Antimicrobial medical device

Abstract

The invention relates to a medical device (1) for applying to the human or animal body (20), comprising a carrier layer (2), a metal oxide layer (5) and an adhesive layer (3), wherein the adhesive layer (3) is applied to the carrier layer (2) and the metal oxide layer (5) is applied to the adhesive layer (3) and the metal oxide layer (5) is configured to form reactive oxygen species and wherein when the medical device (1) is applied to the body (20), the metal oxide layer (5) is arranged on the side of the adhesive layer (3) facing the body (20), characterised in that the adhesive layer (3) and the metal oxide layer (5) are directly adjacent to one another and the metal oxide layer (5) only partially covers the adhesive layer (3).

Description

[0001] Antimicrobial medical device

[0002] The invention relates to a medical device for application to the human or animal body, comprising an adhesive 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 preventing infections.

[0003] 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 treated 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 germ concentrations to safe levels also has a limited lifespan.

[0004] 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.

[0005] The photoelectrochemical activity of titanium oxides (TiOx) has long been known. Titanium oxides are considered one of the few currently known materials suitable for photocatalysis for applications in self-cleaning and antimicrobial coatings, due to 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.

[0006] 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) considered TiCy catalysts that generate reactive oxygen species (ROS). 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.

[0007] 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., ranges of energy levels. The highest energy level of the valence band is separated from the lowest energy level of the conduction band by an energy gap called the band gap. Electrons and holes interact with oxygen species in the vicinity of the semiconductor material to produce reactive oxygen species (ROS), which belong to the free radical family. The electrons interact with oxygen molecules to produce superoxide radicals. The holes can interact with water molecules or adsorbed OH groups to produce hydroxyl radicals. The ROS can react further to produce new radicals.For example, superoxide radicals can react with electrons under acidic conditions to generate hydrogen peroxide molecules. The resulting hydrogen peroxide can then interact either with superoxide radicals or with electrons to form hydroxyl radicals.

[0008] These short-lived radicals induce further ROS such as molecular singlet oxygen through electron transfer or recombination, X O2 and hydrogen peroxide, H2O2. These species efficiently oxidize proteins and lipids in an aqueous environment, thus inactivating bacteria, fungi, and viruses.

[0009] 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.

[0010] Ag nanoislands can be doped onto defective TiOx layers deposited by magnetron sputtering and thus containing oxygen vacancies. Subsequent plasma oxidation can produce a catalyst surface with a pronounced metal oxide nanostructure and 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, 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.

[0011] 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 photocatalytic material, which is 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, which predominantly comprises titanium oxide. The wound dressings have photocatalytic properties that produce antifouling and antimicrobial effects. Further compounds can be added to the metal oxide layer, which can vary the photocatalytic properties of the metal oxide layer consisting predominantly of titanium oxide.

[0012] Self-adhesive medical devices are known from the prior art. They can essentially consist of a carrier material, e.g. a flat nonwoven layer, coated on one side with an adhesive. The adhesive can be covered by a removable cover film, a so-called release liner, to prevent contamination of the adhesive during storage and to simplify application of the medical device. Adhesives with high adhesive strength, such as synthetic rubber-based adhesives, are generally used to coat the carrier material. Such adhesives can ensure secure fixation of the wound dressing to the patient's body.

[0013] A disadvantage compared to the state of the art is that medical devices with antimicrobial layers cannot simply be provided with an adhesive layer, since the antimicrobial properties are lost or reduced by covering them.

[0014] The invention is therefore based on the object of providing an adhesive medical device with antimicrobial properties which is easy to manufacture and has improved adhesive and antimicrobial properties.

[0015] This object is achieved by a medical device for application to the human or animal body. The medical device comprises a carrier layer, a metal oxide layer and an adhesive layer, wherein the adhesive layer is applied to the carrier layer and the metal oxide layer is applied to the adhesive layer. The metal oxide layer is configured to form reactive oxygen species. In the state in which the medical device is applied to the body, the metal oxide layer is arranged on the side of the adhesive layer facing the body, wherein the adhesive layer and the metal oxide layer are in direct contact with one another. The antimicrobial activity of the ROS from the metal oxide layer is not reduced by the structure of the medical device.

[0016] Preferably, the metal oxide layer can contact the body when the medical device is applied to the body. This allows ROS formed in the metal oxide layer to reach the body without the ROS having to diffuse through a covering layer.

