Vehicle for non-antimicrobial composition

Abstract

The present disclosure relates generally to wound care, and more particularly to a wound dressing or debridement tool comprising an absorbent layer at least partially impregnated or coated with a non-antimicrobial composition.

Description

Vehicle for Non-antimicrobial compositionFIELD

[0001] The present disclosure relates generally to wound care, and more particularly to a wound dressing or debridement tool comprising an absorbent layer at least partially impregnated or coated with a non-antimicrobial composition.BACKGROUND

[0002] Owing to an aging population and growing prevalence of vasculopathy, the incidence of chronic wounds is increasing worldwide. Chronic wounds are a major burden on healthcare systems and patient quality of life, often leading to loss of function and amputation. Although their treatment accounts for approximately 3% of total healthcare costs in developed countries, a 2018 cohort study found that fewer than 50% of chronic wounds managed by the UK National Health Service healed within a year. Moreover, chronic wounds recur in up to 60-70% of patients. This poor prognosis underlines the need for new approaches to chronic wound care.

[0003] Normal wound healing comprises four intricate and overlapping phases: haemostasis, inflammation, proliferation, and remodelling. After the formation of a thrombus, leukocytes infiltrate the wound and remove bacteria and debris, preparing the wound for healing. This enables the formation of new connective tissue and blood vessels, known as granulation tissue, and subsequent wound closure and re-epithelialisation. An wound is classed as chronic if it fails to progress through this sequence within 4-6 weeks. Wound chronicity is often attributed to diabetes and vascular diseases. The resulting nerve damage and poor perfusion to extremities alter the wound microenvironment and delay healing. Chronic wound healing stalls in the inflammatory phase due to an imbalance of cytokines, proteases, and their inhibitors. Prolonged inflammation leads to the accumulation of slough, a fibrinous substance composed of dead leukocytes and degraded proteins.

[0004] Often, removal of contaminated and non-viable tissues is required before normal healing can be re-established. An well-qualified medical professional may be able to perform mechanical and / or sharp debridement to remove this non-viable matter, but nurses and less well-qualified carers may not be as competent in performing such tasks or lack confidence. Under these circumstances, less invasive debridement techniques are required. It is well understood that wound irrigation between dressing changes can help mechanically remove some matter and that autolytic debridement can be encouraged by use of moisture donating products and / or moisture retentive dressings. However,autolytic debridement can be a slow process and a wound containing non-viable tissue is highly susceptible to microbial proliferation and infection. Therefore, enhancement or acceleration of autolytic debridement is desirable. The types of non-viable tissue may include necrotic (dead) tissues, slough (accumulating granulation and epithelial cells that are not surviving in the chronic wound environment) and biofilm (microbial matter including viable microorganisms and associated selfproduced mucilage or extracellular polymeric substance (EPS)). Biofilm is are viable microbial tissue that can re-establish and multiply rapidly, returning to its original condition within a few days or even a few hours. Slough is a consequence of the inflammatory phase of wound healing and it comprises dead or redundant white blood cells, fibrin / fibroblasts, cellular debris / components of healing, and liquefied devitalised tissue. Slough can provide a source of nutrients for bacterial cells and a suitable environment for their proliferation, subsequently enabling biofilm formation. Necrotic tissue is an additional source of cellular debris in the form of fibrous proteins (such as collagen) and proteoglycans (components of the extracellular matrix). As a result, failure to adequately prepare the wound bed via removal of detrimental waste material such as slough and necrotic tissue has been shown to impede healing. Commonly associated with chronic wounds, the accumulation of such tissue alongside the poorly regulated proliferation of microorganisms and subsequent biofilm formation are believed to be important factors in the failure of some wounds to heal.

[0005] Broad-spectrum antiseptics are frequently used to control wound infection but are often cytotoxic due to their lack of selectivity. Selective antibiotics may be more effective at preserving host tissue, but their repeated use catalyses antibiotic resistance. Moreover, owing to the sequestration properties of EPS, the single use of antimicrobials to combat wound infection has been largely unsuccessful.

[0006] WO 2021 / 186188 Al describes a wound dressing or debridement tool comprising an absorbent layer impregnated or coated with a composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant.

[0007] However, there remains a need for further improvements in compositions suitable for use in wound dressings or debridement tools that are able to promote autolytic debridement while having physical modes of action against biofilms and the microorganisms comprised therein. In particular, non-antimicrobial compositions that have enhanced physical modes of action against biofilms and the microorganisms comprised therein are desirable. At the same time, there is a need for compositions that are simple, economical and safe to prepare while maintaining efficacy and suitability for use in wound dressings and debridement tools for the purposes discussed above. Moreover, there is also a need for compositions with good stability, e.g. during storage prior to application on a wound dressingor debridement tool to ensure good uniformity and consistency in manufactured articles. Further, due consideration must be given to the mutual compatibility of the components used in such compositions, avoiding deleterious effects on the patient such as cytotoxicity, minimising discomfort e.g. through tonicity and pH, while still ensuring good efficacy.

[0008] Compositions may be applied to substances such as fabrics and sheet-based materials by printing methods such as screen-printing, gravure printing, and rotary pad printing. However, there may be drawbacks associated with the foregoing methods when the substance is to be applied in an accurate manner, particularly where precise volumes or doses of a substance are to be deposited on a substrate. For example, it is known that non-woven fabrics are uneven, porous, stretchable and easily creased materials. Due to the uneven surface structure of the substrate material, transfer of substances from a printing roller may lack uniformity and the substances may not completely transfer from the printing roller to the surface of the substrate material. In any case, compositions known in the art may not be suitable for use (e.g. due to their rheology and / or other physicochemical properties) in one or more printing techniques commonly used in the art, and particularly those capable of achieving higher accuracy applications. Accordingly, there is also need for improved compositions that are compatible with such printing processes so as to enhance the accuracy and / or control of the application of said compositions, for example to a wound dressing or debridement tool.

[0009] The present disclosure seeks to address these needs with the various aspects and embodiments defined herein.SUMMARY

[0010] In a first aspect, the present disclosure provides a non-antimicrobial composition for printing onto an absorbent layer of a wound dressing or debridement tool, said composition comprising (i) at least about 50 wt% of a carrier which is glycerol, triglycerol, or a combination thereof, (ii) a solvent which is one or more C1.4 alcohol, and (iii) one or more excipients, wherein the weight ratio of (i) to (ii) in the composition is from about 2:1 to about 5:1.

[0011] In a further aspect, the present disclosure provides a process for preparing a non-antimicrobial composition as defined herein, said process comprising the steps of (a) combining the amphoteric surfactant and the anionic surfactant, (b) adding the chelating agent to the mixture of step (a), and (c) adding the solvent and carrier to the mixture of step (b), or (a) combining the solvent and the chelating agent, (b) adding the anionic surfactant to the mixture of step (a), (c) adding the amphoteric surfactant to the mixture of step (b), and adding the carrier to the mixture of step (c).

[0012] Another aspect of the present disclosure provides a process for preparing a non-antimicrobial composition as defined herein, wherein the one or more excipients comprise a chelating agent, an amphoteric surfactant, and an anionic surfactant, said process comprising the steps of (a) combining the amphoteric surfactant and the anionic surfactant, (b) adding the chelating agent to the mixture of step (a), and (c) adding the solvent and carrier to the mixture of step (b), or (a) combining the solvent and the chelating agent, (b) adding the anionic surfactant to the mixture of step (a), (c) adding the amphoteric surfactant to the mixture of step (b), and adding the carrier to the mixture of step (c).

[0013] Yet another aspect of the present disclosure provides a process for preparing a nonantimicrobial composition as defined herein further comprising a polyethylene glycol, wherein the polyethylene glycol has a weight average molecular weight of greater than about 1000 to less than about 8000, preferably about 1500 to about 7000, said process comprising the steps of:(a) mixing the polyethylene glycol into the one or more C1-C4 alcohol;(b) heating the mixture of step (a) to a minimum of about 30°C until the polyethylene glycol is fully dissolved in the one or more C1-C4 alcohol;(c) adding the solution of step (b) to the carrier; and(d) adding the one or more excipients to the solution of step (c).

[0014] A further aspect of the present disclosure provides a process for preparing a wound dressing or debridement tool, said process comprising printing the non-antimicrobial composition as defined herein onto a surface of an absorbent layer of the wound dressing or debridement tool.

[0015] Another aspect of the present disclosure provides a wound dressing or debridement tool obtained by the process defined herein, preferably wherein the absorbent layer is at least partially impregnated or coated with the non-antimicrobial composition, and wherein the absorbent layer comprises one or more gel-forming fibres. The present disclosure also provides for the use of the foregoing wound dressing or debridement tool to prevent or minimise slough accumulation in a wound or to de-slough a wound, the use comprising contacting said wound dressing or debridement tool with said wound or contacting said wound with said wound dressing or debridement tool, preferably wherein the wound is a chronic wound, acute wound, or burn.

[0016] These aspects and embodiments are set out in the appended independent and dependent claims. It will be appreciated that features of the dependent claims may be combined with each other and with features of the independent claims in combinations other than those explicitly set out in the claims. Furthermore, the approaches described herein are not restricted to specific embodiments such as those set out below, but include and contemplate any combinations of features presented herein.

[0017] The foregoing and other objects, features, and advantages of the present disclosure will appear more fully hereinafter from a consideration of the detailed description that follows along with the accompanying drawings. It is to be expressly understood, however, that the drawings are for illustrative purposes and are not to be construed as defining the limits of the disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is a representation of the equipment used in the art for screen printing. As depicted therein, ink (1) is applied across the screen (5) by a squeegee (2). The screen comprises an image (3) formed by way of a photoemulsion (4) which makes the screen impermeable to the ink in the areas to which the photoemulsion has been applied and cured (e.g. by UV light). As described herein, a second pass of the squeegee (2) then results in transfer of the ink from the areas of the screen that are permeable to the ink (i.e. where there is no photoemulsion applied) onto the substrate to form a printed image (6).

[0019] Figure 2A is a photograph of Formulation 10 from Experimental 2 consisting of disodium EDTA and oleic acid. Figure 2B is a photograph of Formulation 11 from Experimental 2 consisting of disodium EDTA and sodium oleate.

[0020] Figure 3 is a bar chart showing the efficacy of sodium oleate ink and oleic acid ink prepared in Experimental 5 in a simulated non-viable matter model detailed in Experimental 3. The inks are compared to an AQUACEL® Extra control (% more efficacious than AQUAGEL® Extra) where AQ Clean is solvent flooded with the concentration of excipients stated in Table 2. Sodium oleate ink is AQUACEL® Extra printed with 0.07g of the ink described in Table 9 on one side of a 10x10 cm sample, Oleic acid ink is AQUACEL® Extra printed with 0.07 g of the ink formulation stated in Table 9 on one side of a 10x10 cm sample and Glycerol only ink is AQUACEL® Extra printed with 0.07g of 77.77% glycerol 22.22% IDA ink on one side of a 10x10 cm sample.

[0021] Figure 4 is a table summarising the compatibility - solubility or miscibility - of potential carrier systems for the anionic surfactant, amphoteric surfactant and chelating agent.

[0022] Figure 5 is plot of stress and viscosity against shear rate showing the rheological behaviour of ink with a 50:50 ratio of triglycerol: glycerol throughout a flow ramp protocol as set out in the Examples. The Data is fit to a Newtonian fluid model using TRIOS software (TA Instruments, New Castle, Delaware, USA).

[0023] Figure 6 plots the efficacy of dressing samples printed with printing ink 1 (the formulation of Table 6) and triglycerol ink to disrupt simulated biofilm / non-viable matter substrate compared to an AQUAGEL® Extra control.

[0024] Figure 7 is from Experimental 4 and shows the change in viscosity against shear rate for the PEG thickeners tested in the ink formulation.

[0025] Figure 8 shows the open area pattern on a 120T screen. Black dots show the open area where ink will be printed onto a 10x10 cm AQUAGEL® Extra dressing in Experimental 1.

[0026] Figure 9 is a scatter plot of excipients mass added against total ink mass added to the dressing from Experimental 6. High, medium and low refers to the concentration of ink used.DETAILED DESCRIPTION

[0027] While various exemplary embodiments are described or suggested herein, other exemplary embodiments utilizing a variety of methods and materials similar or equivalent to those described or suggested herein are encompassed by the general inventive concepts. Those aspects and features of embodiments which are implemented conventionally may not be discussed or described in detail in the interests of brevity. It will thus be appreciated that aspects and features of apparatus and methods described herein which are not described in detail may be implemented in accordance with any conventional techniques for implementing such aspects and features.

[0028] As used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Unless otherwise stated, the term "about" modifying the quantity of a component refers to variation in the numerical quantity that can occur, for example, through typical measuring and handling procedures used for making concentrates, mixtures or solutions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the materials employed, or to carry out the methods; and the like. The term "about" also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture. Whether or not modified by the term "about", the claims include equivalents to the quantities. As used herein, the term "at least" includes the end value of the range that is specified. For example, "at least 10 wt%" includes the value 10 wt%.

[0029] The ranges provided herein provide exemplary amounts of each of the components. Each of these ranges may be taken alone or combined with one or more other component ranges.

[0030] As used herein, wt% means "weight percentage" as the basis for calculating a percentage. Unless indicated otherwise, all wt% values are calculated on an actives basis, and are provided with reference to the total weight of the product in which the substance is present. As used herein, w / w means "weight by weight" as the basis for calculating a percentage. Unless otherwise indicated, reference to "% by weight" (or "% by weight") of a product or composition reflects the total wet weight of the product or composition (i.e., including carrier and solvent).

[0031] The amount of composition ingredients may be presented on a wt% basis as well as on an area density (weight per area) basis dependent on the form and application of the product. For example, %w / w may be most appropriate for a fluid product, whereas an area density may be more appropriate to a flat sheet dressing. In such embodiments, the area density refers to the area of an absorbent layer as further described herein and the weight of the specified component comprised in or on said absorbent layer. For example, in various embodiments the composition may be applied to a wound dressing or debridement tool as described herein with an area density about 5 to about 40 g / m2. In specific examples, the composition may be applied at an area density of 30 g / m2or 15 g / m2. An exemplary wound dressing may comprise an absorbent layer of dimensions 10 x 10 cm (width x length), giving an area of 0.01 m2. Thus, for the example wherein the absorbent layer has an area of 0.01 m2, 0.3 g of a composition as described herein would be applied to the absorbent layer to obtain an area density of 30 g / m2. The composition may be applied to a single surface of the absorbent layer, for example in embodiments wherein the absorbent layer is comprised in a multi-layer wound dressing. Alternatively, the composition may be applied to a first surface of the absorbent layer and to a second surface of the absorbent layer opposite to the first surface of the absorbent layer. In such embodiments wherein the composition is applied to a first and second surface of the absorbent layer, the composition may be applied to the wound dressing or debridement tool as described herein to contribute 15 g / m2on each of the first and second surfaces, i.e. such that the total area density applied to the absorbent layer is 30 g / m2. In other words, the area densities recited herein refer to the total area density of composition applied to the absorbent layer, calculated on the basis of the area defined by the dimensions (width and length) of the absorbent layer and the total amount of the composition applied thereto, whether applied only to a single surface of the absorbent layer or applied to both a first surface and a second surface of the absorbent layer. Thus, for the example wherein the absorbent layer has an area of 0.01 m2(10 x 10 cm), 1.5 g of a composition as described herein could be applied to the first surface of the absorbent layer and 1.5 g of the composition applied to the second surface of the absorbent layer to obtain a total area density of 30 g / m2.

