GB2577298A

GB2577298A - Wound dressing

Info

Publication number: GB2577298A
Application number: GB1815373.4A
Authority: GB
Inventors: Zuberi Tania; Zuberi Sheena
Original assignee: Sumitomo Chemical Co Ltd
Current assignee: Sumitomo Chemical Co Ltd
Priority date: 2018-09-21
Filing date: 2018-09-21
Publication date: 2020-03-25
Also published as: GB201815373D0

Abstract

An article 1 for dressing a wound has a substrate 2, a compound-releasing device 3 and a hydrogel layer 4, wherein the hydrogel is cross-linked 5 to the substrate. Preferably, the compound-releasing device is not cross-linked to the substrate in order to support the generation of a reactive oxygen species such as hydrogen peroxide by the compound-releasing device. The hydrogel may be secured to the polymeric substrate by a biocompatible UV-activated cross-linking compound such as benzophenone. The compound-releasing device may contain a power source, two electrodes and a conjugated polymer such as PEDOT:PSS. Preferably, the layer of hydrogel is a polyurethane hydrogel and surrounds the compound-releasing device.

Description

Field

The present disclosure relates to articles for dressing wounds and methods of their 5 manufacture.

Background

The efficient healing of wounds is a desirable objective to maintain quality of life and prevent morbidity. Acute and chronic wounds heal at different rates. A chronic wound ro is a wound that does not heal in an orderly set of stages and in a predictable amount of time; wounds that do not heal within three months are often considered chronic. Moreover, chronic wounds often seem to be detained in one or more of the phases of wound healing. For example, chronic wounds often remain in the inflammatory stage for too long. Additionally, chronic wounds appear to have lost the balance between the production and degradation of molecules such as collagen and so degradation plays too large a role. In contrast, acute wounds appear to have maintained this balance and wound healing proceeds in a predictable fashion.

To make matters worse, chronic wounds (e.g. diabetic ulcers and bed sores) are typically infected and frequently exhibit antibiotic resistance, which makes them costly to treat. Frustratingly, chronic wounds may never heal or may take years to do so. Further, these wounds can cause patients severe emotional and physical stress and can lead to amputation. Chronic wounds therefore are an enormous, and growing, economic and health problem.

Wound healing may be aided by treatment with a suitable therapeutic compound, and wound dressings may therefore comprise a compound-releasing device. For example, such a compound-releasing device maybe capable of releasing reactive oxygen species (ROS), such as hydrogen peroxide (11202). ROS such as hydrogen peroxide can aid 3o several aspects of wound healing, including regulating the formation of new blood vessels (angiogenesis), destroying pathogens (phagocytosis), and recruiting lymphoid cells to the wound site for tissue repair and remodelling.

Wound dressings can comprise hydrogels. A wound-facing hydrogel can aid wound healing, for example by promoting a moist environment at the wound site.

Summary

The present disclosure enables a compound-releasing device to be integrated into a wound dressing together with a hydrogel. Accordingly, a first aspect of the present disclosure provides an article for dressing a wound, the article comprising a substrate, a compound-releasing device and a hydrogel layer, wherein the hydrogel is cross-linked to the substrate.

A hydrated hydrogel is a wet, gel-like material which typically cannot be laminated onto a substrate of a wound dressing using conventional adhesives due to the differing rcr surface energies of the two materials. It may be possible to adhere a hydrogel layer and a compound-releasing device onto a substrate for a wound dressing by forming chemical cross-links between the substrate and the hydrogel, and between the substrate and the compound releasing device. However, it has surprisingly been found that the function of the compound-releasing device can be improved by keeping the interface between the compound releasing device and the substrate free of cross linking.

Accordingly, in some embodiments of the first aspect of present disclosure, the hydrogel is cross-linked to the substrate and the compound-releasing device is not cross-linked to the substrate.

In a second aspect, the present disclosure provides a method of manufacturing an article for dressing a wound according to the first aspect, the method comprising providing a substrate, providing a compound-releasing device on the substrate, and cross-linking a hydrogel to the substrate.