[0017] According to the invention, the metal oxide layer only partially covers the adhesive layer, so that the metal oxide layer is present as a non-closed or open layer. This allows the adhesive layer to form adhesive bonds with the body through the open areas, i.e., the areas of the adhesive layer not covered by the metal oxide layer, when the medical device is applied to the body.

[0018] According to the invention, a non-continuous layer is understood to mean a layer whose coverage is less than or equal to 95%. This means that a maximum of 95% of the surface of the adhesive layer facing the body when applied to the body is covered by the metal oxide layer or is in contact with the metal oxide layer.

[0019] By varying the degree of coverage, the adhesive properties of the medical device can be directly adjusted. The higher the degree of coverage, the lower the possible

[0020] Adhesion to the body . Due to the antimicrobial properties of ROS,

[0021] Colonization of the area of ​​the body covered by the medical device by microorganisms is reduced, thus preventing inflammation. Likewise, already established microorganisms can be killed by the device.

[0022] 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.

[0023] Because the metal oxide layer is on the body-facing side of the adhesive layer, thus constituting an outer layer, the medical device can be manufactured simply and cost-effectively. Since the metal oxide layer is directly adjacent to the adhesive layer, it can be applied to an existing adhesive layer without requiring any design changes. This allows adhesive medical devices to be additionally treated with antimicrobial properties in a simple manner.

[0024] According to the invention, the adhesive layer and the metal oxide layer are in direct contact with each other. This means that the adhesive layer and the metal oxide layer are in almost full contact. Of course, due to manufacturing tolerances, there may be areas where the two

[0025] The layers are slightly spaced apart, but these areas are present only to a very small extent. By definition, however, no further layer, such as a distribution layer, is provided between the adhesive layer and the metal oxide layer.

[0026] For use, the medical device with the metal oxide layer is applied or placed on the human or animal body, where it then adheres by means of the adhesive layer. Essentially, application to the body means application to the skin. However, according to the invention, application to a wound also falls under this formulation, regardless of whether the wound affects the skin or other areas of the body.

[0027] Due to the property of the metal oxide layer to form ROS, the medical device according to the invention makes it possible to provide an antibacterial activity generated by ROS at a site of action much more quickly than is the case with conventional Ag release systems. As already explained at the beginning, 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. The photocatalysis is based on the fact that light generates electron-hole pairs in a semiconductor material such as titanium dioxide (TiCt), which is present in the metal oxide layer, when the energy of the photons is greater than the band gap. An electron changes from the valence band to the conduction band of the material and leaves behind 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.

[0028] Surprisingly, it was found that a metal oxide layer applied in the nanometer range does not negatively influence the adhesive properties of the adhesive layer, or rather, the influence is so small that the adhesion between the medical device and the body is only slightly reduced.

[0029] This is because metal oxides can form nanoislands on the adhesive layer and thus create a non-closed metal oxide layer. The nanoislands can form up to a metal oxide layer thickness of approximately 20 nm to 25 nm. With greater layer thicknesses, complete nanoislands do not form, so the metal oxide layer is present as a closed layer. According to the invention, layer thicknesses are to be understood as nominal thicknesses. This means that the layers are applied in this thickness in a manufacturing process, but can then subsequently change, for example, through curing or cooling. For example, it is possible that metal oxides that are applied as a layer subsequently form nanoislands, i.e. that the metal oxides "contract" in the shape of islands.If one were to measure the layer thickness of an island directly, the layer thickness in the island would be larger than the nominal (applied) layer thickness of the metal oxide due to the contraction.

[0030] In a preferred embodiment of the invention, the metal oxide layer is present in the form of nanoislands on the adhesive layer, whereby the active interface at which the ROS are generated is enlarged and thus the generation of ROS is increased.

[0031] The metal oxide layer can also be applied to the adhesive layer in the form of islands. The islands can have any shape, e.g., circles, ovals, or stars. The islands can also be applied to the adhesive layer in stripes.

[0032] In an alternative embodiment of the invention, the

[0033] Metal oxide layer can have perforations. The perforations can be essentially round and present at regular intervals in the layers. They can 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 configuration. The adhesive layer preferably comprises an adhesive made of acrylate, a synthetic rubber or a silicone. The adhesive layer can also be made of an acrylate adhesive, a synthetic rubber adhesive or a silicone adhesive. Acrylic adhesives and rubber adhesives can have a high adhesive strength and be cost-effective. Silicone adhesive can be gentle on the tissue (atraumatic), but is generally more expensive than the other two adhesive variants mentioned above.

