GB2466979A

GB2466979A - Porous ceramic compositions for use as haemostatic agents

Info

Publication number: GB2466979A
Application number: GB0900727A
Authority: GB
Inventors: Simon James Baker
Original assignee: Individual
Current assignee: Individual
Priority date: 2009-01-19
Filing date: 2009-01-19
Publication date: 2010-07-21
Also published as: GB0900727D0

Abstract

Porous ceramic compositions for promoting haemostatis and sealing a wound comprises a porous ceramic material selected from the group consisting of hydroxyapatite, calcium phosphates, calcium carbonates, calcium sulfates and combinations thereof. The composition may consist of loose porous ceramic particles such that when applied to a wound the particles form a cast or they may be attached to or contained within a substrate wherein the substrate is selected from cotton, wool, linen, rayon, nylon, polyester, polyethylene, mineral wool or metal fibres, a dissolvable material, a water soluble material or combinations thereof. The compositions comprise specified particle sizes between 0.1-2 mm and porosities between 5-80% such that when applied to a bleeding area the composition promotes at least one of stopping blood flow from a wound, forming a cohesive mass, sealing a wound, promoting coagulant activity, absorbing a body fluid and adhering to tissue. The composition may consist entirely of porous ceramic particles or may contain a number of other bio-active agents, haemostatic or absorptive agents. A sterilised unit package having moisture content of between 0.1-13% and a method of selecting a haemostatic composition are also outlined.

Description

HAEMOSTATIC AGENT AND USES THEREOF

BACKGROUND TO THE INVENTION

Blood is a liquid tissue that includes red cells, white cells, corpuscles, and platelets dispersed in a liquid phase. The hquid phase is plasma, which includes acids, lipids.

soluble electrolytes, and. proteins. The proteins are suspended in the liquid phase and can be separated out of the liquid Phase by any of a variety of methods such as filtration, centrifugation, electrophoresis, and immunochemical techniques. One particular protein suspended in the liquid phase is fibrinogen.

When bleeding occurs, the fibrinogen reacts with water and thrombm (an enzyme) to form fibrin, v,'hich is insoluble in blood and polymerizes to form clots. in a wide variety of circumstances, animals, including humans, can be wounded. Often h]eeding is associated with such wounds. in some instances, the wound. and the bleeding are minor, and normal blood clotting functions in addition to the application of simple first aid are all that is required. Unfortunately, however, in other circumstances, substantial bleeding can occur. These situations usually require speciahsed equipment and materials as well as personnel trained to administer appropriate aid. If such aid is not readily available, excessive blood loss can occur, When bleeding is severe, sorrietimes the immediate availability of equipment and trained personnel is still insufficient to stanch the flow of blood in a timely manner.

Moreover, severe wounds can often he inflicted in very remote areas or in situations, such as on a battlefield, where adequate medical assistance is not immediate]y available. in these instances, it is important to stop bleeding, even in less severe wounds, long enough to allow the injured person or animal to recetve medical attention.

in an effort to address the above-described problems. materials have been developed for controlling excessive bleeding in situations where conventional aid is unavailable or less than optimally effective. Although these materials have been shown to be somewhat successful, they are not effective enough for traumatic wounds and can be expensive. Furthermore, these materials are sometimes ineffective in all situations and can be difficult to apply as well as remove from a wound.

Additionally, or alternatively, the previously developed materials can produce undesirable side effects, particularly in instances in which they are misapplied to wounds or applied by untrained personnel. For example, because prior art blood clotting material is generally a powder or in fine particulate form, the surface area of the material is relatively large. The typical moisture content of a large surface area blood clotting material is generally up to about 15% of the total weight of the material.

This combination of surface area and moisture content often produces an exothermic reaction upon the application of the material to blood. Depending upon the specific surface area and the specific amount of moisture, the resulting exothermia may be sufficient to cause discomfort to or even burn the patient. Although some prior art patents specifically recite the resulting exothermia as being a desirable feature that can provide cauterization of the wound, there exists the possibility that the tissue at and around the wound site can be undesirably damaged.

