WO2010010399A2

WO2010010399A2 - Honey wound dressing

Info

Publication number: WO2010010399A2
Application number: PCT/GB2009/050911
Authority: WO
Inventors: Stephen Cotton
Original assignee: Brightwake Limited
Priority date: 2008-07-24
Filing date: 2009-07-23
Publication date: 2010-01-28
Also published as: GB2462005A; GB0813541D0; WO2010010399A3; GB0912815D0

Abstract

A wound dressing material has the form of a pliable solid, and comprises from 1 to 49 wt% honey, from 1 to 45 wt% additional monosaccharide, from 1 to 25 wt% humectant and from 1 to 25 wt% gelling agent. The material may be prepared by a method that involves forming a first mixture comprising honey and monosaccharide, forming a second mixture comprising humectant and gelling agent, combining the the first mixture and the second mixture, and causing or allowing the composition to cure.

Description

Honey wound dressing

The present invention relates to wound dressings containing honey and their medical application.

Wound healing is a complex process involving the integration and orchestration of a number of different biological events. The ultimate aim of the process is to repair the barrier properties of the skin as quickly as possible so that it can continue to perform its key functions in protection of the body from pathological infection and ionising radiation while also regulating body temperature and containing the internal organs. Normal wound healing is often separated, for the purposes of understanding, into three phases, known as Inflammation, Granulation and Maturation. These phases are intrinsically linked to one another but quite often the boundaries of each phase will overlap with one another, adding to the complexity of the process.

The inflammation stage includes the blood clotting processes, the recruitment of macrophages to the wound site, the initiation of the inflammatory pathways and the initiation of keratinocyte reepithelialisation. The granulation phase, which follows, involves the phenotypic alteration of fibroblasts in the dermal layer to myofibroblasts, and further keratinocyte reepithelialisation. The myofibroblasts migrate into the denuded wound space and produce the extracellular matrix (ECM) protein (including collagen, elastin, and fibronectin) that makes up the substance material of the repair. Myofibroblasts are also known to contract the wound boundaries thereby minimising the wound area required for healing. Often this contraction is painful and can continue into the maturation phase, particularly in the development of hypertrophic scars. During maturation a number of proteases are present within the wound (such as matrix metalloproteases and tissue inhibitors of matrix metalloproteases). These degrade unwanted tissue and restore the protein balances, thereby restoring the appearance of the scar to that of normal skin. Different wound types such as normal incisional or burn wounds have different stage lengths. For instance, burn wounds have a long granulation phase, due to the extensive wide area cell death. Scars from burn wounds are often hypertrophic and the maturation phases can take a lifetime to complete. Ulcerated wounds on the other hand have a number of compounding factors leading to increased inflammation and granulation phases. Leg ulceration is most commonly caused by venous hypertension resulting from valvular incompetence in the superficial, deep or perforating veins. Sustained venous hypertension causes swelling, restricted blood flow and damage to the skin and other tissues. The healing of ulcerated wounds is further often compounded by a lack of mobility in the patient which leads to a lack of venous return and a build-up of free radicals in the lower limbs. These cause tissue damage and a small bruise can very rapidly develop into an ulcer.

In the UK, chronic wounds represent a significant burden to patients and the National Health Service (NHS). Some 200,000 patients in the UK have a chronic wound. The impact on their quality of life is well documented. Common symptoms of ulceration include pain, exudate and odour, and these symptoms are frequently associated with poor sleep, loss of mobility and social isolation. The cost to the NHS of caring for patients with a chronic wound is conservatively estimated at £2.3bn-3.1 bn per year (at 2005-2006 costs), around 3% of the total estimated out-turn expenditure on health (£89.4bn) for the same period. With proper diagnosis and treatment, much of this burden should be avoidable.

Commonly used wound dressings, for efficacy, should maintain a moist environment at the wound interface, remove excess exudate without allowing 'strike through' to the surface of the dressing, provide thermal insulation and mechanical protection, act as a barrier to micro-organisms, allow gaseous exchange, be non-adherent and easily removed without trauma, leave no foreign particles in the wound, be non-toxic and be non-allergenic and non-sensitising. No single dressing is appropriate for all wound types and all stages of healing. The following types of dressing are examples of some most commonly used.

