WO2007054117A1

WO2007054117A1 - Medical self-expandable occlusion device

Info

Publication number: WO2007054117A1
Application number: PCT/EP2005/012131
Authority: WO
Inventors: Hans-Reiner Figulla; Susann Klebon; Friedrich Moszner; Robert Moszner; Rüdiger OTTMA
Original assignee: Occlutech Gmbh
Priority date: 2005-11-11
Filing date: 2005-11-11
Publication date: 2007-05-18
Also published as: CA2627196A1; CN101370432A; EP1965706A1; JP2009514625A

Abstract

The invention relates to a medical self-expandable occlusion device for treating heart defects of a patient, especially for closing abnormal holes in the tissue. The occlusion device (1) can be inserted into the body of a patient by means of a catheter system in a minimally invasive manner. The occlusion device (1) consists of an interlaced structure (1) of thin threads, the interlaced structure (10) having a first shape during insertion of the occlusion device into the body of the patient, which shape can be previously determined, and a second shape in the implanted position of the occlusion device, which shape can be previously determined, the occlusion device in the first shape of the interlaced structure (10) being in a folded condition and in the second shape of the interlaced structure (10) being in an expanded condition. The aim of the invention is to provide an occlusion device which can be implanted in as gentle a manner possible for the patient. For this purpose, the threads of the interlaced structure (10) consist of a shape memory polymer composition so that the interlaced structure (10) is deformed under the effect of an external stimulus from a temporary shape to a permanent shape, the temporary shape being the first shape of the interlaced structure (10) and the permanent shape being the second shape of the interlaced structure (10).

Description

"Medical self-expandable occlusion device"

description

The present invention relates to a medical self-expandable occlusion device for treating defects in the heart of a patient, in particular for closing abnormal tissue openings, the occlusion instrument being insertable into the body of a patient in a minimally invasive manner by means of a catheter system and consisting of a braid of thin threads, the braid has a first predeterminable shape during the insertion of the occlusion device into the patient's body and a second predeterminable shape in the implanted state of the occlusion instrument, the occlusion instrument in the first shape of the braid in a folded state and in the second shape of the braid in one expanded state.

Such an occlusion instrument is known, at least in part, from medical technology. For example, DE 10 338 702 dated August 22, 2003 discloses an occlusion instrument for the treatment of septal defects, which consists of a braid of thin wires or threads and is given a suitable shape by means of a shaping and heat treatment process. The well-known occlusal note has a proximal retention area. which is particularly flat, has a distal retention area and a cylindrical web between the proximal and distal retention areas. At the distal retention area the ends of the wires forming the braid converge in a socket. It is provided that the two retention areas of the known occlusion instrument come into contact with a septum on both sides of a shunt to be closed, as a result of a mostly intravascular surgical intervention, while the web runs through the shunt.

In medical technology, efforts have long been made to non-surgeonly close septal defects, such as defects of the atrial septum, by means of a transvenous, interventional access, that is to say without surgery in the actual sense. Various occlusion systems with different advantages and disadvantages have been proposed, without which a particular closure system has so far been able to establish itself. In the following, the various systems are called "occluder" or "occlusion instruments". In all interventional occlusion systems, a self-expanding umbrella system is inserted transvenously over a defect that is to be closed in a septum. Such a system could, for example, consist of two umbrellas, each positioned on the distal side (ie on the side farther from the center or the heart) or on the proximal side (ie on the side closer to the center) of the septum are then screwed into a double umbrella in the septal defect. In the assembled state, the closure system thus usually consists of two open umbrellas, which are connected to one another via a short pin that runs through the defect.

In such occlusion instruments known from the prior art, however, it turns out to be disadvantageous that the implantation procedure is relatively complicated, difficult and complex. Apart from the complicated implantation of the closure system in the septum defect to be closed, there is basically a risk of material fatigue with industry fracture in the umbrellas used. Furthermore, thrombo-bibolic complications are often to be expected.

