Wound dressing with a hydrogel layer and a wound contact layer containing hyaluronic acid

Description

[0001] The present invention relates to a wound dressing comprising a hydrogel layer and a wound contact layer. The wound contact layer is bonded to a wound-facing side of the hydrogel layer. Furthermore, the present invention relates to a manufacturing method and an application of the aforementioned wound dressing.

[0002] WO 2010 / 000451 A1 discloses a multilayer wound dressing comprising a wound contact layer and an absorbent layer. The absorbent layer comprises a hydrophilic polyurethane foam having a water content of at least 10 wt.%. The wound contact layer can comprise a hydrogel. The wound dressing disclosed in WO 451 does not adhere to the wound and can create a moist wound environment that promotes wound healing by absorbing excess moisture from the wound and releasing moisture to the wound as needed.

[0003] WO 2018 / 115257 A1 and EP 3587456 A1 relate to further developments of the wound dressing disclosed in WO 451. According to WO 257, the hydrogel wound contact layer now contains, in particular, glycerol as a humectant instead of propylene glycol. This improves the hydrogel's cell compatibility. According to EP 456, the hydrogel wound contact layer contains chitosan. This gives the hydrogel an antibacterial effect and makes it advantageous for treating infected wounds.

[0004] The wound dressings disclosed in WO 451, WO 257, and EP 456 enable gentle and effective wound treatment in many cases. Nevertheless, it would be desirable if the wound dressings could support the wound healing process even more effectively.

[0005] US 2002 / 0111576 A1 discloses a wound dressing comprising: (a) a first layer disposed adjacent to the wound and comprising a material that is bioabsorbable, porous, and capable of serving as a scaffold for cell adhesion and proliferation; and (b) a second layer in contact with the first layer and comprising an absorbent, gel-forming material capable of serving as a barrier to cell adhesion and penetration.

[0006] The object of the present invention was to provide an improved wound dressing. In particular, the wound dressing was intended to have the potential to particularly effectively support the wound healing process. These objects are achieved by a wound dressing according to claim 1 and a method according to claim 19.

[0007] According to the invention, the wound dressing comprises a hydrogel layer and a wound contact layer. The wound contact layer is bonded to a wound-facing side of the hydrogel layer. The wound dressing according to the invention is characterized in that the wound contact layer comprises hyaluronic acid.

[0008] The hydrogel layer of the wound dressing according to the invention can both absorb and release moisture. Thus, the wound dressing can create a moist wound environment that promotes wound healing in a wide variety of different wound types.

[0009] The wound contact layer of the wound dressing according to the invention contains an active ingredient in the form of hyaluronic acid, which can have diverse wound-healing properties, including at the biological or cellular level. The wound-healing properties of hyaluronic acid have been widely described in the scientific literature and are summarized, for example, in the article "Hyaluronan in wound healing: Rediscovering a major player" (Wound Rep Reg (2014), 22, 579-593). Hyaluronic acid can, among other things, stimulate the migration and proliferation of cells involved in wound healing, such as fibroblasts. Accordingly, the wound dressing can further accelerate and support the wound healing process compared to conventional hydrogel-containing wound dressings, allowing the wound to close and heal more quickly.This can also lead to improved wound healing from a cosmetic point of view, for example, by reducing scarring. Further advantages of the invention emerge from the preferred embodiments of the invention described below.

[0010] The hydrogel layer preferably comprises a polyurethane polymer, in particular a polyurethane-polyurea copolymer. The hydrogel layer particularly preferably consists of a polyurethane polymer, in particular a polyurethane-polyurea copolymer, as the solid phase and an aqueous liquid as the liquid phase. Such hydrogels can be used particularly advantageously in wound treatment.

[0011] Furthermore, the hydrogel layer is preferably obtainable by reacting an amine-terminated prepolymer containing polyalkylene oxide units with an isocyanate-terminated prepolymer containing polyalkylene oxide units in the presence of water and optionally a polyhydric alcohol, in particular glycerol. In such a reaction, the aforementioned advantageous hydrogels can be formed with a polyurethane polymer or polyurethane-polyurea copolymer. The reaction can also take place in the presence of further components. In particular, the reaction can also take place in the presence of one or more salts selected from the group consisting of sodium chloride, potassium chloride, magnesium chloride, and calcium chloride. Of this group of inorganic salts, sodium chloride is particularly preferred.

