WO2025215376A1

WO2025215376A1 - Debridement composition

Info

Publication number: WO2025215376A1
Application number: PCT/GB2025/050781
Authority: WO
Inventors: Bettakeri UDAYAKUMAR; David Parsons; Genevieve HARRIS; Hollie HATHAWAY
Original assignee: Convatec Ltd
Current assignee: Convatec Ltd
Priority date: 2024-04-12
Filing date: 2025-04-11
Publication date: 2025-10-16
Anticipated expiration: 2026-10-12

Abstract

The present disclosure relates generally to wound care, and more particularly, in one aspect, to a wound dressing or debridement tool comprising an absorbent layer at least partially impregnated or coated with a non-antimicrobial composition. In another aspect, a composition, wound dressing or other debridement formulation is provided to promote and enhance the natural cleansing mechanism of autolytic debridement.

Description

Debridement Composition

FIELD

[0001] The present disclosure relates generally to wound care, and more particularly, in one aspect, to a wound dressing or debridement tool comprising an absorbent layer at least partially impregnated or coated with a non-antimicrobial composition. In another aspect, a composition, wound dressing or other debridement formulation is provided to promote and enhance the natural cleansing mechanism of autolytic debridement.

BACKGROUND

[0002] Clean and acute wounds normally heal spontaneously with the aid of simple supportive physical measures such as a protective dressing. Autolytic (spontaneous, biochemically- mediated) debridement of non-viable tissue is part of the process of natural acute wound healing. However, the treatment of contaminated-traumatic, necrotic and chronic wounds can be more challenging and autolytic debridement may be inadequate. 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] 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 self-produced mucilage or extracellular polymeric substance (EPS)). Biofilm 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.

[0004] WO 2021/186188 A1 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.

[0005] 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 dressing or 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.

[0006] 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.

[0007] The present disclosure seeks to address these needs with the various aspects and embodiments defined herein.

SUMMARY

[0008] In a first aspect, the present disclosure provides a wound dressing or debridement tool, wherein the dressing or tool comprises an absorbent layer at least partially impregnated or coated with a non-antimicrobial composition, said composition comprising (i) a chelating agent, (ii) an amphoteric surfactant, and (iii) an anionic surfactant, wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 3: 1 , wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 1 :2 to about 2:1 , wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1 ; and wherein the concentration of chelating agent in the composition is at least about 1 wt.% on an actives basis, based on the total weight of the composition.

[0009] A second aspect of the present disclosure provides a wound dressing or debridement tool, wherein the dressing or tool comprises an absorbent layer at least partially impregnated or coated with a composition, said composition comprising: (i) a chelating agent, (ii) an amphoteric surfactant, (iii) an anionic surfactant, and (iv) a thickening agent, wherein the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof.

[0010] In a further aspect, the present disclosure provides for the use of the wound dressing or debridement tool as defined herein 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. A further aspect also provides a composition as defined herein for use in the treatment of a wound. In preferred embodiments of these aspects, the wound is a chronic wound, acute wound, or burn.

[0011] 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.

[0012] 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

FIG.1 : Bar chart showing the efficacy of sodium oleate ink prepared according to the

Examples and tested in a simulated non-viable matter model as detailed therein. The ink was compared to an AQUAGEL® Extra control (% more efficacious than AQUAGEL® Extra) where AQ Clean is solvent flooded with the concentration of excipients stated in Table 3.

Sodium oleate ink is AQUACEL® Extra printed with 0.07 g of the ink described in Table 2 on one side of a 10x10 cm sample.

FIG.2: Bar chart showing mean optical density (OD595) of solubilised crystal-violet stained biofilms recovered from wells inoculated with P. aeruginosa NCIMB 8626. Wells were treated with dressings containing test formulations according to the Examples with the indicated EDTA concentrations or AQUACEL® Extra™ dressing. Error bars represent standard deviations. ANOVA p value <0.05 and sample means in different Tukey groups are considered to be significantly different (represented by letters above the bars).

FIG.3: Bar chart showing mean CFU recovered from wells inoculated with P. aeruginosa NCIMB 8626 treated with dressings containing test formulations according to the Examples with the indicated EDTA concentrations or AQUACEL® Extra™ dressing. Error bars represent standard deviations. ANOVA p value <0.05 and sample means in different Tukey groups are considered to be significantly different (represented by letters above the bars). FIG.4: Bar chart showing dressing efficacy as measured according to the simulated wound biofilm-slough test detailed herein to assess efficacy for autolytic debridement. Error bars represent standard deviations (n = 5).

FIG. 5: Results of printing the formulations of Table 6 onto a carboxymethyl cellulose wound dressing using hybrid- and screen-printing processes as described in the Examples.

FIG. 6: Results of applying the formulations of Table 6 onto a carboxymethyl cellulose wound dressing by gravure-printing, rotary pad-printing and needle dosing as described in the Examples.

DETAILED DESCRIPTION

[0013] 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.

[0014] 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%.

[0015] 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.

[0016] 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).

[0017] 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. Thus, in various embodiments described herein, amounts may be described as an area density using the units g/m². 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/m² or 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/m² on 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. [0018] 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.

[0019] 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.

[0020] 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.

[0021] As used herein the expression "wound" may include an injury to living tissue and may be caused by a cut, blow, or other impact, abrasion, pressure, heat or chemical; typically, one in which the skin is cut or broken. A wound may often be described as chronic or acute. Acute wounds may occur as a result of surgery or trauma. Typically, when not too severe and where the victim is otherwise in good health, wounds progress through well-defined stages of healing within a predicted timeframe. Chronic wounds begin as acute wounds. 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 wound can be due to an inadequate immune response for example: the patient being immuno-compromised, the wound being insufficiently perfused or being highly contaminated.

[0022] Chronic wounds may include for example: venous ulcers (such as those that occur in the legs due to venous insufficiency), which account for the majority of chronic wounds and mostly affect the elderly; diabetic ulcers (for example, foot or ankle ulcers); arterial ulcers (due to peripheral arterial disease); and pressure injuries due to immobility.

[0023] Wounds may also include a deep tissue injury. Deep tissue injury is a term proposed by the National Pressure Ulcer Advisory Panel (NPUAP) to describe a unique form of pressure ulcers. These ulcers have been described by clinicians for many years with terms such as purple pressure ulcers, ulcers that are likely to deteriorate and bruises on bony prominences. [0024] The term "slough" is known to the skilled person and may be defined as a layer or mass of dead tissue separated from surrounding living tissue, or tissue that is adhered to a wound but capable of being removed as in a wound, sore, or inflammation.

COMPOSITIONS, WOUND DRESSING AND DEBRIDEMENT TOOL

[0025] As described herein, there is provided a non-antimicrobial composition. Also described herein is a composition comprising a chelating agent, an amphoteric surfactant, an anionic surfactant, and a thickening agent, wherein the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof. The compositions are typically at least partially impregnated or coated in or on a wound dressing or debridement tool. In particular, the compositions are suitable 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. The term “wound” is defined herein above. The term “composition” is used interchangeably herein with “compositions”; unless otherwise specified, features apply to the composition of each aspect.

[0026] The compositions of the present disclosure have been found to be suitable for application onto wounds to, inter alia, minimise and/or prevent biofilm formation; improve wound health; accelerate wound healing; promote autolysis and thereby debridement of the wound; prevent or minimise slough accumulation in a wound; and/or remove slough, necrosis or other foreign matter from a wound. In various embodiments, it has also been surprisingly found that the compositions disrupt biofilms that may be comprised in a wound even in the absence of antimicrobial agents.

[0027] The form of the composition is not limited. The composition may be, for example, a mousse, a foam, or a gel that can be generated in situ after being applied as a liquid. Without wishing to be bound by theory, such a mousse, foam, or gel may stay in place in the wound and act as a wound dressing formed in situ. Alternatively, the composition could be pre-formed and removed during or after the debriding process. In further embodiments, the composition may be a foam product; a fabric wipe that is woven to produce a looped fibre surface; a nonwoven or calendared fabric such as a pad, a wipe, or a pan scrub; a brush-like fabric or tool wherein the fibres are either cut to give a flock-like finish or monofilaments. Materials suitable for preparing foams, textiles, and brushes are well known in the art.

[0028] 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.

[0029] 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 a non-antimicrobial composition, said composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant; wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 3:1 , wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 1 :2 to about 2:1 , wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1 ; and wherein the concentration of chelating agent in the composition is at least about 1 wt.% on an actives basis, based on the total weight of the composition.

[0030] 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 a composition, said composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant; wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 3:1 , wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 1 :2 to about 2:1 , wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1 ; and wherein the concentration of chelating agent in the composition is at least about 1 wt.% on an actives basis, based on the total weight of the composition.

[0031] In other embodiments the present disclosure provides a wound dressing, wherein the dressing comprises an absorbent layer at least partially impregnated or coated with a composition, said composition comprising a chelating agent, an amphoteric surfactant, and anionic surfactant and a thickening agent, wherein the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof.

[0032] In yet further embodiments the present disclosure provides a debridement tool wherein the debridement tool comprises an absorbent layer at least partially impregnated or coated with a composition, said composition comprising a chelating agent, an amphoteric surfactant, an anionic surfactant, and a thickening agent, wherein the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof.

[0033] In various embodiments the present disclosure provides a wound dressing, wherein the dressing comprises an absorbent layer at least partially impregnated or coated with a non- antimicrobial composition, said composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant; wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 5:2, wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 2:1 , wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1 ; and wherein the concentration of chelating agent in the composition is at least about 1 wt.% on an actives basis, based on the total weight of the composition.

[0034] 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 a composition, said composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant; wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 5:2, wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 2:1 , wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1 ; and wherein the concentration of chelating agent in the composition is at least about 1 wt.% on an actives basis, based on the total weight of the composition.

[0035] In any of the above embodiments of the wound dressing or debridement tool, the composition may be any of the compositions defined herein.

[0036] 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 for 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.

[0037] 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 gelforming fibre and/or non-gel forming fibre, or gauze. Gauze may be made from a cellulose such as cotton or viscose.

[0038] The wound dressing disclosed herein may have a thickness between 0.5 to 30, or 1 to 20, or 2 to 10, or 3 to 7 mm. [0039] In various embodiments, 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.

[0040] 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, a non-gel-forming fibre an adhesive layer, a wound contact layer, a distribution layer, a debridement layer, and combinations thereof. In some embodiments, a wound dressing includes one or more absorbent layer(s). The absorbent layer may be a foam or a structure derived from a superabsorbent polymeric material. If foam is used, the foam may also act as a distribution layer. 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.

[0041] In some embodiments, the wound dressing comprises an outer cover layer and one or more absorbent layer(s) comprising a gel-forming fibre. In preferred embodiments, the gelforming fibre is in direct contact with the wound, and thus no additional wound contact layer is required.

[0042] The absorbent layer may be a natural or synthetic material and in the form of a liquid or solid foam or mousse, a fabric, a technical textile or brush. Materials known to prepare foams, fabrics, textiles and brushes are known in the art. In various embodiments, the absorbent layer comprises at least one layer composed of a foam, absorbent, superabsorbent, non-gel forming or gel-forming fibre, or a combination thereof. In various embodiments, the wound dressing absorbent layer is a fabric material, preferably a non-woven fabric material. In one embodiment, the absorbent layer may be a foam. The foam may have an open cell and/or closed cell structure. The foam may be derived from polyurethane, polyvinyl alcohol, a collagen, a chitosan. Typically, the foam may be a polyurethane foam. The absorbent may be a super-absorbent material, e.g. a super-absorbent polymer (SAP). Commonly known SAPs include cross-linked polyacrylates and polyacrylamides, cellulose- or starch-acrylonitrile graft copolymers, and cross-linked maleic anhydride copolymers. The superabsorbent may be a fibrous polymer, or a nonwoven material.

[0043] In preferred embodiments, the absorbent layer comprises at least one layer composed of gel-forming fibres, non-gel-forming fibres or a combination thereof. By gel forming fibres is meant hygroscopic fibres which upon the uptake of wound exudate become moist slippery or gelatinous. Gel-forming fibres may also be called gelling fibres. 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.

[0044] 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% saline solution 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 in WO00/01425), 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).

[0045] 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.

[0046] In further preferred embodiments, the gel-forming fibres are carboxymethylcellulose fibres such as sodium carboxymethylcellulose fibres. In a specific embodiment, the absorbent layer comprises gel-forming fibres, and the dressing does not contain additional dressing layers.

[0047] The absorbent layer may be in direct contact with the wound, or the wound dressing may comprise a wound contact layer disposed between the absorbent layer and the wound when the dressing is applied thereto. The wound contact layer is capable of absorbing exudate from the wound and transmitting it to the absorbent layer. The wound contact layer in one embodiment comprises gel-forming fibres, or a silicone gel. In preferred embodiments, the absorbent layer is in direct contact with the wound.

[0048] 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.

[0049] 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.

[0050] 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).

[0051] Thus, in various embodiments, the wound comprises one or more biofilms, wherein “biofilm” is as defined herein. In various embodiments of the wound dressing for use as described herein, the wound comprises one or more biofilms and treating the wound comprises disrupting said one or more biofilms. As used here, “disrupting” in the context of the one or more biofilms means loosening, softening, and detaching the biofilm from the wound bed. For example, the compositions may remove biofilms from the surface of a wound, e.g. by drawing the biofilm into the absorbent layer, which may slow or prevent the biofilm from re-forming in the wound.

[0052] 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 deslough 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.

[0053] Similarly, methods for preventing or minimising slough accumulation in a wound, or for de-sloughing 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. [0054] 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.

[0055] The composition of the present disclosure has been found to have advantageously improved anti-biofilm efficacy even in the absence of antimicrobial agents. Rather, and without wishing to be bound by theory, such anti-biofilm activity is believed to have been unexpectedly obtained by the combination of the chelating agent, amphoteric surfactant, and anionic surfactant when combined in the proportions defined herein. These effects are obtained while also maintaining 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 gel-forming 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.

