WO2011077145A1

WO2011077145A1 - Hemostatic device for administration to a wound cavity

Info

Publication number: WO2011077145A1
Application number: PCT/GB2010/052181
Authority: WO
Inventors: Anthony Dagger; Helene Lecomte; Nicholas Fry; Victoria Beadle; Rhianna Moss
Original assignee: Smith & Nephew Plc
Priority date: 2009-12-21
Filing date: 2010-12-21
Publication date: 2011-06-30
Also published as: GB0922258D0

Abstract

There is provided a device for administration to a wound cavity, the device comprising an expandable body and a haemostatic agent. Methods of manufacturing and using such a device are also provided. Furthermore, a wound treatment apparatus comprising such a device is also provided.

Description

HEMOSTATIC DEVICE FOR ADMINISTRATION TO A WOUND CAVITY

The present invention relates to a device for administration to a wound. In particular it relates to an expandable device having haemostatic properties 5 adapted for administration to a penetrating wound or other wound located in or comprising a cavity. The present invention also relates to methods of manufacturing and using such a device.

Bleeding from penetrating wounds can be difficult to control, as the

0 damaged blood vessels sit within a cavity and cannot easily be directly treated.

Penetrating wounds such as gunshot, shrapnel, or stabbing, create irregular cavities in the soft tissue, sometimes also damaging the bone.5 The cavities created often have a narrow entry wound, essentially

corresponding to the dimension of the projectile or blade, but a larger cavity within the soft tissue, caused by, for example, tissue crushing, cavitation of the projectile, or movement of the stabbing device. 0 Fackler (Annals of Emergency Medicine, 28:2, 1996) describes the type of cavity which may be expected with bullets from different types of weapons. His paper shows that cavity volumes, depending on which part of the body is damaged, can be calculated to reach 50 cm³. Exit wounds can be nonexistent if the projectile is retained in the body (rare), of similar dimensions5 to the entry wound if the projectile path is not hindered, or large and

messy if the projectile has interacted with certain types of tissue such as bone during its trajectory.

Faced with a cavity wound that is haemorrhaging, if the bullet or the0 temporary tissue displacement has damaged a blood vessel, several courses of action can be taken. Direct hand pressure onto the wound may suffice to stop blood flow if the damaged vessel does not sit too deep in the tissue. A tourniquet can be applied upstream from the wound;

however, this is only possible for extremity injuries, and if medical assistance is not too distant, as there are time restrictions on the use of a tourniquet. Similarly, a pressure point upstream from the injury can be found, and manual pressure applied to this point while awaiting further medical assistance. If the cavity is sufficiently accessible (via the exit or entry wound), gauze strips can be inserted into the cavity (often using thin implements, e.g. a pencil, to drive them in) to provide absorbency, and some degree of internal pressure onto the tissue, and thus to limit blood loss. However, these practices are either fiddly (gauze insertion), limited in their success rate, or only applicable to areas of the body where direct pressure can be applied. Many such injuries occur in areas which are not

"tourniquetable", such as the torso, the groin, or the armpit. There is therefore a need for a device and methods of applying the device, which can be applied quickly and efficiently to a penetrating wound, and prevent excessive blood loss until the victim or patient is within reach of organised medical care. This is particularly a need for the far-forward military, remote outdoors enthusiasts, and any civilian at risk of

penetrating injuries.

According to the present invention there is provided a device for

administration to a wound cavity, the device comprising an expandable body and a haemostatic agent. The expandable body has a non-expanded and an expanded form. The expandable body is typically in a non-expanded form prior to

administration to a subject, and adopts an expanded form once in position in the wound cavity.

By expandable or expansion it is meant volumetric expansion of the expandable body, and hence the device, is achieved when the expandable body changes from a non-expanded to an expanded form. This can be achieved, for example, by an expandable material absorbing or being filled with a substance (e.g. absorbing or being filled with a fluid) which drives an increase in volume, or by the expandable body adopting a

conformation or shape which takes up more volume (e.g. expansion of pre-compressed resilient means such as a spring or a foam), or a combination of both of these modes.

Preferably the expandable body is adapted to expand upon absorption of a liquid, especially blood or components thereof (e.g. plasma) or other body fluids. In such embodiments the expandable body comprises an expandable material which is adapted to absorb a liquid.

Alternatively or additionally, the expandable body may be adapted to expand in a manner independent of fluid absorption. To achieve this, the expandable body can comprise an inflatable member, e.g. the device may comprise a balloon in its interior. Alternatively, the device may contain a resilient member which is constrained in a non-expanded form, and which can be caused to adopt an expanded form once in position. For example the device might comprise a coiled member, e.g. a spring or other helical member, which is constrained in a non-expanded form by constraining means, and which expands, either laterally and/or longitudinally relative to the direction of insertion, when the constraining means is removed or released.

It should be noted that the device may comprise more than one

expandable body. Where more than one expandable body is present, the modes of expansion of each of the bodies can be the same or different, e.g. there might be a first resilient expandable body constrained in a compressed form and a second expandable body which expands upon absorption of liquid.

By "absorb", "absorption" and like terms, it is meant that the expandable material of the expandable body is able to take up a liquid into its structure, and that one or more of the dimensions of the body expand as a result of the absorption. It is possible that this absorption might involve some degree of adsorption or capillary action to cause the liquid to enter and be incorporated within the expandable material of the expandable body, but other methods of absorption are possible.

It should be understood that essentially any material which is

biocompatible can be used as the expandable material in the present invention, provided that it can expand in one or more dimensions, as a result of absorption, inflation or independent expansion. In addition, materials which are not inherently biocompatible can be used, provided that they are isolated from the body of the subject, e.g. when they are encased within a barrier which is impermeable to the expandable material.

In a preferred embodiment the expandable body comprises a water absorbing polymer, especially a super-absorbent polymer (SAP). Super absorbent polymers can be defined as polymeric materials capable of absorbing at least 5 times, more preferably at least 10 times, their mass of an aqueous solution containing 0.9 weight % sodium chloride. Typically such a SAP absorbs between 10 and 30 times its own mass of said aqueous solution. The absorbency of such polymers is typically affected by the presence of charged species in the medium to be absorbed; these polymers typically have a much higher absorbency than that stated above in de-ionised water, but the presence of charged species, such as salts or proteins, blocks hydrophilic groups in the polymer. Examples of SAPs suitable for use in the present invention include: - polyacrylic acids (e.g. sodium polyacrylate, polyacrylamide, ethylene maleic anhydride copolymer, copolymers of acrylate and

methacrylate moieties) and derivatives thereof;

starch-acrylic acid graft polymers (e.g. starch grafted copolymer of polyacrylonitrile) and derivatives thereof; and

- hygroscopic polymers, which can be capable of forming hydrogels, including polyvinyl alcohol copolymers, polyethylene oxide, polysaccharides and derivatives thereof (e.g. alginate, carboxy- methyl-cellulose, carboxy-methyl-chitosan). Synthetic polymers are preferred to polymers of natural origin due to the potential for consistency in their composition and supply, which are more difficult to control with natural polymers.