Hydrocolloids, eg Granuflex® (ConvaTec Ltd), consist of a matrix of cellulose and other gel-forming agents such as gelatine and pectin. They are occlusive and therefore are mostly applicable where infection, particularly with anaerobic organisms, is not present. They promote autolysis and aid granulation, but as they can remain in place for up to a week, over-granulation can occur.

Alginates, eg Kaltostat® (ConvaTec Ltd), consist of calcium and sodium salts of alginic acid obtained from seaweed. They are highly absorbent and useful for medium to heavily exuding wounds. Unfortunately, secondary covering is required as the dressing forms a gel in contact with wound exudate.

Foam dressings, eg Lyofoam® (Seton Healthcare Group pic), consist of foam-type material and are useful for moderately exudating wounds. They prevent 'strike through' of exudate to the wound surface and essentially deslough the wounds by maintaining a moist environment.

Hydrogels, eg Intrasite™ Gel (Smith and Nephew Group pic), consist of dressings with a high water content to create a moist wound surface. This debrides wounds by hydration and promotion of autolysis and the dressing will absorb a light exudate. Unfortunately they are not appropriate for heavily exudating wounds.

Debriding agents consist of enzymic or acid treatments to remove eshcar and necrotic tissue. They do not maintain a moist environment, need frequent changes and they damage granulation tissue. Although they debride the wound, they delay healing. Alternatives to the commonly used dressings have been sought because of the increasing requirement for the use of alternative therapies, especially as the development of antibiotic resistance in bacteria is becoming a major problem. Sugar dressings have been developed in the past for their ability to form pastes that can be applied to wounds, and for their inherent ability to cause osmotic shock to bacteria within the wound and thereby prevent bacterial growth. A more complex but more traditional alternative has been to use honey in dressings. Honey is a mixture of sugars, water and other active ingredients such as vitamin C, catalase and chrysin, that are thought to act as antioxidants (Gheldof et al., 2002). As such, it has much greater activity than sugar alone and has been shown to support wound healing through its anti-inflammatory action, its natural antibacterial properties, its debriding action and its stimulatory effect on granulation and epithelialisation. In fact, honey has been shown to have considerable wound and ulcer healing capacity and strong antimicrobial capacity even in moist healing environments.

Unlike other topical antiseptics, honey causes no tissue damage and in animal studies it has been demonstrated histologically that it actually promotes the healing process. It has a direct nutrient effect as well as drawing lymph out of the cells by osmosis. The stimulation of healing may also be due to the acidity of honey. The osmosis creates a solution of honey in contact with the wound surface which prevents the dressing sticking, so there is no pain or tissue damage when dressings are changed. There is much anecdotal evidence to support its use, but randomised controlled clinical trials have shown that honey is more effective than silver sulfadiazine and a polyurethane film dressing (OpSite®, Smith and Nephew Group pic) for the treatment of burns.

Unfortunately, honey has some drawbacks presently as a wound treatment. Its natural fluidity at body temperature is problematic for retaining sufficient amounts within the wound space. One attempt to address this problem is described in US2007/0265585A, which discloses the use of a housing for covering at least a portion of a wound and for sealing to a body surface of a patient. The housing includes a liquid-retention chamber for retaining the honey to avoid it running away; however, the device is cumbersome and relatively non-adaptable to different wound sizes.

Soaking honey with absorbent materials such as gauze, in a dressing to be applied to the wound is an alternative solution, but a rather messy one. The untidiness is further compounded by the fact that the dressing is then held in place by a further covering, which is cumbersome. This risks further infection due to secondary occlusion. Furthermore, the use of gauze or foam has additional complications in that often fragments are left behind when the material is removed.

To overcome these drawbacks, honey has been combined with various gelling agents such as alginate, as described by EP1237561 , or with starch, glycerol, acrylamide or carboxymethyl cellulose (CMC). EP1237561 discloses medical compositions comprising more than 50% honey, that are in the form of formable or pliable solids. However, it has been found that adding just a gelling agent (such as alginate) to honey does not enable sufficient control of the gelling process for it to be possible, on a commercially viable scale, to create sheets of material that are uniform and consistent in nature. Uniformity and consistency are important qualities for wound dressings so as to confer similar properties on the healed structure and for them to fulfil their requirement as protective dressings. It has been found that adding just a gelling agent results in agglutination, whereby the honey is formed rapidly into liquid viscous clumps, which are sticky and not useable in manufacturing processes involving extrusion or moulding. This means that the processes described in the prior art do not enable mass production of honey-based wound dressings in the form of pliable sheets and the like, particularly in the case of large area dressings (such as those required for whole body burns, open heart surgery or graft treatment). There has now been devised an improved wound dressing which overcomes or substantially mitigates the above-mentioned and/or other problems associated with the prior art.

