Absorbent wound dressing effective against biofilms

Abstract

The present invention relates to a highly absorbent wound dressing having an antimicrobial composition. The wound dressing comprises a pad containing an absorbent core. The antimicrobial composition comprises silver, zinc and EDTA and provides a broad spectrum of activity against both harmful microorganisms and the biofilms formed by these pathogens.

Description

[0001] Ref. 93220766-WO-PCT - March 11, 2026

[0002] Title: Absorbent wound dressing with efficacy against biofilms

[0003] Technical field of the invention

[0004] The present invention relates to wound treatment, in particular the treatment of wounds that are infected or where there is a risk of infection. This includes chronic and / or exuding wounds as well as wounds where an existing infection has already led to the formation of a biofilm in the wound.

[0005] Background of the invention

[0006] Chronic wounds remain a problem in modern medicine. Older people and high-risk patients, such as diabetics, are particularly at risk of injuries not healing, or not healing completely. In such cases, the wound healing process is disrupted for various reasons, resulting in a persistent defect in the skin barrier. This leads to a reduction in the quality of life for those affected. Furthermore, the risk of infection increases with the duration of tissue exposure. If such an infection occurs, the prognosis worsens. Because the body's own metabolic processes are impaired in the area of ​​the chronic wound, and a regular immune response is either absent or incomplete, pathogens can subsequently proliferate at the site of infection.In the further course of the infection, a biofilm often forms, in which bacterial pathogens combine to form a community that exhibits increased resistance to biocides and antibiotics, thus making further treatment extremely difficult. This stage increases the likelihood of further complications such as necrosis or sepsis.

[0007] Antibiotic wound dressings are known from current technology. However, these are either insufficiently effective against biofilms or unsuitable for use on exuding wounds due to inadequate absorption properties (inadequate exudate management). Yet, the aforementioned chronic wounds tend to produce large amounts of wound exudate. Undrained wound exudate can soften the wound edges (maceration) and, furthermore, prevent growth factors and fibroblasts from being available within the wound to the necessary extent. Consequently, the healing response stagnates.

[0008] EP 1 755569 B9 describes a wound dressing with ointment that additionally contains an antibacterial metal such as silver. However, this wound dressing is neither suitable for the treatment of weeping wounds nor effective in the treatment of wounds permeated with biofilm.

[0009] Consequently, there is a need for a wound dressing that exhibits sufficient antimicrobial efficacy, even against biofilms, and is capable of absorbing large amounts of wound exudate as part of effective exudate management to prevent tissue softening and softening of the wound edges. To meet the demands of everyday clinical practice, the product of choice should also be ready for immediate use, maintain sufficient stability during prolonged storage, and be resistant to potential temperature fluctuations.

[0010] Summary of the invention

[0011] The aforementioned problem is solved by a wound dressing comprising a cushion, wherein the cushion has a first wound-facing non-woven layer and a second wound-away non-woven layer, wherein the material of the first non-woven layer is fluid-permeable and the material of the second non-woven layer differs from the material of the first non-woven layer, wherein the cushion further comprises an absorbent core comprising a superabsorbent substance, and the first non-woven layer and the second non-woven layer enclose the absorbent core and together form a continuous border surrounding the absorbent core in which the first non-woven layer and the second non-woven layer are connected to each other.

[0012] characterized in that the first nonwoven layer has an antimicrobial composition which protects the ingredients

[0013] a) ionic silver or silver nitrate,

[0014] b) ionic zinc, zinc sulfate or zinc nitrate, and

[0015] c) EDTA or tetra-sodium EDTA

[0016] contains.

[0017] The wound dressing according to the invention is effective against human pathogenic organisms and their biofilms due to its antimicrobial ingredients. Furthermore, the wound dressing according to the invention is able to absorb large quantities of wound exudate and retain the absorbed exudate. The wound dressing can be specifically formulated for the treatment of different wound types and application conditions in order to ensure the best possible care.

[0018] Furthermore, the wound dressing according to the invention can also be used when antibiotic-resistant bacteria are present in the wound to be treated. This is because, while antibiotics are usually organic compounds that can be broken down, cleaved, or otherwise deactivated by resistant bacteria, such resistance has not been observed with regard to the antimicrobial ingredients of the present invention.

[0019] Furthermore, the wound dressing according to the invention can exhibit wound-healing properties. This is achieved through the use of zinc, which stimulates epithelial formation, has cytoprotective properties, and exerts an anti-inflammatory effect.

[0020] The zinc and silver cations released during wound treatment can supply moisture to the wound via their adhering hydration shells. A controlled moist wound environment promotes the healing process.

[0021] The wound dressing can be an absorbent or superabsorbent dressing, an island dressing, or a compress. The first non-woven fabric layer within the wound dressing can serve as the wound contact layer.

[0022] The following explains how the wound dressing can be structurally and chemically designed to provide the greatest possible benefit in practice.

[0023] Detailed description of the invention

[0024] The term "medically acceptable material" as used in the invention refers to a non-toxic, lint-free, and stable substance (e.g., a substrate) that, under normal conditions, is insoluble in both polar and non-polar compounds and cannot be degraded or liquefied to any significant extent by the secretions of animal or bacterial cells. The term "nonwoven" refers to a layer of interconnected fibers that are not woven and are generally not arranged in a repeating pattern.

[0025] The term “colony-forming unit” (CFU) refers to a single dividing cell of a single-celled organism, in particular a human-pathogenic single-celled organism or bacterium.

[0026] "Coated" means that the surface of a solid (e.g., a nonwoven fabric) is at least partially covered or overlaid with a substance that differs from the structure of the solid. In particular, the coating can be fiberless and / or hydrophilic.

[0027] The term "configured for application to a wound" means intended and suitable for application to a wound for a therapeutic purpose in the sense of wound treatment.

[0028] The term "antimicrobial ingredients" refers to a) silver – in particular ionic silver – and silver salts, b) zinc – in particular ionic zinc – and zinc salts, and c) EDTA and EDTA salts. Ingredients a) to c) together constitute the antimicrobial composition according to the invention.

[0029] “t-EDTA” refers to the compound tetrasodium ethylenediaminetetraacetic acid.

[0030] The term "antimicrobial" means, in its broadest sense, that an ingredient, mixture of ingredients, or an article treated with it (e.g., a wound dressing) is able to inhibit or halt the growth of microorganisms or to reduce the number of viable microorganisms. In a narrower sense, it means that such an article is able, in a test according to ISO 20743:2021, to reduce the number of CFUs of Pseudomonas aeruginosa strain ATTC 27853 and / or Staphylococcus aureus strain ATTC 25923 by at least three logarithmic levels, preferably by at least four logarithmic levels, particularly preferably by at least five logarithmic levels, and most preferably by at least six logarithmic levels, compared to an identical article without the active ingredient. Furthermore, the term "antimicrobial" includes the term "antibacterial."The term "biofilm" refers to a thin, spreading layer of slime containing populations of microorganisms. This slime film is formed by the microorganisms and is a matrix of extracellular polymeric material that encloses them. Typically, the microbial populations are mixed. Biofilms form on surfaces, which can include wound tissue. The microorganisms organized within the biofilm exhibit increased resistance to conventional antibiotics, disinfectants, and the immune systems of higher organisms.

[0031] The term "biofilm reducing" encompasses both the killing of bacteria within the biofilm (disinfectant properties) and the breaking of chemical bonds and the removal of chemical bonding partners from the biofilm-forming extracellular matrix. The latter reduces the resistance of the microorganisms previously organized within the biofilm to influences such as disinfectants, antibiotics, the immune system, or environmental factors in general. Within the scope of the present invention, only those substances suitable for application to open wounds without causing significant harm to the individual being treated are considered biofilm reducing.

[0032] "Coated" means that the surface of a solid is at least partially covered or overlaid by a substance that differs from the structure of the solid.