The selection of the SAP can depend upon the required properties of the device and expandable body. For example, polyacrylic acids and derivatives thereof typically have greater absorbency (and thus potential to expand) and retain more fluid under compression than many of the other materials listed above. Furthermore, their greater absorbency means that a smaller volume of such materials can be included in device of the present invention, typically leading to cost saving and dimension reducing benefits. Whereas polysaccharides or derivatives thereof provide versatile backbones which can be functionalised to match desirable properties of the expandable body, for example, to provide tissue adhesion or add ionic moieties to the polymer to enhance the haemostatic properties.

Accordingly, such polysaccharides or derivatives thereof can be

chemically engineered to be absorbent and functional, depending upon the required properties of the expandable body.

In certain embodiments the SAP can be chemically cross-linked to strengthen the expandable material, although this is typically not required for the materials mentioned above.

In general, all the above SAPs are available in powder or granular form, which is generally compatible with the present invention. The most common type of SAP is sodium polyacrylate (a poly-acrylic acid sodium salt), and this is a preferred form of SAP for use in the present invention. Furthermore, it has the benefit of having great absorbency whilst retaining more fluid under compression than the other materials, as is typically present during application of the device of the present invention, making it particularly suitable for such use.

Alternatively or additionally the expandable body may comprise other expandable materials, for example, cellulosic or fiber-based products. In embodiments of the present invention the expandable body can comprise polysaccharides or carbohydrates (e.g. chitosan, cellulose, or alginate), and functionalised derivatives thereof, including

carboxymethylated derivatives. Such materials can be provided in a variety of forms, but a preferred form is in fibres. When in a fibrous format, such materials do not always require the polymer to be chemically cross- linked to maintain their structural integrity. Such fibres can be spun, woven, carded, needled, braided or otherwise processed to form a secondary structure, such as a gauze, mat, felt, cord or garland. In an alternative embodiment, the fibres of such materials may be fixed together by appropriate methods (e.g. stitching or fixing to a node) and then compressed using existing processes in the personal care industry such as automated compression used in the manufacture of sanitary tampons. Accordingly, once in position in the wound cavity, the fibres absorb blood and expand, filling the wound cavity.

Porous, sponge-like materials are a preferred material for use in the expandable body. In particular, cellulose sponge is a highly preferred expandable material for use in the present invention. In one preferred embodiment the expandable body comprises a sponge material, preferably a cellulose sponge, which has been pre-compressed into a compressed form, which is capable of expanding to a non- compressed form upon absorption of a liquid, e.g. blood. Suitably the sponge has been compressed while in a wet state, e.g. while substantially saturated with an aqueous medium, and allowed to dry whilst in the compressed state. Once dry, the compressed dry sponge retains the dimensions to which it was compressed prior to and during the drying process. Such a pre-compressed dry sponge is expandable from its compressed form to an expanded form upon absorption of a liquid.

The expandable body can comprise an expandable material in monolithic or particulate form. Certain expandable materials are predominantly found in particulate form, e.g. SAPs. Other materials, such as sponges, can be provided in either monolithic form, or in particulate form. Where the expandable body comprises particulate expandable material, e.g. granules of SAP or pieces of cellulose sponge, it is generally required that the particulate material is constrained within a barrier, e.g. a

membrane, to ensure the device retains structural integrity before and during use. Where the expandable material requires the absorption of liquid from the wound to expand, then it must, of course, be contained within a liquid-permeable barrier. Even when the expandable material is not in particulate form, it may be desirable to encase it in a

barrier/membrane, e.g. a liquid-permeable barrier. The barrier may suitably take the form of a bag or pouch, within which the expandable material is retained. Such a barrier will typically be porous to liquid, e.g. blood or components thereof, to ensure that fluid within the wound cavity is able to migrate through the barrier and into the expandable material. Generally the liquid-permeable barrier will have pores which allow the passage of liquid into the expandable body, but which are sufficiently small to prevent the migration of the expandable material to the exterior of the liquid-permeable barrier. Suitable pore sizes for the barrier will therefore depend on the size of the particulate materials being used, i.e. the maximum pore size should be smaller than the smallest particle size of the expandable material. In general the pore size will be sufficiently large to allow platelets to enter the expandable body.

It is preferred that the barrier is elastic, such that it is capable of stretching to accommodate expansion of the expandable material. Alternatively or additionally, the barrier could be sized such that, when filled with the required amount of expandable material, it has spare internal volume which will be taken up by expansion of the expandable material. For example the barrier could be non-elastic and be folded or pleated into a compact form such that expansion of the expandable material will be accommodated by unfolding or un-pleating of the barrier. There are a variety of materials which are suitable for forming such a barrier, and the person skilled in the art would be able to select a suitable material. For example, the material may be a fabric pouch comprising woven elastic fibres (e.g. lycra® fibres), or it may comprise porous non- woven materials, such as porous expanded fluoropolymer (e.g. ePTFE) or a polyurethane net.

Where the expandable body comprises a structurally coherent (e.g.

monolithic) expandable material, it is not generally necessary that it is constrained within a barrier. This is the case where the expandable material has sufficient inherent structural integrity such that, during normal use, it is not expected that fragments of the expandable material would become detached; such fragments could undesirably contaminate the wound site. Furthermore, in the case of a structurally coherent expandable material it should be possible that, after the device has served its purpose, it can be removed as a whole. However, it should be noted that there may be situations where it may be desirable to provide a structurally coherent expandable material with a barrier/membrane, e.g. to prevent migration of a particulate haemostatic agent, or for easier application to the wound site. This is discussed further below.

In embodiments of the present invention the expandable body can be wholly or partially encased by a barrier/membrane. As such the outside surface of the device can be provided by such a membrane. As

mentioned above, this may form a barrier to contain a material (e.g. a particulate expandable material or a haemostatic agent), or it may have other purposes. In certain embodiments it is preferred that the

barrier/membrane is degradable within the wound cavity, e.g. it can be water soluble or otherwise degradable in the conditions found within a wound cavity. The membrane can have one or more of the following functions:

- Constrainment - The membrane can constrain the device in an

unexpanded form until it is in location within the wound cavity.

Accordingly such a membrane can provide the constraining means discussed above in respect of expandable bodies comprising pre- compressed resilient members. When the membrane is broken or degrades the device is able to expand to an expanded form.

- Barrier - The role of a membrane as a barrier to prevent the escape of particulates or for other purposes has been discussed above.

