Surface-shaped material for wound treatment

Abstract

The present invention relates to a sheet-like material (10) for treating wounds, comprising a nonwoven fabric (12) made of absorbable polymer filaments (14) and collagen particles (16) having a particle size I of >80 μm arranged on and / or within the nonwoven fabric.

Description

[Technical Field]

[0001] The present invention relates to a sheet-like material for treating wound surfaces.

[0002] Absorbent sheets have been established in medical practice, for example, as skin substitutes for burns and even for the treatment of so-called decollement wounds, i.e., peeling wounds. Such sheets are known, for example, from EP 1 181 941 A1 and are sold by Polymedics GmbH (Germany) under the trademark Suprathel®. This known absorbent sheet does indeed provide analgesic and anti-infective effects when treating open wounds, and at the same time, its good mechanical properties allow for the almost unimpeded formation of granulation tissue. However, in wounds that are bloody or wet with exudate, the sheet's hemostatic effect is limited because it only exhibits slow liquid adsorption and absorption capabilities.

[0003] It is therefore an object of the present invention to provide a wound treatment sheet that exhibits improved hemostasis.

[0004] This problem with respect to sheet materials is solved according to the invention by a sheet material having the features set forth in claim 1. Preferred developments of the invention are set forth in the dependent claims and the description.

[0005] According to the present invention, the sheet-like material has a nonwoven fabric made of absorbent polymer filaments, and collagen particles with a particle size of more than 80 μm are disposed within or on the nonwoven fabric. The swelling ability of fibrous collagen, i.e., collagen with an intact secondary or tertiary structure, promotes water binding to the coating film and increases the water binding capacity per unit area of ​​the coating film. In this application, structurally intact collagen refers to collagen in which α and β bands are detectable in SDS-PAGE analysis. By immobilizing collagen particles within or on the highly porous nonwoven fabric made of absorbent polymer filaments, which itself is water-absorbent, excess plasma and / or wound exudate can be removed more quickly and effectively from the wound surface upon application to the wound.

[0006] Furthermore, highly porous nonwoven fabrics allow for particularly rapid bioavailability of the collagen particles in the sheet material. It is known that contact of fibrous collagen with a wound promotes the binding of von Willebrand factor (vWF) to the fibrillar collagen, as well as platelet binding to the corresponding receptor on the platelet membrane and platelet adhesion. This can increase platelet granule depletion (degranulation), triggering or enhancing plasma coagulation (secondary hemostasis). This is advantageous for accelerated and effective hemostasis, and does not occur when using nanoscale collagen particles, for which the α and β bands are no longer detectable in SDS-PAGE tests. Overall, this can further improve the hemostatic properties of the sheet material and promote vascularization of the wound surface and, ultimately, wound healing in general.

[0007] By designing the sheet material to be suitably flexible and deformable, it can easily conform to the surface of a skin wound, such as a joint area, where even coverage is normally difficult.

[0008] The collagen particles preferably have a particle size in the range of 80 μm to 500 μm, particularly preferably in the range of 100 μm to 250 μm, and very particularly preferably in the range of 100 μm to 150 μm. Surprisingly, it has been found that above an average particle size of approximately 500 μm, the hemostatic effect of the collagen in situ is reduced, and the collagen fixation to the nonwoven fabric is no longer sufficiently stable against the mechanical forces acting during handling and application of the sheet material. This can lead to undesired detachment of the collagen particles from the nonwoven fabric. A particle size of 100 μm to 150 μm allows for particularly reliable hemostasis.

[0009] According to a particularly preferred embodiment of the invention, the sheet material comprises 0.4 to 80% by weight, preferably 0.5 to 25% by weight, of collagen particles. It should be noted that the improvement in hemostatic properties of the sheet material provided by collagen is already achieved with approximately 1% by weight of collagen. In this respect, the sheet material may in particular comprise 0.4 to 2% by weight of collagen particles.

[0010] According to a preferred embodiment of the present invention, at least some of the collagen particles are at least partially arranged on the surface of the nonwoven fabric. Due solely to the size of the collagen particles, the sheet material has a higher hydrophilicity in the collagen particle regions than in other surface regions that do not contain collagen particles. This structure of the sheet material allows for immediate bioavailability of the collagen particles and therefore particularly rapid development of the hemostatic effect of the covering film when applied to a wound. This is also advantageous for possible intraperitoneal use of the sheet material, for example, for adhesion prevention. According to a further embodiment of the sheet material, the collagen particles are all arranged on the surface of the nonwoven fabric.