[0034] Preferably, the adhesive layer comprises an acrylic pressure-sensitive adhesive or polyurethane gels.

[0035] The adhesive layer particularly preferably comprises an adhesive silicone gel. An adhesive silicone gel is a cross-linked silicone polymer with a gel-like consistency. The silicone gel is typically formed by a hydrosilylation (or polyaddition) reaction between a polydimethylsiloxane with alpha-omega vinyl end groups and a Si-H-containing siloxane, which reaction is catalyzed by a platinum catalyst. To accelerate the polymerization process, thermal curing can preferably be carried out. Furthermore, the silicone gel can be solvent-free.

[0036] Adhesive silicone gels are known from the prior art, e.g., from US 2007 / 0270555 A1, and are commercially available. Silicone systems for producing such silicone gels are generally sold by silicone manufacturers as two-component kits.

[0037] The adhesive layer comprising the adhesive silicone gel has the advantage that the medical device can be removed from the patient's skin without causing pain or skin damage and without leaving residue on the skin. At the same time, the adhesive layer comprising the adhesive silicone gel has sufficient adhesive strength to securely fix the medical device to the patient's body. The silicone gel can also be removed from the body and reapplied multiple times, allowing the medical device to be repositioned as needed.

[0038] Alternatively, the adhesive layer may also comprise hydrogels that allow adhesion to the body. Examples of such

[0039] Hydrogels are known from EP 2 338 529 A1. The adhesive layer can have a thickness between 20 pm and 2 mm.

[0040] According to a particularly preferred embodiment of the invention, the medical device can be covered on the body-facing side by a removable cover film, a so-called release liner. The cover film thus covers the metal oxide layer and the adhesive layer to prevent contamination of the body-facing surface of the medical device during storage and to simplify the attachment of the medical device.

[0041] The thickness of the metal oxide layer can be 200 nm or less. Preferably, the thickness of the metal oxide layer is 1 nm to 50 nm, or more preferably 4 nm to 20 nm. In particular, it is preferred that the thickness is 5 nm to 10 nm. A thin metal oxide layer is preferred because less metal oxide is required to manufacture the medical device, thus reducing manufacturing costs. Also, with the preferred thickness of the metal oxide layer, the adhesive properties of the adhesive layer are not significantly affected.

[0042] According to a preferred embodiment, the metal oxide layer comprises a titanium oxide, wherein the titanium oxide is present as TiO, Ti2O3, TiA05 or particularly preferably as TiO2. Preferably, the titanium oxides have oxygen vacancies. Titanium oxides have the

[0043] The advantage is that they are readily available and have a band gap between 3.0 eV and 3.2 eV, which corresponds to a light wavelength of approximately 390 nm.

[0044] To achieve a shift in the range of light wavelengths that can activate photocatalysis, the metal oxide layer can comprise 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. The metal oxide layer is preferably doped with these atoms. The listed compounds and their derivatives are also referred to as dopants.

[0045] The metal oxide layer particularly preferably comprises Ag or Fe, as this enables a shift of the light wavelength into the visible range.

[0046] The proportion of titanium oxide in the metal oxide layer can be up to 100%. It is preferably in a range of 75% to 100%, 50% to 75%, or 25% to 50%.

[0047] Preferably, the metal oxide layer is 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 40%. This enables reliable generation of ROS in the metal oxide layer at

[0048] Activation of photocatalysis by visible light.

[0049] According to a particularly preferred embodiment, the proportion of titanium oxide in the metal oxide layer is 60% and the proportion of silver oxide is 40%. This enables a metal oxide layer comprising titanium oxide with a nominal layer thickness of 6 nm doped with silver oxide with a nominal layer thickness of 4 nm. This metal oxide layer (6 nm TiOx / 4 nm AgOx) only slightly influences the adhesive properties of the medical device while simultaneously maintaining high antimicrobial activity.

[0050] 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.

[0051] Typically, the dopants are homogeneously distributed in or on the metal oxide layer.

[0052] 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 adhesive layer side or on the side facing the body. Regardless of the arrangement of the dopants, the dopants are considered part of the metal oxide layer.