- Lubrication - The membrane may serve to lubricate the device to make it easier to insert into desired location within the wound cavity.

- Delivery of active agents - The membrane may comprise active agents to be delivered to the wound cavity such as, but not restricted to, clotting agents, antiseptics and antibiotics.

- Providing the haemostatic agent - As mentioned above and

discussed in further detail below, the haemostatic agent can be bound to, or otherwise associated with the membrane.

- Clotting scaffold - The membrane may advantageously provide a scaffold to facilitate clotting, and thus augment haemostasis. Such a role is particularly relevant where the expandable material itself has a gelatinous or otherwise amorphous nature. Such materials, e.g. hydrogels and other SAPs, do not provide a scaffold capable of significantly supporting and promoting clot formation.

The membrane/barrier may comprise or consist entirely of one or more degradable material, for example a water soluble polymer.

Examples of such materials include:

- Polyethylene glycol (PEG) - Polyvinyl alcohol (PVA)

- Polyvinyl pyrolidone (PVP)

- Water-soluble polysaccharides or sugars (e.g. hydrophilic cellulose derivatives such as hydroxyethyl cellulose, sodium alginate, xanthan, polydextrose, maltodextrin or hydroxyethyl chitosan)

PVA and PVP are particularly suitable materials as they may be easily formed into films for use in the present invention. PEG has been used for many years in medical devices and is known to be safe for such use. Furthermore, a membrane/barrier formed of PEG can act as a binder to affect adhesion to the tissue in use. Alternatively where a thin film membrane/barrier is required, the material employed may be a mixture of polysaccharide derivatives blended together for optimal flexibility or coating properties, while retaining their water-solubility in thin films.

Where the membrane is required to constrain the expandable body, it is essential that the membrane is sufficiently strong to withstand the expansive force of the expandable body. Suitable membranes can be formed from materials such as woven, non-woven or nets of synthetic polymers (e.g. nylon, lycra, polyurethane, polyester, polylactic acid, polyglycolic acid) or woven or non-woven natural polymers or their derivatives (e.g. cellulose, chitosan, cotton).

There are a wide variety of haemostatic agents available, many of which can be used with the present invention. For example, suitable materials might include one or more of:

clays such as bentonite, smectite, montmorillonite, attaplugite, kaolin or kaolinite - powders of such clays are preferred, and bentonite clay powder is a particularly preferred haemostatic agent for use in the present invention; zeolite, especially in powdered form;

diatomaceous earth (e.g. celite);

self-assembling peptides (e.g. as discussed in Ellis-Behnke et al., Nanomedicine: Nanotechnology, Biology and Medicine, Volume 2, Issue 4, December 2006, Pages 207-215);

keratin (see e.g., Aboushwareb et al, Journal of Biomedical Materials Research Part B: Applied Biomaterials, Volume 90B Issue 1 , Pages 45-54.);

starch-based materials (e.g. Traumadex™ and Medafor™ products); modified glass fibres (Stasilon™ product, paper in press

http://www.entegrion.com/Portals/80/JournalArticles/rational_design. pdf);

chitosan (see e.g. US4394373);

cellulose/oxidated cellulose (see e.g., Surgicel™, Gelita™ products); collagen (e.g. Vitagel™, Avitene™, Gelfoam™ products);

fibrin; and

thrombin.

In general the haemostatic agent is associated with the expandable body or a barrier/membrane surrounding the expandable body. It is essential that the haemostatic agent is able to contact blood within the wound cavity to promote haemostasis. Preferably it is provided as a coating on the expandable material (e.g. a coating on particles or on strands of or on pores within the expandable material) using a binding agent (e.g. a polyol binder), or it may be mixed with the expandable material (e.g. as a mixture of particles of expandable material and haemostatic agent). Alternatively or additionally the haemostatic agent can be coated on a

barrier/membrane surrounding the expandable body. The haemostatic agent can be bonded to the surface of the expandable body or the barrier/membrane, e.g. though covalent bonding. The covalent bonding of a haemostatic agent (e.g. clay particles) to the expandable material (e.g. SAP or cellulose) or barrier/membrane can be achieved by reacting a linker molecule having at least two reactive functions, which can react with reactive groups on the expandable material or barrier/membrane and on the haemostatic agent (e.g. hydroxyl moieties on the clay particle and the cellulose substrate). Examples of such linkers can be aminoalcohols (e.g. ethanolamine, aminopropanol), diamines (e.g. ethylenediamine), organosilanes (e.g. aminopropylsilane), aminoacids, aminoesters and their derivatives (e.g. amino carboxylic acids, where the amino group is protected for the first coupling reaction). Alternatively, the haemostatic agent may be integrated into the structure of a polymeric expandable material by mixing the haemostatic agent with the monomers prior to polymerisation to form the expandable material. The amount of haemostatic agent provided in the device will depend on the properties of the particular haemostatic agent and the desired properties of the device. In this regard it is observed that it is desirable that the device of the present invention expands such that it provides pressure on the interior surface of the cavity of the wound. In many embodiments of the present invention, expansion is determined by absorption of liquid from the wound, typically blood or blood components. Where clotting occurs too rapidly, it may prevent or slow down absorption of liquid by the device, as a layer of clotted blood can form around the device before sufficient expansion to fill the wound cavity has occurred. Thus the level of clotting (as a result of the presence of the haemostatic agent) and the amount of expansion should preferably be balanced. The exact amount of haemostatic agent can be determined by experimentation by the person skilled in the art. In one embodiment of the present invention, the expandable material used to form the expandable body may have dual action, providing expansion and enhancing haemostasis due to desiccation, hence concentration of clotting factors on its surface. Such expandable materials capable of providing this dual action would be materials which absorb liquid blood components such as plasma, thus concentrating the blood components involved in clotting, and would be apparent to the person skilled in the art in view of the exemplified expandable materials listed above.

The device of the present invention preferably comprises anchoring means. Such anchoring means may serve to anchor the device in position in the wound cavity. The expansion of the device may, in many instances, serve to secure the device in the desired position, e.g. in a wound with a relatively narrow opening and a relatively large cavity. However, in other circumstances it may be desirable to further anchor the device in the wound cavity when, for example, expansion of the device may not provide suitably secure anchoring of the device in the wound cavity.

The anchoring means may have various forms, such as:

- One or more barbed members - such barbed members prevent the device from coming out of the wound cavity by engaging with tissue, e.g. within the cavity or in the opening. For example, the device may comprise one or more barbs on the outside of the device.