[0056] 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 layerwith an excipient-containing solution, and removing 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.

[0057] 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.

[0058] 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 more excipients 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.

[0059] 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.

[0060] Further desirable specifications include activity, biocompatibility, stability, and safety. Stability over time is particularly preferred, because precipitation or phase separation of solutions decreases usability during manufacturing. Due consideration should also be given to any scale-up implications.

[0061] The composition of the present disclosure is particularly advantageous for use in screen printing because it meets the requirements discussed above. Additionally, the composition may be formulated without the use of organic phases, e.g. alcohols such as ethanol.

[0062] In summary, the inventors have found a surprisingly efficacious combination of excipients, in particular against biofilms, that when combined in the composition as described herein is 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, while enhancing the autolytic degradation and dissociation of detrimental material to promote wound healing in the absence of an antimicrobial agent. EXCIPIENTS

[0063] 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 may therefore be defined herein as a “non-antimicrobial” composition. This means that the composition does not include any antimicrobial agents, including agents such as hypochlorous acid, silver compounds, polyhexamethylene biguanide, chlorhexidine, and chlorhexidine salts.

[0064] 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 cross-resistance between antibiotics and antiseptics has been detected. With the prospect of a post-antibiotic 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.

[0065] As described herein, the non-antimicrobial compositions of the present disclosure include a chelating agent, an amphoteric surfactant and an anionic surfactant in the proportions defined herein to disrupt and lift the loose components of wounds from their surface. Surprisingly the compositions are particularly effective at disrupting 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

[0066] The compositions of the present disclosure 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 interact with 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. As used herein, the term “microorganism” includes bacteria, fungi, archaea and protists. 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 speciesspecific strategy, rather a more generalised anti-biofilm measure aimed at disrupting the entire wound-associated bacterial ecosystem.

[0067] 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.

[0068] The chelating agent of the compositions is not necessarily limited. Chelating agents include hydroxyl-carboxylic acids and salts, esters and amides thereof; citrates, tartrates, tartramides, tartrimides, lactates, maleates, glycolates, oxalates, gluconates, phosphates; salts of aminopolycarboxylic acids such as ethylenediaminetetraacetic acid (EDTA), 1 ,2-bis(o- aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA), ethylene glycol-bis(|3- aminoethylether)-N,N,N’,N’-tetraacetic acid (EGTA), nitriloacetic acid (NTA), fura-2, indo-1 , pentetic acid; sodium poly(aspartate), haemoglobin, chlorophyll, porphyrins; and amines such as aminoethylethanolamine, diethylenetriamine, ethylenediamine, triethylenetetramine, tetramethylethylenediamine, cyclen and deferoxamine.

[0069] 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. In some embodiments, the chelating agent may be selected from citrates, phosphates, oxalates, salts of ethylenediaminetetraacetic acid, and mixtures thereof. The skilled person will understand that such chelating agents may be added to the composition as a salt or in a non-ionic form (excluding salts of EDTA), e.g. free acid, and the present disclosure is not limited in this respect. For instance, citrates may be added to the composition in the form of citric acid or sodium citrate. Where a chelating agent is added to the composition in a non-salt form, e.g. as a free acid, counter-ions such as sodium ions may be provided by the chelating agent, the amphoteric surfactant and/or the anionic surfactant. 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.

[0070] 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 pH, for example, the pH of the composition, and/or when the wound dressing or debridement tool is applied thereto, 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.

[0071] 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.

[0072] 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.

[0073] 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.

[0074] 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.

[0075] 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. [0076] In various embodiments, the chelating agent comprises a salt of ethylenediaminetetraacetic acid such as tetrasodium EDTA.

Composition of the First Aspect

[0077] The concentration of the chelating agent in the composition, particularly the composition of the first aspect, may be at least about 1 wt% on an actives basis, based on 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 1.2, at least about 1.5, or at least about 2 wt%, of the total weight of the composition. 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.

[0078] Having the chelating agent in the composition at such concentrations have been found to provide unexpectedly improved anti-biofilm efficacy when the composition is applied in the manner described herein. In particular, the recited amounts of chelating agent are associated with reduced levels of biofilm and lower amounts of microorganisms in the biofilm (total viable counts) as detailed in the Examples of the present disclosure.

[0079] 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 3 g/m², up to about 2 g/m² or up to about 1 g/m² on 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 0.6, or at least about 0.7 g/m² on an actives basis.

[0080] In various embodiments, the chelating agent is present in the composition in an amount of from about 1 to about 10 wt%, from about 1.2 to about 10 wt%, from about 1.5 to about 8 wt%, or from about 2 to about 6 wt%, of the 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 1 to about 10 wt%, from about 1 .2 to about 10 wt%, from about 1.5 to about 8 wt%, or from about 2 to about 6 wt%, of the total weight of the composition.

[0081] 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 1 to about 10 wt%, from about 1.2 to about 10 wt%, from about 1.5 to about 8 wt%, or from about 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.

[0082] 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 3 g/m², from about 0.6 to about 3 g/m², from about 0.7 to about 2 g/m², or from about 0.7 to about 1 g/m² on 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 from about 0.1 to about 3 g/m², from about 0.6 to about 3 g/m², from about 0.7 to about 2 g/m², or from about 0.7 to about 1 g/m² on an actives basis.

[0083] 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 from about 0.1 to about 3 g/m², from about 0.6 to about 3 g/m², from about 0.7 to about 2 g/m², or from about 0.7 to about 1 g/m² on an actives basis. The salt of EDTA may in various embodiments be a sodium salt such as a tetrasodium salt.

Composition of the Second Aspect

[0084] In various embodiments, particularly embodiments of the second aspect, the chelating agent may be present in the composition in an amount of at least about 0.01 wt%, at least about 0.1 wt% or at least about 1 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 g/m², or up to about 1.5 g/m² on an actives basis. In various embodiments, the chelating salt is present in the absorbent layer in an amount of at least about 0.01 , at least about 0.1 , or at least about 0.25 g/m² on an actives basis.

[0086] In various embodiments, the chelating agent is present in the composition in an amount of from about 0.1 to about 10 wt%, from about 0.1 to about 5 wt%, or from about 1 to about 5 wt% of the 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 0.1 to about 10 wt%, from about 0.1 to about 5 wt%, or from about 1 to about 5 wt% of the total weight of the composition. [0087] In further embodiments, the chelating agent is a salt of ethylenediaminetetraacetic acid (EDTA) and is present in the composition in an amount of from about 0.1 to about 10 wt%, from about 0.1 to about 5 wt%, or from about 1 to about 5 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 salt is present in the absorbent layer at about 0.1 to about 2 g/m², or from about 0.25 to about 1.5 g/m² on 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 g/m², or from about 0.25 to about 1.5 g/m² on an actives basis.

[0089] In further embodiments, the chelating agent is a salt of ethylenediaminetetraacetic acid (EDTA) and is present in the absorbent layer at about 0.1 to about 2 g/m², or from about 0.25 to about 1.5 g/m² on an actives basis. The salt of EDTA may in various embodiments be a sodium salt such as a tetrasodium salt.

SURFACTANTS

[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] The composition of the present disclosure includes an amphoteric surfactant and an anionic surfactant. It has been found that the amphoteric surfactant and anionic surfactant advantageously operate together to promote debridement and disrupt biofilms in wounds. Without wishing to be bound by theory, it is believed that the chelating agent coordinates 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 surfactants are 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.

AMPHOTERIC SURFACTANT [0092] The composition of the present disclosure comprises an amphoteric surfactant. The amphoteric surfactant is not necessarily limited. 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 Ce to C24, Cs to C24, or C10 to C20, hydrocarbyl or alkenyl groups. Typically, the amphoteric surfactant has a counterion 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.

[0093] 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.

[0094] 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 diunsaturated. 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.

[0095] 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.

[0096] 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.

Composition of the First Aspect [0097] The amphoteric surfactant may be present in the composition in an amount of up to about 15 wt%, up to about 10 wt%, up to about 6 wt%, or up to about 8 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%, at least about 1 .8 wt%, or at least about 2 wt%, of the total weight of the composition.

[0098] 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 g/m² on an actives basis. In various embodiments, the amphoteric surfactant is present in the absorbent layer in an amount of at least about 0.1 , at least about 0.5 g/m², or at least about 0.6 g/m² on an actives basis.

[0099] In various embodiments, the amphoteric surfactant is present in the composition in an amount of from about 1 .8 wt% to about 15 wt%, about 1.8 wt% to about 8 wt% or from about

2 to about 6 wt% of the total weight of the composition.

[0100] 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 1.8 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 1.8 to about 8 wt% or from about 2 to about 6 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.

[0101] 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 0.5 to about 3 g/m², from about 0.5 to about 2 g/m², or from about 0.6 to about 1 g/m², on 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 from about 0.1 to about

3 g/m², from about 0.5 to about 3 g/m², from about 0.5 to about 2 g/m², or from about 0.6 to about 1 g/m², on an actives basis. In any of the foregoing embodiments, the fatty acid amphoacetate may be a cocoamphoacetate. In any of the foregoing embodiments, the amphoteric surfactant may be an alkali metal salt, for example a sodium salt such as sodium cocoamphoacetate. Composition of the Second Aspect

[0102] In various embodiments, the amphoteric surfactant may be present in the composition in an amount of up to 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 0.01 wt%, at least about 0.1 wt%, or at least about 1 wt% of the total weight of the composition. In various embodiments, the amphoteric surfactant is present in the composition in an amount of from about 0.1 to about 10 wt% or from about 0.1 to about 5 wt% of the total weight of the composition. In various embodiments, 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.

[0103] 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/m² on an actives basis. In various embodiments, the amphoteric surfactant is present in the absorbent layer in an amount of at least about 0.01 , at least about 0.1 , or at least about 0.25 g/m² on an actives basis.

[0104] In various embodiments, the amphoteric surfactant comprises a fatty acid amphoacetate and the amphoteric surfactant is present in the composition in an amount of from about 0.1 to about 10 wt% or from about 0.1 to about 5 wt% of the total weight of the composition. In various embodiments, the amphoteric surfactant comprises a fatty acid amphoacetate 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. In any of the foregoing embodiments, amphoteric surfactant may be an alkali metal salt, for example a sodium salt such as sodium cocoamphoacetate.

[0105] In various embodiments, 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/m² on an actives basis. In various embodiments, the amphoteric surfactant comprises a fatty acid amphoacetate and the amphoteric surfactant is 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/m² on an actives basis. In any of the foregoing embodiments, the fatty acid amphoacetate may be a cocoamphoacetate. In any of the foregoing embodiments, the amphoteric surfactant may be an alkali metal salt, for example a sodium salt such as sodium cocoamphoacetate. ANIONIC SURFACTANT

[0106] The composition of the present disclosure comprises an anionic surfactant. The anionic surfactant is not necessarily limited. The anionic surfactant may include all forms of lipophilic oligomeric hydrocarbons and/or polyethoxylates 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.

[0107] In various embodiments, the anionic surfactant is selected from the group consisting of fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof. An example of a sarcosinate is sodium lauroyl sarcosinate. An example of a sulphosuccinate is disodium lauryl sulphosuccinate. An example of a glutamate is sodium cocoyl glutamate.

[0108] 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.

[0109] 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. In some embodiments, the fatty acid or salt thereof may be a C8-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.

[0110] 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.

Composition of the First Aspect [0111] 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 surfactant may be present in an amount of at least about 1 wt%, at least about 2 wt%, or at least about 3 wt% of the total weight of the composition.

[0112] In various embodiments, the anionic surfactant is present in the composition in an amount of from about 1 wt% to about 15 wt%, from about 2 wt% to about 10 wt%, or from about 3 wt% to about 8 wt%, of the total weight of the composition.

[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 composition in an amount of from about 1 wt% to about 15 wt%, from about 2 wt% to about 10 wt%, or from about 3 wt% to about 8 wt%, of the total weight of the composition. In any of the foregoing embodiments, the salt may be a sodium salt.

[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 composition in an amount of from about 1 wt% to about 15 wt%, from about 2 wt% to about 10 wt%, or from about 3 wt% to about 8 wt%, of the total weight of the composition.

[0115] 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%, from about 2 wt% to about 10 wt%, or from about 3 wt% to about 8 wt%, of the total weight of the composition. In any of the foregoing embodiments, the oleic acid salt may be sodium oleate.

[0116] 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 0.5 to about 5 g/m², from about 0.75 to about 2.5 g/m², or from about 0.8 to about 2 g/m² on an actives basis.

[0117] 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 0.5 to about 5 g/m², from about 0.75 to about 2.5 g/m², or from about 0.8 to about 2 g/m² on an actives basis.

[0118] 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 0.5 to about 5 g/m², from about 0.75 to about 2.5 g/m², or from about 0.8 to about 2 g/m² on an actives basis.

[0119] 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 0.5 to about 5 g/m², from about 0.75 to about 2.5 g/m², or from about 0.8 to about 2 g/m² on an actives basis.

[0120] In any of the foregoing embodiments, the oleic acid salt may be sodium oleate.

[0121] 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.

Composition of the Second Aspect

[0122] 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 10 wt%, or up to about 5 wt% of the total weight of the composition. The anionic surfactant may be present in an amount of at least about 0.01 wt%, at least about 0.1 wt% or at least about 0.5 wt% of the total weight of the composition.

[0123] In various embodiments, the anionic surfactant is present in the composition in an amount of from about 0.1 wt% to about 10 wt%, preferably from about 0.5 wt% to about 5 wt% of the total weight of the composition.

[0124] As discussed herein, in certain embodiments it has been found advantageous to reduce the amount of anionic surfactant, in particular relative to the amount of amphoteric surfactant. Thus, in other embodiments the anionic surfactant is present in the composition in an amount of from about 0.1 wt% to about 2 wt% or from about 0.5 wt% to about 2 wt% of the total weight of the composition.

