WO2025131960A1 - Antimicrobial medical device - Google Patents

Abstract

The invention relates to a medical device (1) for applying to a human or animal body (20), in particular to a wound, comprising a carrier layer (2), a metal oxide layer (5), wherein the metal oxide layer (5) is applied to the carrier layer (2) and is configured to form reactive oxygen species, and a contact layer (3), wherein when the medical device (1) is applied to the body (20), the contact layer (3) touches the body (20) and the contact layer (3) and the metal oxide layer (5) lie directly adjacent to one another.

Description

Antimicrobial medical device

The invention relates to a medical device for application to the human or animal body, comprising a carrier layer and a metal oxide layer. The invention also relates to a manufacturing method for this medical device and a method for reactivating photocatalytic properties of the device. Furthermore, the invention relates to a metal oxide for use in a method for treating infected wounds or for preventing infections.

Nosocomial infections represent a major burden for patients and increase healthcare costs. A large proportion of these infections are associated with percutaneous medical devices such as venous and urinary catheters and ventilators, but dressings and wound dressings can also provide a suitable environment for infection-causing germs. To reduce nosocomial infections, critical devices and products can be coated with antimicrobial coatings that slowly release antimicrobial ingredients such as silver or copper ions. However, these coatings are expensive. and require precise control of the amount of silver or copper, its distribution, and its chemical state. The coatings' ability to reduce microbial concentrations to a safe level also has a limited lifespan.

Photocatalytic compositions are another approach to creating contamination-reducing, low-bacteria surfaces. Such photocatalytic compositions can be applied to various surfaces to generate free radicals on-site, which have antimicrobial effects.

The photoelectrochemical activity of titanium oxides (TiOx) has long been recognized. Titanium oxides are considered one of the few currently known materials suitable for photocatalysis for applications in self-cleaning and antimicrobial coatings because of their ability to mineralize organic contaminants, including microorganisms, producing nontoxic byproducts. Furthermore, titanium oxides are environmentally friendly and cost-effective. Unfortunately, titanium oxides, which can be excellent photocatalysts under UV light, have very limited ability to absorb visible light.

To enable a fast-acting antibacterial mechanism without the release of biocidal substances, Hegemann et al. (D. Hegemann et al., Plasma Processes Polym. 2022; 19: e2100246) TiO2 catalysts that generate reactive oxygen species (ROS) are considered. Doping with different metals creates electron-hole pairs with narrow band gaps that promote the formation of ROS. For this purpose, plasma technology is used to deposit Ag nanoislands on defective TiOx films, which are stabilized by plasma post-oxidation to suppress the release of Ag ions. Importantly, ROS generation is maintained upon storage in the dark. Efficacy is known to decrease over time, but can be restored by exposure to visible light.

When a semiconductor material such as TiO2 absorbs a photon whose energy is greater than its band gap, an exciton can be formed. An electron moves from the valence band to the conduction band of the material, leaving an electron hole in the valence band. The valence band and conduction band are energy bands, i.e., energy level ranges. The top energy level of the valence band is separated from the bottom energy level of the conduction band by an energy gap called the band gap. Electrons and holes interact with oxygen species in the environment of the semiconductor material, generating reactive oxygen species (ROS), which belong to the free radical family. The electrons interact with oxygen molecules and generate superoxide radicals. The holes can interact with water molecules or adsorbed OH groups to generate hydroxyl radicals. The ROS can react further to generate new radicals. For example, under acidic conditions, superoxide radicals can react with electrons to generate hydrogen peroxide molecules. The resulting hydrogen peroxide can then interact with either superoxide radicals or electrons to form hydroxyl radicals.

These short-lived radicals induce further ROS such as molecular singlet oxygen, ^x O2, and hydrogen peroxide, H2O2, through electron transfer or recombination. These species efficiently oxidize proteins and lipids in an aqueous environment, thus inactivating bacteria, fungi, and viruses.

In general, ROS include radicals such as the superoxide anion O2 -~, the highly reactive hydroxyl radical OH - , the hydroperoxyl radical HOO - , the peroxyl radical ROO - and the alkoxyl radical RO • of lipids, and stable molecular oxidants such as hydrogen peroxide H2O2 , hydroperoxide ROOH, ozone O3 and the hypochlorite anion OC1~ as well as excited oxygen molecules (singlet oxygen ^2 ). Following oxidation, reactive electrophilic species are formed.

