WO2022157160A1

WO2022157160A1 - Enclosure for receiving an implant, and method for the production thereof

Info

Publication number: WO2022157160A1
Application number: PCT/EP2022/051046
Authority: WO
Inventors: Niels Grabow; Emil REISINGER; Klaus-Peter Schmitz; Stefan Thomas Oschatz; Sabine Illner; Valeria Khaimov
Original assignee: Universität Rostock
Priority date: 2021-01-19
Filing date: 2022-01-18
Publication date: 2022-07-28
Also published as: DE102021101064A1; EP4281177A1

Abstract

A description is given of an enclosure (1) for receiving an implant (2) suitable for being introduced into a human or animal body, and a method for the production thereof. The enclosure (1) has a pocket (3), which is designed for receiving the implant (2) and has a wall (4) which is provided with at least one textile material (5) which, in a state in which the implant (2) is at least partially arranged in the pocket (3), lies against the implant (2), at least in some regions. The technical solution described is distinguished by the fact that the textile material (5) comprises, at least in some regions, microfibres and/or nanofibres (6) which have a diameter smaller than 5 µm and arranged on or in which there is at least one anti-infective agent (7) which, in the implanted state, is released at least for a time in the human or animal body.

Description

Enclosure for receiving an implant and method for its manufacture

The invention relates to a cover for accommodating an implant and a method for producing such a cover. The enclosure is suitable for incorporation with an implant into a human or animal body and has a pocket adapted to receive the implant therein and having an outer wall comprising at least one textile material which is in a condition , In which the implant is at least partially arranged in the pocket, rests against the implant at least in regions.

In the field of implantology, various technical solutions are known for providing an implant intended for insertion into the body of a human or animal, for example a cardiac pulse generator, an endoprosthesis or a cochlear aggregate, with a cover that primarily has a to ensure that the implant remains safe in the intended place in the body and that the tissue surrounding the implant is protected.

Currently, an estimated 1.5 million cardiac pulse generators, which include pacemakers, implantable defibrillators, and resynchronization-plus-defibrillator implants, are implanted worldwide each year. Such implants are preferably transplanted under the skin as so-called pocket implants in the chest area. Above all, cardiac pulse generators are intended to prevent or at least reduce the risk of heart-related unconsciousness in the patient as well as dizziness and weakness attacks that can be attributed to a heartbeat that is too slow or irregular, so that the quality of life of the patient is regularly significantly increased. It does this by continuously monitoring the heart's function and delivering an electrical pulse whenever the heart's rhythm slows.

However, the insertion of the known implants is not completely risk-free, since there is generally a risk of infection by microorganisms that are on the surface of the implant. Approximately 1 to 4% of patients develop an infection after initial implantation, with most occurring within the first year post-implantation. Incidentally, every unit change and every probe revision represents a new risk of infection. If an infection occurs on the implant, it must be removed in order to minimize the health risk for the patient.

For this reason, in some cases, immediate preoperative antibiotic prophylaxis is carried out by means of a single administration of an antibiotic, which reduces the risk of subsequent infection. Furthermore, in vitro studies demonstrated that the risk of infection by preoperatively immersing the implant in an antimicrobial solution significantly reduces the bacterial load on the implant surface. Nevertheless, efforts are still being made to further significantly reduce the risk of infection caused by the insertion of an implant into a human or animal body.

US 2008/132922 A1 discloses a casing for implantable cardiac pacemakers and implantable defibrillators, into which the implant is inserted by the operator immediately before it is inserted into the patient's body. The covering described has a textile material which is formed from a large-pored meshwork. The textile material used is biodegradable and has a polymer coating, with rifampin and minocycline being sprayed onto the intertwined polymer fiber bundles of the coarse-pored meshwork as anti-infective substances. According to the information provided by the property right holder about the product based on the technical solution described, the coating dissolves in the body within around nine weeks.

The problem with the cover described is that the textile material used has a comparatively high coefficient of friction due to its coarse-pored structure and the size of the implant increases by 10-15% due to the cover. The size and rigidity of the covered implant adversely affects surface contact with surrounding tissue. It is also necessary for the surgeon to sew up the cover after the implant has been inserted.

Starting from the coverings for implants known from the prior art, the problems described above and the still existing risk of infection, the invention is based on the object of specifying a covering for an implant and a method for its production, so that an implant is simple introduced into the casing, slipping out is reliably prevented and the risk of infection due to the introduction of the implant into a human or animal body is minimized. With the aid of the technical solution to be specified, it should be possible for a surgeon to easily introduce the implant or the unit to be implanted into the casing, with the casing also being as close as possible to the surface of the implant.