[0125] In various embodiments, the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof, and is present in the composition in an amount of from about 0.1 wt% to about 10 wt%, preferably from about 0.5 wt% to about 5 wt% of the total weight of the composition. In other embodiments, the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof, and is present in the composition in an amount of from about 0.1 wt% to about 5 wt%, or from about 0.5 wt% to about 2 wt% of the total weight of the composition. In any of the foregoing embodiments, the salt may be a sodium salt.

[0126] In various embodiments, the anionic surfactant comprises a fatty acid and/or salt thereof, which is present in the composition in an amount of from about 0.1 wt% to about 10 wt%, preferably from about 0.5 wt% to about 5 wt% of the total weight of the composition. In other embodiments, the anionic surfactant comprises a fatty acid and/or salt thereof, which is present in the composition in an amount of from about 0.1 wt% to about 5 wt%, or from about 0.5 wt% to about 2 wt% of the total weight of the composition. In any of the foregoing embodiments, the fatty acid salt may be a sodium salt.

[0127] 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 0.1 wt% to about 10 wt%, preferably from about 0.5 wt% to about 5 wt% of the total weight of the composition. In other embodiments, the anionic surfactant comprises oleic acid and/or a salt thereof, which is present in the composition in an amount of from about 0.1 wt% to about 5 wt%, or from about 0.5 wt% to about 2 wt% of the total weight of the composition. In any of the foregoing embodiments, the oleic acid salt may be sodium oleate.

[0128] 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 0.01 to about 3 g/m², from about 0.1 to about 2.5 g/m², or from about 0.35 to about 2 g/m² on an actives basis. In other embodiments, the anionic surfactant is present in the absorbent layer in an amount of from about 0.01 to about 1.5 g/m² or from about 0.1 to about 1 g/m² on an actives basis.

[0129] In various embodiments, the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof, and present in the absorbent layer in an amount of from about 0.01 to about 3 g/m², from about 0.1 to about 2.5 g/m², or from about 0.35 to about 2 g/m² on an actives basis. In other embodiments, the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof, and present in the absorbent layer in an amount of from about 0.01 to about 1 .5 g/m² or from about 0.1 to about 1 g/m² on an actives basis. [0130] In various embodiments, the anionic surfactant comprises a fatty acid and/or salt thereof, which is present in the absorbent layer in an amount of from about 0.01 to about 3 g/m², from about 0.1 to about 2.5 g/m², or from about 0.35 to about 2 g/m² on an actives basis. In other embodiments, the anionic surfactant comprises a fatty acid and/or salt thereof and is present in the absorbent layer in an amount of from about 0.01 to about 1.5 g/m² or from about 0.1 to about 1 g/m² on an actives basis. In any of the foregoing embodiments, the fatty acid salt may be a sodium salt.

[0131] 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 0.01 to about 3 g/m², from about 0.1 to about 2.5 g/m², or from about 0.35 to about 2 g/m² on an actives basis. In other embodiments, the anionic surfactant comprises oleic acid and/or a salt thereof, and is present in the absorbent layer in an amount of from about 0.01 to about 1.5 g/m² or from about 0.1 to about 1 g/m² on an actives basis. In any of the foregoing embodiments, the oleic acid salt may be sodium oleate.

COMBINATION OF CHELATING AGENT, AMPHOTERIC SURFACTANT AND ANIONIC SURFACTANT

[0132] It has been found that the chelating agents, the anionic surfactants, and the amphoteric surfactants described herein operate together to disrupt biofilms and debride 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.

[0133] 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(1):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 ZFIC is <0.5, indifferent when the ZFIC is >0.5 but <4.0, and antagonistic when the ZFIC is >4.0. [0134] In the context of the present disclosure, synergy may be seen in that the chelating agent, anionic surfactant and/or amphoteric surfactant do not effectively promote autolytic debridement of a wound when used without the other, but in combination are highly effective. Additionally, or alternatively, it has been found that the combination of anionic surfactant and amphoteric surfactant may allow the amount of anionic surfactant to be reduced without altering the overall efficacy of the composition.

[0135] It would be understood by the person skilled in the art that the definition of the amphoteric and/or anionic surfactant set out above is combinable with one another and/or 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.

[0136] 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.

[0137] 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.

[0138] In the composition of the first aspect of the present disclosure, the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 3:1 , the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 1 :2 to about 2:1 , and the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1. As discussed above, the composition of the present disclosure having a chelating agent, amphoteric surfactant and anionic surfactant in said proportions has been found to provide surprising efficacy against biofilms while promoting autolytic wound debridement in a composition suitable for use in wound dressings or debridement tools, and in particular in processes for preparing such objects, such as screen printing.

[0139] In various embodiments, the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 5:2, the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 2: 1 , and the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1.

[0140] In various embodiments, the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 2:1. In various embodiments, the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 3:2. In various embodiments, the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 2:1 .

[0141] In further embodiments, the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 2:1 , the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 3:2, and the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3:1.

[0142] In further embodiments, the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 2:1 , the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 2: 1 , and the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 2:1.

[0143] In further embodiments, the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 5:2, the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 3:2, and the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 2:1.

[0144] In preferred embodiments, the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 2:1 ; the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 3:2; and the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 2:1 .

[0145] In further embodiments, the molar ratio of amphoteric surfactant : anionic surfactant : chelating agent is 5:5:2 to 10:24:9.

[0146] A person skilled in the art will understand that the amounts recited herein above in respect of each of the chelating agent, amphoteric surfactant, and anionic surfactant may be combined. For example, in various embodiments, the composition comprises about 2.0 wt.% to about 10 wt.% on an actives basis of anionic surfactant; about 1.8 wt.% to about 8.0 wt.% on an actives basis of amphoteric surfactant; and about 1.5 wt% to about 8.0 wt% on an actives basis of chelating agent; the wt% being based on the total weight of the composition. In preferred embodiments, the composition comprises about 3.0 wt.% to about 8.0 wt.% on an actives basis of anionic surfactant; about 2.0 wt.% to about 6.0 wt.% on an actives basis of amphoteric surfactant; and about 2.0 wt% to about 6.0 wt% on an actives basis of chelating agent; the wt% being based on the total weight of the composition.

[0147] Similarly, in 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 absorbent layer may comprise about 0.5 g/m² to about 5.0 g/m² on an actives basis of anionic surfactant; about 0.5 g/m² to about 3.0 g/m² on an actives basis of amphoteric surfactant; and about 0.6 g/m² to about 3.0 g/m² on an actives basis of chelating agent. In preferred embodiments, the absorbent layer comprises about 0.75 g/m² to about 2.5 g/m² on an actives basis of anionic surfactant; about 0.5 g/m² to about 2.0 g/m² on an actives basis of amphoteric surfactant; and about 0.7 g/m² to about 2.0 g/m² on an actives basis of chelating agent. In more preferred embodiments, the absorbent layer comprises about 0.8 g/m² to about 2.0 g/m² on an actives basis of anionic surfactant; about 0.6 g/m² to about 1.0 g/m² on an actives basis of amphoteric surfactant; and about 0.7 g/m² to about 1 .0 g/m² on an actives basis of chelating agent.

[0148] In any of the foregoing embodiments, the chelating agent is preferably a salt of ethylenediaminetetraacetic acid, the anionic acid comprises a fatty acid and/or salt thereof, and the amphoteric surfactant comprises a fatty acid amphoacetate. The salts are typically metal salts, preferably sodium salts. In any of the foregoing embodiments, it is particularly preferred that the chelating agent is a salt of ethylenediaminetetraacetate, the anionic acid is an oleic acid salt, and the amphoteric surfactant is a cocoamphoacetate. For example, the chelating agent may be tetrasodium ethylenediaminetetraacetate, the anionic acid may be sodium oleate, and the amphoteric surfactant may be sodium cocoamphoacetate.

[0149] A person skilled in the art will understand that the thickening agent as defined herein for the second aspect may be combinable with any of the above embodiments set out above. Thus, any of the above embodiments may be combined with a thickening agent comprising at least one poly(meth)acrylic acid and/or salt thereof. In exemplary embodiments, the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof; the chelating agent is selected from citrates, tartrates, tartramides, tartrimides, gluconates, lactates, glycolates, oxalates, phosphates, salts of ethylenediaminetetraacetic acid, and mixtures thereof; the amphoteric surfactant is selected from hydrocarbyl-amphoacetates, alkenyl-amphoacetates, hydrocarbyl-amphodiacetates, alkenyl-amphodiacetates, hydrocarbylampho-propionates, hydrocarbylampho-diproprionates, hydrocarbylamphohydroxypropyl sultaines, and mixtures thereof; and the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof. In preferred embodiments the chelating agent comprises a salt of ethylenediaminetetraacetic acid. In preferred embodiments, the amphoteric surfactant comprises a fatty acid amphoacetate. In preferred embodiments, the anionic surfactant comprises a fatty acid and/or salt thereof. The salt may be an alkali metal salt such as a sodium salt. In further embodiments, the poly(meth)acrylic acid and/or salt thereof may be an interpolymer, preferably a cross-linked interpolymer. The cross-linker may be any cross-linker as defined herein, for example an allyl ether cross-linking agent such as allyl sucrose or allyl pentaerythritol.

[0150] In further embodiments, the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof; the chelating agent comprises a salt of ethylenediaminetetraacetic acid, the amphoteric surfactant comprises a fatty acid amphoacetate, and the anionic surfactant comprises a fatty acid or salt thereof. Preferably, the poly(meth)acrylic acid and/or salt thereof is an interpolymer, preferably a cross-linked interpolymer. The cross-linker may be any cross-linker as defined herein, for example an allyl ether cross-linking agent such as allyl sucrose or allyl pentaerythritol.

[0151] The skilled person would also understand that each of the amounts contemplated for the individual components of the composition of the present disclosure are combinable with each other. Thus, in various embodiments, the chelating agent is present in the composition in an amount of from about 0.1 to about 10 wt% and the anionic surfactant is present in the composition in an amount of from about 0.1 to about 10 wt% of the total weight of the composition. In various embodiments, the chelating agent is present in the composition in an amount of from about 0.1 to about 10 wt% and the amphoteric surfactant is present in the composition in an amount of from about 0.1 to about 10 wt% of the total weight of the composition. In various embodiments, the anionic surfactant is present in the composition in an amount of from about 0.1 to about 10 wt% and the amphoteric surfactant is present in the composition in an amount of from about 0.1 to about 10 wt% of the total weight of the composition. In further embodiments, each of the anionic surfactant, amphoteric surfactant and chelating agent are present in an amount of from about 0.1 to about 10 wt% of the total weight of the composition. In any of the foregoing embodiments, the at least one poly(meth)acrylic acid and/or salt thereof may be present in the composition in an amount of from about 0.1 to about 2 wt% of the total weight of the composition. Preferably, the poly(meth)acrylic acid and/or salt thereof is an interpolymer, preferably a cross-linked interpolymer. The cross-linker may be any cross-linker as defined herein, for example an allyl ether cross-linking agent such as allyl sucrose or allyl pentaerythritol. [0152] Similarly, in various embodiments the chelating agent is present in the absorbent layer in an amount of from about 0.1 to about 2 g/m² and the anionic surfactant is present in the absorbent layer in an amount of from about 0.1 to about 2.5 g/m², each on an actives basis. In various embodiments the chelating agent is present in the absorbent layer in an amount of from about 0.1 to about 2 g/m² and the amphoteric surfactant is present in the absorbent layer in an amount of from about 0.1 to about 2 g/m², each on an actives basis. In various embodiments the amphoteric surfactant is present in the absorbent layer in an amount of from about 0.1 to about 2 g/m² and the anionic surfactant is present in the absorbent layer in an amount of from about 0.1 to about 2.5 g/m², each on an actives basis. In a further embodiment, the chelating agent is present in the absorbent layer in an amount of from about 0.1 to about 2 g/m², the amphoteric surfactant is present in the absorbent layer in an amount of from about 0.1 to about 2 g/m², and the anionic surfactant is present in the absorbent layer in an amount of from about 0.1 to about 2.5 g/m², each on an actives basis. In any of the foregoing embodiments, the at least one poly(meth)acrylic acid and/or salt thereof may be present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis. Preferably, the poly(meth)acrylic acid and/or salt thereof is an interpolymer, preferably a cross-linked interpolymer. The cross-linker may be any crosslinker as defined herein, for example an allyl ether cross-linking agent such as allyl sucrose or allyl pentaerythritol.

[0153] In any of the foregoing embodiments, the poly(meth)acrylic acid and/or salt thereof is preferably a polyacrylic acid and/or a salt thereof.

[0154] As further detailed in the Examples of the present disclosure, it has further been found that the stability of the composition defined herein to separation can be further 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.

[0155] 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.

[0156] 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. In any of the foregoing embodiments, the poly(meth)acrylic acid and/or salt thereof is an interpolymer, preferably a cross-linked interpolymer. The cross-linker may be any cross-linker as defined herein, for example an allyl ether cross-linking agent such as allyl sucrose or allyl pentaerythritol.

CARRIER AND SOLVENT

[0157] In various embodiments, the composition of the first aspect may comprise one or more carriers, solvents, or combinations thereof. These may assist in the application of the composition of the present disclosure to an article such as a wound dressing or debridement tool.

[0158] 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 over time is also required; precipitation or phase separation of solutions decreases usability during manufacturing. Finally, due consideration should be given to any scale-up implications.

[0159] For example, in various embodiments, the composition includes 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.

[0160] 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 C1.4 alcohol (ii) is present in an amount of 28 wt% (2.5:1) to 17.5 wt% (4:1). The one or more C1.4 alcohol is defined further herein.

[0161] 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 C1.4 alcohol (ii) is present in an amount of 23.0 wt% (13:4) to 18.75 wt% (4:1).

[0162] 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.

[0163] 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.

[0164] 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.

[0165] In particularly preferred embodiments, (i) in the composition is glycerol.

[0166] 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 C1.4 alcohol which is important (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), 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%.

[0167] 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%.

[0168] 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%.

[0169] 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. [0170] 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.

[0171] 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.

[0172] 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.

[0173] 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.

[0174] 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. [0175] 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.

[0176] 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%, 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.

[0177] 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.

[0178] 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.

[0179] 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.