[0012] In this reaction, the sum of the masses of amine-terminated prepolymer and isocyanate-terminated prepolymer is preferably 10 to 30 wt. %, the mass of the polyhydric alcohol—if present—is 5 to 35 wt. %, and the mass of water is at least 40 wt. The weights refer to the total mass of all reactants. Furthermore, in this reaction, the molar ratio of reactive isocyanate end groups to reactive amine end groups can be 1.0 to 1.5. Further information on the preparation of such hydrogels can be found in WO 2018 / 115257 A1.

[0013] The polyalkylene oxide units of the two aforementioned prepolymers can be formed by polyethylene oxide and / or polypropylene oxide units, with the weight ratio of ethylene oxide to propylene oxide units preferably being 3:1 to 7:1. Furthermore, the isocyanate-terminated prepolymer is advantageously branched in at least three branches. In particular, the isocyanate-terminated prepolymer is branched in exactly three branches.

[0014] In particular, the amine-terminated prepolymer is a triblock polymer composed of propylene oxide, ethylene oxide, and propylene oxide units, each terminally amine-functionalized with 2-aminopropyl groups. It typically has a reactive amine end group content of 0.9554 mmol / g, an average molecular weight of approximately 2000 g / mol, and a dispersity of 1.08, measured by gel permeation chromatography. The weight ratio of ethylene oxide to propylene oxide units is 3:1 to 7:1, preferably 39:6. Such an amine-terminated prepolymer is commercially available, for example, as Jeffamin®< ED-2003 (Huntsman; Everberg, Belgium).

[0015] In particular, the isocyanate-terminated prepolymer is a three-arm copolymer of ethylene oxide and propylene oxide units, each terminally reacted with one molecule of isophorone diisocyanate. It typically has a content of reactive isocyanate end groups (NCO groups) of 2.5% to 4.0%, preferably 3.0% to 3.4%, particularly preferably 3.2%, and a weight ratio of ethylene oxide units to propylene oxide units of 3:1 to 4:1. Such an isocyanate-terminated prepolymer with aliphatic isocyanate groups is commercially available, for example, as Aquapol®< PI-13000-31 (Carpenter; Richmond, USA).

[0016] The following figure illustrates the schematic structure of a three-arm branched isocyanate-terminated prepolymer containing polyethylene oxide and polypropylene oxide units (as in Aquapol®). A glycerol molecule forms the center of the prepolymer. The three "arms" of the prepolymer, each with a terminal isocyanate group, are linked to the hydroxyl groups of the glycerol molecule. The glycerol molecule itself is not shown in the figure. It would be located in the right half of the image where the three "arms" schematically represented as wavy lines meet. The chemical structure of one "arm" is shown in more detail in the left half of the image.

[0017] In a preferred embodiment of the invention, the hydrogel layer is perforated. The perforations can make the hydrogel layer more permeable to wound exudate, which can be particularly advantageous if the wound dressing comprises an additional absorbent layer. The thickness of the hydrogel layer can be, for example, 0.5 to 5 mm, preferably 0.5 to 3 mm.

[0018] Characteristic and essential for the present invention is the hyaluronic acid contained in the wound contact layer. It is typically present in the wound contact layer essentially free, i.e., in a non-crosslinked form. A salt of hyaluronic acid can also be used for the invention. Thus, the wound contact layer according to the invention can just as well comprise a salt of hyaluronic acid. The salt can be, for example, the potassium salt or the sodium salt of hyaluronic acid. Hyaluronic acids or salts of hyaluronic acid are commercially available from various sources and in various molecular weights. The hyaluronic acid can have a molecular weight of less than 1000 kDa (low molecular weight), preferably 1000 to 1800 kDa (medium molecular weight), or particularly preferably more than 1800 kDa (high molecular weight).Hyaluronic acid with a low molecular weight may be more water-soluble and therefore easier to process. However, hyaluronic acid with a medium or high molecular weight is preferred, as it can have a particularly positive effect on wound healing.

[0019] In particular, within the scope of the present invention, it is provided that the wound contact layer is designed as a sacrificial layer, so that the wound contact layer can at least partially dissolve upon contact with wound exudate and / or the wound contact layer can be at least partially reabsorbed by the wound tissue. In particular, the wound contact layer designed as a sacrificial layer can essentially completely dissolve upon contact with wound exudate and / or essentially completely reabsorbed by the wound tissue. After the wound contact layer has dissolved and / or been reabsorbed, the hydrogel layer can form the wound contact layer of the wound dressing. The hydrogel as the new wound contact layer does not stick to the wound and thus enables gentle dressing changes.This means that the hyaluronic acid is released from the wound dressing to the wound and the hydrogel layer can form the wound contact layer during the wound treatment, whereby particularly good wound healing-promoting effects can be achieved.

