WO2003099160A1

WO2003099160A1 - Medical implant

Info

Publication number: WO2003099160A1
Application number: PCT/EP2003/004681
Authority: WO
Inventors: Jörg PRIEWE
Original assignee: Ethicon Gmbh
Priority date: 2002-05-23
Filing date: 2003-05-05
Publication date: 2003-12-04
Also published as: DE10222872B4; DE10222872A1; AU2003232258A1

Abstract

A medical implant has a knobbed film (40), which is preferably arranged on a basic structure such as, e.g., a surgical mesh.

Description

Medical Implant

The invention relates to a medical implant, in particular an implant with a barrier function, in order, e.g., to prevent the uncontrolled growing in of bodily tissue or adhesions with bodily tissue.

An additional property frequently required of medical implants, in addition to their particular properties, such as elasticity, flexural strength etc., is that they are to fulfil a barrier function. By way of example, surgical meshes that can be used intraperitoneally are coated with a membrane as an anti-adhesive barrier in order that adhesions to the patient's internal structures do not result. However, such membranes are often too rigid or even brittle, so that either a hold on the implant is not guaranteed or its properties, such as, e.g., the elasticity or the flexibility, are adversely affected.

It is the object of the invention to provide an improved medical implant in which in particular a desired barrier function is not linked with the mentioned disadvantages. This object is achieved by a medical implant with the features of claim 1. Advantageous designs of the invention result from the dependent claims. Claims 20 to 22 relate to 5 processes for the preparation of such an implant and claim 23 to a use thereof.

The medical implant according to the invention has a knobbed film. By a knobbed film is meant an areal structure with 0 bulges (protrusions), the knobs. The knobs can be arranged in a more or less regular pattern, but also statistically (randomly) . They can cover the whole of the knobbed film or only part of it.

.5 In preferred versions of the invention the implant has furthermore a basic structure, e.g. a surgical mesh, a stent, a film strip, a perforated film, a polymer foam or a circularly knitted fabric; the knobbed film is preferably at least partly arranged on the outer face of the basic structure. The iO basic structure is preferably porous, the majority of the pores preferably having a size of at least 1.5 mm, e.g. ap- prox. 4 mm.

Compared with smooth films of the same material and same _5 thickness or with corresponding textured films (e.g. with a one-sided pattern) , knobbed films are elastic and can have homogenous or inhomogenous elongation properties depending on the arrangement of the knobs, comparable with an implant mesh. The overall-elastic properties or also the properties 30 of part regions can be defined by parameters such as height, wall thickness, shape and density of the knobs as well as the film thickness and the film material; this is of interest particularly in the case of the combination with an elastic basic structure (such as a surgical mesh) or in skin replace- ment. The knobbed film preferably has an elongation elasticity which is greater than or the same as the elongation elasticity of the basic structure.

The knobbed film can fulfil a barrier or separation function, which, depending on the embodiment, extends essentially to all types of tissue or tissue fluids (tight knobbed film) or is limited to certain organs or structures, so that certain bodily fluids, proteins, etc. can pass through the barrier created by the knobbed film. This can be achieved by holes in the knobbed film, which can be arranged, e.g., in the form of a pattern. The size of such holes is preferably matched to their function; e.g., visible, macroscopic, microscopic or submicroscopic holes are conceivable.

In a preferred version the knobbed film is designed to reduce adhesion and fusions with bodily tissue.

The effective surface of the knobbed film can be varied for different bodily structures. For example, the effective surface can be reduced for organs or organ structures such as, e.g., the intestines, compared to a smooth film, as here only the projecting regions of the knobs or parts thereof are available for possible adhesions to the organ; for smaller structures, such as e.g. cells, whose adhesion can be desired, on the other hand the entire surface of the knobbed film, and thus a surface that is even enlarged compared with a smooth film, is available.

In addition the knobs of the knobbed film can be designed, depending on the version, for an increased or reduced friction of the implant in the body, which can be used for fixing or to increase mobility. Furthermore the knobs can assume additional functions due to their shape, such as, e.g., the ef- fecting of an increased blood supply into certain regions or an increased collagen deposition.

A further advantage of the implant according to the invention is that the correct-sided insertion of the implant or the knobbed film is made easier because the doctor can use the knobs as a visible and tactile aid to orientation. For example, the knobs are orientated to the intestine and the associated recesses to the abdominal wall. In particular, the tactility can also be of help in the case of a premature removal of the implant when determining its position.

