CN115297902A

CN115297902A - Debridement composition

Info

Publication number: CN115297902A
Application number: CN202180022411.9A
Authority: CN
Inventors: D·帕森斯; G·E·哈里斯; H·J·海瑟薇
Original assignee: Trio Healthcare Ltd
Current assignee: Trio Healthcare Ltd
Priority date: 2020-03-20
Filing date: 2021-03-19
Publication date: 2022-11-04
Also published as: CA3175431A1; EP4121129A1; US20210290815A1; AU2021238941A1; CO2022012306A2; BR112022017532A2; JP2023518943A

Abstract

The disclosed technology relates to a wound dressing comprising an absorbent layer impregnated or coated with a composition comprising a chelating agent, an amphoteric surfactant and an anionic surfactant. The invention further relates to methods and uses of the wound dressing.

Description

Debridement composition

Technical Field

The present disclosure relates to the field of wound care, and in particular to compositions, wound dressings or other debriding formulations or adjuvants that promote and enhance the natural cleansing mechanism (natural cleansing mechanism) of autolytic debridement (automatic debridement).

BACKGROUND OF THE DISCLOSURE

The physiology of the skin makes it an extremely elastic organ. The outer layer (stratum corneum) consists of scales formed by dead epithelial cells that have become flattened and compressed by skin oil (sebum). The stratum corneum provides a flexible and effectively water-proof barrier. It is elastic and resilient, but because it is only a compressive layer, it can be eroded by repeated friction, by the action of chemicals, or by traumatic damage to create a wound. Once the outer protective layer is removed, the nerve endings are exposed, causing pain. Loss of the barrier results in weeping (oozing) and the underlying tissue is susceptible to microbial invasion.

Clean and acute wounds typically heal spontaneously by simple supportive physical measures such as protective dressings. Autolytic (spontaneous, biochemically mediated) debridement of non-viable tissue (non-viable tissue) is part of the natural acute wound healing process. However, treatment of contaminated traumatic, necrotic and chronic wounds is more challenging, and autolytic debridement may not be sufficient. Often, it is desirable to remove contaminated and inactive tissue before normal healing can be reestablished. Qualified medical professionals may be able to perform mechanical and/or sharp debridement to remove such inactive substances, but nurses and less qualified caregivers may be unable to adequately perform such tasks or lack confidence. In these cases, less invasive debridement techniques are required. It is well known that wound irrigation between dressing changes facilitates mechanical removal of some material, and autolytic debridement may be facilitated by the use of moisturizing products (moisturizing products) and/or moisture-retaining dressings. However, autolytic debridement is a slow process and wounds containing inactive tissue are very susceptible to microbial proliferation and infection. Therefore, it is desirable to enhance or accelerate autolytic debridement. Types of inactive tissue may include necrotic (dead) tissue, slough (aggregated granulation and epithelial cells that fail to survive in a chronic wound environment), and biofilm (microbial matter, including viable microorganisms and associated self-produced mucus or extracellular polymeric matter (EPS)). Biofilms are living microbial tissues that can rapidly reconstitute and multiply, returning to their original state within days or even hours. Slough is the result of the inflammatory phase of wound healing and includes dead or excess leukocytes, fibrin/fibroblasts, cell debris/healing components, and liquefied, devitalized tissue. The slough may provide a source of nutrients for the bacterial cells and an environment suitable for their proliferation, subsequently enabling the formation of a biofilm. Necrotic tissue is an additional source of cellular debris in the form of fibrin (e.g., collagen) and proteoglycans (components of the extracellular matrix). Thus, failure to adequately prepare the wound bed by removing harmful waste such as slough and necrotic tissue has been shown to impede healing. Often associated with chronic wounds, the accumulation of this tissue and the regulation of undesirable microbial proliferation and subsequent biofilm formation are considered important factors in the failure of some wounds to heal.

Thus, there is a need for compositions that enhance autolytic debridement. Such compositions may control biofilms before infection occurs. In wound dressings, it is desirable to have compositions capable of debonding, softening and destroying inactive materials, which further enhances the ability of the absorbent material to mechanically remove such materials from the wound bed, which is believed to subsequently promote healing.

The use of surfactants appears to be an obvious option to help remove unwanted substances, but they may also be potentially harmful (cytotoxic-causing cell death involved in healing, local or systemic toxicity) and require appropriate consideration for compatibility with other therapies used concurrently. Similar considerations as to the tonicity and pH of the wound environment must also be given for the Anti-biofilm agent (Anti-biofilm agent). Therefore, formulating for enhanced autolytic debridement is complex and requires more than just adaptive or additive approaches. If pain and delayed healing are to be minimized, restoration of barrier function, normal tension and pH is required.

In cases where active debridement by biological debridement (maggots or enzymes), sharp surgical debridement, or other mechanical debridement techniques is not possible, current practice known in the art is to promote autolytic debridement. This is thought to be achieved by the use of occlusive and/or moist wound dressings, which are exchanged for brief wound irrigation (wind irrigation) to remove unwanted material from the wound environment by fluid flow.

Wound cleansing compositions are disclosed in, for example, US 5,284,833. This discloses a physiologically compatible aqueous wound cleanser composition which passes the Draize eye irritation test and primary skin irritation test (primary dermal irritation test), said composition comprising, in weight percent: from about 0.01 to about 50% surfactant such that the surface tension of the composition is less than about 30 dynes/cm; about 0.05 to about 10% of an osmolyte such that the osmolality (osmolality) of the composition is from about 200 to about 320 mOs/liter; about 0.05% to about 3% buffer to maintain a pH of about 6 to about 7.7 in the composition; and sufficient water to establish the above properties. Although safety is a proper consideration, US 5,284,833 does not address the challenge of biofilms or the transient nature of lavage products.

US2017347661 (A1) describes a composition comprising an antimicrobial metal ion and a quaternary cationic surfactant. The composition disrupts biofilm EPS, thereby increasing the effectiveness of the preservative effect of the metal ions and reducing the risk of infection. There is no mention of disrupting or removing non-biological membranous tissue.

Summary of The Invention

There is a need for a product intended to enhance wound debridement with minimal intervention that can be used in any environment. In some cases, it would be beneficial to provide antimicrobial compositions and dressings where appropriate medical supervision is available. However, in other cases, antimicrobial agents may not be needed because debridement and wound cleansing may minimize or prevent biofilm formation.