[0032] As used herein, "substantially free" means no more than trace amounts, i.e. the amount of the substance(s) concerned is negligible. In various embodiments, "substantially free" means no more than 1000 ppm, preferably no more than 100 ppm, more preferably no more than 10 ppm, even more preferably no more than 1 ppm of the substance(s) concerned.

[0033] In all aspects of the present disclosure, the disclosure includes, where appropriate, all enantiomers and tautomers of the compounds disclosed herein. A person skilled in the art will recognise compounds that possess optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and / or tautomers may be isolated / prepared by methods known in the art.

[0034] Some of the compounds disclosed herein may exist as stereoisomers and / or geometric isomers - e.g. they may possess one or more asymmetric and / or geometric centres and so may exist in two or more stereoisomeric and / or geometric forms. The present disclosure contemplates the use of all the individual stereoisomers and geometric isomers of those compounds, and mixtures thereof. The terms used in the claims encompass these forms.NON-ANTIMICROBIAL COMPOSITION

[0035] As described herein, there is provided a non-antimicrobial composition for printing onto an absorbent layer of a wound dressing or debridement tool. It is understood in the art that each of a wound dressing and a debridement tool are devices that are for direct placement on a subject's skin, namely for direct placement on a wound. As used herein the expression "wound" includes an injury to living tissue and may be caused by a cut, blow, or other impact, abrasion, pressure, heat or chemical. Typically the wound is one in which the skin is cut or broken.

[0036] The composition of the present disclosure advantageously maintains the beneficial properties of an absorbent layer in a wound dressing or debridement tool, in particular an absorbent layer which is beneficial in terms of absorbency and conformability, whilst being suitable for use in a printing process, for example screen printing. In some embodiments, the absorbent layer comprises gelforming fibres and the composition advantageously maintains the beneficial properties of gelling, absorbency and conformability whilst being suitable for use in a printing process such as screen printing.

[0037] It is known in the art to use solvent flooding to manufacture absorbent layers for wound dressings or debridement tools because it is efficacious in the delivery of excipients to the dressing. This process may involve saturating the absorbent layer with an excipient-containing solution, andremoving excess solution. With gel-forming fibres in the absorbent layer, the water content of the excipient-containing solution may be minimised in order to avoid premature gelling of the fibres or reduction in absorbency of the layer. Consequently the solvent used in the flooding process is primarily organic, e.g. an alcohol, and this can limit its application for large-scale manufacture both because of cost implications for infrastructure design and process controls, and safety implications surrounding the use of high volumes of volatile solvents. It would be desirable to manufacture absorbent layers on a large scale with improved considerations for safety, feasibility and efficacy. A printing process such as screen printing is attractive for this purpose because a reduced volume of solvent can be used to dose the excipients via a predesigned mesh.

[0038] The process of screen printing involves pressing an ink or pigment through a stencilled mesh using a rubber blade or squeegee. The mesh is stretched over a frame and remains under tension in order to act as the 'screen'. A design or pattern may be created by making areas of the mesh impermeable to the ink. This may be carried out using an emulsion as is known in the art. During use, the blade or squeegee is moved across the screen to fill the open mesh apertures with ink (excipients fully dissolved in a liquid) or pigment (particles suspended in a liquid carrier), and a second pass of the blade or squeegee causes the screen to touch the substrate momentarily along a line of contact. This causes the ink or pigment to wet the substrate and be pulled out of the mesh aperture as the screen springs back after the blade or squeegee has passed.

[0039] Figure 1 is a representative diagram of the equipment used for screen printing. As depicted therein, ink (1) is applied across the screen (5) by a squeegee (2). The screen comprises an image (3) formed by way of a photoemulsion (4) which makes the screen impermeable to the ink in the areas to which the photoemulsion has been applied and cured (e.g. by UV light). As described above, a second pass of the squeegee (2) then results in transfer of the ink from the areas of the screen that are permeable to the ink (i.e. where there is no photoemulsion applied) onto the substrate to form the printed image (6).

[0040] However unlike solvent flooding, the efficacy of excipient dosing using screen printing relies upon both the process and the starting materials. The excipients should be formulated into a liquid, preferably an ink, with the appropriate viscosity and surface tension to allow reproducible printing (which may be a continuous process in the case of rotary screen printing). Both viscosity and surface tension pertain to the intermolecular forces present within the bulk of the liquid, i.e. cohesive forces, and at the liquid interface; with the ability of the ink to wet a surface being reliant on a balance between the adhesive forces (liquid-solid) and cohesive forces (liquid-liquid). This relationship is complicated by the addition of one or more excipients to the ink, particular when the one or moreexcipients comprise a surfactant because as surface active molecules, surfactants are able to reduce the interfacial tension between two distinct phases (here liquid-solid), and this can affect the fluid dynamics of the ink, resulting in a deviation from theoretical ink deposition.

[0041] The properties of the substrate upon which the ink is to be printed must also be taken into account. An absorbent layer such as those included in wound dressings or debridement tools may provide a porous, absorbent scaffold with the ability to wick liquid via capillary action. Thus the ink to be printed must have a suitable surface tension and viscosity to facilitate the printing process, yet resist the favourable adhesive forces offered by such absorbent layers prior to liquid transfer.

[0042] Desirable specifications for a carrier system (irrespective of delivery method) include activity, biocompatibility, stability, and safety. The carrier system should be largely inert and not exhibit activity with respect to the intended effect of the excipients (if still present in the final product), unless predesigned. If the carrier system exhibits a biochemical effect, this may affect the regulatory classification of the device and / or its safety profile. In addition, the carrier should not exhibit any interference with the activity of the excipients via chemical, biological and / or physical means. The carrier system should similarly be biologically safe (especially if still present in the final product); it should not carry any significant additional risk(s) and should not alter the regulatory classification of the device. Stability overtime is also required; precipitation or phase separation of solutions decreases usability during manufacturing. Finally, due consideration should be given to any scale-up implications.

[0043] In summary, the inventors faced significant challenges in formulating a composition (ink) which was not only able to be used in a printing process for reproducible and accurate deposition onto or within an absorbent layer for a wound dressing or debridement tool, but which was inert, biocompatible, biologically safe, stable, and capable of solubilising one or more excipients aimed at enhancing the autolytic degradation and dissociation of detrimental material to promote wound healing in the absence of an antimicrobial agent.Carrier and Solvent

[0044] The above detailed challenges were addressed by the inclusion of two components in the composition at a specific weight ratio: namely (i) a carrier which is glycerol, triglycerol, or a combination thereof, and (ii) a solvent which is one or more C1-4 alcohol at a weight ratio (i):(ii) of from about 2:1 to about 5:1. The carrier is present at a concentration of at least about 50 wt% of the composition. The one or more C1.4 alcohol is defined further herein.

[0045] In preferred embodiments, the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1. For example, if the composition includes 70 wt% glycerol (i), the one or more Ci-4alcohol (ii) is present in an amount of 28 wt% (2.5:1) to 17.5 wt% (4:1). The one or more Ci-4alcohol is defined further herein.

[0046] In particularly preferred embodiments, the weight ratio of (i) to (ii) in the composition is from about 13:4 to about 4:1. For example, if the composition includes 75 wt% glycerol (i), the one or more Ci-4 alcohol (ii) is present in an amount of 23.0 wt% (13:4) to 18.75 wt% (4:1).

[0047] The concentrations are included here for example purposes only. The weight ratio range of (i):(ii) from about 2:1 to about 5:1, preferably from about 2.5:1 to about 4:1, more preferably from about 13:4 to about 4:1, is not limited to 60 wt% glycerol or 70 wt% glycerol or 75 wt% glycerol.

[0048] Glycerol is a colourless, odourless, viscous liquid that is non-toxic and used as a skin humectant since it reduces the rate of water loss. In the present invention, however, glycerol is used to improve the flow properties (rheology) of the composition. Triglycerol is the backbone of triglycerides and is made of three glycerol molecules linked together with ether bonds; like glycerol it is Newtonian in nature, but with a higher viscosity.

[0049] In some embodiments, the carrier is glycerol or a combination of glycerol and triglycerol. The combination of glycerol and triglycerol may have a parts by weight ratio of about 99:1 to about 50:50 parts. For example, the combination of glycerol and triglycerol may have a parts by weight ratio of from about 60:40 to about 99:1, from about 70:30 to about 99:1, from about 80:20 to about 99:1, or from about 90:10 to about 99:1. These ranges may be combined with the above weight ratio ranges for (i):(ii) as well as the concentration ranges described herein. For example, the composition may comprise (i) and (ii) at a weight ratio of from about 2.5:1 to about 4:1, wherein (i) is glycerol or a combination of glycerol and triglycerol, the combination having a parts by weight ratio of about 99:1 to about 50:50. In various embodiments, the composition may comprise (i) and (ii) at a weight ratio of from about 2.5:1 to about 4:1, wherein (i) is glycerol or a combination of glycerol and triglycerol, the combination having a parts by weight ratio of from about 60:40 to about 99:1, from about 70:30 to about 99:1, from about 80:20 to about 99:1, or from about 90:10 to about 99:1.

[0050] In particularly preferred embodiments, (i) in the composition is glycerol.

[0051] The concentration of (i) glycerol, triglycerol, or combination thereof is not critical to the present disclosure. As will be appreciated from the scope of the appended claims and the Examples, it is the relative amount of (i) to (ii) the one or more Ci-4alcohol which is important (from about 2:1 toabout 5:1, preferably from about 2.5:1 to about 4:1, more preferably from about 13:4 to about 4:1), and the concentrations of (i) and (ii) will depend on the concentration of the one or more excipients. Should the skilled person require a lower limit for (i), (i) may be included in the composition in an amount of at least about 50 wt% and preferably about 55 wt%. Should the skilled person require an upper limit for (i), (i) may be included in the composition in an amount of no more than about 90 wt% and preferably no more than about 85 wt%. Combining these lower and upper limits provides a general range of at least about 50 wt% to no more than about 90 wt%, and a preferred range of at least about 55 wt% to no more than about 85 wt%.

[0052] In some embodiments, the carrier (i) is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50, and wherein (i) is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%. Preferably (i) is glycerol, and glycerol is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%.

[0053] In some embodiments, (i) in the composition is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50, and wherein (i) is present in the composition in an amount of at least about 55 wt% to no more than about 85 wt%. Preferably (i) is glycerol, and glycerol is present in the composition in an amount of at least about 55 wt% to no more than about 85 wt%.

[0054] The one or more Ci-4alcohol is included in the composition to assist the glycerol, triglycerol, or combination thereof, in the solubilisation of the one or more excipients. As the alcohol is volatile, it can be evaporated off the absorbent layer after printing. In some embodiments, the one or more Ci-4 alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof, preferably wherein the one or more Ci-4alcohol comprises ethanol. In the examples, industrial denatured alcohol is employed but the present disclosure is not limited to this specific form of the one or more Ci-4alcohol.

[0055] In some embodiments, (i) in the composition is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50; wherein (i) is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%; and wherein (ii) the one or more Ci-4alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof. Preferably (i) is glycerol, and glycerol is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%. Particularly preferably, (i) isglycerol, present in the composition in an amount of at least about 50 wt% to no more than about 90 wt% and the one or more C1.4 alcohol comprises ethanol.

[0056] In some embodiments, (i) in the composition is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50; wherein (i) is present in the composition in an amount of at least about 55 wt% to no more than about 85 wt%; and wherein the one or more C1-4 alcohol comprises ethanol. Preferably (i) is glycerol, and glycerol is present in the composition in an amount of at least about 55 wt% to no more than about 85 wt%. Particularly preferably, (i) is glycerol, present in the composition in an amount of at least about 55 wt% to no more than about 85 wt% and the one or more C1-4 alcohol comprises ethanol.

[0057] In any of the above embodiments, the weight ratio of (i) to (ii) in the composition may be from about 2.5:1 to about 4:1, preferably from about 13:4 to about 4:1.

[0058] In the non-antimicrobial composition of the present disclosure, components (i) and (ii) form the substrate for printing the composition onto an absorbent layer of a wound dressing or debridement tool. In other words, components (i) and (ii) are the vehicle for delivering the one or more excipients to the absorbent layer. As the substrate or delivery vehicle, the parts by weight ratio of (i) to (ii) is from about 60:40 to about 80:20, preferably from about 70:30 to about 80:20. This means that with, for example, 67 wt% glycerol and 19 wt% ethanol in the composition (a weight ratio of about 3.5:1), the substrate has 78 parts glycerol to 22 parts ethanol. Similarly, for example, 53 wt% glycerol and 17.7 wt% ethanol in the composition (a weight ratio of about 3:1), the substrate has 75 parts glycerol to 25 parts ethanol.

[0059] In some embodiments, the carrier (i) is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50, wherein (i) is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%, and wherein (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 60:40 to about 80:20.

[0060] Preferably (i) is glycerol in an amount of at least about 50 wt% to no more than about 90 wt% of the composition, wherein (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 70:30 to about 80:20.

[0061] In some embodiments, the carrier (i) is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50, wherein (i) ispresent in the composition in an amount of at least about 55 wt% to no more than about 85 wt%, and wherein (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 50:40 to about 80:20.

[0062] Preferably (i) is glycerol in an amount of at least about 55 wt% to no more than about 85 wt% of the composition, wherein (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 70:30 to about 80:20.

[0063] The one or more C1-4 alcohol is included in the composition to assist the glycerol, triglycerol, or combination thereof, in the solubilisation of the one or more excipients. As the alcohol is volatile, it can be evaporated off the absorbent layer after printing. In some embodiments, the one or more C1-4 alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof, preferably wherein the one or more C1-4 alcohol comprises ethanol. In the examples, industrial denatured alcohol is employed but the present disclosure is not limited to this specific form of the one or more C1.4 alcohol.

[0064] In some embodiments, (i) in the composition is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50; wherein (i) is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%; and wherein (ii) the one or more C1-4 alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof. Preferably (i) is glycerol, and glycerol is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%. Particularly preferably, (i) is glycerol, present in the composition in an amount of at least about 50 wt% to no more than about 90 wt% and the one or more C1-4 alcohol comprises ethanol.

[0065] In some embodiments, (i) in the composition is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50; wherein (i) is present in the composition in an amount of at least about 55 wt% to no more than about 85 wt%; and wherein the one or more C1.4 alcohol comprises ethanol. Preferably (i) is glycerol, and glycerol is present in the composition in an amount of at least about 55 wt% to no more than about 85 wt%. Particularly preferably, (i) is glycerol, present in the composition in an amount of at least about 55 wt% to no more than about 85 wt% and the one or more C1-4 alcohol comprises ethanol.

[0066] In some embodiments, the carrier (i) is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50, wherein (i) is present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%,wherein (ii) the one or more C1.4 alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof, and wherein (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 60:40 to about 80:20.

[0067] Preferably (i) is glycerol in an amount of at least about 50 wt% to no more than about 90 wt% of the composition, the one or more C1-4 alcohol comprises ethanol, and (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 70:30 to about 80:20.

[0068] In some embodiments, the carrier (i) is glycerol or a combination of glycerol and triglycerol, wherein the combination has a parts by weight ratio of about 99:1 to about 50:50, wherein (i) is present in the composition in an amount of at least about 55 wt% to no more than about 85 wt%, wherein (ii) the one or more C1-4 alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof, and wherein (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 60:40 to about 80:20.

