole blood (from wound) and body fluids;
(2) deionized water,
(3) sodium chloride (ionic, aqueous);

(4) dissolved gelatin (i.e. 2% (aqueous);
(5) carboxyl methacel (aqueous);
(6) carbohydrate solution, i.e. sugar.
The following media controlling factors have been identified as being useful in the present method:
(1) ionic aqueous additive;
(2) viscosity;
(3) osmotic pH control (between pH 2 and 10) of the aqueous media;
(4) heat (5°C - SCC).
EXAMPlE 2 Compound ingredients:
0.1673 grams of anhydrous cation exchange resin RSO3H [0.5% X-L]
.0215g.of K2FeO4
1.020 g. of 2% gelatin (aqueous) Mix the resin and the K2Fe04. Then add the gelatin and mix. Within five (5) minutes, spread this paste-like mixture on the bleeding wound. The resin ferrate applied in this form controls bleeding.

EXAMPLES Compound ingredients:
0.1400 gm RSO3 [2.0% X-L] 0.0120 gmK2Fe04 Mix the resin and K2Fe04 with blood from a victim's wound and then apply this paste-like mixture to the wound from which the blood was previously obtained. Cover the wound evenly with the prepared paste mixture to control the bleeding. ACCELERATED BLOOD CLOTTING
The present invention, in one aspect, deals with the utilization of an inorganic acid containing oxygeh known as an oxyadd in the salt form. Select oxyacid salts alone or in combinations as described herebelow, appear to have a similar beneficial effect upon accelerating the coagulation of blood and other protein based fluids flowing from an open wound.
The oxyadd salts which have been shown to produce this blood coagulation acceleration are as follows:
1. Alkali & alkaline earth salts;
2. Oxyadd salts of transition metals;
3. Halogen oxyadds;
4. Alkali & alkaline oxides. peroxides and superoxides. ELIMINATION OF STINGING
A hydrophilic proton donor may also be added which chemically combines to eliminate the sting caused by the presence of hydroxyl ions produced after the blood dotting reaction is in progress. In general, there are three categories of hydrophilic proton donors which will act as a matrix to accomplish the neutralization of the hydroxyl ions, where present, as follows;
1. Cation exchange resin (sulfonated, phosphorated or carbonated)
2. Add produdng salts
3. Organic adds.
Following are more specific examples of each of the three above-referenced general categories of compounds which will neutralize the hydroxyl adds present in the blood coagulation reaction of the present invention as follows:

1. Hydrogen form cation exchange resins (sulfonates)
2. Hydrogen form cation exchange resins (phosphonates)
3. Hydrogen form cation exchange resins (carbonates)
4. Acidic inorganic salts (e.g. NaHS04)
5. Organic adds (e.g. Citric acid, cartoxylic acids, amino adds, peptides, proteins)

6. Solid desiccants (e.g. CaCI2. CaS04)
7. Porous hydrophilic matrix resins
8. Silicates (e.g. bentonite clay, hydroxy apatite)
9. Three component oxyadd. proton donor, solid desiccant

10. Polyvinyl alcohol
11. Carboxy methylcellulose
Solid desiccants also accelerate blood dotting further by water absorption from the
Another prefered function of the present invention is to create an artifidal scab atop the open wound as the blood is dotted to arrest blood flow while also serving as a potential anti-microbial agent in the form of an oxidant Such artifidal scab forming agents fall into two general categories. The first category is that of a cation exchange material in combination with:
1. K2Fe04;
2. KMnO4;
3. Na202;
4. KIO3
5. K2Fe04+KMn04.
The second category is exemplified by the compound formed as an admixture of:
NaHS04 + K2Fe04 as a unique combination of an oxyadd salt and an acidic inorganic salt respectively, also provide this artifidal scab-forming agent function.
The two major types of oxyadd salts, namely transition metal salts and halogen salt, act differently with respect to the scab-forming aspect of this invention.