In some embodiments of the second aspect of the present disclosure, the hydrogel is 25 adhered to the substrate by cross-linking, and the compound-releasing device is not adhered to the substrate by cross linking.

Brief Description of the Drawings

Figure 1 is a schematic side view of an article according to one embodiment of the first

aspect of the present disclosure.

Figure 2 is a schematic side view of an article according to another embodiment of the first aspect of the present disclosure.

Detailed Description

A first aspect of the present disclosure provides an article for dressing a wound, the article comprising a substrate, a compound-releasing device and a hydrogel layer, wherein the hydrogel is cross-linked to the substrate.

As used herein, the term hydrogel refers to a hydrophilic cross-linked polymeric network that is capable of absorbing water. The term hydrogel, as used herein, encompasses hydrated hydrogels (in which absorbed water is present within the hydrogel polymeric network), and dehydrated hydrogels (in which absorbed water is substantially not present, e.g. not present, within the hydrogel polymeric network).

Yo In some embodiments of the first aspect of the present disclosure, the hydrogel may be suitable for use in a wound dressing. Such hydrogels will be apparent to a skilled person. In non-limiting examples a hydrogel suitable for use in a wound dressing may comprise agarose, alginate, an acrylamide-alginate copolymer, an acrylamide-chitosan copolymer, polyurethane, or poly(N-methyl acryiamide).

As used herein, the term "cross-linked" refers to a polymeric system in which polymer chains within the polymeric system are linked to each other via cross-links, e.g. via chemical bonds, which may be ionic or covalent, or via covalently bound chemical linker moieties. As indicated above, a hydrogel is itself a cross-linked chemical system, indicating that cross-links exist between polymeric chains of the hydrogel. In the first aspect of the present disclosure, the hydrogel is cross-linked to the substrate, indicating that cross-links exist between polymeric chains of the hydrogel and polymeric chains of the substrate. The cross-links between the hydrogel and the substrate are therefore distinct from the internal cross-links within the hydrogel.

In some embodiments of the present disclosure the cross-links between the hydrogel and the substrate may be obtainable by using a UV-activated cross-linking compound. Non-limiting examples of UV-activated cross-linking compounds include benzophenone, acetophenone, riboflavin, glucose, and derivatives thereof, or any combination thereof. Cross-links which are obtainable by using a UV-activated cross-linking compound may comprise a covalently-bound chemical linker moiety which is derived from the UV-activated cross linker compound.

In some embodiments the cross-links between the hydrogel and the substrate may be obtainable by using benzophenone or a derivative thereof as a UV-activated cross-linking compound. A derivative of benzophenone may be a small molecule having a molecular weight of soo gmol or less. For example, a cross-link obtainable by using a benzophenone compound or a derivative thereof may comprise a benzophenone or diphenylmethanol moiety pendant on the backbone of the polymer.

In some embodiments, a cross-link obtainable by using a benzophenone compound or derivative thereof may comprise the moiety, in which each "*" is a direct link (e.g. a chemical bond) to a polymer chain, or an indirect link (e.g. via a further covalently bound linker moiety) to a polymer chain. ;In some embodiments of the present disclosure the cross-links between the hydrogel so and the substrate may be obtainable by using a biocompatible cross-linking compound. Non-limiting examples of biocompatible cross-linking compounds include benzophenone, acetophenone, riboflavin, glucose, and derivatives thereof, or any combination thereof. Cross-links which are obtainable by using a biocompatible cross-linking compound may comprise a covalently-bound chemical linker moiety which is derived from the biocompatible cross linker compound. For example, a cross-link obtainable by using a benzopheone compound may comprise the moiety in which each "*" is a direct link (e.g. a chemical bond) to a polymer chain, or an indirect link (e.g. via a further covalently bound linker moiety) to a polymer chain.

In some embodiments of the present disclosure the cross-links between the hydrogel and the substrate may be present in discrete and/or discontinuous locations. For example, the interface between the hydrogel and the substrate may comprise locations in which cross-linking is present between the hydrogel and the substrate, and may further comprise locations in which there is no cross-linking between the hydrogel and the substrate.