On defective TiOx layers deposited by magnetron sputtering and thus containing oxygen vacancies, Ag nanoislands can be applied by doping. Subsequent plasma oxidation can create a catalyst surface that has a pronounced metal oxide nanostructure with a high interfacial area. Redox processes that take place at the catalyst surface when water and oxygen are present generate the strongly oxidizing radicals O2 and OH • by electron transfer and oxidation at holes, respectively, which are promoted by oxygen vacancies in the plasma-deposited TiOx and narrow band gaps. These radicals lead to the formation of further ROS, which have strong antibacterial activity and enable contact killing within minutes directly at the catalyst surface. However, efficient bacterial inhibition is also possible in a volume above the surface, regardless of the solution used. This ROS-generated antibacterial activity is significantly faster than conventional Ag release systems, while showing only a low initial Ag ion release that stabilizes upon storage.

WO 2020/187377 A1 discloses a transparent photocatalytic coating for the in-situ generation of free radicals to combat microbes, odors, and organic compounds in visible light. The composition comprises TiO2 nanoparticles as the photocatalytic material, which preferably doped with silver ions to extend the photocatalytic activity to visible light .

WO 2010/052190 A2 discloses wound dressings provided with a homogeneous and essentially amorphous layer of a metal oxide, predominantly comprising titanium oxide. The wound dressings exhibit photocatalytic properties that produce antifouling and antimicrobial effects. Additional compounds can be added to the metal oxide layer, which can vary the photocatalytic properties of the metal oxide layer, which consists predominantly of titanium oxide.

However, the disadvantage of the known prior art devices is that the metal oxide layer and the dopants, such as silver, come into contact with the human body. Thus, the silver ions or the metal oxides, for example, can cause undesirable reactions at the contact point.

The invention is based on the object of providing a medical device with antimicrobial properties which reduces the occurrence of undesirable reactions at the point of contact with the human body. This object is achieved by a medical device for application to the human or animal body, in particular to a wound. The medical device comprises a carrier layer and a metal oxide layer, wherein the metal oxide layer is applied to the carrier layer and the metal oxide layer is configured to form reactive oxygen species. The medical device comprises a contact layer, wherein the contact layer, in the state in which the medical device is applied to the body, touches the body and the contact layer and the metal oxide layer lie directly against one another. This enables ROS formed in the metal oxide layer to pass through the contact layer to the body or onto or into the wound without the metal oxide layer having direct contact with the body of a patient. This prevents metal oxides or metal ions from causing undesired reactions in the patient's body.

Due to the antimicrobial properties of ROS, colonization by microorganisms on the body surface covered by the medical device is reduced, thus preventing inflammation. Likewise, already established microorganisms can be killed by the device. The device according to the invention has the advantage that

Microorganisms do not develop resistance to the antimicrobial mechanism of action of ROS, as is often the case with antibiotics.

Because the metal oxide layer - in the case of a medical device applied to the human or animal body - does not come into direct contact with the body, the environment between the medical device and the body can be influenced by the selection of the material for the contact layer. For example, the contact layer can be designed in such a way that it prevents sticking to the body or the wound, or it can also be designed as an adhesive layer. However, the prerequisite is that the contact layer is so permeable that at least some of the ROS formed by the metal oxide layer can pass through the contact layer onto the body.

According to the invention, the contact layer and the metal oxide layer lie directly against each other. This means that the contact layer and the metal oxide layer are in almost full contact. Of course, due to manufacturing tolerances, there may be areas in which the two layers are slightly spaced from each other, but these areas are only present to a very small extent. By definition, however, there is no further layer, such as an adhesive layer or

distribution layer, provided.

For use, the medical device with the contact layer is applied or placed on the human or animal body. Essentially, application to the body means application to the skin. However, according to the invention, this formulation also includes application to a wound, regardless of whether the wound affects the skin or other areas of the body.

Due to the ability of the metal oxide layer to form ROS, the medical device according to the invention enables the delivery of ROS-generated antibacterial activity to a site of action significantly faster than is the case with conventional Ag release systems. As already explained above, a metal oxide layer according to the invention is capable of forming ROS if it has photocatalytic properties. The metal oxide layer is therefore configured to form ROS if it comprises at least one photocatalyst.

Photocatalysis is based on the fact that light in a semiconductor material such as titanium dioxide (Ti02) which is present in the metal oxide layer generates electron-hole pairs if the energy of the photons is larger than the band gap. An electron moves from the valence band to the conduction band of the material, leaving an electron hole in the valence band. The uppermost energy level of the valence band is separated from the lowermost energy level of the conduction band by the band gap. Electrons and holes interact with oxygen species surrounding the semiconductor material, generating ROS.

According to a particularly preferred embodiment of the invention, the contact layer is permeable to water molecules and oxygen molecules. This allows water and oxygen to reach the metal oxide layer, which is then available in the immediate vicinity of the metal oxide to generate ROS.