Furthermore, due to the material properties and the shape of the cover, it should be ensured that the implant is reliably prevented from slipping out of the cover without the need for subsequent closing of the cover, for example sewing. Furthermore, the casing should be designed in this way be that the outer circumference of the implant with a cover is only slightly increased compared to the implant without a cover. Nevertheless, the largest possible contact area with the surrounding tissue should be formed. In this context, it is desirable that the surface of the covering facing the patient's body after the implantation has a structure that is as fine as possible in order to achieve good surface adaptation and a large contact area.

Furthermore, with regard to a cover designed according to the invention and a production method according to the invention, it should be ensured that the residence time of a cover in the body, i.e. the period after implantation has taken place until complete resorption or decomposition, can be reduced by a comparatively simple adjustment of the cover, in particular the materials used. can be adjusted as needed. Furthermore, the cover to be specified should be designed with an anti-infective agent in such a way that it is released in the body over a longer period of time. It is at least desirable here for a larger amount of active ingredient to be released immediately after the insertion of an implant than is the case in the subsequent period. Furthermore, it is of great importance that an enclosure that solves the problems described above can be produced using a known technical manufacturing process, so that an economically sensible production of an enclosure in larger quantities or numbers of pieces is also possible.

The object described above is achieved with a cover according to claim 1 and a method according to claim 14. Claim 13 specifies a combination which has a covering and an implant and which solves the object on which the invention is based. Advantageous embodiments of the invention are the subject matter of the dependent claims and are explained in more detail in the following description with partial reference to the figures.

The invention relates to a cover for accommodating an implant that is suitable for introduction into a human or animal body. The cover has a pocket which is designed to accommodate the implant and which has an outer wall which has at least one textile material which, in a state in which the implant is at least partially arranged in the pocket, at least in regions on the implant is present. According to the invention, the covering is characterized in that the textile material has at least some areas of micro- and/or nano-fibers with a diameter of less than 5 μm, on or in which at least one anti-infective agent is contained which is implanted in State is released at least temporarily in the human or animal body. The invention is thus essentially based on an implantable cover for accommodating implants, such as pacemaker implants, implantable defibrillators, cardiac resynchronization-plus-defibrillator implants and aggregates of implantable neurostimulators, with a micro- and/or nanofiber fleece-based implant pocket with incorporated anti-infective agent . According to the invention, a textile material is used for the pocket, which at least partially has microfibers and/or nanofibers, so that on the one hand a comparatively finely structured surface and on the other hand a pocket for receiving the implant is provided, which has an elastic outer wall which is directly attached to the implant fits. In this way, the implant is reliably prevented from slipping or even slipping out, the build-up of a biofilm on the surface of the implant is prevented and a cover can also be used for implants of different shapes and/or sizes due to the cover being designed to be elastic.

Furthermore, it is advantageous that an opening through which the implant is inserted into or removed from the pocket does not have to be closed after the implant has been inserted, which in turn is achieved by the wall of the pocket directly adjoining the wall of the implant and surrounds it securely. The pocket advantageously has an opening through which the implant can be inserted into and removed from the pocket. It is also conceivable for the pocket to have two openings, with the pocket preferably being designed as a tube which is pulled as a covering over the implant or the unit to be implanted before the implant is inserted into the body.

According to a preferred embodiment of the invention, the anti-infective active ingredient is at least partially not on the surface of the microfibers and/or nanofibers, but is integrated into them, ie incorporated into the textile material used. In this way, a release of the anti-infective active ingredient is made possible in a particularly preferred way, even over longer periods of time. In this context, it is conceivable that the at least one anti-infective active ingredient is selected and integrated into the micro- and/or nanofibers in such a way that a comparatively large amount of the anti-infective active ingredient is released in the body immediately after implantation, while following this first , quasi intermittent release continuously or at least almost continuously a smaller amount of the anti-infective active ingredient is released. The formation of infection foci immediately after implantation is thus reliably prevented. Furthermore, by the drug release over also prevents postoperative infections for a comparatively long period of time or at least reduces the risk of an infection developing.

The microfibers and/or nanofibers of the textile material preferably form a fleece layer or a fleece mat at least in regions. Such a non-woven layer or non-woven mat can be shaped as required into a shaped body which forms a pocket by means of a suitable method such as gluing, welding or sewing. It is also conceivable that the microfibers and/or nanofibers are shaped during production using a 3D free-forming process in such a way that a pocket with one or two openings is produced and further shaping process steps are not required.

In contrast to the solutions known from the prior art, it is ensured here that the anti-infective active ingredient is distributed over a comparatively large area and preferably evenly in the cover.

At the same time, the large surface-to-volume ratio of fleece-like textile material has a positive effect on the release of the anti-infective active ingredient located in the textile material. The initially strong active ingredient release (burst release) represents a positive effect, since an effective active ingredient concentration in the vicinity of the implant is ensured at an early stage, thus inhibiting bacterial growth and preventing the development of resistance. Here, an effect is already achieved when using comparatively small amounts of active ingredient. Overall, this makes it possible to dispense with the systemic administration of antibiotics and thus to minimize the corresponding side effects for a patient.

