POLYMER FILM AND POLYMERIC BAG FOR HOLDING A MEDICAL-TECHNICAL PRODUCT TO BE IMPLANTED

Abstract

The polymer film serves for the embedding of a medical technology product to be implanted in a human organism. The polymer film includes a polymer of natural origin being biodegradable and absorbable by the human body. The polymer film has a polymer content. The polymer film further includes two antimicrobial active ingredients having a different mechanism of action and the polymer film has a total active-ingredient content. The ratio of the total active-ingredient content to the polymer content is at least 15%. The polymer content is greater than the total active-ingredient content. The polymer film is bendable and modulable and uninterrupted. The polymer forms a polymer matrix in which the antimicrobial active ingredients are embedded in a homogeneously distributed manner. The polymer film has, for each of the antimicrobial active ingredients, an individual active-ingredient content deviating from one another by at most 20%.

Claims

1. A polymer film for the embedding of a medical technology product to be implanted in a human organism, wherein a) the polymer film comprises, as main constituent, a polymer of natural origin that is biodegradable and is absorbable by the human body and the polymer film has a polymer content, b) the polymer film comprises, as further constituents, at least two antimicrobial active ingredients having a different mechanism of action in each case and the polymer film has a total active-ingredient content, c) wherein the ratio of the total active-ingredient content to the polymer content is at least 15%, but the polymer content is greater than the total active-ingredient content, d) the polymer film is bendable and modulable, so that the polymer film can be applied closely on the medical technology product, wherein the polymer film at least mostly matches itself to the contours of the medical technology product, e) the polymer film is uninterrupted, f) the polymer forms a polymer matrix in which the at least two antimicrobial active ingredients are embedded in a homogeneously distributed manner, and g) the polymer film has, for each of the at least two antimicrobial active ingredients, an individual active-ingredient content in each case, the individual active-ingredient contents deviating from one another by at most 20%.

2. The polymer film according to claim 1, wherein the polymer film adheres to itself.

3. The polymer film according to claim 1, wherein the polymer film is heat-sealable with itself.

4. The polymer film according to claim 1, wherein the polymer film adheres to a metallic surface.

5. The polymer film according to claim 1, wherein the polymer film is a physically tight barrier layer which prevents bacteria from passing through.

6. The polymer film according to claim 1, wherein the polymer film is transparent.

7. The polymer film according to claim 1, wherein the individual active-ingredient contents of the at least two antimicrobial active ingredients are at least about the same size.

8. The polymer film according to claim 1, wherein a first antimicrobial active ingredient inhibits at least one of the bacterial biosynthesis of proteins and the synthesis of nucleic acids and a second antimicrobial active ingredient inhibits the bacterial synthesis of the cell wall.

9. The polymer film according to claim 1, wherein gentamicin is a first antimicrobial active ingredient and vancomycin is a second antimicrobial active ingredient of the at least two antimicrobial active ingredients, and the polymer film has a gentamicin content and a vancomycin content.

10. The polymer film according to claim 9, wherein the ratio of the gentamicin content to the polymer content and the ratio of the vancomycin content to the polymer content is at most 32% in both cases.

11. The polymer film according to claim 9, wherein the ratio of the gentamicin content to the polymer content and the ratio of the vancomycin content to the polymer content is about 18% in both cases.

12. The polymer film according to claim 1, wherein the polymer of natural origin that is biodegradable and is absorbable by the human body is a polymer from the group of proteins, polypeptides and polysaccharides.

13. The polymer film according to claim 1, wherein the polymer of natural origin that is biodegradable and is absorbable by the human body is a collagen.

14. The polymer film according to claim 13, wherein the polymer film has a collagen basis weight from the range between 2.5 mg/cm.sup.2 and 8.0 mg/cm.sup.2.

15. The polymer film according to claim 1, wherein the polymer film is bendable by at least 120°.

16. The polymer pouch for receiving a medical technology product to be implanted in a human organism, produced from at least one polymer film for the embedding of a medical technology product to be implanted in a human organism, wherein a) the polymer film comprises, as main constituent, a polymer of natural origin that is biodegradable and is absorbable by the human body and the polymer film has a polymer content b) the polymer film comprises, as further constituents, at least two antimicrobial active ingredients having a different mechanism of action in each case and the polymer film has a total active-ingredient content, c) wherein the ratio of the total active-ingredient content to the polymer content is at least 15%, but the polymer content is greater than the total active-ingredient content, d) the polymer film is bendable and modulable, so that the polymer film can be applied closely on the medical technology product, wherein the polymer film at least mostly matches itself to the contours of the medical technology product, e) the polymer film is uninterrupted, f) the polymer forms a polymer matrix in which the at least two antimicrobial active ingredients are embedded in a homogeneously distributed manner, and g) the polymer film has, for each of the at least two antimicrobial active ingredients, an individual active-ingredient content in each case, the individual active-ingredient contents deviating from one another by at most 20%, with one of two polymer films arranged on top of one another being regionally connected to one another on the edge side and two polymer-film sections arranged on top of one another being regionally connected to one another on the edge side.

