SILICONE WITH MODIFIED SURFACE FOR IMPROVING THE SLIDING AND FRICTIONAL PROPERTIES

Abstract

A material comprising a silicone, wherein a polymer is arranged on the surface of the silicone, the polymer is characterized by a higher wear resistance than the silicone, and the polymer is attached to the surface of the silicone by non-covalent bonds.

Claims

1. A material comprising a silicone, wherein a polymer is arranged on the surface of the silicone, wherein the polymer includes a higher wear resistance than the silicone, and the polymer is attached to the surface of the silicone by non-covalent bonds, wherein the polymer is a methacrylic acid-methyl methacrylate copolymer which comprises a residue of a zwitterionic compound, wherein the zwitterionic compound is selected from the group comprising phosphorylcholine, sulfobetaine, carboxybetaine, sulfopyridium betaine, cysteine, phosphatidyl ethanolamine or a sulfobetaine siloxane.

2. The material according to claim 1, wherein in the polymer the methacrylic acid monomer is present in relation to the methyl methacrylate monomer in a molar ratio in the range of from 1:1 to 1:3.

3. The material according to claim 1, wherein the polymer is attached to the surface of the silicone by an entanglement of the chains of the silicone and the chains of the polymer.

4. The material according to claim 1, wherein the silicone is a methyl silicone, the methyl silicone comprising a polydimethylsiloxane, a vinyl-methyl silicone, a phenyl-vinyl-methyl silicone, a phenyl-modified silicone, a fluoroalkyl silicone, or a fluoro-vinyl-methyl silicone.

5. A medical implant comprising a material comprising a silicone, wherein a polymer is arranged on the surface of the silicone, wherein the polymer includes a higher wear resistance than the silicone, and the polymer is attached to the surface of the silicone by non-covalent bonds, wherein the polymer is a methacrylic acid-methyl methacrylate copolymer which comprises a residue of a zwitterionic compound, wherein the zwitterionic compound is selected from the group comprising phosphorylcholine, sulfobetaine, carboxybetaine, sulfopyridium betaine, cysteine, phosphatidyl ethanolamine or a sulfobetaine siloxane.

6. The medical implant according to claim 5, wherein the medical implant comprises an electrode lead.

7. The medical implant according to claim 6, wherein the electrode lead comprises an electrically insulating sheathing which comprises or consists substantially of the material.

8. The medical element according to claim 6, wherein the medical implant comprises a current-generating or current-emitting component and/or a current-detecting component which is connected to the electrode lead, wherein the medical implant is a cardiac pacemaker, a cardioverter-defibrillator or a neurostimulator.

9. The medical implant according to claim 6, wherein the implant comprises a fixing sleeve for fixing an implantable electrode lead, wherein the fixing sleeve comprises or consists substantially of the material.

10. A method for producing a material according to claim 1, comprising the steps: providing a silicone, and arranging a polymer on the surface of the silicone, wherein the polymer is characterised by a greater wear resistance than the silicone, and the polymer is attached to the surface of the silicone by non-covalent bonds, wherein the polymer is a methacrylic acid-methyl methacrylate copolymer which comprises a residue of a zwitterionic compound, wherein the zwitterionic compound is selected from the group comprising phosphorylcholine, sulfobetaine, carboxybetaine, sulfopyridium betaine, cysteine, phosphatidylethanolamine or a sulfobetaine siloxane.

11. The method according to claim 10, wherein the arranging of the polymer on the surface of the silicone comprises the following steps: dissolving the polymer in a suitable solvent yielding a polymer solution; applying the polymer solution to the silicone, preferably by spraying or immersion; and drying the silicone at a temperature in the range from room temperature to approximately 300° C., preferably at temperatures from 180° C. to 260° C., and more preferably at approximately 220° C.

12. The method according to claim 11, wherein the arranging of the polymer on the surface of the silicone comprises the following steps: swelling the silicone in an organic solvent yielding a swollen silicone; contacting the swollen silicone with the polymer, wherein the polymer is present dissolved in a suitable solvent, or contacting the swollen silicone with the precursors of the polymer, wherein the one or more precursors of the polymer are present dissolved in a suitable solvent, and reacting the one or more precursors to form the polymer; and drying the silicone, wherein the precursors of the polymer comprise methacrylic acid, methyl methacrylate and a polymerisable compound with the zwitterionic compound or residue thereof.