[0020] The wound contact layer can exhibit a hyaluronic acid release of at least 50%, preferably at least 60%, more preferably at least 70%, particularly preferably at least 80%, and most preferably at least 90%. The hyaluronic acid release can be determined using the test method described in this document and refers to an incubation period of three days. The test procedure is described in the second section of the test results.

[0021] According to the invention, the wound contact layer is film-like or foil-like. Such a film-like wound contact layer can advantageously release the hyaluronic acid and is easy to produce. Furthermore, such a film-like wound contact layer can be easily bonded to the hydrogel layer. Furthermore, the material from which the wound contact layer is made is non-porous so that the wound contact layer does not dissolve too quickly upon contact with wound exudate. A non-porous wound contact layer can therefore release the hyaluronic acid more evenly and over a longer period of time. The layer thickness of the wound contact layer can be 0.1 to 3.0 mm, preferably 0.1 to 1.5 mm, and particularly preferably 0.1 to 1.0 mm. The specified lower limit for the layer thickness of 0.1 mm can also be higher, for example, 0.2 mm, 0.3 mm, 0.4 mm, or 0.5 mm.A further advantage of the film-like and non-porous wound contact layer is that, like the hydrogel layer, it can be transparent.

[0022] According to a particularly preferred embodiment of the invention, the wound contact layer is obtainable by drying a liquid or gel-like preparation comprising hyaluronic acid and water. This allows the production of a film-like, non-porous, transparent wound contact layer designed as a sacrificial layer.

[0023] Drying may, for example, involve freeze-drying and / or air-drying. However, freeze-drying can result in a porous wound contact layer and is therefore less preferred in this case. Accordingly, air-drying is the preferred drying method in this case. Air-drying can also be performed using a technical aid, such as a drying cabinet, to accelerate the drying process.

[0024] Furthermore, it is preferred if the preparation is only partially dried, so that a residual water remains in the wound contact layer. The wound contact layer can then be more flexible and tear-resistant. For example, the wound contact layer can contain up to 50 wt.%, up to 40 wt.%, up to 30 wt.%, up to 20 wt.%, up to 10 wt.%, or only up to 5 wt.% water, based on the total weight of the wound contact layer.

[0025] As previously mentioned, the preparation used for drying comprises hyaluronic acid and water. The hyaluronic acid concentration of the preparation can be, for example, 1 to 10 wt.%, 1 to 8 wt.%, 1 to 6 wt.%, 1 to 4 wt.%, or 1 to 2 wt.%, based on the total weight of the preparation. The preparation can also contain one or more further components, such as an anti-inflammatory or antimicrobial active ingredient. However, it is also possible for no such further components to be present and for the preparation to consist of hyaluronic acid and water. Such a preparation is simple and cost-effective to produce. In any case, within the meaning of the present invention, it is typically provided that the preparation does not contain any cross-linking agents for the hyaluronic acid.

[0026] The wound contact layer is advantageously perforated. These perforations, similar to the perforations in the hydrogel layer, are intended to increase the permeability of wound exudate. They can also have the beneficial effect of allowing the hydrogel layer to better moisturize a dry wound. If both the hydrogel layer and the wound contact layer are perforated, the perforations in the hydrogel layer and the wound contact layer can preferably overlap, so that the composite of hydrogel layer and wound contact layer has continuous perforations, which allow the unhindered passage of wound exudate through the composite of hydrogel layer and wound contact layer, for example, into an additional absorbent layer of the wound dressing.

[0027] The perforations in the hydrogel layer and in the wound contact layer can be substantially round and present at regular intervals within 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 such that the layers are network-like. The perforations in the hydrogel layer and in the wound contact layer can be created by cutting or punching. Alternatively, it is possible to create the perforations during polymerization or drying of the layers using suitable casting molds. For example, as described in WO 2010 / 000451 A1, a mold with a nub structure can be used to create the perforations.