In some embodiments of the present disclosure the article may be configured to have a wound-facing surface and an air-facing surface. The wound-facing surface may be opposite the air-facing surface. The wound-facing surface may be suitable for contacting a patient's body when the article is in use. The air-facing surface may be suitable for exposure to the atmosphere when the article is in use.

In some embodiments of the present disclosure the hydrogel is located at the woundfaci ng surface of the article.

In some embodiments of the present disclosure the substrate is located at the air-facing surface of the article.

Tn some embodiments of the present disclosure the compound-releasing device is located between the hydrogel and the substrate.

In some embodiments of the present disclosure the substrate may have first and second opposite faces. In some embodiments, the article of the present disclosure may be configured so that the second face of the substrate corresponds to the air-facing surface of the article. In some embodiments, the article of the present disclosure may be configured so that the interface between the hydrogel and the substrate is located at the first face of the substrate. In some embodiments, the article of the present disclosure may be configured so that the interface between the compound-releasing device and the substrate is located at the first face of the substrate.

Tn some embodiments, the interface between the compound-releasing device and the substrate maybe located at a central part of the first face of the substrate.

Tn some embodiments, the interface between the hydrogel and the substrate may be located at a peripheral part of the first face of the substrate.

In some embodiments, the interface between the compound-releasing device and the substrate may be located at a central part of the first face of the substrate and the interface between the hydrogel and the substrate may be located at a peripheral part of the first face of the substrate, wherein the peripheral part of the first surface of the substrate surrounds the central part of the first face of the substrate.

Tn some embodiments of the present disclosure the substrate may comprise a polymeric material suitable for use in a wound dressing. Such polymeric materials will be apparent to a skilled person. Non-limiting examples of a polymeric material suitable for use in a wound dressing include polyamide, polyurethane, polystyrene, polyvinyl chloride, polypropylene, poly-ethylene, polyethylene napthalate (PEN), poly(ethylene-vinyl acetate) and polyethylene terephthalate (PET). The polymeric material suitable for use in a wound dressing is preferably polyurethane.

In some embodiments of the present disclosure the substrate may be flexible. Suitable flexible materials will be apparent to a skilled person. Non-limiting examples of a suitable flexible material include polyamide, polyurethane, polystyrene, polyvinyl chloride, polypropylene, polyethylene, polyethylene napthalate (PEN), poly(ethylenevinyl acetate) and polyethylene terephthalate (PET). The flexible material is preferably polyurethane.

Tn some embodiments of the present disclosure the substrate may be breathable.

ro Suitable breathable materials will be apparent to a skilled person. Non-limiting examples of a suitable breathable material include polyamide, polyurethane, polystyrene, polyvinyl chloride, polypropylene, polyethylene, polyethylene napthalate (PEN), poly(ethylene-vinyl acetate) and polyethylene terephthalate (PET). The breathable material is preferably polyurethane.

Tn some embodiments of the present disclosure the compound-releasing device is an electrochemical device.

In some embodiments of the present disclosure the compound-releasing device may comprise first and second electrodes. The first and second electrodes may be disposed on the first face of the substrate.

In some embodiments of the present disclosure the first electrode is a working electrode and the second electrode is a counter electrode.

In some embodiments of the present disclosure the article may comprise a power source. The power source maybe a battery. The power source may comprise a switch.

Tn some embodiments of the present disclosure the power source maybe connected to the first and second electrodes.

Tn some embodiments of the present disclosure the compound-releasing device may comprise a coating. The coating may comprise a conductive material. In some embodiments the conductive material maybe a conjugated polymer. Non-limiting examples of conjugated polymers which can be comprised in the coating include optionally substituted polymers selected from the group consisting of polythiophene; poly(3,4-ethylenedioxythiophene) (PEDOT); (poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS'); poly(3-alkylthiophene) such as poly(3-hexylthiophene); polyaniline; polypyrrole; polypyridine; polyquinoline; polynapthyridine; polycarbazole; polyindole; polyazepine; polyfluorene; polyphenylene; polypyrene; polyazulene; polynapthalene; and polyacetylene.

