WO2003045461A1

WO2003045461A1 - Surface-modified textile product and a corresponding method for surface modification

Info

Publication number: WO2003045461A1
Application number: PCT/DE2002/004291
Authority: WO
Inventors: Boris Obolenski; Uwe Klinge; Bernd Klosterhalfen; Stefan Schneemelcher; Bernhard Hartwig HÖCKER; Doris Klee; Zahida Ademovic
Original assignee: Feg Textiltechnik Forschungs- Und Entwicklungsgesellschaft Mbh
Priority date: 2001-11-23
Filing date: 2002-11-22
Publication date: 2003-06-05
Also published as: DE10295443D2; AU2002358421A1; DE10295443B4

Abstract

The aim of the invention is to provide a textile product used in medical practice for producing implants, which is highly biocompatible and to simultaneously prevent any potential inflammation from occurring in and around the implant. This is achieved by a textile product, in which a protein-free drug-release matrix is provided on a PVDF substrate. The invention also relates to a method for producing a product of this type.

Description

Textile product with surface modification and corresponding method for surface modification

The invention relates to a textile product with surface modification and a corresponding method for surface modification.

In medicine, especially in surgery, the task is often to insert textile implants into human or animal bodies. It is not only the mechanical compatibility that is decisive for the successful integration of an implant into a tissue. Rather, most of the postoperative complications associated with implants result from inflammation. Experience has shown that these inflammations are difficult to combat, so that an exchange of an inserted implant combined with a new operation can often not be avoided.

In order to prevent such inflammation, EP-A-0 809 997 proposes to subject an implant to a surface modification in which a matrix is arranged on a polymer and in which biomolecules, in particular proteins and collagens, by covalent bonding in the outer region of the Matrix be immobilized. This is based on the idea that a high level of biomolecules on the surface should enable tissue cells to attach quickly and thereby prevent inflammation.

A method is also known from DE-C-196 04 173 in which medical objects to be used extracorporeally or intracorporeally are first provided with a polymer layer and then with a further layer of immobilized biomolecules.

The likelihood of complication-free integration of an implant to be used can be increased enormously, however, if an implant is effectively provided with medicinal substances as a preventive measure to combat any infections that may arise. Unfortunately, too rapid an accumulation of tissue cells as well as an accumulation of proteins on the surface of the matrix prevents any active substances that may be provided from reaching the inflamed area from the matrix. The invention is based on the object of developing a textile product which, when used as an implant, has a hitherto unknown, very high biocompatibility

This task solve em

textile product with surface modification, in which a protein-free drug-release matrix is arranged on a PVDF substrate, and one

Process for the surface modification of a textile polymer, in which a protein-free drug-release matrix is produced on a PVDF substrate

First of all, polyvinylidene fluoride (PVDF) is a class of substances with very advantageous biological properties for use as an implant. Especially as an alternative to the materials polyester and polypropylene, which are also approved in surgery, PVDF is to be preferred. In direct comparison with polyester, it has a significantly better resistance to hydrolysis as time loses flexibility and the material hardens, this phenomenon does not occur with PVDF. No aging processes are known from PVDF

In addition, the textile properties of PVDF are stable within a temperature range of -20 ° C to +150 ° C. The friction resistance of PVDF is on the level of the polyamides and thus considerably exceeds that of the polyester PVDF also shows a high resistance to many organic acids and mineral acids as well as towards ahphatic and aromatic hydrocarbons, alcohols and halogenated solvents. In comparison to polypropylene, the inflammatory foreign body reaction of human tissue is also significantly reduced

By arranging a drug-release matnx, active ingredients can be directly integrated into the implant, which are continuously released after the implant is inserted with such a current that biochemical processes can be specifically prevented and / or required in the tissue area adjacent to the implant is that the implant or the active ingredient contained and delivered can not only exert its effect within the implant or on its surface, but rather the effect penetrates the surrounding tissue to a certain extent

It is of great importance that - with the departure from the common surface modification of implant materials - the matrix arranged on the substrate has a free surface, in particular a surface that is free of bound proteins. In complex test series, emphasized that the release of active substances is much more effective with a free implant surface than with previously known surface-treated implants.