17. The polymer pouch according to claim 16, wherein there is an introduction opening, in the region of which one of two opposing polymer films and two opposing polymer-film end sections of a single polymer film end in a non-flush manner, with the result that, in the region of the introduction opening, one of one polymer film projects beyond the other polymer film and one polymer-film end section projects beyond the other polymer-film end section.

18. The polymer film according to claim 1, wherein the polymer of natural origin that is biodegradable and is absorbable by the human body is an atelocollagen.

19. The polymer film according to claim 1, wherein the polymer of natural origin that is biodegradable and is absorbable by the human body is an atelocollagen of equine origin.

20. The polymer film according to claim 1, wherein the polymer of natural origin that is biodegradable and is absorbable by the human body is a type 1 atelocollagen of equine origin.

21. The polymer film according to claim 13, wherein the polymer film has a collage basis weight from the range between 5.0 mg/cm.sup.2 and 6.2 mg/cm.sup.2

22. The polymer film according to claim 13, wherein the polymer film has a collage basis weight of at least about 5.6 mg/cm.sup.2.

23. The polymer film according to claim 1, wherein the polymer film is bendable by up to 180°.

Description

EXAMPLE 1 PRODUCTION OF A COLLAGEN FILM (AS EXAMPLE OF A POLYMER FILM) CONTAINING THE TWO ANTIMICROBIAL ACTIVE INGREDIENTS GENTAMICIN AND VANCOMYCIN

[0046] 543 g of a collagen cake having a dry content of type 1 atelocollagen of equine origin of 141 g are added to 9000 ml of purified water heated to 40° C. that has been acidified beforehand with dilute acetic acid, and are transformed into a homogeneous suspension by means of a homogenizer The result is a pH of 3.5 to 4.2.

[0047] 32 g of gentamicin sulfate are dissolved in 500 ml of acidified water and 21 g of vancomycin hydrochloride are dissolved in 500 ml of acidified water.

[0048] The gentamicin solution and the vancomycin solution are stirred into the collagen suspension such that a homogeneous mixture of all three components is formed.

[0049] Said homogeneous mixture is filled into flat blister moulds having a fill level of approx. 5 mm.

[0050] The blister moulds are transferred to a climatic cabinet, where the homogeneous mixture is dried for 48 hours with dried, sterile air and a drying regime with temperature levels of 35° C. to 22° C. and a humidity of 10-50% r. h.

[0051] Thereafter, the collagen films, having a collagen basis weight of about 5.6 mg/cm.sup.2 and also a gentamicin basis weight and a vancomycin basis weight of about 1 mg/cm.sup.2 in both cases, are removed from the blister moulds. Said collagen films are transparent, capable of adhesion (both to itself and to metallic surfaces) and bendable, in particular flexible or supple and modulable. The active ingredients gentamicin and vancomycin are distributed homogeneously in the collagen film.

EXAMPLE 2 PRODUCTION OF A COLLAGEN POUCH (AS EXAMPLE OF A POLYMER POUCH)

[0052] Two collagen films at a time, produced as per Example 1, are conditioned in a climatic cabinet at 80% r. h., arranged in an overlapping manner, and pressed on three sides to form a collagen pouch by means of a sealing machine. This involves a pressing pressure of 8 bar and a temperature of 100° C. The pressing process lasts half a minute. During the pressing process, what occurs is a heat-sealing of the three edge regions subjected to the pressing pressure. The pressed regions are linear. There, the result are connection zones, in which there is a mechanically firm and tight connection between the two collagen films. The linear connection zones can also be referred to as sealing seams. On one side edge, there is no sealing seam present, but an introduction opening. There, the two collagen films only rest on top of one another and are, in particular, separable from one another, for example in order to insert into the collagen pouch a device to be implanted.

[0053] The pressed collagen pouch is lastly trimmed to 9×9 cm in dimension. Advantageously, only one pouch size is necessary because of the good bendability. Any empty collagen-pouch edge regions laterally projecting beyond the device to be implanted that has been inserted into the collage pouch can be readily turned over. The size of the collage pouch can thus be adapted to the conditions of the particular application without any problems.