[0180] 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.

[0181] 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.

[0182] 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.

[0183] 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.

[0184] 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.

[0185] 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.

[0186] As noted herein, for some absorbent layers - particularly those including one or more gel-forming 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. Thus, in various embodiments the composition comprises less than about 15 wt%, less than about 12 wt%, or less than about 10 wt% of water relative to the total weight of the composition.

EXEMPLARY NON-ANTIMICROBIAL COMPOSITIONS

[0187] Each of the anionic surfactant, amphoteric surfactant and chelating agent may be present in an amount suitable to provide the desired 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.

[0188] In various embodiments the non-antimicrobial composition comprises:

(i) glycerol;

(ii) one or more C1.4 alcohol;

(iii) a salt of ethylenediamine tetraacetic acid;

(iv) a C6-C24 fatty acid amphoacetate; and

(v) oleic acid or a salt thereof.

[0189] 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 C6-C24 fatty acid amphoacetate; and

(v) oleic acid or a salt thereof.

[0190] 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.

[0191] 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.

[0192] In various embodiments the non-antimicrobial composition comprises:

(i) at least about 50 wt% glycerol;

(iii) a salt of ethylenediamine tetraacetic acid;

(iv) a cocoamphoacetate; and

(v) oleic acid or a salt thereof.

[0193] In any of the foregoing embodiments, the chelating agent may be present in an amount of about 1 wt% to about 10 wt%, about 1.2 wt% to about 10 wt%, about 1.5 wt% to about 8 wt%, or about 2 wt% to about 6 wt%. For example, the chelating agent may be present in an amount of about 1.5 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 2 wt% to about 6 wt%.

[0194] In any of the foregoing embodiments, the anionic surfactant may be present in an amount of about 2 wt% to about 15 wt%, about 2 wt% to about 10 wt%, or about 3 wt% to about 8 wt%. For example, the anionic surfactant may be present in an amount of about 2% 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 3 wt% to about 8 wt% and is oleic acid or a salt thereof.

[0195] In any of the foregoing embodiments, the amphoteric surfactant may be present in an amount of about 1.8 wt% to about 15 wt%, about 1.8 wt% to about 8 wt%, or about 2 wt% to about 6 wt%. For example, the amphoteric surfactant may be present in an amount of about 1.8 wt% to about 8 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 2 wt% to about 6 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.

[0196] 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 wt% to about 10 wt% of a salt of ethylenediamine tetraacetic acid;

(iv) about 1.8 wt% to about 15 wt % of a C6-C24 fatty acid amphoacetate; and

(v) about 2 wt% to about 15 wt% of oleic acid or a salt thereof.

[0197] In various embodiments the non-antimicrobial composition comprises:

(i) at least about 50 wt% glycerol;

(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.

[0198] 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 10 wt% of a salt of ethylenediamine tetraacetic acid;

(iv) about 1.8 wt% to about 8 wt % of a C6-C24 fatty acid amphoacetate; and

(v) about 2 wt% to about 10 wt% of oleic acid or a salt thereof.

[0199] In various embodiments the non-antimicrobial composition comprises:

(i) at least about 50 wt% glycerol;

(iv) about 1.8 wt% to about 8 wt % of a C6-C24 fatty acid amphoacetate; and

(v) about 2 wt% to about 10 wt% of oleic acid or a salt thereof.

[0200] 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 .5 wt% to about 8 wt% of a salt of ethylenediamine tetraacetic acid; (iv) about 2 wt% to about 6 wt % of a C6-C24 fatty acid amphoacetate; and

(v) about 3 wt% to about 8 wt% of oleic acid or a salt thereof.

[0201] 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 1.5 wt% to about 8 wt% of a salt of ethylenediamine tetraacetic acid;

(iv) about 2 wt% to about 6 wt % of a C6-C24 fatty acid amphoacetate; and

(v) about 3 wt% to about 8 wt% of oleic acid or a salt thereof.

[0202] In various embodiments the non-antimicrobial composition comprises:

(i) at least about 50 wt% glycerol;

(ii) one or more C1.4 alcohol;

(iii) about 2 wt% to about 6 wt% of a salt of ethylenediamine tetraacetic acid;

(iv) about 2 wt% to about 6 wt % of a C6-C24 fatty acid amphoacetate; and

(v) about 3 wt% to about 8 wt% of oleic acid or a salt thereof.

[0203] In various embodiments the non-antimicrobial composition comprises:

(i) at least about 50 wt% glycerol;

(iii) about 2 wt% to about 6 wt% of a salt of ethylenediamine tetraacetic acid;

(iv) about 2 wt% to about 6 wt % of a C6-C24 fatty acid amphoacetate; and

(v) about 3 wt% to about 8 wt% of oleic acid or a salt thereof.

[0204] 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%.

[0205] In any of the foregoing embodiments, the one or more C1.4 alcohol may comprise ethanol.

[0206] 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.

[0207] In any of the foregoing embodiments, the anionic surfactant and amphoteric surfactant may be present on an actives basis at a weight ratio of about 2:5 to about 5:2, the amphoteric surfactant and chelating agent may be present on an actives basis at a weight ratio of about 2:3 to about 2:1 , and/or the anionic surfactant and chelating agent may be present on an actives basis at a weight ratio of about 2:3 to about 3: 1 .

[0208] 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.

[0209] 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.

[0210] 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.

EXEMPLARY EMBODIMENTS FOR COMPOSITION OF SECOND ASPECT [0211] In various exemplary embodiments, the composition comprises:

(i) a salt of ethylenediaminetetraacetic acid;

(ii) a fatty acid cocoamphoacetate;

(iii) oleic acid and/or salt thereof;

(iv) a poly(meth)acrylic acid and/or salt thereof.

[0212] In various embodiments, the composition comprises:

(i) a salt of ethylenediaminetetraacetic acid;

(ii) a fatty acid cocoamphoacetate;

(iii) oleic acid and/or salt thereof;

(iv) a cross-linked interpolymeric poly(meth)acrylic acid and/or salt thereof.

[0213] In various embodiments, the composition comprises:

(i) about 0.1 to about 10 wt% of a salt of ethylenediaminetetraacetic acid;

(ii) about 0.1 to about 10 wt% of a fatty acid cocoamphoacetate;

(iii) about 0.1 to about 10 wt% of a oleic acid and/or salt thereof;

(iv) about 0.1 to about 2 wt% of a poly(meth)acrylic acid and/or salt thereof.

[0214] In various embodiments, the composition comprises:

(i) about 0.1 to about 10 wt% of a salt of ethylenediaminetetraacetic acid;

(ii) about 0.1 to about 10 wt% of a fatty acid cocoamphoacetate;

(iii) about 0.1 to about 10 wt% of a oleic acid and/or salt thereof;

(iv) about 0.1 to about 2 wt% of a cross-linked interpolymeric poly(meth)acrylic acid and/or salt thereof.

[0215] In various embodiments, the composition comprises:

(i) about 0.1 to about 5 wt% of a salt of ethylenediaminetetraacetic acid;

(ii) about 0.1 to about 5 wt% of a fatty acid cocoamphoacetate;

(iii) about 0.5 to about 5 wt% of a oleic acid and/or salt thereof;

(iv) about 0.1 to about 1 wt% of a poly(meth)acrylic acid and/or salt thereof.

[0216] In various embodiments, the composition comprises:

(i) about 0.1 to about 5 wt% of a salt of ethylenediaminetetraacetic acid;

(ii) about 0.1 to about 5 wt% of a fatty acid cocoamphoacetate;

(iii) about 0.5 to about 5 wt% of a oleic acid and/or salt thereof; (iv) about 0.1 to about 1 wt% of a cross-linked interpolymeric poly(meth)acrylic acid and/or salt thereof.

[0217] In any of the foregoing embodiments, the composition may further comprise glycerol in an amount of from about 1 wt% to about 90 wt%, preferably from about 10 wt% to about 70 wt%, of the total weight of the composition.

[0218] Thus, in various embodiments, the composition comprises:

(i) about 0.1 to about 5 wt% of a salt of ethylenediaminetetraacetic acid;

(ii) about 0.1 to about 5 wt% of a fatty acid cocoamphoacetate;

(iii) about 0.5 to about 5 wt% of a oleic acid and/or salt thereof;

(iv) about 0.1 to about 1 wt% of a cross-linked interpolymeric poly(meth)acrylic acid and/or salt thereof; and

(v) about 1 wt% to about 90 wt% glycerol.

[0219] In preferred embodiments, the foregoing compositions are substantially ethanol-free.

[0220] Preferably, the molar ratio of (iii) to (ii) in any of the above embodiments is less than about 2.5:1 ; more preferably from about 2:1 to about 1 :1.

THICKENING AGENT

[0221] In some embodiments, the non-antimicrobial composition of the first aspect 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. Non-limiting 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.

[0222] 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.

[0223] 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.

[0224] The concentration of polyethylene glycol included in the composition is dependent on the average molecular weight of the PEG. 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%.

[0001] The composition of the second aspect includes a thickening agent which comprises at least one poly(meth)acrylic acid and/or salt thereof. The skilled person will understand the standard nomenclature “(meth)acrylic” to encompass both “acrylic” and “methacrylic”. Poly(meth)acrylic acids are polymers of (meth)acrylic acid. Such polymers may be prepared by commonly known processes in the art, such as polymerisation with a free radical catalyst (e.g. potassium persulfate or Al BN) in an organic medium (e.g. benzene; more preferably ethyl acetate or a cosolvent mixture of ethyl acetate and cyclohexane) in a closed vessel or autoclave equipped with stirring. Poly(meth)acrylic acids and/or salts thereof are typically available commercially as powders that may be dispersed into liquids, wherein a thickening of said liquid is typically observed. In various embodiments, a gel may be formed.

[0002] It has been found unexpectedly that a thickening agent comprising at least one poly(meth)acrylic acid and/or salt thereof in a composition comprising a chelating agent, an amphoteric surfactant and an anionic surfactant as defined herein provides multiple advantages, particularly relating to the use of the composition in a wound dressing or debridement tool. In particular, the thickening agent of the present disclosure enables compositions with higher viscosities to be obtained while maintaining or improving the composition’s stability to separation (i.e. the separation of one or more of the components of the composition into distinct phases). Stability to separation is advantageous as the composition can be stored for longer before use, and the improved homogeneity of the composition leads to improved homogeneity of the composition once applied to the wound dressing or debridement tool. Increased viscosity compositions may be particularly advantageous for processes such as screen-printing, wherein the composition may be applied to wound dressings or debridement tools more effectively, for example resulting in better- defined patterns as demonstrated in the Examples of the present disclosure. Further advantages have been found to be associated with the inclusion of the thickening agent of the present disclosure. For example, stable compositions can be obtained without the use of less desirable solvents such as ethanol that may complicate the manufacturing process due to the flammable nature of the solvent and the need to remove it prior to packaging the product. The thickening agent may also aid the dispersion/dissolution of other components in the composition during its preparation, aiding and simplifying the formulation process. For example, in various embodiments the composition may be formulated in a ‘one-pot’ process, i.e. in a single mixing vessel. In turn, this may enable less water to be present in the final composition. Advantageously, the effects discussed above are achieved without substantially affecting the efficacy of the composition, e.g. to promote autolytic debridement of wounds and/or minimise/prevent biofilm formation.

[0003] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is at least one polyacrylic acid and/or salt thereof. Polyacrylic acids and/or salts thereof are commonly referred to in the art as “carbomers”. Polyacrylic acids comprise a plurality of repeat units having the formula (CH2-CHCO2H). These compounds are described in more detail in US Patent Nos. 2,798,053; 3,915,921 ; 4,267,103; 5,288,814; and 5,349,030; the contents of each being incorporated herein by reference. A non-limiting example of commercially available polyacrylic acids and/or salts thereof are the Carbopol® range of products available from The Lubrizol Corporation.

[0004] Poly(meth)acrylic acids may be homopolymers, copolymers, or interpolymers. For example, homopolymeric poly(meth)acrylic acids comprise a polymer backbone consisting of repeat units formed from (meth)acrylic acid.

[0005] Poly(meth)acrylic acid copolymers comprise repeat units formed from (meth)acrylic acid and may comprise further repeat units derived from other monomers. Non-limiting examples of such monomers include (meth)acrylate esters, (meth)acrylamides, olefins, maleic anhydrides, vinyl esters, vinyl ethers, and styrenics; as well as unsaturated carboxylic acids other than (meth)acrylic acid. For instance, a poly(meth)acrylic acid copolymer may comprise repeat units formed from (meth)acrylic acid and at least one alkyl acrylate. A non-limiting example of a commonly used alkyl acrylate in such copolymers is C10-C30 alkyl acrylate.

[0006] In various embodiments the poly(meth)acrylic acid and/or salt thereof is an interpolymer. As used herein, the term “interpolymer” refers to a complex comprising at least two polymers. In such interpolymers, one or more of the constituent polymers may be a homopolymer or a copolymer. For example, at least one of the constituent polymers of the interpolymer may be a copolymer of acrylic acid and C10-C30 alkyl acrylate. In various embodiments, and without wishing to be bound by theory, the complex between the at least two polymers arises due to non-covalent interactions. For example one polymer may be entangled within the other and/or be associated via hydrogen bonding. In various embodiments the at least one poly(meth)acrylic acid and/or salt thereof is an interpolymer that comprises a block copolymer comprising polyethylene glycol and a fatty acid ester. In specific embodiments, the fatty acid ester is 12-hydroxystearic acid.

[0007] In any of the embodiments of the at least one poly(meth)acrylic acid and/or salt thereof described above, the poly(meth)acrylic acid and/or salt thereof may be cross-linked. Common cross-linking agents are known in the art. In particular, the at least one poly(meth)acrylic acid and/or salt thereof may be cross-linked with an allyl ether cross-linking agent. In specific embodiments, the allyl ether cross-linking agent is selected from allyl sucrose and allyl pentaerythritol. Interpolymeric polyacrylic acids and/or salts thereof are described in e.g. US Patent Nos. 5,288,814 and 5,349,030, the contents of both being incorporated herein by reference.