In some embodiments the coating may comprise a conjugated polymer selected from the group consisting of PEDOT, PEDOT:PSS, polythiophene, polypyrrole, polypyridine, polyquinoline, polynapthyridine and polyacetylene.

In some embodiments the coating may comprise a conjugated polymer selected from the group consisting of PEDOT and PEDOT:PSS.

ll) In some embodiments the coating may comprise PEDOT:PSS.

In some embodiments of the present disclosure the coating is disposed on the first and/or second electrode.

In some embodiments of the present disclosure the compound-releasing device comprises an anode, a cathode and a conjugated polymer.

/5 In some embodiments of the present disclosure the coating is capable of promoting a redox reaction. In some embodiments the coating may promote a redox reaction which produce ROS. In some embodiments the ROS maybe HnOn. In some embodiments the coating may be capable of promoting the reduction of oxygen to form ROS (e.g. f1202). In some embodiments the reduction of oxygen to form ROS (e.g. FLO') takes place at the working electrode. In some embodiments the working electrode (first electrode) is a cathode and the counter electrode (second electrode) is an anode.

In some embodiments of the present disclosure the compound releasing device is a reactive oxygen species (ROS)-releasing device.

In some embodiments or (he present. disclosure the compound releasing device is a hydrogen peroxide-releasing device.

In some embodiments of the present disclosure oxygen from the atmosphere maybe capable of diffusing through the substrate from the second face of the substrate to the first face of the substrate. In some embodiments diffused oxygen may be able to dissolve in the coating disposed on the electrodes. When a current is applied to the electrodes, the oxygen may be reduced to hydrogen peroxide at the working electrode (cathode). The hydrogen peroxide thus produced may then diffuse through the hydrogel to the wound-facing surface of the article.

In some embodiments of the present disclosure the compound-releasing device may comprise a voltage regulator circuit. A voltage regulator circuit may apply a suitable potential to the working electrode.

In some embodiments of the present disclosure the article is configured such that the voltage applied between the first and second electrodes during operation is in the region of -0.65 V to -0.25 V using a Ag/AgCI reference. In some embodiments the article is configured such that the voltage applied between the first and second ro electrodes during operation is about -0.45 V. In some embodiments of the present disclosure the compound-releasing device may comprise a constant current device. A constant current device may provide a constant current at the working electrode during operation.

In some embodiments of the present disclosure the article is configured such that the /5 current at the working electrode during operation is the region of 5 htA to 0.5 mA. In some embodiments the article is configured such that the current at the working electrode during operation is about 50 pA.

In some embodiments of the present disclosure the compound-releasing device is not cross-linked to the substrate. In some such embodiments the compound-releasing device may be adhered to the first face of the substrate by other means, such as for example a polyurethane adhesive or a cyanoacrylate adhesive. In other such embodiments the compound releasing device may not be adhered to the substrate and may, for example, be held in position by means of the cross-linking between the hydrogel and the substrate around the edges of the compound-releasing device.

In embodiments of the present disclosure in which an ROS-releasing device (e.g. a FLO-releasing device) is not cross-linked to the substrate, the article may be capable of delivering ROS (e.g. H202) to a wound at a greater rate as compared to embodiments in which a ROS-releasing device is cross-linked to the substrate.

The description above of features of the article of the first aspect of the present disclosure will also apply to corresponding features of the method of the second aspect of the present disclosure.

In some embodiments of the method of the second aspect of the present disclosure the compound-releasing device may be provided on a central part of the first face of the substrate.

In some embodiments the compound-releasing device may be adhered to the substrate (e.g. the central part of the first face of the substrate), for example by cross-linking between the compound releasing device and the substrate. In such embodiments a cross-linking compound (e.g. a UV-curable and/or biocompatible cross-linking compound) may be applied to one or more locations on the substrate (e.g. one or more locations on the central part of the first face of the substrate), the compound-releasing device may be placed over said one or more locations, and the cross-linking compound maybe cured (e.g. with the application of UV radiation) in order to form cross-links between the compound releasing device and the substrate.