In addition, it has been shown that a free matrix surface also enables excellent results for loading the matrix with medicinal active ingredients.

It is advantageous here if the drug-release matrix according to the invention has spacer molecules which are connected to the substrate, at least some of the spacer molecules being designed as a hydrogel layer. Spacer molecules are understood in the context of this application to mean matrix-generating or voluminous molecular forms, in particular molecular chains. The spacer molecules then form the matrix on the surface of the substrate. In this respect, the spacer molecules determine the spatial extent of the drug release matrix as well as its density and strength. An embodiment as a hydrogel layer with the absorption of body fluid can produce a very dense matrix. This prevents biomolecules from accessing the substrate surface. An adsorptive binding of the biomolecules is effectively and simply prevented, while the bulk properties of the PVDF substrate remain unchanged.

It is particularly preferred here if the spacer molecules are covalently bound to the substrate. Since a covalent bond has a very high strength, such a bond of the matrix to the substrate enables a high level of reliability and durability even under mechanical stress.

The spacer molecules can advantageously be polyethylene glycols, dialdehydes, diisocyanates and / or dicarboxylic acid chlorides. In particular, glutardialdehyde can be used as the dialdehyde, hexamethyl diisocyanate as the diisocyanate and EDC or DDC as the dicarboxylic acid chloride; For example, methoxy-PEG-aldehydes, PEG-dialdehydes, polyethyleneimines, modified starch, modified dextrans and / or hydrogel-complex polyethyleneimines or polyethylene glycols (PEI / PEG) can be used to design a hydrogel layer.

Due to their toxicity and solubility in aqueous and organic solvents, polyethylene glycols have found a wide range of applications. PEG are characterized by extremely low interactions with proteins and show a high resistance to bacterial attack. The protein absorption on the substrate surface can be suppressed in this way. The graft density of the PEG at the interface is of immense importance. A very high PEG graft density can be achieved by functionalizing the surface with polyethyleneimine-poly (ethylene oxide) (PEI-PEO) hydrogen complexes the. The outer PEI-PEO coating offers additional advantages in terms of the biocompatibility of the implant. The hydrogel layer allows slow and long-term release of an active ingredient from the matrix, which means that the implant remains resistant to infections over a longer period of time.

In a preferred embodiment, the spacer molecules are designed entirely as a hydrogel layer. Such a structure of the drug release matrix can be produced very reliably, it being particularly advantageous if the hydrogel layer is covalently bound to the substrate.

Regardless of this, it is advantageous if the hydrogel layer contains vinyl monomers, in particular acrylic acid or polyacrylic acid. If these substances are present in the hydrogel layer, it is highly hydrophilic and thus contributes to preventing protein adsorption on the substrate.

Extensive tests have shown that very good results are achieved if the acrylic acid or polyacrylic acid has a concentration of 10 ^"8 to 5 * 10 ^{" 7} , preferably 2 * 10 ^'8 to 4 * 10 ^"8 mol COOH / cm ² .

It is desirable that the pH of the drug release matrix be higher than the pKa of the PVDF substrate. Specifically, a threshold of around 4 can be assumed here. This ratio facilitates the storage of active substances in the matrix.

According to the invention, the hydrogel layer can also contain macromonomers, in particular polyethylene glycol methacrylates (PEGMA), polyethylene glycols (PEGs), polyethyleneimines, modified starch, modified dextrans and / or hydrogel-complex polyethyleneimines / polyethylene glycols (PEI / PEG). This also makes the hydrogel layer highly hydrophilic. Vinyl monomers with a reactive residue, such as glycidyl methacrylate (GMA), are used to use the epoxy functions of the monomer for immobilization. For example, a methacrylate with poly (oxyethylene) chain lengths of 4 to 100 can be present as the macromonomer.

The drug-release matrix or the matrix consisting of the hydrogel layer and the spacer molecules advantageously has a thickness of 0.1 to 1 μm, preferably 0.5 to 1 μm. Tests have shown that these values are very suitable.