The knobs of the knobbed film preferably have a base region, which is, for example, round, triangular, quadrangular, pen- tagonal, hexagonal, symmetrical, asymmetrical, circular, elliptic, oval, square, rectangular, trapezoidal or rhombic, and a top region, which is, e.g., areal, pointed, round, concave or convex in design. The base region and the top region can pass into each other without major changes in cross- section, but other designs, e.g. mushroom-shaped knobs, are likewise conceivable.

The knobs of the knobbed film preferably have a width of less than 10 mm and a height of less than 10 mm. The knobs or also the associated recesses on the back of the knobbed film can, however, also be designed such that they have a height or width in the micrometer range, so that a directed cell growth can be achieved, which is of great interest particularly in the field of tissue engineering.

The knobbed film can be connected to a basic structure by its knobs and/or by regions between the knobs, e.g. by welding, stitching, gluing, by securing under pressure or also by simply laying it on. The possibility of a simple mechanical fix- ing to a porous basic structure is of particular advantage if a customary prior fixing, e.g. by thermal welding, gluing, stitching or tacking, to the basic structure is problematical, e.g. if the operating doctor wishes to cut the knobbed

5 film and the porous basic structure of the implant to size separately in order to match them to the respective anatomical requirements. In this case, the knobbed film and the porous basic structure, e.g. a hernia mesh, can be easily connected to an implant by laying or pressing together, such

.0 that a lateral displacement or a detachment of the knobbed film from the basic structure is made more difficult.

In an advantageous version of the invention the knobbed film is designed as a carrier of cells, active agents and/or con-

L5 trast mediums. To this end, the knobbed film can, e.g., be loaded in the recesses created by the knobs with active agents, cells or contrast mediums. This can occur, for example, by simple pouring in of, for example, antibiotics solution into the recesses. The recesses, as vessels, can also be

10 sealed with different known resorbable polymers. Through selection of the materials and thickness of the seals a defined release in terms of location and time can be achieved. Various active agents can be present as a mixture in such chambers or physically separated in different chambers. 5

The knobbed film can also be multilayered, e.g. in the form of two knobbed film layers lying on top of each other with knobs pointing away from each other (the knobs can be aligned with respect to each other, but do not have to be) , in the 0 form of two knobbed film layers lying on top of each other with knobs pointing in the same direction and lying in one another, or in the form of a knobbed film layer with a smooth film layer lying against it, which is preferably connected to the knobbed film layer such that it closes the knobs. In this way chambers can be formed which, e.g., can be filled with active agents (see above) and release the active agents if at least one of the film layers involved is provided with holes or the film layers are not tightly connected to each other.

All these arrangements of knobbed films can be connected on one side to a suitable basic structure (preferably a porous basic structure) . In further versions of the invention the implant has more than one knobbed film, e.g. separate knobbed film pieces on one side of the implant; also advantageous are designs in which an areal basic structure (e.g. a surgical mesh) is arranged between two knobbed films (sandwich structure) . As a borderline case, for example, several knobbed film pieces each with only one knob or with four knobs can be connected to a mesh-like basic structure.

The possible advantages of the implant according to the invention are particularly clear in view of an embodiment in which a basic structure in the form of a flexible hernia mesh is connected to a knobbed film: The surface for the adsorption of cells is increased while the surface for adsorbing organs such as the intestine is reduced (smaller tendency towards adhesions) ; in addition, the extensibility of the knobbed film is greater than that of a comparable smooth film.

Knobbed films are also characterized, because of their structure, by an improved subsequent deformability. As a rule they can be deformed three-dimensionally (thermally and/or me- chanically) , without wrinkling.

Resorbable materials and non-resorbable materials are suitable for a knobbed film, e.g. natural polymers, synthetic and biocompatible polymers, resorbable polymers, hydrophobic polymers and biocompatible metals, but composites made of resorbable and non-resorbable substances are also conceivable. Examples of suitable substances for the implant according to the invention will be found in the claims; in principle such substances can be used both for a knobbed film and for any basic structure.

There are numerous processes for the production of knobbed films. The knobbed film is preferably prepared from a film with a starting thickness of less than 75 μm. For example, heated perforated rollers can be operated at a below- atmospheric pressure, so that a film running over them is deformed in the regions of the holes. Furthermore films can be deformed between a positive roller (knobs) and a negative roller (recesses) . Suitable thick films can also be milled. Films can also be pressed with pressurized air or liquid pressure onto a mould with recesses or be poured out of a solution or melt into a suitable structured mould.