In a further preferred embodiment of the invention, the contact layer comprises a polymer-like material. Polymeric structures enable the ROS formed on the metal oxide layer to diffuse through the contact layer. Thus, during use of the medical device, ROS can reach the human or animal body from the metal oxide layer and exert an antimicrobial effect there.

Preferably, the contact layer may comprise a hydrophobic material or be formed from a hydrophobic material. This is particularly advantageous when the medical device is applied to a wound. By a hydrophobic Contact layer can reduce adhesion to the wound.

The contact layer can particularly preferably comprise a silicone, in particular polydimethylsiloxane, since silicone is permeable to water molecules, oxygen and formed ROS on the one hand and can prevent sticking to the body surface on the other hand.

Alternatively, the contact layer may comprise a siloxane (SiO:CH compound with variable CH content), which can be obtained by plasma polymerization of hexamethyldisiloxane (HMDSO).

But also gels, especially hydrogels, ointments, hydrocolloids, porous films and (meth)acrylates are suitable materials that the contact layer can comprise individually or in combination.

The contact layer can have a thickness between 1 nm and 1000 nm, preferably less than 100 nm. The thickness of the contact layer is particularly preferably between 1 nm and 10 nm. It is important that the thickness of the contact layer is selected such that water and the ROS can diffuse through it. Layer thicknesses of this small thickness can be achieved primarily by plasma polymerization. If the contact layer is applied using conventional coating methods, the thickness can preferably be 50 to 250 pm.

The contact layer can be either a closed layer or an open layer. According to the invention, a closed layer is understood to be a layer that almost completely covers the metal oxide layer or is adjacent to the metal oxide layer. By definition, the coverage should be 95% or more.

If the coverage is less than 95%, the contact layer is formed as an open layer. For example, the contact layer can be applied to the metal oxide layer in an island-like pattern, or the contact layer can have perforations.

According to one embodiment, the wound contact layer can be perforated. These perforations are intended to increase the permeability to water, ROS, or wound exudate. Furthermore, the perforations can allow unhindered passage of wound exudate through the contact layer to the metal oxide layer and, if applicable, into an additional absorbent layer of the medical device.

The perforations in the contact layer can be essentially round and arranged at regular intervals in the layers They may also have a diameter of 0.5 to 5 mm, preferably 1 to 3 mm. The number and size of the perforations can be selected so that the layer has a net-like structure.

The thickness of the metal oxide layer may be 200 nm or less, preferably about 50 nm or less, and more preferably 20 nm or less. A thin metal oxide layer is preferred because it requires less metal oxide to manufacture the medical device, thus reducing manufacturing costs.

According to a preferred embodiment, the metal oxide layer comprises a titanium oxide, wherein the titanium oxide is present as TiO, Ti ₂ O ₂ , TiA0 s, or particularly preferably as TiO ₂ . The titanium oxides preferably have oxygen vacancies. Titanium oxides have the advantage of being readily available and having a band gap between 3.0 eV and 3.2 eV, which corresponds to a light wavelength of approximately 390 nm.

In order to achieve a shift in the range of light wavelengths that can activate photocatalysis, the metal oxide layer may comprise one or more compounds selected from the group consisting of N, C, S, Gl, Ag, Au, Pd, Pt, Fe, Ce, Cl, F, Pb, Si, Zn, Zr, B, Br, Gr, Hg, Sr, Cu, I, Sn, Ta, V, W, Co, Mg, Mn and Cd. Preferably, the metal oxide layer doped with these atoms. The listed compounds and their derivatives are also called dopants.

The metal oxide layer particularly preferably comprises Ag or Fe, since this enables a shift of the light wavelength into the visible range.

The proportion of titanium oxide in the metal oxide layer can be up to 100%. Preferably, it is in a range from 75% to 100%, from 50% to 75%, or from 25% to 50%.

The metal oxide layer is preferably doped with silver oxide (AgOx). The proportion of silver oxide in the metal oxide layer can be between 1% and 75%, preferably 25% to 50%, and particularly preferably approximately 25%. This enables reliable generation of ROS in the metal oxide layer upon activation of the photocatalysis by visible light.

In a further preferred embodiment of the invention, the dopant, in particular silver oxide, is applied in the form of nanoislands in or on the metal oxide layer, whereby the active interface between the metal oxide layer and the dopant is increased and the generation of ROS is increased.

According to the invention, the layer thicknesses are to be understood as nominal thicknesses. This means that the layers are applied in this thickness in a manufacturing process, but then can then change, for example, through curing or cooling. For example, it is possible for the dopants to be applied as a layer, but then to form nanoislands, i.e. the dopant "contracts" into islands. If one were to measure the layer thickness of an island directly, the contraction would cause the layer thickness in the island to be greater than the nominal (applied) layer thickness of the dopant.