[0008] Examples of commercially available interpolymeric polyacrylic acids and/or salts thereof suitable for use in the present disclosure include Carbopol® ETD 2020 and Carbopol® Ultrez 10.

[0009] The salts of the at least one poly(meth)acrylic acid are not limited. Poly(meth)acrylic acids are polyanionic polymers, i.e. the carboxylic acid side-groups of the polymer chain can be deprotonated and thereby acquire negative charge. Accordingly, the at least one poly(meth)acrylic acid when deprotonated may be associated with any compatible cation, for example when supplied in salt form, or when formulated in the composition as described herein such that cationic species are provided by other components present in the composition. In various embodiments, the poly(meth)acrylic acid and/or salt thereof comprises a sodium salt of poly(meth)acrylic acid. In specific embodiments, counter-ions such as sodium ions may be provided by the chelating agent, the amphoteric surfactant and/or the anionic surfactant. The skilled person will understand that the degree of deprotonation of the poly(meth)acrylic acid will depend on various factors including the pH of the composition, and thus the poly(meth)acrylic acid may be present in the composition of the present disclosure in varying proportions of free acid and (poly)anionic forms thereof. In various embodiments, the pH of the composition is from about pH 4 to about pH 10, from about pH 5 to about pH8, or from about pH 5.5 to about pH 6.5. [0010] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is present in the composition of the present disclosure in an amount of at least about 0.1 wt%, at least about 0.2 wt%, or at least about 0.3 wt% of the total weight of the composition.

[0011] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is present in the composition of the present disclosure in an amount of up to about 2 wt%, up to about 1.5 wt%, up to about 1 wt%, or up to about 0.5 wt% of the total weight of the composition. In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is present in the composition of the present disclosure in an amount of at least about 0.01 wt%, at least about 0.1 wt%, at least about 0.2 wt%, or at least about 0.3 wt% of the total weight of the composition.

[0012] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is present in the composition of the present disclosure in an amount of from about 0.1 to about 2 wt%, from about 0.2 to about 1 .5 wt%, or from about 0.3 to about 1 wt% of the total weight of the composition.

[0013] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is present in the composition of the present disclosure in an amount of from about 0.1 wt% to about 0.7 wt%, from about 0.2 wt% to about 0.7 wt%, or from about 0.3 wt% to about 0.7 wt% of the total weight of the composition.

[0014] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked and an interpolymer that is present in the composition in an amount of from about 0.1 to about 2 wt%, from about 0.2 to about 1.5 wt%, from about 0.3 to about 1 wt%, or from about 0.3 to about 0.7 wt% of the total weight of the composition. In further embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is at least one polyacrylic acid and/or salt thereof that is cross-linked and an interpolymer, said at least one polyacrylic acid and/or salt thereof being present in the composition in an amount of from about 0.1 to about 2 wt%, from about 0.2 to about 1.5 wt%, from about 0.3 to about 1 wt%, or from about 0.3 to about 0.7 wt% of the total weight of the composition. In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked and an interpolymer comprising a block copolymer comprising polyethylene glycol and a fatty acid ester; said at least one poly(meth)acrylic acid and/or salt thereof being present in the composition in an amount of from about 0.1 to about 2 wt%, from about 0.2 to about 1.5 wt%, from about 0.3 to about 1 wt%, or from about 0.3 to about 0.7 wt% of the total weight of the composition. In any of the foregoing embodiments, the cross-linking agent may be an allyl ether cross-linking agent, for example allyl sucrose or allyl pentaerythritol. The fatty acid ester may be 12-hydroxystearic acid [0015] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® llltrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the composition in an amount of from about 0.1 to about 2 wt% of the total weight of the composition.

[0016] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® llltrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the composition in an amount of from about 0.3 to about 1.5 wt% of the total weight of the composition.

[0017] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® Ultrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the composition in an amount of from about 0.3 to about 1 wt% of the total weight of the composition.

[0018] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® Ultrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the composition in an amount of from about 0.3 to about 0.7 wt% of the total weight of the composition.

[0019] In some embodiments, the thickening agent comprising at least one poly(meth)acrylic acid and/or salt thereof may be supplied to the composition in the form of a ready-formulated gel. Such gels are commercially available and non-limiting examples include Lubrajel™ RR CG and Lubrajel™ MG, produced by United-Guardian, Hauppage, NY. In such gels, at least one polyacrylic acid and/or salt thereof is formulated in the gel with one or more of glycerol, water, propylene glycol, and parabens such as methyl or propylparaben. In such embodiments, the gel may be added to the composition of the present disclosure in an amount such as to provide at least one polyacrylic acid and/or salt thereof in an amount of from about 0.1 to about 2 wt%, from about 0.2 to about 1.5 wt%, or from about 0.3 to about 1 wt% of the total weight of the composition. In various embodiments of the gel, the at least one polyacrylic acid and/or salt thereof comprises a glyceryl acrylate/acrylic acid copolymer.

[0020] 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 at least one poly(meth)acrylic acid and/or salt thereof is present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis. [0021] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked and an interpolymer that is present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis. In further embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is at least one polyacrylic acid and/or salt thereof that is cross-linked and an interpolymer, said at least one polyacrylic acid and/or salt thereof being present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis. In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked and an interpolymer comprising a block copolymer comprising polyethylene glycol and a fatty acid ester; said at least one poly(meth)acrylic acid and/or salt thereof being present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis. In any of the foregoing embodiments, the cross-linking agent may be an allyl ether cross-linking agent, for example allyl sucrose or allyl pentaerythritol. The fatty acid ester may be 12-hydroxystearic acid

[0022] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® llltrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis.

[0023] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® llltrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis.

[0024] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® Ultrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis.

[0025] In various embodiments, the at least one poly(meth)acrylic acid and/or salt thereof is selected from Carbopol® ETD 2020, Carbopol® Ultrez 10, and mixtures thereof; said at least one poly(meth)acrylic acid and/or salt thereof being present in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis. [0026] In some embodiments, the thickening agent comprising at least one poly(meth)acrylic acid and/or salt thereof may be supplied to the composition in the form of a ready-formulated gel. Such gels are commercially available and non-limiting examples include Lubrajel™ RR CG and Lubrajel™ MG, produced by United-Guardian, Hauppage, NY. In such gels, at least one polyacrylic acid and/or salt thereof is formulated in the gel with one or more of glycerol, water, propylene glycol, and parabens such as methyl or propylparaben. In such embodiments, the gel may be added to the composition of the present disclosure in an amount such as to provide at least one polyacrylic acid and/or salt thereof in the absorbent layer in an amount of from about 0.01 g/m² to about 1 g/m², or from about 0.1 to about 0.5 g/m² on an actives basis. In various embodiments of the gel, the at least one polyacrylic acid and/or salt thereof comprises a glyceryl acrylate/acrylic acid copolymer.

[0225] In various embodiments, the composition may comprise one or more additional components. For instance, the composition of the second aspect will typically comprise water, which may be added during the formulation process or may already be present in one of the components described herein above. For example, the amphoteric surfactant may be supplied as an aqueous solution (typically about 30-40% active) and thus will contribute water to the composition. 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.

[0226] Preferably, the water content of the composition is controlled. As noted above, this is because too much water in the composition may lead to premature swelling if it is applied, for example, to an absorbent layer comprising gel-forming fibres such as a carboxymethyl cellulose-based wound dressing, and thereby lead to a loss of performance of the dressing. As detailed herein, when the amphoteric surfactant or another component (e.g. a ready- formulated polyacrylate gel such as Lubrajel®) is supplied in a form comprising water, the chelating agent may be dissolved directly in the amphoteric surfactant, which can reduce the amount of water used to prepare the compositions described herein.

[0227] Accordingly, in various embodiments the composition comprises less than about 15 wt%, less than about 12 wt%, or less than about 10 wt% of water relative to the total weight of the composition.

[0228] In various embodiments, the wound dressing or debridement tool is dried after the composition has been at least partially coated or impregnated in or on the absorbent layer. Thus, after drying the contribution of water from the composition to the absorbent layer will generally be negligible.

[0229] In various embodiments, the composition of the second aspect comprises glycerol. For instance, glycerol may be added to adjust the viscosity of the composition. Typically, compositions according to the present disclosure comprising higher amounts of glycerol will have lower viscosities than compositions according to the present disclosure comprising lower amounts of glycerol. In this way, the viscosity may be tailored to a particular application while still benefiting from the advantageous effects of the thickening agent comprising at least one poly(meth)acrylic acid and/or salt thereof as described herein. In some embodiments, the active ingredients, e.g. the chelating agent, amphoteric surfactant, anionic surfactant, and thickening agent may be formulated together as a ‘pre-mix’ that does not comprise glycerol. Glycerol may then be added to such a pre-mix prior to printing to obtain a desired viscosity for a particular application such as a printing process for at least partially impregnating or coating an absorbent layer of a wound dressing or debridement tool.

[0230] In various embodiments, a thicker composition may be advantageous, for example for use in the hybrid- or screen-printing processes described herein. Accordingly, in various embodiments glycerol is present in the composition in an amount of from about 1 wt% to about 90 wt%, from about 1 wt% to about 80 wt%, from about 1 wt% to about 70 wt%, or from about 1 wt% to about 60 wt% of the total weight of the composition. In various embodiments, glycerol is present in the composition in an amount of from about 10 wt% to about 90 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 70 wt%, or from about 40 wt% to about 60 wt% of the total weight of the composition.

[0231] In various embodiments, the composition of the second aspect comprises glycerol, water, or mixtures thereof. For example, the composition may comprise less than about 15 wt%, less than about 12 wt%, or less than about 10 wt% of water relative to the total weight of the composition and glycerol in an amount of from about 1 wt% to about 90 wt%, from about 1 wt% to about 80 wt%, from about 1 wt% to about 70 wt%, or from about 1 wt% to about 60 wt% of the total weight of the composition. In various embodiments, the composition comprises glycerol, water, or mixtures thereof. For example, the composition may comprise less than about 15 wt%, less than about 12 wt%, or less than about 10 wt% of water relative to the total weight of the composition and glycerol in an amount of from about 10 wt% to about 90 wt%, from about 20 wt% to about 80 wt%, from about 30 wt% to about 70 wt%, or from about 40 wt% to about 60 wt% of the total weight of the composition. In various embodiments, the composition comprises less than about 10 wt% of water relative to the total weight of the composition, and glycerol in an amount of from about 10 wt% to about 60 wt% of the total weight of the composition. In various embodiments, the composition comprises less than about 10 wt% of water relative to the total weight of the composition, and glycerol in an amount of from about 40 wt% to about 60 wt% of the total weight of the composition.

[0232] The pH of the composition of the present disclosure is not limited. However, in preferred embodiments, the pH of the composition is from about 4 to about 10, or from about 5 to about 8, or from about 5.5 to about 6.5. Compositions within said range of pH values may cause less discomfort upon application, for example from stinging sensations.

[0233] 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).

[0234] 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).

[0235] 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.

[0236] 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.

[0027] In some embodiments, the composition of the first aspect does not include a non-ionic surfactant.

[0028] In some embodiments, the composition of the second aspect may further comprise an alcohol such as a hydrocarbyl alcohol. For example, the composition may comprise a C1-C4 alcohol. In specific embodiments, the composition may comprise ethanol. The amount of the alcohol present in the composition is not limited and may, for example, be less than about 50 wt%, less than about 40 wt%, or less than about 30 wt% of the total weight of the composition. The alcohol may be present in the composition in an amount of at least about 0.1 wt%, at least about 1 wt%, or at least about 10 wt% of the total weight of the composition.

[0029] However, in various embodiments it is preferred to avoid the use of alcohols, in particular C1-C4 alcohols such as ethanol because such alcohols generally need to be removed from the composition once applied to the wound dressing or debridement tool, which can introduce cost and complexity into the manufacturing process, in particular due to safety requirements for removing volatile flammable solvents. Thus, in preferred embodiments the composition is substantially free of ethanol. In further embodiments, the composition is substantially free of C1-C4 alcohols.

[0237] Such embodiments are advantageous because the manufacturing process is simplified and process safety is improved. Without wishing to be bound by theory, it is believed that the use of the thickening agent as defined herein with the other components of the composition surprisingly enables the formulation of an efficacious, stable composition as described herein while avoiding the use of less desirable components such as alcohols, and in particular ethanol. Moreover, such compositions are suitable for use in a variety of processes for application to wound dressings or debridement tools as described herein.

[0238] 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.

[0239] In various embodiments, the wound dressing or debridement tool may comprise one or more additional components selected from a medicament, an adhesive, a deodorant, an electrically conductive formulation, a thermoresponsive agent, an exothermic agent, an endothermic agent, and combinations thereof. Said one or more additional components may be comprised in or on the absorbent layer, for example in various embodiments the composition may comprise one or more of a medicament, an adhesive, a deodorant, an electrically conductive formulation, a thermoresponsive agent, an exothermic agent, an endothermic agent, and combinations thereof. In other embodiments, the one or more additional components are comprised in another layer of the wound dressing or debridement tool. PROCESSES

[0240] As well as the components of the 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 for preparing a composition of the first aspect comprises the steps of (a) mixing the carrier with the solvent, and (b) adding the chelating agent, anionic surfactant and amphoteric surfactant to the mixture of (a), preferably 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.

[0241] 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.

[0242] 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).

[0243] The polyethylene glycol and its concentration is defined hereinabove. Similarly, the one or more excipients are defined hereinabove.

[0244] When the composition includes a thickening agent which is a polyacrylic acid and/or salt thereof, the composition may be prepared by a process comprising the steps of:

(a) mixing the polyacrylic acid and/or salt thereof into the carrier; and

(d) adding the one or more excipients to the solution of step (a).

[0245] In some embodiments including a thickening agent which is a polyacrylic acid and/or salt thereof, a solvent as defined herein above, in particular one or more C1-C4 alcohols, is not necessary. Without wishing to be bound by theory, this is believed to be due to the thickening agent assisting in the dispersion/dissolution of the excipients.