The transition metal oxyadd salts form metal oxides which are important in the matrix formation, or scab formation, when combined with the cation exchange material or any other hydrophilic proton donor. Halogen oxyacid salts do not possess this quality, nor do alkali or alkaline oxides, peroxides or superoxides. Although this later group does create an oxidizing environment that facilitates dotting, they do not act as efficiently as do the transition metal oxyadd salts to form a protective scab over the wound.
MODES OF DELIVERY AND APPLICATIONS Modes of product delivery and applications include the following: Medical applications include a variety of hemostasis usages for arresting blood flow caused by minor wounds and potentially more serious wounds such as gunshots, stabs, or other severe lacerations creating blood loss. The material is expected to assist in stabilizing blood pressure and to allow the patient to maintain minimal blood loss in the most rapid manner possible. A. Fine powder spray system.
Inert propellants such as nitrogen, nitrous oxide and/or carbon dlioxide may be utilized to optimize product performance, stability and extended shelf life. The spray is highly controlled so that the operator can direct the spray and apply desired amount of product until satisfadory wound healing occurs. Canister size would be attractive and compact to fit in small EMT equipment container or into a small pocket For example; the significant cost benefit of the spray embodiment will allow for larger use of the product Military personnel equipped with such a spray will be able to keep a can of material for use in emergency situations. The smaller the size, the more attractive and mobile it would become, thereby achieving larger martlet appeal. B. Bandage wound dressing.
Such delivery systems would contain the subjed material in an impregnated form. The base material might be a biocompatible material such as natural or man-made material such as Dacron or cellulose that would provide additional tensile strength to an open wound. This added benefit could allow for more severe wounds to be treated. The impregnated bandage would need to be packaged in a way such that the material was not subjected to moisture in open air until immediately prior to

use. maximizing effectiveness. Bandages of different sizes can be created to accommodate various size wounds. C. Impregnated Sponge
Application of the hemostatic agent into a sponge or sponge-like material will enable the sponge to be easily manipulated within the body cavity during surgical operations offers distinct advantages. This embodiment would maintain the advantages of arresting blood flow from sources within the body in a structure that would retain its shape and create a barrier between the source of blood flow and the surgery area. The impregnated sponge would also absorb excess blood.
D. Tea Bag Form
The hemostatic agent can also be loaded into porous "tea bags" to achieve the maximum absorbency effect for blood or other body fluids inside the body. This concept can be applied to feminine hygiene products or the like.
E. Foam
• The use of a foam has the benefit of conforming to the exact geometry that the body cavity or wound has created. The direct benefit of the hemostatic agent reacting immediately by direct application of a foam upon contact with blood and body fluids flowing from a wound requires a specialized applicator design such that the active powder and foam is co-applied simultaneously upon demand. The container may have two separate chambers that house the foam material and the dry hemostatic agent independently to prevent activaton prior to use.
F. Pouring and Sprinkling
Direct disponing of the hemostatic agent directly onto the wound will arrest blood flow and produce a dot
G. Cotton Swab Applicator
This caeeier embodiment consists of a bottle containing the dry coagulating
agent into which a cotton swab could be dipped and then applied to smaller localized
wound areas. Altematively, powder may be poured onto gauze and the swab rolled
in the powder. The use of the material for arresting nose bleeds could be in the form
of a cotton swap applicator or the like which may have been moistened and
previously been dipped into the material which is then applied directly to the nasal

cavity. This should prevent further damage to the sensitive membranes within the nose that is caused by the use of other products such as cauterization, H. Direct Container Application
Another method of applying the invention is via a round plastic dispenser that fits snugly into a bleeding nose, the container filled with the hemostatic agent or dipped into the material immediately prior to application. SPECIALIZED USES
The present invention is suitable for healing bed sores or decubitus ulcers by creating a protective surface barrier or temporary skin that is flexible while producing oxidative capacity at the surface of the wound, which in tum promotes healing. These ulcers sometimes have extreme difficulty in healing because of the lack of blood flow (especially in cases of diabetics) in the wound area. The product should stimulate wound recovery by providing oxidative capacity and killing bacteria as well as providing protection from contaminated air and other aerosolized or suspended infection canriers.
The present invention is also suitable for the treatment of skin and tissue bums through the creation of a protective surface or crust over the bum area and promoting natural tissue healing by producing oxidative capacity under the damaged tissue area.
Another use includes surgical sealants for mating and/or keeping trauma-separated surfaces together. This invention could be also used in conjunction with surgical staples and other such devices and with femoral artery plug systems useful during cardiac catheterization. Ferrate promotes tissue healing and growth by providing oxidative capacity under the surface of the hard clot that is created upon contact.
A further advantage of the combined ferrate and resin product is that of meaningful fluid absorbency upon contact with resin which expands as fluid is absorbed, further acting as a plug inside of a wound. This addition of pressure further enhances the ability to arrest the flow of blood. The crosslinking of the resin polymer, which is an insoluble add. could also be changed to control the clot matrix and structure allowing for control of dot flexidbility and rigidity which is useful for applying to the surface of a wound.