Typically, the dopants are distributed homogeneously in or on the metal oxide layer.

The dopants can be arranged either within the metal oxide layer or on one of the two surfaces of the metal oxide layer, namely on the carrier layer side or the contact layer side. Regardless of the arrangement of the dopants, the dopants are considered part of the metal oxide layer.

Particularly preferably, the dopant, in particular silver oxide, is arranged on the carrier layer side of the metal oxide layer. Thus, the dopant can be covered by the remaining metal oxide layer, in particular titanium oxide. This reduces the risk that ions from the dopant can penetrate into the contact layer and thus onto the body. Especially with silver oxide as a dopant, a release of the substances considered harmful The silver ions present are reduced. In this embodiment, the ions are kept away from the body both by the structure of the metal oxide layer and by the contact layer.

This effect can also be increased if the metal oxide layer is present as a closed layer.

However, the metal oxide layer, like the contact layer, can also be formed as an open layer.

The medical device is preferably a medical textile. The medical device is particularly preferably designed as a wound dressing, a bandage, an elastic bandage, a foam, a mask, or an incision film. This is advantageous because wound dressings, bandages, elastic bandages, foams, or incision films can usually be applied to the body and are intended to prevent infections at the application site. In particular, the medical device is designed as a wound dressing because preventing infection in the wound area is particularly important.

The carrier layer can preferably be selected from the group consisting of polyurethane (PUR, TPU, PCU), polyamide (PA), polyether, polyethylene (PE), polyester, polypropylene (PP), Poly (tetrafluoroethylene) (PTFE), silicones, viscose, cellulose and cotton.

Particularly preferred are nonwovens that can be made from the above materials. Examples of such nonwovens are nonwovens made from 90% viscose and 10% polyethylene/polypropylene, nonwovens made from polypropylene (hydrophobic), nonwovens made from polypropylene with a hydrophilic finish, needle-punched nonwovens made from polyethylene terephthalate (PET), and nonwovens made from 70% viscose and 30% polyethylene terephthalate. Furthermore, polyurethane films, scrims made from polyethylene terephthalate, cellulose gauze, and knitted fabrics made from polypropylene are also particularly preferred.

The medical device according to the invention can comprise, in addition to the carrier layer, the metal oxide layer, and the contact layer, further layers or bandage layers. For example, the medical device can comprise a backing layer as the outermost, body-facing layer. The backing layer can comprise a water-impermeable and water vapor-permeable plastic film, in particular a polyurethane film. In addition, a body-facing side of the backing layer can be adhesively coated, for example with an acrylate adhesive.

If the medical device is designed as a wound dressing, the adhesive-coated backing layer can advantageously encompass the other layers of the medical device and form an adhesive edge, whereby the medical device can then be designed in the manner of an island dressing. The adhesive edge can be used to attach the wound dressing to the patient's body.

Furthermore, it is particularly preferred, especially when the medical device is designed as a wound dressing, that the medical device further comprises an absorbent layer, in particular an absorbent foam layer. This allows the medical device to absorb more fluid. For example, the wound dressing is then also suitable for the treatment of more heavily exuding wounds. A foam layer in the form of a hydrophilic polyurethane foam is particularly suitable, which can advantageously comprise a water content of at least 10% by weight. The absorbent layer is preferably connected to a side of the carrier layer facing away from the body. The usually present backing layer is then connected to a side of the absorbent layer facing away from the body, so that the absorbent layer is arranged between the backing layer and the carrier layer. The layer thickness of the absorbent layer can be, for example, 0.5 to 5 mm, preferably 0.5 to 3 mm. Further possible

Features and advantages of the absorbent layer are described in WO

2010/ 000451 Al of fenbart . As an alternative to the absorbent foam layer, the absorbent layer can also comprise superabsorbent fibers (SAF) or superabsorbent particles (SAP), particularly superabsorbent fibers or superabsorbent particles made of polyacrylate. This allows even more wound exudate to be transported away from a wound and stored than with a conventional absorbent layer.

The wound dressing according to the invention, in combination with an absorbent layer, also has the advantage that germs that may develop in the absorbent layer cannot reach the body or the wound, since the germs cannot overcome the metal oxide layer. The ROS formed in the metal oxide layer kill the germs, thus preventing reinfection from the absorbent layer.

The medical device designed as a wound dressing is particularly well suited for treating wounds on the human or animal body in the granulation or epithelialization phase. Accordingly, the invention also relates to a medical device according to the invention for treating wounds on the human or animal body in the granulation or epithelialization phase. Likewise, the medical device, particularly designed as an incision film, is suitable for use in traumatic or surgical wounds.