[0033] The term "wound-facing" means that an object or material in use is oriented towards the wound or skin, but does not necessarily have to touch it. Another term for "wound-facing" is "proximal".

[0034] The term "distal" means that an element in use points away from the wound or skin, or is turned away from the wound.

[0035] The present invention relates to a wound dressing. This wound dressing can be used alone or, after being applied to a wound, secured at the wound site as needed by a secondary dressing, adhesive film, adhesive strips, or other fixatives. The invention also relates to wound dressings equipped with optional adhesive surfaces that can be applied to the wound area without any additional aids. One possible embodiment of such a wound dressing is the so-called island dressing with a circumferential adhesive border. This adhesive border can be provided using skin-compatible adhesives, with acrylic and silicone adhesives being among the most common. These also have the advantage of being completely removable. Another possible embodiment of the wound dressing according to the invention is a so-called sandwich dressing.In this design, the wound dressing cushion is completely covered on all sides by both a cover layer facing away from the wound and a wound contact layer facing the wound, forming a continuous rim around the cushion. The cover layer and the wound contact layer are at least partially bonded (e.g., glued) to each other at the edges. The outer surface of the wound contact area of ​​such a sandwich dressing can be fully or partially coated with an adhesive to secure the dressing to the skin and / or wound. For full-surface adhesive coating, the use of atraumatic, wound-compatible adhesives such as silicone adhesive is recommended.

[0036] The wound dressing according to the invention is suitable for acute (e.g., bleeding) wounds as well as chronic wounds. In particular, it is ideally suited to the treatment of weeping (exuding) and / or infected wounds that frequently occur in chronic wounds. Examples of possible exuding wounds include pressure ulcers, leg ulcers, and ulcerating tumors. In practice, mixed forms of the aforementioned wound types often occur, in which the pathogens are already present in the form of a biofilm. In such cases, the advantageous properties of the wound dressing according to the invention become particularly evident.

[0037] The cushion contained in the wound dressing comprises the following components:

[0038] - A first non-woven layer, oriented towards the wound during use. This first non-woven layer can act as the wound contact layer. It is usually hydrophilic or contains hydrophilic components to facilitate the absorption of fluids into the pad. However, this layer may also contain hydrophobic fibers. Furthermore, it may contain hydrophobic fibers that have undergone prior hydrophilization. - A second non-woven layer, made of a different material or material blend than the first, oriented away from the wound during use. This layer is usually hydrophobic. This offers the advantage that fluid absorbed into the pad does not penetrate through this layer, and that fluids that come into contact with the pad from the outside (e.g., during personal hygiene) are repelled from the pad's surface.

[0039] - A continuous edge area in which the first nonwoven layer and the second nonwoven layer are connected.

[0040] - An absorbent core surrounded by the outer layer and thus enclosed by the first and second nonwoven layers. The absorbent core contains a superabsorbent substance.

[0041] - An antimicrobial composition that contains the ingredients

[0042] a) ionic silver or silver nitrate,

[0043] b) ionic zinc, zinc sulfate or zinc nitrate, and

[0044] c) EDTA or tetra-sodium EDTA

[0045] It contains. Preferably, these ingredients are suitable for forming a metal complex. Particularly preferably, this metal complex is Ag2Zn(EDTA).

[0046] Optionally, a third fleece layer may be present, which overlays the first fleece layer on the wound side.

[0047] Both the first and second nonwoven layers of the pillow, and an optional third nonwoven layer, may each contain synthetic fibers. The presence of synthetic fibers does not preclude the addition of other fiber types (e.g., natural fibers or regenerated fibers). Suitable synthetic fiber types include: acrylonitrile butadiene styrene (ABS), polyamide (PA), polylactic acid (PLA), polymethyl methacrylate (PMMA), polycarbonate (PC), polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), polystyrene (PS), polyetheretherketone (PEEK), or polyvinyl chloride (PVC). Preferably, the synthetic fibers contained in the first and second nonwoven layers consist of polyamide (PA), polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), or polyvinyl chloride (PVC).Possible mixtures of fiber types are a mixture of polyamide fibers and viscose fibers, a mixture of polypropylene fibers and viscose fibers, a mixture of polyethylene fibers and viscose fibers, a mixture of polyester fibers with cotton fibers, or a mixture of polyester fibers with viscose fibers.

[0048] The material of the first and / or second nonwoven layer, as well as any optional third nonwoven layer, can be thermally bonded. This significantly reduces the likelihood of fibers detaching from the textile composite and entering the wound. In this sense, the nonwoven fabric according to the invention can be an air-laid nonwoven, a thermally bonded nonwoven, a mechanically bonded nonwoven, a staple fiber nonwoven, a meltblown nonwoven, a spunbond nonwoven, a wet-cast nonwoven, a random lay nonwoven (isotropic nonwoven), or an anisotropic nonwoven (oriented nonwoven).

[0049] The nonwoven fabric or its fibers may contain or consist of the following materials or material mixtures: synthetic fibers, polyolefin-based fibers, polyethylene, polyetheretherketone (PEEK), polyvinyl chloride (PVC), polymethyl methacrylate (PMMA), polycarbonate (PC), polyester, polyethylene terephthalate (PET), polypropylene (PP), polystyrene (PS), polyamide, acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), viscose, cellulose-based fibers, or mixtures of two or more of the aforementioned materials. When polyamide is used as the fiber material, the polyamide may be in the form of nylon.

[0050] Synthetic fibers such as polyamide and polyester have the advantage of being resistant to decomposition by microorganisms. Furthermore, many of these fibers, such as polypropylene or polyamide, possess excellent thermoplastic properties, which simplifies the processing and joining of layers (e.g., by welding). Joining layers is also possible when the thermoplastic fibers are mixed with non-thermoplastic fibers (e.g., viscose or cotton).

[0051] The nonwoven fabric contains fibers or consists exclusively of fibers. These fibers can be made from the materials mentioned above, such as polyamide fibers (especially nylon fibers), polyester fibers, polypropylene fibers, cotton fibers, viscose fibers, etc. Furthermore, blended fibers can also be used, which combine two or more of the listed materials in a single fiber.

[0052] It is possible that the first and / or second nonwoven layer, as well as any optional third nonwoven layer, contain exclusively fibers of synthetic origin and / or fibers classified as man-made fibers. Furthermore, the first nonwoven layer and the optional third nonwoven layer, in particular, may also contain regenerated fibers such as viscose.

[0053] Furthermore, it is also possible that the nonwoven fabric according to the invention contains exclusively fibers that are of natural origin and / or biodegradable. Biodegradability can refer to biodegradability as defined in standard EN ISO 14851:2019. Examples of fibers of natural origin are cotton fibers. Fibers considered biodegradable in the context of the present invention include, for example, cotton fibers and viscose fibers. In contrast, synthetic fibers are not biodegradable.

[0054] Regardless of whether the first nonwoven layer consists of a single layer or several individual nonwoven layers, it can contain a total of 50 to 70 wt.% synthetic fibers and 30 to 50 wt.% viscose fibers. The same applies to an optional third nonwoven layer. This ensures that the first nonwoven layer, as well as the optional third nonwoven layer, wicks wound fluid into the core (wicking effect). A composition of the first and third nonwoven layers that has proven particularly advantageous is 60 to 70 wt.% polypropylene fibers and 30 to 40 wt.% viscose fibers. The first and third nonwoven layers can each have a basis weight of 30 to 60 g / m². 2 have, preferably 40 to 50 g / m² 2 The second nonwoven layer can have a basis weight of 20 to 50 g / m². 2 have, preferably 20 to 30 g / m² 2 and in particular 23 to 27 g / m² 2. In general, a low basis weight promotes the breathability and suppleness of a textile material, whereas high basis weights can slow down the passage of liquids.

[0055] Furthermore, the linear density of the nonwoven fabric or its layers can be 60 to 100 dtex, preferably 70 to 90 dtex, measured according to DIN EN ISO 2060. The toughness of the nonwoven fabric can be 30 to 50 cN / tex, preferably 35 to 40 cN / tex, measured according to DIN EN ISO 2062.

