Wound dressing for antimicrobial wound treatment

Description

[0001] The present invention relates to a wound dressing for the treatment of wounds for the local treatment of microbial contamination, infections and biofilms by plasmon resonance-induced thermal microablation.

[0002] Microbial contamination and infections pose a challenge in wound treatment, particularly in the treatment of chronic wounds. When treating infected wounds with antimicrobial agents, resistance to these agents can develop.

[0003] The use of plasmon resonance is known in the cosmetic field. US2014 / 0371664 describes a method in which nanoparticles are applied to a cosmetic carrier and stimulated to plasmon resonance in close proximity to the skin. This method can be used for hair removal and acne treatment.

[0004] In the field of wound treatment, the use of nanoparticles for antibacterial or bacteriostatic therapy is described in WO2017 / 122224. For this purpose, silver nanoparticles are combined with cellulose nanocrystals in an ointment.

[0005] In WO2012 / 031282, nanoparticles embedded in fibroin are stimulated to undergo plasmon resonance. The resulting photothermal effect can be used in thermotherapy.

[0006] FR2 986 156 relates to a transdermal patch for application to the skin surface or mucous membrane, in which the active ingredient is bound via a photolabile bond in the substrate. The active ingredient is released by a light pulse in the ultraviolet range. The light pulse is generated by an LED positioned opposite the edge of the substrate.

[0007] TW M 586 146 D2 discloses a wound dressing with gold nanoparticles in a heating layer that can be stimulated to plasmon resonance. The heat generated by the plasmon resonance is used to deliver an active ingredient directly to the wound.

[0008] US 2018 / 289723 concerns the photoeradication of microorganisms using a flexible light source. The target, which may be a wound, is irradiated with blue and violet light. The light source comprises electrodes and a light emitter. The light emitter is located between two electrodes. At least the electrode facing the skin must be transparent. The transparent electrodes may contain graphene as well as nanoparticles, which can be used to excite surface plasmons.

[0009] The object underlying the invention is to reduce the risk of wound infections during wound treatment. A further object is to reduce the microbial colonization of already infected wounds. Furthermore, the formation of biofilms in wounds should be suppressed and existing biofilms should be eliminated as effectively as possible.

[0010] These problems are solved by a wound dressing according to claim 1. The invention enables the improvement of the therapy of chronic, especially infected, wounds through thermal inactivation and optional removal of microorganisms and biofilms. This heat treatment can be applied precisely to the wound site or, optionally, to the surrounding area.

[0011] The wound dressing comprises a wound contact layer positioned on the wound side when the dressing is in use, a covering layer positioned on the opposite side of the wound when the dressing is in use, and a light source positioned between the wound contact layer and the covering layer.

[0012] The wound dressing according to the invention is further characterized in that nanoparticles are present in the wound contact layer. These nanoparticles are capable of being excited to plasmon resonance. The light source is suitable for exciting the nanoparticles to plasmon resonance.

[0013] Using the wound dressing according to the invention, plasmon resonance can be stimulated both over a wound area and over the intact skin of a patient in the surrounding area. The resulting thermal microablation leads to the inactivation and / or removal of harmful microorganisms or biofilms in a wound or on the skin of a patient. Thermal microablation is understood to mean the thermal inactivation and, if applicable, removal of microorganisms and biofilms.

[0014] The interaction of the nanoparticles present in the wound contact layer with light excites the conduction electrons in the nanoparticles to oscillation. The quasiparticle that describes this oscillation is the plasmon. The excitation of a plasmon is accompanied by the absorption of light and is called plasmon resonance.

[0015] In the context of the present invention, nanoparticles are understood to be particles with a maximum spatial dimension of 1 nm to 500 nm. Preferably, the maximum spatial dimension of the nanoparticles is between 2 nm and 200 nm, more preferably the maximum spatial dimension of nanoparticles is between 5 nm and 150 nm, and particularly preferably the maximum spatial dimension of nanoparticles is between 6 nm and 100 nm.

[0016] The maximum spatial extent of the nanoparticles is preferably determined in connection with the invention by means of scanning electron microscopy.

[0017] The maximum size of the nanoparticles is subject to a distribution and can therefore vary by a few nanometers from nanoparticle to nanoparticle.

[0018] According to the present invention, nanoparticles are introduced into or applied to a surface of a wound contact layer. Irradiation with light excites these nanoparticles to vibrations. Through the plasmon resonance described above, heat can be generated locally in the wound area or surrounding tissue. Thermal microablation can then be used to remove harmful microorganisms or biofilms from the wound or the patient's skin.