[0028] According to the invention, the wound contact layer is bonded to the wound-facing side of the hydrogel layer. The wound contact layer can be bonded to the hydrogel layer by bringing the layers into contact with one another when the hydrogel layer is not yet fully polymerized. Alternatively, the wound contact layer can be bonded to the hydrogel layer by a bonding agent. Surprisingly, it has been found that an isocyanate-terminated prepolymer containing polyalkylene oxide units can also be used as the bonding agent. This prepolymer, as described above, is preferably used to produce the hydrogel layer. The same isocyanate-terminated prepolymer can advantageously be used to produce the hydrogel layer and to bond the wound contact layer to the hydrogel layer. The bonding agent is then particularly well compatible with the hydrogel layer from a chemical point of view.

[0029] If the wound contact layer is bonded to the hydrogel layer as described above, a covalent bond between the two layers can occur when a portion of the isocyanate-terminated prepolymer contained in the hydrogel or bonding agent reacts with a portion of the hyaluronic acid contained in the wound contact layer. The portion of the wound contact layer covalently bonded to the hydrogel layer can then no longer be released into the wound and can become a component of the hydrogel layer. In order to release as much hyaluronic acid as possible, it is therefore proposed to bond the wound contact layer and the hydrogel layer only in certain areas. For example, it is conceivable to provide the bonding agent only at specific points between the wound contact layer and the hydrogel layer.

[0030] Normally, the wound dressing according to the invention comprises further layers or dressing layers in addition to the hydrogel layer and the wound contact layer. For example, the wound dressing typically further comprises a backing layer as the outermost, non-wound dressing layer. The backing layer can comprise a water-impermeable and water vapor-permeable plastic film, in particular polyurethane film. Furthermore, a wound-facing side of the backing layer can be adhesively coated, for example with an acrylate adhesive. In this case, the backing layer advantageously overlaps the other layers of the wound dressing and forms an adhesive edge, whereby the wound dressing can then be designed in the manner of an island dressing. The adhesive edge can be used to attach the wound dressing to the patient's body. The backing layer can be bonded to a non-wound side of the hydrogel layer.

[0031] Furthermore, it is particularly preferred that the wound dressing further comprises an absorbent layer, in particular an absorbent foam layer.

[0032] This allows the wound dressing to absorb more fluid. The wound dressing is then particularly suitable for treating more heavily exuding wounds. A foam layer in the form of a hydrophilic polyurethane foam is particularly suitable, which can advantageously contain a water content of at least 10% by weight. The absorbent layer is preferably bonded to a side of the hydrogel layer facing away from the wound. The usually present backing layer is then bonded to a side of the absorbent layer facing away from the wound, so that the absorbent layer is arranged between the backing layer and the hydrogel layer. The layer thickness of the absorbent layer can be, for example, 0.5 to 5 mm, preferably 0.5 to 3 mm. Further possible features and advantages of the absorbent layer are disclosed in WO 2010 / 000451 A1.

[0033] The invention also relates to a method for producing the wound dressing according to the invention comprising the following steps: i. Providing a hydrogel layer, ii. Providing a wound contact layer comprising hyaluronic acid, iii. Connecting the wound contact layer to a wound-facing side of the hydrogel layer.

[0034] Providing the wound contact layer may include the following steps: i. Dissolving hyaluronic acid in an aqueous solution, thereby forming a hyaluronic acid-containing preparation, ii. Drying the hyaluronic acid-containing preparation, thereby forming a hyaluronic acid-containing layer.

[0035] For step ii., the hyaluronic acid-containing preparation can, for example, be transferred to a Petri dish or applied to a film carrier and then exposed to air drying.

[0036] The wound dressing according to the invention is particularly well suited for treating wounds on the human or animal body in the granulation or epithelialization phase. Accordingly, the invention also relates to the use of the wound dressing according to the invention for treating wounds on the human or animal body in the granulation or epithelialization phase. In other words, the invention also relates to the wound dressing according to the invention for use in treating wounds on the human or animal body in the granulation or epithelialization phase. The subject matter of the invention also encompasses the therapeutic use of the hyaluronic acid contained in the wound dressing for wound healing, in particular for phase-appropriate wound healing.Accordingly, the invention is directed to hyaluronic acid for use in the treatment of wounds on the human or animal body in the granulation or epithelialization phase, wherein the hyaluronic acid is contained in the wound dressing according to the invention.