[0011] The collagen particles may in particular be made from native collagen of type I and / or type III, in particular bovine, porcine or murine collagen, which is commercially available in sufficient quantities and with high purity.

[0012] According to the present invention, the polymer filaments may be absorbable polymers, in particular polymers (copolymers, especially terpolymers) composed of at least two different monomers, such as lactide, glycolide, trimethylene carbonate, ε-caprolactone, and / or 1,4-dioxane-2-one monomers, or polyhydroxybutyrate (PHB), or mixtures of these polymers, which allow the sheets to exert their anti-infective and pain-relieving effects while retaining their full hydrolytic and enzymatic degradability in vivo, just like the sheets described above.

[0013] According to a preferred embodiment of the present invention, the sheet comprises a polymer filament-containing nonwoven fabric composed of 20% to 99.5% by weight of copolymer and / or polyhydroxybutyrate and 0.4% to 80% by weight of collagen particles with a particle size of >80 μm, preferably 0.5% to 25% by weight of collagen particles, and very particularly preferably 0.5% to 2% by weight of collagen particles. Such sheets have a wide range of clinical applications, with good hemostatic properties.

[0014] According to the invention, the polymer filaments of the nonwoven fabric may comprise a terpolymer consisting of 65-87% by weight of lactide, 5-20% by weight of trimethylene carbonate, and 5-20% by weight of ε-caprolactone, in which the lactide, trimethylene carbonate, and ε-caprolactone monomers may be present in a ratio of 87 / 8 / 5 to 70 / 20 / 10% by weight.

[0015] The sheet-shaped material preferably has a (nominal) thickness d of 50 to 3,000 μm, preferably 80 to 500 μm or 800 to 2,500 μm. By reducing the (nominal) thickness of the sheet-shaped material, even wound surfaces with very complex shapes can be covered. This limits the water-binding capacity of the nonwoven fabric, but this can be compensated for, if necessary, by appropriately increasing the weight percentage of collagen particles. On the other hand, increasing the nominal thickness of the nonwoven fabric allows for particularly high water-binding capacity, allowing the sheet-shaped material to be used on wounds with heavy bleeding or high moisture content.

[0016] Depending on the intended field of use of the sheet material, nonwoven fabrics can be produced in various ways. For example, the nonwoven fabric can be meltblown, i.e., the polymer filaments of the nonwoven fabric are produced by the so-called meltblown method. This allows for a filament thickness of less than 15 μm. The polymer filaments according to the present invention can also be produced by the known electrospinning or centrifugal spinning method. In the latter two cases, nanopolymer filaments with a filament thickness of a few nanometers can be produced. Other known nonwoven fabric-forming processes can also be used to produce microfiber or nanofiber nonwoven fabrics, such as short-fiber nonwoven fabrics.

[0017] In the production of sheet-like materials, collagen particles are preferably added to the nonwoven fabric after the nonwoven fabric has been produced, since collagen particles cannot withstand the mechanical loads that occur during the production of polymer filaments. According to the present invention, this can be achieved by sprinkling (preferably dried) collagen particles onto the nonwoven fabric, followed by pressing or calendering the nonwoven fabric on which the collagen particles have been sprinkled. Alternatively, this can be achieved by wet coating, followed by drying the nonwoven fabric covered with collagen particles. In calendering, the collagen particles applied to the nonwoven fabric are pressed together with the nonwoven fabric under heat. In this way, the collagen particles can be fixed particularly reliably and easily on the nonwoven fabric.

[0018] In each wet coating method, collagen particles are suspended in an aqueous solution. In this case, the suspension of fibrous collagen particles must be carried out very carefully so as not to further damage the collagen particles directly mechanically or by shear forces, especially to avoid further crushing. It is important to maintain the integrity and desired function of the collagen. Therefore, care must be taken to suspend the collagen particles in a manner that maintains their size and structure. According to the present invention, this can be achieved, in particular, by dispersing or suspending the collagen particles in a solvent, especially an aqueous solution, with stirring for a maximum of 2 minutes, preferably a maximum of 1 minute. Furthermore, the aqueous solution according to the present invention can be used in a sugar-rich state, or even an n-hexane solution, which will protect the collagen.