[0246] When the process is for preparing a composition of the second aspect, the process comprises the steps of:

(a) mixing the chelating agent with the amphoteric surfactant;

(b) mixing the anionic surfactant with the product of step (a); and

(c) mixing the product of step (b) with the thickening agent.

[0247] The chelating agent, amphoteric surfactant, anionic surfactant and thickening agent are defined herein above.

[0248] In various embodiments, the one or more solvents of the composition comprise glycerol and step (c) comprises mixing the product of step (b) with the thickening agent and the glycerol. In various embodiments, the amount of glycerol may be as defined herein above. In further embodiments, step (c) comprises first mixing the thickening agent with the product of step (b) and then mixing the resulting mixture with the glycerol. In alternative embodiments, step (c) comprises first mixing the thickening agent and glycerol and then mixing the resulting product with the product of step (b). Advantageously, the inventors have found that when a thickening agent as defined herein is used, the process can be carried out in a single vessel, simplifying the process.

METHODS AND USES

[0249] 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.

[0250] 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. [0251] 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.

[0252] 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 non-antimicrobial 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.

[0253] 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.

[0254] 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 gelforming 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.

[0255] In various embodiments, the fabric material is a non-woven material consisting of gelforming fibres and/or non-gel forming fibres.

[0256] The wound dressing disclosed herein may have a thickness between 0.5 to 20, or 2 to 10, or 3 to 7 mm.

[0257] 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.

[0258] 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.

[0259] 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 gel-forming fibre is in direct contact with the wound, and thus no additional wound contact layer is required.

[0260] 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.

[0261] 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 in WO00/01425), 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).

[0262] 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. [0263] 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.

[0264] 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 non-gelling fibres are present in an amount of from about 5 to about 40 wt% of the absorbent layer.

[0265] 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.

[0266] 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, the gelling 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. I n 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 present in 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. I n 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. I n 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.

[0267] 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, noncellulose synthetic fibres, superabsorbent fibres, such as polyacrylate fibres, and combinations thereof.

[0268] In a preferred embodiment, the gelling fibres are carboxymethylcellulose fibres or derivatives thereof (e.g. HYDROGEL™).

[0269] In various embodiments, the non-gelling fibres are selected from: cellulosic fibres, modified cellulosic fibres, polyester fibres, polypropylene fibres, polyamide fibres, or combinations thereof.

[0270] 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™).

[0271] 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.

[0272] 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.

[0273] 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.

[0274] 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 deslough 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.

[0275] Similarly, methods for preventing or minimising slough accumulation in a wound, or for de-sloughing 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.

[0276] 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.

[0277] 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).

[0278] 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 more biofilms. As used here, “disrupting” in the context of the one or more biofilms means loosening, softening, and detaching the biofilm from the wound bed. [0279] 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.

[0280] The generally accepted criterion for an antimicrobial composition is a 3-log10 reduction in microbial cell number in a given contact time period. Thus, in various embodiments, the non-antimicrobial compositions described herein cause less than about a 3-log10 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-log10 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 -Iog10 reduction in the number of microbial cells in the wound when contacted with the wound for about 10 minutes.

[0281] 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.

[0030] 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. For example, where the absorbent layer comprises fibres, the composition may be added to the dope (the liquid from which the fibres are spun (extruded)). In other embodiments, the composition may be co-extruded in a hot melt process. The composition may be washed into the fibre by a soaking process. The composition may be coated onto the formed fibre by passing through a bath containing the technology in a liquid or solution form (where the solute may be removed by a drying process known in the art, such as by forced air or any other gas, particularly nitrogen if flammable solvents are involved, or by heat, or by heat and forced air) or as a molten liquid. The composition may be sprayed onto the formed fibre in a liquid form or from a solution (where the solute may be removed by a drying process known in the art such as by forced air or any other gas, particularly nitrogen if flammable solvents are involved, or by heat, or by heat and forced air) or as a molten liquid in a hot-melt inkjet process. The composition may be added as a powder coating where adhesion could be encouraged by electrostatic effects or by increasing the adhesive tack properties of the receiving fibre (say by partial hydration using humidity or by pre-treating the fibre with a viscous liquid such as an alcohol (for example hexanol), a polyol (for example propan-1 , 2-diol or glycerol), a hydrophilic hydrocarbon (for example a polyethylene oxide) or by the order of addition of the composition itself (for example a liquid surfactant such as liquid fatty acid or fatty acid salt or a liquid fatty acid that will form the salt in situ).

[0031] When the dressing/debridement tool is pre-formed, for example as a fabric or a foam, the technology may be added via similar washing, coating, spraying or powder coating. Additionally, the composition may be added by suspending the composition in a non-solvent and passing this through the dressing/debridement tool such that the suspended technology is mechanically trapped (i.e. positively added by filtration).

[0282] 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 floodcoating, 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.

[0283] 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.

[0284] 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.

[0285] 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.

[0286] 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.

[0287] 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.

[0288] 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”.

[0289] 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.

[0290] The process described above may also be referred to as a “soft gravure printing” process or method. [0291] 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.

EXAMPLES

Example 1

[0292] 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(ethylene glycol)-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.

[0293] AQUAGEL® EXTRA dressings are commercially available from ConvaTec.

Efficacy Testing

[0294] Compositions 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 1.

Table 1 [0295] 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.

[0296] To prepare the simulated biofilm/non-viable matrix fortesting, 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.

[0297] To prepare the dressings for testing, ink was prepared at the corresponding concentrations on a %w/w basis as shown in Table 2.

Table 2

[0298] 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 10x10 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. [0299] Once prepared, 2 x 2 cm sections were cut from the printed dressings were hydrated with 1 ml Test Solution A 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.

[0300] “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.

[0301] Figure 1 shows the efficacy of the ink of Table 2 compared to an AQUAGEL® Extra control (% more efficacious than AQUAGEL® Extra) where AQ Clean is solvent flooded with the concentration of excipients stated in Table 3. Sodium oleate ink is AQUACEL® Extra printed with 0.07g of the ink described in Table 2 on one side of a 10x10 cm sample. Increased efficacy compared to AQUACEL® Extra and solvent flooded AQUACEL® Clean was seen as apparent from Figure 1.

Table 3

Effect of chelating agent concentration

[0302] The effect of chelating agent concentration on biofilm and organism recovery was investigated.

Bacterial challenge test method

Materials used

Tryptone Soy Broth (TSB)

Maximum Recovery Diluent (MRD) Foetal Bovine Serum (FBS)

Pre-dried Tryptone Soy Agar (TSA) plates

MRD + 0.01 % Tween 80

Crystal violet (CV)

2- propanol

Challenge organism: P. aeruginosa NCIMB 8626.

Formulations

[0303] Formulations were prepared with the compositions as set out in Table 4 and printed onto dressings as described above.

Table 4

Test Plate Set Up - dressings

[0304] Representative colonies of the challenge organism were dispersed in TSB to achieve an optical density equivalent to ~1 x 10⁸ CFU/ml at 540 nm. This suspension was diluted in 50:50 v/v TSB: FBS (sterile filtered) to achieve a final concentration of ~1 x 10⁶ CFU/ml. A standard plate count was performed on this suspension to determine the total number of viable organisms inoculated per ml.

[0305] 12-well microtitre plates were inoculated with 750 pl of the previously prepared inoculum (n = 3 per dressing type) and a 15 mm diameter section of dressing added. The negative control consisted of 750 pl of uninoculated 50:50 v/v TSB: FBS. 1.5 ml of SDWwas added to the spaces between wells to help prevent moisture loss during incubation. The plates were sealed with parafilm and incubated at 30-35°C. Following incubation, test plates were stained with crystal violet to generate optical density data or processed for total viable counts.

Test Plate Set Up - solutions

[0306] Representative colonies of the challenge organism were dispersed in TSB to achieve an optical density equivalent to ~1 x 10⁸ CFU/ml at 540 nm. This suspension was diluted in 50:50 v/v TSB:FBS (sterile filtered) to achieve a concentration of ~1 x 10⁷ CFU/ml. A 1 ml volume of this challenge suspension will be added to 1 ml of test sample solution (sterile filtered or autoclaved) and 8 ml of 50:50 v/v TSB:FBS (sterile filtered) to achieve a ~1 x 10⁶ CFU/ml working suspension. A standard plate count was performed on this suspension to determine the total number of viable organisms inoculated per ml.

[0307] The above working suspension was added in 500 pl volumes to wells of a 12-well microtitre plate (n = 3 per dressing type). A 500 pl volume of uninoculated 50:50 v/v TSB:FBS was added into wells of a 12-well microtitre plate (n = 3) to form the negative control. 1.5 ml of SDW was added to the spaces between wells to help prevent moisture loss during incubation. The plates were sealed with parafilm and incubated at 30-35°C for either 48 or 72 hours. Following incubation, test plates were stained with crystal violet to generate optical density data or processed for total viable counts.

Crystal violet (CV) biofilm staining

[0308] Dressings were discarded, if applicable, and any liquid tipped out. The wells were rinsed twice with SDW to remove any planktonic cells or unbound biofilm and the plate left to air dry on the benchtop with the lid removed (approximately 1 hour). Once dry, 1 ml of 1% crystal violet (prepared by adding 1 ml of crystal violet Gram stain to 99 ml SDW) was added to each well and left for 15 minutes. The crystal violet was discarded, and the wells washed twice with SDW to remove any unbound stain. Bound stain was solubilised in 70% 2-propanol and the plate sonicated within a sonicating water bath for 5 minutes. 200 pl volumes (n = 3) were sampled and transferred to a 96-well microtitre plate and optical density read at 595 nm using the plate reader. Data will be normalised by subtraction of the negative control (TSB:FBS only).

Total viable counts (TVC)

[0309] Dressings were discarded, if applicable, and any liquid tipped out. The wells were rinsed twice with SDW to remove any planktonic cells or unbound biofilm and MRD + 0.01 % Tween-80 added to each well. The plate was sonicated within a sonicating water bath for 5 minutes and 1 pl sterile loops were used to scrape the bottom and sides of each well to resuspend any remaining attached biofilm. Serial dilutions were performed on the resulting suspensions in MRD and the most appropriate dilutions plated out onto pre-dried TSA plates in duplicate. The plates were spread using L-shaped spreaders, left to dry before being inverted and incubated at 35 ± 3°C for at least 48 hours. TVCs were only performed on wells with dressings, not the negative control.

Results

[0310] OD595 results shown in Figure 2 demonstrate a 20-30% serial reduction between dressing concentrations. Figure 3 shows a -15% decrease in bacterial cells (TVC results) recovered from x1.25 EDTA dressing treated wells compared to x1 EDTA and a <1 % reduction between wells treated with x1.25 EDTA and x1.5 EDTA. These reductions were observed to be a consequence of loosening and lifting of the biofilm from the plate by the dressing, i.e. physical action, rather than an antimicrobial effect.

In vitro testing

[0311] The test formulations with x1 , x1.25, x1.5 and x2 concentrations of EDTA as described above were also tested in the simulated wound biofilm-slough test as detailed above to assess efficacy for autolytic debridement. As can be seen from Figure 4, similar efficacy was seen for each formulation, which in each case was significantly higher than the Aquacel dressing control that did not comprise a composition according to the present disclosure.

[0312] The effect of increased EDTA concentrations on the pH of the wound dressing was also assessed. As can be seen from Table 5, while a slight increase in pH is seen for the printed dressings compared to unprinted textile, the pH values fall within an acceptable range. A slight decrease is observed following sterilisation.

Table 5

[0313] In summary, increasing the concentration of EDTA was found to result in a reduction in the amount of biofilm and total viable counts (TVC) in the above assays while maintaining the advantageous properties of the composition and wound dressing as described herein. Example 2

Preparation of compositions

Composition A (reference)

[0314] A reference composition that does not comprise a thickening agent as defined herein was prepared.

[0315] A 4L glass beaker equipped with a paddle mixing blade connected to Caframo Constant Torque Brushless Mixer was used to formulate a 2 kg batch of the composition. Composition A was prepared by PART A: sequentially adding 398 g of denatured ethanol (Sigma Aldrich), 90 g of oleic Acid (Sigma Aldrich), 1330 g of glycerol (Sigma Aldrich) and 84 g of sodium cocoamphoacetate (BASF, Dehyton® MC (CAS 61791-32-0)) with mixing. PART B was prepared by: dissolving 28 g of tetrasodium EDTA (Sigma Aldrich) in 70 g of deionised (DI) water (MilliQ Synergy IIR-R, Type 1 , M HHQ-M2D2) in a 250 mL glass beaker using a magnetic stir bar and sonication. While mixing, Part B was added to Part A with mixing. The resulting composition was a clear liquid with a light yellowish tinge.

Composition B (reference)

[0316] A 300 mL glass beaker with two built in baffles (Rokko) was used to prepare a 200 g batch of Composition B with fumed silica as the thickening agent.

[0317] A propeller blade shaft connected to a motor was used for mixing. Glycerol, denatured ethanol, oleic acid and tetrasodium EDTA (pre-dissolved in DI water) were sequentially added to the glass beaker with mixing. Subsequently, 8 g of untreated fumed Silica (System Three or Sigma Aldrich) was added in increments with mixing. The solution was hazy in appearance and multiple layers appeared within a week.

Composition C (reference)

[0318] A 300 mL glass beaker with two built in baffles (Rokko) was used to prepare a 200 g batch. A propeller blade shaft connected to a motor was used for mixing. 4 g of hydroxyethylcellulose (Essential Wholesale Lab) was dispersed in 140 g of glycerol with stirring. After mixing 8.19 g of oleic acid pre-dissolved in 30 g of denatured ethanol was added, followed by 8.60 g of Dehyton® MC. Finally 2.22 g of Na4EDTA predissolved in 6.99 g of DI water was added with mixing. Two-layer separation was observed on leaving the composition to stand overnight. Composition D (reference)

[0319] Similar results as Composition C were observed when the same composition but with carboxymethylcellulose (2%) as the thickening agent was prepared.