[0037] The manufacturing method and use of the wound dressing according to the invention also relate to the specific embodiments of the wound dressing described above. This means that the additional features of the specific embodiments of the wound dressing described above are also part of the manufacturing method and use of the wound dressing. Examples and figures

[0038] The following examples and figures are intended to explain and illustrate the invention in more detail. Similar structural elements in the figures may be identified by the same reference numerals.

[0039] Figure 1shows a sectional view of a wound dressing according to the invention 1 in a first embodiment. The wound dressing 1 includes a hydrogel layer 2, which preferably consists of a polyurethane-polyurea hydrogel. The wound dressing 1 also includes a wound contact layer 3, which has a wound-facing side of the hydrogel layer 2 The wound contact layer 3 contains hyaluronic acid and is designed as a "sacrificial layer." "Sacrificial layer" means that the wound contact layer 3 can be at least partially or preferably substantially completely dissolved and / or resorbed during the wound treatment, whereby the hyaluronic acid is removed from the wound contact layer 3 as a wound-healing agent. When the wound contact layer 3 has dissolved, the hydrogel layer can 2come into direct contact with the wound surface. It then forms the new wound contact layer of the wound dressing 1 Finally, the wound dressing includes 1 another one with a side of the hydrogel layer facing away from the wound 2 connected backing layer 4. This limits the wound dressing 1 to the outside and protects the wound dressing 1 especially against contamination. The backing layer 4 consists of a waterproof and water vapor-permeable plastic film, for example a polyurethane film. The wound dressing 1 can advantageously be transparent to allow observation of the wound condition during treatment. In use, the wound dressing 1 placed on the wound and, if necessary, fixed with additional dressing material such as a bandage or film dressing.

[0040] The wound dressing 1can be produced by the backing layer 4 coated with a reaction mixture which, after polymerization, forms the hydrogel layer 2 The wound contact layer, which is obtained in particular by air drying an aqueous preparation containing hyaluronic acid 3 can then be bonded to the hydrogel layer with a bonding agent, preferably an isocyanate-terminated prepolymer, as described above 2 be connected.

[0041] Figure 2 shows a sectional view of a wound dressing according to the invention 5 in a second embodiment. The wound dressing 5 differs from the wound dressing 1 out of Figure 1 because the wound contact layer 3 perforated. The perforations 6 Both the absorption of exudate from the wound and the release of moisture to the wound through the hydrogel layer 2by increasing the permeability of the wound contact layer 3 for fluid is increased. This improvement is particularly noticeable at the beginning of wound treatment when the wound contact layer 3 has not yet dissolved. The perforations 6 can thus accelerate and promote the maintenance of a moist wound climate that promotes wound healing.

[0042] In Figure 3 is the wound dressing 5 shown with a view of the underside. As can be seen Figure 3 As can be seen, the perforations 6 in a regular pattern in the wound contact layer 3 present and rounded. The perforations 6 can preferably have a diameter of 1 to 3 mm. The perforations 6 However, they can also be larger and / or more numerous than in Figure 3 shown so that the wound contact layer 3 can have a net-like structure.

[0043] Figure 4 shows a sectional view of a wound dressing according to the invention 7 in a third embodiment. In addition to the three layers 2, 3 and 4 the wound dressing 1 the wound dressing 7 a further layer of dressing with full adhesive 8, 9 The reference symbol 8 refers to the adhesive, which can preferably be an acrylate adhesive. Reference symbol 9 is then directed to the carrier layer of the additional bandage layer. 9 As with the layer 4 It is a waterproof, yet water vapor permeable film material made of polyurethane, for example. The new bandage layer 8, 9 is by means of the adhesive 8 on the side of the layer facing away from the wound 4 attached so that the bandage layer 8, 9 or their layer 9now as the actual backing layer of the wound dressing 7 As in Figure 4 and in particular Figure 5 (View of the underside of the wound dressing 7 ), the bandage layer overlaps 8, 9 the layers 2, 3 and 4 the wound dressing 7 and forms an adhesive edge 10 With the adhesive edge 10 the wound dressing can 7 can be permanently and easily attached to the patient's body without the need for a separate secondary dressing. The wound dressing 7 can be used as a wound dressing 5 a perforated wound contact layer 3 and also be transparent so that the patient and nursing staff can inspect the wound even if the wound dressing 7 covered the wound.