In order to ensure that the occlusion instrument according to the invention can be inserted by means of an introducer or a guide wire, it is provided that the end of the distal retention area has a socket which can be brought into engagement with the introducer or filler wire. It is provided that the intervention in the defect can be easily released after the occlusion instrument has been positioned. For example, it is possible to grasp the braid at the end of the distal retention area of the occlusion device in such a way that a Internal thread is produced, with which the introducer comes into engagement. Of course, other embodiments are also conceivable here.

In another type of occlusion instrument, the so-called lock clamshell arm system, two steel screens, preferably covered with Dacron, are provided, which are stabilized by four arms each. This type of occluder is implanted through the patient's venous access. With the lock clamshell occluder, however, it has proven to be problematic that the introducer required for the implantation must be made relatively large. Another disadvantage is that other systems, such as. B. Amplatzer occluder, many different occluder sizes are required to meet the respective proportions of the septum defect to be closed. It has been found that the Scbirmcheiα does not flatten out completely when the length or diameter of the web used in the defect does not fit optimally. This leads to incomplete endothelialization. Furthermore, it has been shown that many of the systems implanted in the patient's body have material fatigue and fractures in the metallic structures over a longer period of time due to the considerable mechanical stress. This is particularly the case if there is permanent tension between the implant and the septum.

In order to overcome these disadvantages, self-centering occlusion instruments have been developed which are introduced into the patient's body using minimally invasive procedures, for example via a catheter and guide wires, and inserted into the septal defect to be closed. The design is based on the principle that the occlusion device can be tapered to the size of the introducer or catheter used for intravascular surgery. Such a tapered occlusion device is then inserted via the catheter into the septal defect to be closed or into the shunt of the septal defect to be closed. The occluder then emerges from the catheter, whereupon the self-expanding umbrellas or retention disks unfold, which attach to both sides of the septum. The screens in turn contain, for example, fabric inserts made of Dacron or are spanned by them, which closes the defect or shunt. The ira-plantals remaining in the body are more or less completely enclosed by the body's own tissue after a few weeks to months. An example of a self-centering occlusion device of the type mentioned at the outset and according to the preamble of claim 1 is known from WO 99/12478 A1, which is a further development of the occlusion device known under the name "Amplatzer occluder" according to US Pat. No. 5,725,552 It consists of a braid made from a multitude of fine, braided Nitinol wires in the form of a yo-jos.The braid is produced in its original form as a round braid, which has both its beginning (or its proximal side) and its end When the round braid is further processed, these loose ends must each be gripped and welded in a sleeve. After this corresponding further processing, both the proximal side and the distal side of the finished occlude each have one protruding sleeve into the distal and proximal retention shield u nd Dacron patches are sewn into the bridge between them. Due to the memory effect of the Nitinol material used, the two retention umbrellas unfold independently when leaving the catheter. This is initially done via a balloon-like intermediate stage, the retention umbrellas ultimately taking on either side of the septum finally taking on a more or less flattened shape. The bar centers itself in the shunt to be closed while the umbrella is being opened.

However, it has been shown in the case of the occlusion instruments known from the prior art and previously discussed that the shape memory material nitinol for occlusion instruments has certain disadvantages. Nitinol, which is an equiatomic alloy of nickel and titanium, is only of limited suitability as a shape memory material for use in medical occlusion instruments, since with Nitinol the maximum deformation between the first predetermined shape that is present in the patient's body during insertion of the occlusion instrument, and the second predetermined shape, which is present in the implanted state of the occlusion device, is only about 8%. In other words, the shape memory material Nitinol is only of limited use for folding a medical occlusion device for implantation surgery as small as possible. Accordingly, the implantation intervention when using a medical occlusion device, the braid of which is made of Nitinol, is not particularly gentle for the patient. Furthermore, nitinol as an alloy of nickel and titanium is a permanent foreign body, so that defense reactions of the body may be expected when implanted. On the basis of the problem outlined, which is particularly associated with the use of nitinol as shape memory material for medical occlusion instruments, the present invention is based on the object of further developing a medical self-expandable occlusion instrument of the type mentioned at the outset in such a way that the instrument evolves with implants a treatment procedure that is gentler on the patient.