According to a first aspect of the invention there is provided a wound dressing material in the form of a pliable solid, the material comprising from 1 to 49 wt% honey, from 1 to 45 wt% additional monosaccharide, from 1 to 25 wt% humectant and from 1 to 25 wt% gelling agent.

The wound dressing material according to the invention is advantageous principally because the mixture of honey, additional monosaccharide (eg glucose syrup), humectant (eg propylene glycol) and gelling agent (eg carboxymethyl cellulose (CMC)), can be formed into a sheet, layer or pliable putty. The dressing material is suitable for mass production as a sheet material whereby the physical and compositional qualities of the dressing are replicable, clean and sterile. The messiness and uncontrollable containment of the honey, that is conventionally associated with honey soaked gauzes, is no longer present.

The wound dressing material according to the invention is further advantageous because by altering the composition, the consistency of the dressing can be altered and therefore the material can release honey into the wound space over a period of hours, days or weeks, allowing for a sustained efficacy. In so doing, the wound dressing material according to the invention can draw exudate from the wound whilst maintaining a moist environment at the wound site over a long period of time.

Honey may be present in the wound dressing material according to the invention at a level in the range of 1 to 49 wt%. In some embodiments, the honey is present at a level in the range of 10 to 43 wt% or in the range of 20 to 38 wt%. In the presently most preferred compositions, the honey is present at a level of about 32 wt%. Being a natural substance, honey is of variable composition, and this results in some variability in the characteristics and performance of the dressings that incorporate it. The selection of Manuka honey from bees that have gathered pollen from the flowers of the Manuka tree {Leptospermum scoparium) is particularly preferred because it is believed to contain an additional antibacterial phytochemical component. The Manuka tree is indigenous to New Zealand and Manuka honey is widely produced in that country. Another form of honey that may be particularly useful in the present invention is that produced by bees that have gathered pollen from the flowers of Leptospermum polygalifolium, which is related to the Manuka tree and is native to Australia. The most preferred honey for use in the present invention is "UMF Manuka Honey", also called Active Manuka Honey. Active Manuka honey is sold with its activity rated on a "UMF" scale, the UMF (Unique Manuka Factor) being the equivalent concentration of phenol with the same antibacterial activity against Staphylococcus aureus (ie UMF 15 = 15% phenol). Preferred compositions according to the invention comprise Manuka honey with a UMF rating greater than 10, more preferably UMF 12 or above.

The wound dressing material comprises an amount of one or more additional monosaccharides. By this is meant an amount of monosaccharide over and above those present in the honey. Suitable monosaccharides may include ketotriose, aldotriose, ketotetrose, erythrulose, erythrose, threose, ketopentose, ribulose, xylulose, aldopentose, ribose, arabinose, xylose, lyxose, deoxyribose, hexoses, ketohexose, psicose, fructose, sorbose, tagatose, aldohexose, allose, altrose, glucose, mannose, gulose, idose, galactose, talose, deoxy sugar, fucose, fuculose, rhamnose, heptose and sedoheptulose. Mixtures of monosaccharides may be used, eg mixtures of glucose and fructose.

The additional monosaccharide may be incorporated into the wound dressing material as a dry solid, but is more preferably utilised in the form of a concentrated aqueous solution or syrup. Typically, such a solution or syrup may contain more than 50 wt% of monosaccharide, eg more than 60 wt% or more than 70 wt%.

The wound dressing material comprises preferably glucose syrup. The glucose syrup may be present in the wound dressing material according to the invention at a level in the range of 1 to 45 wt%. In some embodiments, the glucose syrup is present at a level in the range of 10 to 43 wt%, or more preferably in the range of 20 to 38 wt%. In the presently most preferred compositions, the glucose syrup is present at a level of about 32 wt%.

The inclusion of glucose syrup into the wound dressing according to the invention is advantageous primarily because the it improves the smoothness and pliability of the wound dressing material.

The invention thus further provides a wound dressing material in the form of a pliable solid, the material comprising from 1 to 49 wt% honey, from 1 to 49 wt% of an additional monosaccharide, and from 1 to 25 wt% gelling agent.