Regardless of this, it is advantageous if the hydrogel layer is loaded directly with active ingredients. This ensures uniform release of the active ingredients over a long period of time. In addition, there are also practical reasons for this, especially if the hydrogel layer makes up a large part of the drug-release matrix. It is particularly preferred if the active substances are adsorptively deposited in the drug release matrix. In particular on PVDF substrates which are grafted with poly (acrylic acid) chains (PAAc-PVDF), it is advisable to realize the release of active substances by means of an adsorptive storage.

In order to be able to prevent inflammation in a particularly reliable manner, the active ingredients can include an antibiotic, preferably the cationically charged gentamycin. In general, however, active ingredients with cationic groups are highly suitable for use in the textile product according to the invention, since the cationic action facilitates adsorptive incorporation into the drug release matrix.

In addition, a release of the active ingredient is achieved in a desired quantity. It has been found in medical experiments that it is sufficient if an active level of 0.5 μg / ml to 1000 μg / ml gentamycin is calibrated in the immediate vicinity of the implant. For economic reasons, it is proposed that an active level of 0.5 μg / ml to 100 μg / ml be achieved.

The textile product according to the invention can preferably be present as a knitted fabric, a knitted fabric, a woven fabric, a mesh, a scrim, a thread or, in particular, directly as at least part of an implant. The biocompatible effect is largely independent of the specific constructive design of the implant that will ultimately be used. Rather, the advantages described are already achieved by surface modification of the materials mentioned or similar when used as an implant.

For this reason, the task described also solves the method for surface modification of a textile polymer, in which a protein-free drug release matrix is generated on a PVDF substrate. In this case, however, it is advantageous if the PVDF substrate is plasma-activated, since the spacer molecules can thereby be bound particularly well to the PVDF substrate.

In particular, in order to generate and bind the spacer molecules to the PVDF substrate in the case of a plasma ignition with micro- or radio wave-induced low-pressure plasmas, radicals can be generated on the PVDF substrate by inert gas, which radicals react after ventilation with atmospheric oxygen to form peroxy radicals and finally to hydroperoxides, which subsequently react with Thermal and / or photochemical cleavage form free radicals, via which monomers are graft-copolymerized. In this plasma activation process, the hydroperoxides formed after ventilation of the plasma system act as initiators of the radical graft copolymers due to their radicals. on. Thus, the graft copolymerization is a method which is advantageous for the hydrophilization and functionalization of surfaces and the associated possibility of increasing the biocompatibility.

As an alternative to this, it would be possible, for example, to generate radicals on the PVDF substrate by inert gas in order to generate and bind the spacer molecules to the PVDF substrate during plasma ignition under atmospheric pressure. Irrespective of the selection of the plasma activation, argon and / or N ₂ can advantageously be used as the plasma gas.

According to the invention, UV-induced cleavage can also be carried out using an excimer lamp for photochemical cleavage. In contrast to high-pressure and low-pressure mercury lamps, excimer lamps allow the emission of incoherent narrow-band UV radiation.

After the graft copolymerization, excess, non-covalently bound homopolymers can be removed. For this purpose, the textile product can preferably be washed extensively with water or an aqueous solution.

To produce the drug release matrix, however, it is generally preferred if monomers produced in the gas phase as chemical spacers by means of chemical vapor deposition polymerization processes (CVD polymerization processes) are polymerized by cooling at reduced temperature and these polymerized monomers in the form of a polymer matrix be bound to the PVDF substrate. Depending on the starting compounds used, the temperatures or pressures required to prepare the monomers are between 500 and 1000 ° C. and less than 500 Pa. The monomers are polymerized at temperatures below 120 ° C.