[0044] Figure 6 shows a sectional view of a wound dressing according to the invention 11in a fourth embodiment. The wound dressing 11 contains the layers 2, 3, 8 and 9 the wound dressing 7. Between the adhesive layer 8 and the hydrogel layer 2 However, in this design there is an absorbing layer 12, which can be an absorbent foam layer, for example in the form of a hydrophilic polyurethane foam. The additional absorbent layer 12 the wound dressing can 11 absorb more wound exudate than the versions from Figures 1 to 5 . It is therefore better suited for the treatment of more exuding wounds. The absorbent layer 12but can also be beneficial in the treatment of dry wounds, namely when it is mixed with a proportion of water or another suitable liquid such as isotonic saline solution or Ringer's solution by the manufacturer.

[0045] The wound dressing 11 can be produced by the surface of the wound-facing side of the absorbent layer 12 with the not yet fully polymerized hydrogel layer 2 is brought into contact, whereby the hydrogel layer 2 partially into the porous absorbing layer 12 penetrates and thus bonds the two layers. After that, on the side of the absorbent layer facing away from the wound, 12 the adhesive film 8, 9 Further details on these steps are contained in WO 2010 / 000451 A1, which has already been mentioned several times. Finally, the wound contact layer can 3as previously in connection with wound dressing 1 described with the hydrogel layer 2 be connected.

[0046] The wound dressing 11 can also advantageously have perforations 6 in the wound contact layer 3 have, whereby the perforations 6 preferably also the hydrogel layer 2 This allows fluid to flow freely between the wound and the layers 2, 3 as well as 12 In particular, excess wound exudate can damage the layers 2 and 3 pass through unhindered and from the absorbent layer 12 recorded and stored. Such a design of the wound dressing is Figure 7 on average and in Figure 8 shown looking at the bottom and marked with the reference symbol 13 shown.

[0047] For protection during storage and to facilitate application, the wound dressings may have at least one additional cover layer (not shown). The cover layer is releasably connected to the wound contact layer and is removed before the wound dressing is applied to the wound. Application systems for wound dressings with such a cover layer are extensively described in the prior art. The cover layer may, for example, comprise a two-part film layer made of siliconized polypropylene. Test results

[0048] Several samples of a composite consisting of a hydrogel layer and a hyaluronic acid-containing layer were prepared and investigated with regard to hyaluronic acid release, absorption capacity and pH value. 1. Preparation of samples

[0049] i. A hydrogel layer was prepared by reacting an amine-terminated prepolymer containing polyalkylene oxide units with an isocyanate-terminated prepolymer containing polyalkylene oxide units in the presence of demineralized water, glycerol, and sodium chloride. Jeffamin® ED-2003 (Huntsman; Everberg, Belgium) was used as the amine-terminated prepolymer, and Aquapol® PI-13000-31 (Carpenter; Richmond, USA) was used as the isocyanate-terminated prepolymer. The hydrogel layer thus contained a polyurethane-polyurea copolymer as the solid phase and a mixture of water, glycerol, and sodium chloride as the liquid phase. The hydrogel produced had the following composition based on the total weight of the materials used: 7.58 wt% amine-terminated prepolymer (Jeffamin) 13.03 wt% isocyanate-terminated prepolymer (Aquapol) 61.54 wt% water 16.85 wt% glycerol 0.99 wt% sodium chloride ii.A hyaluronic acid-containing layer was prepared by dissolving hyaluronic acid in demineralized water to saturation and transferring the resulting preparation to a Petri dish. The preparation contained in the Petri dish was then air-dried in a drying cabinet at 55°C for 3 days. A film-like layer formed on the bottom of the Petri dish. The hyaluronic acid used had a molecular weight of 1800 kDa and was obtained from Pharmasports GmbH & Co. KG (Bergen, Germany). iii. Sample pieces measuring approximately 1 cm x 1 cm (length x width) were punched or cut from the hydrogel layer and the hyaluronic acid-containing layer. The weight of the individual sample pieces was determined. iv.The hydrogel specimens were thinly and evenly coated on one side with the isocyanate-terminated prepolymer (Aquapol®< PI-13000-31) using a spatula and brought into contact with the hyaluronic acid specimens, resulting in the desired specimens with the hydrogel layer and the hyaluronic acid-containing layer. The prepolymer bonded the two layers together, acting as an adhesive. The weight of each individual specimen was determined. Thus, the weight of the layers encompassed by the specimen, as well as the total weight of the specimen, was known for each individual specimen.