[0069] Preferably (i) is glycerol in an amount of at least about 55 wt% to no more than about 85 wt% of the composition, the one or more C1.4 alcohol comprises ethanol, and (i) and (ii) form the substrate for printing the composition onto the absorbent layer with a parts by weight ratio of (i) to (ii) in the substrate of from about 70:30 to about 80:20.

[0070] In any of the above embodiments, the weight ratio of (i) to (ii) in the composition may be from about 2.5:1 to about 4:1, preferably from about 13:4 to about 4:1.

[0071] As noted herein, for some absorbent layers - particularly those including one or more gelforming fibres - the exposure to water can be detrimental to the properties of said layer. It can, for example, cause premature gelling of the fibre(s) and thereby reduce the absorbent layer's absorbency and / or conformability. In some embodiments it is therefore desirable to minimise the amount of water in the composition. As the skilled person will understand, surfactants are often available from commercial sources as diluted solutions. For example, sodium cocoamphoacetate is typically supplied as an aqueous solution comprising about 30-40% active. The "amount of water" in the composition is therefore used herein to refer to both water contributed by aqueous solutions of one or more excipients (e.g. the anionic or amphoteric surfactant), and water added during manufacture. In some embodiments, the composition includes no more than about 15 wt% water, preferably no more thanabout 12 wt% water, and more preferably no more than about 10 wt% water. In some embodiments, the composition is prepared without addition of water.Excipients

[0072] In some embodiments of the present disclosure, the composition includes one or more excipients aimed at enhancing or promoting the autolytic degradation and dissociation of detrimental material from a wound, thereby improving the healing of said wound. Such an effect is surprisingly achieved without the inclusion of an antimicrobial agent in the composition. The composition of the present disclosure is therefore defined herein as a "non-antimicrobial" composition. This means that the composition does include any antimicrobial agents, including agents such as hypochlorous acid, silver compounds, polyhexamethylene biguanide (also known as polyhexanide biguanide), chlorhexidine, and chlorhexidine salts.

[0073] Whilst the use of antiseptic wound cleansers or debridement solutions is popular (owing to their ability to affect multiple cellular target sites in a non-specific way, thus reducing the likelihood of selecting for resistant strains of microorganisms), some resistance has been observed, and crossresistance between antibiotics and antiseptics has been detected. With the prospect of a postantibiotic era looming, ways to maintain our antimicrobial armamentarium should be considered in all aspects of healthcare, including wound treatment. Normal saline is frequently employed for the cleansing of both acute and chronic wounds, although is often accompanied by a need for increased mechanical action during debridement, thereby resulting in increased patient discomfort. In contrast, the non-antimicrobial compositions disclosed herein can effectively aid subsequent wound debridement and the removal of biofilm even in the absence of antimicrobial agents.

[0074] As described herein, the non-antimicrobial compositions of the present disclosure include one or more excipients to disrupt and lift the loose components of wounds from the surface. Surprisingly the compositions further disrupt one or more biofilms. The latter is advantageous because the presence of microbes in wounds is an additional and common impediment to the healing of wounds and can lead to clinical complications.CHELATING AGENT OR CHELATOR

[0075] The one or more excipients included within the non-antimicrobial composition of the present disclosure may comprise a chelating agent or chelator. Chelating agents are organic or inorganic compounds capable of binding metal ions to form complex ring or cage-like structures called 'chelates'. In the case of chronic wound care, chelation of metal ions removes their ability to interactwith the surrounding biochemical matrix, thereby limiting their effects and rendering them effectively inert. Metal ions such as Mg2+ and Ca2+ have been shown to stabilise biofilms formed by a variety of microorganisms. Multi-valent metal ions enhance the structural integrity of bacterial biofilms via electrostatic interactions that serve to crosslink the polyanionic alginate and similar polysaccharide chains. Despite the association of high-density EPS formation with specific species of bacteria, the resultant polymeric architecture is not an exclusive resource belonging to the producing organism. Instead, it can act as a shared housing utilised by additional species of bacteria less adept at EPS production. Therefore, removal of the ions holding the matrix together is not a species-specific strategy, rather a more generalised anti-biofilm measure aimed at disrupting the entire wound- associated bacterial ecosystem.

[0076] Multi-valent metal ions are also implicated in stabilising extracellular DNA (eDNA), an integral matrix component of multiple, clinically relevant biofilms, including those formed by Pseudomonas aeruginosa and Staphylococcus aureus. Specifically, negatively charged eDNA binds to divalent metal ions which promotes bacterial aggregation via cationic bridging. As such, chelation of metal ions can result in EPS disruption, prevention of EPS formation, dispersal of planktonic cells (free-living, single cells) from the biofilm and, in high concentration, cellular lysis. Therefore, removal of such cations from the biofilm matrix may enhance wound cleansing via alteration of both the cellular phenotype and genotype.

[0077] In the present disclosure, the chelating agent may be selected from citrates, tartrates, tartramides, tartrimides, gluconates, lactates, glycolates, oxalates, phosphates, salts of ethylenediaminetetraacetic acid, and mixtures thereof. In some embodiments, the chelating agent may be selected from citrates, phosphates, oxalates, salts of ethylenediaminetetraacetic acid, and mixtures thereof. In various embodiments the salts are metal ion or ammonium salts. The metal ion of said salts is not limited. In various embodiments, metal ion salts are preferred and may be selected from sodium and / or potassium salts. In particularly preferred embodiments, the salts are sodium salts.

[0078] In preferred embodiments the chelating agent comprises a salt of ethylenediaminetetraacetic acid. The ethylenediaminetetraacetate salt may be a mixture of di-, tri-, or tetra-basic salts of ethylenediaminetetraacetate (EDTA). The EDTA salt may, for instance, be a di-sodium salt of EDTA, or calcium di-sodium salt of EDTA, or tetra-sodium salt of EDTA. In various embodiments, the salt of EDTA is a mixture of salts of EDTA. It is believed that EDTA, when present, will have a form which is dependent on the pH of the wound site. In preferred embodiments, EDTA may be added to the composition as a tetra-basic salt of EDTA such as tetrasodium EDTA. In some embodiments, EDTA is not in the form of the disodium salt.

[0079] The citrate salt may similarly be a mono-, di- or tri-citrate salt. In various embodiments the citrate salt may be mono-, di- or tri-potassium citrate or mono-, di- or tri-sodium citrate. In preferred embodiments, the citrate salt is a tri-citrate salt such as trisodium citrate.

[0080] The tartrate may be a mono-, or di-tartrate salt. In various embodiments, the tartrate salt may be mono- or di-potassium tartrate; or mono- or di-sodium tartrate. In specific embodiments, the tartrate salt is a di-tartrate salt such as disodium tartrate.

[0081] The gluconate may be potassium gluconate or sodium gluconate. In specific embodiments, the gluconate salt is sodium gluconate. Similarly, the lactate may be potassium lactate or sodium lactate. In specific embodiments, the lactate salt is sodium lactate. The glycolate may be potassium glycolate or sodium glycolate. In specific embodiments, the glycolate salt is sodium glycolate.

[0082] The oxalate may be a mono-, or di-oxalate salt. In various embodiments, the oxalate salt may be mono- or di-potassium oxalate; or mono- or di-sodium oxalate. In specific embodiments, the oxalate salt is a di-oxalate salt such as disodium oxalate.

[0083] The phosphate salt may be an ortho-phosphate, a pyrophosphate, a tripolyphosphate or a derivatised phosphate. The phosphate is typically in the form of a potassium or sodium salt. Examples include potassium phosphate dibasic, potassium pyrophosphate, tri-sodium ascorbate phosphate, disodium phosphate and sodium tripolyphosphate. In preferred embodiments the phosphate salt is a di-phosphate salt such as disodium phosphate.

[0084] The chelating agent may be present in the composition in an amount of up to about 10 wt%, up to about 8 wt%, or up to about 6 wt% of the total weight of the composition. In various embodiments, the chelating agent may be present in the composition in an amount of at least about 0.5 wt%, at least about 1.0, or at least about 1.2 wt% of the total weight of the composition.

[0085] In various embodiments wherein the composition described herein is at least partially impregnated or coated in or on an absorbent layer comprised in a wound dressing or debridement tool, the chelating agent is present in the absorbent layer at up to about 2.5 g / m2, up to about 1.5 g / m2or up to about 1.0 g / m2on an actives basis. In various embodiments, the chelating salt is present in the absorbent layer in an amount of at least about 0.1, at least about 0.2, or at least about 0.25 g / m2on an actives basis.

[0086] In various embodiments, the chelating agent is present in the composition in an amount of from about 0.5 to about 10 wt%, from about 1 to about 8 wt%, or from about 1.2 to about 6 wt% ofthe total weight of the composition. In various embodiments, the chelating agent is selected from citrates, tartrates, tartramides, tartrimides, gluconates, lactates, glycolates, oxalates, phosphates, salts of ethylenediaminetetraacetic acid, and mixtures thereof, and is present in the composition in an amount of from about 0.5 to about 10 wt%, from about 1 to about 8 wt%, or from about 1.2 to about 6 wt% of the total weight of the composition.

[0087] In further embodiments, the chelating agent is a salt of ethylenediaminetetraacetic acid (EDTA), preferably a tetra-salt of ethylenediaminetetraacetic acid, and is present in the composition in an amount of from about 0.5 to about 10 wt%, from about 1 to about 8 wt%, or from about 1.2 to about 6 wt% of the total weight of the composition. The salt of EDTA may in various embodiments be a sodium salt such as a tetrasodium salt.

[0088] In various embodiments wherein the composition described herein is at least partially impregnated or coated in or on an absorbent layer comprised in a wound dressing or debridement tool, the chelating agent is present in the absorbent layer from about 0.1 to about 2.5 g / m2, from about 0.2 to about 1.5 g / m2, or from about 0.25 to about 1.0 g / m2on an actives basis. In various embodiments, the chelating agent is selected from citrates, tartrates, tartramides, tartrimides, gluconates, lactates, glycolates, oxalates, phosphates, salts of ethylenediaminetetraacetic acid, and mixtures thereof, and is present in the absorbent layer at about 0.1 to about 2.5 g / m2, from about 0.2 to about 1.5 g / m2, or from about 0.25 to about 1.0 g / m2on an actives basis.

[0089] In further embodiments, the chelating agent is a salt of ethylenediaminetetraacetic acid (EDTA), preferably a tetra-salt of ethylenediaminetetraacetic acid, and is present in the absorbent layer at about 0.1 to about 2.5 g / m2, from about 0.2 to about 1.5 g / m2, or from about 0.25 to about 1.5 g / m2on an actives basis. The salt of EDTA may in various embodiments be a sodium salt such as a tetrasodium salt.SURFACTANT

[0090] Surfactants are widely used as detergents, emulsifiers, wetting agents, foaming agents and dispersants in the cosmetics, hygiene, food and oil industries. They are also used in a clinical setting including advanced wound care. As surface-active agents, surfactants are amphiphilic; they contain both hydrophilic and hydrophobic components and are therefore capable of lowering the surface tension at the solid / liquid interface, allowing for greater penetration of fluids into the wound bed and subsequent removal of biological materials by irrigating agents such as water or saline.

[0091] Non-ionic surfactants (e.g. poloxamer) are reported to be effective in the solubilisation and disaggregation of proteins. They are seemingly able to block the adhesion of certain proteins thus reducing microbial adhesion. Indeed, wound irrigation solutions containing non-ionic surfactants have been demonstrated to effectively cleanse and remove debris from wounds.

[0092] The present inventors found, however, that a combination of an anionic surfactant and an amphoteric surfactant is surprisingly able to effectively cleanse and remove debris from wounds when used in combination with the chelating agent defined above.AMPHOTERIC SURFACTANT

[0093] The one or more excipients may comprise an amphoteric surfactant. In various embodiments, the amphoteric surfactant is selected from hydrocarbyl-amphoacetates, alkenyl-amphoacetates, hydrocarbyl-amphodiacetates, alkenyl-amphodiacetates, hydrocarbylampho-propionates, hydrocarbylampho-diproprionates, hydrocarbylamphohydroxypropyl sultaines, and mixtures thereof. In various embodiments, the hydrocarbyl and alkenyl groups are C6 to C24, C8 to C24, or CIO to C20, hydrocarbyl or alkenyl groups. Typically, the amphoteric surfactant has a counter-ion of an alkali metal such as sodium or potassium, or an ammonium ion. In preferred embodiments, the amphoteric surfactant has an alkali metal counter-ion, and more preferably the counter-ion is sodium.

[0094] As used herein, the term "hydrocarbyl" includes a group such as alkyl, aryl, aralkyl, alkaryl, cycloalkyl or alkenyl, which may be linear or branched, and / or saturated or unsaturated. In one embodiment, the hydrocarbyl may be a linear or branched alkyl or alkenyl group.

[0095] In various embodiments the amphoteric surfactant is a hydrocarbyl-amphoacetate salt, preferably a fatty acid amphoacetate. The fatty acid or salt thereof may be a C6-C24 fatty acid or salt thereof, or a mixture thereof. The fatty acid or salt thereof may be saturated or unsaturated. When unsaturated, the unsaturated fatty acid or salt thereof may be mono- or di-unsaturated. The unsaturated fatty acid or salt thereof may comprise cis- or trans- double bonds or mixtures thereof. In further embodiments, the fatty acid or salt thereof is a C12-C18 monounsaturated fatty acid or salt thereof. Examples of fatty acids include stearic acid, ricinoleic acid, oleic acid, eladic acid, petrolselinic acid, palmitic acid, erucic acid, behenic acid, lauric acid, myristic acid, or linoleic acid.

[0096] In preferred embodiments, the amphoteric surfactant comprises a cocoamphoacetate. The counter-ion of the cocoamphoacetate is preferably sodium. Sodium cocoamphoacetate is commercially available, for example under the trade name Dehyton® MC (BASF) or Amphosol® 1C(Stepan®). Such commercial preparations are typically solutions of sodium cocoamphoacetate, typically containing from about 30 to about 40 wt% sodium cocoamphoacetate on an actives basis.

[0097] In various embodiments, the metal ions of the salt of the chelating agent and the salt of the amphoteric surfactant are the same. Preferably, both the chelating agent and surfactant are sodium salts.

[0098] The amphoteric surfactant may be present in the composition in an amount of up to about 15 wt%, up to about 10 wt% or up to about 5 wt% of the total weight of the composition. In various embodiments, the amphoteric surfactant may be present in the composition in an amount of at least about 1 wt% of the total weight of the composition.

[0099] In various embodiments wherein the composition described herein is at least partially impregnated or coated in or on an absorbent layer comprised in a wound dressing or debridement tool, the amphoteric surfactant is present in the absorbent layer in an amount of up to about 3 g / m2, up to about 2 g / m2, or up to about 1.5 g / m2on an actives basis. In various embodiments, the amphoteric surfactant is present in the absorbent layer in an amount of at least about 0.1 or at least about 0.25 g / m2.

[0100] In various embodiments, the amphoteric surfactant is present in the composition in an amount of from about 1 wt% to about 15 wt%, about 1 wt% to about 10 wt% or from about 1 to about 5 wt% of the total weight of the composition.