[0019] The nanoparticles can, for example, be embedded in a silicone matrix. Alternatively, they can be applied to the wound contact layer, for instance, by dip coating or solvent evaporation. In solvent evaporation, the nanoparticles are mixed in a solvent. The solvent is then removed at reduced pressure, causing the nanoparticles to precipitate and adhere to the surface of the wound contact layer.

[0020] The covering layer is intended to create an environment conducive to wound healing in the wound area and prevent contaminants from entering the wound. The covering layer can be an integral part of the wound dressing. Alternatively, the covering layer can be provided as a separate component and applied only when the wound dressing is used. The covering layer can be self-adhesive.

[0021] The wound dressing includes a wound contact layer. When the dressing is applied, this wound contact layer lies directly on the patient's skin or wound area.

[0022] The wound contact layer may have an adhesive area for attaching the wound dressing.

[0023] Preferably, the wound dressing comprises an intermediate layer. The intermediate layer is positioned between the cover layer and the wound contact layer. The intermediate layer preferably comprises a fluid-absorbing material, such as cellulose fibers, cotton fibers, viscose fibers, alginate fibers, hydrophilic synthetic polymers, or superabsorbent particles or fibers. The material can be, for example, in the form of a non-woven fabric, polymer foam, or hydrogel. Preferably, the intermediate layer contains a non-woven fabric or airlaid into which superabsorbent polyacrylate particles or fibers are incorporated. Multiple intermediate layers, particularly those made of different materials, are also possible.

[0024] The one or more intermediate layers can be one or more transfer layers. A transfer layer, in particular, enables the unidirectional transport of wound exudate released from the wound. Preferred embodiments of such a transfer layer include materials that allow capillary action or exhibit hygroscopic properties, such as fleece, superabsorbent fibers or particles, or three-dimensionally perforated films.

[0025] In a preferred embodiment, the nanoparticles are nanorods. These have, in particular, a maximum spatial dimension of 45 nm. The nanoparticles can also exist in other shapes, e.g., cubes, spheres, tetrahedrons, octahedrons, platelets, or tubes. One possible embodiment of the nanoparticles can include nanotubes, nanorods, nanofibers, but also nanoplatelets or hollow, closed molecules. Examples of such embodiments are gold nanorods or gold nanoshells around a silicon oxide core.

[0026] Preferably, the nanoparticles comprise metallic starting materials or metallic salts and oxides. Particularly preferably, the nanoparticles consist of the aforementioned metallic starting materials or metallic salts and oxides. According to a particularly advantageous embodiment, the nanoparticles comprise or consist exclusively of gold or zinc oxide.

[0027] Nanoparticles can also include silver, ruthenium, platinum, rhodium, osmium, iridium, copper, zinc, nickel, chromium, magnesium, iron, palladium, gold, titanium, titanium dioxide, silver, silver nitrate and other silver derivatives.

[0028] In another preferred embodiment, the wound dressing comprises at least one intermediate layer and at least one light source. In this embodiment, the at least one light source is located on the side of the at least one intermediate layer facing away from the wound. The intermediate layer includes a transparent area and / or a recess, creating a translucent zone between the at least one light source and the wound contact layer. The light emitted by the light source penetrates through the transparent areas and / or recesses to the wound contact layer and excites the nanoparticles embedded in the wound contact layer to plasmon resonance.

[0029] To ensure sufficient irradiation of the nanoparticles, all layers positioned between the light source and the wound contact layer (if present) generally include a transparent area and / or a recess. The transparent areas and / or recesses are arranged in such a way that a translucent zone exists between the light source and the wound contact layer.

[0030] In a further, particularly preferred embodiment, the light source is arranged between the wound contact layer and the intermediate layer such that the light source rests directly on the wound contact layer. This embodiment has the advantage that the light loses very little intensity on its way from the light source to the wound contact layer. Intensity losses can occur, for example, through absorption or reflections at interfaces.

[0031] The light source is preferably a laser LED or an LED. It can also be an array of multiple laser LEDs or LEDs.

[0032] If a laser is used for plasmon excitation, the laser's area power must not exceed 330 to 350 mW / cm² for 10 to 100 s; otherwise, cell and skin damage may occur. The wavelength range of 650 nm to 940 nm in the near-infrared range and / or 1000 nm to 1350 nm in the infrared range is preferred.

[0033] The light source used to generate the plasmon resonance emits light in the wavelength range between 300 nm and 2000 nm.

[0034] Preferably, the light source emits monochromatic light, for example, light with a wavelength of 420 nm. Preferably, the light source emits monochromatic light that is tuned to the size and shape of the nanoparticles so that plasmon resonance occurs. According to another preferred embodiment, a multimodal light source is used. The multimodal light source emits light with different discrete frequencies.

[0035] In general, during irradiation of 10 to 100 s, the light emitted by the light source should not exceed 350 mW / cm 2<, otherwise cell or skin damage may occur in the patient.