[0019] Further advantages of the present invention will become apparent from the detailed description and drawings in which the exemplary embodiments shown are not to be understood as a definitive enumeration, but are of an exemplary nature for the purpose of explaining the invention. [Brief explanation of the drawings]

[0020] [Figure 1] 1 is a schematic side view of a wound treatment sheet according to the present invention, comprising a nonwoven fabric made of absorbent polymer filaments and collagen particles having a particle size I of >80 μm. [Figure 2] 1 is a detailed cross-sectional view (at 250x magnification) of a sheet material having a nonwoven fabric and collagen particles, taken under a microscope. [Figure 3] 3 is a detailed cross-sectional view (magnification 500x) of the sheet material of FIG. 2, taken under a microscope. [Figure 4] FIG. 10 is an enlarged detailed cross-sectional view under a microscope of a planar material in which collagen particles are sprinkled onto a nonwoven fabric and then the nonwoven fabric is subjected to a calendaring process.

[0021] FIG. 1 shows a schematic cross-sectional view of a wound treatment sheet 10. The sheet 10 includes a nonwoven fabric 12 made of absorbent polymer filaments 14. The nonwoven fabric 12 has a nominal thickness d, which can be 50 to 3,000 μm, preferably 80 to 500 μm, or 1,000 to 2,500 μm, depending on the mechanical requirements of the sheet 10. Depending on the desired diameter of the polymer filaments 14 (not shown in the drawings), the nonwoven fabric 12 can be produced by the so-called meltblowing method, electrospinning, centrifugal spinning, or other known nonwoven fabric forming processes for producing microfibers or nanofibers.

[0022] The absorbable polymer filaments 14 are made of an absorbable polymer composed of at least two monomers, in particular copolymers or terpolymers based on lactide, trimethylene carbonate, ε-caprolactone, and / or 1,4-dioxane-2-one monomers, polyhydroxybutyrate (PHB), or mixtures of these polymers, and are therefore biocompatible, degradable in vivo by hydrolysis or endogenous enzymes, and completely absorbable.

[0023] The sheet-like material further comprises collagen particles 16 having a particle size I of more than 80 μm. The collagen particles 16 are arranged on or within the nonwoven fabric 12 and are responsible for improving hemostasis or for more rapid absorption of blood and wound fluids. The collagen particles 16 are all made of pulverized native collagen, such as type I and / or type III collagen, and may be of bovine, murine, or porcine origin. The collagen particles 16 may have a particle size I of 80 μm to 500 μm, preferably 100 μm to 500 μm, and particularly preferably 100 μm to 250 μm.

[0024] The inherent high porosity of the nonwoven ensures particularly high and rapid bioavailability of collagen, allowing its functional benefits during wound treatment to be fully utilized at an early stage. These include, in particular, the known hemostatic properties of fibrous collagen, its swelling properties with significant absorption of blood and wound exudate, and its beneficial effects on rapid vascularization and wound healing of the wound surface. The fibrous collagen particles 16 of the sheet material rapidly draw moisture from bleeding wounds, thereby promoting hemostasis. The combination of collagen particles 16 with a synthetic absorbable polymer nonwoven fabric 12 (e.g., poly-lactide-caprolactone-trimethylene carbonate) combines the favorable properties of both materials. The absorbable polymer filaments 14 of the sheet material 10 directly contact the wound (e.g., burn) and can improve wound healing by enzymatically releasing lactic acid, exerting analgesic and anti-infective effects. It has been shown that even a small weight percentage of collagen particles 16 is beneficial for the aforementioned effects. In this respect, the sheet material 10 can contain 0.4 to 80% by weight of collagen particles 16, preferably 0.5 to 25% by weight, very particularly preferably 0.4 to 2% by weight of collagen particles 16.

[0025] Compared to an absorbent nonwoven fabric 12 of the same structure that does not contain collagen particles 16, the collagen-containing nonwoven fabric 12 is highly hydrophilic and therefore less prone to adhesion to itself, making the sheet material 10 easier to handle in clinical settings.

[0026] The collagen particles 16 can be added to the nonwoven fabric 12 in a variety of ways. For example, by scattering collagen particles 16 and calendering under pressure and heat; or by spraying, sprinkling, or rolling a solution containing finely dispersed collagen particles16, followed by drying; or By immersing the nonwoven fabric 12 in a collagen suspension and then drying it. The addition of collagen particles 16 to the nonwoven fabric can be performed.