[0101] In various embodiments, the amphoteric surfactant comprises a fatty acid amphoacetate as defined herein, and the amphoteric surfactant is present in the composition in an amount of from about 1 to about 15 wt%. In various embodiments, the amphoteric surfactant comprises a fatty acid amphoacetate as defined herein, and the amphoteric surfactant is present in the composition in an amount of from about 1 to about 10 wt% or from about 1 to about 5 wt% of the total weight of the composition. In any of the foregoing embodiments, the fatty acid amphoacetate may be a cocoamphoacetate, preferably sodium cocoamphoacetate.

[0102] In various embodiments wherein the composition described herein is at least partially impregnated or coated in or on an absorbent layer comprised in a wound dressing or debridement tool, the amphoteric surfactant may be present in the absorbent layer in an amount of from about 0.1 to about 3 g / m2, from about 0.1 to about 2 g / m2, or from about 0.25 to about 1.5 g / m2on an actives basis. In various embodiments, the amphoteric surfactant comprises a fatty acid amphoacetate as defined herein and the amphoteric surfactant is present in the absorbent layer in an amount of fromabout 0.1 to about 3 g / m2, from about 0.1 to about 2 g / m2, or from about 0.25 to about 1.5 g / m2on an actives basis. In any of the foregoing embodiments, the fatty acid amphoacetate may be a cocoamphoacetate. In any of the foregoing embodiments, amphoteric surfactant may be an alkali metal salt, for example a sodium salt such as sodium cocoamphoacetate.ANIONIC SURFACTANT

[0103] The anionic surfactant may include all forms of lipophilic oligomeric hydrocarbon and / or polyethoxylate with a negatively charged hydrophilic head group such as carboxylate, sulphate, sulphonate, sulphonated ester, sulphated ester, sulphated amide, carboxylated amide, or phosphate anionic head group. For example, including a fatty acid or fatty acid salt. The fatty acid may comprise 6 to 24 carbon atoms, such as 10 to 20 carbon atoms, preferably 12 to 18 carbon atoms.

[0104] In various embodiments, the anionic surfactant comprises a fatty acid or salt thereof. The fatty acid may comprise 6 to 24 carbon atoms, such as 10 to 20 carbon atoms, preferably 12 to 18 carbon atoms. Examples of fatty acids include stearic acid, ricinoleic acid, oleic acid, eladic acid, petrolselinic acid, palmitic acid, erucic acid, behenic acid, lauric acid, myristic acid, or linoleic acid.

[0105] In some embodiments, the anionic surfactant may be a fatty acid or salt thereof which is a C6- C24 fatty acid or salt thereof, or a mixture thereof. The salt may be an alkali metal or alkaline earth metal salt, preferably an alkali metal salt. In preferred embodiments, the alkali metal is sodium or potassium, more preferably sodium. The fatty acid or salt thereof may be saturated or unsaturated. When unsaturated, the unsaturated fatty acid or salt thereof may be mono- or di-unsaturated. The unsaturated fatty acid or salt thereof may comprise cis- or trans- double bonds or mixtures thereof. In further embodiments, the fatty acid or salt thereof is a C12-C18 monounsaturated fatty acid or salt thereof.

[0106] In particularly preferred embodiments, the fatty acid or salt thereof is oleic acid or a salt thereof. The salt of oleic acid is not limited and may be a metal salt of oleic acid. In various embodiments the salt of oleic acid may be sodium oleate. In various embodiments, the salt of oleic acid may be formed by adding oleic acid to the composition such that the metal ions, e.g. sodium ions, are provided by provided by the chelating agent, the thickening agent and / or the amphoteric surfactant.

[0107] The amount of anionic surfactant in the composition is not necessarily limited. The anionic surfactant may, for example, be present in the composition in an amount of up to about 15 wt%, up to about 10 wt%, or up to about 8 wt% of the total weight of the composition. The anionic surfactantmay be present in an amount of at least about 1 wt%, or at least about 1.5 wt% of the total weight of the composition.

[0108] In various embodiments, the anionic surfactant is present in the composition in an amount of from about 1 wt% to about 15 wt%, preferably from about 1 wt% to about 10 wt%, more preferably from about 1.5 wt% to about 8 wt% of the total weight of the composition.

[0109] In various embodiments, the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof, wherein the fatty acid comprises 6 to 24 carbon atoms, and the anionic surfactant is present in the composition in an amount of from about 1 wt% to about 15 wt%, preferably from about 1 wt% to about 10 wt% of the total weight of the composition. In any of the foregoing embodiments, the salt may be a sodium salt.

[0110] In various embodiments, the anionic surfactant comprises a fatty acid and / or salt thereof, wherein the fatty acid comprises 6 to 24 carbon atoms, and the anionic surfactant is present in the composition in an amount of from about 1 wt% to about 15 wt%, preferably from about 1 wt% to about 10 wt% of the total weight of the composition.

[0111] In various embodiments, the anionic surfactant comprises oleic acid and / or a salt thereof, which is present in the composition in an amount of from about 1 wt% to about 15 wt%, preferably from about 1 wt% to about 10 wt% of the total weight of the composition. In any of the foregoing embodiments, the oleic acid salt may be sodium oleate.

[0112] In various embodiments wherein the composition described herein is at least partially impregnated or coated in or on an absorbent layer comprised in a wound dressing or debridement tool, the anionic surfactant may be present in the absorbent layer in an amount of from about 0.1 to about 3 g / m2, from about 0.25 to about 2.5 g / m2, or from about 0.5 to about 2 g / m2on an actives basis.

[0113] In various embodiments, the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof, wherein the fatty acid comprises 6 to 24 carbon atoms, and the anionic surfactant is present in the absorbent layer in an amount of from about 0.1 to about 3 g / m2, from about 0.25 to about 2.5 g / m2, or from about 0.5 to about 2 g / m2on an actives basis.

[0114] In various embodiments, the anionic surfactant comprises a fatty acid and / or salt thereof, wherein the fatty acid comprises 6 to 24 carbon atoms, and the anionic surfactant is present in the absorbent layer in an amount of from about 0.1 to about 3 g / m2, from about 0.25 to about 2.5 g / m2, or from about 0.5 to about 2 g / m2on an actives basis.

[0115] In various embodiments, the anionic surfactant comprises oleic acid and / or a salt thereof, which is present in the absorbent layer in an amount of from about 0.1 to about 3 g / m2, from about 0.25 to about 2.5 g / m2, or from about 0.5 to about 2 g / m2on an actives basis.

[0116] In any of the foregoing embodiments, the oleic acid salt may be sodium oleate.

[0117] In various embodiments, the metal ions of the salt of the chelating agent and the salt of the anionic surfactant are the same. Preferably, both the chelating agent and surfactant are sodium salts.CHELATING AGENT, AMPHOTERIC SURFACTANT AND ANIONIC SURFACTANT

[0118] It has been found that the chelating agents and the anionic and amphoteric surfactants described herein operate together to disrupt biofilms and cleanse wounds. Without wishing to be bound by theory, it is believed that each of the chelating agent and the surfactant exert their action via different physicochemical means. For example, the chelating agent is believed to coordinate metal ions such as those present in the matrix and biofilm, weakening the structure of the biofilm. On the other hand, the anionic and amphoteric surfactant is believed to aid wetting (and hence aiding penetration of fluids into the wound bed), to solubilise proteins, DNA, and other components present in the wound.

[0119] In various embodiments, the combination of chelating agent and surfactant have been found to be synergistic. Synergy in the context of the present disclosure can be measured in a number of ways that conform to the generally accepted opinion that "synergy is an effect greater than additive". One of the ways to assess whether synergy has been observed is to use the "chequerboard" technique. This is a well-accepted method that leads to the generation of a value called the fractional inhibitory concentration index (FICI). Orhan et al J. Clin. Microbiol. 2005, 43(l):140 describes the chequerboard method and analysis in the paragraph bridging pages 140-141, and explains that the FICI value is a ratio of the sum of the MIC (Minimum Inhibitory Concentration) level of each individual component alone and in the mixture. The combination is considered synergistic when the IFIC is <0.5, indifferent when the 1 FIC is >0.5 but <4.0, and antagonistic when the FIC is >4.0.

[0120] In the context of wounds hygiene as described herein, synergy may be exhibited in that the chelating agent and anionic and amphoteric surfactant do not cleanse / irrigate the wound effectively and / or disrupt the biofilm when used without the other, but in combination said chelating agent and anionic and amphoteric surfactant are effective at cleansing the wound and / or disrupting the biofilm.

[0121] It would be understood by the person skilled in the art that the definition of the amphoteric and anionic surfactant set out above is combinable with the definition of the chelating agent. For example, in various embodiments the chelating agent is selected from the group consisting of a citrate salt, a phosphate salt, an oxalate salt, an ethylenediaminetetraacetate salt, and mixtures thereof, the anionic surfactant is selected from a fatty acid or salt thereof, a glutamate salt, a sarcosinate salt, and an isethionate salt, wherein the fatty acid comprises 6 to 24 carbon atoms, and the amphoteric surfactant is a hydrocarbyl-amphoacetate salt. The salts are metal ion salts, preferably sodium salts.

[0122] In various embodiments, the chelating agent is an ethylenediaminetetraacetate salt, the anionic surfactant is a fatty acid or salt thereof, wherein the fatty acid comprises 6 to 24 carbon atoms, and the amphoteric surfactant is a fatty acid amphoacetate salt, wherein the fatty acid has 10 to 20 carbon atoms. The salts are metal ion salts, preferably sodium salts.

[0123] In preferred embodiments, the chelating agent is an ethylenediamine tetraacetate salt, the anionic surfactant is oleic acid or a salt thereof, and the amphoteric surfactant is a cocoamphoacetate. The salts are metal ion salts, preferably sodium salts.EXEMPLARY NON-ANTIMICROBIAL COMPOSITIONS

[0124] Each of the anionic surfactant, amphoteric surfactant and chelating agent may be present in an amount suitable to provide the desired cleansing and / or irrigation effect on the wound. The specific combination of surfactants and chelating agent and their concentrations have been found by the inventors to provide a composition with antibiofilm activity without the need for an antimicrobial agent. In particular, the surfactants and chelating agent are shown to disrupt non-viable proteins / carbohydrates and demonstrate enhanced efficacy when compared to commercially available products.

[0125] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1-4 alcohol;(iii) a salt of ethylenediamine tetraacetic acid;(iv) a Ce-C24fatty acid amphoacetate; and(v) oleic acid or a salt thereof.

[0126] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1-4 alcohol; wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) a salt of ethylenediamine tetraacetic acid;(iv) a C6-C24 fatty acid amphoacetate; and(v) oleic acid or a salt thereof,

[0127] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol;(iii) a salt of ethylenediamine tetraacetic acid;(iv) a cocoamphoacetate; and(v) oleic acid or a salt thereof.

[0128] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1-4 alcohol; wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) a salt of ethylenediamine tetraacetic acid;(iv) a cocoamphoacetate; and(v) oleic acid or a salt thereof.

[0129] In any of the foregoing embodiments, the chelating agent may be present in an amount of about 0.5 wt% to about 10 wt%, about 1 wt% to about 8 wt% or about 1.2 wt% to about 6 wt%. For example, the chelating agent may be present in an amount of about 1 to about 8 wt% of the composition and selected from a citrate salt, a phosphate salt, an ethylenediaminetetraacetate salt, and mixtures thereof. Preferred are EDTA salts such as tetrasodium EDTA, present in an amount of about 1.2 wt% to about 6 wt%.

[0130] In any of the foregoing embodiments, the anionic surfactant may be present in an amount of about 1 wt% to about 15 wt%, about 1 wt% to about 10 wt%, or about 1.5 wt% to about 8 wt%. For example, the anionic surfactant may be present in an amount of about 1% to about 10% by weight of the composition and selected from fatty acids and / or salts thereof, wherein the fatty acid comprises 6 to 24 carbon atoms. Preferably the anionic surfactant is present in an amount of about 1.5 wt% to about 8 wt% and is oleic acid or a salt thereof.

[0131] In any of the foregoing embodiments, the amphoteric surfactant may be present in an amount of about 1 wt% to about 15 wt%, about 1 wt% to about 10 wt%, or about 1 wt% to about 5 wt%. For example, the amphoteric surfactant may be present in an amount of about 1 wt% to about 10 wt% and selected from a hydrocarbyl-amphoacetate salt, a hydrocarbyl-amphodiacetate salt, and mixtures thereof, wherein the hydrocarbyl groups contain 6 to 24 carbon atoms. Preferably the amphoteric surfactant is present in an amount of about 1 wt% to about 5 wt%, and is a fatty acid amphoacetate salt, wherein the fatty acid comprises 8 to 24 carbon atoms. In a particularly preferred embodiment, the amphoteric surfactant is a cocoamphoacetate salt.

[0132] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more Ci-4alcohol;(iii) about 0.5 wt% to about 10 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 15 wt % of a C6-C24fatty acid amphoacetate; and(v) about 1 wt% to about 15 wt% of oleic acid or a salt thereof.

[0133] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more Ci-4alcohol; wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 0.5 wt% to about 10 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 15 wt % of a C6-C24fatty acid amphoacetate; and(v) about 1 wt% to about 15 wt% of oleic acid or a salt thereof.

[0134] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more Ci-4alcohol;(iii) about 1 wt% to about 8 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 10 wt % of a Cs-C24 fatty acid amphoacetate; and(v) about 1 wt% to about 10 wt% of oleic acid or a salt thereof.

[0135] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol; wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 1 wt% to about 8 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 10 wt % of a C6-C24fatty acid amphoacetate; and(v) about 1 wt% to about 10 wt% of oleic acid or a salt thereof.

[0136] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1-4 alcohol;(iii) about 1.2 wt% to about 6 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 5 wt % of a C6-C24fatty acid amphoacetate; and(v) about 1.5 wt% to about 8 wt% of oleic acid or a salt thereof.

[0137] In various embodiments the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol; wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 1.2 wt% to about 6 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 5 wt % of a C6-C24fatty acid amphoacetate; and(v) about 1.5 wt% to about 8 wt% of oleic acid or a salt thereof.

[0138] In any of the foregoing embodiments, glycerol may be present in the composition in an amount of at least about 50 wt% to no more than about 90 wt%.

[0139] In any of the foregoing embodiments, the one or more C1.4 alcohol may comprise ethanol.

[0140] In any of the foregoing embodiments, the weight ratio of (i) to (ii) in the composition may be from about 13:4 to about 4:1.

[0141] In some embodiments, it has further been found that the stability of the composition defined herein to separation can be enhanced by way of a lower ratio of amphoteric surfactant to anionic surfactant while maintaining sufficient efficacy. Thus, in various embodiments, the molar ratio of the anionic surfactant to the amphoteric surfactant is less than about 2.5:1, less than about 2:1, or less than about 1.5:1. The skilled person will understand that the molar ratio is to be calculated on an actives basis. In various embodiments, the molar ratio of the anionic surfactant to amphoteric surfactant is at least about 1:2. Thus, in various embodiments, the molar ratio of the anionic surfactant is from about 2.5:1 to about 1:2, or from about 2:1 to about 1:1.