- One or more tying members - such members allow the device to be secured in place by tying the tying members. For example, the device may comprise one or more elongated strips or strands of flexible material extending from the device which can be tied around the wounded part of the body. For example, the device may comprise two lengths of bandage material extending from the device which, in use, extend from the device when located in the wound cavity, and can be wrapped around the body part and tied. Such an embodiment conveniently allows additional dressings to be held in place over the wound by the tying members and/or allows additional pressure to be applied to the wounded area, e.g. by using the tying members in the manner of a tourniquet. In one embodiment, the tying members may comprise self-adhesive means at each end of the tying members, preferably the self- adhesive means are hook and loop fasteners.

- Adhesive - An adhesive suitable to adhere to tissue can be

provided on at least a portion of the outside of the device such that it will bind to tissue within the wound cavity. Suitable tissue adhesives are known in the art and include fibrin glues and cyanoacrylates, amongst others. Alternatively, a pressure sensitive medical adhesive may be coated to one or more portions of the device located externally of the wound cavity, such that portions adhere to the skin proximate to the wound site to fix the device in position.

- Plug - A plug can be associated with the device to plug the

entrance to the cavity to prevent the device from escaping the cavity prematurely.

In one particularly preferred embodiment of the present invention the expandable body comprises SAP (e.g. polyacrylate polymer), preferably in particulate or fibrous form, and a particulate haemostatic agent, provided within a stretchable liquid-permeable pouch. The stretchable liquid- permeable pouch can be formed, for example, from a fabric such as a nylon/lycra blend. Preferably the haemostatic agent is zeolite powder, although other haemostats could be used provided they are compatible with the SAP. In one embodiment a mixture of approximately 50:50 by weight SAP and haemostatic agent is used, although other ratios can be selected depending on the balance of clotting versus expansion desired, e.g. from 10:90 to 90:10, by weight, more preferably from 25:75 to 75:25. In another particularly preferred embodiment the device comprises an expandable body formed from a structurally coherent expandable material, the expandable body having a haemostatic agent associated therewith, e.g., by coating. The device may comprise a membrane at least partially encasing the expandable body. In such a device the membrane is not required to contain the expandable body, but may be included to provide additional functionality to the device, as discussed above.

In a preferred embodiment of the present invention the device comprises a monolithic expandable body formed of a sponge material, such as cellulose sponge, wherein a haemostatic agent is associated with the sponge. The expandable body suitably has a shape suited for insertion into the cavity of a wound to be treated; a particularly suitable shape for a typical puncture wound is an elongate shape, such as a cylinder, but other shapes may also be suitable depending on the wound to be treated.

Preferably the sponge is provided in a dry, pre-compressed form, as discussed above. The sponge is associated with a haemostatic agent, which can suitably be disposed on the surface of the sponge, for example on the outer surface and/or on the surface within the pores of the sponge, e.g. as a coating on the surface of the sponge. In a preferred embodiment the haemostatic agent is bentonite clay, but other haemostatic agents could be used. The ratio of clay to sponge material (by weight) is suitably from 70:30 (clay:sponge) to 20:80, more preferably from 45:55 to 25:75, especially around 35:65. Such ratios give a preferable balance of clotting and expansion of the expandable body. Such ratios are particularly appropriate for a device comprising a clay (e.g. bentonite) and cellulose sponge.

Preferably the haemostatic agent (e.g. clay) is loaded into the sponge as a coating on the surface of the sponge; this can be achieved by immersing the sponge in a solution or suspension of the haemostatic agent and drying the sponge to leave the haemostatic agent on the surface of the sponge. Other methods of loading the sponge with the haemostatic agent would be apparent to the person skilled in the art.

It is possible that the device or expandable body comprises regions having differing loading of haemostatic agent. For example, the haemostatic agent might be provided only on the outside of the device, e.g. on a barrier/membrane, or alternatively the device (e.g. a cylindrical device) might have a gradient, e.g. a radial gradient, of loading with a haemostatic agent (e.g. bentonite clay) such that the outer regions of the device have a higher loading of haemostatic agent than inner regions, or vice versa. Such gradient might be stepped or it might be smooth. One way in which such a gradient can be achieved is through use of a plurality of discrete cylinders of sponge which are sized such that they can be nested to form a single expandable body. The discrete cylinders can suitably be fixed together by a fixing means, for example a suitable adhesive or a suture or the like. Alternatively, friction between the cylinders may be sufficient to hold the expandable body together during use. Where an adhesive is used to hold cylinders together, the adhesive may suitably comprise acrylate-based and/or silicone-based adhesives. In general, it is preferred that the adhesive is used in a manner which does not prevent or significantly reduce the passage of liquid from one cylinder to another, e.g. the adhesive may be provided at one or more loci, with the majority of the surface area of the interface between adjacent cylinders being free from adhesive, and/or the adhesive may be porous to liquid.

Regions of expandable body with reduced or substantially no haemostatic agent may be provided. Such regions can suitably allow penetration of liquid (e.g. blood) into the device once clotting has become well established on or in regions of the device where the haemostatic agent is present; clotting on the outer surface of the expandable body, particularly when forming a thick layer, can slow or prevent further ingress of liquid into the expandable body, thus limiting expansion of the expandable body to some extent. By providing regions with a sufficiently low loading of haemostatic agent that clotting occurs slowly compared with the fully loaded regions of the device, this allow these regions to act as ports to facilitate penetration of liquid. Such regions might take the form of an outer layer of the expandable body, e.g. a cylinder of material, or it might be one or more channels which penetrate towards the centre of the expandable body.

The device of the present invention can comprise additional active agents. Such agents may be desirable to have a therapeutic effect at the wound site. Such agents may include antiseptics, antibacterials, antibiotics, antiinflammatories, NSAIDs, growth factors, etc.

The device may further comprise binding means to bind the haemostatic agent or other particulate materials to the device, e.g. the expandable body or barrier/membrane. Such binding means may be, for example, adhesives, polyols or polysaccharides. Suitable polyols include, for example, one or more of polyethylene glycol, polyvinyalcohol and polymeric polyols, glycerol and derivatives, sorbitol, xylitol or maltol. An exemplary polysaccharide is polydextrose, although there are others which are suitable. Suitable adhesives may include acrylate-based and silicone-based adhesives.

The device of the present invention may further comprise a removal means to facilitate removal of the device from the wound. For example, the removal means may comprise a member attached to the device, e.g. to the expandable body, which is adapted to extend from the wound cavity when the device is in position in the wound. The member may be, for example, a string or tab. The member may be integral with the

expandable body, or it may be connected thereto in a suitable manner. In any event the expandable body and the removal means should be sufficiently strongly linked to allow application of sufficient force to remove the expanded device from the wound cavity. One suitable removal means is a tying member which is attached to the device to provide an anchoring function. Once the device has performed its function, the tying means can be untied and then used to pull the device from the cavity. Preferably the removal means is radiopaque such that it can easily be located by x-ray should this be required.