The disclosed technology relates in one embodiment to a composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant.

In one embodiment, the composition further comprises a nonionic surfactant.

The composition may be impregnated or coated into or placed on a device placed in direct contact with the wound. The device may include a wound dressing (wound dressing) or a debridement tool (debridement tool). Both the wound dressing and the debridement tool may have an absorbent layer (absorbent layer).

The debridement tool may have an absorbent layer, which may be a natural or synthetic material and in the form of a liquid or solid foam or mousse (mousse), fabric, technical textile or brush.

The composition may, for example, be in the form of a mousse or foam which is generated in situ after application as a liquid. Without being bound by theory, the mousse or foam may remain stationary in the wound and act as a wound dressing formed in situ. Alternatively, the composition may be pre-formed and removed during or after debridement; a conventional foam product; a fabric wipe woven to produce a loop fiber surface; a nonwoven or calendered fabric, such as a pad, wipe, or pan brush (pan scrub); brush-like fabrics or tools in which the fibres are cut to produce a fleece-like finish or are for example monofilaments.

Materials known for making foams, fabrics, textiles and brushes are known in the art.

The disclosed technology, in one embodiment, relates to the debridement tools disclosed herein. Debridement tools are commonly available for mechanical debridement.

The debridement tool may be, for example, a sponge or pad. A common material used to make sponges or pads is foam, typically polyurethane foam, polypropylene foam, polyester foam, or polyvinyl alcohol (PVA) foam. Polyester foams are useful for wipes.

The disclosed technology relates in one embodiment to the wound dressings disclosed herein. Wound dressings are typically debrided by autolysis.

In one embodiment, the disclosed technology relates to a wound dressing comprising an absorbent layer impregnated or coated with a composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant. The absorbent layer may be in direct contact with the wound, or the absorbent layer may have a wound contact layer between the absorbent and the wound. In one embodiment, the absorbent layer is in direct contact with the wound.

In one embodiment, the disclosed technology relates to a wound dressing comprising an absorbent layer impregnated or coated with a composition comprising a chelating agent, an amphoteric surfactant, an anionic surfactant, and a nonionic surfactant.

The term "hydrocarbyl" as used herein includes groups such as alkyl, aryl, aralkyl, alkaryl, cycloalkyl or alkenyl groups, which may be linear or branched, and/or saturated or unsaturated, or may be ester derivatives thereof. In one embodiment, the hydrocarbyl group may comprise a linear or branched alkyl or alkenyl group, typically an alkyl group.

The amount of the composition ingredients, both in weight% and in areal density (weight per unit area), depends on the form and application of the product. For example,% w/w may be most suitable for fluid products such as liquids, gels or mousses, while areal density may be more suitable for flat sheet dressing (flat sheet dressing). In the example, 150gm is used ^-2 The fabric, therefore, calculates the areal density basis by multiplying the wt% by a factor of 1.5.

Anionic surfactants

The disclosed technology defines anionic surfactants. In various embodiments, the anionic surfactant may be present from 0.05 to 1.5 wt.%, or from 0.1 to 1 wt.%, or from 0.1 to 0.5 wt.%.

The amount of anionic surfactant can be from 0.075 to 2.25gm, based on area density ^-2 Or 0.15 to 1.5gm ^-2 Or 0.15 to 0.75gm ^-2 。

Anionic surfactants may include all forms of lipophilic oligohydrocarbons and/or polyethoxylates having a negatively charged hydrophilic head group, such as a carboxylate, sulfate, sulfonate, sulfonated ester, sulfated amide, carboxylated amide, or phosphate anionic head group. For example, fatty acids or fatty acid salts, glutamates, sulfosuccinates, sarcosines, sarcosinates, isethionates and taurates are included.

The anionic surfactant may be a salt, or a hydrocarbyl or hydrocarbyl ester derivative thereof, wherein the hydrocarbyl group contains from 6 to 24, or from 8 to 24, or from 10 to 20 carbon atoms, typically in the form of a salt.

In one embodiment, the anionic surfactant may include sulfosuccinates, sarcosines, glutamates.

An example of sarcosine is sodium lauroyl sarcosinate.

For example, the sulfosuccinate may include disodium lauryl sulfosuccinate.

An example of glutamate is sodium cocoyl glutamate.

In one embodiment, the anionic surfactant comprises a fatty acid or a fatty acid salt.

The fatty acid or fatty acid salt may be a C8-24 fatty acid or fatty acid salt or a mixture thereof. The salt may consist of a fatty acid and an alkali or alkaline earth metal, typically an alkali metal. The alkali metal may for example comprise sodium or potassium, typically sodium.

The C8-20 fatty acid can have 10 to 20, or 12 to 18 carbon atoms.

The fatty acid or fatty acid salt may be saturated or unsaturated. When unsaturated, the unsaturation may be mono-or di-unsaturated, i.e., the fatty acid is a mono-or di-unsaturated fatty acid.

The unsaturated fatty acids may contain cis-or trans-double bonds.

In one embodiment, the fatty acid or fatty acid salt is a monounsaturated fatty acid having 12 to 18 carbon atoms and is classified as a monosaturated fatty acid (monosaturated fatty acid).

Examples of fatty acids include stearic acid, ricinoleic acid, oleic acid, elaidic acid (eladic acid), petroselinic acid (pellicinic acid), palmitic acid, erucic acid, behenic acid, lauric acid, myristic acid or linoleic acid (e.g., 9,11-linoleic acid or 9,12-linoleic acid).

In one embodiment, the fatty acid may be selected from oleic acid, elaidic acid or petroselinic acid.

In one embodiment, the fatty acid may be selected from oleic acid or elaidic acid, typically oleic acid.

The fatty acid may be a di-unsaturated fatty acid, such as 9,12 linoleic acid, and the salt is sodium linoleate.

Amphoteric surfactant

In one embodiment, the amphoteric surfactant is present at 0.01 to 1.5 wt.%, or 0.02 to 0.8 wt.%, or 0.05 to 0.5 wt.%.