Composition E

[0320] Compositions were prepared with and without the use of denatured ethanol. Both compositions were prepared in a 300 mL glass beaker with a propeller blade mixing shaft.

[0321] The composition comprising denatured ethanol was prepared by adding pre-mixed oleic acid and denatured ethanol to Lubrajel® RR CG to form a final composition comprising 70% w/w Lubrajel® RR CG. Na₄EDTA was then added which resulted in a decrease in viscosity. Subsequent addition of sodium cocoamphoacetate (Dehyton® MC) gave rise to a watery solution.

[0322] The composition not comprising denatured ethanol was prepared as a 200 g batch. 181 g of Lubrajel® RR CG was added to the beaker, followed sequentially by 8.18 g of oleic acid, 2.22 g of Na₄EDTA, and 8.60 g of Dehyton® MC. The resulting composition was a viscous white gel. Negligible layer separation was observed on aging.

Composition F

[0323] Composition F was prepared in the same manner as Composition E but using Lubrajel® MG instead of Lubrajel® RR CG. Similar results were observed.

Composition G

[0324] 865.0g of glycerol was placed in a 2 L thick-walled glass beaker equipped with a propeller blade mixer. 5 g of Carbopol® ETD 2020 NF was dispersed in the glycerol. Subsequently, 40.94 g of oleic acid was added followed by 11 .12 g of Na₄EDTA pre-dissolved in 34.90 g of DI water. 43.18 g of Dehyton® MC were then added. An increase in viscosity was observed following the addition of Dehyton® MC. The resulting composition appeared slightly hazy and uniform.

[0325] Similar results were obtained when the amount of Carbopol® ETD 2020 NF was increased to 1 % and 2%, respectively, resulting in viscous gels. No separation was observed.

Composition H

[0326] A 500g batch comprising 2 wt% Carbopol® 974PNF was prepared in a 1 L beaker by dispersing 10 g of Carbopol® 974 P NF powder in 332.50 g of glycerol with mixing. Dehyton® MC and Na₄EDTA were subsequently added. A decrease in viscosity was observed following the addition of Dehyton MC and Na₄EDTA.

Composition I

[0327] A 300g scale batch of comprising 0.5 wt% Carbopol® llltrez 10 was prepared in a 500 mL thick-walled beaker fitted with a propeller blade shaft connected to an electrical motor.

[0328] 1.50 g of Carbopol® llltrez 10 was dispersed in 259.51 g of glycerol (Sigma Aldrich) with mixing. Subsequently, 12.28 g of oleic acid, 12.91 g of sodium cocoamphoacetate (Dehyton® MC) and 3.33 g of Na₄EDTA pre-dissolved in 10.47 g of DI water were added. Separation was only observed after 5 weeks of standing at room temperature.

Composition J

[0329] Composition J was prepared using Carbopol® Ultrez 10 as the thickening agent and a 1.5:1 molar ratio of oleic acid to sodium cocoamphoacetate.

[0330] 463.25 g of glycerol was added to a 1 L thick-walled glass beaker. 3.00 g of Carbopol® Ultrez 10 was then dispersed in the glycerol with mixing, followed by 9.48 g of oleic acid and 5.55 g of Na₄EDTA. Subsequently, 18.73 g of Amphosol® 1C were added with mixing.

Composition K

[0331] Composition K was prepared using Carbopol® Ultrez 10 as the thickening agent and a 1 :1 molar ratio of oleic acid to sodium cocoamphoacetate.

[0332] 278.16 g of glycerol was added to a 600 mL thick-walled glass beaker. 1.80 g of Carbopol® Ultrez 10 was then dispersed in the glycerol with mixing. Subsequently, 3.83 g of oleic acid, 12.91 g of Dehyton® MC and 3.33 g of Na₄EDTA were added with mixing. The resulting composition had a clearer appearance than Composition J.

Composition L

[0333] Composition L was prepared using Carbopol® Ultrez 10 as the thickening agent and a 2:1 molar ratio of oleic acid to sodium cocoamphoacetate. Composition L was prepared as a pre-mix of active ingredients that could subsequently be mixed with glycerol to obtain a desired viscosity. In particular, it was observed that the proportion of glycerol could be reduced to obtain higher viscosity compositions. [0334] 89.20 g of Dehyton® MC was placed in a 250 mL vessel, to which was added 23.68 g of Na₄EDTA with mixing. Then, 54.38 g of oleic acid was added, which turned the solution to solid chunks that with mixing resulted in a white creamy solid.

Results

[0335] Compositions A to L were evaluated in terms of stability to separation as well as their suitability for screen printing, gravure printing, rotary pad printing and needle dose printing, in particular whether a suitable viscosity for such printing processes could be obtained.

[0336] While Composition A is suitable for spray coating, it was found to be too thin for the above-mentioned printing methods. Additionally, as Composition A comprises denatured ethanol, deposition of such a composition onto a dressing such as a gel-forming fibre-based dressing would require additional processing steps to remove the ethanol. This is disadvantageous as ethanol is a volatile and flammable solvent and so such a process would require additional safety and regulatory precautions. Additionally, removal of the ethanol may in some instances lead to an undesirable separation of the oleic acid out of the composition to form oily droplets on the wound dressing.

[0337] Fumed silica as used in Composition B was found to be unsuitable as a thickening agent for the purposes of the present disclosure. While fumed silica did lead to a thickening of the composition, the composition was unstable to separation into layers. Additionally, the composition comprised denatured ethanol and so was less desirable for the same reasons as discussed above for Composition A.

[0338] Cellulose-based thickening agents were also found to perform poorly. In particular, Compositions C and D were found to have extremely poor stability and rapidly separated into layers. Said compositions also comprised denatured ethanol and therefore are less desirable for the same reasons as set out above.

[0339] Carbopol® thickeners were found to be particularly suitable for the purposes of the present disclosure. Best results were obtained with Carbopol® ETD 2020 NF and Carbopol® llltrez 10. Additionally, it was surprisingly found that the use of Carbopol® thickeners allowed stable compositions to be obtained without the use of denatured ethanol. This is particularly advantageous as the formulation process is simplified and manufacturing safety is improved. Further, the packaging process is simplified because the ethanol does not need to be removed prior to packaging of the wound dressing or debridement tool. It was also found that less water could be used in the formulation process, e.g. for dissolution of the Na₄EDTA, leading to further efficiencies. In particular, having a lower amount of water in the composition may be advantageous when the composition is at least partially impregnated into or coated onto a wound dressing or debridement tool comprising an absorbent layer comprising gel-forming fibres, where too much water in the composition may cause the fibres to prematurely gel prior to drying and a consequent reduction in performance of the dressing.

[0340] Similar advantages were found with the use of Lubrajel® gels. However, these ready- formulated gels may be somewhat less advantageous than the use of powdered reagents such as Carbopols® because the Lubrajel gels comprise a significant amount of water, which for the reasons already discussed above may lead to premature swelling of gel-forming fibres such as those that may be used in an absorbent layer of a wound dressing or debridement tool.

[0341] Further improvements in stability were unexpectedly found when the ratio of oleic acid to sodium cocoamphoacetate was decreased, e.g. as tested in Compositions J, K, and L. Thus, in comparison to a molar ratio of 3:1 (e.g. as used in Composition A), compositions having molar ratios of 2:1 , 1.5:1 , or 1 :1 of oleic acid to sodium cocoamphoacetate were found to have greater stability to separation over time.

[0342] Additionally, it was also found that the proportion of glycerol in the composition could be reduced to obtain higher viscosity compositions that may be suitable for alternate deposition processes.

[0343] Finally, it was found that the chelating agent could be dissolved directly into the amphoteric surfactant to form a ‘pre-mix’ prior to mixing with the remaining active ingredients rather than pre-dissolving the chelating agent in water. This has the advantage that the process can be performed on a ‘one-pot’ basis. Compositions prepared via this ‘pre-mix’ process were found to have comparable performance to compositions wherein the chelating agent and amphoteric surfactant were added sequentially.

Printing tests

[0344] Formulations prepared as above and as detailed in Table 6 were evaluated for their transfer performance on the surface of a carboxymethyl cellulose wound dressing. A red dye was added to visualise the shapes of the dots produced by the various processes.

Table 6

¹The molar ratio of anionic surfactant to amphoteric surfactant (oleic acicksodium cocoamphoacetate) for Formulations “Ink A”, “Ink B”, “061422A”, “061422B”, and “061722A” was 3:1.

²No water added other than water contributed by the sodium cocoamphoacetate solution.

[0345] Illustrative results of the printing tests using screen-printing, hybrid printing, gravure printing, rotary pad printing, and needle dosing are shown in Figures 5 and 6.

[0346] The inventive formulations were found to perform better in the tested printing processes. Additionally, the further increased viscosity of Formulation 061722A was found to produce better-defined dots with both the hybrid printing and screen printing processes.

NUMBERED CLAUSES - FIRST ASPECT

1. A wound dressing or debridement tool, wherein the dressing or tool comprises an absorbent layer at least partially impregnated or coated with a non-antimicrobial composition, said composition comprising (i) a chelating agent, (ii) an amphoteric surfactant, and (iii) an anionic surfactant, wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 3:1 , wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 1:2 to about 2:1 , wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 2:3 to about 3: 1 ; and wherein the concentration of the chelating agent in the composition is at least about 1 wt.% on an actives basis, based on the total weight of the composition.

2. The wound dressing or debridement tool of clause 1 , wherein the chelating agent is selected from citrates, tartrates, tartramides, tartrimides, gluconates, lactates, glycolates, oxalates, phosphates, salts of ethylenediaminetetraacetic acid, and mixtures thereof

3. The wound dressing or debridement tool of clause 1 or clause 2, wherein the chelating agent comprises a salt of ethylenediaminetetracetic acid, preferably the tetrasodium salt of ethylenediaminetetracetic acid.

4. The wound dressing or debridement tool of any preceding clause, wherein the amphoteric surfactant is selected from hydrocarbyl-amphoacetates, alkenyl- amphoacetates, hydrocarbyl-amphodiacetates, alkenyl-amphodiacetates, hydrocarbylampho-propionates, hydrocarbylampho-diproprionates, hydrocarbylamphohydroxypropyl sultaines, and mixtures thereof; preferably wherein the hydrocarbyl or alkenyl groups are Ce to C24 hydrocarbyl or alkenyl groups.

5. The wound dressing or debridement tool of clause 4, wherein the amphoteric surfactant comprises a fatty acid amphoacetate, preferably a cocoamphoacetate. The wound dressing or debridement tool of any preceding clause, wherein the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof. The wound dressing or debridement tool of clause 6, wherein the anionic surfactant comprises a fatty acid or salt thereof, preferably oleic acid or a salt thereof. The wound dressing or debridement tool of any preceding clause, wherein the concentration of anionic surfactant in the composition is from about 2.0 wt.% to about 15.0 wt.% on an actives basis, based on the total weight of the composition, preferably wherein the concentration of anionic surfactant in the composition is from about 2.0 wt% to about 10.0 wt% on an actives basis, based on the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the concentration of amphoteric surfactant in the composition is from about 1 .8 wt.% to about 15.0 wt.% on an actives basis, based on the total weight of the composition, preferably wherein the concentration of amphoteric surfactant in the composition is from about 1.8 wt% to about 8.0 wt% on an actives basis, based on the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the concentration of chelating agent in the composition is 1.2 wt.% to about 10.0 wt.% on an actives basis, based on the total weight of the composition, preferably wherein the concentration of chelating agent in the composition is from about 1 .5 wt% to about 8.0 wt% on an actives basis, based on the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the composition further comprises a non-ionic surfactant, preferably wherein the nonionic 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 wound dressing or debridement tool of any preceding clause, wherein the composition further comprises a thickening agent. The wound dressing or debridement tool of clause 12, 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 wound dressing or debridement tool of clause 12, wherein the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof. The wound dressing or debridement tool of any preceding clause, wherein the concentration of water in the non-antimicrobial composition is less than about 10%. The wound dressing or debridement tool of any preceding clause, wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 2:1. The wound dressing or debridement tool of any preceding clause, wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 3:2. The wound dressing or debridement tool of any preceding clause, wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 2: 1. The wound dressing or debridement tool of any preceding clause, wherein the molar ratio of amphoteric surfactant : anionic surfactant : chelating agent is 5:5:2 to 10:24:9. The wound dressing or debridement tool of any preceding clause, wherein the composition comprises: about 2.0 wt.% to about 10 wt.% on an actives basis of anionic surfactant; about

1.8 wt.% to about 8.0 wt.% on an actives basis of amphoteric surfactant; and about 1.5 wt% to about 8.0 wt% on an actives basis of chelating agent; the wt% being based on the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the composition comprises: about 3.0 wt.% to about 8.0 wt.% on an actives basis of anionic surfactant; about 2.0 wt.% to about 6.0 wt.% on an actives basis of amphoteric surfactant; and about 2.0 wt% to about 6.0 wt% on an actives basis of chelating agent; the wt% being based on the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the absorbent layer comprises: about 0.5 g/m² to about 5.0 g/m² on an actives basis of anionic surfactant; about 0.5 g/m² to about 3.0 g/m² on an actives basis of amphoteric surfactant; and about 0.6 g/m² to about 3.0 g/m² on an actives basis of chelating agent. The wound dressing or debridement tool of any preceding clause, wherein the absorbent layer comprises: about 0.75 g/m² to about 2.5 g/m² on an actives basis of anionic surfactant; about 0.5 g/m² to about 2.0 g/m² on an actives basis of amphoteric surfactant; and about 0.7 g/m² to about 2.0 g/m² on an actives basis of chelating agent. The wound dressing or debridement tool of any preceding clause, wherein the absorbent layer comprises: about 0.8 g/m² to about 2.0 g/m² on an actives basis of anionic surfactant; about 0.6 g/m² to about 1.0 g/m² on an actives basis of amphoteric surfactant; and about 0.7 g/m² to about 1 .0 g/m² on an actives basis of chelating agent. The wound dressing or debridement tool of any preceding clause, wherein the composition further comprises glycerol and one or more C1.4 alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2:1 to about 5:1 , preferably wherein glycerol and the one or more C1.4 alcohol form the carrier system of the composition and the weight ratio of glycerol to the one or more C1.4 alcohol in the carrier system is from about 60:40 to about 80:20. The wound dressing or debridement tool of clause 25, 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. 27. The wound dressing or debridement tool of any preceding clause, wherein the absorbent layer impregnated or coated with the composition comprises at least one layer composed of a foam, absorbent, superabsorbent, non-gel forming or gel-forming fibre, or a combination thereof.