The invention additionally relates to a method for reactivating and/or enhancing photocatalytic properties of the medical device by photoactivating the metal oxide layer with visible light. Photoactivation of the metal oxide layer, i.e. activating or restoring the ability of the metal oxide layer to generate ROS, enables the medical device to regain its antimicrobial properties, for example after storage in the dark. For this purpose, the medical device, after being removed from light-tight packaging, for example, can be exposed to visible light for approximately 5 to 15 minutes in order to restore the almost complete ability of the metal oxide layer to generate ROS. For example, photoreactivation can take place within 5 minutes using visible light with a wavelength of 400-780 nm and a light intensity of 200 mW/ ^cm2 . It is also possible to expose the medical device to daylight and/or visible ambient light after it has been attached to the human or animal body. This has the advantage of that photoactivation does not have to be carried out in a separate step but can be carried out during the actual intended use of the medical device.

Particularly preferably, the carrier layer can be transparent, opaque, or substantially permeable to visible light. Thus, visible light can pass through the carrier layer to the metal oxide layer and be used for photocatalysis and/or photoactivation.

Furthermore, the invention also relates to a method for producing a medical device according to the invention. In a first step, a carrier layer is provided. By means of plasma deposition, one or more metals are deposited onto the carrier layer and oxidized to form a metal oxide layer. Subsequently, a contact layer is applied to the metal oxide layer by means of plasma deposition.

The method according to the invention enables a simple and cost-effective production of the medical device. The carrier layer can be fed as a web-like material to a plasma reactor, where it is continuously coated, enabling a high throughput. In contrast to wet-chemical impregnation processes known from the prior art, with which, for example, silver is deposited on me- medical devices, the inventive production takes place in a dry state of the carrier layer. Thus, semi-finished products comprising the carrier layer and other moisture-sensitive substances can also be added to the production process. Examples of moisture-sensitive substances are activated carbon and superabsorbent fibers/particles. This allows throughput to be increased and production costs to be reduced.

The oxidation can take place either during the deposition of the metals or in a subsequent step.

According to a preferred embodiment, the carrier layer can be activated by means of the plasma. If the carrier layer has been subjected to plasma pretreatment, the adhesion between the metal oxide layer and the carrier layer can be increased, depending on the material of the carrier layer.

The invention also relates to a plasma-activated metal oxide for use in a method for treating infected wounds. The plasma-activated metal oxide is present on a carrier layer and is covered by a contact layer formed as a gas-permeable polymer layer, so that direct contact between the metal oxide and the wound surface is avoided. The invention also relates to a plasma-activated metal oxide for use in a method for the prevention of infections on the human or animal body, wherein the metal oxide is present on a carrier layer and is covered by a contact layer which is designed as a gas-permeable polymer layer, so that direct contact between the metal oxide and the body is avoided.

The advantage of this type of application is that the contact layer prevents the plasma-activated metal oxide from coming into contact with the body or wound, thus avoiding irritation caused by the metal oxide. The contact layer can also be used to functionalize the metal oxide in order to influence its interaction with the body or wound during application. For example, the contact layer can be hydrophobic to prevent it from sticking to the wound. Alternatively, the metal oxide can be covered with an adhesive, for example, to attach the metal oxide to the body.

Covered should be understood according to the invention in such a way that the covered layer is essentially in direct contact with the covering layer over its entire surface, i.e. touches it. However, this does not mean that the covering layer is closed. The covering layer can, for example, be porous or have perforations.

The invention and further advantageous embodiments and developments thereof are described and explained in more detail below with reference to the examples shown in the drawings. The features shown in the description and the drawings can be used individually or in any combination according to the invention.

Figure 1 shows a schematic sectional view of a first embodiment of a medical device,

Figure 2 shows a schematic sectional view of a medical device designed as a wound dressing,

Figure 3 shows the results of a touch test as proof of the antimicrobial activity of the medical device with a carrier layer comprising a PP nonwoven,

Figure 4 shows the results of a touch test as proof of the antimicrobial activity of the medical device with a carrier layer comprising a needle felt, Figure 5 shows the results of a touch test as proof of the antimicrobial activity of the medical device with a carrier layer comprising a PU film and

Figure 6 shows a diagram of the ROS activity of different metal oxide layers after dark storage and after photoactivation.

Figure 1 shows a sectional view of a medical device 1 according to the invention in a first embodiment. The medical device 1 comprises a carrier layer 2, which consists for example of a polyurethane film. The metal oxide layer 5 is applied to the side of the carrier layer 2 facing the body. The carrier layer 2 serves to carry the metal oxide layer 5 and as a base for applying the metal oxide layer 5. The contact layer 3 is arranged on the side of the metal oxide layer 5 facing the body 20 when the medical device 1 is in use.