[0056] The nonwoven fabric or its layers can have an elongation according to DIN EN ISO 1798:2008-04 of at least 25%, preferably at least 35%. Elongation is understood to mean that, under tensile stress, the material does not elongate under load or fiber breakage. Preferably, the elongation is reversible, such that the material essentially returns to its original length after the tensile stress is removed. Reversible elongation also exists if, after the tensile stress is removed, the material assumes a length that is at most 105% of the original length. The length has the same spatial orientation as the tensile force and is therefore measured in the direction of the tensile force. Preferably, the specified elongation values ​​apply in the fiber direction.The elasticity improves both the resilience of the wound dressing and its ability to maintain the patient's mobility in the area of ​​the wound (especially in joint areas).

[0057] Due to its nonwoven structure, the fabric contains openings, which are spaces between individual fibers or fiber filaments. These openings can be microscopic and invisible to the naked eye. They allow liquid to pass through. Their size can vary and they do not have to be uniform.

[0058] A preferred form of the edge region, where the first and second nonwoven layers are joined, comprises a weld seam. The term "weld seam" encompasses both a single weld seam and multiple weld seams. Preferably, the weld seam is produced by ultrasonic welding and is thus an ultrasonically welded seam. The seam can have a width of up to 5 mm, preferably 2 to 5 mm, and particularly preferably 3 to 4 mm. Preferably, the seam is the only type of connection within the edge region and preferably represents the only permanent connection between the first and second nonwoven layers. If the wound dressing includes an optional third nonwoven layer, this third nonwoven layer can also be joined to the first and second nonwoven layers in the edge region by means of the aforementioned weld seam.It is also preferred that the aforementioned edge area, and optionally the weld seam within it, have rounded corners. This improves the tactile experience for the patient, as sharp corners can be uncomfortable for the skin and can also snag on clothing fibers. Furthermore, rounded corners improve the strength of the bond between the first and second nonwoven layers.

[0059] The aforementioned rounded corners are particularly recommended for a substantially rectangular design (in top view) of the wound dressing cushion. However, it should be noted that the wound dressing according to the invention, as well as the cushion contained therein, can also have a round or oval shape (also in top view), which inherently has no corners. Round and oval shapes improve adhesion to convex body areas (such as elbows or heels). If the wound dressing is intended for use on the abdomen, back, thigh, or calf, shapes that are substantially rectangular or square are typically used. Such shapes offer the advantage of more efficient use of the volume of the almost always rectangular outer packaging.

[0060] Furthermore, the aforementioned wound dressing can contain an optional, additional cover layer. This cover layer is attached to the second (wound-facing) non-woven layer, thus overlapping it and forming an outer protective layer. Preferably, the cover layer is in the form of a film and can, for example, contain or consist of polyurethane or polyethylene. It is also preferred that the cover layer is permeable to water vapor and essentially impermeable to liquids. This results in a wound dressing that is resistant to, for example, splashing water, but at the same time retains its breathability, so that the covered skin or wound is not sealed airtight, which could otherwise impair wound healing and promote tissue maceration.The water resistance of a wound dressing with a top layer exceeds that of a wound dressing that only has a hydrophobic, water-repellent second non-woven layer (facing away from the wound). The breathability of the top layer can be achieved by making it porous. Preferably, the top layer has a thickness of 15 to 25 µm. It has been shown that even this thickness combines optimal breathability with sufficient protection for the wound dressing and also allows for material savings. The top layer can be attached to the second non-woven layer of the wound dressing using an adhesive. The use of an acrylic adhesive is recommended. The acrylic adhesive can, for example, first be applied to the underside of the top layer, and the top layer then adhered to the second non-woven layer.It is recommended to apply the adhesive in a pattern to the underside of the topcoat, with the uncoated area allowing for improved air exchange, which further enhances breathability. Examples of possible coating patterns include parallel waves, a grid-like arrangement, or speckles in the form of distinct, clearly defined dots. Preferably, 30 to 50%, and particularly preferably 35 to 45%, of the underside surface of the topcoat is coated with adhesive.

[0061] The surface area of ​​the top layer can be such that it extends beyond other components of the wound dressing, forming a circumferential adhesive border that allows the dressing to adhere to the skin – e.g., to a patient's skin – during use. Accordingly, the present invention comprises a variant of the wound dressing with a circumferential adhesive border. The adhesive border forms a portion of the adhesive-coated top layer. In this arrangement, the wound dressing according to the invention represents the aforementioned island dressing.

[0062] The superabsorbent substance contained in the absorbent pad can be a superabsorbent polymer and can be in the form of particles and / or fibers. These swell upon contact with fluids, forming a gel that binds the fluids. The swelling properties of the superabsorbent substance help to bring the first nonwoven fabric, along with the antimicrobial composition, closer to the wound tissue, thus maximizing the surface area for the exchange of substances between the antimicrobial composition and the wound tissue. This enhances the antimicrobial efficacy.

[0063] Preferably, the superabsorbent polymer contains a polyacrylate. Polyacrylate-based superabsorbents can contain said polyacrylate in the form of a polymer or a copolymer and are capable of binding large quantities of liquid, thus providing the absorbent core with immense absorption capacity. Furthermore, this superabsorbent substance can be mixed within the pillow with one or more other hydrophilic, absorbent materials. The other hydrophilic, absorbent material(s) can be fibers or flakes of cellulose, cotton, and / or viscose. Preferably, it is an absorbent cellulose material, particularly preferably cellulose flakes or cellulose wadding, and most preferably smooth-fibered cellulose flakes or smooth-fibered cellulose wadding. Typically, the cellulose flakes or cellulose wadding consist of cellulose fibers.The best choice is smooth cellulose flakes. The absorbent core can contain 30 to 60 wt% superabsorbent polymer and 40 to 70 wt% cellulose fibers; preferably, it contains 40 to 50 wt% superabsorbent polymer and 50 to 60 wt% cellulose fibers, preferably in the form of cellulose flakes. Cellulose flakes have the advantage of being easier to incorporate into the wound dressing's core during production than loose fibers and blending more readily with the superabsorbent substance. This results in homogeneous absorption properties across the entire surface of the wound dressing and allows its full absorption capacity to be utilized. Preferably, the superabsorbent polymer is dispersed and embedded within the cellulose flakes or cellulose wadding.

[0064] The pillow, and in particular the absorbent core of the pillow, can have an absorption capacity of at least 50 g / 100 cm². 2 , preferably of at least 100 g / 100 cm 2 and especially preferably of at least 140 g / 100 cm² 2 These absorption capacities can be achieved by using a sufficient amount of superabsorbent polymer in the absorbent core. A recommended amount is in the previously mentioned range of 30 to 60 wt%. However, it is also possible to limit the absorption capacity of the pillow, and especially of the absorbent core, to 220 g / 100 cm². 2 , 250 g / 100 cm 2 or 300 g / 100 cm 2The advantage of limiting the absorption capacity is that some weeping wounds only produce limited amounts of exudate, and the full utilization of an excessively high absorption capacity would not be achieved, leaving some of the material unused.

[0065] It has been shown that with an embodiment of the wound dressing according to the invention, which has an absorption capacity of 140 g / 100 cm² 2 up to 220 g / 100 cm 2 It features a design that allows for the optimal treatment of a wide variety of exuding wounds without significant material waste. Both the absorption capacity of the pad and the absorbent core can be determined according to the standard DIN EN 13726-1:2002-06 (Chapter 3.2).