[0142] A person skilled in the art will understand that the foregoing molar ratios are combinable with the definitions of the anionic surfactant and amphoteric surfactant set out above. Thus, in various embodiments, the anionic surfactant comprises a fatty acid amphoacetate, the amphoteric surfactant comprises a fatty acid and / or salt thereof, and the molar ratio of the anionic surfactant to the amphoteric surfactant is less than about 2.5:1, less than about 2:1, or less than about 1.5:1. In further embodiments, the anionic surfactant comprises a fatty acid amphoacetate, the amphoteric surfactant comprises a fatty acid and / or salt thereof, and the molar ratio of the anionic surfactant to the amphoteric surfactant is from about 2.5:1 to about 1:2, or from about 2:1 to about 1:1. In further embodiments, the chelating agent comprises a salt of ethylenediaminetetraacetic acid, the amphoteric surfactant comprises a fatty acid amphoacetate, the anionic surfactant comprises a fatty acid or salt thereof, and the molar ratio of the anionic surfactant to the amphoteric surfactant is less than about 2.5:1, less than about 2:1, or less than about 1.5:1. In further embodiments, the chelating agent comprises a salt of ethylenediaminetetraacetic acid, the amphoteric surfactant comprises a fatty acid amphoacetate, the anionic surfactant comprises a fatty acid or salt thereof, and the molar ratio of the anionic surfactant to the amphoteric surfactant is from about 2.5:1 to about 1:2, or from about 2:1 to about 1:1.

[0143] In particularly preferred embodiments, the chelating agent comprises a salt of ethylenediaminetetraacetic acid, the amphoteric surfactant comprises a cocoamphoacetate, the anionic surfactant comprises oleic acid and / or a salt thereof, and the molar ratio of the anionic surfactant to the amphoteric surfactant is less than about 2.5:1, less than about 2:1, or less than about 1.5:1. In further embodiments, the molar ratio of the anionic surfactant to the amphoteric surfactant is from about 2.5:1 to about 1:2, or from about 2:1 to about 1:1.THICKENING AGENT

[0144] In some embodiments the non-antimicrobial composition comprises a thickening agent. Thickening agents, which may also be referred to as thickeners, are commonly used to modify the rheological properties of liquids. For instance, thickening agents may be used to increase the viscosity of a liquid, preferably without substantially altering the other properties of said liquid. Some thickening agents may form gels when dispersed in a liquid, or may act as a thixotropic additive. For example, certain liquids containing thickening agents may exhibit shear-thinning properties, i.e. wherein the viscosity is non-Newtonian and becomes lower as the shear force or time increases. Nonlimiting examples of thickening agents include fumed silica, polysaccharides and derivatives thereof including cellulose derivatives such as hydroxyethylcellulose and carboxymethylcellulose, polyethylene glycols, vegetable gums, and poly(meth)acrylic acids and / or salts thereof.

[0145] In some embodiments the non-antimicrobial composition comprises a thickening agent which is a polyethylene glycol. Polyethylene glycol or PEG is a polyether compound derived from petroleum with many applications from industrial manufacturing to medicine. It is typically prepared by polymerization of ethylene oxide and commercially available over a wide range of molecular weights from 300 g / mol to 10,000,000 g / mol. The numbers that are included in the names of PEGs indicate their average molecular weights. For example, a PEG 600 would have a weight average molecular weight of approximately 600 Daltons.

[0146] In the present disclosure, the polyethylene glycol included in the non-antimicrobial composition may have a weight average molecular weight of greater than 1000 to less than about 8000, preferably about 1500 to about 6000, i.e. the composition may comprise a PEG 1500 to a PEG 6000. PEGs of suitable molecular weights are commercially available, from, for example, Dow Chemical.

[0147] The concentration of polyethylene glycol included in the composition is dependent on the average molecular weight of the PEG. This clearly shown in Figure 7. When the thickening agent is PEG1500, the polyethylene glycol is present in an amount of about 10 wt% to about 20 wt%. When the thickening agent is higher than PEG 1500 (e.g. PEG3350 or PEG6000), the polyethylene glycol is present in an amount of about 0.5 wt% to about 10 wt%, preferably from about 1 wt% to about 8 wt%.ADDITIONAL FEATURES

[0148] The pH of the composition of the present disclosure is not limited. However, in preferred embodiments, the pH of the composition is from about 5 to about 9. In various embodiments, the pHof the composition is from about 5 to about 8. In various embodiments, the pH of the composition is from about 6 to about 8. Compositions within said range of pH values may cause less discomfort upon application, for example from stinging sensations. In some embodiments, it has been surprisingly found that a mildly alkaline pH, for example about pH 8 may enhance the efficacy of the wound cleansing composition.

[0149] In various embodiments, the composition may further comprise a non-ionic surfactant. The non-ionic surfactant is not necessarily limited. Exemplary non-ionic surfactants include esters of fatty acids, fatty acid amides, fatty acid ethoxylates, fatty acid amide ethoxylates, polyethoxylated compounds and polyalkyl ethers, polyhydroxyl compounds, hydrocarbyl glucosides and amine oxides. For example, polyoxyethylene fatty acid esters (polyoxyethylene sorbitan fatty acid ester), polyoxyethylene glycol fatty acid esters (polyoxyethylene glycol fatty acid ester), sucrose fatty acid esters (sucrose fatty acid ester), polyoxyethylene hydrogen carbonate castor oils and polyoxyethylene alkyl ethers (polyoxyethylene hydrogenated castor oil) ether (polyoxyethylene alkyl ether).

[0150] The nonionic surfactant may comprise polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, PEG-40 stearate, PEG-100 stearate, sucrose stearate, sucrose myristate, isopropyl myristate, sucrose oleate, sucrose palmitate, sucrose laurate, laureth-21 (laureth field 21), ceteth-15 (ceteth field 15), steareth-20 (steareth field 20), oleth-15 (oleth field 15), beheneth-20 and ceteareth- 20 (beheneth field 20).

[0151] In one embodiment, the non-ionic surfactant may be a polysorbate, typically polysorbate 20. Polysorbate 20 is also known by the trade name Tween® 20.

[0152] In various embodiments, the non-ionic surfactant is present in the composition in an amount of from about 0.01 wt% to about 1 wt%, or from about 0.1 wt% to about 0.5 wt% of the total weight of the composition. For example, the non-ionic surfactant may be a polysorbate, such as polysorbate 20, that is present in the composition in an amount of from about 0.01 wt% to about 1 w%, or from about 0.1 wt% to about 0.5 wt% of the total weight of the composition.

[0153] In some embodiments the composition does not include a non-ionic surfactant.

[0154] In various embodiments, the compositions of the present invention do not contain further components other than those already described above. In such embodiments, the compositions are preferably supplied as a sterile solution, e.g. wherein such solutions are prepared from sterilised components in a sterile environment, or wherein the final solution is sterilised by methods commonly known in the art.PROCESSES

[0155] As well as the components of the non-antimicrobial composition defined herein, the present disclosure provides a process for preparing the composition. Whilst the process is not limiting, any suitable process may be used to prepare the composition, in some embodiments the process comprises the steps of (a) mixing the carrier with the solvent, and (b) adding the one or more excipients to the mixture of (a), preferably wherein the one or more excipients comprise a chelating agent, an anionic surfactant and an amphoteric surfactant, and wherein the anionic surfactant is added to the mixture of step (a) before the chelating agent and the amphoteric surfactant. The carrier, solvent, chelating agent, anionic surfactant, and amphoteric surfactant are defined hereinabove.

[0156] In some embodiments, the process for preparing the non-antimicrobial composition comprises the steps of (a) combining the amphoteric surfactant and the anionic surfactant, (b) adding the chelating agent to the mixture of step (a), and (c) adding the solvent and carrier to the mixture of step (b), or (a) combining the solvent and the chelating agent, (b) adding the anionic surfactant to the mixture of step (a), (c) adding the amphoteric surfactant to the mixture of step (b), and adding the carrier to the mixture of step (c). The carrier, solvent, chelating agent, anionic surfactant, and amphoteric surfactant are defined hereinabove.

[0157] When the composition includes a thickening agent which is a polyethylene glycol, the composition may be prepared by a process comprising the steps of:(a) mixing the polyethylene glycol into the one or more C1-C4 alcohol;(b) heating the mixture of step (a) to a minimum of about 30°C until the polyethylene glycol is fully dissolved in the one or more C1-C4 alcohol;(c) adding the solution of step (b) to the carrier; and(d) adding the one or more excipients to the solution of step (c).

[0158] The polyethylene glycol and its concentration is defined hereinabove. Similarly the one or more excipients are defined hereinabove.METHODS AND USES

[0159] As described herein, the compositions of the present disclosure are useful for the treatment of wounds, including initial treatment in first response settings, as well as in ongoing wound management such as in primary care settings. A wound is often described as chronic or acute.

[0160] Acute wounds occur as a result of surgery or trauma, typically when not too severe and where the subject is otherwise in good health. Wounds progress through well-defined stages of healing. Chronic wounds begin as acute wounds. For example, an acute wound can become a chronic wound when it does not follow the normal healing pathway resulting in a lengthened recovery. It is believed that the transition from acute to chronic can be due to an inadequate immune response, for example the patient being immuno-compromised, the wound being insufficiently perfused or being highly contaminated. Chronic wounds may include venous ulcers, diabetic ulcers, arterial ulcers, and pressure injuries due to immobility. Wounds may also include a deep tissue injury; this is an expression used to describe a unique form of pressure ulcers.

[0161] In various embodiments, the composition described herein is comprised in a wound dressing or debridement tool. In such embodiments, the wound dressing or debridement tool comprises an absorbent layer and the composition is at least partially impregnated or coated with the composition. As used herein, "debridement" refers to deeply removing adherent, dead or contaminated tissue from a wound.

[0162] Thus, in various embodiments the present disclosure provides a wound dressing, wherein the dressing comprises an absorbent layer at least partially impregnated or coated with the nonantimicrobial composition as defined herein. In other embodiments the present disclosure provides a debridement tool wherein the debridement tool comprises an absorbent layer at least partially impregnated or coated with the non-antimicrobial composition as defined herein.

[0163] Wound dressings and debridement tools are devices suitable for placement in direct contact with a wound. A debridement tool may typically be used for mechanical debridement. The debridement tool may form instance be a sponge or pad. A common material used to prepare a sponge or pad is a foam, typically a polyurethane foam, polypropylene foam, polyester foam or polyvinyl alcohol (PVA) foam. A polyester foam may be useful for a wipe.

[0164] A wound dressing may typically debride by autolysis. Autolytic debridement refers to the lysis or breakdown of necrotic debris and devitalised tissues from a wound through the body's own mechanisms, such as moist environments and endogenous enzymes. In various embodiments, the wound dressing comprises at least one layer comprising a foam, fabric, or technical textile. For example, the textile may be a non-woven or woven fibrous layer, a gel-forming fibre, or gauze. Gauze may be made from a cellulose such as cotton or viscose. In preferred embodiments the absorbent layer comprises one or more gel-forming fibres.

[0165] The wound dressing disclosed herein may have a thickness between 0.5 to 20, or 2 to 10, or 3 to 7 mm.

[0166] In one embodiment, the wound dressing may be buffered to have a pH of from about 4 to about 10, or from about 5 to about 8, or from about 5.5 to about 6.5. In various embodiments, said buffering may be achieved by the composition of the present disclosure without requiring any additional buffering agents.

[0167] The wound dressing may be comprised of one or more layers selected from the group comprising an outer cover layer, an absorbent layer, a gel-forming fibre, an adhesive layer, a wound contact layer, a distribution layer, and combinations thereof. In some embodiments, a wound dressing includes one or more absorbent layer(s). The outer cover layer of the dressing is a bacterial and viral barrier layer which typically resists the ingress of liquid but allows moisture vapour transmission. In one embodiment, the absorbent layer may be a superabsorbent.

[0168] In some embodiments, the wound dressing comprises an outer cover layer and one or more absorbent layer(s) comprising one or more gel-forming fibres. In preferred embodiments, the gelforming fibre is in direct contact with the wound, and thus no additional wound contact layer is required.

[0169] By gel forming fibres is meant hygroscopic fibres which upon the uptake of wound exudate become moist slippery or gelatinous. The gel forming fibres can be of the type that retain their structural integrity on absorption of exudate or can be of the type that lose their fibrous form and become an amorphous or structureless gel. The gel forming fibres are typically sodium carboxymethylcellulose fibres, chemically modified cellulosic fibres, alkyl sulphonate modified cellulosic fibres such as those described in WO2012 / 061225, pectin fibres, alginate fibres, chitosan fibres, hyaluronic acid fibres, or other polysaccharide fibres or fibres derived from gums, as well as non-cellulose synthetic fibres such as poly(vinyl alcohol) and polyacrylate.

[0170] The gel forming fibres are typically chemically modified cellulosic fibres in the form of a fabric and in particular carboxymethylated cellulose fibres as described in PCT WO00 / 01425. Sodium carboxymethylcellulose fibres typically have a degree of substitution of at least 0.05 carboxymethyl groups per glucose unit. The gel forming fibres typically have an absorbency of at least 2 grams (or at least 8 grams, or at least 10 grams), 0.9% solution A (8.298 g / L sodium chloride and 0.368 g / L calcium chloride dehydrate) per gram of fibre (as measured by BS EN 13726-1 (2002) "Test methods for primary wound dressings", section 3.2 "Free swell absorptive capacity"). The carboxymethylated cellulosic fabrics typically have a degree of substitution between 0.12 to 0.35 (as defined inWO00 / 01425), more typically a degree of substitution of between 0.20 and 0.30, such that the absorbency of a fabric produced from is increased when compared to the unmodified cellulose. Particular useful fabrics have an absorbency of from about 10 g / g to about 30 g / g of isotonic aqueous solution as measured by the method described in BS EN 13726-1 (2002).

[0171] The cellulosic fabric typically consists solely of cellulosic fibre but may contain a proportion of a textile fibre or gel forming fibre. This textile fibre may be for example a cellulose fibre of a known kind and may comprise continuous filament yarn and / or staple fibre.

[0172] In further preferred embodiments, the gel-forming fibres are carboxymethylcellulose fibres such as sodium carboxymethylcellulose fibres. In a specific embodiment, the absorbent layer consists of the gel-forming fibres, and the dressing does not contain additional dressing layers.

[0173] In various embodiments, the wound dressing or debridement tool consists of an absorbent layer, where the absorbent layer consists of a nonwoven fabric and the nonwoven fabric consists of gelling (gel-forming) fibres and non-gelling (non-gel-forming) fibres; preferably wherein the gelling fibres are present in an amount of from about 60 to about 95 wt% of the absorbent layer and the nongelling fibres are present in an amount of from about 5 to about 40 wt% of the absorbent layer.

[0174] In some embodiments, a wound dressing or debridement tool is provided comprising an absorbent layer, wherein the absorbent layer comprises a nonwoven fabric, the nonwoven fabric comprising gelling fibres and non-gelling fibres, wherein the gelling fibres are present in an amount of from about 60 to about 95 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 5 to about 40 wt% of the absorbent layer.

[0175] In various embodiments, the gelling fibres are present in an amount of from about 65 to about 95 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 5 to about 35 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 70 to about 95 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 5 to about 30 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 75 to about 95 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 5 to about 25 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 80 to about 95 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 5 to about 20 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 85 to about 95 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 5 to about 15 wt% of the absorbent layer. In various embodiments, thegelling fibres are present in an amount of from about 90 to about 95 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 5 to about 10 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 65 to about 90 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 10 to about 35 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 70 to about 90 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 10 to about 30 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 75 to about 90 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 10 to about 25 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 80 to about 90 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 10 to about 20 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 85 to about 90 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 10 to about 15 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 65 to about 85 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 15 to about 35 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 70 to about 85 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 15 to about 30 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 75 to about 85 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 15 to about 25 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 80 to about 85 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 15 to about 20 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 90 to about 85 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 15 to about 10 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 65 to about 80 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 20 to about 35 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 70 to about 80 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 20 to about 30 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 75 to about 80 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 20 to about 25 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 85 to about 80 wt% of the absorbent layer and the non-gelling fibres are presentin an amount of from about 20 to about 15 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 90 to about 80 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 20 to about 10 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 65 to about 75 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 25 to about 35 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 70 to about 75 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 25 to about 30 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 80 to about 75 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 25 to about 20 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 85 to about 75 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 25 to about 15 wt% of the absorbent layer. In various embodiments, the gelling fibres are present in an amount of from about 90 to about 75 wt% of the absorbent layer and the non-gelling fibres are present in an amount of from about 25 to about 10 wt% of the absorbent layer.