If a knobbed film is connected to a basic structure, this can take place before or after the development of the knobs. A continuous process is also conceivable in which a knobbed film is prepared and glued or welded to a surgical mesh.

The invention is explained in the following using embodiments. The drawings show in

Figure 1 a cross-section through a knobbed film with cylindrical, rounded knobs,

Figure 2 a cross-section through a knobbed film with thickened knobs,

Figure 3 a cross-section through a two-layered knobbed film, Figure 4 a perspective view of a knobbed film with ellipsoid-like knob,

Figure 5 a top view of a knobbed film with cylindrical knobs which are arranged offset in rows,

Figure 6 a top view of a knobbed film with knobs which have a hexagonal base region, and

Figure 7 a top view of a knobbed film in which, in the central region, knobs with a rhombic base region and a drop-shaped ellipsoid-like top region are arranged.

Figures 1 to 7 illustrate different versions of a knobbed film which can be used individually or in conjunction with a basic structure not represented in the Figures (e.g. a flexible surgical mesh) as a medical implant.

There is shown in Figure 1 a cross-section (enlarged section) through a knobbed film^' 10 with knobs 12 which extend from the film plane 14. The knobs 10 have a cylindrical base region 16 and a rounded top region 18.

Figure 2 shows a cross-section through a knobbed film 20 with knobs 22 which have a cylindrical base region 26 and a thickened top region 28. The knobs 22 thus have a mushroom-like shape.

The version of a knobbed film 30 shown in Figure 3 in cross- section has two layers and consists of a knobbed film layer 30' with knobs 32' and a knobbed film layer 30" with knobs 32". The respective knobs 32' and 32" are aligned with respect to each other and point away from each other. The two knobbed film layers 30' and 30" are welded to each other in the regions 34 between the respective knobs 32' and 32". In this way chambers 35 form, which can be used, e.g., for acco- modating contrast mediums or active agents. If, e.g., one of the knobbed film layers 32' or 32" or both knobbed film layers 32' and 32" are provided with holes, active agents can be released from the chambers 35 into the surrounding regions.

Figure 4 is a perspective view of a knobbed film 40 with el- lipsoid-like knobs 42, which are represented in the front region of Figure 4 in cross-section.

Figure 5 shows a top view of a knobbed film 50 with cylindrical knobs 52. The knobs 52 are arranged offset in rows, larger regions 54 being provided between the knobs 52.

Figure 6 is a top view of a knobbed films 60 with knobs 62 which each have a hexagonal base region 66. Due to the regular shape of the base regions 66 the knobs 62 can be arranged relatively densely.

In Figure 7 a top view is shown of a knobbed film 70 in which in the central area knobs 72 with a rhombic base region 76 and a drop-shaped ellipsoid-like top region 78 are densely arranged. In this embodiment the peripheral areas 79 of the knobbed film 70 do not contain knobs.

Some examples of the preparation of knobbed films and of medical implants which contain a knobbed film and a basic structure are explained in the following. Moreover, further details for the design of the respective knobbed film can be seen. Example 1

An approx. 200 μm thick film made of poly-p-dioxanone, such 5 as is used in the Ethicon GmbH product "Orbitermembran" , was fixed on a metal grid with rhombic meshes at the edges with adhesive tape and heated between two heating plates so that it was slightly softened. The grid was then pressed with the film side onto a suction bottle which was operated by co - L0 pressed air. A knobbed film formed, the knobs of which had a rhombic base region (approx. 3 mm by 5 mm) and a drop-shaped ellipsoid-like top region (see Figure 7) .

The rhombuses were arranged in the manner of a mesh. The L5 knobbed film was clearly more elastic than the original film and had a direction-dependent elasticity.

Example 2

20

An approx. 50 μm thick knobbed film made of poly-p-dioxanone, which is also used as film in the Ethicon GmbH product "Dura- patch", was prepared using a steel/aluminium deep-drawing mould. The deep-drawing mould with an area of 10 cm by 10 cm 25 contained a rectangular field of approx. 3.5 cm by 7.5 cm with hemispherical bores (radius 1.5 mm), which were spaced 5 mm apart from each other. The bores were offset in rows and each had in addition a ventilation channel with a radius of 0.4 mm.