Finally, the medical device 1 also comprises a backing layer 4 connected to a side of the carrier layer 2 facing away from the body 20 during use of the medical device 1. This delimits the medical device 1 to the outside and protects the medical device 1 in particular from contamination. The backing layer 4 consists of a water-impermeable and water vapor-permeable plastic film, for example a polyurethane film. The medical device 1 can advantageously be transparent in order to allow the passage of light, in particular visible light, to the metal oxide layer 5. In use, the medical device 1 can be placed on the body 20 and, if necessary, fixed with an additional dressing material such as a bandage or a film dressing.

Layers 2, 3, 4 and 5 form an essentially stable bond, so that no additional means are required to hold the individual layers 2, 3, 4 and 5 together.

Figure 2 shows a sectional view of a medical device according to the invention, which is designed as a wound dressing 11. In addition to the carrier layer 2, the metal oxide layer 5 and the contact layer 3, the wound dressing 1 has an absorbent layer 12. This is arranged on the side of the carrier layer 2 facing away from the body 20. The absorbent layer 12 is in particular an absorbent foam layer, for example in the form of a hydrophilic polyurethane foam. The absorbent layer 12 can, however, also comprise superabsorbent fibers (SAF) or superabsorbent particles (SAP). Due to the additional absorbent Layer 12 allows the wound dressing 11 to absorb more wound exudate.

It is therefore particularly suitable for the treatment of heavily exuding wounds. However, the absorbent layer 12 can also be advantageous in the treatment of dry wounds, namely when it is impregnated by the manufacturer with a proportion of water or another suitable liquid, such as isotonic saline solution or Ringer's solution.

The backing layer 4 of the wound dressing 11 in Figure 2 is fully adhesively coated. The adhesive 8 is preferably an acrylate adhesive. The backing layer 4 is attached by means of the adhesive 8 to the side of the absorbent layer 12 facing away from the body 20. The backing layer 4 coated with the adhesive 8 overlaps the layers 12, 2, 5 and 3 and thus forms an adhesive edge 10. With the adhesive edge 10, the wound dressing 11 can be permanently and easily attached to the body 20 of the patient without the need for a separate secondary dressing.

For protection during storage and to facilitate application of the medical device 1, it may have at least one cover layer (not shown). The cover layer is detachably connected to the contact layer 3 and is removed before the medical device 1 is applied to the body 20. The cover layer can, for example, comprise a two-part film layer made of siliconized polypropylene.

The medical device 1 can be manufactured by placing the carrier layer 2, for example comprising a polymer film, in particular a polymer film made of polyurethane or a nonwoven, on the drum electrode of a roll-to-roll plasma reactor. The plasma reactor is equipped with a high-frequency plasma generator connected to the drum electrode and with two magnetron sputtering sources mounted at a distance of 10 cm opposite the inner drum electrode. One sputtering source is equipped with a titanium (Ti) target and the other with a silver (Ag) target. After evacuating the vacuum system to a base pressure of at least 0.0001 Pa, the plasma reactor is flooded with argon to reach a pressure of 10 Pa. A plasma pretreatment is carried out for 10 minutes by generating a plasma with 400 W input power around the drum electrode to activate the carrier layer 2.

Subsequently, the pressure is reduced to 0.8 Pa using argon as the process gas. The carrier layer 2 on the drum electrode is rotated once through the Ti sputtering zone with a 2000 W magnetron power supply at a speed of 0.3 revolutions per minute (rpm), whereby a nominal Ti layer thickness of 20 nm is achieved on the carrier layer 2. In the next round, the carrier layer 2 on the drum electrode is rotated once through the Ag sputtering zone using a 600 W magnetron power supply at a speed of 1.2 rpm, forming a nominal Ag layer of 4 nm on the Ti layer. The gas supply is then switched to a 4:1 argon/oxygen mixture at a pressure of 10 Pa to perform a 10-minute plasma post-treatment, during which a plasma is generated around the drum electrode with 400 W input power to oxidize the Ag/Ti layer. The gas supply is then switched to a 5:1 argon/HMDSO mixture at a pressure of 7 Pa. The layer composite of carrier material 2 and metal oxide layer 5 is exposed to the plasma generated around the drum electrode with 400 W input power for 8 to 12 seconds in order to deposit a hydrophobic siloxane contact layer 3 with a nominal layer thickness of approximately 4 nm to 6 nm onto the oxidized metal oxide layer 5.