Furthermore, the fleece layers or fleece mats provided according to this special embodiment have a comparatively high mechanical load capacity. For this reason, it is conceivable in an advantageous manner to use a textile material selected in this way to make the wall of a pocket elastic for receiving an implant to be inserted into a body and thus to create a stretchable covering which deforms elastically and after the implant has been inserted form-fitting to the implant, in particular its surface. Mechanical irritation of the tissue surrounding the implant after implantation is minimized and the formation of a biofilm on the surface of the implant is reliably prevented due to the positive fit. Furthermore, later infiltration and the associated colonization of germs is prevented. Due to an elastic configuration of the non-woven textile material, which at least partially forms the wall of the pocket, it is also possible to provide a cover for different implants, since a corresponding implant adapts to different sizes and shapes of an implant. It must be taken into account here that, depending on the area of application and medical indication, the implants placed in the body of a human being or an animal have different sizes and/or shapes. The inventive design of a cover for an implant, in particular the mechanically stable yet elastic design, not only allows implants used differently in the area of the human breast, such as cardiac pacemakers, implantable defibrillators and cardiac resynchronization-plus-defibrillator implants, but also others Implants are used that are used in the area of hearing, the eyes, the oral cavity or the head and/or for stimulating nerves, such as aggregates of implantable neurostimulators.

According to a particular embodiment of the invention, it is provided that a diameter Df of the microfibers and/or nanofibers is less than 3 pm, in particular less than 1 pm.

Furthermore, it is advantageously provided that a diameter Df of the micro- and/or nanofibers is in a diameter range of 5 μm>Df>0.05 μm, preferably in a diameter range of 3 μm>Df>0.05 μm and very particularly preferred lies in a diameter range of 1 pm > Df > 0.05 pm.

Such a configuration of the micro- and / or nano-fibers covers for implants are provided with previously unknown properties, as using micro- and / or nano-fibers that have such diameters, fleece layers, fleece mats or other fleece structures are produced in an advantageous manner, the one particularly low surface roughness and high elasticity. Due to these properties of the textile material, the coverings produced therefrom lie particularly tightly on the implant and irritation of the tissue surrounding the covered implant after implantation is reliably avoided or at least minimized.

Implementation of the invention thus creates a particularly tight-fitting cover that flexibly nestles against the surface of the respective implant, thereby reliably preventing the implant from slipping or even slipping out of the cover and preventing microorganisms from settling on the surface of the implant be prevented.

According to a special development of the invention, it is provided that the textile material has at least one textile material that is resorbable or degradable in the human or animal body. According to this embodiment it is provided that with an implant in a human or animal body introduced envelope dissolves in such a way that the material used is absorbed by the body or that this decomposes and is excreted from the body over a certain period of time. According to an alternative embodiment, it is provided that the covering at least partially has at least one biostable textile material that is neither resorbed by the body nor decomposed in it. Such a textile material therefore remains stable in a human or animal body over a comparatively long period of time.

Furthermore, it is particularly advantageous if the textile material that is absorbable or degradable in the human or animal body or the biostable textile material has at least one polymer.

If the textile material is resorbable or degradable, at least one polymer from a polymer group including polyester, polyanhydride, polyglycol, polyether, polycarbonate, polysaccharide, polysuccinimide and polyamino acid is preferably used. It is also conceivable that the polymer alternatively or additionally comprises a copolymer of the aforementioned polymers and/or a blend of at least one of the aforementioned polymers.

If the textile material is biostable, at least one polymer is advantageously selected from a group of polymers including polyurethane, polyamide, polysulfone, polymide, polyether and polyolefin. Alternatively or additionally, it is also conceivable in this case to use a copolymer and/or a blend of at least one of the aforementioned polymers.

According to a preferred embodiment of the invention, an active substance from a group of active substances which includes aminoglycosides, rifampin, minocycline, daptomycin, cephalosporin, vancomycin, β-lactam, ampicillin, amoxicillin, dalbavancin, octenidine dihydrochloride and gentamicin is used as the anti-infective active substance. It is also conceivable to use a combination of at least two of the aforementioned active ingredients as the anti-infective active ingredient, so that long-term active ingredient release for local infection prophylaxis in the body is advantageously ensured.

The at least one selected anti-infective active substance is preferably integrated or incorporated into the textile material, which is in particular an absorbable, degradable or biostable polymer.

According to a special development of the invention, the pocket of the cover has an opening on one side and/or is tubular. The textile material, which at least partially has microfibers and/or nanofibers, is preferably designed in such a way that it is at least in one for receiving an implant required size range is elastically deformed and thus adaptable to implants of different sizes and shapes. Furthermore, it is advantageous if the textile material is designed in such a way that it evenly adjoins the implant placed in the pocket, so that on the one hand an enlargement of the object to be implanted due to the use of the cover is minimized and on the other hand the risk of biofilms forming on the accumulate surface of the implant is reduced.