The monomers to be polymerized can advantageously 4-amino [2,2] -paracyclophane (amino-pcp), 4-hydroxymethyl- [2,2] -paracyclophane (hydroxymethyl-pcp), 4-carboxyl- [2,2] - Paracyclophane (car-boxyl-pcp) and / or [2,2] -paracyclophane-4,5,12,13-tetracarboxylic acid dianhydride (anhydride-pcp). However, the good insulating properties and chemical resistance of poly-p-xylylenes to practically all solvents can also be used advantageously for numerous applications. Objects coated with poly-2-chloro-p-xylylene have received FDA approval for various applications such as catheters or pacemakers. A toxic or carcinogenic effect of poly-p-xylylene is not known.

For the reasons explained in the description of the implant, it is advantageous if the monomers to be grafted vinyl monomers, in particular acrylic acid (Aac), and / or macromonomers, in particular include special polyethylene glycol methacrylates (PEGMA) to form a highly hydrophilic hydrogel layer.

It is alternatively and cumulatively advantageous if a solution with a concentration of 0.1 to 10 mg / ml, preferably between 0.2 and 0.3 mg / ml, of gentamycin is used to incorporate gentamycin into the drug-release matrix , The investigations carried out have shown that loading concentrations in this range of values ensure a very effective loading of the active substance, while if the loading concentration is increased further, only insignificantly more gentamycin is incorporated in the drug-release matrix.

In view of the advantageous suitability of a surface-modified textile product for intracorporeal use in the manner described, it is particularly advantageous if, with the method according to the invention, a multilayer textile product, a band replacement, an esophagus replacement, an intestinal replacement, a catheter, a membrane or a vascular prosthesis will be produced.

A knitted fabric, a knitted fabric, a woven fabric, a braid, a scrim, a thread or in particular at least part of an implant can preferably be produced using the method according to the invention.

It should be mentioned that all optional features described as advantageous are also advantageous and inventive in themselves, provided that they do not explicitly relate only to previous features.

The investigations carried out are discussed in more detail below and the method according to the invention is finally explained using examples.

Here, reference is made to the drawing. Show there

FIG. 1 shows schematically the molecular structure of a surface modified according to the invention,

FIG. 2 shows the results of crystallinity studies in a diagram,

FIG. 3 shows basic measurement values in a table,

FIG. 4 shows measured values for the release of gentamycin as a function of the loading concentration and the incubation time, FIG. 5 shows, in a further diagram, results of an experiment for loading with gentamycin as a function of the loading concentration and the pre-swelling and

Figure 6 in a diagram results of an experiment for the release of gentamycin in

Depends on the loading concentration and the incubation time.

For the investigation, a polyacrylic acid coating was first carried out on PVDF nets. The influence of the plasma treatment on graft copolymerization was then examined, whereupon a process control was carried out using a staining test. After the subsequent crystallinity investigations, attempts were then made in particular to optimize the loading and the release kinetics with gentamycin on two-dimensional PVDF networks.

The modified surface shown in FIG. 1 represents the invention schematically. Here, a matrix of polyacrylic acid 2a, 2b, 2c is arranged on a PVDF substrate 1 and covalently bound to the substrate 1. The cationic gentamycin G is adsorptively attached to the anionic COO ^" groups. Gentamycin G is found within the entire matrix 2a, 2b, 2c. The outer openings 3a, 3b, which lie between the polyacrylic acid 2a, 2b, 2c, are free of proteins.

Incorporation of gentamycin into the polyacrylic acid matrix was reliably achieved with a loading solution with a concentration of 0.1 to 10 mg / ml gentamycin and with a pH greater than 6.

The diagram in FIG. 2 shows DSC thermograms of PVDF filament blue (curve profile 10) and PVDF filament green (curve 11). Here, the heat flow in W / g is plotted on an axis 12 above the temperature in ° C, as it resulted from the crystallinity tests on PVDF filaments. More detailed information on the thermal properties of PVDF materials after the DSC measurements have been carried out is shown in the table which is shown in FIG. 3. Line 20 contains data for curve 10 (blue) and line 21 data for curve 11 (green). In the further subdivision, the lines Hl denote values for a first heating up and the line H2 measurement values for a second heating up. Column 22 shows the values for the melting peak, while column 23 contains measurements for the crystallization peak. The value in column 24 indicates the degree of crystallinity with the associated melting temperature T _m and mass-related energy difference ΔH _m , while T ₀ and ΔH _{0 represent} the respective values during crystallization.