In a further embodiment, the device according to the present invention may comprise a rigid elongate member attached to the device allowing the device to be urged into a desired location in a wound cavity. For example, the device may comprise a rigid rod attached to the device which allows the device to be urged into and/or within the wound cavity. Such a rigid elongate member could be formed from, for example, metal or a polymeric material (e.g. a plastics material). An advantage of having such an elongate member attached to the device is that the device can be urged against a particular site in the wound cavity where it is desirable to maximise the pressure applied. This pressure can be applied before, during or after expansion of the expandable member. In a further aspect the present invention provides a device according to the present invention in association with an applicator, thus providing a wound treatment apparatus. Suitably the device is loaded into the applicator, ready for application to a wound. The applicator may suitably comprise a hollow housing, e.g. a shaft, having a lumen of a suitable shape and size to accommodate the device in its non-expanded form. The shaft has an opening at one end to allow the device to pass therefrom and into the wound. Preferably ejection means is provided to allow a user to eject the device from the applicator and into the wound cavity. Suitably the ejection means comprises a pusher, e.g. a plunger or piston, which is moveably, e.g. slideably, mounted in the shaft, to allow force to be applied to the device to eject it from the applicator. The pusher may be actuated by being directly urged by a user, e.g. pushing with a finger or thumb, or it might be actuated via additional mechanical means such as a screw, rack and pinion or other such mechanical means, which might allow the application of a mechanical advantage. Alternative ejection means may comprise a resilient means, such as a spring which can be activated to urge the device from the applicator.

Preferably the applicator comprises a cylindrical portion for receiving the device. According to a further aspect the present invention provides a method of making a device for administration to a wound cavity, the method comprising;

a) providing an expandable body;

b) providing a haemostatic agent; and

c) associating the haemostatic agent with the expandable body.

Details of various expandable bodies, haemostatic agents and other details of the device which may be provided in accordance with the method are set out above.

The method may further comprise providing a barrier/membrane around the expandable body, such that an expandable material within the expandable body is at least partially, preferably completely, encased by the barrier/membrane. This is particularly appropriate where the expandable body comprises a particulate expandable material.

In certain embodiments step a) may comprise providing an expandable material in a wet, expanded form, compressing said material, and drying said material while it is in a compressed form. This is particularly appropriate for sponge materials, e.g. cellulose sponge.

Alternatively or additionally step a) may comprise providing a particulate expandable material, e.g. a SAP. Such a particulate expandable material is encased within a barrier/membrane.

Alternatively or additionally step a) may comprise providing a resilient means, pre-compressing said resilient means into a non-expanded form, and constraining said resilient means in said non-expanded with a constraining means. Alternatively or additionally step a) may comprise providing an inflatable member. Step c) may comprise coating an expandable material with the

haemostatic agent. This can be achieved by immersing the expandable material into a solution or suspension of the haemostatic agent and allowing the material to dry, thus coating the material in the haemostatic agent. Immersion and drying can be repeated to provide additional loading. This is particularly well suited to use on porous materials such as cellulose sponge. Where sponge is being loaded, it can be beneficial to compress and release compression of the sponge while immersed to cause the solution/suspension to penetrate into the interior of the sponge. In a preferred embodiment the expandable body is immersed in a solution or suspension of haemostatic agent, optionally compressed and released one or more times to encourage penetration of the haemostatic agent into the expandable body, and then compressed and dried to form a non- expanded expandable body.

Alternatively or additionally step c) may comprise mixing a particulate haemostatic agent with a particulate expandable material. Typically such a mixture would then be encased within a barrier/membrane. Alternatively, step c) may comprise associating the haemostatic agent with a barrier/membrane surrounding the expandable body, e.g. by bonding or adsorbing the haemostatic agent to the barrier/membrane. For example, a barrier made from a stretchable material encasing an expandable material might be impregnated with a suitable haemostatic material. This could conveniently be achieved through immersing the membrane in a solution or suspension of the haemostatic agent and allowing the material to dry, thus coating the material in the haemostatic agent.

According to a further aspect, the present invention provides a method of treating a wound, especially a puncture wound, the method comprising:

• providing a device as set out above; and

• applying said device to the cavity of the wound.

Preferably the device is provided in an applicator. Suitable applicators are described above. Using such an applicator, the device can be applied by actuating the ejection means to eject the device from the applicator.

The method may further involve utilising an anchoring means to anchor the device in position in the wound cavity. For example the device could be tied or adhered in position, a plug could be used to plug the wound opening, or a barb member could be engaged with tissues in or around the wound cavity.

Preferably the method further comprises removing the device from the wound by pulling on a removal means provided on the device.

Preferably a device is sized and shaped to suit the wound to be treated. Typically the device should be adapted such that it expands to

substantially fill the wound cavity. Accordingly the expanded volume of the device should be approximately the same, or slightly larger, than the volume of the wound cavity, so that it applies pressure to the surface of the wound cavity. Accordingly the method may comprise selecting a device, e.g. from a plurality of differently dimensioned devices, which is suitably sized and shaped for the particular wound to be treated. It should be noted that, although the present invention is well suited to penetrating wounds such as bullet or stab wounds (i.e. blast wounds), it may be applied in other situations, such as where haemostasis is required in a cavity during a surgical procedure, or to stop bleeding within a body cavity such as the nose or ear. For example the device could be used during vascular or arterial access surgery to prevent bleeding (e.g. as a femoral vascular closure device). Another suitable use is in the care of tunnelling wounds, keeping the surface channel open while the inside of the wound closes up and heals.

An advantage of the present invention is that it can both enhance clotting through the haemostatic agent, and apply pressure to tissue within the cavity through the expandable body. Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying figures in which:

Fig. 1 shows an applicator with an SAP filled lycra/nylon pouch (a) and pouch after 3 min immersion in porcine blood (b);

Fig. 2 shows a schematic flow diagram of the preparation of clay-loaded, compressed cellulose sponge cylinder;

Fig. 3 shows an uncompressed, raw cellulose sponge cylinder (top) and a compressed, dried, clay-loaded sponge (bottom).

Fig. 4 shows compressed, dried, 2:1 clay-loaded samples, before immersion (a), and after >6min immersion (b) (b-left: in PBS, b-right: in porcine blood).

Fig. 5 shows the diameter recovery for samples with different clay loadings when immersed in blood.

Fig. 6 shows examples of clotting on the device surface: (a) no clotting, and (b) enhanced clotting. Fig. 7 shows an embodiment of a device according to the present invention having a tying means.

Fig. 8 shows an embodiment of a device according to the present invention having an expandable body comprising an inflatable member. Fig. 9 shows an embodiment of a device according to the present invention comprising a garland of fibres of expandable material joined at a node, and coated in a haemostatic agent.