[0050] Figures 9 and 10The figures show examples of one of the manufactured samples, viewed from above and from the side, respectively. The lower layer is the hydrogel, and the upper layer is the hyaluronic acid film, which is intended for use as a wound contact layer. As can be seen from the figures, the sample is transparent. 2. Hyaluronic acid release from the samples

[0051] i. A sample prepared as described above was placed in a Petri dish of known weight filled with demineralized water and incubated for 1 to 7 days at room temperature. Care was taken to ensure that at least the hyaluronic acid-containing layer of the sample was always below the water surface. ii. After the incubation period, the sample was removed from the Petri dish. The Petri dish containing the liquid was then stored in a drying cabinet at 55°C until the liquid had completely evaporated. A residue remained in the Petri dish, which was assumed to consist of released hyaluronic acid and, if present, glycerol and sodium chloride. iii. The Petri dish was weighed to determine the weight of the dried residue. The percent amount of hyaluronic acid released from the sample (HAFp) was calculated using the following formula: HAF P = m RP − m RK / m HAS * 100 The abbreviation mRP stands for the weight of the sample residue. The abbreviation mRK stands for the weight of the control residue. This consisted of only one piece of hydrogel and was treated in the same way as the sample. Finally, the abbreviation mHAS stands for the weight of the hyaluronic acid-containing layer of the sample. iv. To verify that the residue no longer contained any water and consisted primarily of hyaluronic acid, an IR spectrum of the residue was recorded after the weighing step.

[0052] Figure 11 shows the IR spectrum of the hyaluronic acid used (reference spectrum). Figure 12 shows the IR spectrum of a residue as an example. The similarity of the two spectra indicated that the residue consisted primarily of hyaluronic acid.

[0053] Figures 13 and 14show examples of residues from the samples. As can be seen in the figures, these were present as transparent films that could also be removed from the bottom of the Petri dishes (see especially Figure 14 The presence and appearance of these film-like residues, in conjunction with the results of the IR spectroscopic investigations, demonstrated that the samples can release hyaluronic acid upon contact with an aqueous fluid.

[0054] In Figure 15The test results for hyaluronic acid release are presented as average values ​​of two to three different samples per incubation period. The tests showed that the produced samples released almost 50% of the hyaluronic acid after one day and over 70% after three days. A higher hyaluronic acid release could not be observed with the selected incubation times of up to 7 days. This could have two causes. Firstly, the water possibly contained in the hyaluronic acid-containing layers of the samples, due to which the values ​​for hyaluronic acid release in the present test procedure can tend to be calculated too low. Secondly, the portion of hyaluronic acid that may be inextricably bound to the hydrogel layer, which can be formed by the reaction of the prepolymer with the hydrogel layer and the hyaluronic acid-containing layer (see previous point 1iv).In any case, the tests conducted have shown that the samples can release the hyaluronic acid they contain at a rate and in quantities suitable for wound healing. The resulting hyaluronic acid-containing layers can thus at least partially dissolve and act as a sacrificial layer. 3. Absorption capacity of the samples

[0055] i. A sample prepared as described above was placed in a beaker filled with demineralized water and incubated for 4 to 72 hours at room temperature. The sample was always below the water surface. ii. After the incubation period, the sample was removed from the beaker and weighed. The absorption capacity of the sample in percent (AB P ) was then calculated using the following formula: AK P = m PNI / m PVI * 100

[0056] The abbreviation m PNI refers to the weight of the sample after incubation. The abbreviation m PVI, on the other hand, refers to the weight of the sample before incubation.

[0057] Figure 16shows the determined absorption capacities, which, as in the previous release studies, are average values ​​from two to three different samples per incubation period. The samples were therefore able to absorb more than three times their own weight in water. The decrease in absorption from the 48-hour value to the 72-hour value may be due to the fact that the hyaluronic acid-containing layer of the sample dissolves more and more with increasing incubation time, and this process follows different kinetics than the water absorption by the hydrogel. It is therefore conceivable that the sample, or rather the hydrogel layer of the sample, reached its maximum absorption capacity after 48 hours, but the hyaluronic acid-containing layer of the sample had not yet completely dissolved at this time ( Figure 15(also confirms this). Thus, as observed, the sample would lose weight again upon prolonged incubation. However, this does not mean that the hydrogel layer can only bind water for a limited time; rather, it is due to the weight loss resulting from the dissolving sacrificial layer containing hyaluronic acid. 4. Influence of samples on pH

[0058] i. A sample prepared as described above was placed in a beaker filled with demineralized water and incubated for 4 to 72 hours at room temperature. The sample was always below the water surface. The water used for the test had a pH of 6.1. ii. The pH of the liquid contained in the beaker was then determined.