13. The method according to claim 12, wherein the organic solvent is toluene, chloroform, dichloromethane, dimethyl acetamide, dimethyl formamide, dimethyl sulfoxide, cresol, ortho-dichlorobenzene, sulfolane, tetrahydrofuran, trichlorethylene, N-methyl-2-pyrrolidone, or a methacrylate or methyl methacrylate solution.

14. The method according to claim 12, wherein the organic solvent comprises N-methyl-2-pyrrolidone in combination with n-heptane.

15. The method according to claim 10, wherein the arranging of the polymer on the surface of the silicone comprises the following steps: dissolving the polymer in a suitable solvent yielding a polymer solution; applying the polymer solution to the silicone, preferably by spraying or immersion; and drying the silicone at a temperature in the range from 180° C. to 260° C.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0081] Further features and embodiments of the present invention will be explained hereinafter with reference to the drawings, in which:

[0082] FIG. 1 shows suitable polymers for use in the material according to the present invention;

[0083] FIG. 2 schematically shows a possible method for producing the material according to the present invention;

[0084] FIG. 3 shows an embodiment of an implant according to the present invention comprising an electrode lead;

[0085] FIG. 4 shows a further embodiment of a medical implant according to the present invention comprising an electrode fixing sleeve; and

[0086] FIG. 5 shows the results of growth efforts from cell culture attempts on different materials.

DETAILED DESCRIPTION

Examples

[0087] The present invention in particular provides an insulation material which displays the known positive properties of silicone, but additionally no longer has the known disadvantages. Here, problems in particular with regard to abrasion and wearing through are reduced or avoided. Both the lead-to-lead abrasion phenomenon and inside-outside wear-through properties may thus be avoided or eliminated. On the whole, the produced materials according to the present invention have a high stability with respect to frictional influences.

[0088] By way of the subject matters according to the present invention, two production steps advantageously may be spared in the production of an electrode lead. The production of a correctly sized cover sleeve and the fitting of same are replaced by the method according to the present invention. Customary or established electrode lead designs advantageously may be improved by the method according to the present invention or adapted to market requirements. In particular, the known major problems of the implantable electrode leads, that is to say the fact that they abrade and wear through, are solved, without detriment to the handling properties.

[0089] To this end, silicone in particular is coated with suitable materials. The coating is long-lasting and is not abrasive. Apart from the sliding and frictional properties, the mechanical properties advantageously are not influenced by the coating. The surface of the silicone modified in this way makes it possible to use devices or apparatuses produced from this silicone as permanent implants.

[0090] In particular, the silicone surface may be modified such that an adhesion to tissue following implantation is reduced. An electrode lead produced from this material may also be removed from the body after a number of years, without difficulty. A further point is the antimicrobial coating. Synergies are present between the two impact directions. This means that a low, unspecific protein adsorption also constitutes an advantage in the case of infections associated with the implant.

[0091] Silicone rubber, referred to hereinafter simply as silicone, offers groups that are hardly reactive and which make possible a chemical modification. Silicone swells in some organic solvents, such as toluene or xylene. A monomer is able diffuse into this expanded matrix, which monomer is converted by radical polymerisation to form polymer chains. Following the removal of the swelling agent, these newly formed chains are then mechanically fixed in the matrix. On the other hand, suitable polymers are able to diffuse into the matrix after the swelling. Following the removal of the solvent, these polymers are then also fixed at, and on the surface.

Determination of the Swelling Behaviour of Silicone in Different Solvents

[0092] The silicone samples were weighed and kept for 24 h in the solvent to be tested. Following swelling, the sample slices were dabbed at the surface and weighed again.

[0093] The swelling factor was calculated in accordance with the following formula Q/100=(a−b)/b): Q is the swelling factor, and a is the weight after expansion, and b is the original weight. The results are shown in the following table.

TABLE-US-00001 TABLE 1 Swelling factors of silicone in different solvents DMF Toluene Xylene Water Methanol DMSO MMA 3 32 86 1 2 3 60
Test Polymerisation with MMA: [0094] i) The silicone slices were pre-swollen for 24 h at room temperature in toluene. They were then placed in the three differently concentrated polymerisation solutions. The solutions were degassed beforehand with N2. The polymer solutions consisted of 40 ml water with either a) 1 ml MMA; b) 2.5 ml MMA, or c) 5 ml MMA. The reaction was started with 2,2′-azobis(2-methylpropionamidine)dihydrochloride at 80° C. [0095] ii) Alternatively, the silicone samples were swollen in MMA, and then placed in the polymerisation solutions described under i). [0096] iii) Swelling in DMF as relatively poor swelling agent over 24 h. Polymerisation was then performed in 40 ml water with 5 ml MMA. The MMA should displace the DMF because the affinity of the MMA to silicone is much higher than to the solvent water. Thereafter according to approach i).

