Method for producing a layered wound dressing

p0001The invention relates to a method for producing a layered wound dressing. Such wound dressings are used in particular as a hemostatic and wundversiegelndes means and for connecting separate Körpergewebsbereichen uses a wound dressing produced by the process.

p0002Wound dressings, for the purposes and methods for their preparation are well known.

p0003From the <patcit id="pcit0001" dnum="EP0815879A2"><text>EP 0815879 A2</text></patcit> is shown a method which relates to the preparation of a bioabsorbable unit and dissolving a cellulose derivative, which consists of the group consisting of methylcellulose, carboxymethylcellulose or cellulose acetate in water and comprises subsequently oxidizing the Celluslosederivates. This unit should be able to be provided in the form of a film, a gel, a powder, a fibrous mat or a sponge available.

p0004The <patcit id="pcit0002" dnum="EP1378255B1"><text>EP 378 255 B1 1</text></patcit> also describes a method for producing a single hemostatic wound dressing. It comprises providing a solution having therein a substantially dissolved water-soluble or water-swellable biocompatible polymer, and also the provision of a composed of fibers of a biocompatible polymer and flexibility, strength and porosity containing substance and immersing this material in the solution, followed by freeze-drying to obtain a porous polymeric matrix.

p0005A single absorbable composite of an insoluble collagen matrix with chlorhexidine and calcium alginate for use in the treatment of periodontal disease of the tooth revealed the <patcit id="pcit0003" dnum="DE69428312T2"><text>DE 694 28 312 T2</text></patcit>, Washed fibrous collagen is suspended in clean deionised pyrogen free water and homogenised and then acidified to a fine fibrous suspension, to obtain a swollen, fibrous dispersion. This is mixed with a suspension of homogenized Calziumalginatfasern and chlorhexidine digluconate, degassed, the mixture obtained thereafter and dried at room temperature. The dried material can then be cut into strips.

p0006A well-layered washi absorbable hemostatic agent discloses the <patcit id="pcit0004" dnum="DE10318802A1"><text>DE 103 18 802 A1</text></patcit>, At least one is in solution or in a gel state polymer, preferably polysaccharide is transferred by freeze-drying in a solid dry form.

p0007A method for producing a multi-layer collagen matrix for reconstruction commercial clear from the <patcit id="pcit0005" dnum="DE60018480T2"><text>DE 600 18 480 T2</text></patcit> forth. Two layers of a porous matrix of biocompatible collagen are combined at uniform and simultaneous insertion of mechanical pressure and elevated temperature to form a multilayer sheet.

p0008Another method for producing a multilayer wound dressing based on collagen discloses <patcit id="pcit0006" dnum="DE69724243T2"><text>DE 697 24 243 T2</text></patcit>, The individual layers can contain thrombin or a precursor of thrombin. As Thrombinstabilisator serve, among other polysaccharides. The adhesion of the layers for example, by simultaneous or sequential freezing, lyophilization, by cross-linking or bonding.

p0009A layered wound dressing with at least one biocompatible carrier material and at least a polysaccharide and a method for their preparation describes the <patcit id="pcit0007" dnum="DE102006020498A1"><text>DE 10 2006 020 498 A1</text></patcit>, At least one dispersion of the carrier material in a liquid dispersion medium is solidified by cooling and freezing to form at least one solid base layer, onto which the polysaccharide is applied, which is solidified by further cooling to a solid layer of the polysaccharide on the carrier layer. With removal of the dispersing agent, the two layers are to be joined together.

p0010In this method, which requires at least a two-fold freezing, there is the danger that the first frozen layer again thaws. By inhibited in their motion the molecules of the frozen layer, the adhesion of the two layers is also weak. Thus, an enhanced uptake of wound exudate cause the individual layers loosen from one another again. In addition, the freezing process is very cumbersome, because the product has to be removed after the first freezing from the chamber of Einfrierapparates and thereby the chamber and the product reheated. Connecting is again the cooling down of the chamber and the freezing of the frozen layer with the thereon not yet frozen layer.

p0011The object of the invention is therefore to provide a multilayer wound dressing, which is easier to manufacture, while retaining the advantages of the use of biocompatible materials, has a greater stability of the connection between the materials in layers used and an advantageous for effective secretion removal pore structure of the polysaccharide.