[0053] Preferably, the dopant, in particular silver oxide, is arranged on the metal oxide layer on the adhesive layer side. Thus, the dopant can be covered by the remaining metal oxide layer, in particular titanium oxide. This reduces the risk of ions from the dopant being transferred to the body. Especially when silver oxide is used as the dopant, the release of silver ions, which are considered harmful, can be reduced.

[0054] The medical device is preferably a wound dressing, a plaster, a fixation plaster, an adhesive bandage, an adhesive tape, an adhesive film, or an incision film. This is advantageous because such medical devices 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 an incision film or adhesive film, since preventing infection in the surgical field is particularly important.

[0055] 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.

[0056] The carrier layer can particularly preferably be a film, in particular a film made of polyurethane. The polyurethane film can preferably be water-impermeable and water vapor-permeable.

[0057] The medical device according to the invention can comprise further layers in addition to the carrier layer, the metal oxide layer, and the adhesive layer. 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 coated adhesively, for example with an acrylate adhesive.

[0058] Furthermore, it is particularly preferred, particularly when the medical device is designed as a wound dressing, for the medical device to further comprise an absorbent layer, in particular an absorbent foam layer. This enables the medical device to absorb more fluid. For example, the wound dressing is then also suitable for treating more heavily exuding wounds. A foam layer in the form of a hydrophilic polyurethane foam is particularly suitable and can advantageously contain 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 backing layer which is usually present 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 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 disclosed in WO 2010 / 000451 A1.

[0059] 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.

[0060] The medical device 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 penetrate the metal oxide layer. The ROS formed in the metal oxide layer kill the germs, thus preventing reinfection from the absorbent layer.

[0061] The medical device, in particular designed as an incision film, is particularly suitable for use in traumatic or surgical wounds.

[0062] The invention also 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 a 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 be carried out with visible light with a wavelength of 400-780 nm and a light intensity of 200 mW / cm 2within 5 minutes. It is also possible to expose the medical device to daylight and / or visible ambient light after it has been applied to the human or animal body. This has the advantage that photoactivation does not have to be performed in a separate step, but can take place during the medical device's intended use.

[0063] 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.

[0064] Furthermore, the invention also relates to a method for producing a medical device according to the invention. In a first step, a carrier layer, in particular a polyurethane film, which has an adhesive layer on at least one side, is provided. By means of plasma deposition, one or more metals are deposited onto the adhesive layer and oxidized to form a metal oxide layer.

[0065] The method according to the invention enables simple and cost-effective production of the medical device. The carrier layer comprising the adhesive layer can be fed as a web-like material to a plasma reactor, where it is continuously coated, enabling high throughput. In contrast to wet-chemical impregnation processes known from the prior art, with which, for example, silver is applied to medical devices, the production according to the invention 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 fed into the production process. Examples of moisture-sensitive substances are activated carbon and superabsorbent fibers / particles. Thus, throughput can be increased and production costs reduced.

[0066] Since the metal oxide layer is applied to the adhesive layer, which is present as an outer layer, existing adhesive products can easily be subsequently provided with antimicrobial properties.

[0067] The oxidation for the targeted production of the metal oxide layer can take place either during the deposition of the metals or in a subsequent step.

[0068] According to a preferred embodiment, the adhesive layer can be activated by means of the plasma. If the adhesive layer has been subjected to a plasma pretreatment, the adhesion between the metal oxide layer and the adhesive layer can be increased. The invention also relates to a plasma-activated metal oxide for

[0069] Use in a method for preventing infections on the human or animal body. The metal oxide is applied to an adhesive layer. The metal oxide can be fixed to the body by the adhesive layer, so that the metal oxide lies directly on the body.

[0070] The advantage of this type of application is that the adhesive layer adheres the plasma-activated metal oxide directly to the body and fixes it there. This also helps prevent infections in the area where the adhesive layer adheres to the body.

[0071] According to the invention, "covered" should be understood to mean that the covered layer is essentially in direct contact with the covering layer over its entire surface, i.e., it touches it. However, this does not mean that the covering layer must be closed. The covering layer can, for example, also be porous or have perforations.

[0072] 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. They show:

[0073] Figure 1 is a schematic sectional view of an embodiment of a medical device,

[0074] Figure 2 is an electron microscopic view of a metal oxide layer according to the invention and

[0075] Figure 3 shows the results of a touch test as proof of the antimicrobial activity of the medical device with a silicone adhesive layer.