EXAMPLE 3 TESTING OF SEALING-SEAM STRESSABILITY

[0054] A pacemaker dummy weighing 24 g is introduced into the collagen pouch as per Example 2. The stability of the collagen pouch and of the sealing seam is tested by strong swinging and shaking of the filled collagen pouch. Both the two collagen films of the collagen pouch and the sealing seam regionally connecting the two collagen films hold out. Neither the collagen films nor the sealing seam split open.

[0055] Moreover, the collagen pouch as per Example 2 is filled with 30 ml of water and thereby to about ¾. There is no water loss within 30 min.

EXAMPLE 4 TESTING OF FILM FLEXIBILITY—BENDING TEST

[0056] Collagen films as per Example 1 are cut into strips having a width of 1.5 cm. One such strip at a time is clamped into two opposing pairs of clamping jaws of a tensile testing machine (Zwick 2.5), with the result that the strip clamped at its two longitudinal ends is arranged between the two pairs of clamping jaws. The initial distance between the pairs of clamping jaws is 10 mm In this state, the strip running from one pair of clamping jaws to the other pair of clamping jaws is unbent.

[0057] For the test, the first pair of clamping jaws is moved to the second pair of clamping jaws at a speed of 300 mm/min until there is only a distance of 1 mm between them. After that, the first pair of clamping jaws is moved back to its initial position. This process is repeated 20 times. During the movement of the first pair of clamping jaws, the film strip clamped on both sides performs a repeated bending yielding movement in a sideward manner, wherein the closer the first pair of clamping jaws approaches the second pair of clamping jaws, the stronger the film strip bends.

[0058] During this bending test, none of the tested strips breaks. The collagen film is thus very supple. It can be highly bent without any damage. During the bending test, bends by up to about 170° were carried out.

[0059] By contrast, in the case of comparative films of a different composition, breakage of the tested strips occurred during the bending test.

EXAMPLE 5 TESTING OF ADHESION

[0060] Collagen films as per Example 1 are cut into strips having a width of 1.5 cm and a length of more than 5 cm. A sub-region of 2 cm in length serves in each case as adhesion surface to be tested, which is also marked.

[0061] For each test, two of the film strips at a time are placed on top of one another, briefly wetted in the marked sub-regions containing the adhesion surfaces which are to be tested and are placed on top of one another (because the moistening distinctly increases again the adhesion, which is anyway already good, and thus also makes said adhesion better measurable), and pulled apart after various holding times (3-22 min) by means of the tensile testing machine (Zwick 2.5) already used in the tests as per Example 4.

[0062] Although the adhesive force increases with longer holding duration, a holding time of 10 min is chosen for the further comparative tests, since, firstly, the measurement accuracy is then already sufficiently good and, secondly, in the case of a real implantation operation as well what is realistic is a holding or preparation time of at most 10 min until the introduction of the device to be implanted, for example a pacemaker, into the tissue pouch of the patient.

[0063] In the case of the strips obtained from the collagen films as per Example 1, the average measured adhesive force is 625 mN, and this is a very good value which is close to the comparable adhesive force of a pure collagen film without any antimicrobial active ingredient. In the case of comparative films of products from other manufacturers, which likewise serve for the embedding of pacemakers to be implanted, the average measured adhesive force is distinctly lower in contrast. A comparative film has a thus ascertained adhesive force of just 20 mN. In the case of another comparative film, there is even no adhesive force at all. The ascertained value is 0 mN.

EXAMPLE 6 TESTING OF ANTIBIOTIC ACTION

[0064] The microbiological activity of the collagen film as per Example 1 is tested in the presence of 3 Gram-positive and 3 Gram-negative pathogens. The pathogens used are Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia. Moreover, the microbial action against a Gentamicin-resistant pathogen (Staph. aureus,>16 mg/ml) is tested.

[0065] For the tests, 3 pieces at a time, each 3×3 cm, of the collagen film are incubated with 2.5×10.sup.6 CFU/inoculum at 37° C. for 24 hours in accordance with ASTM E 2180 in comparison with non-microbially loaded collagen films.

[0066] The collagen film as per Example 1 exhibits a reduction of more than 4 logarithmic levels against all the pathogens tested. In accordance with the relevant definitions, an antimicrobial test is considered to be passed when a pathogen reduction of at least 99.9% (i.e. at least 3 logarithmic levels) is achieved in comparison with the reference. This assessment criterion is met in the present case. The collagen film has thus passed the antimicrobial test.