[0036] A suitable light source, for example, is an LED with a power output of 900 mW at a nominal wavelength of 850 nm.

[0037] Preferably, either a laser LED or an LED is used. LEDs in an array are also a possible embodiment for a light source integrated into the wound dressing.

[0038] Conductors, such as conductive threads, can be used to power the light source. The conductors are preferably routed out from under the cover layer and fitted with a connector so that a power source can be connected to the wound dressing.

[0039] The light source can have an integrated power supply element. This power supply element can be a thin-film energy source, such as a flexible battery. Examples of flexible batteries include J.Flex flexible lithium polymer batteries, Panasonic flexible lithium-ion batteries, GrePow flexible high-discharge LiFePO4 batteries, flexible lithium-sulfur batteries, or sodium-ion batteries (SIBs).

[0040] The light source is preferably powered by external energy sources and contactless energy transfer via electromagnetic fields. In one embodiment, the power supply element is an energy harvesting element. The energy harvesting element preferably uses electromagnetic radiation as its energy source. Radio waves with frequencies from 30 kHz to 300 GHz are particularly preferred. These radio waves can originate, for example, from radio towers, radar systems, Wi-Fi networks, or Bluetooth connections. For Wi-Fi networks, radio waves with frequencies of 2.4 GHz and a power output of up to 100 mW, as well as those with frequencies of 5 GHz and a power output of up to 1 W, are of particular interest. Radio waves based on mobile networks / GSM have frequencies of 850 MHz, 900 MHz, 1800 MHz, and 1900 MHz according to GSM standards.

[0041] In a preferred embodiment, the power supply to the light source includes an energy storage module.

[0042] In another preferred embodiment, the light source is supplied with energy via inductive charging.

[0043] The electronic components of the wound dressing according to the invention are preferably partially elastic or fully elastic. The laser LEDs of a laser LED array are applied to or embedded in a flexible substrate and are contacted by flexible electrical conductors. The flexible substrate can be a silicone layer.

[0044] According to one embodiment, the wound dressing comprises at least two light sources. The light sources are individually controllable, i.e., the activation of a first light source occurs independently of the activation of a second light source.

[0045] If multiple light sources are available, those light sources that are present over a wound area when the dressing is in use are preferentially activated, while those light sources over intact skin areas are deactivated. This allows the treatment to be limited locally to the wound area.

[0046] The wound area can be determined using sensors integrated into the wound dressing. A periodic arrangement of multiple sensors is preferred. This periodic arrangement can, for example, be a matrix of sensors.

[0047] In another embodiment, a first image of the wound area to be treated is captured by a camera. This first image is then segmented using a digital image analysis method, so that the one or more segments of the first image representing the wound are identified as the wound area. Subsequently, a wound dressing according to the invention is applied to the wound area to be treated. A second image of the wound area to be treated, including the applied wound dressing, is then captured. The first image is aligned with the second image using a digital method. This can be done, for example, by means of points appearing in both images. Successful alignment of the two images then makes it possible to determine the position of the applied wound dressing, as captured in the second image, relative to the wound area determined from the first image.Based on the position information, precisely those light sources that lie above the wound surface can now be activated in a targeted manner. Figure 1

[0048] Schematic representation of an embodiment of the wound dressing with integrated light source Figure 2

[0049] Schematic representation of another embodiment of the wound dressing with integrated light source Figure 3

[0050] Schematic representation of an intermediate layer comprising a multitude of periodically arranged light sources.

[0051] All translucent layers 30 are shown as dotted lines.

[0052] Figure 1Figure 1 shows a preferred embodiment of the wound dressing 100. The wound dressing 100 comprises a cover layer 1, a wound contact layer 20, and an absorbent intermediate layer 12, wherein the intermediate layer 12 is arranged between the cover layer 1 and the wound contact layer 20. The wound contact layer 20 contains gold nanorods 21, advantageously using the gold particles disclosed in the publication "Bacterial biofilm elimination using gold nanorod localised surface plasmon resonance generated heat" by Maria Pihle et al. (2017) (https: / / doi.org / 10.1016 / j.msec.2017.05.067). The maximum spatial extent of the nanorods 21 is 45 nm. When the wound dressing is used, the wound contact layer 20 lies directly on the patient's skin and / or wound site.

[0053] The wound dressing 100 comprises a layer 42 with an integrated light source 41. The light source 41 can be a laser-LED array. The light source 41 is an LED with a nominal wavelength of 850 nm and a power of 3.5 mW / cm² at a total power of 322 mW.