A - Superabsorbent polymer in a nylon pouch with haemostatic powder

An inherently expandable nylon/lycra (lycra®, also known as spandex ®, is a well known polyurethane-polyurea copolymer fibre) pouch, is filled with a predetermined quantity of superabsorbent polymer powder such as a polyacrylate polymer, or other such composition. Other expandable pouches could, of course, be used.

Additives can be introduced to the superabsorbent polymer, such as bentonite clay powder, or zeolite powder, to encourage blood clotting.

The filled pouch is fitted inside an applicator similar to that used for hygienic tampons. Delivery of the pouch to the wound can be performed with the aid of the applicator, e.g. through the small entry aperture of a puncture or bullet wound.

Fig. 1A shows an applicator containing a lycra pouch filled with

superabsorbent polymer (polyacrylate polymer) and zeolite powder (50:50 by weight).

Once inserted into the wound, or in the present example into an in vitro sample of porcine blood, the superabsorbent polymer powder expands greatly in the presence of blood so as to fill the cavity it was placed in, while allowing exposure of the active particles which are known to enhance the natural clotting mechanism, as illustrated in Figure 1 B. Removal of the pouch is performed by gently pulling on a radiopaque string, attached to the pouch, which is intended to be left outside of the wound. Provision of a larger pouch than the average cavity size will ensure that the contents of the pouch can be taken out through the same opening of wound as it was placed through. As the device is removed from the wound, its compressible nature allows it to adapt to the size of the opening through which it is being drawn, typically adopting an elongate and relatively narrow conformation. In practice, when the device is removed, the wound entrance may well be enlarged surgically, e.g. to allow cleaning and debriding of the wound, and this will facilitate removal of the device.

In use the particulate SAP allows for expansion of the device while the haemostatic agent facilitates clotting. Furthermore, the barrier provides a scaffold which assists in the formation of an effective clot.

B - Monolithic cellulose sponge with clay particles

B.1 - Fabrication

A medical-grade cellulose sponge cylinder is cut out of a sponge block. It is then impregnated with a suspension of bentonite clay (Aldrich, 28523-4) in deionised water. The composition of the suspension will dictate how much clay is loaded onto the cylinder - in the present example several loadings were tried. The raw cellulose sponge is then compressed, squeezed, shaken, and left to re-expand within the suspension several times, to ensure that the clay particles have penetrated to the centre of the sponge cylinder. The cylinder of sponge is then purged of its excess suspension by manual compression, and inserted into a cylindrical receptacle of a smaller diameter than the cylinder itself, so as to put the device under

compression diametrically.

The compressed, clay-loaded cylinder is then dried overnight, or until constant mass; this is suitably carried out in a vacuum oven at room temperature. Fig. 2 summarises the process. Item 1 is the raw cellulose sponge cylinder. Item 2 is the wet, clay-loaded sponge cylinder. Item 3 is the cylindrical drying mould, of smaller diameter than the initial sponge. Item 4 is the compressed, wet, clay-loaded cellulose sponge cylinder being held in the drying mould. After drying, the compressed, clay-loaded sponge cylinder substantially retains the shape and dimensions given by the drying mould, providing dimensional constraint, compared to the initial raw cellulose sponge device highlighted earlier, as shown in Fig. 3. In the present example the sponge retains a diameter around 1 1 mm, down from an initial diameter of 23 mm for raw sponge.

B.2 - Behaviour on Exposure to Animal Blood

On exposure to "uncoagulated", citrated porcine blood, the compressed, clay-loaded sponge can expand back to its initial dimension, providing the self-expansion property desired. In doing so, the clay particles present on the sponge allow the blood to start clotting, providing the desired effect of enhanced haemostasis. The rate of expansion, and the ultimate diameter attained, depend on: extent of compression of the sponge (ratio of initial versus

compressed diameter),

the clay-loading level of the compressed sponge, and

the absorption capacity of the sponge.

In particular, it was observed that for high clay loadings, blood clotting is so efficient on the device that a layer of gelatinous clot forms on the surface of the non-expanded device, blocking further access of fluid to the sponge, and thus limiting the expansion of the cylinder. This may be undesirable if it is desired that the device expands to fill a wound cavity, which would not be permitted due to prevention of further expansion once the clot has formed.

Figure 4 shows the difference in expansion reached, for the same material immersed in phosphate buffer saline (PBS), which reaches its initial diameter immediately, and immersed in citrated porcine blood, which remains at a very similar diameter as its compressed version.

This particular sample was loaded using a clay suspension in water at 33% by weight (20g clay in 40 g water), giving a clay:cellulose ratio of around 2:1 in the dried sample. It is therefore understandable that very efficient clotting due to the large amount of clay present may limit the expansion of the sponge cylinder.

B.3 - Determination of Optimal Clay Loading

Different concentration of loading solution were used to load 23 mm sponge cylinders:

20g clay in 40g water (33% clay)

10g clay in 40g water (20% clay)

4g clay in 40g water (9% clay) These cylinders were then dried in a mould overnight, yielding compressed, clay-loaded samples of 1 1 mm in diameter.

Weighing enabled estimation of the clay loadings on these cylinders to be:

(1 ) around 70% weight clay to total device (2:1 clay to cellulose)

(2) around 35% weight clay to total device (1 :2 clay to cellulose)

(3) around 20% weight clay to total device (1 :4 clay to cellulose)

One sample of each cylinder was immersed either in PBS or in

uncoagulated porcine blood, and taken out and photographed at regular intervals to monitor and compare the rates of expansion, and ultimate diameters reached. Each picture contained a scale, which enabled estimation of the expansion of the cylinders and calculation a percentage recovery, based on the initial cylinder diameter of 23 mm. Table 2 summarises the expansion recovery at different time points.

Table 2: Summary of expansion recovery over time for different loadings

Fig. 5 is a graphical representation of some of the Table 2 data, namely the samples immersed in blood only. It highlights that the samples with lower clay loadings expand much faster than if the clay loading is high. This can be linked to the difficulty of wetting a sponge sample which contains a large amount of clay. As well as rapidity of expansion, it is of course highly desirable that intra- cavity haemostat devices promote blood clotting. Ability to promote clotting can be observed and assessed by photographing at each time point; if clotting has been enhanced by the device, a layer of dark, gelatinous clot will be present on the surface. Some good examples are shown in Fig. 6.

These observations show that while the 20% clay loaded device expands more rapidly than the others, it does not promote clotting of citrated porcine blood to the same extent that the higher clay loadings do. It is possible that this behaviour may differ in non-citrated, fresh blood, however it is impractical to use this in the lab as the blood clots within minutes of collection. Nevertheless, optimisation of the levels of haemostatic agent for use with non-citrated, fresh blood would be a simple procedure for the person skilled in the art in light of the teaching of the present application, e.g. through animal studies.