In order to technically and economically optimize the desired processes of drug delivery through a drug release matrix, studies were carried out to optimize the loading concentration and studies on the dependence on the pre-swelling. Results of the first-mentioned investigation are shown in the diagram shown in FIG. 4. The diagram shows the influence of the gentamycin concentration in the loading solution on the subsequent release of the active substance from the matrix examined. The abscissa 30 shows the incubation time in serum at 37 ° C. in minutes, while the ordinate shows the release of gentamycin normalized to 25 mg of the matrix in micrograms per milliliter. The measuring points on the curves 31, 32, 33, 34 represent measured values which resulted after a loading concentration of 10 mg, 1 mg, 0.25 mg or 0.5 mg / ml.

Results of a further experiment on the influence of the loading concentration and the pre-swelling are shown in diagram 40 in FIG. 5. The difference from the starting amount of gentamycin before loading in micrograms is plotted on ordinate 41, which represents the incubation time in hours. The loading test was carried out at 24 ° C and the samples were shaken. In diagram 40, the measurement points on curves 42, 43, 44, 45, 46 show measurement values that have been set for different parameters. A loading concentration of 0.5 mg / ml gentamycin was used for the measured values marked with triangles on curves 42 and 45, the measured values represented by solid triangles on curve 45 on a loading solution of 0.5 mg / ml gentamycin in PBS (unswollen ) are based, while the measured values on curve 42 were caused by twelve hours of swelling in Aqua bidest. The parameters on which the measured values shown by the filled-in IC circles on curve 46 are based differ from those that led to curve 45 only in the loading concentration, because curve 46 contains a loading solution with a concentration of 0.25 mg / ml gentamycin in PBS (not swollen). The parameter combinations that did not swell to the measured values of curve 44 (0.25 mg / ml gentamycin in PBS, 12 hours swelling in aqua bidest at 22 ° C) or 43 (0.25 mg / ml gentamycin in H ₂ 0) ) are apparently just as unsuitable for loading with gentamycin as the parameter combination that led to the measured values on curve 42.

Diagram 50 in FIG. 6 shows measurement results for the release of gentamycin, the amount of gentamycin being normalized to 25 mg of the matrix, given in micrograms per milliliter, on which ordinate 51 is plotted. The abscissa 52 represents the incubation time in serum at 37 ° C. in minutes. The measured values on the curve 53 result from a loading concentration of 0.5 mg / ml, the measured values on the curve 54 from a concentration of 0.25 mg / ml. It should be noted here that the curves 53, 54 were each placed along the lowest measured values (numbered 55a, b for example), while significantly higher measured values (numbered 56a, b for example) have resulted. Medical examinations have shown that a release of 20 μg / ml is definitely therapeutically sufficient.

On the one hand, the tests show that the technically and economically optimal loading concentration of the PVDF networks with gentamycin is 0.25 mg / ml. In addition, the PVDF networks grafted with polyacrylic acid should be loaded from PBS buffer in the non-pre-swollen state. In this way, release amounts are achieved which ensure a therapeutically sufficient amount.

Specific process examples for the invention are given below.

Process for acrylic acid distillation

For acrylic acid distillation, a magnetic stirrer with heating plate, a heating hood with temperature control device, a round bottom flask, a Vigreux column, a Claisen still with a Liebig cooler and vacuum connection, a thermometer, a Schlenk flask with nitrogen connection and a vacuum system with HV pump with cold trap and nitrogen connection are used.

The chemicals used are acrylic acid with stabilizer (2-hydroxyethyl metacrelate, 99%), 4-methoxyphenol (hydroquinone monomethyl ether) with 1 g / 1 acrylic acid, ultra-pure nitrogen 5.0 and liquid nitrogen to cool the cold trap.