30

The initially smooth poly-p-dioxanone film was placed in the two-part deep-drawing mould. Then the mould was closed, heated to approx. 70°C on a heating plate and then subjected for 2 minutes to slight nitrogen pressure. Knobs formed which were arranged similarly to Figure 5 and had a domed, but not exactly hemispherical form.

Example 3

Firstly a knobbed film was prepared as in Example 2.

A partly resorbable commercial surgical mesh serving as a basic structure (Vypro^®, Ethicon GmbH; composite mesh made of polypropylene and, as resorbable portion, Vicryl^®, a copoly- mer of glycolide and lactide in the ratio 9:1) was held for approx. 5-10 minutes with an (initially smooth) 50 μm thick film of poly-p-dixoanone in a heating press at 125°C between baking paper, mesh and film being held for a short while under pressure. The film was completely molten after this time, had hardly any still-intact film regions and was present as a coating over the individual meshes of the mesh.

In the meantime the knobbed film was precisely placed with the knobs into the hemispherical bores of the deep-drawing mould from Example 2 and fixed with adhesive tape. The still hot mesh was then placed with the polydioxanone-rich side onto the knobbed film, and the deep-drawing mould was held at 125 °C for 5 seconds in the heating press and then removed from the heating press. Film and mesh were immediately removed from the mould. The knobbed film was firmly pasted to the mesh and still had the knobs. Example 4

A knobbed film was prepared analogously to Example 2, with the difference that the mould was held for 15 minutes at 4 bar and 70 °C.

Domed or semicircular knobs with a diameter of 3 mm and a height of approx. 0.4 mm resulted. The knobs were identical as regards height, distance and shape. The knobbed film was clearly more elongation-elastic than the 50 μm-thick smooth original film.

Example 5

A knobbed film was prepared analogously to Example 2, with the difference that a 120-μm thick film made of poly-p- dioxanone was held for 4 hours at 4 bar and 103 °C, then was held for 20 minutes at 4 bar at room temperature and then was removed from the mould.

The knobbed film had a thickness - of 120 μm in the peripheral area and a thickness of approx. 700 μm in the knob region, which corresponds to a knob height of approx. 580 μm.

Example 6

An approx. 25 μm-thick film made of poly-p-dioxanone, such as is used in the Ethicon GmbH product "Durapatch", was held, analogously to Example 2 for 30 minutes at 70°C and 4 bar and then cooled under pressure to room temperature. The film had roundish knobs and was more elastic than the original film.

Claims

1. Medical implant which has a knobbed film (10; 20; 30; 40; 50; 60; 70) .

2. Implant according to claim 1, characterized by a basic structure which is preferably selected from the following group: surgical mesh, stent, film strip, perforated film, polymer foam, circularly knitted fabric.

3. Implant according to claim 2, characterized in that the basic structure is porous and in that preferably the majority of the pores has a size of at least 1.5 mm.

4. Implant according to claim 2 or 3, characterized in that the knobbed film (10; 20; 30; 40; 50; 60; 70) is arranged at least partly on the outer face of the basic structure.

5. Implant according to one of claims 2 to 4, characterized in that the knobbed film_, (10; 20; 30; 40; 50; 60; 70) is connected to the basic structure by its knobs (12; 22; 32', 32"; 42; 52; 62; 72) and/or by regions (54) between the knobs (52) .

6. Implant according to one of claims 2 to 5, characterized in that the knobbed film (10; 20; 30; 40; 50; 60; 70) is arranged at the basic structure in one of the following ways: welded, stitched, glued, secured by pressing, laid on.

7. Implant according to one of claims 2 to 6, characterized in that the knobbed film (10; 20; 30; 40; 50; 60; 70) has an elongation elasticity which is greater than or the same as the elongation elasticity of the basic structure.

8. Implant according to one of claims 1 to 7, characterized in that the knobbed film (10; 20; 30; 40; 50; 60; 70) is set up to reduce adhesion and fusions with bodily tissue.

9. Implant according to one of claims 1 to 8, characterized in that the knobs (12; 22; 32', 32"; 42; 52; 62; 72) of the knobbed film (10; 20; 30; 40; 50; 60; 70) are arranged on the knobbed film in at least one of the following ways: in the manner of a pattern, statistically, complete coverage of the knobbed film (10; 20; 30; 40; 60), partial coverage of the knobbed film (50; 70).