In some embodiments the compound-releasing device may be adhered to the substrate (e.g. the central part of the first face of the substrate) without cross-linking between the compound releasing device and the substrate, for example by application of an adhesive 25 such as for example a polyurethane adhesive or a cyanoacrylate adhesive.

In some embodiments the compound-releasing device may be provided on the substrate (e.g. on the central part of the first face of the substrate) without being adhered to the substrate.

In some embodiments of the method of the second aspect, the hydrogel is cross-linked to the substrate after the compound-releasing device has been provided on the substrate. In such embodiments the compound releasing device may be provided on part of the substrate, leaving part of the substrate exposed. A cross-linking compound (e.g. a UV-curable and/or biocompatible cross-linking compound) may be applied to one or more locations on the exposed part of the substrate, and the hydrogel may be placed over the said one or more locations of the exposed part of the substrate, and the cross-linking compound may be cured (e.g. with the application of UV radiation) in order to form cross-links between the hydrogel and the substrate.

In some embodiments the hydrogel is cross-linked to the peripheral part of the first face of substrate after the compound-releasing device has been provided on the central part of the first face of the substrate. In such embodiments a cross-linking compound (e.g. a UV-curable and/or biocompatible cross-linking compound) may be applied to one or more locations on the peripheral part of the first face of the substrate, the 1() hydrogel may be placed over the substrate so as to cover the central part of the first face carrying the compound-releasing device and said one or more locations of the peripheral part of the first face, and the cross-linking compound may be cured (e.g. with the application of UV radiation) in order to form cross-links between the hydrogel and the substrate.

A skilled person would be able to select appropriate curing conditions to form cross-links for the particular cross-lining agent used.

The present disclosure is described below with reference to the figures.

Figure 1 is a schematic side view of an article according to one embodiment of the first aspect of the present disclosure. An article 1 for dressing a wound comprises a substrate 2, a compound-releasing device 3 and a hydrogel layer 4. Cross-links 5 are present between the hydrogel 4 and the substrate 1, and between the compound-releasing device 3 and the substrate 1.

Figure 2 is a schematic side view of an article according to another embodiment of the first aspect of the present disclosure. An article 1 for dressing a wound comprises a substrate 2, a compound-releasing device 3 and a hydrogel layer 4. Cross-links 5 are present between the hydrogel 4 and the substrate 1. Cross-links 5 are not present between the compound releasing device 3 and the substrate 1.

The following non-limiting examples illustrate the present disclosure.

Example

A wound dressing having an H,02-releasing device and a hydrogel, with both the device and the hydrogel cross-linked to the substrate, was prepared as follows.

An optically active adhesive (Norland Optical Adhesive 85) was applied to the electrode-side of a substrate, taking care to avoid contact with the metal of the electrodes. The optically active adhesive was also applied to the edges of one side of a poly(N-methyl acrylamide) hydrogel with an ionic calcium component (ActiFormCool _to available from L&R Medical). A pre-curing step was carried out for 3o-6o secs using a UVGL-58 Handheld UV lamp (wavelength 254/365 nm) and the H202-generating device was placed in the centre of a substrate -of a wound dressing. Following pre-cu ring the H2Orreleasing device was placed on the substrate so as to be in contact with the adhesive which had been applied to the substrate, leaving the edges of the substrate free. The hydrogel was then placed over the H202-releasing device and the substrate so that the edges of the hydrogel to which adhesive had been applied were in contact with the free edges of the substrate. The substrate with HoOrreleasing device and hydrogel attached was irradiated for 30 mins using a UV -H 255 hand lamp (80 MIN-cm 2).

Example 2

A wound dressing was prepared according to the same procedure as for Example 1, except that a polyurethane hydrogel (KerraLite Cool from Crawford Healthcare) was used instead of the poly(N-methyl acrylamide) hydrogel.