The cold trap is first cooled with the liquid nitrogen. After connecting the cooling water system, 800 ml of acrylic acid and 800 mg of hydroclünone are added to the template and the stirring magnet is added. After setting a vacuum of at least 6 * 10 ^"2 mbar in the system, the system is purged with nitrogen so that it can be distilled under an inert gas atmosphere.

After these preparatory steps, the template is slowly heated to 80 ° C. The mixture is constantly stirred so that the distillation takes place evenly and can be monitored optically. Since the distillation requires a temperature of 80 ± 5 ° C, it is first heated to 65 ° C and then heated further in steps of 2 ° C. From the start of the distillation, the temperature reached is kept constant, a temperature window of ± 5 ° C being permitted.

The first 10 ml of the distillate is discarded in order to rule out any expected deviations during the start of the process. The usable distillate obtained is stored under nitrogen at a maximum of 4 ° C in the refrigerator. Thermal graft copolymerization of PVDF nets

For thermal graft copolymerization, a heating element, a round bottom flask, teflon stones, a Soxhlet, a reflux condenser, a tripod plate, a tripod rod, solid clamps and a circulating air drying cabinet are used on devices. M-Hexane and ethanol are used as solvents. To extract the nets, they are placed in the Soxhlet so that they are free on all sides. The solvent is then added to the round bottom flask with a hexane to ethanol ratio of 79 to 21 w / w. After an extraction period of approx. 48 hours, the nets are dried in the drying cabinet at approx. 30 ° C for twelve hours.

After the nets have been plasma activated with argon for 180 seconds, they are processed within 30 minutes.

To prepare this, the distilled acrylic acid is thawed and a 20% acrylic acid solution with H ₂ 0 is prepared. Then a quartz glass tube or another suitable container with a screw cap is attached to the stand with a clamp and the acrylic acid solution is added to the container. After careful degassing with nitrogen, the sample rack with the nets is added. The vessel is now tightly closed and hung in a water bath, which is then heated to 90 ° C and stirred. This process is continued until the solution becomes viscous.

The mesh films are then washed briefly once and five times within four hours with distilled H ₂ O. It is then washed several times with distilled H ₂ O over a period of one day. Finally, the foils are dried for about three hours at 30 ° C and then stored dry.

Example 3

Using plasma activation, for the graft copolymerization of PVDF substrate, a PVDF substrate is applied to a pulsed microwave plasma (pulse duration 1600 μs, period duration 2000 μs) of 1.5 to 2 kW power with argon (flow rate 5 1 / h) as plasma gas under pressure of 10 exposed to 15 Pa and varying the treatment time from 15 to 300 seconds. The PVDF substrate is further processed after an air exposure of 20 to 150 minutes. The graft copolymerization of the argon plasma-treated PVDF substrate is carried out in each case under a nitrogen atmosphere. Since the OO binding energy in hydroperoxides is low at 150 kJ / mol, it is possible to split hydroperoxides by adding appropriate amounts of energy. Temperatures of 50 to 100 ° C are sufficient to achieve such a split. Graft copolymerization is initiated by thermal hydroperoxide cleavage at 90 ° C.

Alternatively, a UN-induced cleavage can also be carried out. In contrast to high-pressure mercury lamps and low-pressure mercury lamps, excimer lamps enable the emission of incoherent narrow-band UN radiation. A xenon chloride emitter with an emission maximum of 308 is used. The energy of these photons is around 400 kJ / mol.

Example 4

After plasma activation, the coating of a PVDF surface is functionalized in a first step by a radical-induced graft copolymerization of acrylic acid (PVDF-PAAc).

Acrylic acid (AAc) provides a hydrophilic, carboxyl group-containing surface on PVDF substrate. The thermal plasma-induced graft copolymerization of acrylic acid is carried out using a monomer concentration of 5 to 50%, preferably approx. 25%, in deionized water (v / v), preferably 20 to 30% (v / v), and a polymerization time of 15 to 90, preferably 30 to 60. minutes at 90 ° C thermally or by a 2.5 to 5 minute irradiation with UV light. After the termination of the polymerization, homopolymer that is not covalently bound to the PVDF substrate is removed by extensive washing with water or an aqueous solution.