[0176] The gelling fibres may be any of the gelling fibres already described herein above. In various embodiments, the gelling fibres are selected from: carboxymethylcellulose fibres and derivatives thereof, modified cellulosic fibres, alkyl sulphonate modified cellulosic fibres, pectin fibres, alginate fibres, chitosan fibres, hyaluronic acid fibres, fibres derived from gums, non-cellulose synthetic fibres, superabsorbent fibres, such as polyacrylate fibres, and combinations thereof.

[0177] In a preferred embodiment, the gelling fibres are carboxymethylcellulose fibres or derivatives thereof (e.g. HYDROGEL™).

[0178] In various embodiments, the non-gelling fibres are selected from: cellulosic fibres, modified cellulosic fibres, polyester fibres, polypropylene fibres, polyamide fibres, or combinations thereof.

[0179] In a preferred embodiment, the non-gelling fibres are cellulosic fibres, modified cellulosic fibres, or a combination thereof. Highly preferred non-gelling fibres are lyocell fibres (e.g. LYOCELL™).

[0180] In various embodiments, the gelling fibres and non-gelling fibres are present in the nonwoven fabric at a weight ratio of from about 85:15 to about 65:35. In a various embodiments, the gelling fibres and non-gelling fibres are present in the nonwoven fabric at a weight ratio of about 80:20 to about 70:30. In a preferred embodiment the gelling fibres and non-gelling fibres are present in the nonwoven fabric at a weight ratio of about 75:25.

[0181] In various aspects of the present disclosure, the composition, wound dressing or debridement tool as defined herein is used for the treatment of a chronic wound, acute wound, or burn. Such use typically comprises contacting the composition, wound dressing or debridement tool with the wound or contacting the wound with the composition, wound dressing or debridement. In various embodiments, the chronic wound, acute wound or burn comprises a biofilm.

[0182] Accordingly, the present disclosure also contemplates a method of treating a wound, wherein said method comprises contacting the wound with a composition, wound dressing or debridement tool as defined herein, or contacting the composition, wound dressing or debridement tool as defined herein with the wound. In various embodiments, the wound is a chronic wound, acute wound, or burn. The chronic wound, acute wound or burn may comprise a biofilm.

[0183] In various aspects of the present disclosure, the wound dressing or debridement tool as defined herein is used to prevent or minimise slough accumulation in a wound or to de-slough a wound. The term "slough" is defined herein above. Such uses typically comprise contacting said wound dressing or debridement tool with said wound or contacting said wound with said wound dressing or debridement tool. In various embodiments, the wound is a chronic wound, acute wound, or burn. The chronic wound, acute wound or burn may comprise a biofilm.

[0184] Similarly, methods for preventing or minimising slough accumulation in a wound, or for desloughing a wound are also contemplated; wherein said methods comprise contacting the wound with a composition, wound dressing or debridement tool as defined herein. In various embodiments, the wound is a chronic wound, acute wound, or burn. The chronic wound, acute wound or burn may comprise a biofilm.

[0185] The present disclosure also contemplates use of the composition, wound dressing or debridement tool described herein to remove slough, necrosis or other foreign matter from a wound.

[0186] It has surprisingly been found that compositions according to the present disclosure are effective at disrupting biofilms even in the absence of an antimicrobial agent. As used herein, "biofilm" means a syntrophic consortium of microorganisms in which cells stick to each other and optionally also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs).

[0187] Thus, in various embodiments, the wound comprises one or more biofilms, wherein "biofilm" is as defined herein. In various embodiments of the composition for use as described herein, the wound comprises one or more biofilms and treating the wound comprises disrupting said one or morebiofilms. As used here, "disrupting" in the context of the one or more biofilms means loosening, softening, and detaching the biofilm from the wound bed.

[0188] As discussed herein, it is preferable to avoid use of an antimicrobial agent, for example to avoid the risk of resistance to said antimicrobial agent, and / or due to intolerance to the antimicrobial agent in the subject whose wound is to be treated. Compositions for treating wounds that do not contain antimicrobial agents may also be preferable in certain applications because they may not be classed as medicaments.

[0189] The generally accepted criterion for an antimicrobial cleanser solution is a 3-loglO reduction in microbial cell number in a given contact time period. Thus, in various embodiments, the nonantimicrobial compositions described herein cause less than about a 3-loglO reduction in the number of microbial cells in the wound when contacted with the wound for about 10 minutes. Preferably, the non-antimicrobial compositions described herein cause less than about a 2-logl0 reduction in the number of microbial cells in the wound when contacted with the wound for about 10 minutes. More preferably, the non-antimicrobial compositions described herein cause less than about a 1-loglO reduction in the number of microbial cells in the wound when contacted with the wound for about 10 minutes.

[0190] In various embodiments, the composition described herein is comprised in a wound dressing or debridement tool, wherein said wound dressing or debridement tool comprises an absorbent layer at least partially impregnated or coated with said composition. Various methods by which the composition is at least partially impregnated or coated in or on the absorbent layer are known in the art and the present disclosure is not limited in this respect.

[0191] Inclusion of the disclosed technology in a wound dressing or similar wound treatment device (for instance a debridement tool) can be achieved by addition to the material from which the dressing or device is constructed or by addition to the finished dressing / device. In preferred embodiments, the composition may be added as an ink by a printing process, for example a screen-printing process, where the addition can be closely controlled by use of the screen. The print could be a continuous, for example as achieved by flood-coating, or, more preferably as a discontinuous coating (regular or random patterned) as it has less impact on porosity / breathability, flexibility and ability to contour to the complex topography of the wound bed and both the macroscopic (physiology) and microscopic (cellular) levels.

[0192] The composition may be added as a separate layer, for example as a gel coating directly onto the dressing / debridement tool, for example by way of a knife- over-roll or gravure coating technique.In further embodiments, the composition may be cast as a film by a similar coating technique and then adhered to the wound device by tackifying the device or the film by, for example humidification, or by the addition of an adhesive.

[0193] It is generally known that printing on fabrics or other sheet-based materials may be carried out in a substantially direct or indirect manner, by discharge or by resist independently of the type of process used. The direct printing method consists of applying a formulation directly onto the material and subsequently fixing said formulation onto the fibres of the material. Particularly, direct printing may be carried out by using conventional roller printing or flat screen-printing procedures.

[0194] Generally, with reference to roller printing methods (e.g. flexographic, serigraphic and intaglio techniques), the method utilises equipment generally consists of a plurality of cylinders and / or rollers on which a number of engraved rollers may apply a particular formulation to an interceding material, such as a fabric material or other sheet-based materials.

[0195] In the case of the roller printing methods, such as a Gravure printing process or a Rotary Pad printing process, there are typically at least two rollers, one used for transporting a formulation (i.e. a printing roller) and the other acts as an impression member. Passing between the rollers is the substrate material to be printed on. The formulation is typically provided to the printing roller by passing through an underlying tray, where the printing roller takes up the formulation from the underlying tray, while a doctor blade eliminates any excess ink. This printing typology allows the application of substances on a material in a rapid and economical manner.

[0196] Such are often used for applying substances onto fabrics, such as woven or nonwoven fabrics, and sheet-based materials, such as foams or plastic sheet materials. As discussed above, the compositions of the present disclosure are particularly suited for the above discussed processes, and in particular processes for producing discontinuous coatings such as regular or random patterns such as dot arrays. For example, the compositions of the present disclosure are particularly suitable for screen-printing as discussed above.

[0197] Further, the compositions of the present disclosure are also specifically adapted for novel printing processes, such as the process referred to herein as "hybrid printing".

[0198] Said process can be defined as a process for applying one or more substance(s), for example a composition as described herein, to one or more substrate layers (e.g. an absorbent layer as described herein) of a wound dressing or debridement tool (e.g. as described herein. Such a process typically comprises:(a) providing at least one transfer means comprising an impression member and a transfer member, wherein the transfer member comprises one or more cells with outward facing apertures, and wherein the transfer member is provided on the exterior of the impression member;(b) introducing the one or more substance(s) into the one or more cells of the transfer member; and(c) contacting the substrate layer with the transfer member as the substrate layer is conveyed along a transport path in a machine direction, wherein force applied by the impression member to at least the one or more cells comprised within the transfer member causes the one or more substance(s) comprised within the one or more cells to transfer to the substrate layer.

[0199] The process described above may also be referred to as a "soft gravure printing" process or method.

[0200] Having generally described this disclosure, a further understanding can be obtained by reference to certain specific examples illustrated below which are provided for purposes of illustration only and are not intended to be all inclusive or limiting unless otherwise specified.EXAMPLESEXPERIMENTAL 1Materials and Methods

[0201] Tetrasodium EDTA tetrahydrate, tetrasodium EDTA dihydrate, disodium EDTA, glycerol, propylene glycol, glyceryl trioleate, triglycerol, polyethylene glycol (PEG) 200, PEG 400, PEG 600, PEG 1500, poly(ethyleneglycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), sorbitan laurate (Span® 20), Polyoxyethylene (20) sorbitan monolaurate (Tween® 20), polyoxyethylene (20) sorbitan monopalmitate (Tween® 40), polyoxyethylene (20) sorbitan monostearate (Tween® 60), polyoxyethylene (20) sorbitan monooleate (Tween® 80), and mineral oil, were obtained from a commercial source. Sodium cocoamphoactetate (Dehyton MC) was supplied as a sample from BASF. Sorbitan monooleate (Span®80), cetyl alcohol and oleic acid (Priolene 6907 and Super Refined™ Oleic Acid NF) were received as samples from CRODA Europe Ltd.

[0202] AQUACEL® EXTRA dressings are commercially available from ConvaTec.

[0203] Initial prototype wound dressings were manufactured by solvent flooding using 90% or more industrial denatured alcohol (IDA; containing 96% ethanol) with 10% or less water and tested for efficacy. The formulations of excipients for inclusion within the absorbent layer are set out in Table 1.Table 1*Mass corrected for activity - sodium cocoamphoacetate was supplied at 39.1% active.**Mass corrected for the tetrahydrate salt.

[0204] Using the above formulation, 1500 ml / m2of dope solution was added to the absorbent layer - AQUAGEL® EXTRA (a nonwoven fabric material comprising gel-forming fibres) and dried in a vacuum oven for 30 minutes at 70°C. Owing to the cost and potential safety implications associated with this method of manufacture, primarily due to the large volume of volatile solvent required to adequate saturate the absorbent layer, further investigations were carried out using a printing process. Screen printing was explored as a route to manufacture because of the advantages discussed hereinabove.

[0205] Calculations were first undertaken in order to establish the theoretical ink deposition using a pre-designed 120T screen (120 thread count) with an open area of 961 mm2[per 10,000 mm2] in the form of 4.9 mm2regularly interspaced circles. The equation below can be used to calculate the theoretical volume of ink (ml / m2), printed through open areas of screen onto a fabric, based on screen and fabric parameters only:

[0206] Where Vth = theoretical ink deposit, W = mesh aperture, d = wire diameter, D = cloth thickness.

[0207] Figure 8 is a drawing of the open area used to print a 10x10 cm AQUACEL® Extra dressing to make the initial screen printed prototypes. This has dots with a 2.5 mm diameter and covers a total of9.51% of the dressing surface area. The mesh aperture was 50 microns; the wire diameter was 50 microns; and the cloth thickness was 90 microns; resulting in a Vth = 22.5 ml / m2.

[0208] Hence, a 10x10 cm dressing with an open area of 961 mm2should have the following volume of ink added per application:Volume of ink added to a 10x10 cm dressing (ml) = 0.000961 x 22.5Volume of ink added to a 10x10 cm dressing = 0.024025 ml

[0209] To prepare the screen-printed dressings, the screen was clamped into place on a screenprinting rig (as shown in Figure 1) and a 2.6 kg weight was added on top of the squeegee to provide an appropriate pressure. The 10x10 cm AQUAGEL® Extra dressing was placed onto the loading tray, which is moved under the screen with a bottom switch. Approximately 5 ml of ink was poured onto the screen between the squeegee and open pattern. An upper switch moved the squeegee across the screen, pushing ink through the mesh.

[0210] The dressings were weighed before and after printing to determine the ink deposited and as predicted from the properties of the absorbent layer and the alteration in fluid dynamics using surfactant-based ink, the theoretical ink deposition did not match the experimentally calculated mass of ink transferred to the substrate. Briefly, the mass deposited equated to 0.15 g per 10 x 10 cm dressing (15 g nr2).

[0211] Based on this empirical measurement, the required concentration of excipients in the ink was calculated to match the final weight per unit area each as given in Table 2. These values are given in Table 3.Table 2Table 3

[0212] As shown from the change in % w / w of the ink formulation, the excipients are required in concentrations 100 times greater than those required for the dope solution during solvent flooding. This is owing to the greatly reduced mass added to the dressing; 15 g nr2during printing compared to 1500 ml m'2during solvent flooding.Investigation of carrier systems

[0213] Suitable carrier systems were investigated with the intention of reducing the volume of volatile solvent used during solvent flooding and replacing it with a non-volatile viscous liquid. Owing to the largely oil-based properties of viscous liquids, the investigated carrier systems included a proportion of alcohol-based solvent, namely industrial denatured alcohol (IDA) containing 96% ethanol. This was intended to assist in solubilising the three components and to decrease the overall viscosity of the ink formulation in order to facilitate printing. The immiscibility of oil / water and the detrimental effect of water on the gel-forming fibres in the absorbent layer meant that the aqueous phase was excluded in the first instance. However, the addition of surfactants to the formulation was considered as this has the potential to encourage the formation of emulsions, allowing a proportion of water, for example up to 15 wt% (including water contributed by e.g. commercial aqueous solutions of excipients such as amphoteric surfactants), to be included in order to solubilise the water-soluble excipients (namely EDTA).

[0214] Tween 20, Tween 40, Tween 60, Tween 80, Span 20, Span 80, PEG 200, PEG 400, PEG 600, glycerol, propylene glycol (PG), mineral oil (MO), glyceryl trioleate, triglycerol, polyethylene glycol)- poly(propylene glycol)-poly(ethylene glycol) block copolymer (PEG-PPG PEG), Super Refined™ Arlasolve™ (dimethyl isosorbide, proprietary formulation from CRODA; SRA), lanolin (LN), and Polyoxamer 188 (P188) were chosen as example carriers to be evaluated with respect to the different structural analogues of the excipients. The excipients were mixed at their intended % w / w without the addition of a carrier to form a paste which was subsequently diluted with the carrier of choice.

[0215] The excipient in highest concentration in the ink is sodium oleate (or oleic acid), this compound requires a dual component solvent, requiring a minimum amount of alcohol within the carrier system. Based on this information, initial testing evaluated miscibility with IDA in order to assess carrier suitability as co-solvents for sodium oleate. The results are shown in Figure 4.