The amount of amphoteric surfactant may be from 0.015 to 2.25gm, based on area density meter ^-2 Or 0.03 to 1.2gm ^-2 Or 0.075 to 0.75gm ^-2 。

In one embodiment, the amphoteric surfactant is present at 0.05 to 0.4 weight% (or 0.075 to 0.6 gm) ^-2 ) Are present.

The amphoteric surfactant may comprise hydrocarbyl-amphoacetate, alkenyl-amphoacetate, hydrocarbyl-amphodiacetate, alkenyl-amphodiacetate, hydrocarbyl amphopropionate, hydrocarbyl amphodipropionate, or hydrocarbyl amphohydroxypropyl sulfobetaine, wherein the hydrocarbyl and alkenyl groups contain 6 to 24, or 8 to 24, or 10 to 20 carbon atoms. Typically, amphoteric surfactants have a counterion of the alkali metal, such as sodium or ammonium.

Specific examples of amphoteric surfactants include sodium cocoamphoacetate or cocamidopropyl betaine, lauryl betaine, and hydroxysultaine. In one embodiment, the amphoteric surfactant may be sodium cocoamphoacetate.

Chelating agents

The technology disclosed herein comprises a chelating agent as defined herein. The chelating agent may be in the form of a salt comprising a negatively charged ion and a positively charged ion. The positively charged ions may include ammonium, or an alkali metal of group I of the periodic table, such as sodium or potassium.

In various embodiments, the chelating agent may be present at 0.01 to 1 wt.%, or 0.1 to 0.75 wt.%, or 0.1 to 0.5 wt.%.

The amount of chelating agent may be from 0.015 to 1.5gm, based on area densitometer ^-2 Or 0.15 to 1.125gm ^-2 Or 0.15 to 0.75gm ^-2 。

The wound dressings disclosed herein may be impregnated or coated with a chelating agent, and the chelating agent may comprise a hydroxycarboxylic acid ester or amide, acid or salt thereof (such agents include, for example, citrate or citric acid, tartrate or tartaric acid, tartrate or tartrate imide, lactate or lactic acid), maleate or maleic acid, glycolate (glycolate) or glycolic acid (glycolic acid), oxalate or oxalic acid, gluconate (gluconate) or gluconic acid (gluconic acid), phosphates such as orthophosphate, polyphosphate, pyrophosphate, or salts of aminopolycarboxylic acids such as ethylenediaminetetraacetic acid (EDTA), 1,2-bis (o-aminophenoxy) ethane-N, N '-tetraacetic acid (BAPTA), ethyleneglycol-bis (β -aminoethyl ether) -N, N' -tetraacetic acid (EGTA), nitrilotriacetic acid (NTA)), fura-2, indo-1, triaminepentaacetic acid (pentaacetic acid) or sodium poly (aspartic acid), sodium, chlorophyll, or sodium hemoglobin. Amines, such as aminoethylethanolamine, diethylenetriamine, ethylenediamine, triethylenetetramine, tetramethylethylenediamine, macrocyclic polyamines (cyclen) or deferoxamines (deferoxamine).

In one embodiment, the chelating agent may be a salt of EDTA.

The chelating agent may in one embodiment be EDTA, and EDTA is a mixture of di-, tri-or tetra-salts of EDTA. The EDTA salt may be, for example, the disodium salt of EDTA, or the calcium disodium salt of EDTA, or the tetrasodium salt of EDTA. In one embodiment, the salt of EDTA may be a mixture of salts of EDTA. Without being bound by theory, it is believed that EDTA, when present, may be in the form of a binary or ternary salt or quaternary salt, and the particular form of the salt depends on the pH of the wound site.

In one embodiment, EDTA may be added to the composition as tetrasodium ethylenediaminetetraacetate (tetra-sodium EDTA).

In one embodiment, the chelating agent comprises an oxalate salt.

In one embodiment, the chelating agent comprises a hydroxycarboxylic acid ester, salt thereof, or amide. When the chelant comprises a salt of a hydroxycarboxylic acid, the salt may be a citrate salt, for example mono-or di-or tri-potassium citrate, or mono-or di-or tri-sodium citrate.

In one embodiment, the chelant comprises a salt of a hydroxycarboxylic acid, and the salt may be mono-or di-or trisodium citrate, typically trisodium citrate.

In one embodiment, the chelating agent comprises a phosphate. The phosphate may be an orthophosphate, pyrophosphate, tripolyphosphate or a derivatized phosphate. The phosphate is usually in the form of a potassium or sodium salt. Examples of the phosphate include dipotassium hydrogen phosphate (potassium phosphate dibasic), potassium pyrophosphate, trisodium ascorbyl phosphate (tri-sodium ascorbyl phosphate), and sodium tripolyphosphate. An example of a derivatized phosphate is sodium ascorbyl phosphate (sodium ascorbyl phosphate).

In one embodiment, the composition may be impregnated or coated in a wound dressing or debridement tool, which may comprise:

the chelating agent is present at 0.01 to 1 wt% (or 0.015 to 1.5 gm) ^-2 ) Exist of a step of,

anionic surfactant at 0.05 to 1.5 wt% (or 0.075 to 2.25 gm) ^-2 ) Exist, and

the amphoteric surfactant is present in an amount of 0.01 to 1.5 wt% (or 0.015 to 2.25 gm) ^-2 ) Are present.

the chelating agent is present at 0.1 to 0.75 wt% (or 0.15 to 1.125 gm) ^-2 ) Exist of,

the anionic surfactant is present in an amount of 0.1 to 1 wt.% (or 0.15 to 1.5 gm) ^-2 ) Exist, and

the amphoteric surfactant is present in an amount of 0.02 to 0.8 wt.% (or 0.03 to 1.2 gm) ^-2 ) Are present.

the chelating agent is present at 0.1 to 0.5 wt% (or 0.15 to 0.75 gm) ^-2 ) Exist of,

the anionic surfactant is present in an amount of 0.1 to 0.5 wt% (0.15 to 0.75 gm) ^-2 ) Exist, and

the amphoteric surfactant is present in an amount of 0.05 to 0.5 wt% (or 0.075 to 0.75 gm) ^-2 ) Are present.