10. Implant according to one of claims 1 to 9, characterized in that knobs (12; 22; 32', 32"; 42; 52; 62; 72) of the knobbed film (10; 20; 30; 40; 50; 60; 70) have a base region (16; 26; 66; 76) which preferably has a shape selected from the ^' following group: round, triangular, quadrangular, pentagonal, hexagonal, symmetrical, asymmetrical, circular, elliptic, oval, square, rectangular, trapezoidal, rhombic, and a top region (18; 28; 78) which preferably has a shape selected from the following group: areal, pointed, round, concave, convex.

11. Implant according to one of claims 1 to 10, characterized in that the knobs (12; 22; 32', 32"; 42; 52; 62; 72) of the knobbed film (10; 20; 30; 40; 50; 60; 70) have a width of less than 10 mm and a height of less than 10 mm.

12. Implant according to one of claims 1 to 11, characterized in that the knobbed film (10; 20; 30; 40; 50; 60; 70) has holes.

13. Implant according to claim 12, characterized in that the holes are arranged in the form of a pattern.

14. Implant according to one of claims 1 to 13, characterized in that the knobbed film (10; 20; 30; 40; 50; 60; 70) is set up as a carrier of cells, active agents and/or contrast mediums.

15. Implant according to one of claims 1 to 14, characterized in that the knobbed film (30) is multilayered, the multilayered knobbed film (30) preferably having a form selected from the following group: two knobbed film layers lying on top of each other with knobs pointing away from each other, two knobbed film layers (30', 30") lying on top of each other with knobs (32', 32") aligned with respect to each other and pointing away from each other, two knobbed film layers lying on top of each other with knobs pointing in the same direction and lying in one another, one knobbed film layer with a smooth film layer resting against it, one knobbed film layer with a smooth film layer closing the knobs.

16. Implant according to one of claims 1 to 15, characterized in that the implant has more than one knobbed film (10; 20; 30; 40; 50; 60; 70), an areal basic structure preferably being arranged between two knobbed films.

17. Implant according to one of claims 1 to 16, characterized in that the knobbed film (10; 20; 30; 40; 50; 60; 70) contains at least one of the materials selected from the following group: natural polymers, synthetic and biocompatible polymers, resorbable polymers, hydrophobic polymers, biocompatible metals.

5 18. Implant according to one of claims 1 to 17, characterized in that the implant has at least one of the substances selected from the following group: polyalkenes, polypropylene, polyethylene, fluorinated polyolefins, polytetrafluoroethylene,- polyvinylidene fluoride, poly- ι0 amides, polyurethanes, polyisoprenes, polystyrenes, polysilicones, polycarbonates, polyaryletherketones, polymethacrylic acid esters, polyacrylic acid esters, aromatic polyesters, polyimides, polyhydroxy acids, polylactides, polyglycolides, polyhydroxybutyrates,

_5 polyhydroxyvaleriates, polycaprolactones, polydiox- anones, synthetic and natural oligo- and polyamino acids and their derivatives such as poly (γ-benzyl-L- glutamines), pseudopolyamino acids, proteins, collagens, polyphosphazenes, polyanhydrides, polyorthoesters, poly-

20 phosphates, polyphosphonates, polyalcohols, polysaccha- rides, dextrans, dextran,_ sulfates, chitosans, starches, hydroxyethyl starches, hydr xypropyl starches, oxygenated regenerated cellulose, hyaluronic acids, polyeth- ers, polyethylene glycols, poly (ethylene glycols-co-

25 propylene glycols) , polycyanoacrylates, polyvinylpyrro- lidones, mixtures of such substances, copolymers of such substances.

19. Implant according to one of claims 1 to 18, character- i0 ized in that the knobbed film is produced from a film with a starting thickness of less than 75 μm.

20. Process for the manufacture of a medical implant according to claim 2 or 3, characterized in that a knobbed film (50) is produced from a resorbable polymer film using a thermal deforming process and the knobbed film

5 (50) is fused with a surgical mesh by pressing it onto the heated surgical mesh.

21. Process for the manufacture of a medical implant according to claim 2 or 3, characterized in that a resorbable

L0 polymer film is glued or welded to a surgical mesh and subsequently knobs are pressed into the polymer film and/or drawn from the polymer film using a thermal deforming process.

L5 22. Process for the manufacture of a medical implant according to claim 2 or 3, characterized in that a knobbed film (10; 20; 30; 40; 50; 60; 70) is prepared and glued or welded to a surgical mesh in a continuous process.

.0 23. Use of an implantable knobbed film as a carrier of cells, active agents and/or contrast mediums.