[0059] The results of the pH measurements are in Figure 17Here, too, these are averages of two to three different samples per incubation time point. The measured pH values ​​remain in the slightly acidic range, which can be beneficial for wound healing.

Claims

1. Wound dressing (1, 5, 7, 11, 13) comprising - a hydrogel layer (2) and - a wound contact layer (3) which is connected to a wound-facing side of the hydrogel layer (2) and comprises hyaluronic acid, characterized in that the wound contact layer (3) is film-like and the material of which the wound contact layer (3) consists is not porous.

2. Wound dressing according to Claim 1, characterized in that the hydrogel layer (2) comprises a polyurethane polymer, more particularly a polyurethane-polyurea copolymer.

3. Wound dressing according to Claim 1 or 2, characterized in that the hydrogel layer (2) is obtainable by reacting an amine-terminated prepolymer containing polyalkylene oxide units with an isocyanate-terminated prepolymer containing polyalkylene oxide units in the presence of water and optionally a polyhydric alcohol, more particularly glycerol.

4. Wound dressing according to any of the preceding claims, characterized in that the hydrogel layer (2) is perforated.

5. Wound dressing according to any of the preceding claims, characterized in that the hyaluronic acid has a molecular weight of 1000 to 1800 kDa or of more than 1800 kDa.

6. Wound dressing according to any of the preceding claims, characterized in that the wound contact layer (3) is configured as a sacrificial layer.

7. Wound dressing according to any of the preceding claims, characterized in that the wound contact layer exhibits a hyaluronic acid release of at least 50%, preferably of at least 60%, more preferably of at least 70%, very preferably of at least 80% and especially preferably of at least 90%.

8. Wound dressing according to any of the preceding claims, characterized in that the wound contact layer (3) is obtainable by drying a liquid or gel-like preparation comprising hyaluronic acid and water.

9. Wound dressing according to Claim 8, characterized in that the drying comprises a freeze drying and / or an air drying.

10. Wound dressing according to Claim 8 or 9, characterized in that the preparation is only partially dried, and so a residue of water is present in the wound contact layer (3).

11. Wound dressing according to any of Claims 8 to 10, characterized in that the preparation consists of hyaluronic acid and water.

12. Wound dressing according to any of the preceding claims, characterized in that the wound contact layer (3) is perforated, wherein - if the hydrogel layer (2) is likewise perforated - the perforations in the hydrogel layer (2) and in the wound contact layer (3) preferably overlap one another.

13. Wound dressing according to any of the preceding claims, characterized in that the wound contact layer (3) is connected to the hydrogel layer (2) by bringing the layers into contact with one another when the hydrogel layer (2) is not yet completely polymerized.

14. Wound dressing according to any of Claims 1 to 12, characterized in that the wound contact layer (3) is connected to the hydrogel layer (2) by a connecting agent, wherein the connecting agent is preferably an isocyanate-terminated prepolymer containing polyalkylene oxide units.

15. Wound dressing according to Claim 14, characterized in that for producing the hydrogel layer (2) an isocyanate-terminated prepolymer containing polyalkylene oxide units is used, wherein the same isocyanate-terminated prepolymer is used for producing the hydrogel layer (2) and for connecting the wound contact layer (3) to the hydrogel layer (2).

16. Wound dressing according to any of the preceding claims, characterized in that the wound dressing further comprises a backing layer (4, 9), wherein the backing layer (4, 9) preferably comprises a water-impermeable and water vapour-permeable plastics foil, more particularly polyurethane foil.

17. Wound dressing according to any of the preceding claims, characterized in that the wound dressing further comprises an absorbent layer (12), more particularly an absorbent foam layer.

18. Wound dressing according to any of the preceding claims for use in the treatment of wounds on the human or animal body in the granulation or epithelialization phase.

19. Method for producing a wound dressing according to any of Claims 1 to 17, comprising the steps of i. providing a hydrogel layer (2), ii. providing a wound contact layer (3) comprising hyaluronic acid, iii. connecting the wound contact layer (3) to a wound-facing side of the hydrogel layer (2).