The modified surface obtained in this way is highly hydrophilic and has a high concentration of carboxyl groups. Now it can be used in particular for loading with antibiotics.

The surface-bound carboxyl groups are treated for 20 minutes with an aqueous EDC / NHS solution (0.2 M / 0.1 M) for activation. The surfaces are then rinsed briefly with deionized water and incubated for several hours in a solution of 1 mg / ml GRGDS peptide in 0.1 M sodium hydrogen carbonate buffer (pH 8.4). The unbound peptide is removed by repeated intensive rinsing with deionized water.

Example 5 A PVDF substrate is coated by means of plasma activation. The graft copolymerization of acrylic acid and the subsequent activation take place as described above.

In order to prevent the unwanted protein adsorption, a hydrogel complex is immobilized. For this purpose, the activated PVDF-PAAc substrate is immersed in a PEI solution (1 mg / ml) for 1 hour at room temperature. Then the PVDF substrate in a buffer solution (NaHPO4 / Na0H pH 6.4) at 11% K ₂ S0 ", 1 mg ml PEG- (aldehyde) ₂ (MW 3400), 3 mg / ml NaCNBEL, as Incubating agent incubated for 8-12 h at 30 to 60 ° C (best results: 8h, 60 ° C) and then washed with water. Then the sample is mixed with an RGD peptide solution (1 mg / ml in phosphate buffer, reducing agent NaCNBH4) at room temperature for 2 hours.

Example 6

The plasma-induced graft copolymerization of a methacrylate by means of plasma activation can be carried out using a monomer concentration of 5 to 50% (v / v), preferably 20 to 30% (v / v) in a water / methanol mixture and a polymerization time of 1 to 4 hours , preferably 2 to 3 hours, at 90 ° C thermally or by 10 minutes to 30 minutes of exposure to UV light. In a subsequent step, the free carboxyl or hydroxyl groups of the material surface generated by means of plasma graft polymerization are activated. As activating agents for the carboxyl groups e.g. EDC [1- (3-dimethylaminopropyl) -3-20 ethyl carbodiimide hydrochloride] or DDC [1,2-dicyclohexyl carbodiimide] and for the hydroxyl groups e.g. Diisocyanate such as hexamethyl diisocyanate or 2,2,2-trifluoroethanesulfon chloride (tresyl chloride) can be used. A PVDF surface modified with glycidyl methacrylate can be used without prior activation.

Claims

claims:

1. Textile product with surface modification, characterized in that a protein-free drug release matrix is arranged on a PVDF substrate.

2. Textile product according to claim 1, characterized in that the drug release matrix has spacer molecules which are connected to the substrate, at least some of the spacer molecules being designed as a hydrogel layer.

3. Textile product according to claim 1 or 2, characterized in that the spacer molecules are covalently bound to the substrate.

4. Textile product according to one of the preceding claims, characterized in that the spacer molecules are polyethylene glycols, dialdehydes, diisocyanates and / or dicarboxylic acid chloride.

5. Textile product according to one of the preceding claims, characterized in that the spacer molecules have free carboxyl, hydroxyl and / or amino groups.

6. Textile product according to one of the preceding claims, characterized in that the spacer molecules are completely formed as a hydrogel layer.

7. Textile product according to one of the preceding claims, characterized in that the hydrogel layer is covalently bound to the substrate.

8. Textile product according to one of the preceding claims, characterized in that the hydrogel layer contains vinyl monomers, in particular acrylic acid or polyacrylic acid.

9. Textile product according to one of the preceding claims, characterized in that the acrylic acid or polyacrylic acid has a concentration of 10 ^"8 to 5 * 10 ^{" 7} , preferably 2 * 10 ^"8 to 4 * 10 ^{" 8} , mol COOH / cm ² , Has.

10. Textile product according to one of the preceding claims, characterized in that the hydrogel layer contains macromonomers, in particular polyethylene glycol methacrylates (PEGMA), polyethylene glycols (PEGs), polyethyleneimines, modified starch, modified dextrans and / or hydrogel-complex polyethyleneimines / polyethylene glycols (PEI / PEG).