According to a special development of the cover designed according to the invention, the pocket is produced by means of an electrospinning process. Here, micro- and/or nanofibers and non-woven layers, non-woven mats or suitable non-woven hollow bodies are produced from a polymer-active substance solution by electrospinning, with the anti-infective active substance being integrated or incorporated into the non-woven fabric used as textile material, so that a preferred release of the active substance is achieved can be realized in the body.

In addition, it is conceivable in a preferred way that the textile material has microfibers and/or nanofibers that have different properties. According to this configuration, the microfibers and/or nanofibers thus preferably have different polymers and/or different active substances that are incorporated into the microfibers and/or nanofibers.

Furthermore, the invention also relates to a method for producing an envelope with a pocket for receiving an implant, which is suitable for introduction into a human or animal body, in which at least one polymer-active substance solution, the components at least one polymer and has at least one anti-infective active substance, is provided, from the active substance-polymer solution by electrospinning micro- and/or nano-fibers with a diameter of less than 5 μm, and from the micro- and/or nano-fibers a fleece is produced and in which the Fleece is designed and arranged in such a way that the fleece at least partially forms a wall of the pocket and, in a state in which the implant is at least partially arranged in the pocket, rests at least in regions on the implant.

According to a particular embodiment of the invention, it is provided that microfibers and/or nanofibers with a diameter Df of less than 3 μm, in particular less than 1 μm, are produced. Furthermore, it is advantageously provided that microfibers and/or nanofibers with a diameter Df that is in a diameter range of 5 μm>Df>0.05 μm, preferably in a diameter range of 3 μm>Df

> 0.05 pm and most preferably in a diameter range of 1 pm > Df

> 0.05 pm can be generated. The method according to the invention for producing a micro- and/or nano-fiber-based implant with an integrated anti-infective active substance, in particular at least one antibiotic, is therefore based on the use of electrospinning. Electrospinning is a known process that can be used to produce microfibers and/or nanofibers from solutions, suspensions or melts of different materials, such as natural or synthetic polymers and inorganic, metallic or ceramic materials, using a strong electric field. In this context, it is again conceivable that the microfibers and/or nanofibers as well as the fleeces have at least one biostable polymer or one that is resorbable or degradable in the body.

In a particular embodiment of the method according to the invention, an absorbable or degradable fleece material is produced which has at least one polymer from a polymer group which includes polyester, polyanhydride, polyglycol, polyether, polycarbonate, polysaccharide, polysuccinimide and polyamino acid. It is also conceivable that, alternatively or in addition, a copolymer and/or a blend of at least one of the aforementioned polymers is used for the production of the fleece material.

In another embodiment of the method according to the invention, a biostable nonwoven material that remains stable in the human or animal body for at least a longer period of time is produced, which has at least one polymer from a polymer group including polyurethane, polyamide, polysulfone, polyimide, polyether and polyolefin belong. Alternatively or in addition, it is conceivable that a copolymer and/or a blend of at least one of the aforementioned polymers is used to produce the fleece material.

With the aid of the method according to the invention, a covering for implants or aggregates to be implanted can be produced in a flexible manner, which has a special mechanical stability and is nevertheless designed so elastically that it adapts to implants of different shapes or sizes in a respectively definable size range. The implant pocket created in this way fits around the implant in a form-fitting manner, regardless of the model, regardless of whether it is a cardiac pulse generator, a cochlear implant, an endoprosthesis or an osteosynthesis system.

By using the method according to the invention, the anti-infective active substance used is embedded directly in the microfibers and/or nanofibers, so that local release of the active substance in a human or animal body is ensured over a comparatively long period of time. Since electrospinning does not lead to strong heating of the polymer-active substance solution, a large number of known antibiotics can preferably be used as active ingredients. According to the recommendation for the conventional therapy of an isolated local pocket infection, at least one antibiotic is used as the active ingredient that covers the known spectrum of germs and takes into account the local resistance situation, especially in relation to the MRSA prevalence. An active substance selected from the group consisting of the aminoglycosides, rifampin, minocycline, daptomycin, cephalosporins, vancomycin, β-lactams, ampicillin, amoxicillin, dalbavancin and gentamicin is therefore preferably used as the active substance. At least one active substance from the group of cephalosporins is used in a particularly advantageous manner, since these are distinguished by a broad spectrum of action and their effectiveness against both Gram-positive and Gram-negative pathogens.

In a specific embodiment of the method according to the invention, at least two polymer-active substance solutions are provided, which differ in at least one of the components used. These at least two polymer-active substance solutions, which differ in at least one component, are preferably processed at the same time and fed to an electrospinning process, so that micro- and/or nano-fibers with different properties are produced and nonwoven layers from these micro- and/or nano-fibers, Non-woven mats or non-woven hollow bodies with heterogeneous, ie locally different, properties are produced. Due to this technical solution, it is conceivable to produce a fleece material from different micro- and/or nano-fibers, which are characterized by different resorption or degradation times and/or by which different active substances are released.