Based on the foregoing, it is a general object of the present invention to provide a haemostatic agent that overcomes or improves upon the problems and drawbacks

associated with the prior art.

STATEMENT OF INVENTION

The present invention solves these problems by identifying a porous ceramic substrate having a composition, pore size, porosity and granule size to treat a bleeding wound, contacting the bleeding wound with the porous ceramic substrate causing the blood of a human or animal to clot.

The porous calcium containing haemostatic agent may contain a material selected from the group consisting of hydroxyapatite, tricalciurn phosphate, calcium phosphates, calcium carbonates, calcium sulphates, and combinations thereof In another aspect, the invention also provides a composition comprising the porous ceramic substrate with a bioactive agent such as a healing promotion agent, a growth factor, an anti-inflammatory agent or a topical anaesthetic to improve coagulation and prevent infection.

The invention also provides a method of inducing haemostasis in a mammal comprising the step of applying to the bleed site of a mammal with a composition comprising the porous ceramic substrate and optionally a binder and/or a bioactive agent.

in another aspect. the invention also ProvIdes a method of forming a bioodciouing composition includes the steps of providing the porous ceramic substrate such that upon appiiicaiion of the conipositton to a wound, a hezu of hydration ts reduced and thereby the heat transferred to tissue surrounding the wound is reduced.

In yet another aspect of the present invention, a method of cdotting blood flowing from a wound includes applying a porous ceramic substrate to the wound where bleeding is present and maintaining the porous ceramic substrate in contact with the wound for a predetermined amount of time. Preferably, the porous calcium containing material has an adjusted calcium content and causes controflable Hood clothing, thereby stopping or minimizing the flow of blood.

One advantage of the present invention is that it is easily applied to an open wound.

Particularly when the composition is in the form of particles, pellets, pastes, gels, beads, rods, or granules, it can be readily removed from a sterilized packaging and deposited directly at the points from which blood emanates to cause clotting.

Another advantage of the present invention is that unlike other materials, such as, for example zeolites, the porous ceramic substrate produces no exothermic reaction with blood. Eliminating the generation of heat at a wound site is useful in minimising discomfort and/or further injury to a patient and may be especially useful in the treatment of certain patients such as pediatric or geriatric patients or when the wound being treated is in a particularly sensitive or delicate area.

Still another advaniage of the present invention is that it rapidly and effectively promotes the clotting rate of blood. The porous nature of the ceramic haemostatic agent allows water to be wicked away to cause thickening of the blood, thereby facilitating the formation of clots. By causing blood to clot rapidly, a flow of blood can be reduced or stopped quickly.

DETAILED DESCRIPTION

In order that the invention herein described may be fully understood, the following

detailed description is set forth.

"Porous ceramic" refers to the haemostatic agent being a hydroxyapatite, calcium phosphate, 13-tricalcium phosphate or other calcium sulphate material. The present invention is not limited in this regard, however, as other materials are also within the scope of the present invention. As used herein, the term "porous ceramic" also refers to a porous ceramic substrate having the ability to be dehydrated without experiencing significant changes in the crystalline structure.

"Biocompatible refers to a material that does not elicit detrimental effects associated with the body's various protective systems, such as cell and humoralassociated immune responses, e. g., inflammatory responses and foreign body fibrotic responses. The term biocompatible also implies that no specific undesirable cytotoxic or systemic effects are caused by the material when it is implanted into the patient.

The terms "haemorrhage' or "acute haemonhage" mean the loss of blood from one or more anatomical sites of a patient that, if left untreated, would jeopardise the health of the patient. Haemorrhage typically results from rupture of one or more blood vessels, which may occur accidentally (e.g. as in accidental wounds) or purposefully (e.g. during surgical procedures). A haemorrhaging wound can involve blood flow leaving the wound at a high pressure making the haemorrhaging wound difficult to seal.