In conclusion, the above experiments highlight the presence of an operating window of clay loading onto cellulose sponge, to enable rapid expansion while also promoting clotting. Out of the loadings tried here, the 35% clay loaded sample seems to fulfil both conditions.

Other embodiments of a device according to the present invention Numerous other embodiments of the present invention can be envisaged, a number of which are briefly described below:

C - Device with integral tying means A device as described above in Examples A and B, or in any of the below examples, can comprise a tying means, such as a bandage, attached to the device, e.g. attached at one end of the device. An example of a device 701 comprising tying means 702 and 703 is shown in Figure 7. The tying means suitably comprises two lengths of a bandage material

702 and 703 extending from one end 704 of the device 701 . In one embodiment of the present invention, the two lengths of bandage material can be tied around the external region of the body where the device is placed. Alternatively, as in the illustrated embodiment, the two lengths of bandage material 702 and 703 comprise self-adhesion means 705 and 706 such as a hook and loop fasteners, disposed at the far ends of the material 702 and 703 which can secure the ends of the materials 702 and

703 together once passed around the external region of the body. In a further embodiment, an adhesive may be applied to the ends of the materials 702 and 703 so that the ends may be secured together or to the surrounding skin. In another alternative, substantially the entire tying means could be provided with an adhesive. In these ways, the tying means help to anchor the device in position, allow additional dressing to be held in place, and/or allow pressure to be applied to the area of the wound, e.g. as a tourniquet.

In the embodiment illustrated in Figure 7, the device 701 comprises a compressed, expandable material of any of the types discussed above. The compressed, expandable material may be loaded or coated with the haemostatic agent and/or the device 701 may further comprise a membrane/barrier (not shown) to maintain the material in a compressed state, to lubricate the device 701 to aid insertion into the wound cavity, to provide the haemostatic agent or to provide a clotting scaffold. Depending upon the function of the membrane/barrier, it may be formed of a material capable of degrading when in position within the wound cavity. In a preferred embodiment a spacer is provided extending from the device, to which the tying means are attached. The spacer prevents tension on the bandages from pulling the device from the wound cavity. Suitably the spacer can be formed from a length of bandage material which then bifurcates to form the tying means, although other spacer means can easily be envisaged. The length of the spacer should be sufficient to extend from the device within the cavity to the body surface when the device is in position. For example, 5 to 20 centimetres may be suitable depending on the depth of the wound.

D - Inflatable balloon inside an elastic membrane.

As illustrated in Figure 8A, the device 801 in accordance with one embodiment of the present invention comprises a balloon 802, suitably having a one way valve 803 or other such means, to allow inflation, and an elastic pouch 804. The balloon 802, e.g. formed of a biocompatible elastomeric polymer, e.g. polyurethane or silicone, is provided within the elastic pouch 804, e.g. formed from a lycra™. A conduit 805 leading to the valve 803 extends from the pouch 804 such that it can be attached to a source of fluid to inflate the balloon 802, e.g. a hand pump. The pouch 804 also contains a particulate haemostatic agent, e.g. zeolite powder, which is coated thereon. When the device 801 is placed within the wound cavity, the balloon 802 is inflated such that the device 801 expands to fill the wound cavity and thus applies pressure to the walls of the cavity. Figure 8B shows the device 801 in an expanded state following inflation of the balloon 802. In a variant of this embodiment the haemostat can be coated onto the material of the pouch 804, e.g. by immersing the pouch 804 in a

suspension of the zeolite powder and allowing it to dry. E - Constrained resilient member within a membrane.

In a further embodiment of the present invention, the device comprises a resilient member formed of a monolithic expandable material, such as medical-grade cellulose sponge. However, rather than being pre- compressed in a wet form and dried to form a sponge of smaller diameter, as in example B, the cellulose sponge is compressed held in the compressed form by a constraining means. The constrainment can be achieved by encasing the expandable body in a membrane which is strong enough to withstand the expansive force of the body, thereby maintaining the expandable body in a non-expanded, i.e. compressed form, and which at least partially degrades once in position within the wound cavity to allow the expandable body to adopt an expanded form. Such membranes might primarily comprise a pouch formed from a non-elastic polymer such as nylon, or the like, shaped and sized to constrain the expandable body in its non-expanded form, but having weakened, frangible portions or

perforations which are adapted to tear under the expansive force of the expandable body. These weakened portions are reinforced with a degradable polymer, e.g. PEG, PVA or PVP, such that the pouch is strong enough to resist the expansive forces. Then in use the degradable polymer degrades in the wound cavity until the pouch tears allowing expansion of the expandable body. For each specific device the precise specifications of the pouch can be optimised by routine optimisation. In such an embodiment, a haemostatic agent is suitably coated or loaded onto the sponge. F- Fibrous expandable material in a pouch

In a variant of device A, rather than provide a powdered SAP, a plurality of strands or strips of an expandable material, e.g. a SAP, can be contained within a pouch, in association with a haemostatic agent. As with device A, the haemostatic agent and the SAP can be mixed together, or the haemostatic agent can be provided on the barrier.

G - Device with non-constrained expandable body formed of

strands/strips

As illustrated in Figure 9, a further device 901 may comprise a plurality of strands or strips 902 of a structurally coherent fibrous expandable material, for example carboxymethyl-cellulose or carboxymethyl-chitosan. All the strands/strips 902 are connected together to form the expandable body of the device 901 . Suitably the strands/strips 902 are connected together at a single node 903, e.g. tied or bonded together or fixed into a suitable nodal housing (e.g. with an adhesive). Preferably the node 903 has a removal means 904 attached to it, e.g. a length of string, such that pulling on the string 904 allows the device 901 to be conveniently removed.

The expandable material is provided with a haemostatic agent, for example, where it is involved in the coagulation cascade, the haemostatic agent may be calcium salts (i.e. Ca²⁺), thrombin, fibrin or factor VII, or where it has a surface-activation mode of action, the haemostatic agent may be chitosan particles or films, clay or zeolite powders, as described above. This can be achieved by integration of the haemostatic agent within the structure of the fibres during polymerisation, by coating on the surface of the strands/strips using a simple dip coat or e.g. a polyol binder, or by covalently bonding the agent to the expandable material using coupling agents, as described above.

In use the device 901 is delivered to the wound cavity from an applicator (not shown) comprising a hollow tube from which the device 901 is pushed by a pusher, e.g. a manually operated plunger, into the wound cavity.

Preferably the device 901 is orientated in the applicator such that the node 903 is delivered to the wound last, and thus remains close to the opening. The removal means 904 extends from the node 903 out of the wound cavity to facilitate easy removal of the device 901 when required.