[0066] The first nonwoven layer of the wound dressing according to the invention can comprise two individual nonwoven layers that are at least partially bonded together, so that the first nonwoven layer is a double nonwoven layer. Preferably, the first nonwoven layer consists exclusively of the two aforementioned individual nonwoven layers. The inner of the two individual nonwoven layers is the layer facing away from the wound, and the outer of the two individual nonwoven layers is the layer facing the wound. The inner and outer individual nonwoven layers form the underside of the wound dressing cushion, with the inner individual nonwoven layer having direct contact with the absorbent core. The outer individual nonwoven layer can be in direct contact with the wound during use.

[0067] Preferably, the first non-woven layer of the wound dressing cushion consists of two individual non-woven layers bonded together across their entire surface. The two individual non-woven layers are considered fully bonded if the user perceives them visually and haptically as a single layer, or if one individual non-woven layer cannot be lifted from the other—or only in a destructive manner—so that a gap is created between the two layers when lifted. Such a full-surface bond allows for rapid and unimpeded fluid transfer from the outer to the inner individual non-woven layer. Furthermore, the full-surface bond results in greater durability—especially when removing a moisture-saturated wound dressing from the wound.

[0068] The inner and outer nonwoven layers can be bonded together, for example, thermoplastically or by needle punching. The latter results in a needle-punched nonwoven fabric.

[0069] If the first nonwoven fabric of the wound dressing comprises two individual nonwoven layers, both the inner and the outer individual nonwoven layers can each contain at least 30 wt.%, preferably at least 40 wt.%, particularly preferably at least 50 wt.%, and most preferably at least 60 wt.% synthetic fibers, independently of each other. The outer individual nonwoven layer can even consist entirely of synthetic fibers. Furthermore, the inner individual nonwoven layer can have a basis weight of, for example, 20 to 35 g / m². 2 or 25 to 30 g / m² 2 The outer single layer of nonwoven fabric can have a basis weight of, for example, 10 to 30 g / m². 2 or 12 to 15 g / m² 2 have.

[0070] It is recommended that the two individual nonwoven layers differ at least partially in their properties, characteristics, structure, and / or composition. If the difference is based on a different composition, this can be achieved, for example, by using entirely or partially different fiber types in the two individual nonwoven layers, or by using different proportions of the same fiber types. This is explained in more detail below:

[0071] It is recommended that the outer nonwoven layer contain polyamide and / or polypropylene fibers, while the inner nonwoven layer consists of a mixture of polyamide or polypropylene fibers together with viscose fibers. This arrangement creates a hygroscopic gradient that draws fluids from the wound through the first nonwoven layer into the absorbent core and locks them in. Furthermore, the hydrophobic properties of the material reduce the likelihood of the outer nonwoven layer adhering to the wound.

[0072] It is particularly recommended that both individual nonwoven layers contain at least a proportion of the same thermoplastic synthetic fiber type. This allows for a particularly stable bond between the inner and outer individual nonwoven layers, especially when achieved through thermal processes (e.g., welding). A particularly successful example is the combination of an outer individual nonwoven layer made of polypropylene fibers and an inner individual nonwoven layer containing polypropylene fibers in combination with viscose fibers. Within the scope of the present invention, viscose fiber is not considered a synthetic fiber.

[0073] A particularly preferred embodiment of the wound dressing according to the invention provides that both the second nonwoven layer and the inner and outer individual nonwoven layers of the first nonwoven layer contain at least a proportion of this thermoplastic synthetic fiber. It has been shown that the use of polypropylene achieves particularly good results in this context, and that a weld seam produced from it exhibits surprisingly high strength in the edge region. In this way, it is possible to keep the weld seam narrow and / or reduce the number of individual weld seams, thereby increasing the effectively available interior space of the pad. This allows the absorbent core within the pad to either be filled with more absorbent material or to have more room to expand as a result of fluid absorption.At the same time, a reduced weld seam area leads to better conformity of the wound dressing to uneven skin areas and to a more pleasant tactile sensation for the treated patient.

[0074] The present invention further comprises a form of wound dressing in which the first nonwoven layer—regardless of whether it is composed of one or more individual nonwoven layers—contains a total of 50 to 70 wt.% polypropylene fibers and 30 to 50 wt.% viscose fibers. Preferably, the first nonwoven layer contains 55 to 65 wt.% polypropylene fibers and 35 to 45 wt.% viscose fibers. It has been shown that such a composition combines particularly good absorption properties with particularly good permeability, thus ensuring rapid transport of fluids from the wound toward the absorbent core. If the second nonwoven layer also contains or consists of polypropylene fibers, the first and second nonwoven layers can also be joined—as explained above—by a particularly durable thermoplastic weld between the two layers.

[0075] If the first nonwoven layer contains synthetic fibers, these may have undergone hydrophilization, giving them hydrophilic properties. These hydrophilized synthetic fibers may be, in particular, polypropylene or polyamide fibers. Hydrophilization can be achieved through chemical or physical treatment (e.g., using oxygen plasma). An example of chemical hydrophilization is the application of 2-hydroxyethyl methacrylate, and an example of physical hydrophilization is the application of oxygen plasma. In this way, the nonwoven fabric can benefit from the advantageous properties of synthetic fibers—such as good processability (e.g., weldability), low cost, and high durability—while simultaneously exhibiting particularly good absorption and permeability.

[0076] Furthermore, the wound dressing according to the invention can contain a first non-woven layer which is constructed as a double layer consisting of an inner and an outer single non-woven layer, wherein the outer, wound-side oriented single non-woven layer consists of polypropylene fibers and carries and / or contains the antimicrobial composition according to the invention.

[0077] Since the first and second non-woven layers can look similar or even identical, the antimicrobial composition also serves as an indicator or marker of which side of the dressing should be applied to the wound. The first non-woven layer appears darker than the second due to its antimicrobial composition. The second non-woven layer can also be colored, for example, green, to improve visual differentiation. Furthermore, a green second non-woven layer makes the saturation of the dressing's absorption capacity more readily apparent to the user because a moistened green layer contrasts more strongly with a dry one than a white layer would.

[0078] Furthermore, the absorbent core of the wound dressing according to the invention can be wrapped in a cellulose nonwoven fabric. The absorbent core can be partially or completely wrapped in the cellulose nonwoven fabric. This cellulose nonwoven fabric can be arranged such that it is located between the absorbent core and the first and second nonwoven layers. The absorbent core can be wrapped by the cellulose nonwoven fabric in such a way that the cellulose nonwoven fabric is arranged in a tubular shape. Preferably, this tubular cellulose nonwoven fabric has overlapping areas in which the beginning and end of the cellulose nonwoven fabric lie one on top of the other and in which the overlapping cellulose nonwoven fabrics are permanently bonded together.Particularly preferred are the closed ends of the tube (inlet and outlet of the tube), which can be achieved, for example, by crimping or cutting these protruding tube ends during the production process. This is preferably done by crimping. The advantage of crimping lies both in the elimination of the use of chemicals such as adhesives and in the elimination of energy-intensive methods such as welding. In this sense, the absorbent core of the wound dressing according to the invention can be completely encased in a cellulose nonwoven fabric, this nonwoven fabric preferably being partially crimped to itself so that the absorbent core is fixed within the nonwoven fabric.

[0079] The aforementioned cellulose fleece serves as a distribution layer within the wound dressing, which evenly distributes the fluid passed through by the first fleece layer onto the absorbent core (from below, from the sides and from above), so that the superabsorbent substance in the absorbent core swells evenly without the resulting gel blocking the further flow of fluid into the core center.

[0080] According to one embodiment, the antimicrobial composition can contain the individual ingredients in the following concentration ranges: EDTA can be present in a concentration of 20 to 93 wt.% or 70 to 85 wt.%. The concentration of EDTA can also be at least 30 wt.% or at least 70 wt.%. Silver can be present in a concentration of 5 to 50 wt.% or 8 to 20 wt.%. The concentration of silver can also be at least 5 wt.% or at least 10 wt.%. Zinc can be present in a concentration of 2 to 50 wt.% or 3 to 20 wt.%. The concentration of zinc can also be at least 3 wt.% or at least 10 wt.%.