The active control of haernolThage is referred to as "haemostasis." In some embodiments, "haemostasis" refers to the cessation of bleeding from a wound. The promotion of haemostasis involves, for example: slowing or stanching the flow of blood (e.g., through direct pressure and/or mechanical means such as a tourniquet or cast); and enhancing, facilitating or causing the blood to clot, particularly at the site of a The particles of the present invention have desirable sorptive properties. The terms "sorb" and "sorptive refer to the ability of a particle to take up a liquid either by adsorption, by absorption, or by a combination of both. For example, the particles of the present invention can be used to sorb blood. The particles of some embodiments of the present invention can sorb blood in amounts up to about ten times their dry weight.

In some embodiments, the particles of the present invention can absorb blood, adsorb blood, or adsorb and absorb blood when applied to a wound.

This present invention provides, a composition for promoting haemostasis, said composition comprising: a porous ceramic substrate; and wherein upon contact with a bleeding wound said haernostatic agent causes blood flowing from said bleeding wound to clot. The porous ceramic body described in this invention comprises the ceramic having a multiplicity of pores.

In another preferred embodiment, the porous ceramic haernostatic agent may contain a material selected from the group consisting of hydroxyapatite, tricalcium phosphate, calcium phosphates, calcium carbonates, calcium sulphates, and combinations thereof.

In a more prefened embodiment the porous ceramic substrate is a tricalcium phosphate.

In the most prefened embodiment the porous ceramic substrate is 13-tricalciurn phosphate.

Tricalcium phosphate (TCP) has the formula of Ca3(P04)2 with the Ca/P ratio being about 1.5. TCP powder has an apatite crystal structure. Upon sintering, the apatite structure converts to the rhombic 13-TCP structure. At high temperatures, the metastable, a-TCP structure can also form. a-TCP is known to have excessive solubility. In addition, ct-TCP is capable of generating harmful inflammatory responses. In a preferred embodiment, the TCP is sintered at high temperatures of 1100-1200°C. Above 1300°C, TCP is converted to the metastable c-TCP. Sintering the TCP reduces its solubility in body fluids, which leads to a corresponding reduction in its chemical activity so that the porous TCP is well tolerated in the body and acute inflammatory reactions are avoided. Therefore, the porous 13-TCP is preferably sintered. More preferably the 13-TCP comprises 13-TCP that is 95-100% pure.

The compositions of the present invention, in some embodiments, begin by selecting the desired particle sizes of the desired porous ceramic for use in the composition.

These particles are also referred to as "granules" and the two terms are intended to be synonyms. The mixture that passes through any particular sieve has a particle size less (or no greater) than that of the opening in that sieve. The desired particle size distribution of the compositions of the present invention may be directly achieved by selective drying, crushing, and screening of the porous ceramic.

Particles of differing particle sizes, or different particle size ranges, can also be blended together in varying amounts or ratios, e.g., via back blending, to produce the compositions useful for treating a haemorrhaging wound. For example, larger particles can be blended with smaller ones in varying ratios, amounts, or percentages. As one of skill in the art will appreciate, particle size ranges can also be produced by blending two or more granular porous ceramic products having different particle size distributions to achieve the desirable particle size distribution or the desired particle size.

The porous ceramic substrate of the present invention may have any shape and size. In one embodiment, the porous ceramic substrate is granular and has a particle size between 0.1 to 2 mm. In a preferred embodiment, the particle size is 0.5-1.7 mm. In a more preferred embodiment the particle size is 1.0-1.7 mm. In a most preferred embodiment, the particle size is 0.5-1 mm. The porous ceramic substrate having a granule size of less than 0.1 mm is not appropriate because it will be readily displaced by flowing body fluids.

The porosity of the porous ceramic substrate influences the resorption rate. If the porosity is too high, the strength of the granules will be decreased. If the porosity is too low, the i-ate of resorption will be slow.

The total porosity is measured using the mercury intrusion parameter method or equivalent methods. In one embodiment, the total porosity is in the range of 5-80%. In another embodiment, the total porosity is in the range of 40-80%. In a more preferred embodiment, the total porosity is 65-75%. In a most preferred embodiment, the total porosity is 70%.