In one embodiment, the composition may be impregnated or coated in a wound dressing or debridement tool comprising:

the chelating agent is present at 0.1 to 0.5 wt% (or 0.15 to 1.5 gm) ^-2 ) Exist of,

the anionic surfactant is present in an amount of 0.1 to 0.5 wt% (or 0.15 to 1.5 gm) ^-2 ) Exist, and

the amphoteric surfactant is present in an amount of 0.05 to 0.4 wt% (or 0.075 to 0.6 gm) ^-2 ) Are present.

In one embodiment, the composition may be impregnated or coated in the wound dressing or debridement tool disclosed above, which may comprise:

the amphoteric surfactant may be selected from the group consisting of alkyl-amphoacetates, alkenyl-amphoacetates, alkyl amphopropionates, alkyl amphodipropionates, or alkyl amphohydroxypropyl sulfobetaines, wherein the alkyl group contains from 6 to 24, or from 8 to 24 carbon atoms;

the anionic surfactant may be selected from fatty acids or fatty acid salts, sodium alkyl sulphate, ammonium alkyl sulphate, alkyl sulphosuccinates, alkyl sarcosinates and alkyl isethionates and alkyl taurates; and

the chelating agent may be selected from hydroxy carboxylic acid esters or amides, acids or salts thereof (which agents include, for example, citrate, tartrate or tartrate imides, lactate, lactic or glycolic acid or glycolate salts), oxalate, gluconic acid, gluconate, phosphate or salts of ethylenediaminetetraacetic acid (EDTA).

the amphoteric surfactant may be selected from the group consisting of alkyl-amphoacetates, alkenyl-amphoacetates, alkyl-amphodiacetates, alkenyl-amphodiacetates, alkyl-amphopropionates, alkyl-amphodipropionates, or alkyl-amphohydroxypropyl sulfobetaines, wherein the alkyl group contains from 6 to 24, or from 8 to 24 carbon atoms;

the anionic surfactant may be selected from fatty acids or fatty acid salts, sulfosuccinates, sarcosines or sarcosinates; and

the chelating agent may be selected from salts of oxalate, phosphate, citrate or EDTA.

the chelating agent is a salt of EDTA and is present at 0.01 to 1 wt% (or 0.015 to 1.5 gm) ^-2 ) Exist of,

anionic surfactant in an amount of 0.05 to 1.5 wt% (0.075 to 2.25 gm) ^-2 ) Exist, and

the chelating agent is a salt of EDTA and is present at 0.1 to 0.75 wt% (or 0.15 to 1.125 gm) ^-2 ) Exist of,

the anionic surfactant is present in an amount of 0.1 to 1 wt% (0.15 to 1.5 gm) ^-2 ) Exist, and

the amphoteric surfactant is added in an amount of 0.02 to 0.8 wt% (0.03 to 1.2 gm) ^-2 ) Are present.

the chelating agent is a salt of EDTA and is present at 0.1 to 0.5 wt% (or 0.15 to 0.75 gm) ^-2 ) Exist of,

the anionic surfactant is present in an amount of 0.1 to 0.5 wt.% (or 0.15 to 0.75 gm) ^-2 ) Exist of,

the chelating agent is a salt of EDTA and is present at 0.01 to 1 wt% (0.015 to 1.5 gm) ^-2 ) Exist of,

the anionic surfactant is a fatty acid or fatty acid salt and is present at 0.2 to 1% by weight,

In one embodiment, the composition may be impregnated or coated in a wound dressing or debridement implement, which may comprise:

the anionic surfactant is a fatty acid or fatty acid salt and is present at 0.25 to 0.7 wt%,

the amphoteric surfactant is present in an amount of 0.02 to 0.8 wt% (or 0.03 to 1.2 gm) ^-2 ) Are present.

the chelating agent is a salt of EDTA and is present at 0.1 to 0.5 wt% (or 0.15 to 0.75 gm) ^-2 ) Exist of

The anionic surfactant is a fatty acid or fatty acid salt and is present in an amount of 0.1 to 0.5 wt.% (or 0.15 to 0.75 gm) ^-2 ) Exist of,

In one embodiment, the composition may be impregnated or coated in a wound dressing or debridement tool, which may further comprise a nonionic surfactant. The nonionic surfactant can provide additional stability to the composition impregnated or coated in the wound dressing absorbent layer or debridement tool.

When present, the nonionic surfactant can be present from 0.01 to 0.7 wt%, or from 0.05 to 0.5 wt%, or from 0.1 to 0.3 wt%.

The amount of nonionic surfactant can be from 0.015 to 1.05gm based on area densitometer ^-2 Or 0.075 to 0.75gm ^-2 Or 0.15 to 0.45gm ^-2 。

In one embodiment, the composition may be impregnated or coated in a wound dressing or debridement implement, which may further comprise a nonionic surfactant and the compositions disclosed herein may contain:

the chelating agent is present at 0.01 to 1 wt% (or 0.015 to 1.5 gm) ^-2 ) Exist of,

anionic surfactant in an amount of 0.05 to 1.5 wt% (or 0.075 to 2.25 gm) ^-2 ) Exist of,

the amphoteric surfactant is present in an amount of 0.01 to 1.5 wt% (or 0.015 to 2.25 gm) ^-2 ) Exist, and

the nonionic surfactant can be 0.01 to 0.7 wt% (or 0.015 to 1.05 gm) ^-2 ) Are present.

Nonionic surfactants may include esters of fatty acids, fatty acid amides, fatty acid ethoxylates, fatty acid amide ethoxylates, polyethoxylates, and polyalkyl ethers, polyhydroxy compounds, hydrocarbyl glucosides, and amine oxides. For example, polyoxyethylene fatty acid esters (polyoxyethylene sorbitan fatty acid esters), polyoxyethylene glycol fatty acid esters (polyoxyethylene glycol fatty acid esters), sucrose fatty acid esters (sucrose fatty acid esters), polyoxyethylene hydrogen carbonate castor oil, and polyoxyethylene alkyl ether (polyoxyethylene hydrogenated castor oil) ethers (polyoxyethylene alkyl ethers).

Nonionic surfactants can include Polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, PEG-40stearate (PEG-40 stearate), PEG-100 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 (Beheneth field 20), and cetereth-20 (Beheneth field 20).

In one embodiment, the nonionic surfactant may be a Polysorbate, typically Polysorbate 20.