[0216] Of the components that were miscible with IDA (the first row of data), only Span 20, PEG 200, triglycerol and propylene glycol (PG) were able to successfully solubilise sodium oleate (the second row of data). Tetrasodium EDTA remained insoluble in PG and PEG200 despite sonication and regardless of the order of addition, while changing the order of addition allowed Span 20 to solubilise all components. Triglycerol solubilised all components provided solutions were both heated and sonicated. Glycerol solubilised all components.

[0217] Oleic acid on the other hand, does not require IDA in the presence of the other excipients, meaning it could (in theory) be mixed directly with the carriers. However, addition of tetrasodium EDTA caused the in-situ conversion to the oleate anion, which mirrored the solubility characteristics seen with the original sodium oleate starting material. Therefore, carriers were mixed with IDA prior to oleic acid addition in order to account for the eventual presence of the anion upon addition of EDTA, and the subsequent reaction with sodium ions to form solid aggregates. Only glycerol and triglycerol were compatible with all components.

[0218] Sodium Cocoamphoacetate was added to the formulations in place of Na4EDTA, this was part of small side study to analyse the behaviour of oleic acid in combination with high pH, ionic compounds, particularly sodium salts. The change in pH caused by the presence of the amphoteric surfactant resulted in the precipitation of sodium oleate in the form of solid soap (generated in-situ from the change in pH and newly available sodium ions). Owing to the failure to dissolve the oleate (as seen when using sodium oleate as the original raw material), these formulations were not taken forward to evaluate suitability with Na4EDTA. Of the water-soluble compounds (such as Poloxamer 188), additional experiments utilised a small proportion of water to facilitate dissolution, however none demonstrated suitable properties (such as viscosity) to elicit further investigation.

[0219] In conclusion, 18 different carriers with varying degrees of polarity were tested in isolation and alongside a polar protic solvent (IDA). Glycerol and Span 20 were able to solubilise all of the ink components without the use of sonication when sodium oleate was used as the anionic surfactant. Glycerol was able to solubilise oleic acid provided aggregates were broken up using sonication (although sonication may be replaced with another suitable means such as vigorous stirring, optionally using a homogenizer and / or a paddle stirrer). Triglycerol was also able to solubilise all of thecomponents using heat and sonication. Despite the numerous experiments investigating other carrier systems, glycerol-based inks are the preferred printing medium.EXPERIMENTAL 2Glycerol:Alcohol Weight Ratio

[0220] Glycerol proved most promising from Experimental 1 and so was taken forward for proof of concept studies. Table 4 shows the initial formulations and their properties. The table details the difference in properties of the ink according to the species present, each change in formulation is highlighted in bold to show the difference from the previous row. The excipient concentrations correspond to those in the formulation of Table 3 (albeit with sodium oleate where used).

[0221] The order of addition was controlled for Formulations 7 to 13. The glycerol was mixed with the solvent (alcohol) followed by the anionic surfactant (sodium oleate / oleic acid), and the solution sonicated. The amphoteric surfactant (sodium cocoamphoacetate; SCAA) and chelating agent (EDTA) were then added followed by further sonication if required.Table 4

[0222] Based on the table above, the most favourable formulations were determined as 8 and 9. It was determined that glycerol is required to solubilise the tetrasodium EDTA, and adding too much IDA causes the EDTA to precipitate out of solution. Tetrasodium EDTA is required to encourage miscibility when using oleic acid. Without being bound by theory, this was believed to be linked to the above- mentioned in-situ reconversion of oleic acid to the oleate anion which is then soluble in glycerol / IDA. Preliminary work also demonstrated the need of both glycerol and IDA to solubilise sodium oleate.

[0223] Representative images of Formulations 10 and 11 are shown in Figure 2. It can be seen how Formulation 10 is a three-phase system: oleic acid remains at the surface, followed by glycerol as thebulk of the solution, and disodium EDTA remaining undissolved at the bottom. Formulation 11 also shows the undissolved disodium EDTA at the base of the vial while the sodium oleate exists in the glycerol above.

[0224] Formulations 8 and 9 were refined further to reduce the volume of solvent. The resulting formulation is shown in Table 5. The excipient concentrations were the same as shown in Table 3.

[0225] The formulation was prepared by either combining the amphoteric surfactant (SCAA) and the anionic surfactant (Na Oleate / Oleic Acid), adding chelating agent (EDTA), adding IDA, adding glycerol, heating and stirring, or combining IDA and chelating agent (EDTA), adding anionic surfactant (Na Oleate / Oleic Acid), adding amphoteric surfactant (SCAA), adding glycerol, and heating and stirring. Sonication was only used if needed.

[0226] Without being bound by theory, it was hypothesised that glycerol is able to solubilise the ionic oleate (which is the predominant species even when using oleic acid as a result of the in-situ conversion mediated by tetrasodium EDTA), via the formation of stable micelles. If this occurs prior to addition of EDTA, the EDTA cannot be solubilised in the glycerol as it is likely excluded from the ionic interactions in the closed molecular structure.Table 5EXPERIMENTAL 3Efficacy Testing

[0227] Formulations 8 and 9 from Experimental 2 were tested for efficacy in a simulated biofilm / non- viable material test model. This model measures the ability of the test formulations to disrupt and loosen an artificial substance designed to mimic biofilm and slough. The key components included in the simulated biofilm / non-viable material wound matrix are set out below in Table 6.Table 6

[0228] The proteins, polysaccharides, and water mimic the hydrated EPS matrix found in biofilm, and the deactivated yeast represents the cellular debris present in inflammatory wounds. Crystal violet was incorporated into the substrate to enable the quantification of efficacy.

[0229] To prepare the simulated biofilm / non-viable matrix for testing, 100 ml of liquid substrate was warmed to room temperature and spread across a cellulose acetate sheet to a wet thickness of 1.5 mm. The substrate film was soaked in 1.5% w / w calcium chloride solution for 18 hours. This enabled calcium ions to penetrate and bind to the alginate polymers in the substrate, causing gelation. This mimicked the ionic bridging between divalent cations and EPS polymers in biofilm. The substrate gel was removed from the calcium chloride and rinsed with deionised water.

[0230] To prepare the dressings for testing, the inks detailed in Table 4 were prepared at their corresponding concentrations on a %w / w basis as shown in Table 3 (oleic acid was used in place of sodium oleate at the same concentration in the case of Formulation 9). A screen was clamped into place on a screen-printing rig and a 2.6 kg weight was added on top of the squeegee to provide an appropriate pressure. A 2x2 cm AQUAGEL® Extra dressing (commercially available from ConvaTec) was then placed onto the loading tray, which is moved under the screen with a bottom switch. Approximately 5 ml of ink was poured onto the screen between the squeegee and open pattern. An upper switch moved the squeegee across the screen, pushing ink through the mesh.

[0231] Once prepared, 2 x 2 cm sections were cut from the printed dressings and hydrated with 1 ml Test Solution A, wherein Test Solution A is according to BS EN 13726-1:2002. Test Solution A is an artificial exudate. Finally, the dressings with Test Solution A were placed onto the substrate prepared above and incubated at 37°C for 18 hours.

[0232] "Biofilm" disruption was characterised by the change in colour of the dressings resulting from absorption of the stained material. This was quantified by extraction of the crystal violet stain from the dressings. Dressings were removed from the substrate, added to 2 ml of 33% acetic acid and the crystal violet stain extracted for 30 minutes on a roller mixer. The absorbance of each solution was read at 595 nm.

[0233] The efficacy of the test dressings to disrupt the simulated biofilm / non-viable material is shown in Figure 3.

[0234] Figure 3 highlights the observed efficacy of both screen-printed dressings in their ability to disrupt the simulated non-viable matter. AQCIean is a solvent-flooded dressing used as a comparative, which was prepared as set out in Experimental 1. The Glycerol Only ink was used as a control to ensure no significant change in efficacy resulting from the use of the non-volatile carrier (which unlike the volatile solvent will remain on the dressing post - manufacture). Despite the change in formulation and the addition of a carrier, the screen-printed dressings retain efficacy similar to the original solvent- printed dressings (~200% more effective than AQUAGEL® Extra), using the same % w / w excipients on the dressings. These data highlight the potential to use either sodium oleate or oleic acid without a significant change in efficacy.EXPERIMENTAL 4Optional addition of thickening agents

[0235] Further experiments were undertaken evaluating additives to the preferred formulation (Table 5 above), in order to thicken the ink, with the intention of reducing liquid transfer to packaging post-manufacture. Pectin precipitated out of solution upon addition of excipients, cetyl alcohol (a long chain alcohol, commonly used as a thickener in personal care products) was insoluble in the ink and PEG 800 required a complex addition synthesis involving heat and sonication (without direct sonication of the PEG 800 as this can result in toxic by-products), only to precipitate out of solution upon cooling, remaining as a suspension.

[0236] Further experiments were then carried out with the formulation detailed in Table 7 below.Table 7 ti r

[0237] The values are specified as the concentration of the active mass for each excipient within the ink. The purity of raw materials may vary from batch to batch; therefore, the actual mass of each component added should be calculated each time. For example, if the purity of oleic acid is 70% then the concentration of the raw material that should be added to the ink to give a concentration of 3.2345% (w / w) is 4.6206%. The remainder of the ink consists of glycerol and IDA at a pbw ratio of 77 : 23. The actual concentration of glycerol and IDA is adjusted depending on the purity of excipients.Replacing glycerol with triglycerol

[0238] As triglycerol has such a similar chemical structure to glycerol it was considered as an alternative. A mixture of 50:50 glycerol and triglycerol at 77 parts to 23 parts IDA resulted in a homogenous solution.Adding a thickener

[0239] The second option for increasing the viscosity of the printing ink is not to change the carrier system, but to add a thickener to the current formulation. Table 8 shows the thickeners which were trialled and rejected. The solubility in IDA and glycerol both separately and combined in the 23:77 pbw ratio was tested; heat was applied if the thickener had not dissolved after stirring at ambient temperature for one hour. Initially, 1% (w / w) of thickener was tested, from here the concentration was increased or decreased depending on the solubility and thickening capacity of each thickener. If the thickener was found to be soluble in the carrier system, an ink including the three excipients and the thickener was formulated. Adding the excipients to the formulation reduced the solubility of many thickeners.

[0240] All formulations trialled here were anhydrous or only contained the small amounts of water present in the raw materials. The reasons for rejection are listed in Table 8 and were either being insoluble in the ink, or not sufficiently increasing the viscosity. Solubility of polyethylene glycol in the ink formulation decreased with increasing molecular weight. Due to these solubility limitations, lower concentrations of the higher molecular weight PEGs were used.Table 8MethodsRheology

[0241] Viscosity was measured using a Discovery HR2 hybrid rheometer with a 40mm stainless steel 2° cone geometry with a 55 pm truncation and a solvent trap filled with IDA to prevent evaporation during longer tests. A flow ramp with the above protocol was used to determine the viscosity of inks over a range of shear rates. A temperature ramp with the above protocol was used to determine the viscosity of inks over a range of temperature at a constant low shear rate.Dressing efficacy

[0242] The efficacy of dressings for disrupting and retaining non-viable wound matter and biofilm was tested using the simulated non-viable matter and biofilm model described above. AQUACEL® Extra was used as a control and results displayed as percent better than AQUACEL Extra with 0% equal to AQUAGEL Extras performance and 100% being twice as effective as AQUAGEL Extra.Stability

[0243] Visual assessment was carried out to determine the stability of the inks made. If a homogenous ink with all components fully dissolved was produced, then the physical stability was observed over one month. Precipitation and phase separation were the main signs of instability looked for, other physical changes such as a change in colour was also noted.ResultsReplacing glycerol with triglycerol

[0244] The triglycerol ink has Newtonian rheological behaviour and an average viscosity 0.19 Pa. s. Figure 5 shows the rheological behaviour of this ink throughout the flow ramp protocol. The Data was fitted to a Newtonian fluid model using TRIOS software (TA Instruments, New castle, Delaware, USA).

[0245] The triglycerol ink was then printed onto n=3 AQUACEL Extra 10x10 cm dressings. An average of 0.1252 g (S.D = 0.0025) was printed onto a single side of each sample. The target mass of ink for one side of a 10x10 cm sample is 0.15 g. These samples were then tested using the simulated non- viable matter / biofilm model. The triglycerol ink resulted in a 34% improvement relative to AQUACEL Extra (Figure 6). Hence, triglycerol is a possible alternative to glycerol, either alone or in combination therewith.Adding a thickener

[0246] Polyethylene glycol was the only thickener tested which could make a homogenous ink which was also thickened sufficiently. Therefore, a range of different molecular weight PEGs were the only thickeners investigated further. The series of polyethylene glycols (PEGs) of different molecular weights trialled are shown above in Table 8.

[0247] The viscosity provided by polyethylene glycol increased with molecular weight and concentration, therefore a lower concentration of higher molecular weight PEGs was required to obtain the same viscosity. At a low concentration or molecular weight, the inks maintained a lowviscosity and Newtonian rheology; but PEGs with a molecular weight of 1500 and above increased the viscosity sufficiently and modified the rheology. These inks are opaque and white to light yellow in appearance. They behave as soft solids at zero shear, rapidly decreasing in viscosity when shear force is applied, showing pseudoplastic rheology.

[0248] Figure 7 shows the rheology of the inks formulated with different molecular weights of PEG during a flow ramp as outlined above with shear rates from 1 to 800 1 / s.

[0249] A molecular weight below 1000 did not produce a shear thinning ink, this is seen in the flat lines for these inks in Figure 7. Over a molecular weight of 1000 the inks produced were shear thinning, with the initial viscosity increasing with molecular weight. PEG 6000 showed the greatest stability, not phase separating after a month of storage.EXPERIMENTAL 5

[0250] The following ink formulations were prepared by adding oleic acid / sodium oleate, sodium cocoamphoacetate, and tetrasodium EDTA to the glycerol / IDA mixture. The raw materials were as outlined in Experimental 1. Once prepared, the inks were used to prepare screen-printed dressings according to Experimental 1.Table 9

[0251] Dressings printed with the oleic acid ink or sodium oleate ink were tested in the simulated non-viable matter / biofilm model as detailed in Experimental 3. The results are shown in Figure 3.

[0252] Figure 3 shows the efficacy of sodium oleate ink and oleic acid ink compared to an AQUACEL® Extra control (% more efficacious than AQUAGEL® Extra) where AQ Clean is solvent flooded with the concentration of excipients stated in Table 2. Sodium oleate ink is AQUAGEL® Extra printed with 0.07g of the ink described in Table 9 on one side of a 10x10 cm sample, Oleic acid ink is AQUACEL® Extra printed with 0.07g of the ink formulation stated in Table 9 on one side of a 10x10 cm sample and Glycerol only ink is AQUACEL® Extra printed with 0.07g of 77.77% glycerol 22.22% IDA ink on one side of a 10x10 cm sample.