The nominal layer thicknesses can be adjusted by the rotation speed of the drum electrode.

To enhance the antimicrobial activity of the medical device

1, samples with a diameter of 9 mm were taken from of the medical device 1, which was produced according to the aforementioned method, and subjected to a contact test on agar plates 32. For this purpose, the samples were placed in triplicates for 10 minutes on a bacterial lawn 30 that had been pre-cultivated on an agar plate 32. The bacterial lawn 30 consists either of a strain of Escherichia coli (DSM 1103) or Staphylococcus aureus (ATCC 6538). After a 10-minute exposure time at room temperature, the samples were removed and the agar plates 32 were incubated overnight at 37°C. The agar plates 32 were then photographed with a Scan 300 colony counter. Example results for different carrier layers 2 are shown in Figures 3 to 5.

Figure 3 shows the results of the contact test for the medical device 1, which comprises a carrier material 2 made of a PP nonwoven. On the carrier material 2 is the metal oxide layer 5, which comprises a TiOx layer with a nominal thickness of 20 nm doped with an AgOx layer with a nominal thickness of 6 nm. Directly adjacent to the metal oxide layer 5 is the contact layer 3, which has a nominal thickness of 4 nm and comprises a hydrophobic siloxane. Under letter a) of the figure, as a reference, the uncoated carrier layer 2 has come into contact with the bacterial lawn 30, consisting either of S. aureus (upper row) or E. coli (lower row) in the region of contact surfaces 31. Under letter b) the carrier layer 2 coated with the metal oxide layer 5

(TiOx 20 nm / AgOx 6 nm) is shown (sample b). However, sample b does not have a contact layer 3. Under letter c), the carrier material 2 is coated with the metal oxide layer 5, onto which in turn a 6 nm thick contact layer 3 made of siloxane is applied (sample c).

The contact test, the results of which are shown in Figure 4, was carried out identically to that described for Figure 3. However, a needle-punched nonwoven was used as the carrier layer 2. The needle-punched nonwoven comprises two PET nonwovens, between which an absorbent body made of PET, PP and/or SAF is arranged.

Figure 5 shows the results of the touch test of the medical device 1 with a carrier layer 2 comprising a PU film.

The results of Figures 3 to 5 show that the medical device 1 has antimicrobial efficacy against S. aureus and E. coli, independent of the carrier material 2. At the contact surfaces 31, where the samples and the reference were placed on the bacterial lawn 30 for 10 minutes, the bacteria of the almost closed bacterial lawn 30 in samples b and c, which comprise the metal oxide layer 5, were killed, so that the bacterial lawn 30 is translucent to the light of the scanner in the region of the contact point 31. The Contact surfaces 31 appear in white in the figures.

The bacteria have not been killed at the contact surfaces 31 of the reference (letter a), i.e., the uncoated carrier material 2. The bacterial lawn 30 in the region of these contact surfaces 31 is not translucent to light and is therefore black. The bacterial lawn 30 was at most slightly disturbed by the application of the reference samples.

The ROS formed in the metal oxide layer 5 can be absorbed by the contact layer 3 according to the invention, so that the antimicrobial effectiveness is retained even with the contact layer 3.

The formed ROS can be detected indirectly using the fluorescent dye dihydrorhodamine 123 (DHR). The dye is oxidized by the H2O2 formed by the ROS. The measurement is performed at an excitation of 488 nm and an emission of 535 nm.

To demonstrate the reactivation or photoactivation of ROS formation in medical device 1, Ag and Ti-containing metal oxides, which had been stored in the dark for at least one month, as well as freshly prepared Fe and Ti-containing metal oxides were selected from the medical devices to be tested, and 6 mm samples were punched out. Half of the samples from each of the medical devices to be tested was treated for 5 minutes with light from a light source (hydrosun 575,

Hydrosun Medizintechnik GmbH) that emits visible light (400-780 nm). The samples were then exposed to DHR 123, and the fluorescence was measured in triplicate. The results are shown as relative values of the ROS signal in the diagram in Figure 6.

Figure 6 shows the ROS formed from medical devices 1 with a PU film as carrier material 2. The carrier material 2 without a metal oxide layer 5 serves as a reference. Sample 1 comprises a metal oxide layer 5 consisting of a 10 nm thick TiOx layer doped with a 4 nm thick AgOx layer. Sample 2 comprises a metal oxide layer 5 consisting of a 50 nm thick co-sputtered TiOx/AgOx layer comprising TiOx and AgOx in a ratio of 75:25. Sample 3 comprises a metal oxide layer 5 consisting of a 49 nm thick co-sputtered FeOx/TiOx layer comprising FeOx and TiOx in a ratio of 75:25.