The composition may consist entirely of porous ceramic or a variety of other bioactive agents may be added to the porous ceramic, examples of which include vitamins, living cells such as chondrocytes, bone marrow cells, mesenchymal stem cells, tissue transplants, immuno-suppressants, antimicrobial agents (e.g. antibiotic, antifungal, and/or antiviral), electrostatic agents (e.g. dendrimers in which the charge density is varied or similar compounds), preservatives, various carriers which modulate viscosity, various colorants, and various medicaments which promote wound healing. Other appropriate haemostatic or absorptive agents may also be added. These include but are not limited to chitosan and its derivatives, fibrinogen and its derivatives (represented herein as fibrin(ogen), e.g. fibrin, which is a cleavage product of fibrinogen), super-absorbent polymers of many types, cellulose of many types, alkaline earth cations such as iron, barium and sodium, metallic cations such as silver, or various anions, other ion exchange resins, and other synthetic or natural absorbent entities such as super-absorbent polymers with and without ionic or charge properties. In some embodiments of the invention, exchangeable cations of one type on the porous ceramic may be substituted with cations of another type (e.g. silver cations).

In addition, the porous ceramic substrate may have added to it vasoactive or other agents which promote vasoconstriction and haemostasis. Such agents might include catecholamines or vasoactive peptides or agents such as chitosan, thrombin, etc. This may be especially helpful in its dry form so that when blood is absorbed, the additive agents become activated and are leached into the tissues to exert their effects. These agents may be coated onto the particles of the porous ceramic substrates via processes like spray drying. In addition, antibiotics and other agents which prevent infection (any bactericidal or bacteriostatic agent or compound) and anesthetics/analgesics may be added to enhance healing by reducing pain.

In one especially preferred embodiment, the bioactive agent is a topical antibiotic.

More preferably, the topical antibiotic is selected from the group consisting of chioramphenicol, chiortetracycline, clyndamycin, clioquinol, erythromycin, framycetin, gramicidin, fusidic acid, gentarnicin, mafenide, murpiroicin, poly-myxin B, bactitracin, silver sulfadiazine, tetracycline, tetracycline, chloroetracycline, and combinations thereof.

In another embodiment, the bioactive agent is preferably an antimicrobial or antibiotic including but not limited to erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracycline, viomycin, chloromycetin and streptomycin, cefazolin, ampicillin, azactam, tobramycin, clindamycin and gentamycin. The concentrations of the antibiotic to be used are well known in the art. Such antibiotics have been known and used in connection with medical devices. See, for example, Hoff et al., J. Bone Joint Surq., 63A, pp. 798, (1981); and Dueland et al,, Clin. Orthop., 169, pp. 264-268, (1982). The teachings of these two references are incorporated herein by reference.

In another preferred embodiment, the bioactive agent is a repair cell. In a preferred embodiment, the repair cell is a mammalian cell, more preferably, a human cell of the same type as that of the tissue being repaired or reconstructed. Suitable examples of repair cells include.

In some embodiments, the compositions of the present invention are sterilised or sterile. As used herein, the terms "sterilised and sterile" refer to compositions free of microbes including bacteria, fungi, and/or viruses or a composition that has passed a standard sterility test. For example, the compositions can be sterilised using radiation, heat, or treatment with various gaseous agents known to one of skill in the art without disrupting the desirable characteristics of the compositions, e.g., the particle size and/or moisture content.

Some embodiments of the present invention use formulations of particles with specific particle sizes for the direct application of the particles to a wound. These particles can be in the form of a loose powder or mixture of granules. These formulations can be applied directly to a bleeding wound. This application of a loose powder or a mixture of granules can be used to fill the cavity of the wound, seal the ruptured blood vessel, and/or form an adherent seal within the wound or on top of the wound.