With the aid of the production method according to the invention, a cover can thus be produced comparatively easily, which can be flexibly adapted to the respective situation as required. The active ingredient integrated into the fleece material of the cover is released from the micro- and/or nanofibers in a diffusion-controlled manner over a longer period of time, thereby enabling local prophylaxis. As a result, postoperative infections in the tissue surrounding the implant can be avoided or the risk can at least be minimized.

The textile material produced according to the invention, designed as a fleece, which has micro- and/or nano-fibers, can be used for coverings for a large number of implants that are introduced into a human or animal body.

It is conceivable to use a correspondingly produced fleece material for a cover, for example for endoprostheses, cochlear aggregates, aggregates of implantable neurostimulators, cardiac pulse generators such as pacemaker aggregates, but also as a supporting material in vascular reconstruction. Because of the engagement of biodegradable polymers, it is also ensured in an advantageous manner that the covering is resorbed by the body or degraded after the release of the active substance has ended. The micro- and/or nanofiber webs produced with the method according to the invention are characterized by an extremely high surface-to-volume ratio. This allows active substances to be released quickly, which is particularly advantageous when antibiotics are used. This enables a sufficient concentration of the active ingredient at the site of action to inhibit bacterial growth and prevent the development of resistance. The sustained release also ensures long-term effectiveness.

According to a particularly suitable embodiment of the method according to the invention, an envelope that has anti-infective properties and has at least one material that is comparatively slowly degradable in the human or animal body is produced from PLLA-gelatine composite fibers (PLLA=poly(L-lactide)) as follows :

In a first step, two polymer/active substance solutions for dual electrospinning are provided on an xyzelectro spin system. The polymer solutions provided are composed of

2-7 m% poly-L-lactide in a solvent mixture of trifluoroethanol and chloroform (ratio: 4:1) with the addition of 1-3% lecithin based on the polymer mass (solution 1) and

5-15 wt% gelatin dissolved in trifluoroethanol (Solution 2).

After successful homogenization for 6 to 72 hours, the active ingredient doxycycline (dissolved in methanol, 5-20m% based on the polymer mass) is added to solution 1 and the active ingredient dalbavancin (dissolved in trifluoroethanol, 5-20m% based on the polymer mass) to solution 2 ) added as anti-infectives. Each of these solutions is then filled into a separate syringe, the two filled syringes are inserted into the electrospin system and processed into a fleece using the process parameters given below.

Process parameters used according to this embodiment: One hour spinning time with a collector-emitter distance of 150-200 mm at a voltage difference of 10-20 kV (collector: emitter) and a controlled rel. Humidity of 20-40% at 22-25 °C (room temperature). In this way, a planar fleece approximately 0.1 mm thick is obtained, which is annealed at 60-80° C. for 12 to 24 hours after the spinning process is complete.

In order to produce a covering suitable for use as an implant pocket, two flat fleeces produced as described above are placed one on top of the other and thermally joined to form a pocket using a hot-wire welding process in such a way that that a pocket with 3 joined side edges and an opening is created. In the collapsed state, the base area of the cover produced in this way is preferably 4×5 cm ² .

According to an equally suitable, alternative embodiment of the method according to the invention, an envelope that has anti-infective properties and has at least one material that is comparatively slowly degradable in the human or animal body is made from PLLA-gelatine blend fibers (PLLA=poly(L-lactide) ) made as follows:

In a first step, a polymer/active substance solution for electrospinning is provided on an xyzelectro spin system. The polymer solution provided is composed of 2-7 wt% poly-L-lactide in a solvent mixture of trifluoroethanol in which 5-15 wt% gelatin has previously been dissolved and chloroform (ratio of 4:1) with the addition of 1-3 % lecithin based on the polymer mass.

After successful homogenization for 6 to 72 hours, the active ingredient dalbavancin (dissolved in trifluoroethanol, 5-20 m% based on the total polymer mass) is added to the solution as an anti-infective.

This solution, which is now a PLLA/gelatine/dalbavancin solution, is then filled into a syringe, this syringe is integrated into the electro-spin system and processed into a fleece using the process parameters listed below.

Process parameters used according to this embodiment: One hour spinning time with a collector-emitter distance of 150-200 mm at a voltage difference of 10-20 kV (collector: emitter) with a controlled rel. Humidity of 20-40% at 22 - 25 °C (room temperature). In this way, a planar fleece approximately 0.1 mm thick is obtained, which is annealed at 60-80° C. for 12 to 24 hours after the spinning process is complete.