As in the first aspect of the invention, such a wound dressing material may further comprise from 1 to 25 wt% of a humectant.

A variety of types and forms of glucose can be used in the wound dressing material according to the invention. As noted above, the glucose can be in the form of a liquid, syrup, or solution in water. Alternatively, the glucose can be in the form of a solid or semi solid suitable for mixing with a solution for preparation before addition into the wound dressing material. The glucose may be admixed with one or more other monosaccharides, eg fructose. In preferred embodiments of the invention, the additional monosaccharide comprises a major proportion (eg more than 70, more than 80 or more than 85 wt%) of glucose and a minor proportion (eg less than 30, less than 20 or less than 15 wt%) of fructose. The glucose that may be used in the composition according to the invention can be in the so called "D" configuration or the "L" configuration, ie the two stereoisometric forms of the glucose molecule.

The wound dressing material according to the invention may comprise one or more of a variety of gelling agents. A gelling agent is an additive used to thicken and stabilize the material. Suitable gelling agents for the purposes of the invention include jellies, stabilizers, solidifiers, thickening agents, natural gums, starches, pectins, agar-agar, gelatine, various polysaccharides, various proteins, alginic acid, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, polysaccharides from brown algae, agar, polysaccharides obtained from red seaweeds, carrageenan, locust bean gum, natural gum from the seeds of the Carob tree, pectin, polysaccharides obtained from apple or citrus-fruits and gelatine. Preferably the gelling agent is a synthetic cellulose derivative. Preferably the gelling agent is carboxymethyl cellulose (CMC) or a salt thereof. CMC or salts thereof may be included in the composition in a range from 1 to 25 wt% CMC. In some embodiments, the CMC is present at a level in the range of 5 to 20 wt%, or in the range of 10 to 17 wt%. In the presently most preferred compositions, the CMC is present at a level of about 12 wt%.

The composition according to the first aspect of the invention further comprises a humectant, ie an ingredient that attracts or retains moisture. Examples of humectants that may be suitable for use in the invention include glycerine, glyceryl triacetate, various polyols such as sorbitol, xylitol, maltitol, polymeric polyols such as polydextrose or other natural extracts such as quillaia, lactic acid or urea. Preferably the humectant is a polyol, in particular a diol or triol. Most preferably the humectant is propylene glycol (also known as monopropylene glycol, propane-1 ,2-diol, propylene glycol or propyleneglycol). Propylene glycol may be present in the composition according to the invention at a level in the range of 1 to 25 wt%. In some embodiments, the propylene glycol is present at a level in the range of 10 to 25 wt%, or in the range of 15 to 25 wt%. In the presently most preferred compositions, the propylene glycol is present at a level of about 22 wt%. The wound dressing material according to the invention may comprise additional ingredients to improve its physical properties such as flexibility and adherence. For example, it is desirable for a wound dressing material according to the invention to have some adherence to the skin on application, so that it stays in place, for instance while additional bandages or tapes are secured in order to fasten it in place more permanently. However, it is also desirable that a wound dressing material according to the invention is non-adherent, so that it can be peeled away from the wound without causing damage. The wound dressing material according to the invention may comprise other active ingredients, such as antibiotics, anti-inflammatory agents, and other wound healing agents. Such ingredients may include silver, which is known for its antimicrobial properties.

The wound dressing material of the invention will generally contain a low proportion of water, arising from the water content of the honey and the glucose syrup or the like (if used). Typically, the water content of the wound dressing material will be less than 10 wt%, or less than 5 wt%.

If honey and a gelling agent are mixed together it has been found that setting of the gel is uncontrollable, resulting in agglutination. This does not allow for the end product materials to be shaped into usable or reproducible structures that could be applicable as wound dressings. It has now surprisingly been found that adding humectant enables more control of the gelling process. This then allows the manufacture of a wound dressing material according to the invention with a desired shape and size.

The invention thus further provides a wound dressing material in the form of a pliable solid, the material comprising from 1 to 70 wt% honey, from 1 to 25 wt% of a humectant, and from 1 to 25 wt% gelling agent. As in the first aspect of the invention, such a wound dressing material may further comprise from 1 to 45 wt% additional monosaccharide.

It has been found that by preparing a mixture of honey and monosaccharide and a separate mixture of humectant and gelling agent, and then combining the two, the gelling reaction that subsequently occurs is controllable. This allows for mixtures to be manufactured into wound dressing material as sheets or other physical forms such as blocks, cubes, strings, fibres etc. Without using this process the formation of wound dressing material on an industrial scale has been found not to be possible.