The compositions of the present invention can, in some embodiments, be affixed, enmeshed, intertwined, coated onto, or otherwise adhered to a substrate. The substrate may be composed of any suitable material, either natural or man-made and organic or inorganic, e.g., cotton, woos, linen, rayon, nylon, po'yester, poyethy1ene, minera' woos or metal fibres, or blends of these materials, and may be in any suitable form, e.g., formed meshes, grids or matrixes, woven fabrics or non-woven fabrics, as well as mixtures of these forms, that is suitable for, and may facilitate the use of, the compositions of the present invention. It should be understood that the examples given should not be interpreted to limit in any way the range of substrates that are provided herein.

Some embodiments of the invention include unit packages of a measured amount of the mixture of porous ceramic particles. The unit package can be, but is not limited to, a pouch, sachet, sack, bag, box, can, bottle, tube, or other equivalent container capable of holding a measured amount of porous ceramic. The unit package can be a single use package or part of a multi-pack.

The measured amount of the porous ceramic particles varies depending on the haemostatic application the composition will be used for but can be between about 0.01 grams to about 250 or more grams. For example, embodiments can use a measured amount of about 0.01, 0.1, 1.0, 5, 10, 15, 20, 25, 50, 100, 200, or 250, or more, or less, grams. The unit package with the measured amount will generally be less than 1 kg or 500 g in weight.

As discussed above, the unit package can hold a sterilised composition and is designed to preserve the sterile condition of its contents until use. The unit packages can also be designed and/or packaged in a manner that will prevent the particles of porous ceramic from being broken down, degraded, contaminated, dried, or hydrated during shipping, storage, or during or prior to use of the composition.

The compositions, formulations, and unit packages described herein are useful in methods of treating a haemorrhaging wound, promoting haernostasis in a wound, and/or other conditions related to the loss of blood or other fluids (e.g., lymph). These methods can be used on any animal, mammal, or in particular human, in need of treatment.

The compositions and formulations of the present invention may be administered to a site of bleeding by any of a variety of means that are well known to those of skill in the art. Examples include, but are not limited to, internally, directly to a wound, (e.g. by pouring or shaking powdered or granulated forms of the material directly into or onto a site of haemorrhage, followed by kneading if necessary), by placing a material such as a bandage that contains or is impregnated with the material into or onto a wound, or otherwise coating the wound with the material.

Many applications of the present invention are based on the known problems of getting the surfaces of bandages to conform to all surfaces of a bleeding wound. The use of granules and / or powders allows the preparations of the invention to cover all surfaces no matter how inegular they are. For example, a traumatic wound to the groin is very difficult to control by simple direct pressure or by the use of a simple flat bandage.

However, treatment can be carried out by using the porous ceramic substrate in the form of, for example, a powder or granule preparation that can be poured into the wound, followed by application of pressure if needed. One advantage of the preparations of the present invention is their ability to be applied to irregularly shaped wounds, and for sealing wound tracks, i.e. the path of an injurious agent such as a bullet, knife blade, etc. Compositions comprising porous ceramic may be utilised to control bleeding in a large variety of settings, which include but are not limited to: a) External bleeding from wounds (acute and chronic) through the use of powder, granules, or the coating of bandages with these preparations.

b) Gastrointestinal bleeding through the use of granules or powder.

c) Epistaxis through the use of an aerosolized powder, patches, or coated tampon.

d) Control of internal solid organ (e.g., liver or spleen) or boney injury through the use of powder; granules; or bandages having powder or granules enmeshed in the bandage, intertwined with the bandage, coated onto the bandage, or otherwise adhered to the bandage.

e) Promotion of haemostasis, fluid absorption and inhibition of proteolytic enzymes to promote healing of all types of acute and/or chronic wounds including the control of pain from such wounds.