The wound dressing disclosed herein may comprise at least one layer consisting of foam, fabric or technical textile. For example, the textile may be a non-woven or woven fibrous layer, or a gel-forming fibre (gel-forming fibre) or gauze (gauze).

The gauze may be made of cellulose, such as cotton or viscose.

In one embodiment, the wound dressing absorbent layer is a gel-forming fiber impregnated or coated with a composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant.

In one embodiment, the wound dressing absorbent layer is a gel-forming fiber impregnated or coated with a composition comprising a chelating agent, an amphoteric surfactant, an anionic surfactant, and a nonionic surfactant.

In one embodiment, the disclosed technology relates to the use of a wound dressing for treating a wound, wherein the wound contains a biofilm.

In one embodiment, the disclosed technology relates to the use of a wound dressing for removing slough, necrosis or other foreign material from a wound.

In one embodiment, the disclosed technology relates to the use of a wound dressing for preventing or minimizing slough accumulation in a wound by contacting the wound dressing disclosed herein with the wound.

In one embodiment, the disclosed technology relates to a method of preventing or minimizing slough accumulation in a wound by contacting a wound dressing disclosed herein with the wound. In one embodiment, the wound dressing does not provide a chemically induced antimicrobial effect.

In another embodiment, the disclosed technology relates to a composition comprising a chelating agent, an amphoteric surfactant, and an anionic surfactant for treating a wound, such as a chronic wound, an acute wound, a burn, a wound comprising a bacterial biofilm, or a wound comprising slough. The composition may be as described above for any other embodiment of the invention.

Detailed description of the disclosure

The expression "wound" as used herein may include damage to living tissue and may be caused by cutting, hammering or other impact, friction, pressure, heat or chemicals; usually the skin is cut or broken. Wounds can be generally described as chronic or acute. Acute wounds may result from surgery or trauma. Often, when less severe and the victim is otherwise healthy, the wound goes through a clearly defined healing stage within a predicted time frame. Chronic wounds begin with acute wounds. Acute wounds can become chronic when they do not follow the normal healing pathway such that the recovery period is extended. It is believed that the transition from acute to chronic wounds may be due to an inadequate immune response, such as: patients are immunocompromised, have inadequate wound perfusion, or are highly contaminated.

Chronic wounds may include, for example: venous ulcers (such as those occurring in the legs due to venous insufficiency) which cause most chronic wounds and affect mainly the elderly; diabetic ulcers (e.g., foot or ankle ulcers); arterial ulcers (due to peripheral arterial disease); and stress damage caused by inactivity.

Wounds may also include deep tissue damage. Deep tissue damage is a term proposed by National Pressure Ulcer Advisory Panel (NPUAP) to describe a unique form of Pressure Ulcer. Clinicians have described these ulcers for many years with terms such as purple pressure ulcers (purple pressure ulcers), ulcers that may worsen and bruises on the bony prominences.

The disclosed technology relates to the subject matter as defined above.

The term "slough" is known to the skilled person and may be defined as a dead tissue layer or mass separated from surrounding living tissue, or tissue adhering to a wound but capable of being removed as in a wound, ulcer or inflammation.

Wound dressing

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

In one embodiment, the wound dressing may be buffered to have a pH of 4-10 or 5-8 or 5.5-6.5.

The wound dressing may be comprised of one or more layers selected from the group consisting of an outer cover layer, an absorbent layer, gel-forming fibers, an adhesive layer, a wound contact layer, a distribution layer, and combinations thereof.

In some embodiments, the wound dressing comprises one or more absorbent layers. The absorbent layer may be a foam or a structure derived from a superabsorbent polymer material. If foam is used, the foam may also act as a distribution layer.

In some embodiments, the wound dressing comprises an outer cover layer and one or more absorbent layers associated with the gel-forming fibers. The gel-forming fibres are typically in direct contact with the wound and therefore no additional wound contact layer is required.

Gel-forming fibers refer to absorbent fibers that become slippery or gelatinous upon absorption of wound exudate. The gel-forming fibers may be of the type that maintain their structural integrity upon absorption of exudate, or may be of the type that lose their fibrous form and become an amorphous or unstructured gel. Gel-forming fibres are typically sodium carboxymethylcellulose fibres, chemically modified cellulose fibres, alkyl sulphonate modified cellulose 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, and non-cellulosic synthetic fibres, such as polyvinyl alcohol and polyacrylates.

In one embodiment, the gel-forming fibers may be chemically modified carboxymethyl cellulose fibers, typically sodium carboxymethyl cellulose fibers. In a particular embodiment, the absorbent layer is a gel-forming fiber and the dressing is free of an additional dressing layer.

The gel-forming fibres are typically chemically modified cellulosic fibres in the form of a fabric, in particular carboxymethylated cellulosic fibres as described in PCT WO 00/01425. Sodium carboxymethyl cellulose fibers typically have a degree of substitution of at least 0.05 carboxymethyl groups per glucose unit. Gel-forming fibers typically have an absorbency of at least 2 grams (or at least 8 grams or at least 10 grams) of 0.9% saline solution per gram of fiber (as measured by BS EN 13726-1 (2002) "Test methods for primary wind forces", section 3.2 "Free swing absorbent capacity"). Carboxymethylated cellulosic fabrics typically have a degree of substitution (as defined in WO 00/01425) of between 0.12 and 0.35, more typically between 0.20 and 0.30, such that the absorbency (absorbency) of the fabric made therefrom is increased compared to unmodified cellulose. Particularly useful fabrics have an absorbency of 10g/g to 30g/g of an isotonic aqueous solution (isotonic aqueous solution) as measured by the method described in BS EN 13726-1 (2002).

Cellulosic fabrics are generally composed of only cellulosic fibres, but may contain a proportion of textile fibres (textile fibres) or gel-forming fibres. Such textile fibres may be, for example, cellulose fibres of known kind and may comprise continuous filament yarns and/or staple fibres.

The absorbent layer may be in direct contact with the wound or comprise a wound contact layer between the wound and the absorbent layer. The wound contact layer is capable of absorbing exudate from the wound and transferring it to the absorbent layer.

The wound contact layer in one embodiment comprises gel-forming fibres or silicone gel.

The outer cover of the dressing is a bacterial and viral barrier that generally prevents liquid ingress but allows moisture vapor to pass through.