Thus, in a second aspect of the invention there is provided a process for the manufacture of a wound dressing material in the form of a pliable solid, the material comprising honey, additional monosaccharide, humectant and gelling agent, which process comprises the steps of: a) providing a first mixture comprising honey and additional monosaccharide, b) providing a second mixture comprising humectant and gelling agent, c) combining the first mixture and the second mixture, c) causing or allowing the composition to cure.

The first mixture may be provided by adding an amount of honey and an amount of monosaccharide to a first container and mixing. Similarly, the second mixture may be provided by adding an amount of humectant and an amount of gelling agent to a second container and mixing. The separation of the two mixtures prevents premature gelling and agglutination. Appropriate amounts of the first and second mixtures are then combined to form a single mixture which is preferably then further mixed for a period of time. The single mixture is then preferably applied to a surface on which the mixture is caused or allowed to cure. Where the finished material is intended to have the form of a sheet, the single mixture is preferably poured and/or spread onto a surface, preferably using a scraper blade or the like to ensure uniform thickness and distribution of the material. The surface to which the mixture is applied is preferably chilled.

Curing of the material to form the wound dressing material according to the invention may be brought about by various means, but preferably involves the application of heat. Most preferably, the material, once spread onto a surface, is exposed to one or more heating elements. A particularly preferred form of heating element is a medium wave Infra Red (IR) source. Such a heating element has been found to be highly controllable, so that the amount of energy delivered can be adjusted as required for the formation of the wound dressing material. Most preferably, the material is transported past the heating element(s), such that the degree of curing can be controlled by varying the time taken for the material to pass the heating element(s). By altering the speed of passage of the material and the energy provided to the heating element(s), it is possible to control the curing of the material. This is particularly important when dressing materials produced according to the invention are of widely different shapes and sizes.

The wound dressing materials according to the invention may have sufficient strength and integrity to be self-supporting structures. Alternatively, or in addition, the materials may be applied to a flexible scaffold. This may be achieved by spreading the single mixture referred to above onto a scaffold material, eg in the form of a gauze, a foam, a sponge, or the like. When the material cures, it may become intimately bonded to the scaffold structure.

Preferably, individual dressings comprising the wound dressing material of the invention are cut to shape. Such individual dressings may have a backing material applied to one or more of their surfaces. Preferably, this backing material is selected from paper, plastics film, metal foil, non-woven material, or woven material (such as gauze). Preferably the backing material that is applied extends beyond at least one edge of the dressing, to facilitate its removal. The wound dressings according to the invention are generally packaged as individual units in envelopes that are bacteria-proof. Most preferably, the package is sterilised, most commonly using ethylene oxide or by irradiation with γ-radiation.

The wound dressing material according to the invention is useful in the treatment of wounds in animals or humans.

Thus, in a further aspect of the invention, there is provided the use of a wound dressing material in the form of a pliable solid, the material comprising from 1 to 49 wt% honey, from 1 to 45 wt% additional monosaccharide, from 1 to 25 wt% humectant and from 1 to 25 wt% gelling agent, as a wound healing agent.

In another aspect of the invention there is provided a method of treating a wound, which method comprises the application to the wound of a wound dressing material in the form of a pliable solid, the material comprising from 1 to 49 wt% honey, from 1 to 45 wt% additional monosaccharide, from 1 to 25 wt% humectant and from 1 to 25 wt% gelling agent.

A wound may be regarded as any injury to living tissue. This may include but is not limited to a type of physical trauma wherein the tissue is torn, broken, pierced, lacerated, cut, punctured and burnt. This may also include but is not limited to a type of physical trauma wherein the tissue is ulcerated, infected, inflamed, infested and necrotic. This may also include but is not limited to situations in which blunt force trauma causes a contusion resulting in a so called "closed wound".

The wound dressing material according to the invention may be prepared in the form of a sheet that is applied to a wound in that form. Alternatively, the material may be formed into any other desired shape suitable for application to a wound, or packing of a wound cavity, ie the material may be used as a putty. The invention will now be described in greater detail, by way of illustration only, with reference to the following Example.

Example

A honey based wound dressing was prepared as follows:

A first mixture of 32.49kg Manuka honey and 32.49kg liquid glucose (approx 77% dry substance, including 8-10% fructose) was prepared.