11. Textile product according to one of the preceding claims, characterized in that the pH of the drug release matrix is higher than the pKa of the PVDF substrate.

12. Textile product according to one of the preceding claims, characterized in that the drug-release matrix or the matrix consisting of the hydrogel layer and the spacer molecules has a thickness of 0.1 to 1 μm, preferably of 0.5 to 1 μm ,

13. Textile product according to one of the preceding claims, characterized in that the hydrogel layer is loaded with active ingredients.

14. Textile product according to one of the preceding claims, characterized in that the active substances are adsorptively attached.

15. Textile product according to one of the preceding claims, characterized in that the active ingredients contain an antibiotic, preferably gentamycin.

16. Textile product according to one of the preceding claims, characterized in that the active substances have cationic groups.

17. Textile product according to one of the preceding claims, characterized in that an active level of more than 0.5 μg / ml and preferably less than 100 μg / ml gentamycin is achieved in the immediate vicinity during implantation.

18. Textile product according to one of the preceding claims, characterized in that it forms a knitted fabric, a knitted fabric, a woven fabric, a mesh, a scrim, a thread or in particular at least part of an implant.

19. Process for the surface modification of a textile polymer, characterized in that a protein-free drug-release matrix is produced on a PVDF substrate.

20. The method according to claim 19, characterized in that the PVDF substrate is plasma activated.

21. The method according to claim 19 or 20, characterized in that to generate and bind the spacer molecules to the PVDF substrate in a plasma ignition with micro- or radio-wave-induced low-pressure plasmas by inert gas radicals are generated on the PVDF substrate, which after ventilation with Atmospheric oxygen to peroxy radicals and eventually to React hydroperoxides, which then form free radicals by thermal and / or photochemical cleavage, via which monomers are graft-copolymerized.

22. The method according to claim 19 or 20, characterized in that radicals are generated on the PVDF substrate by inert gas for generating and binding the spacer molecules to the PVDF substrate during plasma ignition under atmospheric pressure.

23. The method according to any one of claims 19 to 22, characterized in that argon and / or N _{2 is} used as the plasma gas.

24. The method according to any one of claims 19 to 23, characterized in that a UV-induced cleavage is carried out by means of an excimer lamp for photochemical cleavage.

25. The method according to any one of claims 19 to 24, characterized in that as spacer molecules by means of chemical vapor deposition polymerization (CVD polymerization) in the gas phase monomers are polymerized by cooling at a reduced temperature and these polymerized monomers in the form of a polymer matrix be bound to the PVDF substrate.

26. The method according to any one of claims 19 to 25, characterized in that the monomers to be polymerized 4-amino [2.2] -paracyclophane (amino-pcp), 4-hydroxymethyl- [2,2] - paracyclophane (hydroxymethyl-pcp ), 4-carboxyl- [2,2] -paracyclophan (carboxyl-pcp) and / or [2,2] -paracyclophan-4,5.12, 13-tetracarboxylic acid dianhydride (anhydride-pcp).

27. The method according to any one of claims 19 to 26, characterized in that the monomers to be grafted contain vinyl monomers, in particular acrylic acid (AAc), and / or macromonomers, in particular polyethylene glycol methacrylates (PEGMA), to form a highly hydrophilic hydrogel layer.

28. The method according to any one of claims 19 to 27, characterized in that spacer molecules with a pH value which is greater than the pKa value of the PVDF substrate are used.

29. The method according to any one of claims 19 to 28, characterized in that the drug-release matrix with active ingredients, in particular with antibiotics, preferably with gentamycin. is loaded adsorptively.

30. The method according to any one of claims 19 to 29, characterized in that a gentamycin solution with a concentration of 0.1 to 10 mg / ml, preferably between 0.2 and 0.3 mg / ml, is used for incorporation.

31. The method according to any one of claims 19 to 30, characterized in that a multi-layer textile product, a band replacement, an esophagus replacement, an intestinal replacement, a catheter, a membrane or a vascular prosthesis is produced.