To produce a covering suitable for use as an implant pocket, two nonwoven fabrics produced as described above are placed one on top of the other and thermally joined to form a pocket using hot-wire welding methods in such a way that a pocket with 3 joined side edges and an opening is created. In the collapsed state, the base area of the cover produced in this way is preferably 4×5 cm ² .

Due to the use of a cover designed according to the invention or produced with the aid of the method according to the invention, a systemic administration of medication, in particular the preoperative administration of an antibiotic, can be dispensed with. The large surface of the invention used or produced textile material, which is formed from micro and/or nano fibers, also ensures the rapid removal of degradation products that can form during biodegradation and minimizes the resulting potential side effects.

The invention is explained in more detail below, without restricting the general inventive concept, on the basis of specific exemplary embodiments and with reference to figures. show:

Fig. 1: Representation of an inventively designed cover for a

Implant insertable into a human or animal body;

FIG. 2: Sectional view of a covering designed according to the invention with an implant arranged therein; FIG.

Fig. 3: Schematic representation of three for one designed according to the invention

Covering used textile materials with different properties;

Fig. 4: Schematic representation for comparison of the textile material used according to the invention with other textile materials and

Fig. 5: Representation of the introduction of a pacemaker implant in a cover designed according to the invention.

1 shows a cover 1 designed according to the invention for an implant 2 which is suitable for being implanted in a human or animal body. The case 1 shown is a case 1 for a cardiac pulse generator, such as a pacemaker implant, an implantable defibrillator or a resynchronization-plus-defibrillator implant, which is used as an implant 2 in the region of a patient's chest.

It is essential for the casing 1 shown that, after implantation in the body, it releases an anti-infective agent 7, in particular an antibiotic, over a longer period of time and that a pocket 3 suitable for receiving the implant 2 is provided, the wall 4 of which consists of a Fleece material used as textile material 5 is formed with microfibers and/or nanofibers 6, which preferably have a diameter of less than 5 nm. The release of the anti-infective active ingredient 7 over a longer period of time is primarily ensured by the fact that the active ingredient 7 is at least partially arranged in the micro- and/or nano-fibers 6 . The micro- and/or nanofiber fleece material of the cover 1 shown in FIG. 1 is produced by first providing a polymer-active substance solution, which is then processed by electrospinning into a suitable fleece material loaded with active substance. During electrospinning, microfibers and/or nanofibers 6 are continuously produced from the polymer/active substance solution by the rapid evaporation of the solvent in the electric field, with the desired microfiber and/or nanofiber fleece material being deposited on the collector. The advantage of using this process is that practically any polymer can be spun, provided it is soluble in a solvent. It is noteworthy that the micro- and/or nanofiber fleeces produced have a structure which corresponds to or is at least similar to the fibrillar structure of materials of biological origin.

The cover 1 shown in FIG. 1 has a pocket 3 with an opening 8 for inserting an implant, for example a pacemaker unit. According to the exemplary embodiment shown in FIG. 1, the pocket 3 is produced from a micro- and/or nano-fiber fleece mat by first bending over the edges of the spun planar fleece material and then joining them together by welding, gluing or sewing to form seams 12 . According to an alternative embodiment, it is conceivable to produce such a pocket 3 without a joining method, in that the desired pocket shape is produced directly as a 3D shape in a controlled electrospinning process.

The cover 1, in particular the pocket 3, is elastically stretchable in such a way that implants 2 of different sizes or shapes can be inserted into the pocket 3 and the wall 4 of the pocket, which is formed from a micro- and/or nano-fiber fleece material, fits tightly the outer wall of the implant 2 applies.

View “X” in FIG. 1 shows a structural image of the textile material 5 embodied as a micro- and/or nano-fiber fleece, which forms the wall 4 of the pocket 3 of the cover 1 . The structure of the material with randomly intertwined, material-loaded micro- and/or nano-fibers 6 is essential for this material. In addition, the view “Y” in FIG. 1 shows schematically the process of the release of the anti-infective agent 7, in particular an antibiotic, in the patient's body. The anti-infective active substance incorporated into the microfibers and/or nanofibers 6 after the production of the textile material 5 of the pocket 3 is initially released to a large extent (burst release), while the active substance 7 is then continuously released over a longer period of time . In this way, an anti-infective effective level of the active substance 7 in the vicinity of the implant 2 is guaranteed instantaneously, in particular to inhibit bacterial growth and prevent the development of resistance. Long-term effectiveness is then ensured by the sustained release of active ingredients.

FIG. 2 shows a view of the section “AA” drawn in FIG. This sectional view shows the cover 1 with a pacemaker unit inserted therein as an implant 2 . In addition, view “Z” in FIG. 2 shows a detailed view of the interface between the implant 2 and the wall 4 of the pocket 3 of the cover 1 . The micro- and/or nanofiber fleece material, which forms the wall 4 of the pocket 3 as a textile material 5, lies tightly and positively on the surface of the implant 2.