Referring now to Figure 3. the enhancement of the resin in the form of substantially increased fluid uptake will now be described in detail. As seen in Figure 3. a typical strong add cation resin (SAC) cross-linked at a nominal 2.0% exhibits a moisture uptake capacity of approximately 80% prior to any enhancement A 0.5% cross-link SAC resin exhibits a 95% moisture uptake capadty. These percentages are in terms of total weight of a fully water-saturated quantity of the resin. In other terms, at 80% saturation, the resin itself would represent 20% of the total weight, a weight ratio of 4:1 water-to-resin.
Because the fluid uptake or absorption of the resin is an extremely important aspect of this invention, increasing that moisture uptake capadty of the resin is highly desirable in accelerating the dotting action of the invention. To accomplish

this enhancement, the resin is boiled in a time concentration of H2O2 (hydrogen peroxide) for a time period of up to approximately 8 hours. After boiling, the resin is
filtered, washed and dried, and then infused in an admixture process with the selected salt ferrate or oxy acid salt
The process of enhancement with respect to the 2% cross-linked resin maintains the original spherical fomri of the bead; however, the original spherical form of the 0.5 cross-linked bead substantially deteriorates and looses its ability to absorb fluid almost entirely. Moreover, the manufacturing economy of 2% vs. 0.5%
cross-linked resin is substantial in favor of 2% cross-linking and needs less waer to
effect neutrolization fo the HOH' radicals described hereabove.
The enhancement process may be viewed as breaking free radicals from the
resin polymer which may also be accomplished by high energy light, sonic exposure,
radiation and the application of immersion in bleach. A flow diagram of the process -

The benefit of this enhancement of the resin for increased moisture or fluid absorption is shown in Figure C. This benefit increases steadily with the time for boiling the resin in the heated hydrogen peroxide, increasing up to a percentage of moisture uptake of approximately 98% following boiling for approximately 450 minutes with lesser levels of enhancement achieved with shorter boiling times as shown in Figure 3.
While the instant invention has been shown and described herein in what are conceived to be the most practical and preferred embodiments, it is recognized that departures may be made therefrom within the scope of the invention, which is therefore not to be limited to the details disclosed herein, but is to be afforded the full scope of the claims so as to embrace any and all equivalent apparatus and articles.

What is claimed is:
1. A method of arresting the flow of blood from a bleeding wound comprising the steps of.
A. mixing a substantially anhydrous compound of an oxyacid salt
ferrate (VI) which hydrates in the presence of blood or an
aqueous media to produce polyvalent metal ions with blood
flowing from a wound;
B. applying the mixture from Step A to the wound for a time
sufficient to effect sufficient clotting of the blood to arrest
substantial further blood flow from the wound.
2. The method of Claim 1, wherein:
said compound provided in Step A is formed of said salt ferrate (VI) and H, Li, Be. Na, Mg, K, Ca, Rb, Sr. Cs. Ba, Fr. Ra. Ti, V, Cr. Mn, Fe, Co, Ni. Cu, Zn, Ga, Ge. Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd. In. Sn, Hf, Ta. W. Re. Os, Ir. R. Au. Hg. TI, Pb, Bi, Al, As, NH4 and N(C4H9)4.
3. The method of Claim 1, wherein:
said compound provided in Step A is K2 Fe O4.
4. The method of Claim 1, wherein:
said compound provided in Step A is formed of a salt which combines with water in the blood or aqueous media to eliminate substantially all hydroxide (OH") which cause a stinging sensation. 5. The method of Claim 1, wherein said aqueous media includes: whole blood, plasma, and/or lymph taken directly from the wound; deionized water; sodium chloride solutioin; aqueous dissolved gelatin; aqueous carboxy methacel; and aqueous carbohydrate solution.

6. A method of arresting the flow of blood and other body fluids containing protein from an open skin wound comprising the steps of:
A. mixing a substantially anhydrous compound of a monovalent, divalent or a trivalent salt ferate which hydrates in the presence of blood to produce Fe+++, thereby promoting clotting of the blood, with a quantity of an aqueous media to form a paste; B. applying said paste to the wound for a time sufficient to effect sufficient clotting of the blood to arrest substantial further blood or body fluid flow from the wound. 7. A hemostatic agent adapted to be applied directly onto a bleeding wound comprising:
an effective amount of a oxyacid salt combined with an effective amount of an insoluble cation exchange material, said oxyacid salt combining with blood to promote blood clotting at the wound, said cation exchange material forming a protective cover over the wound as blood is thereby clotted. 8- A hemostatic agent as set forth in Claim 7, wherein said oxyacid salt is taken from the group consisting of:
alkali and alkaline salts; oxyacid salts of transition elements; halogen oxyacids; and
alkali and alkaline oxides, peroxides and superoxides. 9. A hemostatic agent as set forth in Claim 7, wherein said cation exchange material is an admixture which is a cation exchange resin and a compound taken from the group that includes;
K2 Fe O4; KMnO4, Na2 O2; and