[0081] According to another embodiment, the weight ratio of the ingredients within the antimicrobial composition is 80 to 90 wt.% T-EDTA, 5 to 12 wt.% AgNO3 and 5 to 15 wt.% ZN(NO3)2.

[0082] According to another embodiment, the antimicrobial composition contains 3 to 45 wt.% of one of the following ingredients: ionic silver, silver nitrate, ionic zinc, zinc nitrate, or zinc sulfate. Simultaneously or independently, the antimicrobial composition may contain 15 to 95 wt.% EDTA.

[0083] According to a particularly preferred embodiment, the antimicrobial composition can contain a total of 8 to 12 wt.% silver and zinc, preferably 8 to 10 wt.%.

[0084] The stoichen ratio of the amount of EDTA to the sum of the amounts of Ag + and Zn 2+ The ratio can range from 4:1 to 4:32. A preferred stoichiometric ratio of EDTA : Ag + : Zn 2+The ratio is 0.9 to 1.1 : 0.14 to 0.2 : 0.14 to 0.2. The amount of substance can be determined in the standard unit mol. The ratio of the constituents to each other is a factor that partly determines the proportion of free cations (Ag+, Zn+) to the complexed cations bound to EDTA. Surprisingly, it has been shown that both free cations and free binding sites on the EDTA molecule are advantageous. It is assumed that these are primarily available for the desired reactions against pathogens and biofilms. Preferred ranges derived from this are a weight ratio of 9:30 to 9:36 (9 represents parts of EDTA) and a molar ratio of 4:28 to 4:32 (4 represents parts of EDTA).

[0085] To prepare the antimicrobial composition, it is recommended to first dissolve or disperse the ingredients in a polar, non-toxic liquid. Water is recommended for this purpose; deionized or distilled water is particularly recommended, as it does not contain interfering ions (such as sodium). + The liquid contains substances that could react with the ingredients of the antimicrobial composition. Preferably, the liquid in question is a volatile substance that evaporates completely or partially after the antimicrobial composition is introduced into the wound dressing. Upon subsequent contact with wound exudate, the ingredients of the antimicrobial composition are redissolved and released into the wound.

[0086] According to a preferred embodiment, the polar liquid with the antimicrobial composition contains free cations of silver and zinc. This can be achieved by ensuring that both silver and zinc are present in excess relative to EDTA. For example, the sum of the amounts of silver and zinc can be at least three times, preferably at least five times, the amount of EDTA. The free cations are thus available for biochemical reactions that have a direct or indirect beneficial effect on wound healing.

[0087] It has been shown that silver primarily has an effect against pathogenic single-celled organisms. Zinc is able to activate immune cells. Through its function as a cofactor in various transcription factors and enzymatic reactions, zinc promotes wound healing and also protects cells from apoptosis induced by oxidative stress or bacterial toxins. By binding calcium, EDTA can break down existing biofilms and also suppress their formation.

[0088] The release of the cations (Ag + and Zn 2+ ) from the first non-woven layer of the wound dressing according to the invention, at a rate of 1 to 200 pg per 100 cm², the amount of product can be extracted within 24 hours. 2The substrate should be dissolved (in 100 ml of water for 24 hours at 37°C). The release rate is preferably between 10 and 180 pg, even better between 20 and 160 pg or between 30 and 100 pg. Surprisingly, it was found that the amount of silver required within the antimicrobial composition to achieve the desired antimicrobial effect can be lower than expected. It is assumed that the other components, EDTA and zinc, potentiate the effect of silver. A reduced amount of silver offers the advantage of decreased cytotoxicity and / or increased cell compatibility.

[0089] The antimicrobial composition can be produced particularly quickly and conveniently and exhibits particularly good stability when the ingredients are in the form of certain salts. Accordingly, the wound dressing according to the invention can comprise an antimicrobial composition in which the ingredients are in the form of salts. For example, silver can be in the form of silver nitrate. Zinc can be in the form of zinc nitrate or zinc sulfate, and EDTA can be in the form of tetrasodium EDTA.

[0090] The “antimicrobial composition” can be present in the following states in particular within the scope of the present invention:

[0091] a) as a mixture of ionic silver and / or silver nitrate as well as ionic zinc and / or zinc nitrate and / or zinc sulfate as well as EDTA or tetrasodium EDTA - unless otherwise stated, the "antimicrobial composition" is primarily in this form, preferably in the ionic forms

[0092] b) as the complex compound Ag2Zn(EDTA),

[0093] c) as a solution of the complex compound mentioned under b) in a polar liquid such as water or another non-toxic, polar solvent, or

[0094] d) as a solution of the salts silver nitrate, zinc sulfate or zinc sulfate monohydrate, and tetrasodium EDTA in a polar liquid such as water or another non-toxic, polar solvent, so that the complex compound mentioned in b) is formed within the solution through the reaction of the aforementioned salts with each other. The zinc nitrate can also be added to the antimicrobial composition in the form of the hexahydrate Zn(NOa)₂X₆H₂O, and the tetrasodium EDTA as a tetrahydrate or dihydrate. It is not necessary for all cations of silver and zinc to react to form the complex. The formation of a chemical equilibrium in the sense of a dissociation with forward and reverse reactions is not a disadvantage. Likewise, other salts of silver and zinc can be used as their nitrates, as long as the complex compound mentioned in b) can be formed by the reactants.

[0095] Should some of the ingredients in the antimicrobial composition precipitate out of the solution, this does not automatically impair its subsequent effectiveness. In such a case, it is recommended to stir or shake the undissolved particles into a suspension that is as homogeneous as possible immediately before applying the solution to the wound dressing.

[0096] According to a preferred embodiment, the wound dressing contains 17 to 32 g of the antimicrobial composition per m² 2 wound-facing surface or wound contact area. Even better results can be expected in the range of 20 to 26 g / m². 2 .

[0097] The antimicrobial composition can also be present in an amount such that 2 to 5% by weight of the wound dressing, first non-woven layer, or wound contact layer consists of the antimicrobial composition. For example, a wound dressing, non-woven layer, or wound contact layer weighing 50 g may contain 1 to 2.5 g of antimicrobial composition. Even better results can be expected in the range of 3 to 4% by weight.

[0098] According to a particularly preferred embodiment, the wound dressing contains the antimicrobial ingredients in a weight ratio of 80 to 92 wt.% EDTA to 5 to 10 wt.% silver to 3 to 10 wt.% zinc. This embodiment offers particularly good biocompatibility due to its extremely low cytotoxicity. Biocompatibility is especially good when the antimicrobial composition with the aforementioned weight ratio of ingredients constitutes 2 to 3% of the weight of the first nonwoven layer, the wound contact layer, or the total weight of the wound dressing.

[0099] Advantageously, the wound dressing according to the invention contains the antimicrobial composition within the first nonwoven layer. In particular, the first nonwoven layer can be coated, impregnated, or saturated with the composition. If the first nonwoven layer is a double nonwoven layer, at least the outer of the two single nonwoven layers should be equipped with the antimicrobial composition. Impregnation and saturation lead to at least partial, and preferably complete, penetration of the fiber structure of the first nonwoven layer with the antimicrobial composition. This offers the advantage of a depot effect and simultaneously reduces the likelihood of pathogens multiplying in the wound dressing. Saturation of the wound dressing or the nonwoven layer of the wound dressing can be carried out, for example, by dipping, while impregnation can be carried out, for example, by spraying.Other techniques are also possible. For example, the wound dressing can be coated with the antimicrobial composition using a roller or by brushing (e.g., with a brush). After application, the solvent can be removed. This can be done, for example, by active or passive drying or evaporation.

[0100] Surprisingly, it has been shown that the first nonwoven fabric of the wound dressing according to the invention, which is equipped with the antimicrobial composition, is permeable to wound exudate and other fluids.