[0076] Figure 1 shows a schematic 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 adhesive layer 3 is applied to the side of the carrier layer 2 facing the body. The carrier layer 2 serves to carry the adhesive layer 3. The metal oxide layer 5 is arranged on the side of the adhesive layer 3 facing the body 20 during use of the medical device 1. The metal oxide layer 5 only partially covers the adhesive layer 3, it is designed as a non-closed metal oxide layer 5. In the illustrated embodiment, the metal oxide layer 5 is in the form of individual nanoislands 8 on the

[0077] Adhesive layer 3 is provided so that the adhesive layer 3 can contact the body 20 through the open areas, i.e. the areas between the nanoislands 8 in which the adhesive layer 3 is not covered by the metal oxide layer 5.

[0078] In use, the medical device 1 can be placed on the body 20. The adhesive layer 3 forms adhesive bonds through the non-closed metal oxide layer 5, with which the medical device 1 adheres to the body 20.

[0079] The medical device 1 can advantageously be designed to be transparent in order to allow light, in particular visible light, to pass through to the metal oxide layer 5.

[0080] Layers 2, 3 and 5 form an essentially stable bond, so that no additional means are required to hold the individual layers 2, 3 and 5 together.

[0081] For protection during storage and to facilitate application of the medical device 1, it can have at least one cover layer (not shown) on the side that contacts the body 20 during use. The cover layer is releasably bonded to the metal oxide layer 5 and the adhesive layer 3 and is removed before the medical device 1 is placed on the body 20. The cover layer can, for example, comprise a two-part film layer made of siliconized polypropylene.

[0082] The medical device 1 can be manufactured by placing an adhesively coated carrier layer 2, for example a polymer film made of polyurethane coated with a silicone adhesive, onto 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 adhesive layer 5 .

[0083] The pressure is then reduced to 0.8 Pa using argon as the process gas. The carrier layer 2 comprising the adhesive layer 5 is rotated on the drum electrode once through the Ti sputtering zone using a 2000 W magnetron power supply at a speed of 0.9 revolutions per minute (rpm), thereby achieving a nominal Ti layer thickness of 5 nm on the adhesive layer 5. In the next round, the carrier layer 2 comprising the adhesive layer 5 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, thereby producing a nominal Ag layer of 4 nm on the Ti layer.Subsequently, the gas supply is 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 with 400 W input power is generated around the drum electrode to oxidize the Ag / Ti layer. This process deposits a metal oxide layer 5 with a nominal thickness of approximately 9 nm on the adhesive layer 3.

[0084] The nominal layer thicknesses can be adjusted by the rotation speed of the drum electrode.

[0085] Figure 2 shows a medical device 1 produced according to the method according to the invention. The scanning electron micrograph shows the surface of the medical device 1 facing the body 20. Titanium oxide with a nominal layer thickness of 10 nm was deposited on the adhesive layer 3 (black) according to the above method and doped with silver oxide with a nominal layer thickness of 4 nm. After oxidation, the metal oxides are present as nanoislands 8, which are shown in white in the electron microscopic view. In this exemplary embodiment, the metal oxide layer 5 only partially covers the adhesive layer 3. The metal oxide layer 5 is thus designed as a non-closed layer.

[0086] It was shown that the medical device 1 according to the invention, which was produced using the production method according to the invention, no longer has sufficient adhesive properties until the nominal layer thickness of the titanium oxide reaches 20 nm (+ 4 nm nominal layer thickness of a silver oxide). For this purpose, TiOx layers with nominal thicknesses of 5 nm, 10 nm and 20 nm were deposited on samples of a polyurethane film (Acrysil™ from Advanced Silicone Coating) coated with a silicone adhesive, and each layer was doped with 4 nm (nominal thickness) of AgOx. Compared to the polyurethane film which does not have a metal oxide layer 5, the sample with 5 nm TiOx was imperceptibly easier to peel off from a smooth surface. The sample with 10 nm TiOx was slightly easier to peel off from the smooth surface, but the adhesive properties are sufficient for an application.Only the sample with 20 nm TiOx no longer adheres sufficiently firmly to the smooth surface.

[0087] In order to demonstrate the antimicrobial activity of the medical device 1, samples with a diameter of approximately 10 mm square were cut out of the medical device 1, which was produced according to the aforementioned method, and subjected to a touch test on agar plates 32. For this purpose, the samples were placed in triplicates on a bacterial lawn 30 that had been pre-cultured on an agar plate 32. The bacterial lawn 30 consists of either a strain of Escherichia coli (DSM 1103) or Staphylococcus aureus (ATCC 6538). After a 60-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 using a Scan 300 colony counter.