[0097] All samples were dried at 80° C. under vacuum.

Coating of the Outer Surface of an Electrode Lead Made of Silicone with PVDF or PSU.

[0098] The known biocompatible PVDF, which is stable against wearing through, may be applied by different methods.

[0099] On the one hand, a coating method with an annealing process may be used. To this end, PVDF was dissolved, sprayed or immersed in a suitable solvent. The annealing process at temperatures of 240° C. was no problem for the silicone matrix. A pre-treatment of the silicone with a primer or adhesion promoter is feasible, but not absolutely necessary. The cleaning of the silicone before the application of the PVDF is mandatory. The cleaning methods are known to a person skilled in the art.

[0100] A further suitable way of fixing PVDF on silicone rubber may be realized with the aid of solvents, which cause the silicone to swell. The silicone was swollen with cyclohexane or cycloheptane, generally a hydrocarbon. PVDF was added to this swollen matrix in a suitable solvent, which resulted in reverse swelling. PVDF was immobilized on the silicone surface in a bristle-like manner by entanglement or looping mechanisms. A pre-treatment of the silicone with a primer or adhesion promoter is possible, but is not absolutely necessary.

[0101] Apart from the preferred PVDF, polysulfone or polyether sulfone are also suitable as coating material. Here, the coating was performed from a solvent under usage of hydrocarbons in order to avail of the reversible swelling of silicone. Also utilized, as above, was the fact that the silicone matrix enlarges, and thus the coating polymers may become integrated in the matrix.

[0102] Due to the material combination, an “old” electrode design may also be used, which constitutes an attractive selling point due to the surface modification. In contrast to common sleeving methods, a simple immersion process is more cost-effective. Electrode leads having comparable surface properties thus may be produced more cost-effectively. The sliding properties as well as the frictional properties are improved in comparison to silicone. Coatings with PVDF, but also polysulfone or polyether sulfone, are also superior to TPU surfaces. This is thus the case in particular because all TPU materials are subjected to a hydrolytic breakdown.

[0103] Polysulfone (PSU) is used as separating membrane for dialysis membranes. The polymer also demonstrates only a low tendency to protein adsorption. It is also used as membrane material in biotechnology, in particular if protein-containing solutions are to be filtered, but should not remain on the filter.

[0104] In experiments, PSU was tested with great success in animal testing. Here, no protein adhesion or cell adhesion could be observed, even after 4 months.

##STR00001##

[0105] The following polymers from the class of polysulfones are particularly suitable for the surface-penetrating coating according to the solution according to the present invention: polysulfone (CAS no. 25135-51-7), polyether sulfone (CAS no. 25608-63-3), polyphenylene sulfone (CAS no. 25608-64-4) or polyphenylene ether sulfone, (PPSP, CAS no. 25608-63-3). The trade names of BASF are used in FIG. 1.

[0106] Potential solvents are: chloroform, dichloromethane, dimethylacetamide and N-methyl-2-pyrrolidone, wherein N-methyl-2-pyrrolidone is preferred. N-methyl-2-pyrrolidone may be combined well with solvents such as n-heptane in order to achieve the desired expansion of the silicone.

[0107] Further suitable solvents are toluene, dichloromethane, dimethyl acetamide, dimethyl formamide, dimethyl sulfoxide, cresol, ortho-dichlorobenzene, sulfolane, tetrahydrofuran, trichlorethylene.

Coating of a Silicone Electrode Lead with PSU or PPSP

[0108] The coating differs from conventional coatings in that there is no cohesion layer provided, and instead the coating material also penetrates the surface and reaches into the silicone.

[0109] The silicone material was made to swell using n-heptane. This was performed at room temperature for 1 min to 24 h. The extent of the swelling, and thus also the depth to which the polysulfone penetrates into the carrier material (silicone rubber) may be influenced over time. Only a swelling time of from 15 to 45 min was preferably used. The swollen material was then passed through a 5% polysulfone solution in N-methyl-2-pyrrolidone. In order to produce the polysulfone solution, the polysulfone was weighed in, and the solvent added. The solution is then stirred for 24 h at 80° C. The reaction time of the solution as the carrier material was 1 to 120 min. The silicone was preferably left in the polymer solution for 2 to 20 min. The solvent was removed by evaporation at room temperature over 3 to 4 days. Solvent residues were then removed fully by a vacuum treatment at 80° C. for 7 days.