In one embodiment, the absorbent layer may be a superabsorbent. The superabsorbent may be a fibrous polymer or a nonwoven material.

The superabsorbent may be a polyacrylate or a starch polymer.

In one embodiment, the absorbent layer may be a foam. The foam may have an open and/or closed cell structure. The foam may be derived from polyurethane, polyvinyl alcohol, collagen, chitosan (chitosan). Typically, the foam may be a polyurethane foam.

The wound dressings disclosed herein may be prepared by a method comprising applying a composition comprising a chelating agent, an amphoteric surfactant, as disclosed herein, to an absorbent layer.

Incorporation of the disclosed techniques into a wound dressing or similar wound treatment device (e.g., debridement tool) may be accomplished by addition to the materials comprising the device or by addition to the finished device.

For example, in the case of a device composed partially or entirely of fibres, the technique may:

addition to the spin dope (liquid for spinning [ extruded ] fibers)

Coextruding in a Hot melt Process

Washing into the fibres by a soaking process

By passing it through a bath containing a liquid or solution form { in which the solute can be removed by drying (known in the art-for example by forced ventilation (or any other gas-in particular nitrogen if a flammable solvent is involved) } or this technique as a molten liquid }or

In the hot-melt ink-jet process in liquid form or from solution { in which the solute can be removed by drying (known in the art-for example by forced ventilation (or any other gas-in particular nitrogen if flammable solvents are involved) } or sprayed onto the shaped fibers as a molten liquid

Added as a powder coating where adhesion can be promoted by electrostatic effects or by improving the adhesive properties of the receiving fiber (e.g. by partial hydration with moisture or by pre-treating the fiber with a viscous liquid such as an alcohol (e.g. hexanol), a polyol (e.g. propane-1,2-diol or glycerol), a hydrophilic hydrocarbon (e.g. poly (ethylene oxide)), or by the addition sequence of the invention itself (e.g. a liquid surfactant such as a liquid fatty acid or fatty acid salt or a liquid fatty acid that will form a salt in situ).

Alternatively, where the device is preformed, for example as a fabric or foam, the technique may be added by a similar washing, coating, spraying or powder coating process.

Alternatively, the technology may be added by suspending it in a non-solvent and passing it through the apparatus to mechanically trap suspended technology (i.e. actively added by filtration of the technology);

or as an ink or pigment by a printing process, for example a screen printing process, wherein the addition can be closely controlled by using a screen. The footprint may be continuous, for example by flow-coating, or more preferably as a discontinuous coating (regular or random patterning), as it has less impact on device porosity/breathability, flexibility and ability to conform to the complex topography of the wound bed, as well as on the macro (physiological) and micro (cellular) levels.

Addition as separate layers:

added directly to the wound device, e.g. as a gel coat, by e.g. knife over roll (knife-over-roll) or gravure coating techniques

Or cast into a film by similar coating techniques and then adhered to the wound device by, for example, moisturizing or tackifying the device or film by the addition of an adhesive.

While the invention has been explained in relation to its preferred embodiments, it is to be understood that various modifications thereof will become apparent to those skilled in the art upon reading the specification. It is, therefore, to be understood that the invention disclosed herein is intended to cover such modifications as fall within the scope of the appended claims.

Example 1

The following examples were prepared and evaluated using a simulated wound matrix composition. Preparing a wound matrix to contain:

simulated wound matrices were cross-linked with 1.5% w/w calcium chloride onto a solid phase screening system (96-peg microtiter plate cover) for 18 hours. The pegs were dipped into a simulated wound matrix and immediately transferred to a calcium chloride bath to effect cross-linking. Solutions of the test materials were prepared in 96-well microtiter plates at 1%w/w. After crosslinking, the pegs were inserted into the wells and incubated at 37 ℃ for 1 hour. The efficacy is characterized by the change in color of the test solutions caused by the destruction of the stained material and quantified by reading the absorbance at 595nm of each solution. The results are given relative to 1%w/w aqueous Benzethonium chloride (Benzenthonium chloride). Benzethonium chloride is a comparative example and is disclosed in WO2012/136968 as part of the invention disclosed therein.

AKZO Nobel published values, using modified Davies HLB groups numbers (Cosmetic Emulsions,

Sikora,ISBN/ISSN:978-83-65991-50-8)

with pH and _P CO ₂ to determine calcium salt solubility, simulating a changing gastrointestinal environment. Goss SL et al Journal of Pharmacy and Pharmacology 59;11;1485-1492.

Also based on commercially available products (

Ag + Extra) containing 0.39% w/w disodium ethylenediaminetetraacetate and 0.135% w/w benzethonium chloride. The effect of this composition is 30% lower than the comparative example with 1% benzethonium chloride, outlined above.

Interpretation of the results

The HLB value is predictive of the detergency efficacy of certain surfactants and is often used to guide selection, with higher HLB values giving greater predicted detergency. 1%w/w surfactants (with published HLB values) do not appear to be capable of disrupting the wound matrix of a mock testThe phases are related. Sodium Lauryl Sulfate (SLS) is often used as a benchmark for high detergency, but is also considered too irritating (hash) for conventional use in personal care products. Disodium lauryl sulfosuccinate is considered a milder alternative to SLS. Sodium oleate, the basis of traditional soap bars, is also recognized as a cleanser that is inferior to SLS, but both sodium oleate and disodium lauryl sulfosuccinate are orders of magnitude more effective in destroying the simulated wound matrix than SLS. Similarly, sodium oleate and disodium lauryl sulfosuccinate are more potent than benzalkonium chloride, cocamidopropyl betaine, and Poloxamer ^TM 188 (these are all commonly used in liquid wound cleansing products) by an order of magnitude higher. Therefore, the choice of surfactant cannot be predicted by the expected detergency or by the choice of the usual components.

The simulated test wound matrix was cross-linked and fixed to the test surface by treatment with calcium chloride. It therefore appears obvious that this fixation can be reversed by applying compounds that compete for calcium and remove it, for example by precipitation as a poorly soluble salt. It seems reasonable to believe that the lack of solubility of the calcium chelator can be used as a predictor of the ability of the agent to remove calcium from the matrix and therefore the higher potential for matrix destruction. Calcium citrate (pH 7.5) is significantly more soluble than calcium oxalate at the same pH, but citrate shows greater efficacy in a simulated test wound matrix than an equivalent w/w of oxalate. Furthermore, while lowering the pH of the citrate system to that of citric acid does both increase the solubility of the calcium salt and reduce matrix damage as predicted, it is still more effective than sodium dihydrogen phosphate at higher pH with less soluble calcium salts. Therefore, the choice of chelating agent cannot be predicted by calcium salt solubility or pH effect.