All samples with a relative ROS signal of at least 4 show antibacterial activity in the touch test. It was further demonstrated that with only 5 minutes of photoactivation with visible light, the ROS formation in samples 1 and 2 could be successfully reactivated and increased, after the ROS formation had decreased due to storage in the dark. The values for the activated samples corresponded to the values of the samples that were not stored in the dark or to which the metal oxide layer 5 had been freshly applied (not shown). The values for sample 3, the FeOx/TiOx, could not be increased by photoactivation. However, they were approximately in the range greater than 4, so that antimicrobial activity can be assumed for sample 3 as well.

Claims

Claims 1. Medical device (1) for application to the human or animal body (20), in particular to a wound, comprising a carrier layer (2), a metal oxide layer (5), wherein the metal oxide layer (5) is applied to the carrier layer (2) and configured to form reactive oxygen species, and a contact layer (3), wherein the contact layer (3) in the state in which the medical device (1) is applied to the body (20) touches the body (20) and the contact layer (3) and the metal oxide layer (5) lie directly against one another. 2. Medical device (1) according to claim 1, characterized in that the contact layer (3) comprises a hydrophobic material or is formed from a hydrophobic material. 3. Medical device (1) according to claim 1 or 2, characterized in that the contact layer (3) is permeable to water vapor and oxygen. 4. Medical device (1) according to one of the preceding claims, characterized in that the contact layer (3) a polymer, preferably a silicone, in particular Polydimethylsiloxane. 5. Medical device (1) according to one of the preceding claims, characterized in that the thickness of the metal oxide layer (5) is 200 nm or less, preferably about 50 nm or less and particularly preferably 20 nm or less. 6. Medical device (1) according to one of the preceding claims, characterized in that the metal oxide layer (5) comprises a titanium oxide, wherein the titanium oxide is present as TiO, Ti ₂ O 3, TiA0 5 or preferably as TiO ₂ . 7. Medical device (1) according to one of the preceding claims, characterized in that the metal oxide layer (5) additionally comprises one or more compounds selected from the group consisting of N, C, S, Cl, Ag, Au, Pd, Pt, Fe, Ce, Cl, F, Pb, Si, Zn, Zr, B, Br, Cr, Hg, Sr, Cu, I, Sn, Ta, V, W, Co, Mg, Mn and Cd, particularly preferably Ag or Fe. 8. Medical device (1) according to one of the preceding claims, characterized in that the metal oxide layer (5) comprises silver oxide. 9. Medical device (1) according to claim 8, characterized in that the silver oxide is present in the form of nanoislands in or on the metal oxide layer (5). 10. Medical device (1) according to claim 8 or 9, characterized in that the proportion of silver oxide in the metal oxide layer (5) is 1% to 75%, preferably 25% to 50% and particularly preferably 25%. 11. Medical device (1) according to one of the preceding claims, characterized in that the metal oxide layer (5) is present as a closed layer. 12. Medical device (1) according to one of the preceding claims, characterized in that the medical device (1) is a wound dressing, a bandage, an elastic bandage, a foam, a mask or an incision film. 13. Medical device (1) according to one of the preceding claims, characterized in that the carrier material (2) is selected from the group consisting of polyurethane (PUR, TPU, PCU), polyamide (PA), polyether, polyethylene (PE), polyester, polypropylene (PP), poly(tetrafluoroethylene) (PTFE), silicones, viscose, cellulose and Cotton . 14. Medical device (1) according to one of the preceding claims, characterized in that the carrier material (2) is designed as a fleece. 15. Medical device (1) according to one of the preceding claims, characterized in that the medical device comprises an absorbent layer (12). 16. A method for reactivating and/or enhancing photocatalytic properties of a medical device (1) according to one of the preceding claims by photoactivating the metal oxide layer (5) with visible light. 17. Method for manufacturing a medical device (1) according to any one of the preceding claims, wherein the method comprises the following steps: - Providing a carrier layer (2), - applying at least one metal by plasma deposition, - oxidizing the at least one metal to form a metal oxide layer (5) and - Applying a contact layer (3) by means of plasma deposition. 18. The method according to claim 17, wherein the carrier layer (2) is activated by means of plasma. 19. Plasma-activated metal oxide for use in a method for the treatment of infected wounds, wherein the metal oxide is present on a carrier layer (2) and is covered by a gas-permeable polymer layer so that direct contact between the metal oxide and the wound surface is avoided. 20. Plasma-activated metal oxide for use in a method for the prevention of infections on the human or animal body (20), wherein the metal oxide is present on a carrier layer (2) and is covered by a gas-permeable polymer layer so that direct contact between the metal oxide and the body (20) is avoided.