[0101] The antimicrobial composition, and thus the wound dressing equipped with it, has antimicrobial, and in particular antibacterial, properties, with the antibacterial properties including an effect against the human pathogenic germs S. aureus and P. aeruginosa. The antimicrobial effect occurs upon initial contact with the pathogens and can intensify over time, whereby a contact time (e.g.,

[0102] Preferred application durations are (duration of application on a wound) of 1 to 72 hours or 1 to 24 hours.

[0103] The incorporation of the antimicrobial composition into the first nonwoven layer creates a spatial separation of the metals from the superabsorbent substance of the absorbent core. This ensures that metals, which are present in the form of positively charged, dissolved cations, are not bound to the negatively charged acrylic acid, which may be part of the superabsorbent substance, through electromagnetic interaction. Such an undesirable interaction would render bound cations unavailable for the intended reactions of pathogen defense or healing promotion. In this respect, the present invention may provide that the absorbent core of the wound dressing does not contain zinc or silver. According to a preferred embodiment, the wound dressing includes the aforementioned third nonwoven layer. The third nonwoven layer overlaps the first nonwoven layer on the wound side.

[0104] This covers the antimicrobial composition. In this way, the antimicrobial composition is additionally protected, and any potential unwanted adhesion to an adhesive release liner is prevented. This also counteracts any potential staining of the antimicrobial coating onto, for example, the clothing or hands of medical personnel. Preferably, the third nonwoven layer has the same chemical composition, structure, and composition as the first nonwoven layer. Accordingly, all features mentioned above in connection with the first nonwoven layer are also applicable to the third nonwoven layer. In particular, it can be provided that the first and third nonwoven layers are identical.

[0105] Furthermore, the cushion can have an additional perforated silicone layer attached to the first non-woven layer or, if present, the third non-woven layer. Such a silicone layer can further improve the atraumatic properties of the cushion. The silicone in the silicone layer can be a silicone gel with adhesive properties. In particular, this silicone layer can comprise a perforated film, with one side of the film facing the first or third non-woven layer of the cushion coated with an acrylic adhesive and the opposite side of the same film coated with a silicone gel. In use, the cushion thus contacts the wound with the atraumatic silicone gel. Preferably, the film is made of polyurethane. The perforations mentioned are, in this case, openings in the film, silicone gel, and acrylic adhesive. The perforations allow wound exudate to pass through the silicone layer into the absorbent cushion.Simultaneously, the ingredients of the antibacterial composition can penetrate the wound through the perforations. The perforations can be circular, for example, and have a diameter of 2.3 to 2.5 mm. The open area created by the perforations can be, for example, 18 to 27%. The film can have a thickness of 10 to 20 µm.

[0106] Furthermore, within the scope of the present invention, the first or third nonwoven layer, or the individual nonwoven layers optionally present in the first nonwoven layer, can optionally be free of certain substances. For example, the nonwoven fabric can be free of gelatin and / or collagen, or generally free of substances of animal origin (e.g.,

[0107] Chitosan). Nonwovens free of such substances generally exhibit longer shelf life and a lower allergy potential. Furthermore, an undesirable interaction of such additional substances with the antimicrobial composition can be ruled out.

[0108] Furthermore, it may be provided that the wound dressing according to the invention does not contain any hydrogels, foams or woven, knitted or crocheted textiles.

[0109] Before use, the lower (wound-facing) side of the dressing may be covered by a protective layer such as a release liner. This protective layer may be in the form of a film and is removed by the user immediately before application.

[0110] The wound dressing according to the invention is resistant to sterilization and retains its functional and structural properties after sterilization. In particular, the antimicrobial properties are retained. Sterilization can be carried out, for example, by means of ethylene oxide, steam sterilization (auto-sterilization), or hot air sterilization.

[0111] Furthermore, the invention also includes a kit comprising

[0112] a) a wound dressing according to the invention as described herein, including the antimicrobial composition

[0113] b) A fastening device, wherein the fastening device is suitable for attaching the wound dressing to a wound. The fastening device may be an adhesive film. The kit may be packaging or a set.

[0114] Another aspect of the invention relates to the wound dressing according to the invention for use in a method for treating wounds, preferably infected wounds, particularly preferably wounds infected with S. aureus and / or P. aeruginosa, or in a method for wound therapy and / or for reducing the bacterial count in wounds and / or for preventing wound infections. The application can take place over a period of 0.1 to 24 hours, or over a period of at least 24 hours, the latter being necessary, for example, in cases of severe infections or in patients with immunodeficiency. The wounds can be, in particular, ulcers, traumatic wounds (including lacerations and surgical wounds), chronic wounds, bleeding wounds, suppurating wounds, necrotic wounds, coated (fibrin-containing) wounds, and exuding (weeping) wounds.

[0115] The characters will be explained in more detail below.

[0116] Figures 1-5 show the release of the antimicrobial composition from wound dressings. Measurements were taken after 4h, 24h, and 72h in these release tests, showing the concentrations of the individual antibacterial ingredients Ag, Zn, and EDTA in mg per kg of the respective solvent.

[0117] Fig. 1 shows the release of the antimicrobial composition A (see Example 1) from a wound dressing into water. The wound dressing contained this composition in an amount of 2% of its own weight.

[0118] Fig. 2 shows the release of the antimicrobial composition A (see Example 1) from a wound dressing into water. The wound dressing contained this composition in an amount of 2.5% of its own weight.

[0119] Fig. 3 shows the release of antimicrobial composition A (see Example 1) from a wound dressing into simulated wound fluid. The wound dressing contained this composition at a concentration of 2.5% of its own weight.

[0120] Fig. 4 shows the release of antimicrobial composition B (see Example 1) from a wound dressing into water. The wound dressing contained this composition in an amount of 2.5% of its own weight.

[0121] Figure 5 shows the release of antimicrobial composition B (see Example 1) from a wound dressing into simulated wound fluid. The wound dressing contained this composition at a concentration of 2.5% of its own weight.

[0122] Figures 6-7 show the antibiotic effect of wound dressings with antimicrobial composition B.

[0123] Figure 6 shows the antibiotic effect of wound dressings with antimicrobial composition B (see Example 1) against selected pathogenic microorganisms after a contact time of 24 hours. Each wound dressing contained the antimicrobial composition at a concentration of 3% of its own weight. The ordinate shows the decrease in the number of organisms using the logarithmic scale.

[0124] Fig. 7 shows the effect of wound dressings with antimicrobial composition B (see Example 1) against biofilms of selected pathogenic microorganisms after a contact time of 24 h. Each wound dressing contained the antimicrobial composition at a concentration of 3% of its own weight. The ordinate shows the decrease in the number of organism cells using the logarithmic scale.

[0125] Example 1: Provision of antimicrobial compositions

[0126] The water used was demineralized.

[0127] 1.1 Antimicrobial composition with excess cations (Composition A) In this variant of the antimicrobial composition, the molar ratio of EDTA to zinc to silver was 11 : 44.5 : 44.5. This composition was prepared according to the following procedure:

[0128] First, three separate solutions of tetrasodium EDTA (T-EDTA), AgNO3, and ZnNO3 were prepared. For this purpose,

[0129] - 0.8 g T-EDTA in 6.2 g water

[0130] - 1.45g AgNO3 in 5.55g water and

[0131] - 2.53 Zn(NO3)2x 6 H2O in 25.47 g of water

[0132] stirred until a clear and colorless solution was formed.

[0133] The T-EDTA solution was then mixed with the ZnNO3 solution. Finally, the AgNOa solution was added and mixed, so that all three components of the antimicrobial composition were present in one solution.

[0134] The aqueous solution produced in this way had a total salt concentration of approximately 9%.

[0135] 1.2 Composition with excess EDTA (Composition B) In this variant of the antimicrobial composition, the molar ratio of EDTA to zinc to silver was: 78 : 11 : 11. Due to the reduced silver content compared to Example 1.1, this composition shows better cell compatibility with human tissue.