Example 2

Investigating the combined effect of the surfactant and the chelating agent when present as a coating on a wound dressing which gels in the presence of water

Extra，ConvaTec PLC]. Use of dressing without surfactant or chelating agent as control。

The test model from example 1 was adjusted to accommodate the solid test material. To achieve this, simulated wound matrix was cast onto cellulose acetate sheet using a film applicator (1.5 mm wet thickness) and immersed face down into 1.5% w/w calcium chloride for 24 hours. Test dressings were cut to 2cm ² Hydrated with 1 ml of test solution a (BS EN 13726-1. The efficacy is characterized by the change in color of the dressing caused by absorption of the liquefied test matrix containing the crystal violet dye. The dissolved fraction was quantified by extracting the crystal violet dye from the dressing by adding 2 ml 33% v/v acetic acid and extracting on a roller mixer for 30 minutes. The absorbance of each solution was read at 595 nm.

Results in% w/w:

results based on weight per unit area:

interpretation of the results

The test substances are described as weight percent of dry dressing. Since the dressing in this example absorbs a large amount of aqueous liquid (in this case about 23 g/g) and moisture facilitates the function of the test substance, the dilution effect must be properly considered. 1.0% w/w in this example is similar to the 0.043% solution tested in example 1. Therefore, a great reduction in effect may be expected. However, a significant improvement was achieved over both the control and the cationic surfactant/chelator control.

No performance improvement was observed when increasing the concentration of the test substances, alone or in combination.

Example 3

As with any medical treatment, patient safety is paramount, and where skin lesions there is always a risk that components may remove essential lipids from the tissue, absorb into local tissues or into the blood and lymphatic circulation. To reduce risk, it is recommended to select the safest candidate and minimize exposure to any soluble or absorbable material, most easily by minimizing the amount and/or concentration applied. Anionic surfactants are considered irritating due to their relatively high detergency, while amphoteric surfactants are generally less effective but have better skin compatibility. Therefore, three-component systems (three-component systems) consisting of one chelating agent and two surfactants on gel dressings were investigated. The test is as described in example 2.

Results in% w/w:

results based on weight per unit area:

interpretation of the results

A linear relationship between component concentration and activity could not be determined when an amphoteric surfactant (sodium cocoamphoacetate) was added which seemingly reduced activity (compare examples 3B and 2C). However, a synergistic combination was found (example 3D) in which the addition of amphoteric surfactant enables a significant reduction in anionic surfactant and chelating agent, while still achieving significant performance improvements compared to the base dressing.

Unless expressly stated otherwise or otherwise understood in the context of usage, conditional words such as "may" or "may" are generally intended to convey that certain embodiments include certain features, elements, and/or steps, while other embodiments do not. Thus, such conditional language is not generally intended to imply that features, elements, and/or steps are in any way required for one or more embodiments or that one or more embodiments necessarily include logic (with or without user input or prompting) to determine whether such features, elements, and/or steps are included or are to be performed in any particular embodiment.

In this specification, the use of the singular includes the plural unless the context clearly dictates otherwise. In this application, the use of "or" means "and/or" unless stated otherwise. Furthermore, the use of the term "including" as well as other forms, such as "include", "include" and "included", is not limiting.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter belongs. It is to be understood that both the foregoing summary of the disclosure and the following examples are exemplary and explanatory only and are not restrictive of any subject matter claimed.

Each of the documents mentioned above is incorporated herein by reference. Except in the examples, or where otherwise explicitly indicated, all numerical quantities in this description specifying amounts of material, device dimensions, and the like, are to be understood as modified by the word "about".

Unless otherwise indicated, each chemical or composition referred to herein should be interpreted as being a commercial grade material which may contain the isomers, by-products, derivatives, and other such materials which are normally understood to be present in the commercial grade.

Each of the documents mentioned above is incorporated herein by reference. Except in the examples, or where otherwise explicitly indicated, all numerical quantities in this description specifying amounts of material, reaction conditions, molecular weights, number of carbon atoms, and the like, are to be understood as modified by the word "about".

The term "consisting essentially of", as used herein, is allowed to include materials that do not materially affect the basic and novel characteristics of the compositions involved.

It is to be understood that at least some of the figures and descriptions of the present disclosure have been simplified to focus on elements that are relevant for a clear understanding of the present disclosure, while eliminating, for purposes of clarity, other elements that those of ordinary skill in the art will recognize may also be desirable. Because such elements are well known to those skilled in the art, and because they do not necessarily facilitate a better understanding of the present disclosure, a description of such elements is not provided herein.

Claims

1. A wound dressing or debridement implement comprising an absorbent layer impregnated or coated with a composition comprising a chelating agent, an amphoteric surfactant and an anionic surfactant.

2. The wound dressing or debridement implement of claim 1 wherein anionic surfactant is present at 0.05 to 1.5 wt.%, or 0.1 to 1 wt.%, or 0.1 to 0.5 wt.%.

3. The wound dressing or debridement implement of claim 1 or claim 2 wherein the anionic surfactant is selected from fatty acids or fatty acid salts, sulfates, sulfosuccinates, sarcosines, sarcosinates, isethionates, glutamates or taurates.

4. The wound dressing or debridement implement of any one of the preceding claims, wherein the amphoteric surfactant is present at 0.01 to 1.5 wt.%, or 0.02 to 0.8 wt.%, or 0.05 to 0.5 wt.%.

5. The wound dressing or debridement implement according to any one of the preceding claims, wherein the amphoteric surfactant is selected from the group consisting of alkyl-amphoacetates, alkenyl-amphoacetates, alkyl-amphodiacetates, alkenyl-amphodiacetates, alkyl amphopropionates, alkyl amphodipropionates, or alkyl amphohydroxypropyl sulfobetaines, wherein the alkyl and alkenyl groups contain from 6 to 24, or from 8 to 24 carbon atoms.