The compositions, formulations, and unit packages described herein are also useful in methods of forming a cast to cover, close, seal, or otherwise stop the bleeding from a wound. These methods involve applying a sterile composition described herein in a quantity sufficient to form a cast over the wound. The cast is formed from one or more porous ceramic minerals and blood from said haemorrhaging wound. The cast can be pliable or rigid, as clinical conditions dictate. As described in the examples below, the pliability of the cast formed can be controlled by the selection of porous ceramic particles having certain particle sizes and including them in the composition used to form the cast. These casts are particularly advantageous for battlefield conditions because they can be administered to a wounded person quickly, form a cast rapidly, and have sufficient pliability to remain over the wound until the wounded person can be taken to a hospital for additional care.

The formation of the cast can be done, in some embodiments, by applying the compositions described herein directly to the wound. For example, a granular product can be poured directly into or onto the wound, kneaded to more rapidly or completely incorporate the blood or other body fluids into the granular porous ceramic if required, and allowed to seal the wound for the required amount of time. Once the porous ceramic has become sufficiently wetted and has developed sufficient cohesion between porous ceramic particles and adhesion to the wound tissue a durable, pliable cast is formed and the blood flow will be stopped.

In some embodiments, the pliable cast can consist essentially of blood mixed with the porous ceramic but also will include smaller amounts of other fluids absorbed from the This stoppage of blood flow in a wound using the compositions described herein can be attributed, at east in part, to the formation of a tight, adhesive seas between the tissue surrounding the wound and the edges of the cast, the formation of a tight, adhesive seal between the ruptured blood vessel and the composition within the wound, and to the pressure imparted to the wound by the presence of the cast itself. The adhesive and sealing qualities of the cast, as well as its adsorptive and absorptive characteristics, can be controlled by the selection of specific particle sizes for inclusion in the composition.

In some embodiments, the compositions described herein can stop bleeding and/or promote haemostasis in under 2 minutes or under 1 minute after being applied to a haemorrhaging wound.

In some embodiments, the pressure exerted by the composition once packed into the wound substantially remains even after manual pressure being applied to the wound (e.g., a medic pressing gauze on the wound to stop bleeding) is removed. This application of pressure from the composition after being packed into the wound can stop bleeding even without clotting of the blood, making these compositions desirable to persons who cannot effectively clot blood (e.g, coagulopathic patients) or are taking blood thinning medications. The compositions can be used on patients with congenital or acquired coagulopathy, which refers to a defect in the body's mechanism for blood clotting. An example of a congenital coagulopathy is haemophilia. An example of an acquired coagulopathy includes persons who take warpharin and cannot clot blood. As one of skill in the art will appreciate, these examples of coagulopathy are not limiting.

Tin some embodiments, the porous ceramic composition used for generating pressure in the wound is in the form of granules, a bandage impregnated or otherwise coated with porous ceramic as described herein, a perforated pouch or mesh bag containing the porous ceramic, or other form described herein. Such bags or pouches may be made of a dissolvable material such as pullulan, dextran, gelatin, cellulose-derivatives, hydrocolloids, polysaccharides, or mixtures thereof. Thus, the porous ceramic particle mixture may be either loose or fixed.

In some embodiments, the porous ceramic composition used for generating pressure in the wound is in the form of particles of porous ceramic contained within a sealed, un-perforated pouch or bag composed of a water soluble material. The term "water soluble" as used herein includes compositions that are dissolvable or otherwise dispersible in water.

The water soluble material can be a water soluble plastic. Suitable water soluble plastics include, but are not limited to, polyvinyl alcohol, ethylcellulose, hydroxypropyl methylcellulose or polyethylene oxide, or mixtures thereof. In some embodiments, the water soluble or dissolvable material can be a film.

In some embodiments, the water soluble or dissolvable substrates containing porous ceramic can be applied to a wound and the water soluble or dissolvable material will dissolve in the wound fluids including blood. The water soluble or dissolvable substrate can be formed into a container of suitable shape to contain the sterile composition and allow it to be conveyed to a wound as an intact mass.

Such substrates can be packaged within an exterior container as described herein (e.g., a foil package) to preserve the structure and sterility of the composition until use.