10. A hemostatic agent as set forth in Claim 7. wherein said hemostatic
agent includes:
K2 Fe O4 as said oxyacid salt;
Na H S O4 as an acidic inorganic salt.
11. A method of arresting the flow of blood from a bleeding wound
comprising the steps of:
A. providing an effective amount of a substantially anhydrous
compound of an oxyacid salt combined with an effective
amount of hydrophilic proton donor which will hydrate in the
presence of blood to thereby promote clotting of the blood;
B. applying said compound to the wound for a time sufficient to
effect sufficient clotting of the blood to an-est substantial
further blood flow from the wound.
12. A hemostatic agent adapted to be applied directly onto a bleeding wound comprising:
an effective amount of an oxyacid salt combined with an effective amount of a hydrophilic proton donor material, said oxyacid salt combining with blood to promote blood clotting at the wound, said hydrophilic proton donor material combining with, and thereby neutralizing, hydroxyl ions formed as said oxyacid salt combines with blood to effect clotting.
13. A hemostatic agent as set forth in Claim 12, further comprising:
a solid desiccant combined with said oxyacid salt and said hydrophilic proton donor material, said solid desiccant further accelerating blood clotting by absorbing water in the blood.
14. A hemostatic agent adapted to be applied directly onto a bleeding
wound comprising:
an effective amount of a substantially anhydrous salt ferrate compound combined with an effective amount of an isoluble cation exchange material, said salt ferrate combining with blood to promote blood clotting at the wound, said cation

exchange material forming a protective cover over the wound as blood is thereby clotted; said cation exchange material being a resin which is cross-linked greater than 0.5% and has been pretreated for increased moisture uptake to substantially exceed 80% by weight of the total weight of said resin when fully saturated with water. 15. A delivery vehicle for a hemostatic agent adapted to be applied to a bleeding wound, said hemostatic agent comprising:
a substantially anhydrous compound of a monovalent, divalent or trivalent salt ferrate which hydrates in the presence of blood or an aqueous media to produce FE+++; a substantially anhydrous oxyacid salt combined with an effective
amount of an insoluble cation exchange material; or a substantially anhydrous oxyacid salt combined with an effectie amount of a hydrophillic proton donor material; said delivery vehicle taken from the group comprising:
a fiber material impregnated with said hemostatic agent;
a powder spray carrier within a pressurized container combining with
said hemostatic agent as a dry powder upon discharging of
the spray carrier from a spray nozzle of the container;
a cotton swab impregnated with said hemostatic agent;
a bandage impregnated with said hemostatic agent;
a sponge impregnated with said hemostatic agent;
a porous tea bag-like enclosure containing a quantity of said
5 hemostatic agent; and
a foam canier within a pressurized foam container combining with said hemostatic agent upon discharge of the foam canier from a discharge nozzle of the foam container.

16. A method of arresting the flow of blood from a bleeding wound substantially as herein described with reference to the accompanying drawings.
17. A delivery vehicle for a hemostatic agent substantially as herein described with reference to the accompanying drawings.




in-pct-2002-1760-che-claims filed.pdf

in-pct-2002-1760-che-claims grand.pdf



in-pct-2002-1760-che-description(complete) filed.pdf

in-pct-2002-1760-che-description(complete) grand.pdf


in-pct-2002-1760-che-form 1.pdf

in-pct-2002-1760-che-form 18.pdf

in-pct-2002-1760-che-form 26.pdf

in-pct-2002-1760-che-form 3.pdf

in-pct-2002-1760-che-form 5.pdf

in-pct-2002-1760-che-other documnents.pdf


in-pct-2002-1760-che-priority documents.pdf

Patent Number 208928
Indian Patent Application Number IN/PCT/2002/1760/CHE
PG Journal Number 38/2007
Publication Date 21-Sep-2007
Grant Date 16-Aug-2007
Date of Filing 25-Oct-2002
Name of Patentee BIOLIFE, L.L.C
Applicant Address 1235 Tallevast Road, Sarasota, FLORIDA 34243
# Inventor's Name Inventor's Address
1 PATTERSON James A 2070 Twentieth Street Sarasota, FL 34234
2 THOMPSON John A Post Office Box 6206 Nassau
3 REDING James W 1235 Tallevast Road Sarasota, FL 34243
4 KEENE Talmadge Kelly 910 Birdie Way Apollo Beach, FL 33572
PCT International Classification Number A61K9/00
PCT International Application Number PCT/US2001/013765
PCT International Filing date 2001-04-27
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 60/200,207 2000-04-28 U.S.A.
2 09/592,344 2000-06-13 U.S.A.