H - Provision of a rod to facilitate positioning and removal

Any of devices A to G can be provided with a rigid rod formed from a metal or plastics material. One end of the rod is connected to the device, e.g., to the node of the device of example G, or by being lodged inside the expandable body of examples A to C, E or F. The rod is relatively narrow, e.g. from 5 to 15 mm, so that it can easily pass through the opening of the wound. When the device is placed within wound cavity, the user can use the rod to urge the device into a desired location within the cavity, e.g. against a blood vessel where significant bleeding is occurring. Such pressure can be release once the device has expanded or become adhered to the tissue, or can be maintained even after the device has expanded. Once the device is to be removed from the wound cavity, this can be achieved by pulling on the rod.

/ - Device encased within lubricious membrane

Any one of the devices of Examples A to H can be provided at least partially encased within a membrane which has lubricating properties. Suitable materials for the membrane include fluoropolymers (e.g. ePTFE), silcones or materials containing silicone.

Such a lubricious membrane helps with insertion of the device into the wound cavity and also with dispensing the device from an applicator. The lubricious membrane can conveniently be liquid permeable such that liquid can penetrate the device, and/or it may be degradable such that it degrades once the device is in position within the wound cavity.

Claims

A device for administration to a wound cavity, the device comprising an expandable body and a haemostatic agent.

The device of claim 1 wherein the expandable body is adapted to expand upon absorption of a liquid.

The device of claim 1 wherein the expandable body is adapted to expand in a manner independent of fluid absorption.

The device of claim 1 comprising a resilient member which is constrained in a non-expanded form, and which is adapted to adopt an expanded form once in position in the wound cavity.

The device of any preceding claim wherein the expandable body comprises a water absorbing polymer, especially a super-absorbent polymer.

The device of claim 5 wherein the expandable body comprises a particulate water absorbing polymer.

The device of claim 5 wherein the expandable body comprises a water absorbing polymer in the form of strands or strips.

The device of any preceding claim wherein the expandable body comprises one or more of:

polyacrylic acids (e.g. sodium polyacrylate, polyacrylamide, ethylene maleic anhydride copolymer, copolymers of acrylate and methacrylate moieties) and derivatives thereof; starch-acrylic acid graft polymers (e.g. starch grafted copolymer of polyacrylonitrile) and derivatives thereof; and

hygroscopic polymers, which can be capable of forming hydrogels, including polyvinyl alcohol copolymers, polyethylene oxide, polysaccharides and derivatives thereof (e.g. alginate, carboxy-methyl-cellulose, carboxy-methyl-chitosan).

9. The device of any preceding claim wherein the expandable body comprises cellulosic or fiber-based materials.

10. The device of any preceding claim wherein the expandable body comprises a sponge material, such as cellulose sponge.

1 1 . The device of claim 10 wherein the expandable body comprises a sponge material which has been pre-compressed into a compressed form, which is capable of expanding to a non-compressed form upon absorption of a liquid, e.g. blood.

12. The device of any preceding claim in which the expandable body is at least partially enclosed in a barrier/membrane.

13. The device of claim 12 wherein the expandable body is entirely

enclosed by a barrier/membrane. 14. The device of claim 12 wherein the barrier/membrane is liquid

permeable.

15. The device of any one of claims 12 to 14 wherein the membrane comprises or consists of a degradable material.

16. The device of any preceding claim in which the haemostatic agent comprises one or more of clays such as bentonite, smectite, montmorillonite, attaplugite, kaolin or kaolinite; zeolite; diatomaceous earth; self-assembling peptides; keratin; starch-based materials; modified glass fibres; chitosan; cellulose/oxidated cellulose; collagen; fibrin; and thrombin.

17. The device of any preceding claim in which the haemostatic agent is associated with the expandable body or a barrier/membrane surrounding the expandable body.

18. The device of the present invention comprising anchoring means.

19. The device of claim 18 wherein the anchoring means comprises one or more of:

- one or more barbed members;

- one or more tying members;

- adhesive; and

- a plug.

20. The device of claim 1 comprising a SAP located inside a liquid- permeable pouch, and wherein the haemostatic agent is associated with the pouch and/or located inside the pouch. 21 . The device if claim 20 wherein the SAP is particulate.

22. The device of claim 1 comprising an expandable body formed from structurally coherent expandable material, the expandable body having a haemostatic agent associated therewith.

23. The device of claim 22 comprising a monolithic expandable body formed of a sponge material and a haemostatic agent is associated with the sponge. 24. The device of claim 23 wherein the sponge is provided in a dry, pre- compressed form.

25. The device of claim 22 or 23 wherein the haemostatic agent is

associated with the sponge as a coating on the surface of the sponge.

26. The device of any preceding claim comprising regions having

different loading of haemostatic agent. 27. The device of any preceding claim comprising one or more additional active agents.

28. The device of any preceding claim comprising binding means to bind the haemostatic agent or other particulate materials to the device.

29. The device of any preceding claim comprising a removal means to facilitate removal of the device from the wound.

30. A wound treatment apparatus comprising the device of any

preceding claim loaded in an applicator.

31 The wound treatment apparatus of claim 30 wherein the applicator comprises a hollow housing having a lumen of a suitable shape and size to accommodate the device in its non-expanded form and an opening at one end to allow the device to pass therefrom and into the wound.

The wound treatment apparatus of claim 30 or 31 wherein the applicator comprises ejection means to eject the device from the applicator and into the wound cavity.

A method of making a device for administration to a wound cavity, the method comprising;

a) providing an expandable body ;

b) providing a haemostatic agent; and

c) associating the haemostatic agent with the expandable body.

The method of claim 33 comprising providing a barrier/membrane around the expandable body, such that the expandable body is at least partially encased within the barrier/membrane.

The method of claim 33 or 34 wherein step a) comprises providing expandable material in a wet, expanded form, compressing said material, and drying said material while it is in a compressed form.

36. The method of claim 33 or 34 wherein step a) comprises providing a water absorbing polymer, especially a super-absorbent polymer. 37. The method of claim 33 or 34 wherein step a) comprises providing a resilient means, pre-compressing said resilient means into a non- expanded form, and constraining said resilient means in said non- expanded with a constraining means.

38. The method of any one of claims 33 to 37 wherein step c) comprises coating an expandable material with the haemostatic agent.

39. The method of claim 33 wherein step c) comprises mixing a

particulate haemostatic agent with a particulate expandable material and encasing the mixture within a barrier.

40. The method of claim 33 wherein step c) comprises associating the haemostatic agent with a barrier/membrane surrounding the expandable body.

41 . A method of treating a wound, the method comprising:

- providing a device or apparatus as claimed in any one of claims 1 to 32; and

- applying said device to the cavity of the wound.

42. The method of claim 41 comprising utilising an anchoring means to anchor the device in position in the wound cavity. 43. The method of claim 41 or 42 comprising removing the device from the wound by pulling on a removal means provided on the device.