p0012According to the invention the object is achieved by a method for producing a multilayer wound dressing with at least one biocompatible material and at least one polysaccharide, dissolved, which comprises the following steps, providing at least one dispersion of the polysaccharide in a liquid dispersion medium, solidifying the dispersion under laminar formation of the polysaccharide by receiving water from the liquid dispersion medium and / or recording of the dispersing agent in the polysaccharide and / or by evaporation of the dispersant, by the supply of water swelling of the layered solidified polysaccharide to form a gel, and setting the thickness and pore structure, applying a suspension or solution of biocompatible material onto the swollen gel, or on the sheet-shaped solidified polysaccharide and simultaneously cooling and freeze-drying of the gel with the applied suspension or solution of the biocompatible material or the layered solidified polysaccharide with the applied suspension or solution of the biocompatible material respectively to form a fixed connection between the two layers.

p0013A preferred embodiment of the method provides that, for the suspension or solution of the biocompatible material, a saccharide, lipid, synthetic polymer, preferably polyvinyl alcohol or polyethylene glycol or a polypeptide, more preferably collagen, preferably with an addition of elastin, or a mixture of these materials and is used as a polysaccharide, preferably alginate, amylose, amylopectin, cellulose, chitosan, chondroitin sulfate, dextran, hyaluronic acid, starch and / or a derivative of these substances.

p0014Preferably, an organic liquid containing mostly water as the liquid dispersing agents or more organic liquids containing mostly water, preferably ethanol, isopropanol or glycerol, are used.

p0015Preferably, the organic liquid comprises up to 30 wt.%, Preferably 15 wt.%, Water and the Polysacchariddispension is at a concentration of up to 40 wt.% Of the polysaccharide, preferably having a concentration of 20 wt.%, Based on the total weight the Polysacchariddispension provided.

p0016According to a further embodiment of the invention, as the suspension of the biocompatible material is a collagen suspension at a concentration of up to 1.5 wt.%, Preferably from 1.0 wt.% Collagen, based on the total weight of the suspension, is provided.

p0017Preferably, the wound dressing having a thickness of the sheet-shaped polysaccharide of 0.5 mm to 5 mm, particularly preferably from 2 mm to 4 mm produced.

p0018Further embodiments of the method provide that the wound dressing with a thickness of the layered biocompatible material from 0.02 mm to 5 mm, preferably from 2 mm to 4 mm, produced and that for the determination of wound dressing, the polysaccharide and / or the biocompatible material to be colored, preferably by means of riboflavin.

p0019A particularly preferred embodiment of the invention is formed that the surface of the wound dressing and modified example smoothed or textured wave or waffle-shaped and the wound dressing contains antimicrobial and / or anti-inflammatory agents. These are preferably antimicrobial agents, particularly antibiotics, such as gentamycin, chitosan, chlorhexidine salts, furanone derivatives, polyhexanide, polyhexamethylene biguanide (PHMB), silver, thymol, triclosan and / or derivatives thereof. Similarly, wound-healing agents, especially Allatoin, beta-sitosterol, Bromalain, dexpanthenol, flavonoids, riboflavin, saponin, Soledum-cineol, and / or tocopherol, may be used.

p0020According to a further particularly preferred embodiment of the method, the wound dressing using a crosslinking agent, preferably an aldehyde or more aldehydes and / or of a plasticizer, preferably 1,2-propanediol.

p0021According to a particularly preferred embodiment of the invention can be applied consisting of a frozen layered wound dressing made of a biocompatible material and a polysaccharide, a new layer, and then formed by freeze-drying a three layer wound dressing.

p0022Finally, a preferred embodiment of the invention provides that as collagen, preferably bovine collagen, equine and / or porcine origin, more preferably of porcine origin is used.

p0023The invention further relates to a layered wound dressing comprising the features of claim eleventh

p0024The term "biocompatible" in the sense of the present invention, the property of a material is to be understood that does not cause undesirable side effects in contact with body tissues.

p0025The invention combines the special advantage that a multilayer wound dressing can be made in a single freeze drying process.

p0026By the invention it is further possible, for a given biocompatibility and resorbability to improve the stability of the wound dressing in particular. This is achieved in particular by the much stronger adhesion of the opposite surfaces of the biocompatible material and the polysaccharide, due to the only unique freezing process of the two materials. The separate formation of a support layer proves in the present process, in contrast to prior art no more than necessary. Furthermore, the wound dressing produced by this invention is characterized by a better and controllable wound exudate absorption capacity. This is influenced by the polysaccharide and the structure of the polysaccharide in the wound dressing used. The wound exudate absorption capacity can be used to selectively adjust the dispersant of the polysaccharide dispersion, the polysaccharide used and the swelling of the polysaccharide dispersion solidified. It is also possible, wound dressings according to the application with very different grammages in the range of 0.01 g / cm² and 0.15 g / cm² produce. Furthermore, the density and the strength of the biocompatible material and the polysaccharide may be influenced.