[0027] In producing the sheet material 10, advantageously dried native bovine, porcine or even murine collagen is milled to obtain collagen particles 16 with a particle size greater than 80 μm, preferably greater than 100 μm.

[0028] In a further step, a nonwoven fabric made of polymer filaments is produced by meltblowing, electrospinning or centrifugal spinning of a statistical terpolymer of D,L-lactide-trimethylene carbonate-caprolactone.

[0029] Example 1 - Dry coating of nonwoven fabric According to the first embodiment, collagen particles are sprinkled onto the nonwoven fabric 12 and then pressed together with the nonwoven fabric 12 at 40° C. and 10 bar for 40 seconds. As shown in Figures 2 and 3, a sheet-like material 10 is obtained having collagen particles 16 on the surface of the nonwoven fabric 12, the particle size or particle diameter I of which is >80 μm.

[0030] Example 2 - Wet coating of nonwoven fabric According to a further embodiment, an aqueous suspension of collagen particles 16 having a particle size of >80 μm is provided. Care must be taken to ensure that the collagen particles 16 maintain their size and functionality. During suspension of the collagen particles 16, very gentle stirring, particularly for a limited time, is recommended to avoid further crushing or destruction of the collagen particles 16 directly or by shear. For this purpose, for example, a dispersing device from the Ultra Turrax® series manufactured by IKA® Werke GmbH & CO. KG (Germany) can be used.

[0031] The nonwoven fabric 12 is then immersed in the aqueous collagen suspension, or the aqueous collagen suspension is sprayed, rolled, or brushed onto the nonwoven fabric 12 .

[0032] Finally, the nonwoven fabric 12 with the added collagen particles 16 is dried, preferably in a vacuum at room temperature, to obtain the sheet material 10 of absorbent nonwoven fabric 12 with collagen particles >80 μm, as shown in FIG.

Claims

1. A wound treatment sheet material (10) for use in hemostasis, comprising a nonwoven fabric (12) made of absorbable polymer filaments (14) and collagen particles (16) having a particle size I of >80 μm arranged on and / or within the nonwoven fabric, wherein the polymer filaments (14) Polymers based on lactide, trimethylene carbonate, glycolide, ε-caprolactone and / or 1,4-dioxane-2-one monomers, or polyhydroxybutyrate (PHB) or a mixture of the polymers Including, The sheet-like material (10) is characterized in that the polymer filaments (14) contain a terpolymer composed of 65 to 87% by weight of lactide, 5 to 20% by weight of trimethylene carbonate, and 5 to 20% by weight of ε-caprolactone.

2. 2. The sheet material (10) of claim 1, wherein the collagen particles (16) have an average particle size I in the range of 80 μm to 500 μm.

3. 3. The sheet material (10) according to claim 1 or 2, wherein the sheet material (10) comprises 0.4 to 80% by weight of collagen particles (16).

4. 4. The sheet material (10) according to claim 1, wherein the collagen particles (16) are arranged on the surface side of the nonwoven fabric (12).

5. 5. The sheet material (10) according to claim 1, wherein the collagen particles (16) are made from native collagen of type I and / or type III.

6. The sheet material (10) of any one of claims 1 to 5, wherein the lactide monomers, the trimethylene carbonate monomers, and the ε-caprolactone monomers are present in the terpolymer in a range of 87 / 8 / 5 to 70 / 20 / 10 wt %.

7. The sheet material (10) according to any one of claims 1 to 6, wherein the sheet material (10) has a nominal thickness d of 50 μm to 3,000 μm.

8. A method for producing a sheet material (10) according to any one of claims 1 to 7, comprising: The collagen particles (16) are sprinkled onto the nonwoven fabric (12), and the nonwoven fabric (12) with the collagen particles is then subjected to a calendering process, or Alternatively, the collagen particles (16) are suspended in a solution, the collagen suspension thus obtained is then applied to the nonwoven fabric (12), and finally the nonwoven fabric (12) with the collagen particles is dried. method.

9. In a second alternative embodiment, the method of claim 8, wherein a sugar is added to the solution or an n-hexane solution is used to stabilize the collagen particles.

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