6. The wound dressing or debridement implement of any one of the preceding claims, wherein the chelating agent is present at 0.01 to 1 wt.%, or 0.1 to 0.75 wt.%, or 0.1 to 0.5 wt.%.

7. The wound dressing or debridement implement of any one of the preceding claims wherein the chelating agent is selected from a hydroxycarboxylic acid ester or an amide, acid or salt thereof (e.g. citrate, tartrate or tartrimide, gluconic acid, gluconate, lactate, lactic acid, glycolic acid or glycolate), oxalate, phosphate or a salt of ethylenediaminetetraacetic acid (EDTA).

8. The wound dressing or debridement implement of any of the preceding claims, wherein the composition is impregnated or coated in a wound dressing comprising:

the chelating agent is present at 0.01 to 1 wt%,

the anionic surfactant is present at 0.05 to 1.5 wt%,

the amphoteric surfactant is present at 0.01 to 1.5% by weight.

9. The wound dressing or debridement implement of any of the preceding claims, wherein the composition is impregnated or coated in a wound dressing comprising:

the chelating agent is present at 0.1 to 0.75 wt%,

the anionic surfactant is present at 0.1 to 1% by weight, or

The amphoteric surfactant is present at 0.02 to 0.8 wt%.

10. The wound dressing or debridement implement of any of the preceding claims, wherein the composition is impregnated or coated in a wound dressing comprising:

the chelating agent is present at 0.1 to 0.5 wt%,

the anionic surfactant is present at 0.1 to 0.5 wt%

The amphoteric surfactant is present at 0.05 to 0.5 wt%.

11. The wound dressing or debridement implement of any one of the preceding claims, wherein the composition impregnated or coated in the wound dressing or debridement implement comprises:

12. The wound dressing or debridement implement of any one of the preceding claims, wherein the composition impregnated or coated in the wound dressing or debridement implement comprises:

the amphoteric surfactant is selected from the group consisting of alkyl-amphoacetates, alkenyl-amphoacetates, alkyl-amphopropionates, alkyl-amphodipropionates, or alkyl-amphohydroxypropyl sulfobetaines, wherein the alkyl group contains 6 to 24, or 8 to 24 carbon atoms;

the anionic surfactant is selected from fatty acids or fatty acid salts, sulfates, sulfosuccinates, sarcosines, sarcosinates, isethionates, taurates and glutamates; and

the chelating agent is selected from a hydroxycarboxylic acid ester or an amide, acid or salt thereof (e.g. citrate, tartrate or tartrimide, gluconic acid, gluconate, lactate, lactic acid, glycolic acid or glycolate), oxalate, phosphate or a salt of ethylenediaminetetraacetic acid (EDTA).

13. The wound dressing or debridement implement of any of the preceding claims, wherein the composition is impregnated or coated in a wound dressing comprising:

the amphoteric surfactant is selected from the group consisting of alkyl-amphoacetates, alkenyl-amphoacetates, alkyl-amphopropionates, alkyl-amphodipropionates, or alkyl-amphohydroxypropyl sulfobetaines, wherein the alkyl group contains from 6 to 24, or from 8 to 24 carbon atoms;

the anionic surfactant is selected from fatty acid or fatty acid salt, glutamate, sulfosuccinate, sarcosine or sarcosinate; and

the chelating agent is selected from oxalate, citrate, phosphate or a salt of EDTA.

14. The wound dressing or debridement implement of any one of the preceding claims, wherein the composition is impregnable or coatable in a wound dressing, further comprising: a nonionic surfactant.

15. The wound dressing of claim 14, wherein the non-ionic surfactant is present at 0.01 to 0.7 wt% (or 0.015 to 1.05 gm) ^-2 ) Or 0.05 to 0.5 wt% (or 0.075 to 0.75 gm) ^-2 ) Or 0.1 to 0.3 wt% (or 0.15 to 0.45 gm) ^-2 ) Are present.

16. The wound dressing or debridement implement of any one of the preceding claims, wherein the composition is impregnable or coatable in a wound dressing or debridement implement comprising:

17. The wound dressing or debridement implement according to any one of the preceding claims 14 to 16, wherein the non-ionic surfactant is selected from the group consisting of polyoxyethylene fatty acid esters (polyoxyethylene sorbitan fatty acid esters), polyoxyethylene glycol fatty acid esters (polyoxyethylene glycol fatty acid esters), sucrose fatty acid esters (sucrose fatty acid esters), polyoxyethylene hydrogen carbonate castor oil and polyoxyethylene alkyl ethers (polyoxyethylene hydrogenated castor oil) ethers (polyoxyethylene alkyl ethers).

18. The wound dressing or debridement implement of any of the preceding claims, wherein the absorbent layer impregnated or coated with the composition comprises at least one layer consisting of foam, absorbent (typically superabsorbent) or gel-forming fibers.

19. The wound dressing or debridement implement of any one of the preceding claims, wherein the wound dressing absorbent layer is a gel-forming fiber.

20. The wound dressing or debridement implement of any of the preceding claims, wherein the wound dressing absorbent layer is a gel-forming fiber and the fiber is a chemically modified carboxymethyl cellulose fiber, typically sodium carboxymethyl cellulose fiber.

21. A wound dressing according to any one of claims 1 to 20 which is a wound dressing.

22. A debridement tool according to any one of claims 1-20.

23. Use of a wound dressing for preventing or minimizing slough accumulation in a wound by contacting the wound dressing or debridement implement of any one of the preceding claims 1 to 22 with the wound, wherein the wound is a chronic wound, an acute wound or a burn.

24. Use of a wound dressing or debridement implement according to any one of the preceding claims 1 to 23 for the treatment of chronic wounds, acute wounds or burns, wherein the chronic wounds, acute wounds or burns have a bacterial biofilm.

25. Use of a wound dressing or debridement tool according to any one of the preceding claims 1 to 24 for wound sloughing (de-slough a wind), wherein the wound is a chronic wound, an acute wound or a burn.

26. A composition comprising a chelating agent, an amphoteric surfactant and an anionic surfactant for use in treating a wound, such as a chronic wound, an acute wound, a burn, a wound comprising a bacterial biofilm, or a wound comprising slough.

27. The composition for use according to claim 26, wherein the composition is as described in any one of claims 1 to 22.