p0027The effect of polysaccharides on the rate of absorption of exudate is known. The more polysaccharide used for wound dressing, the more you can absorb this wound secretions. However, as well as the wound dressings are becoming harder and harder. There is therefore a need to improve the wound exudate absorption capacity without substantially increasing the basis weight of the wound dressing.

p0028The dispersing agent used mainly influenced the rate of exudate through the dressing. Easily vaporizable dispersant escape during the drying out of the wound dressing, thereby remain pores which are for rapid secretion collection of meanings. In contrast, a high concentration of heavy vaporizable dispersant leads to compression and therefore to the destruction of the polysaccharide and the matrix of the biocompatible material. This pore structure of the polysaccharide is far negatively affected, the wound dressing can only relatively slowly absorb secretions.

p0029By defined addition of water for the swelling process, the thickness and the pore structure of the polysaccharide matrix can be specifically influenced. This is connected with the advantage that the rate of absorption of exudate controlled in this manner and can be oriented for typical applications of the wound dressing.

p0030If the swelling of the polysaccharide almost completed and is to this one Polypeptidsuspension, preferably a collagen suspension, applied, the thickness of the surface-moderately present polysaccharide will change only in small tolerances. By contrast, if the swelling process of the polysaccharide only the addition of relatively little water and is applied to the solidified polysaccharide the Polypeptidsuspension, so the water is extracted for further swelling process from this. Thus, the polypeptide is condensed. There arise wound dressings with a relatively thick stratiform polysaccharide and a relatively very thin layer shaped polypeptide only can absorb exudate to a small extent, and so the wound dressing seals outwardly.

p0031The invention is illustrated in embodiments.

Example 1:

p0032There 11 g carboxymethylcellulose and 18 ml of glycerol were mixed to form a dispersion having a water content of 15% and, in Gießschalen. By including the water from the dispersion solution in the polysaccharide, the dispersion solidified. In this 75 ml of ultrapure water were added in order to achieve swelling. The swelling time was 1 hour. Then, 100 ml of a collagen suspension were on the swollen gel added. The collagen suspension% collagen was a pig skin by a known process, the extraction of collagen and swelling in water at a pH between 3 to 5, obtained suspension with a content of 1 wt. Used. Both materials were then cooled and frozen and freeze-dried together. With removal of water, the two materials joined to a surface formed as a moderate nonwoven layered wound dressing. It is soft, deformable and cuttable. The wound dressing has a basis weight of 0.125 g / cm², Both the carboxymethyl cellulose and the collagen each having a thickness of 1.5 mm to 2.5 mm.

p0033Depending on the intended use, the wound dressing provided with active ingredients and are cut according to the requirements in the desired size, sterilized, packaged and aseptically filled.

p0034The so prepared dressing can absorb up to 100 ml exudate.

Example 2:

p0035It 3 g of carboxymethylcellulose with 10 ml of 96% ethanol were mixed to form a dispersion. After evaporation of the ethanol, the polysaccharide was solidified. On the polysaccharide 60 ml of ultrapure water were added. Subsequently, as described in Example 1, a collagen suspension, where the after one hour fully swollen polysaccharide. The further treatment steps were carried out as described in Example 1st The wound dressing is also soft, deformable and cuttable. The wound dressing has a basis weight of 0.016 g / cm², Both the carboxymethyl cellulose and the collagen each having a thickness of 1.5 mm to 2.5 mm.

p0036The layered polysaccharide of the wound dressing can absorb small volume of exudate about 10 ml in less than 10s.

Example 3:

p0037A dispersion was prepared as described in Example 2 and solidified. However, the solidified polysaccharide dispersion was not swollen with ultrapure water, but immediately it - as described in Example 1 - where a collagen suspension. The swelling time was 3 hours. Thereafter, the steps were carried out as described in Example 1st The wound dressing differs from the wound dressings prepared according to Examples 1 and 2, characterized in that the layer-like polysaccharide is formed considerably thicker with 3 mm to 4 mm than the layered collagen with here about 0.05 mm.

p0038The wound dressing has with respect to the polysaccharide, the same properties as the wound dressing prepared according to the Example 2. FIG. The polypeptide is compressed against and prevents the escape of wound exudate.

p0039If an identification of the wound dressing should be based on the intended use, the polysaccharide or collagen can be dyed, preferably by means of riboflavin