This object is achieved with a medical self-expandable occlusion instrument of the type mentioned at the outset in that, according to the invention, the threads of the braid consist of a shape memory polymer composition, so that the braid deforms from a temporary shape to a permanent shape under the action of an external stimulus, the Temporary shape in the first shape of the braid and the permanent shape in the second shape of the braid.

The solution according to the invention has a number of significant advantages over the medical occlusion instruments known from the prior art and explained above. In particular, because a shape memory polymer composition has significantly better memory performance than nitinol, a much gentler implantation method is possible when implanting the medical occlusion device. Compared to known shape memory materials such as the shape memory alloy Nitinol, i.e. an equiatomic alloy of nickel and titanium, shape memory polymers are many times superior in terms of their memory performance. Only a little effort (heating or cooling) is required to program the temporary shape or to restore the permanent shape. In addition, with Nitinol, for example, the maximum deformation between permanent and temporary form is only 8%. Shape memory polymers, on the other hand, have significantly higher deformability of up to 1,100%.

The polymer composition according to the invention also has advantages over the prior art with regard to the production method, since conventional processing methods can be used. It would be conceivable, for example, to first bring the polymer into conventional form by conventional processing methods, such as Ouet ExLxUSlOii injection molding. Then kaüii dci KtuisL & loff can be deformed and fixed in the desired temporary shape, which is known as "programming". On the one hand, this process can be carried out with polymers by heating, deforming and then cooling the sample the polymer or plastic is deformed even at a low temperature, which is known as "cold stretching". The permanent shape is thus saved while the temporary shape is currently present. If an external stimulus is now acted on the polymer molded body, it is triggered of the shape memory effect and thus to restore the stored permanent shape. When the ptobe cools down, the temporary shape does not reverse, which is why we speak of a so-called one-way shape memory effect. The original temporary shape - but also one others - can be re-programmed by mechanical deformation again.

Shape memory polymers belong to the group of intelligent polymers (eng. Smart polymers) and are polymers that show a shape memory effect. can change their external shape under the influence of an external stimulus, such as a change in temperature. The previously described process of programming and restoring the form is shown schematically in FIG. 1.

Advantageous further developments of the medical occlusion device according to the invention are specified in the subclaims.

In a particularly preferred implementation it is provided that the external stimulus is a definable switching temperature. It is thus conceivable that in order to trigger the shape memory effect and thus to restore the stored permanent shape of the braid, the molded polymer body must be heated to a temperature higher than the switching temperature. A certain switching temperature can be determined in advance by a suitable choice of the chemical composition of the polymer composition.

For example, the switching temperature is particularly preferably set in the range between the room temperature and the body temperature of the patient. This is particularly advantageous with regard to the area of use of the occlusion device as an implant in a patient's body. Therefore, when implanting the occlusion device, it is only necessary to ensure that the instrument only warms up to the patient's KöipeiLeinperalur (36 ° C) in the implanted state and thus the shape memory effect of the polymer is triggered. In one possible implementation of the occlusion instrument according to the invention, in which the external stimulus is a definable switching temperature, it is provided that the polymer composition has polymer switching elements, the temporary shape of the braid being stabilized below the definable switching temperature with the aid of characteristic phase transitions of the polymer switching elements.

For example, it is conceivable that if the polymer composition has a crystalline or partially crystalline polymer network with crystalline switching segments, the temporary shape of the braid is fixed and stabilized by freezing the crystalline switching segments during the crystallization transition, the switching temperature being determined by the crystallization temperature or switching temperature of the crystalline ones Switching segments is determined.

On the other hand, it is conceivable with a polymer composition such as an amorphous polymer network with amorphous switching segments that the temporary shape of the braid is fixed and stabilized by freezing the amorphous switching segments during the glass transition of the switching segments, the switching temperature being determined by the glass transition temperature of the amorphous switching segments .