[0054] Layer 42 is applied to the wound-facing side of intermediate layer 12. Layer 42 comprises a laser-LED array mounted on a substrate with a mesh structure. Due to the substrate's mesh structure, layer 42 has numerous openings, allowing wound exudate to pass from the wound to the intermediate layer. Intermediate layer 12 consists of microfibers with a high absorption capacity for fluids. Therefore, cell and bacterial debris dispersed in wound exudate, which has been detached from the wound by thermal microablation, can be absorbed and bound in intermediate layer 12.

[0055] The light generated by the laser-LED array strikes the nanorods 21 in the wound contact layer 20 unimpeded and excites them to plasmon resonance. The resulting local heating leads to thermal microablation and / or inactivation of harmful microorganisms or biofilms in a patient's wound.

[0056] The laser-LED array 43 is powered by an energy harvesting element. This element converts ambient energy into electrical energy. It preferentially utilizes electromagnetic radiation at frequencies of 2.4 GHz and powers up to 100 mW, as well as at frequencies of 5 GHz and powers up to 1 W, as its energy source.

[0057] The wound dressing 100 is applied to the patient so that the wound contact layer lies over the wound surface. The light source 41 is switched on, and the gold nanorods 21 are stimulated to plasmon resonance. The light source 41 remains active for 5 minutes. Depending on the need, the light source 41 can be activated several times during the course of treatment.

[0058] In Figure 2Another preferred embodiment of the wound dressing 100 is shown schematically. The wound dressing comprises a cover layer 1 and a wound contact layer 20, which contains silver nanorods 21. The nanorods 21 are embedded in translucent silicone. The nanorods are excited to plasmon resonance by an integrated light source 41, such as a laser-LED array. The laser-LED array is integrated into an intermediate layer 42. The laser-LED array 41 is powered by the power supply 43. The power supply 43 is a flexible battery, such as Panasonic flexible lithium-ion batteries. The wound contact layer 20 is translucent.

[0059] Figure 3Figure 1 shows a schematic representation of an intermediate layer 42 with several integrated light sources 41. The light sources 41a,a to 41f,c can be individually activated by the control element 50. The control element 50 comprises a microcontroller and a receiver element. The receiver element sends activation instructions to the control element from an external processing unit that is not part of the wound dressing. An activation instruction can be the command to activate all light sources 41a,a to 41f,c that are located above the wound surface. The external processing unit determines which light sources 41a,a to 41f,c are to be activated. A flexible battery 43 supplies power to the control element 50 and the light sources 41.

Claims

1. Wound dressing (100) for use in the inactivation and / or removal of harmful microorganisms or biofilms in a wound of a patient by means of plasmon resonance-induced thermal microablation, comprising: - a wound contact layer (20) arranged on the wound side, - a cover layer (1) arranged on the non-wound side, - a light source (41) arranged between wound contact layer (20) and cover layer (1), characterized in that the wound contact layer (20) contains nanoparticles (21) which are suitable for excitation to plasmon resonance, and in that the light source (41) is suitable for exciting the nanoparticles (21) to plasmon resonance.

2. Wound dressing (100) according to Claim 1, wherein the wound contact layer (20) comprises transparent regions.

3. Wound dressing (100) according to Claim 1 or 2, wherein the wound dressing (100) comprises at least one intermediate layer (12) and the at least one intermediate layer (12) is arranged between the cover layer (1) and the wound contact layer (20).

4. Wound dressing (100) according to Claim 3, wherein all the layers which are arranged between light source (41) and wound contact layer (20) comprise a transparent region (30) and / or a cutout, so that a light-permeable region (30) is present between the light source (41) and the wound contact layer (20).

5. Wound dressing (100) according to any of Claims 1 to 3, wherein the light source (41) on the non-wound side lies directly on the wound contact layer (20).

6. Wound dressing (100) according to any of Claims 3 to 5, wherein the at least one intermediate layer (12) has fluid-absorbing properties.

7. Wound dressing (100) according to at least one of the preceding claims, wherein the wound contact layer (20) has an adhesive region.

8. Wound dressing (100) according to at least one of the preceding claims, wherein the nanoparticles (21) are nanoparticles (21) composed of metal or metallic salts.

9. Wound dressing (100) according to at least one of the preceding claims, wherein the nanoparticles (21) have a maximum spatial extent of between 1 nm and 500 nm, preferably between 2 nm and 200 nm, more preferably between 5 nm and 150 nm, more particularly between 6 nm and 100 nm.

10. Wound dressing (100) according to at least one of the preceding claims, wherein the light source (41) more particularly is an LED.

11. Wound dressing (100) according to at least one of the preceding claims, wherein the wound dressing comprises at least two light sources (41).

12. Wound dressing (100) according to Claim 11, wherein the light sources (41) can be driven individually and wherein only those light sources (41) of the at least two light sources (41) that are located over the wound surface are activated.