[0088] The following samples were subjected to the touch test:

[0089] Figure 3 shows the results of the contact test for the samples of medical device 1 from the table. A polyurethane film coated with a silicone adhesive (Acrysil™ from Advanced Silicone Coating) and without a metal oxide layer 5 serves as a negative control (ref-S, ref-E). The samples are also Acrysil™ from Advanced Silicone Coating, coated with metal oxide layers 5 of varying thicknesses.

[0090] In order to demonstrate that a thin metal oxide layer 5 with a nominal layer thickness of less than 10 nm does not impair the antimicrobial properties, a positive control (pos-S, pos-E) was introduced, which has a metal oxide layer 5 of a conventional, closed layer thickness with 40 nm TiOx doped with 4 nm AgOx.

[0091] The results shown in Figure 3 show that the medical device 1 exhibits antimicrobial effectiveness against S. aureus and E. coli even with a very thin metal oxide layer 5, namely a nominal layer thickness of 5 nm of titanium oxide doped with 4 nm (nominal layer thickness) of silver oxide. In these tests, deposition directly onto the adhesive layer 3 impairs neither the adhesive properties nor the antimicrobial effectiveness of the ROS formed in the metal oxide layer 5. At the contact surfaces 31, where the samples and the controls were placed on the bacterial lawn 30 for 60 minutes, the bacteria of the almost closed bacterial lawn 30 in the positive control (pos-S, pos-E) and samples a to d, which comprise the metal oxide layer 5, were killed, so that the bacterial lawn 30 in the area of ​​the contact point 31 is translucent to the light of the scanner.The contact surfaces 31 appear white in the figure. At the contact surfaces 31 of the negative control (ref-S, ref-E), i.e., the carrier material 2 with the adhesive layer 3, but without the metal oxide layer 5, the bacteria were not killed. 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 removal of the negative control.

Claims

Claims 1. A medical device (1) for application to the human or animal body (20), comprising a carrier layer (2), a metal oxide layer (5) and an adhesive layer (3), wherein the adhesive layer (3) is applied to the carrier layer (2) and the metal oxide layer (5) is applied to the adhesive layer (3), and the metal oxide layer (5) is configured to form reactive oxygen species, and wherein the metal oxide layer (5) is arranged on the side of the adhesive layer (3) facing the body (20) when the medical device (1) is applied to the body (20), characterized in that the adhesive layer (3) and the metal oxide layer (5) lie directly against one another and the metal oxide layer (5) only partially covers the adhesive layer (3).

2. Medical device (1) according to claim 1, characterized in that in the state in which the medical device (1) is applied to the body (20), the metal oxide layer (5) contacts the body (20).

3. Medical device (1) according to claim 1 or 2, characterized in that the adhesive layer (3) comprises or is formed from an acrylate or silicone.

4. Medical device (1) according to one of the preceding claims, characterized in that the thickness of the metal oxide layer (5) is 1 nm to 50 nm, preferably 4 nm to 20 nm and particularly preferably 5 nm to 10 nm.

5. 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, Ti2O3, TiA05 or preferably as TiO2.

6. Medical device (1) according to one of the preceding claims, characterized in that the metal oxide layer (5) is in the form of nanoislands on the adhesive layer (3).

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 proportion of silver oxide in the metal oxide layer (5) is 1% to 75%, preferably 25% to 50% and particularly preferably 40%.

10. Medical device (1) according to one of the preceding claims, characterized in that the medical device (1) is a wound dressing, a plaster, a fixing plaster, an adhesive plaster, a bandage, a bandage or in particular an incision film.

11. 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.

12. Medical device (1) according to one of the preceding Claims, characterized in that the carrier material (2) is designed as a film, in particular as a polyurethane film.

13. 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.

14. 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) which has an adhesive layer (3) on at least one side, - applying at least one metal by means of plasma deposition onto the adhesive layer (3) and - oxidizing the at least one metal to form a metal oxide layer (5).

15. The method according to claim 14, wherein the adhesive layer (2) is activated by plasma.

16. 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 an adhesive layer (3) and by the Adhesive layer (3) can be fixed on the body (20) so that the metal oxide lies directly on the body (20).

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