According to these preferred further developments, the characteristic phase transitions can be used in the shape memory polymers to stabilize the temporary shape, ie the crystallization in the case of crystalline or partially crystalline polymers and the glass transition in the case of amorphous polymers. Accordingly, in the case of elastic polymers that are made up of covalently crosslinked polymer networks, the mechanism of the shape memory transition is based on the one hand on stabilizing the permanent shape through chemical crosslinking of the polymer chains and on the other hand on fixing the temporary shape through crystallization of segments (partially crystalline polymer networks ) or freezing of the switching segments at the glass transition (amorphous polymer networks). The switching _temperature T _ttans , _above which the shape memory effect is triggered, is therefore dependent on the melting temperature T _m or glass transition temperature T _{g of} the plastic in the corresponding temperature interval.

In Fig. 2 the molecular mechanism of a thermally induced Foinigedäclitnis transition of a partially crystalline polymer network is shown schematically. If the ambient temperature is higher than T _trans (T ₁ J of the crystalline switching segments, these are Segments flexible and can be deformed elastically, for example stretched

The temporary shape formed is fixed by cooling under T _trans (T _m ), ie by the crystalline regions formed on cooling, which act as physical crosslinking points. If the polymer is heated higher than T _trans (T _1n ) again, the permanent shape is restored. The thermodynamic driving force for the restoration of the permanent shape is the entropy gain realized in the process. Analogous to the semi-crystalline polymer networks with shape memory effects, amorphous polymer networks with shape memory effects work, the switching temperature representing the glass transition temperature and the temporary shape being fixed by freezing the mobility of the amorphous switching segments.

In a further advantageous realization or further development of the aforementioned embodiments of the occlusion instrument according to the invention, it is provided that the polymer composition has a linear, phase-segregated multiblock copolymer network, which can be in at least two different phases, the first phase being a hard segment-forming phase, in which a plurality of hard segment-forming blocks are formed in the polymer, which serve for the physical crosslinking of the polymer structure and determine and stabilize the permanent shape of the braid, and wherein the second phase is a switching segment-forming phase in which a multiplicity in the polymer of switching segment-forming blocks are used, which serve to fix the temporary shape of the braid, the transition temperature of the switching segment-forming phase to the hard segment, the phase being the switching temperature, and above the transition temperature the har tsegment-forming phase, the shape of the braid can be adjusted by conventional processes, in particular by injection molding or extrusion processes.

With regard to the chemical composition of the polymer composition from which the braid of the medical occlusion instrument according to the invention is constructed, in a preferred implementation of the occlusion instrument according to the invention, which consists of a braid consisting of a shape memory polymer composition gcbilderr, it can be provided that the polymer composition thermoplastic polyurethane Have elastomers with a multiblock structure, the hard segment-forming phase being obtained by reacting diisocyanates, in particular methylene bis (4-phenyl isocyanate) or hexamethylene diisocyanate, with diols, in particular 1,4-butanediol, is formed, and wherein the Schalttsegment-bilden.de phase consists of oligomeric polyethylene or. Polyester diols, in particular starting from OH-terminated poly (tetrahydrofuran), poly (ε-caprolacetone), poly (ethylene adipate), poly (ethylene glycol) or poly (propylene glycol).

In an alternative but nevertheless advantageous implementation, it is conceivable that the polymer composition has phase-segregated diblock copolymers with an amorphous A block and a partially crystalline B block, the glass transition from the amorphous A block forming the hard segment-forming phase, and the melting temperature of the semi-crystalline B block serves as the switching temperature for the thermal shape memory effect.

In the last-mentioned preferred implementation with regard to the polymer composition, it is advantageously provided that this composition has polystyrene as an amorphous A block and poly (1,4-butadiene) as a partially crystalline B block.

Accordingly, an important group of shape memory polymers are the linear, phase-segregated multiblock copolymers. These polymers have two separate phases, one phase with the higher transition temperature acting as a physical crosslinking and determining the permanent shape. Above this melting temperature, the shaping can be carried out by conventional methods such as injection molding or extrusion. As explained above, the second phase then serves as a molecular switch and serves to fix the temporary shape, the transition temperature of the switching phase (T _ttans ) being a melting or glass transition temperature.

Shape memory polymers based on this principle of action, based on linear block copolymers, include thermoplastic polyurethane elastomers with a multiblock structure.