Those compositions and packages that can be used to treat a wound or in another medical use are considered to be "suitable for medical use." Additives may optionally be mixed with the porous ceramic particles in the composition to enhance the composition's ability to generate pressure by increasing inter-porous ceramic particle adherence and/or adherence of the porous ceramic particles at the site of the bleeding. Such additives include, but are not limited to, polyacrylamides, polysaccharides, polyacrylates, muco-adhesive compounds, and mixtures thereof.

The embodiments that generate pressure in the wound can be used in a wide variety of medical situations. For example, to promote haemostasis in a haemorrhaging wound.

These compositions are useful in rainy or high moisture battlefield conditions because they can effectively seal the wound despite elevated water content in and around the wound area. Such e'evated water content during tactica' situations can impair the ability of pro-coagulant devices and compositions by washing away the active ingredients or diluting their effects in the wound.

In addition to the description above, the following non-limiting example further illustrates the invention described herein.

EXAMPLES

EXAMPLE 1

Comparison of Calcium Phosphate Particles to Zeolite Pellets The heat of adsorption of porous 13-tricalcium phosphate particles were compared to the heat of adsorption of comparably sized zeolite pellets. The porous 13-tricalciurn phosphate particles (25 grams) were combined with distilled water (19 grams). Both the calcium phosphate particles and the distilled water were at room temperature before combining. Upon stirring, a peak temperature of 20°C was recorded. The same test using 5A zeolite particles produced a peak temperature of 79°C. Thus, a given amount & porous D-tricalcium phosphate particles produced significantly less adsorption heat than the same amount of zeolite particles.