By using electrospinning in the production of coverings 1 for implants 2, either planar micro- and/or nanofiber fleece mats can be produced, from which implant pockets 3 can be produced by shaping and using suitable joining methods such as gluing, sewing or welding. Alternatively, it is conceivable to use cylindrical collectors for the electrospinning process in order in this way to produce micro- and/or nanofiber fleece tubes loaded with active substance, which can then be placed around the implant 2 to be encased.

3 shows, in views a), b) and c), in schematic representations, differently designed textile materials 5 which form the wall 4 of a pocket 3 of a cover 1 designed according to the invention for receiving an implant 2 .

In this context, FIG. 3a) shows the structure of a micro- and/or nano-fiber fleece material with an anti-infective active ingredient 7 incorporated into the micro- and/or nano-fibers 6. In contrast, FIG. 3b) shows an embodiment in which the fleece material has micro- and/or nanofibers 6 with two different properties. The two different microfibers and/or nanofibers 6 differ in that the polymer-active substance solutions used to produce the microfibers and/or nanofibers 6 contained the same polymer, but different active substances 7a, 7b. The microfiber and/or nanofiber fleece material produced in this way therefore has microfibers and/or nanofibers 6 in which different active ingredients 7a, 7b are incorporated.

3c) shows a further possible embodiment of the textile material 5 provided according to the invention. According to this embodiment, the textile material 5 has a micro- and/or nano-fiber fleece material whose micro- and/or nano-fibers 6 were produced from different polymer-active substance solutions, with different polymers 11a, 11b and different active ingredients 7a, 7b were used. In Fig. 4, the structures of three textile materials 5 are shown in views a), b) and c), which are characterized by a different arrangement of the fibers forming the respective textile material 5. Here, FIG. 4a) shows the micro- and/or nanofiber fleece material used according to the invention for the wall 4 of an enveloping pocket 3 as textile material 5. FIG. What is essential for this textile material 5, which was produced by electrospinning, is that the fiber structure is characterized by randomly intertwined micro- and/or nanofibers 6, preferably with a diameter of less than 5 μm but not less than 0.05 μm . In comparison to this, FIG. 4b) shows a textile material 5 which has looped meshes, so that a comparatively coarse-pored meshwork is formed. FIG. 4c) also shows a woven textile material 5 which, in comparison to the textile material according to FIG. 4b), has a finer structure which, however, is also ordered evenly.

As can be seen clearly in FIG. 4, the micro- and/or nano-fleece material used according to the invention is characterized by an unordered fiber structure, which provides suitable mechanical stability, a particular elasticity of a pocket wall 4 of the cover 1 for an implant 2 and also a Surface which, on the one hand, rests true to shape on an implant 2 and, on the other hand, prevents irritation of the adjacent tissue. In addition, the significantly larger surface-to-volume ratio of such a nonwoven material has a positive effect on the release of the active ingredient incorporated into the individual microfibers and/or nanofibers 6 .

5 shows a special area of application for a cover 1 designed according to the invention, which is suitable for accommodating an implant 2 suitable for introduction into a human or animal body, as well as one each in views a), b) and c). State during the insertion of the implant 2 into the casing 1. The implant 2 shown in FIG. 5 is a pacemaker assembly which has connection contacts 9 for attaching electrodes, the opposite ends of which are arranged in the implanted state in the region of the heart.

In the view shown in FIG. 5a), the implant 2 is still completely outside the envelope 1, which, according to the embodiment shown, has a pocket 3 into which the implant 2 is inserted through an opening 8 by the operator. FIG. 5 b ) also shows a state in which the implant 2 with its element 10 to which the connection contacts 9 are attached is already partially inside the pocket 3 of the cover 1 . For this purpose, the operator has slipped the cover 1 with its opening 8 onto the implant 2, whereupon the wall 4 of the cover pocket 3 stretches due to its elasticity and has moved outwards. Fig. 5c) shows the condition in which the implant 2 is implanted in the chest area of a patient and in which it remains within the chest area. The wall 4 of the pocket 3 of the envelope 1, in which the implant 2 is located, is tight and form-fitting on the outer wall of the implant 2, so that it can neither slide out nor out of the pocket 3 and there is no risk of a biofilm forming the surface of the implant 2 consists. Due to the elasticity of the wall 4 of the pocket 3, the cover 1 adapts to the shape and contour of the implant 2 in a particularly suitable manner.

The cover 1 shown in FIG. 5 is produced by electrospinning a planar micro- and/or nano-fleece material loaded with an anti-infective agent 7 and finally a pocket 3 is produced by bending and welding this planar fleece material. The envelope 1 thus produced can be sterilized by the usual sterilization methods, taking into account the durability of both the polymer used and the anti-infective agent 7 incorporated. For implantation, a covering 1 sterilized in this way is slipped over the respective implant 2 used by a surgeon in the operating theater immediately before implementation. Due to the elastic extensibility of the micro- and/or nano-fiber fleece material, the wall 4 of the enveloping pocket 3 forms a form-fitting fit around the implant 2 and can therefore be used at least largely independently of the model.