3 and 4, the hard segment-forming phase is usually achieved by the reaction of commercial diisocyanates such as, for example, methylene bis (4-phenyl isocyanate) (MDI) or hexamethylene diisocyanate (HMDI), with commercial diols. such as 1,4-butane diol. The Ss-nalisegmcnt-forming phase then results from the commercially available oligomeric polyether or polyester diols used, for example starting from OH-terminated poly (tetrahydrofuran), poly (ε-caprolactone), poly (ethylene adipate), poly (ethylene glycol) or poly (propylene glycol). For example, MDI / 1,4-butanediol as the hard segment-forming phase and poly (ε-caprolactone) with a molecular weight of from 1600 to 8000 g / mol result in partially crystalline linear block copolymers with a shape memory effect and a switching temperature of T _1n = 44-55 ⁰ C. In contrast, linear shape memory block copolymers with an amorphous phase and a switching temperature of T _g = -5 to 48 ° C from MDI / 1,4-butanediol as the hard segment-forming phase and more flexible poly (ethylene adipate) with a molecular weight of 300 to 2000 g / mol can be obtained.

As an alternative to the embodiment in which the polymer composition from which the braid of the medical occlusion instrument according to the invention is constructed has a phase-segregated diblock copolymer, it is provided that the polymer composition is a phase-segregated triblock copolymer with a partially crystalline central B block and with two has amorphous terminal A blocks, the A blocks building up the hard segmetite, and the B block determining the switching temperature.

It would be conceivable here that the polymer composition has partially crystalline poly (tetrahydrofuran) as the central B block and amorphous poly (2-methyloxazoline) as the terminal A blocks.

Accordingly, other shape memory polymers which are based on linear block copolymers and which function according to the principle of action described above are the claimed phase-segregated diblock or triblock copolymers. These include, for example, AB block copolymers composed of 34% by weight of polystyrene (PS) as an amorphous A block and 66% by weight of poly (1,4-butadiene) (PB) as a partially crystalline B block.

5 shows the structure of such diblock or triblock copolymers with a shape memory effect. The glass transition from PS is known to be 90 ° C and forms the hard segment-forming phase. The melting temperature of the PB crystallites serves as the switching temperature for the thermal shape memory effect and is between 45 and 65 ° C.

Another example also shown in FIG. 5 are ABA triblock copolymers of partially crystalline poly (tetrahydrofuran) (PTHF) as the central B block and amorphous poly (2-methyloxazoline) (POX) as terminal A blocks. Blocks with an average molecular weight of 1500 g / mol have a glass transition temperature of 80 ° C and build up the hard segment. The B block with a molecular weight between 4100 and 18800 g / mol is partially crystalline and, depending on the molecular weight, melts between 20 and 40 ° C. The switching temperature can be varied in this range.

With regard to the chemical composition of the polymer composition used in the medical occlusion device according to the invention, it has been found that the polymer composition advantageously comprises polynorbornene, polyethylene-nylon-6 graft copolymers and / or crosslinked poly (ethylene-co-vinyl acetate) copolymers.

It has also proven to be advantageous if the polymer composition has a covalent crosslinked polymer network which is built up by polymerization, polycotidation and / or polyaddition of difunctional monomers or macromers with the addition of trifunctional or higher functional crosslinkers, with a suitable selection of the monomers, whose functionality and the proportion of crosslinker the chemical, thermal and mechanical properties of the polymer network formed can be specifically adjusted. It is thus possible to precisely define the properties of the occlusion device in advance during the transition from the first shape which can be predetermined to the second shape which can be predetermined. In particular, the sequence of events when expanding the occlusion device can be precisely defined in advance.

In a particularly preferred implementation of the last-mentioned embodiment, it is provided that the polymer composition is a covalent polymer network which is built up by crosslinking copolymerization of stearyl acrylate and methacrylic acid with N, N'-methylenebisacrylamide as crosslinker, the shape memory effect of the polymer composition on crystallizing stearyl side chains is based.

It is also conceivable that the polymer composition has a covalently cross-linked polymer network, which is formed by subsequent cross-linking of linear or branched polymers.

It would be conceivable, for example, for the crosslinking to be triggered by ionizing radiation or by thermal cleavage of radical-forming groups.