Claims

CLAIMS1. A composition for promoting haemostasis, said composition comprising: a porous ceramic substrate; and wherein upon contact with a bleeding wound said haemostatic agent causes blood flowing from said bleeding wound to clot.
2. The haemostatic promoting composition of claim 1, wherein the porous ceramic substrate comprises a material selected from the group consisting of hydroxyapatite, calcium phosphates, calcium carbonates, calcium sulphates, and combinations thereof.
3. The haemostatic promoting composition of claim 1, wherein the porous ceramic substrate comprises tricalcium phosphate.
4. The haemostatic promoting composition of claim 1, wherein the porous ceramic substrate comprises 3-tricalcium phosphate.
5. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate is sintered.
6. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate is granular and has a particle size of 0.1-2 mm.
7. The haemostatic promoting composition of claims 1,-4 wherein the porous ceramic substrate is granular and has a particle size of 0.5-1.7 mm.
8. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate is granular and has a particle size of 1-1.7 mm.
9. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate is granular and has a particle size of 0.5-1.0 mm.
10. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate, wherein the total porosity is in the range of 5-80%.
11. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate, wherein the total porosity is in the range of 40-80%.
12. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate, wherein the total porosity is in the range of 65-75%.
13. The haemostatic promoting composition of claims 1-4, wherein the porous ceramic substrate, wherein the total porosity is 70%.
14. A unit package comprising a measured amount of a sterile composition comprising the particles of the haemostatic promoting composition of claims 1-4, wherein the particles provides at least one of the following activities: sorbing a body fluid, forming a cohesive mass, adhering to tissue, sealing a wound, promoting coagulant activity, and stopping blood flow from a wound.
15. The unit package of claim 14, wherein the fluid sorbed is blood or a wound fluid.
16. The unit package of claim 14, wherein the mixture of ceramic particles forms an adherent seal by mixing with blood to create a pliable cast within a wound that applies pressure to the wound.
17. The unit package of claim 14, wherein the package contains multiple units, each unit containing a sufficient amount of the ceramic particles for application to a
18. The unit package of claim 14, wherein the measured amount is between 0.01 gram to about 100 grams.
19. The unit package of claim 14, wherein the measured amount is between 1 gram to about 50 grams.
20. The unit package of claim 14, wherein the measured amount is between 50 grams and 250 grams.
21. The unit package of claim 14, wherein the unit package is sterilised.
22. The unit package of claim 14, wherein the composition has a specified moisture content.
23. The unit package of claim 22, wherein the moisture content is between about 0.1% to about 13%.
24. A method of promoting haemostasis in a haemolThaging wound, comprising applying the sterile composition of claims 1-4 in a quantity sufficient to promote one or both of the following: i) haemostasis and ii) formation of a cast comprising the one or more porous ceramic particles and blood from said haemorrhaging
25. The method of claim 24, wherein the cast forms a seal over a point of rupture in a blood vessel.
26. The method of claim 24, wherein the cast forms a seal over the wound.
27. The method of claim 24, wherein the cast forms a seal over the wound and also over a point of rupture in a blood vessel.
28. The method of claim 24, wherein the composition is applied directly to the
29. The method of claim 24, wherein the composition is loose porous ceramic particles.
30. The method of claim 24, wherein the composition is attached to or contained within a substrate.
31. The method of claim 24, wherein the substrate is selected from the group consisting of cotton, wool, linen, rayon, nylon, polyester, polyethylene, mineral wool or metal fibres, a dissolvable material, a water soluble material, and blends of these materials.
32. The method of claim 24, wherein the wound is either internal or external.
33. The method of claim 24, wherein the cast consists essentially of wound fluids and blood mixed with porous ceramic particles.
34. The method of c'aim 24, wherein the cast is pliaNe and duraNe, and capaNe of remaining structurally intact.
35. The method of claim 24, wherein the cast forms an adhesive seal within the
36. A method of forming a cast to cover a haemorrhaging wound, comprising applying the sterile composition of claims 1-4 in a quantity sufficient to form a cast comprising one or more porous ceramic particles and blood from said haemorrhaging wound.
37. The method of claim 36, wherein the composition is applied directly to the
38. The method of claim 36, wherein the cast is administered to a coagulopathic mammal.
39. The method of claim 36, wherein the cast consists essentially of wound fluids and blood mixed with porous ceramic particles.
40. The method of claim 36, wherein the cast is pliable and durable, and capable of remaining structurally intact.
41. The method of claim 36, wherein the cast forms an adhesive seal within the
42. A method of selecting a haemostatic composition of claims 1-4 comprising selecting a particle size mixture; testing the particle size mixture for at least one of the following: cohesion between particles, absorption, adsorption, or pliability; analysing the test results to select the components of a mixture; and producing a haemostatic composition comprising the mixture.
43. A method of forming a cast comprising applying directly to a wound a measured amount of a sterile composition comprising a mixture of porous ceramic particles, wherein the particles are of different specified particle sizes, to form a cast that adheres to the wound.
44. The method of claim 43, wherein the cast consists essentially of wound fluids and blood mixed with porous ceramic particles.
45. A unit package comprising a measured amount of a sterile composition comprising a mixture of porous ceramic particles, wherein the particles are of at least two different specified particle sizes and the mixture forms a cohesive, pliable mass after sorbing a fluid.
46. The unit package of claim 45, wherein the fluid is blood.
47. The unit package of claim 45, wherein the wetted mass stops the flow of blood from a wound in a mammal.
48. The unit package of claim 47, wherein the mammal is a human.
49. The unit package of claim 47, wherein the cohesive, pliable mass is durable and remains structurally intact when moving the mammal.
50. The unit package of claim 45, wherein the ceramic mixture is loose porous ceramic particles.
51. The unit package of claim 45, wherein the porous ceramic particle mixture is fixed to a substrate.
52. The unit package of claim 45, wherein the substrate is selected from the group consisting of cotton, wool, linen, rayon, nylon, polyester, polyethylene, mineral wool or metal fibres, a dissolvable material, a water soluble material, and blends of these materials.
53. The unit package of claim 45, wherein the packaged mixture is enmeshed in the substrate, intertwined with the substrate, coated onto the substrate, contained within, or adhered to the substrate.
54. The unit package of claim 51, wherein the substrate comprises polyvinyl alcohol, ethylcellulose, hydroxypropyl methylcellulose, polyethylene oxide, or mixtures thereof.
55. The unit package of claim 52, wherein the water soluble material is a water soluble plastic.