[0110] The PSU coating was repeated with dimethylacetamide (DMAC) as solvent, wherein the silicone material was expanded for 2 days in a dimethylacetamide solution with 0.5 wt % PSU (CAS no. 25135-51-7) and was then dried at 85° C. for 1 day.

[0111] The PPSP (polyphenylene ether sulfone) coating was repeated with dimethyl acetamide (DMAC) as solvent, wherein the silicone material was expanded for 2 days in a dimethyl acetamide solution with 0.5 wt % PPSP (CAS no. 25608-63-3) and was then dried at 85° C. for 1 day.

Production of Silicone Rubber with MMA/MAA/PC Modification:

[0112] The following exemplary embodiment describes the surface modification of a silicone rubber matrix with methyl methacrylate (MMA)/methacrylic acid (MAA) and a zwitterionic molecule.

[0113] The silicone matrix was swollen using a solvent. As a result of the swelling, a volume was provided in which monomers could be converted to form prepolymers and polymers. The schema shown at the top of FIG. 2 shows the build-up of this interpretation network (IP network).

[0114] A series of compounds may be used as zwitterion. A number of zwitterions will be shown in the following schema.

##STR00002##

[0115] Phosphorylcholine (PC) is particularly preferred here.

[0116] In order to couple the PC to the MMA/MAA, the PC was used with a vinyl group, which was attached to the MMA/MAA prepolymer by radical polymerisation.

##STR00003##

[0117] For surface modification the synthesis schema shown at the bottom in FIG. 2 was applied [swelling silicone (arrow down), add monomer to swollen matrix (arrow down), wash surface with initiator and PC (arrow down) polymerisation].

Synthesis Procedure:

[0118] Substrates made of the silicone Nusil® Med 45xx were added to a solution of MMA/MAA (2:1). 100 ml MMA were mixed with 50 ml MAA and the substrates were stored for 24 h at room temperature and swollen. Following the introduction of the samples, the solution was gassed for 2 min with nitrogen so as to remove oxygen from the solution. For the further treatment, 10 mg/ml of 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AIBN) were dissolved in water, and 10 mg/ml of 2-methacryoxyethyl PC were added and also dissolved at room temperature. The solution was degassed for 5 min with nitrogen. The swollen silicone samples were added to this aqueous solution and washed for 1 to 3 min. The samples were removed and incubated for 24 h at 80° C.

[0119] For repetition of the above-mentioned synthesis, an expansion solution with 40 ml MMA (methyl methacrylate, CAS: 80-62-6, Sigma Aldrich) and 20 ml methacrylic acid (MAA, CAS:79-41-4, Sigma Aldrich) was produced. Silicone substrates made of Nusil MED4765 were cleaned and incubated for 3 days in the swelling solution. The silicone substrates were then removed from the expansion solution, wherein the expansion solution was then allowed to drain off. The incubated silicone substrate was then transferred into a rinsing solution, which contained 100 ml demineralised water (Millipore), 100 mg AIBN (radical starter) 2,2-azobis(2-methyl-propionamidine)dihydrochloride CAS: 2997-92-4 (Sigma Aldrich) and 1000 mg methacryloyloxyethyl phosphorylcholine (zwitterion) CAS:67881-98-5 (Sigma Aldrich), and was rinsed for 5 min with turning. The silicone substrates were then placed on a glass plate or the like and dried for 2 days at 85° C. in a furnace. The dried samples were then sterilized.

[0120] In this exemplary embodiment, one monomer is the swelling agent at the same time. Alternatively, the swelling agent may also be cyclohexane, cycloheptane, N-heptane or generally a hydrocarbon.

[0121] The exemplary embodiment produces surfaces which have been found to be antimicrobial (see FIG. 5).

[0122] In a further exemplary embodiment, the silicone matrix was also swollen. Not only cyclohexane, cyclopentane, n-heptane or generally a hydrocarbon, but also dimethyl acetamide and N-methyl-2-pyrrolidone were used as particularly preferred solvents. In this example, it was not a monomer that was added, but a polymer, so as to produce an IP network by diffusion. PESU and PSU were used as polymers.