Accordingly, a large group of shape memory polymers form the covalently cross-linked polymer networks mentioned above. When building them, two different synthesis strategies are advantageously followed: a) Polymerization, polycondensation or polyaddition of difunctional monomers or macromers with the addition of trifunctional or higher functional crosslinkers. The chemical, thermal and mechanical properties of the polymer network formed can be set in a targeted manner via the suitable selection of the monomers, their functionality and the proportion of crosslinking agent.

b) A second synthesis variant for covalent shape memory polymer networks consists in the subsequent crosslinking of linear or branched polymers. The density of crosslinking is strongly dependent on the chosen reaction conditions. The crosslinking is usually triggered by ionizing radiation or by the thermal cleavage of radical-forming groups. For example, polyethylene films with heat shrink properties are obtained by irradiating polyethylene with γ-steels, or crosslinked polyethylene-polyvinyl acetate copolymers with a shape memory effect are obtained by kneading in the free radical initiator dicumyl peroxide.

6 shows possible monomers for covalent shape memory polymer networks. Thus, covalent polymer networks with Shape Memory Effect by crosslinking copolymerization of stearyl acrylate and methacrylic acid MAA STA with N, N-methylenebisacrylamide MBA ^V are obtained as a crosslinking agent, for example, the shape memory effect is based on the crystallizing stearyl. Depending on the stearyl acrylate content, a melting or switching temperature of between 35 and 50 ^° C. results.

In summary, it should be noted that the two basic types of shape memory polymers, ie thermoplastic elastomers and covalent polymer networks, differ in their properties, processing and programming processes. The thermoplastic elastomers require a minimum proportion by weight of the hard segment-forming polymer chains in order to ensure the physical network points. In the case of covalent networks, this proportion of hard segment-forming polymer chains can be higher. It is of course conceivable that the potential applications of the shape memory polymers described can extend over wide areas of technology, for example from self-repairing car bodies, switching elements, sensors to intelligent packaging. All of the aforementioned shape memory polymers are claimed according to the invention for biomedical applications of the occlusion instruments mentioned at the beginning. The use of biodegradable shape memory polymers is also claimed, which will be described in more detail below.

In particular, synthetically biodegradable implant materials are of interest for use in medical occlusion instruments. Degradable materials or polymers contain cleavable bonds under physiological conditions. One speaks of biodegradability if the material is degraded by or in a biological system while losing its mechanical properties. The external shape and mass of the implant may be retained during dismantling. If one speaks of a degradation time without additional quantifying information, it means the time in which the complete loss of the mechanical property occurs. Biostable materials are those that are stable in biological systems and that are at least partially degraded in the long term.

According to the invention, it is provided that the medical occlusion instrument of the type mentioned at the beginning and according to the preferred developments mentioned above consists of a braid which is constructed from a polymer composition which has at least one biodegradable material.

In a particularly preferred implementation of the last-mentioned further development, it is provided that the polymer composition has a hydrolytically degradable polymer, in particular poly (hydroxycarboxylic acids) or corresponding copolymers. The advantage of hydrolytic degradation is that the rate of degradation is independent of the location of the implantation, since water is everywhere.

In a further development, however, it is conceivable that enzymatically degradable polymers are used. In particular, it is conceivable that the polymer composition has a biodegradable thermoplastic amorphous polyurethane copolyester polymer network.

It is also required for the medical occlusion instrument for the chemical composition of the polymer composition that the polymer composition has a biodegradable elastic polymer network which is obtained by crosslinking oligomeric diols with diisocyanate. Alternatively, it is conceivable that the polymer composition is based on covalent networks starting from oligo (ε-captolactone) dimethacrylate and butyl acrylate.

With the present invention, both hydrolytically and enzymatically degradable polymer compositions are claimed for the braid from which the occlusion instrument according to the invention is constructed with regard to the degradable polymers. As already mentioned, hydrolytic degradation has the advantage that the rate of degradation is independent of the location of the implantation. In contrast, the concentration of enzymes is very different locally. In the case of biodegradable polymers or materials, the degradation can take place by pure hydrolysis, enzymatically induced reactions or by a combination thereof.