A second mixture was prepared by dispersing 12.73kg CMC powder in 22.29kg monopropylene glycol.

The first and second mixtures were combined to produce a curable composition with the following composition:

32.49 wt% liquid glucose 32.49 wt% honey 22.29 wt% monopropylene glycol 12.73 wt% CMC

The composition was poured onto a moving conveyor belt that was chilled. A spreading knife was used to control the thickness of the material on the belt and suction was applied from underneath so as to hold the material onto the belt as it travelled towards a curing station with heating elements. The heating elements were a number of banks of medium wave Infra Red elements disposed above the conveyor belt, all of which were electronically controlled. As the wound dressing material passed underneath the banks of IR lamps, the material was cured to form a sheet that was flexible, malleable and of sufficient tensile strength as to avoid breakage during handling. The cured product was then cut to the size required using a cutting blade and then paper backing sheets were applied to both sides. The backing sheets were of greater size than the product, to facilitate removal of the backing sheets.

Claims

1. A wound dressing material in the form of a pliable solid, the material comprising from 1 to 49 wt% honey, from 1 to 45 wt% additional monosaccharide, from 1 to 25 wt% humectant and from 1 to 25 wt% gelling agent.

2. A wound dressing according to Claim 1 , wherein the honey is Manuka honey.

3. A wound dressing according to Claim 2, wherein the honey has a UMF rating greater than 10.

4. A wound dressing according to Claim 3, wherein the honey has a UMF rating of 12 or above.

5. A wound dressing material according to any preceding claim, wherein the honey is present at a level in the range of 10 to 43 wt%.

6. A wound dressing material according to any preceding claim, wherein the honey is present at a level in the range of 20 to 38 wt%.

7. A wound dressing material according to any preceding claim, wherein the honey is present at a level of about 32 wt%.

8. A wound dressing material according to any preceding claim, wherein the additional monosaccharide is present at a level in the range of 10 to 43 wt%.

9. A wound dressing material according to any preceding claim, wherein the additional monosaccharide is present at a level in the range of 20 to 38 wt%.

10. A wound dressing material according to any preceding claim, wherein the additional monosaccharide is present at a level of about 32 wt%.

1 1. A wound dressing material according to any preceding claim, wherein the additional monosaccharide comprises glucose.

12. A wound dressing material according to any preceding claim, wherein the additional monosaccharide comprises fructose.

13. A wound dressing material according to any preceding claim, wherein the additional monosaccharide is employed in the form of a concentrated aqueous solution or syrup.

14. A wound dressing material according to any preceding claim, wherein the humectant is present at a level in the range of 10 to 25 wt%.

15. A wound dressing material according to any preceding claim, wherein the humectant is present at a level in the range of 15 to 25 wt%.

16. A wound dressing material according to any preceding claim, wherein the humectant is present at a level of about 22% wt%.

17. A wound dressing material according to any preceding claim, wherein the humectant is a polyol.

18. A wound dressing material according to Claim 17, wherein the polyol is propylene glycol.

19. A wound dressing material according to any preceding claim, wherein the gelling agent is present in a range from 5 to 20 wt%.

20. A wound dressing material according to any preceding claim, wherein the gelling agent is present at a level in the range of 10 to 17 wt%.

21. A wound dressing material according to any preceding claim, wherein the gelling agent is present at a level of about 12 wt%.

22. A wound dressing material according to any preceding claim, wherein the gelling agent is a synthetic cellulose derivative.

23. A wound dressing material according to Claim 22, wherein the gelling agent is carboxymethyl cellulose or a salt thereof.

24. A process for the manufacture of a wound dressing material in the form of a pliable solid, the material comprising honey, additional monosaccharide, humectants and gelling agent, which process comprises the steps of a) providing a first mixture comprising honey and monosaccharide, b) providing a second mixture comprising humectant and gelling agent, c) combining the first mixture and the second mixture, c) causing or allowing the composition to cure.

25. A process for the manufacture of a wound dressing material according to Claim 24 whereby the wound dressing material is in the form of a sheet.

26. A process as claimed in Claim 24 or Claim 25, wherein the wound dressing material is as claimed in any one of Claims 1 to 23.

27. The use of a wound dressing material according to any one of Claims 1 to 23 as a wound healing agent.

28. A method of treating a wound, which method comprises the application to the wound of a wound dressing material according to any one of Claims 1 to 23.