[0136] This composition was prepared according to the following procedure:

[0137] First, three separate solutions of tetrasodium EDTA (T-EDTA), AgNCh, and ZnNOa were prepared. For this purpose,

[0138] - 2.8 g T-EDTA in 5.5 g water

[0139] - 0.18 g AgNOa in 3.5 g water and

[0140] - 0.32g Zn(NOa)2 x 6 H2O in 12g water

[0141] stirred until a clear and colorless solution was formed.

[0142] The T-EDTA solution was then mixed with the ZnNCh solution. Finally, the AgNOa solution was added and mixed, so that all three components of the antimicrobial composition were present in one solution.

[0143] The aqueous solution produced in this way had a total salt concentration of approximately 14%.

[0144] 1.3 Other compositions

[0145] Analogous to those in Examples 1.1 and 1.2, antimicrobial compositions were produced with the following ratio of ingredients:

[0146] Composition: C = 33 EDTA : 33 Ag : 34 Zn

[0147] Composition D = 55.5 EDTA : 34.5 : Ag : 10 Zn

[0148] Example 2: Wound dressings with antimicrobial compositions

[0149] 2.1 Treatment of Nonwoven Layers with Antimicrobial Compositions Nonwoven layers measuring 11 cm x 11 cm were provided, each consisting of two individual nonwoven layers: one layer made of polypropylene fibers facing downwards (wound-side in use) and one layer made of 64 wt% polypropylene fibers and 36 wt% viscose fibers facing upwards (away from the wound in use). The two individual nonwoven layers were bonded together across their entire surface using heat and the thermoplastic properties of the polypropylene fibers. Each resulting (double) nonwoven layer had a mass of approximately 0.54 g.

[0150] The provided nonwoven layers were either immersed in the solution of composition A (according to example 1.1) or composition B (according to example 1.2) for 30 seconds (immersion method) and then rolled up between two layers of paper towels to squeeze out excess liquid.

[0151] The nonwoven layers treated with composition A or B were adjusted by pressing out the liquid to a weight such that the salts within the subsequently generated (dry) wound dressings constituted 2% by weight, 2.5% by weight and 3% by weight of the finished wound dressings.

[0152] In the case of the targeted final concentration of 3 wt% salts in the wound dressing, this corresponded to a weight of 2.92 g of the pressed nonwoven layer, of which 2.38 g was saline solution. Due to the 14% solution concentration, the pure salt mass within the nonwoven layer was approximately 0.33 g. The remaining mass (still missing at this point) was added later by incorporating the other structures of the wound dressing (see 2.2), thereby achieving the targeted 3 wt% salts within the finished wound dressing.

[0153] The treated nonwoven layers, which had been pressed to the desired target weight, were dried in a drying oven at 60°C with circulating air for approximately one hour. Open Petri dishes, onto which the nonwoven layers were placed, served as spacers to prevent direct contact with the drying oven.

[0154] 2.2 Incorporation of antimicrobially treated nonwoven layers into wound dressings

[0155] The nonwoven layers treated with antimicrobial compositions, as described in Example 2.1, were cut to a size of 3 cm x 3 cm and then assembled with other components to form cushions. The antimicrobially treated nonwoven layers were incorporated as the first layer (oriented towards the wound when in use). A hydrophobic nonwoven material made of polypropylene fibers, also measuring 3 cm x 3 cm, served as the second layer (oriented away from the wound when in use). Cellulose flakes, in which superabsorbent polymer particles were embedded, formed the absorbent core within the cushion.

[0156] The other components of the pad had a mass of approximately 0.72 g. To achieve a concentration of the antimicrobial composition in the wound dressing of, for example, 3% by weight, these components were combined with a treated, re-dried non-woven layer weighing approximately 0.064 g (of which approximately 0.024 g were salts). The first and second non-woven layers were bonded together at their perimeter, where they were in direct contact, by applying heat, thus sealing the pad.

[0157] The 3 cm x 3 cm size allowed for subsequent testing of antimicrobial efficacy in Petri dishes. For practical use in wound treatment, wound dressings with a larger surface area can be produced according to the same principle as explained in this example.

[0158] Example 3: Determination of cytotoxicity

[0159] Cytotoxicity was determined according to standard IS010993-5, section 8.3, "Direct Contact Testing." Cell viability was determined using the Invitrogen™ CyQUANT™ Cell Proliferation Assay Kit from Thermo Fisher Scientific. The cells used for the test were derived from the L929 cell line (mouse fibroblasts; ECACC No. 1000).

[0160] 88102702). Cell viability was determined as a percentage comparison value relative to control cells in Dulbecco's Modified Eagle Medium (DMEM). The test specimens were nonwoven layers composed of two individual nonwoven layers (prepared according to embodiment 2.1). The nonwoven layers each measured 1 x 1 cm. The results are shown in the following table:

[0161] Table 1: Results of the cytotoxicity tests

[0162] wt% Type of ratio EDTA : AG : ZN Quality Cell viability [% in antimicrobial combination compared to control composition in DMEM ] in wound dressing [A, B, C, D]

[0163]

[0164] 2 A 11 : 44.5 : 44.5 3 65 2 C 33: 33: 34 3 57 2 B 78 : 11 : 11 3 69 2 D 55.5: 34.5 : 10 3 55 2.5 B 78 : 11 : 11 3 71 2.5 A 11 : 44.5 : 44.5 3 51 3 B 78 : 11 : 11 3 34 0 nana 0 97

[0165]

[0166] Example 4: Release experiments

[0167] The release of antimicrobial ingredients from wound dressings with different antibacterial compositions was tested. The following served as test media (11 ml / sample):

[0168] I) distilled water

[0169] II) Simulated wound fluid (50% bovine serum; 50% aqueous peptone solution)

[0170] Table 2: Candidates:

[0171] wt.% Type Ratio Number Test medium antimicrobial composition EDTA : AG : tested composition setting ZN Test specimens

[0172] in wound dressing [A, B, C, D]

[0173] 2 A 11 : 44.5 : 44.5 6 I

[0174] 2.5 A 11 : 44.5 : 44.5 6 I + II 2.5 B 78 : 11 : 11 6 I + II

[0175]

[0176] The test specimens were incubated in the respective test medium at 37°C under constant agitation (120 rpm). The incubation periods were 4h, 24h and 72h.

[0177] After the respective time period, 4 ml of the liquid were taken and the EDTA concentration was determined. The remaining liquid was mixed with 20 liters of nitric acid (65%) and used to determine the Ag concentration. + and Zn 2+The EDTA concentration was determined using high-performance liquid chromatography (HPLC-UV / DAD). The cation concentration was determined using inductively coupled plasma optical emission spectrometry according to DIN EN ISO 11885.

[0178] The results are shown in Fig. 1-5.

[0179] The graphs show that in some cases, the measured values ​​of the dissolved components of the antimicrobial composition decrease again after an initial release (value after 4 hours) (values ​​after 24 hours and 72 hours). Possible causes for this are deposition on the wall of the glass container, reabsorption into the wound dressing, and possible measurement fluctuations.

[0180] Overall, it can be stated that all tested amounts (2 and 2.5 wt%) of the two antimicrobial compositions (A and B) in both liquids (water and simulated wound fluid) led to a significant release of the antimicrobial ingredients (Ag, Zn, EDTA).

[0181] Example 5: Demonstration of the antimicrobial efficacy of wound dressings according to AATCC 100

[0182] Wound dressings manufactured according to Example 2 served as test samples for determining antimicrobial efficacy. These dressings contained antimicrobial composition B at a concentration of 3% by weight of the dressing. The antimicrobial composition was located in the first non-woven layer.