Typical hydrolyzable chemical bonds that can be contained in the polymer composition of the occlusion device are amide, ester or acetal bonds. There are two mechanisms observed during dismantling. During surface degradation, the hydrolysis of chemical bonds takes place exclusively on the surface. Due to the hydrophobic character, the polymer degradation is faster than the diffusion of water into the interior of the material. This mechanism is observed particularly in the case of poly (anhydrides) n or poly (orthoesters) n.

For the poly (hydroxycarboxylic acids), such as poly (lactic acid) or poly (glycolic acid) or corresponding copolymers, which are particularly important for the present invention, the polymer is degraded in the entire volume. The rate-determining step here is hydrolytic bond cleavage, since the diffusion of water in the rather hydrophilic polymer matrix takes place relatively quickly.

It is crucial for the use of biodegradable polymers that on the one hand they degrade at a controllable or adjustable speed and on the other hand the degradation products are non-toxic.

The term resorption of a polymer material refers to the decomposition of the substance or the mass up to the complete removal of a material from the body via the natural metabolism. In the case of homogeneous implants (occlusion instruments) made from only one degradable polymer, absorption begins from the point in time when the mechanical properties are completely lost. The information The resorption time covers the period from the implantation to the complete elimination of the implant.

The most important biodegradable synthetic polymer classes from which the braid of the occlusion device according to the invention are advantageously formed include:

Polyesters, such as poly (lactic acid) PLA, poly (glycolic acid) PGA, poly (3-hydroxybutyric acid) PBA, poly (4-hydroxyvaleric acid) PVA or poly (ε-caprolaton) PCL or corresponding copolymers.

Polyanhydrides, which are formed from dicarboxylic acids such as, for example, glutar-PAG, amber-PAB or sebacic acid PAS. Poly (amino acid) n or polyamides such as poly (serine ester) PSE or poly (aspartic acid) PAA (Fig. 9).

FIG. 7 shows examples of biodegradable polyesters, while FIG. 8 shows examples of biodegradable polyanhydrides, poly (amino acid) or polyamides.

In summary, it should be noted that shape memory properties play a major role in implants, particularly in minimally invasive medicine. Degradable implants with shape memory properties are particularly effective. Such degradable implants can, for example, be introduced into the body in a compressed (temporary) form through a small incision, where they take on their stored, application-relevant shape after heating to body temperature. The implant is removed after a predetermined time; a second operation to remove it can thus be omitted.

Structural elements for the construction of biodegradable shape memory polymers can be derived on the basis of the known biodegradable polymers. Suitable network points that fix the permanent shape and network chains that serve as switching elements must be selected so that on the one hand the switching temperature can be achieved through the physiological conditions, and on the other hand toxicological problems of the possible degradation products must be excluded. ^• So let ausgelifciiu on the thermal properties of the already known degradable implant materials suitable switching segment for biodegradable shape memory polymers Select. A thermal transition of the switching elements in the range between room temperature and body temperature is of particular interest. For this The transition temperature range allows biodegradable polymer segments to be specifically tailored by varying the stoichiometric ratio of the known starting monomers and the molecular weights of the polymers formed in the range from approximately 500 to 10,000 g / mol.

Suitable polymer segments are for example poly (ε-caprolactone) diols with melting temperatures of 46-64 ⁰ C or amorphous copolyesters based on lactic and glycolic acid with glass transition temperatures between 35 and 50 ⁰ C. The phase transition temperatures can be, that the melting or glass transition temperature further reduce the polymeric switching segments with their chain length or end groups determined by the installation. The polymer switching elements tailored in this way can then be incorporated into physically or covalently networked polymer networks, resulting in the specifically designed biodegradable shape memory polymer material.

In one possible implementation, biodegradable thermoplastic amorphous polyurethane copolyester polymer networks with shape memory properties are used as the material for the occlusion instrument according to the invention. Suitable biodegradable star-shaped copolyester polyols based on commercially available Dilactid DL (cyclic lactic acid dimer), Diglyocolid DG (cyclic.es glycolic acid dimer) and Trimethylolpropane TP (functionality F = 3) or Pentaerythritol PE (F = 4) with glass transition temperatures between 36 and 59 ⁰ C produced, which are then crosslinked with the commercial trimethylhexamethylene diisocyanate TMDI to form a biodegradable polyurethane network.