28. The wound dressing or debridement tool of any preceding clause, wherein the wound dressing absorbent layer is a fabric material, preferably a non-woven fabric material

29. The wound dressing or debridement tool of clause 28, wherein the fabric material is a non-woven material consisting of gel-forming fibres and/or non-gel forming fibres.

30. The wound dressing or debridement tool of any preceding clause, wherein the non-antimicrobial composition comprises:

(i) glycerol;

(ii) one or more C1.4 alcohol;

(iii) a salt of ethylenediaminetetraacetic acid;

(iv) a C6-C24 fatty acid amphoacetate; and

(v) oleic acid or a salt thereof.

31. Use of the wound dressing or debridement tool according any one of clauses 1 to 30 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.

32. A composition as defined in any of clauses 1 to 30 for use in the treatment of a wound, preferably wherein the wound is a chronic wound, acute wound, or burn.

NUMBERED CLAUSES - SECOND ASPECT

1. A wound dressing or debridement tool, wherein the dressing or tool comprises an absorbent layer at least partially impregnated or coated with a composition, said composition comprising:

(i) a chelating agent; (ii) an amphoteric surfactant;

(iii) an anionic surfactant; and

(iv) a thickening agent, wherein the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof. The wound dressing or debridement tool of clause 1 , wherein the at least one poly(meth)acrylic acid and/or salt thereof is an interpolymer, preferably wherein the at least one poly(meth)acrylic acid and/or salt thereof comprises a block copolymer comprising polyethylene glycol and a fatty acid ester. The wound dressing or debridement tool of clause 1 or clause 2, wherein the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked, preferably wherein the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked with an allyl ether cross-linking agent. The wound dressing or debridement tool of any one of clauses 1 to 3, wherein the at least one poly(meth)acrylic acid and/or salt thereof is present in the composition in an amount of from about 0.1 to about 2 wt%, preferably from about 0.3 to about 1 wt%, of the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the at least one poly(meth)acrylic acid and/or salt thereof is at least one polyacrylic acid and/or salt thereof. The wound dressing or debridement tool of any preceding clause, wherein the chelating agent 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 wound dressing or debridement tool of any preceding clause, wherein the chelating agent is present in the composition in an amount of from about 0.1 to about 10 wt%, preferably from about 0.1 to about 5 wt%, of the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the chelating agent is present in the absorbent layer at 0.1 to 2 g/m² on an actives basis, preferably wherein the chelating agent is present in the absorbent layer at 0.25 to 1.5 g/m² on an actives basis. The wound dressing or debridement tool of any preceding clause, wherein the amphoteric surfactant is selected from hydrocarbyl-amphoacetates, alkenyl- amphoacetates, hydrocarbyl-amphodiacetates, alkenyl-amphodiacetates, hydrocarbylampho-propionates, hydrocarbylampho-diproprionates, hydrocarbylamphohydroxypropyl sultaines, and mixtures thereof; preferably wherein the hydrocarbyl or alkenyl groups are Ce to C24 hydrocarbyl or alkenyl groups. The wound dressing or debridement tool of clause 9, wherein the amphoteric surfactant comprises a fatty acid amphoacetate, preferably a cocoamphoacetate. The wound dressing or debridement tool of any preceding clause, wherein the amphoteric surfactant is present in the composition in an amount of from about 0.1 to about 10 wt%, preferably from about 0.1 to about 5 wt%, of the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the amphoteric surfactant is present in the absorbent layer at 0.1 to 2 g/m² on an actives basis, preferably wherein the chelating agent is present in the absorbent layer at 0.25 to 1.5 g/m² on an actives basis. The wound dressing or debridement tool of any preceding clause, wherein the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof. The wound dressing or debridement tool of clause 13, wherein the anionic surfactant comprises a fatty acid or salt thereof, preferably oleic acid or a salt thereof. The wound dressing or debridement tool of any preceding clause, wherein the anionic surfactant is present in the composition in an amount of from about 0.1 to about 10 wt%, preferably from about 0.5 to about 5 wt%, of the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the anionic surfactant is present in the absorbent layer at 0.1 to 2.5 g/m² on an actives basis, preferably wherein the chelating agent is present in the absorbent layer at 0.25 to 2 g/m² on an actives basis. The wound dressing or debridement tool of any preceding clause, wherein the molar ratio of the anionic surfactant to the amphoteric surfactant is less than about 2.5:1 , preferably from about 2:1 to about 1 :1. The wound dressing or debridement tool of any preceding clause, wherein the composition comprises glycerol, water or mixtures thereof. The wound dressing or debridement tool of any preceding clause, wherein the composition comprises less than about 10 wt% of water relative to the total weight of the composition. The wound dressing or debridement tool of clause 18, wherein the glycerol is present in the composition in an amount of from about 1 wt% to about 90 wt%, preferably from about 10 wt% to about 70 wt%, of the total weight of the composition. The wound dressing or debridement tool of any preceding clause, wherein the composition is substantially ethanol-free. The wound dressing or debridement tool of any preceding clause, wherein the composition further comprises a non-ionic surfactant, preferably wherein the nonionic 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 wound dressing or debridement tool of any preceding clause, wherein the absorbent layer at least partially impregnated or coated with the composition comprises at least one layer composed of a foam, absorbent, or gel-forming fibres; preferably wherein the wound dressing absorbent layer comprises at least one layer composed of gel-forming fibres. A process for preparing a composition as defined in any one of clauses 1 to 23, said process comprising, in order, the steps of:

(a) mixing the chelating agent with the amphoteric surfactant;

(b) mixing the anionic surfactant with the product of step (a); and

(c) mixing the product of step (b) with the thickening agent. The process of clause 24, wherein the one or more solvents of the composition comprise glycerol and step (c) comprises mixing the product of step (b) with the thickening agent and the glycerol. The process of clause 25, wherein step (c) comprises first mixing the thickening agent with the product of step (b) and then mixing the resulting mixture with the glycerol, or wherein step (c) comprises first mixing the thickening agent and glycerol and then mixing the resulting product with the product of step (b). The process of clause 24 or clause 25, wherein said process is carried out in a single vessel. A process for preparing a wound dressing or debridement tool according to any one of clauses 1 to 23, said process comprising applying the composition as defined in any one of clauses 1 to 23 onto a surface of said absorbent layer of the wound dressing or debridement tool. The process of clause 28, wherein the composition is applied by printing, preferably screen printing. The process of clause 28 or clause 29, wherein the process comprises applying the composition onto a first surface of the absorbent layer and a second surface of the absorbent layer opposite to the first surface. Use of the wound dressing or debridement tool of any one of clauses 1 to 23 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. Use of the wound dressing or debridement tool of any one of clauses 1 to 23 to disrupt one or more biofilms in a wound, preferably wherein the wound is a chronic wound, acute wound, or burn. A composition as defined in any one of clauses 1 to 23. A composition as defined in any one of clauses 1 to 23 for use in the treatment of a wound, preferably wherein the wound is a chronic wound, acute wound, or burn. The composition for use according to clause 34, wherein treating the wound comprises disrupting one or more biofilms of the wound.

Claims

2. The wound dressing or debridement tool of Claim 1 , wherein the composition further comprises a thickening agent, optionally wherein the thickening agent comprises: (i) a polyethylene glycol, preferably wherein the polyethylene glycol has a weight average molecular weight of greater than about 1000 to less than about 8000; or (ii) at least one poly(meth)acrylic acid and/or salt thereof.

3. A wound dressing or debridement tool, wherein the dressing or tool comprises an absorbent layer at least partially impregnated or coated with a composition, said composition comprising:

(i) a chelating agent;

(ii) an amphoteric surfactant;

(iii) an anionic surfactant; and

(iv) a thickening agent, wherein the thickening agent comprises at least one poly(meth)acrylic acid and/or salt thereof.

4. The wound dressing or debridement tool of Claim 3, wherein the at least one poly(meth)acrylic acid and/or salt thereof is an interpolymer, preferably wherein the at least one poly(meth)acrylic acid and/or salt thereof comprises a block copolymer comprising polyethylene glycol and a fatty acid ester.

5. The wound dressing or debridement tool of Claim 3 or Claim 4, wherein the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked, preferably wherein the at least one poly(meth)acrylic acid and/or salt thereof is cross-linked with an allyl ether cross-linking agent.

6. The wound dressing or debridement tool of any preceding claim, wherein the chelating agent 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 ethylenediaminetetracetic acid.

7. The wound dressing or debridement tool of any preceding claim, wherein the amphoteric surfactant is selected from hydrocarbyl-amphoacetates, alkenyl- amphoacetates, hydrocarbyl-amphodiacetates, alkenyl-amphodiacetates, hydrocarbylampho-propionates, hydrocarbylampho-diproprionates, hydrocarbylamphohydroxypropyl sultaines, and mixtures thereof; preferably wherein the hydrocarbyl or alkenyl groups are Ce to C24 hydrocarbyl or alkenyl groups.

8. The wound dressing or debridement tool of Claim 7, wherein the amphoteric surfactant comprises a fatty acid amphoacetate, preferably a cocoamphoacetate.

9. The wound dressing or debridement tool of any preceding claim, wherein the anionic surfactant is selected from fatty acids, fatty acid salts, sulphates, sulphosuccinates, sarcosinates, isethionates, glutamates, taurates, and mixtures thereof, optionally wherein the anionic surfactant comprises a fatty acid or salt thereof, preferably oleic acid or a salt thereof.

10. The wound dressing or debridement tool of any preceding claim 1, 2 or 6 to 9, wherein the concentration of anionic surfactant in the composition is from about 2.0 wt.% to about 15.0 wt.% on an actives basis, based on the total weight of the composition; preferably wherein the concentration of anionic surfactant in the composition is from about 2.0 wt% to about 10.0 wt% on an actives basis, based on the total weight of the composition.

11. The wound dressing or debridement tool of any preceding claim 1, 2 or 6 to 10, wherein the concentration of amphoteric surfactant in the composition is from about 1.8 wt.% to about 15.0 wt.% on an actives basis, based on the total weight of the composition; preferably wherein the concentration of amphoteric surfactant in the composition is from about 1.8 wt% to about 8.0 wt% on an actives basis, based on the total weight of the composition.

12. The wound dressing or debridement tool of any preceding claim 1 , 2 or 6 to 11 , wherein the concentration of chelating agent in the composition is 1.2 wt.% to about 10.0 wt.% on an actives basis, based on the total weight of the composition; preferably wherein the concentration of chelating agent in the composition is from about 1.5 wt% to about 8.0 wt% on an actives basis, based on the total weight of the composition.

13. The wound dressing or debridement tool of any preceding claim 3 to 9, wherein the anionic surfactant is present in the composition in an amount of from about 0.1 to about 10 wt%, preferably from about 0.5 to about 5 wt%, of the total weight of the composition; and/or wherein the amphoteric surfactant is present in the composition in an amount of from about 0.1 to about 10 wt%, preferably from about 0.1 to about 5 wt%, of the total weight of the composition; and/or wherein the chelating agent is present in the composition in an amount of from about 0.1 to about 10 wt%, preferably from about 0.1 to about 5 wt%, of the total weight of the composition.

14. The wound dressing or debridement tool of any preceding claim 3 to 9 or 13, wherein the anionic surfactant and amphoteric surfactant are present on an actives basis at a weight ratio of about 2:5 to about 2:1 ; and/or wherein the amphoteric surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 3:2; and/or wherein the anionic surfactant and chelating agent are present on an actives basis at a weight ratio of about 4:5 to about 2: 1 .

15. The wound dressing or debridement tool of any preceding claim 3 to 9, 13 or 14, wherein the composition further comprises glycerol and one or more C1.4 alcohol, wherein the weight ratio of (i) to (ii) in the composition is from about 2:1 to about 5:1 , preferably wherein glycerol and the one or more C1.4 alcohol form the carrier system of the composition and the weight ratio of glycerol to the one or more C1.4 alcohol in the carrier system is from about 60:40 to about 80:20.

16. The wound dressing or debridement tool of claim 15, 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.

17. The wound dressing or debridement tool of any preceding claim, wherein the concentration of water in the composition is less than about 10%, based on the total weight of the composition.

18. The wound dressing or debridement tool of any preceding claim, wherein the molar ratio of amphoteric surfactant : anionic surfactant : chelating agent is 5:5:2 to 10:24:9; wherein the molar ratio of the anionic surfactant to the amphoteric surfactant is less than about 2.5:1 , preferably from about 2: 1 to about 1 :1.

19. The wound dressing or debridement tool of any preceding claim, wherein the composition further comprises a non-ionic surfactant, preferably wherein the nonionic 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.

20. The wound dressing or debridement tool of any preceding claim, wherein the absorbent layer impregnated or coated with the composition comprises at least one layer composed of a foam, absorbent, superabsorbent, non-gel forming or gel-forming fibre, or a combination thereof; preferably wherein the wound dressing absorbent layer comprises at least one layer composed of gel-forming fibres.

21 . The wound dressing or debridement tool of any preceding claim, wherein the wound dressing absorbent layer is a fabric material, preferably a non-woven fabric material, more preferably wherein the fabric material is a non-woven material consisting of gel-forming fibres and/or non-gel forming fibres.

22. Use of the wound dressing or debridement tool according any one of claims 1 to 21 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.

23. A composition as defined in any of Claims 1 to 21 for use in the treatment of a wound, preferably wherein the wound is a chronic wound, acute wound, or burn.