Example 3

A wound dressing was prepared according to the same procedure as for Example 2, except that no adhesive was applied to the area between the substrate and the H202-releasing device.

Comparative Example 1 A wound dressing was prepared according to the same procedure as for Example 2, 35 except that no adhesive was applied to the area between the substrate and the H202-releasing device, or the area between the hydrogel and the substrate.

Results The wound dressings of Examples i to 3 and Comparative Example I were tested for 5 1-1202 generation by running the H2O releasingdevices for 4o mins at an applied voltage of -0.45 V in 8.5 ml of phosphate-buffered saline (PBS) solution. The results are set out in the table below.

Dressing Rate of H202 generation / pMmi n i

Example 1 0.2

Example 2 0.4

Example 3 0.7

Comparative 0.8

Example 1

In the dressings of Examples I to 3, the hydrogel remained adhered to the substrate.

As can be seen from the results above, the wound dressings of Examples Ito 3 maintained their integrity during operation while still generating H202 at a therapeutically-relevant rate. Example 3 shows that the integrity of the dressing can be preserved by cross-linking between hydrogel and substrate only (i.e. without cross linking between the compound-releasing device and the substrate), with only a minimal reduction in the ability to generate ROS (cf. Comparative Example 1 with no adhesion between device and substrate or hydrogel and substrate).

It will be appreciated that various modifications may be made to the embodiments hereinbefore described. Such modifications may involve equivalent and other features which are already known in the design, manufacture and use of wound dressings and component parts thereof and which may be used instead of or in addition to features already described herein. Features of one embodiment may be replaced or supplemented by features of another embodiment.

Although claims have been formulated in this application to particular combinations of features, it should be understood that the scope of the disclosure of the present invention also includes any novel features or any novel combination of features disclosed herein either explicitly or implicitly or any generalization thereof, whether or not it relates to the same invention as presently claimed in any claim and whether or not it mitigates any or all of the same technical problems as does the present invention. The applicants hereby give notice that new claims maybe formulated to such features and/or combinations of such features during the prosecution of the present application or of any further application derived therefrom.

Claims

CLAIMS1. An article for dressing a wound, the article comprising a substrate, a compound-releasing device and a hydrogel layer, wherein the hydrogel is cross-linked to the 5 substrate.
2. An article according to claim 1, wherein the compound-releasing device is not cross-linked to the substrate.
3. An artide according to claim 1 or 2, wherein cross-links between the hydrogel and the substrate are obtainable by using a UV-activated cross-linking compound.
4. An article according to claim 3, wherein the UV-activated cross-linking compound is biocompatible.
5. An article according to claim 4, wherein the UV-activated cross-linking compound is selected from benzophenone, acetophenone, riboflavin, glucose, and derivatives thereof, or any combination thereof.is
6. An artide according to any preceding claim, wherein the hydrogel comprises agarose, alginate, an acrylamide-alginate copolymer, an acrylamide-chitosan copolymer, polyurethane, or poly(N-methyl acrylamide).
7. An artide according to any preceding claim wherein the substrate comprises a polymeric material.
8. An article according to claim 7 wherein the substrate comprises polyamide, polyurethane, polystyrene, polyvinyl chloride, polypropylene, polyethylene, polyethylene napthalate (PEN), poly(ethylene-vinyl acetate), or polyethylene terephthalate (PET).
9. An article according M any preceding claims wherein the compound-releasing device is an electrochemical device.to.
An article according to claim 9 further comprising a power source.it.
An article according to claim 9 or 10 wherein the compound-releasing device comprises an anode, a cathode and a conjugated polymer.
12. An article according to any preceding claim, wherein the compound releasing device is a reactive oxygen species (ROS)-releasing device.
13. An article according to claim 12, wherein the compound releasing device is a hydrogen peroxide-releasing device.
14. A method for manufacturing an article for dressing a wound according to claim 1, the method comprising providing a substrate, providing a compound releasing device on the substrate, and cross-linking a hydrogel to the substrate.
15. A method according to claim 14 wherein the compound-releasing device is not cross-linked to the substrate. /0