[0123] To this end, the silicone matrix was swollen for 48 h in the solvent at room temperature. The polymer was added as solid substance and was dissolved in the solvent at room temperature over 24 h in the presence of the silicone samples to be treated. The silicone samples were then incubated in this solution for a further 24 h and were then removed, freed from any adhering solution, and were pre-dried at 40° C. for 8 h and were then freed from residual material at 40° C. and 0.01 bar under vacuum.

Exemplary Embodiment of the Electrode Lead

[0124] An embodiment of the implant according to the present invention is shown in FIG. 3 and has an electrode lead 1. The electrode lead comprises a plurality of conductors 10, 11, which extend longitudinally along the z-axis of the electrode lead 1. The conductors 10, 11 are wound here in the form of a helix around the longitudinal axis z of the electrode lead.

[0125] The electrode lead 1 has an outer (for example tubular) electrical insulation 100, which extends along the longitudinal axis z of the electrode lead 1 and surrounds the conductors 10, 11. The electrical insulation 100 here comprises the material according to the present invention or consists substantially thereof.

[0126] The conductors 10, 11 are preferably formed as cables which may comprise a plurality of wires, which for example may comprise silver or tantalum or may consist substantially thereof.

[0127] In the detailed view of the region A shown in FIG. 3 it is clear that the conductors 10, 11 forming a helix may be wound along the z-axis with different pitch p, p′ of the helix (see reference signs 10a, 10b and 11b).

[0128] The electrode lead 1 in its distal region 1a comprises electrode terminals E1 to E8 for contacting bodily tissue. In its proximal region 1b the electrode lead also has contacts C1 to C8, by which the electrode lead may be connected to an active electrical implant, such as an implantable pulse generator for example an implantable cardiac pacemaker or an implantable neurostimulator or an ICD. The contacts C1 to C8 are connected here to the electrode terminals E1 to E8 by means of electrical conductors 10, 11. For this purpose the electrode lead may have more than two conductors 10, 11, as shown schematically in FIG. 3. In particular, the electrode lead may have a dedicated electrical conductor for connection of the electrode pole E1 to the contact C1. The same is true also for the other electrode terminal-contact pairs E2 and C2, E3 and C3, etc.

Exemplary Embodiment of the Electrode Fixing Sleeve

[0129] Another embodiment of the implant according to the present invention relates to an electrode fixing sleeve 2, as shown by way of example in FIG. 4. The fixing sleeve is used to fix an elongate element 2, here for example in the form of an implantable electrode lead 1. The electrode lead 1 has an elongate lead body, in which, in the known manner, there is arranged at least one electrical conductor—not shown here—which is connected in particular to an electrode contact, which may be arranged on a surface of the lead body so as to contact tissue of the patient. In the example according to FIG. 4 the electrode lead 1 pierces a vessel G of the patient and is connected to muscle tissue MG of the patient by fixing elements 41, 42, which are secured to the fixing sleeve 2. The fixing elements 41, 42 are also used to compress or constrict the fixing sleeve 2, in such a way that the electrode lead 1 is securely clamped in a lumen 30 of the sleeve 3. The electrode lead 1 bears against an inner side 3a of the sleeve 2. The fixing elements 41, 42 are placed around the sleeve 2 in order to exert a force into corresponding grooves 31, 32, such that the sleeve may be constricted by means of the fixing elements 41, 42, resulting in a compression of the sleeve 3, at least in the region of the grooves 31, 32, such that the electrode lead 1 is securely clamped in the lumen 30 of the sleeve 2. It is provided in accordance with the present invention that the electrode sleeve and/or the electrode lead comprises the material according to the present invention. In particular it is provided that the electrode lead has an electrical insulation which comprises the material according to the present invention, in particular on the outer surface, or the electrical insulation consists substantially of the material according to the present invention. It is also provided in particular that the electrode fixing sleeve is produced substantially from the material according to the present invention.

Antimicrobial Properties of the Material According to the Present Invention

[0130] FIG. 5 shows the results of growth efforts with different customary materials, such as thermoplastic polyurethane elastomers (Pellethane 55DB or 80 AE), silicones (silicone 4765), and materials according to the present invention (silicone modified with MMA or PSU). The materials according to the present invention have a lower level of growth of S. aureus or S. epidermidis.

[0131] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teachings of the disclosure. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention, which is to be given the full breadth thereof. Additionally, the disclosure of a range of values is a disclosure of every numerical value within that range, including the end points.