[0253] No statistical difference was found between dressings printed with sodium oleate ink and oleic acid ink. However, dressings printed with glycerol and IDA only, without any of the excipients, did not have any improved efficacy compared to AQUACEL® Extra. This shows that the increased efficacy compared to AQUACEL® Extra and solvent flooded AQUACEL® Clean is caused by the excipients within the ink and not the carrier or solvent within the ink formulation.EXPERIMENTAL 6Screen and Ink Optimisation

[0254] Three screens with three different thread counts and three different concentrations of ink were used. The three screens were 32T, 55T and 120T, these were used to control the mass of ink printed onto a sample, the higher the thread count, the lower the theoretical mass of ink that will be added. Using the average mass of ink printed onto a dressing from each screen in previous experiments, the three concentrations of ink were calculated such that the high concentration ink with the 120T screen should add the same concentration of excipients g / g of dressing as the medium concentration ink with the 55T screen and the low concentration ink with the 32T screen. Table 10 shows the quantitative formulation of the three inks used.Table 10

[0255] Three 10x10 cm dressings were single side printed with every combination of screen and ink. Figure 9 shows the range of ink masses and excipient masses printed onto each sample. There is an identifiable trend in mass of excipients added to total ink mass added demonstrating the reproducibility of the manufacturing method with the composition (ink) of the present disclosure.NUMBERED CLAUSES1. A non-antimicrobial composition for printing onto an absorbent layer, said composition comprising (i) at least about 50 wt% of a carrier which is glycerol, triglycerol, or a combination thereof, (ii) a solvent which is one or more C1.4 alcohol, and (iii) one or more excipients, wherein the weight ratio of (i) to (ii) in the composition is from about 2:1 to about 5:1.2. The non-antimicrobial composition of Clause 1, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to 4:1, preferably from about 13:4 to about 4:1.The non-antimicrobial composition of Clause 1 or Clause 2, wherein (i) and (ii) form the vehicle for the one or more excipients, and the parts by weight ratio of (i) to (ii) in the vehicle is from about 60:40 to about 80:20, preferably from about 70:30 to about 80:20. The non-antimicrobial composition of any preceding clause, wherein (i) is glycerol or a combination of triglycerol and glycerol, preferably wherein (i) is glycerol. The non-antimicrobial composition of any preceding clause, wherein the one or more Ci.4alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof, preferably wherein the one or more Ci.4alcohol comprises ethanol. The non-antimicrobial composition of any preceding clause, wherein the one or more excipients comprise a chelating agent; an amphoteric surfactant; and an anionic surfactant. The non-antimicrobial composition of any preceding clause, further comprising a chelating agent which is selected from citrates, tartrates, tartramides, tartrimides, gluconates, lactates, glycolates, oxalates, phosphates, salts of ethylenediaminetetraacetic acid, and mixtures thereof, preferably wherein the chelating agent comprises a salt of ethylenediaminetetraacetic acid. The non-antimicrobial composition of any preceding clause, further comprising an amphoteric surfactant which is selected from hydrocarbyl-amphoacetates, alkenyl- amphoacetates, hydrocarbyl-amphodiacetates, alkenyl-amphodiacetates, hydrocarbylampho-propionates, hydrocarbylampho-diproprionates, hydrocarbylamphohydroxypropyl sultaines, and mixtures and salts thereof; preferably wherein the hydrocarbyl or alkenyl groups are C6to C24hydrocarbyl or alkenyl groups. The non-antimicrobial composition of Clause 8, wherein the amphoteric surfactant comprises a fatty acid amphoacetate or salt thereof, preferably a cocoamphoacetate or salt thereof. The non-antimicrobial composition of any preceding clause, further comprising an anionic surfactant which is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof. The non-antimicrobial composition of Clause 10, wherein the anionic surfactant comprises a fatty acid or salt thereof, preferably oleic acid or a salt thereof.The non-antimicrobial composition of any preceding clause, wherein the non-antimicrobial composition comprises an anionic surfactant at a concentration from about 1 wt.% to about 15 wt.% on an actives basis, based on the total weight of the composition, preferably from about 1 wt.% to about 10 wt.% on an actives basis, based on the total weight of the composition. The non-antimicrobial composition of any preceding clause, wherein the non-antimicrobial composition comprises an amphoteric surfactant at a concentration from about 1 wt.% to about 15 wt.% on an actives basis, based on the total weight of the composition, preferably from about 1 wt.% to about 10 wt.% on an actives basis, based on the total weight of the composition. The non-antimicrobial composition of any preceding clause, wherein the non-antimicrobial composition comprises a chelating agent at a concentration from about 0.5 wt.% to about 10 wt.% on an actives basis, based on the total weight of the composition, preferably from about 1 wt.% to about 8 wt.% on an actives basis, based on the total weight of the composition. The non-antimicrobial composition of any preceding clause wherein the non-antimicrobial composition comprises: a. an anionic surfactant and an amphoteric surfactant on an actives basis at a weight ratio of about 2:5 to about 5:2, b. the amphoteric surfactant and a chelating agent on an actives basis at a weight ratio of about 2:3 to about 2:1, and c. the anionic surfactant and the chelating agent on an actives basis at a weight ratio of about 2:3 to about 3:1. The non-antimicrobial composition of any preceding clause, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more Ci.4alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) a salt of ethylenediamine tetraacetic acid;(iv) a C3-C24fatty acid amphoacetate; and(v) oleic acid or a salt thereof. The non-antimicrobial composition of any preceding clause, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 0.5 wt% to about 10 wt% of a salt of ethylenediamine tetraacetic acid;( iv) about 1 wt% to about 15 wt% of a C6-C24 fatty acid amphoacetate; and(v) about 1 wt% to about 15 wt% of oleic acid or a salt thereof. The non-antimicrobial composition of any preceding clause, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 1 wt% to about 8 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 10 wt% of a C6-C2 fatty acid amphoacetate; and(v) about 1 wt% to about 10 wt% of oleic acid or a salt thereof. The non-antimicrobial composition of any preceding clause, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 1.2 wt% to about 6 wt% of a salt of ethylenediamine tetraacetic acid;(iv) about 1 wt% to about 5 wt% of a C6-C24 fatty acid amphoacetate; and(v) about 1.5 wt% to about 8 wt% of oleic acid or a salt thereof. The non-antimicrobial composition of any preceding clause, wherein the composition further comprises a non-ionic surfactant, preferably wherein the non-ionic surfactant is selected from polyoxyethylene fatty acid esters, polyoxyethylene glycol fatty acid esters,sucrose fatty acid esters, polyoxyethylene hydrogen carbonate castor oils, polyoxyethylene alkyl ethers, and mixtures thereof. The non-antimicrobial composition of any preceding clause, wherein the composition further comprises a thickening agent. The non-antimicrobial composition of Clause 21, wherein the thickening agent is a polyethylene glycol, preferably wherein the polyethylene glycol has a weight average molecular weight of greater than about 1000 to less than about 8000. The non-antimicrobial composition of Clause 22, wherein the polyethylene glycol has a weight average molecular weight of about 1500 to about 7000. The non-antimicrobial composition of any preceding clause, wherein the concentration of water in the non-antimicrobial composition is less than about 15wt%, preferably less than about 12 wt%. A process for preparing a non-antimicrobial composition as defined in any of Clauses 1 to 18, said process comprising the steps of (a) mixing the carrier with the solvent, and (b) adding the one or more excipients to the mixture of (a). The process of Clause 25, wherein the one or more excipients comprise a chelating agent, an anionic surfactant and an amphoteric surfactant, and wherein the anionic surfactant is added to the mixture of step (a) before the chelating agent and the amphoteric surfactant, or wherein the anionic surfactant and chelating agent are combined prior to their addition to the mixture of step (a). A process for preparing a non-antimicrobial composition as defined in any of Clauses 21 to23, said process comprising the steps of:(a) mixing the polyethylene glycol into the one or more C1-C4 alcohol;(b) heating the mixture of step (a) to a minimum of about 30°C until the polyethylene glycol is fully dissolved in the one or more C1-C4 alcohol;(c) adding the solution of step (b) to the carrier; and(d) adding the one or more excipients to the solution of step (c).A process for preparing a wound dressing or debridement tool, said process comprising printing the non-antimicrobial composition as defined in any one of clauses 1 to 24 onto a surface of an absorbent layer of the wound dressing or debridement tool. The process of clause 28, wherein the composition is screen printed onto the surface of the absorbent layer. A wound dressing or debridement tool obtained by the process of Claim 28 or 29. The wound dressing or debridement tool of Clause 30, wherein the absorbent layer is at least partially impregnated or coated with the non-antimicrobial composition, and wherein the absorbent layer comprises one or more gel-forming fibre. Use of the wound dressing or debridement tool of Clause 30 or 31 to prevent or minimise slough accumulation in a wound or to de-slough a wound, the use comprising contacting said wound dressing or debridement tool with said wound or contacting said wound with said wound dressing or debridement tool. The use of Clause 32, wherein the wound is a chronic wound, acute wound, or burn. A composition as defined in any of Clauses 1 to 24 or wound dressing or debridement tool as defined in Clause 30 or 31, for use in the treatment of a wound, preferably wherein the wound is a chronic wound, acute wound, or burn.

Claims

CLAIMS1. A non-antimicrobial composition for printing onto an absorbent layer of a wound dressing or debridement tool, said composition comprising (i) at least about 50 wt% of a carrier which is glycerol, triglycerol, or a combination thereof, (ii) a solvent which is one or more C1-4 alcohol, and (iii) one or more excipients, wherein the weight ratio of (i) to (ii) in the composition is from about 2:1 to about 5:1.

2. The non-antimicrobial composition of Claim 1, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1, preferably from about 13:4 to about 4:1.

3. The non-antimicrobial composition of Claim 1 or Claim 2, wherein (i) and (ii) form the substrate for printing the composition onto the absorbent layer, and the parts by weight ratio of (i) to (ii) in the substrate is from about 60:40 to about 80:20, preferably from about 70:30 to about 80:20.

4. The non-antimicrobial composition of any preceding claim, wherein (i) is glycerol or a combination of triglycerol and glycerol, preferably wherein (i) is glycerol.

5. The non-antimicrobial composition of any preceding claim, wherein the one or more C1-4 alcohol is selected from methanol, ethanol and propanol, or isomers and mixtures thereof, preferably wherein the one or more C1.4 alcohol comprises ethanol.

6. The non-antimicrobial composition of any preceding claim, wherein the one or more excipients comprise a chelating agent; an amphoteric surfactant; and an anionic surfactant.

7. The non-antimicrobial composition of any preceding claim, further comprising a chelating agent which is a salt of ethylenediaminetetracetic acid, preferably the tetrasodium salt of ethylenediamine tetracetic acid.

8. The non-antimicrobial composition of any preceding claim, further comprising an amphoteric surfactant which is C6to C24 fatty acid amphoacetate or salt thereof, preferably a cocoamphoacetate or salt thereof.

9. The non-antimicrobial composition of any preceding claim, further comprising an anionic surfactant which is a C6to C24 fatty acid or salt thereof, preferably oleic acid or a salt thereof.

10. The non-antimicrobial composition of any preceding claim, wherein the non-antimicrobial composition comprises an anionic surfactant at a concentration from about 1 wt.% to about 15 wt.% on an actives basis, based on the total weight of the composition, preferably from about 1 wt.% to about 10 wt.% on an actives basis, based on the total weight of the composition.

11. The non-antimicrobial composition of any preceding claim, wherein the non-antimicrobial composition comprises an amphoteric surfactant at a concentration from about 1 wt.% to about 15 wt.% on an actives basis, based on the total weight of the composition, preferably from about 1 wt.% to about 10 wt.% on an actives basis, based on the total weight of the composition.

12. The non-antimicrobial composition of any preceding claim, wherein the non-antimicrobial composition comprises a chelating agent at a concentration from about 0.5 wt.% to about 10 wt.% on an actives basis, based on the total weight of the composition, preferably from about 1 wt.% to about 8 wt.% on an actives basis, based on the total weight of the composition.

13. The non-antimicrobial composition of any preceding claim, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) a salt of ethylenediamine tetracetic acid;(iv) a C6-C24 fatty acid amphoacetate; and(v) oleic acid or a salt thereof.

14. The non-antimicrobial composition of any preceding claim, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more C1.4 alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 0.5 wt% to about 10 wt% of a salt of ethylenediamine tetracetic acid;(iv) about 1 wt% to about 15 wt% of a Ce-C24 fatty acid amphoacetate; and(v) about 1 wt% to about 15 wt% of oleic acid or a salt thereof.

15. The non-antimicrobial composition of any preceding claim, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more Ci.4alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 1 wt% to about 8 wt% of a salt of ethylenediamine tetracetic acid;( iv) about 1 wt% to about 10 wt% of a C6-C2fatty acid amphoacetate; and(v) about 1 wt% to about 10 wt% of oleic acid or a salt thereof.

16. The non-antimicrobial composition of any preceding claim, wherein the non-antimicrobial composition comprises:(i) at least about 50 wt% glycerol;(ii) one or more Ci.4alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2.5:1 to about 4:1;(iii) about 1.2 wt% to about 6 wt% of a salt of ethylenediamine tetracetic acid;(iv) about 1 wt% to about 5 wt% of a C6-C24fatty acid amphoacetate; and(v) about 1.5 wt% to about 8 wt% of oleic acid or a salt thereof.

17. The non-antimicrobial composition of any preceding claim, further comprising a polyethylene glycol, wherein the polyethylene glycol has a weight average molecular weight of greater than about 1000 to less than about 8000, preferably about 1500 to about 7000.

18. The non-antimicrobial composition of any preceding claim, wherein the concentration of water in the non-antimicrobial composition is less than about 15wt%, preferably less than about 12 wt%.

19. A process for preparing a non-antimicrobial composition as defined in any of Claims 1 to 18, said process comprising the steps of (a) mixing the carrier with the solvent, and (b) adding the one or more excipients to the mixture of (a), preferably wherein the one or more excipients comprise a chelating agent, an anionic surfactant and an amphoteric surfactant, and wherein the anionic surfactant is added to the mixture of step (a) before the chelating agent and the amphoteric surfactant.

20. A process for preparing a non-antimicrobial composition as defined in any of Claims 6 to 18, said process comprising the steps of (a) combining the amphoteric surfactant and the anionic surfactant, (b) adding the chelating agent to the mixture of step (a), and (c) adding the solvent and carrier to the mixture of step (b), or (a) combining the solvent and the chelating agent, (b) adding the anionic surfactant to the mixture of step (a), (c) adding the amphoteric surfactant to the mixture of step (b), and adding the carrier to the mixture of step (c).

21. A process for preparing a non-antimicrobial composition as defined in Claim 17, said process comprising the steps of:(a) mixing the polyethylene glycol into the one or more C1-C4 alcohol;(b) heating the mixture of step (a) to a minimum of about 30°C until the polyethylene glycol is fully dissolved in the one or more C1-C4 alcohol;(c) adding the solution of step (b) to the carrier; and(d) adding the one or more excipients to the solution of step (c).

22. A process for preparing a wound dressing or debridement tool, said process comprising printing the non-antimicrobial composition as defined in any one of claims 1 to 17 onto a surface of an absorbent layer of the wound dressing or debridement tool.

23. The process of claim 22, wherein the composition is screen printed onto the surface of the absorbent layer.

24. A wound dressing or debridement tool obtained by the process of Claim 22 or 23, preferably wherein the absorbent layer is at least partially impregnated or coated with the non- antimicrobial composition, and wherein the absorbent layer comprises one or more gelforming fibres.

25. Use of the wound dressing or debridement tool of Claim 24 to prevent or minimise slough accumulation in a wound or to de-slough a wound, the use comprising contacting said wound dressing or debridement tool with said wound or contacting said wound with said wound dressing or debridement tool, preferably wherein the wound is a chronic wound, acute wound, or burn.

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