[0183] The test was carried out in contact testing according to the AATCC 100 standard, following the scheme below:

[0184] An overnight culture of each microorganism was prepared by inoculating 10 ml of TSB with a single colony. Subsequent incubation took place at 37°C and 125 rpm in a shaking incubator. The overnight cultures were transferred to 1 x 10 8 CFU / ml was set. The wound dressings were tested in triplicate for each pathogen. For this purpose, the wound dressings were transferred to Petri dishes (one dressing per Petri dish) and moistened with 0.85% NaCl solution. Subsequently, the wound dressings were individually placed in 50 ml Falcon tubes, mixed with 10 ml TSB, and inoculated with 100 pl of the overnight culture, so that the target concentration was reached at 1 x 10 6 CFU / ml was the rate.

[0185] The wound dressings were incubated at 37°C and 125 rpm on a shaking incubator. Subsequently, 1 ml of each sample was transferred into new 50 ml Falcon tubes and 9 ml of neutralization solution was added.

[0186] The next step was performed in a 96-well plate, with 200 pl of cell solution being added to the wells of the first plate column. 180 pl were added to the wells of plate columns 2 to 7. A 10-fold serial dilution of the cell solution was then carried out by transferring 20 pl of the solution to each subsequent well column.

[0187] Two 50 pl of each dilution were plated onto TSA agar plates and incubated overnight at 37 °C. The colonies were counted the following day.

[0188] The results are shown as mean values ​​in Fig. 6.

[0189] Example 6: Demonstration of the effectiveness of the wound contact layers according to the invention against biofilms using a drip-flow bioreactor

[0190] The effect of the wound dressings according to the invention was tested on biofilms generated in a drip-flow reactor. The tests were conducted in accordance with the ASTM y-13 standard, but with minimal modifications to allow for the generation of data from different microorganism species. These organisms are listed in the following table:

[0191] Table 3 Biofilm-producing organisms

[0192] Gram-positive organisms, deposit number or...

[0193]

[0194] Staphylococcus aureus strain ATCC 29213,

[0195] MRSA ATCC BAA-43 Staphylococcus epidermidis ATCC 35984 Enterococcus faecalis ATCC 29212 gram-negative organisms

[0196] Pseudomonas aeruginosa ATCC 15442

[0197] ATCC 700888 Acinetobacter baumannii ATCC 19606

[0198] Klebsiella Pneumoniae ATCC 700603 fungal organisms

[0199] Candida albicans ATCC 10231

[0200]

[0201] Candida auris NCPF 8971

[0202] The tests were performed according to the following protocol: First, 10 ml of TSB was inoculated with a single colony of each strain and incubated overnight at 37 °C and 125 rpm in a shaking incubator. Absorbent pads were attached to the microscope slides using adhesive, and the chambers of the drip flow reactor were loaded with the slides. The reactor was then sterilized in an autoclave.

[0203] The absorbent pads were moistened with 1 ml of TSB and fitted with polycarbonate filters (2 cm x 2 cm; 0.2 pm). The overnight cultures were transferred to 1 x 10 8 The concentration of CFU / ml was set. The filters were then wetted with 10 pl of this solution and allowed to dry.

[0204] The reactor covers were attached and the reactor was secured with a 10-liter glass carboy (270 mg / l TSB). The tubing for the nutrient solution was connected to a pump, and the nutrients were added at a rate of 5 ml / min / chamber.

[0205] After 24 hours, the wound dressings (2.5 cm x 2.5 cm) were completely saturated with simulated wound fluid (50:50 – maximum recovery diluent: fetal calf serum). The dressings were then placed on top of the inoculated filters, the chamber covers were secured, and the reactor was restarted for another 24 hours.

[0206] After the allotted time, the filters were removed, placed in 10 ml of Dey-Engley neutralizing broth, and sonified for 30 minutes. The samples were distributed onto 96-well plates, and a 1:10 dilution series was generated from each sample using PBS. The dilutions were plated onto TSA (20 l). After incubation at 37 °C overnight, the colonies were counted.

[0207] The results of the experimental evaluation are shown as a logarithmic reduction in the cell number of the tested organisms in Fig. 7.

[0208] Example 7: Determination of the minimum inhibitory concentration

[0209] To determine the minimum inhibitory concentration (MIC) of antimicrobial compositions A and B, series of wound dressings with the same antimicrobial composition but in different coating amounts were tested. The tests were performed against P. aeruginosa and S. aureus. The organisms were treated with a concentration of 10 5 The concentration of each antimicrobial composition was set to CFU / mL and the dressings were in contact with each other for 18 hours at 37 °C. The lowest concentration at which no visually detectable pathogen growth was observed is given as MIC in the following table:

[0210] Table 4: Minimum inhibitory concentrations

[0211] MIC [%] Composition P. aeruginosa S. aureus

[0212] A 0.002 0.0057

[0213]

[0214] B 0.001 0.0048

Claims

Patent claims 1. Wound dressing comprising a cushion, wherein the cushion has a first wound-facing non-woven layer and a second wound-away non-woven layer, wherein the material of the first non-woven layer is fluid-permeable and the material of the second non-woven layer differs from the material of the first non-woven layer, wherein the cushion further comprises an absorbent core comprising a superabsorbent substance, and the first non-woven layer and the second non-woven layer enclose the absorbent core and together form a continuous border surrounding the absorbent core in which the first non-woven layer and the second non-woven layer are joined together. characterized in that the first nonwoven layer has an antimicrobial composition which protects the ingredients a) ionic silver or silver nitrate, b) ionic zinc, zinc sulfate or zinc nitrate, and c) EDTA or tetra-sodium EDTA contains.

2. Wound dressing according to claim 1, characterized in that the wound dressing further comprises a cover layer which is attached to the second nonwoven layer and contains a water vapor permeable and substantially liquid-impermeable film material.

3. Wound dressing according to one of the preceding claims, characterized in that the absorbent core further contains an absorbent cellulose material.

4. Wound dressing according to one of the preceding claims, characterized in that the first nonwoven layer comprises or consists of two different and at least partially interconnected individual nonwoven layers, namely an inner, wound-away individual nonwoven layer and an outer, wound-facing individual nonwoven layer.

5. Wound dressing according to claim 4, characterized in that the inner and outer single-layer nonwoven fabrics are fully bonded together.

6. Wound dressing according to claim 4 or 5, characterized in that the outer single-layer nonwoven fabric consists of polyamide fibers or polypropylene fibers and the inner single-layer nonwoven fabric consists of a mixture of polyamide fibers or polypropylene fibers with viscose fibers.

7. Wound dressing according to one of the preceding claims, characterized in that the first nonwoven layer contains a total of 50 to 70 wt.% polypropylene fibers and 30 to 50 wt.% viscose fibers.

8. Wound dressing according to claim 6 or 7, characterized in that the polypropylene fibers or the polyamide fibers have been subjected to hydrophilization.

9. Wound dressing according to one of claims 4 to 8, characterized in that the outer single nonwoven layer consists of polypropylene fibers and carries and / or contains the antimicrobial composition.

10. Wound dressing according to one of the preceding claims, characterized in that the absorbent core is partially or completely wrapped in a cellulose nonwoven fabric which is located between the absorbent core and the first and second nonwoven layers.

11. Wound dressing according to one of the preceding claims, characterized in that the antimicrobial composition contains the following proportions: a) 5 to 50 wt.% ionic silver or silver nitrate, b) 2 to 50 wt.% ionic zinc, zinc nitrate or zinc sulfate, and c) 20 to 93 wt% EDTA or tetrasodium EDTA.

12. Wound dressing according to one of the preceding claims, characterized in that the antimicrobial composition contains 80 to 92 wt.% EDTA, 5 to 10 wt.% silver and 3 to 10 wt.% zinc.

13. Wound dressing according to any one of the preceding claims, characterized in that the antimicrobial composition contains a total of 8 to 10 wt.% silver and zinc.

14. Wound dressing according to any one of the preceding claims, characterized in that the first nonwoven layer is coated, impregnated or saturated with the antimicrobial composition.

15. Wound dressing according to one of the preceding claims additionally comprising a third non-woven layer which overlays the first non-woven layer on the wound side.

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