Reference List

1 serving

2 implant 3 pocket

4 wall

5 textile material

6 micro and/or nanofiber

7 anti-infective agent 7a first anti-infective agent

7b second anti-infective agent

8 opening

9 connection contacts

10 element for attaching the connection contacts 11a first polymer

11b second polymer

12 interface

Claims

patent claims

1. Enclosure (1) for receiving an implant (2), which is suitable for introduction into a human or animal body, with a pocket (3) which is designed to accommodate the implant (2) and the one wall (4) which has at least one textile material (5) which rests at least in regions on the implant (2) in a state in which the implant (2) is at least partially arranged in the pocket (3), characterized in that characterized in that the textile material (5) has, at least in certain areas, micro- and/or nanofibers (6) with a diameter of less than 5 μm, on or in which at least one anti-infective agent (7) is arranged, which in the implanted state is at least temporarily released in the human or animal body.

2. Cover according to claim 1, characterized in that the micro- and/or nano-fibers (6) form at least partially a non-woven layer, a non-woven mat and/or a non-woven hollow body.

3. Cover according to claim 1 or 2, characterized in that the textile material (5) has at least regionally micro- and/or nano-fibers (6) with a diameter of less than 1 μm.

4. Cover according to one of the preceding claims, characterized in that a diameter Df of the micro- and/or nanofibers (6) is in a diameter range of 5 μm>Df>0.05 μm.

5. Cover according to one of the preceding claims, characterized in that the textile material (5) has at least one textile material which can be absorbed or degraded in the human or animal body.

6. Cover according to one of the preceding claims, characterized in that the textile material (5) has at least one biostable textile material

7. Cover according to one of the preceding claims, characterized in that the textile material (5) comprises at least one polymer.

8. Cover according to claim 7, characterized in that the at least one polymer is selected from a group which includes polyester, polyanhydride, polyglycol, polyether, polycarbonate, polysaccharide, polysuccimide, polyamino acid and/or a copolymer and/or has a blend of at least one polymer from this group.

9. Cover according to claim 7, characterized in that the at least one polymer is selected from a group which includes polyurethane, polyamide, polysulfone, polyimide, polyether and polyolefin, and/or a copolymer and/or a blend of at least one Having polymers from this group.

10. Cover according to one of the preceding claims, characterized in that the anti-infective active substance (7) is selected from a group of active substances including aminoglycosides, rifampin, minocylin, daptomycin, cephalosporins, vancomycin, ß-lactams, ampicillin, amoxillin, dalbavancin, gentamicin and octenidine dihydrochloride.

11. Cover according to one of the preceding claims, characterized in that the pocket (3) has an opening (8) on one side and/or is tubular.

12. Cover according to one of the preceding claims, characterized in that the textile material (5) has micro- and/or nano-fibers (6) which have different properties.

13. Cover according to one of the preceding claims with a pacemaker implant, resynchronisation-plus-defibrillator-implant, implantable defibrillator, cochlear implant, aggregate of implantable neurostimulators and/or with an endoprosthesis arranged in this.

14. A method for producing an envelope (1) for receiving an implant (2), which is suitable for introduction into a human or animal body, in which at least one polymer-active substance solution, the components at least one polymer and at least one anti-infective active substance (7) is provided, from the active substance-polymer solution by electrospinning micro- and/or nano-fibers (6) with a diameter which is at least partially smaller than 5 μm, and from the micro- and/or nano-fibers a textile material (5) in the form of a fleece material are produced and in which the fleece material is designed and arranged in such a way that the fleece material at least partially forms a wall (4) of a pocket (3) and in a state in which the implant (2) is at least partially in the pocket (4) is arranged, at least partially applied to the implant.

15. The method according to claim 13, characterized in that at least two polymer-active substance solutions are provided, which differ in at least one of the components used.

16. The method according to claim 11 or 12, characterized in that microfibers and/or nanofibers with a diameter Df in a diameter range of 5 μm>Df>0.05 μm are produced at least temporarily.

17. The method according to any one of claims 11 to 13, characterized in that the at least one polymer is selected from a group consisting of polyester, polyanhydride, polyglycol, polyether, polycarbonate, polysaccharide, polysuccimide, polyamino acid, polyurethane, polyamide, polysulfone, polyimide , Polyether and polyolefin is one and / or has a copolymer and / or a blend of at least one polymer from this group.

18. The method according to any one of claims 11 to 14, characterized in that the anti-infective active ingredient is selected from a group of active ingredients to the aminoglycosides, rifampin, minocycline, daptomycin, cephalosporins, vancomycin, ß-lactams, ampicillin, amoxillin, dalbavancin, gentamicin and octenidine dihydrochloride.