9 shows, for example, monomer components for amorphous polyurethane copolyester polymer networks with shape memory properties.

The amorphous polyurethane-copolyester-polymer networks formed with shape memory properties show a glass transition temperature T _g between 48 and 66 ° C with a tensile modulus of elasticity between 330 and 600 MPa or tensile strength between 18.3 and 34.7 MPa. By heating these networks about 20 ⁰ C above this switching temperature, rubber-elastic materials are formed, which can be deformed between 50 and 265% to a temporary shape. By cooling to room temperature, deformed polymer dyes were formed, which showed a significantly higher tensile modulus of elasticity from 770 to 5890 MPa. In this way, deformed samples were produced which, when heated again to 70 ^° C., had changed back into the corkscrew-like permanent shape after approx. 300 s. Finally, it could be demonstrated, the polyurethane copolyester polymer networks that in an aqueous phosphate buffer at 37 ⁰ C übet a period of between about 80 and 150 days can completely degrade. By optimizing the composition of the biodegradable switching segments, biodegradable polyurethane copolyester polymer networks with shape memory properties can be produced much faster, for example within 14 days.

Analogous biodegradable elastic shape memory polymer networks could be obtained by crosslinking oligomeric diols with the diisocyanate TMDI, which show melting temperatures between 38 and 85 ° C, and which are also suitable for the occlusion device according to the invention. A fiber was made from these materials and stretched by 200% into a temporary longer fiber, from which a loose knot was formed. After fixing the two ends of the knot and heating the knot to 40 ^° C., ie higher than the switching temperature, the knot pulled itself back into half the permanent length after approx. 20 s due to the transition of the thread. Finally, the degradability was also investigated, a 50% loss in mass being found after approximately 250 days in an aqueous phosphate buffer at 37 ° C. for these polymers.

In one possible implementation of the occlusion instrument according to the invention, the braid is formed from a biodegradable shape memory polymer based on covalent networks based on oligo (ε-caprolactone) dimethacrylate and butyl acrylate. It has been shown that this polymer composition has no negative influence on wound healing after subcutaneous implantation. The synthesis of these biodegradable shape memory polymers can be carried out starting from n-butyl acrylate, which can be used from -55 ⁰ C as the soft segment-forming component because of the low glass transition temperature of pure poly (n-butyl acrylate).

Figure 10 shows monomer components for covalent biodegradable networks. The biodegradable segments were installed here via the crosslinker oligo (ε-caprolactone) dimethacrylate. The network was synthesized by photopolymerization. The switching temperature and the mechanical properties of the covalent Neti-wciLca can be controlled via the molecular weight of the macromolecular oligo (ε-caprolactone) dimethacrylate and the content of comonomer n-butyl acrylate. Thus, in a realization of the solution according to the invention, the molar mass of the oligo (ε-caprolactone) dimethacrylate was varied between 2000 and 10000 g / mol and the n-butyl acrylate content was between 11 and 90 mass%. With a polymer network based on a mixture of low molecular weight oligo (ε-caprolactone) dimethacrylate with 11 mass% of n-butyl acrylate was realized a melting point of 25 ⁰ C.

The biodegradable covalent and physical polymer networks with shape memory effect described above can also be used as a matrix for a controlled release of active ingredient. Biodegradable polyurethane multiblock copolymers with a memory effect based on poly (p-dioxanone) PDO as a hard segment and TMDI as a diisocyanate would also be conceivable.

Figure 11 shows polymer segments in biodegradable poly (p-dioxanone) polyurethane multiblock copolymers. By combination with the switching segments poly (lactide-co-glycolide) PDLG or poly (ε-caprolactone) PCL multiblock copolymers to give having a switching temperature of 37 or 42 ⁰ C. The hydrolytic degradation of the polymers indicates that the polymers based on degrading less from PCL. For example, in an experiment with PCL polymers after 266 days of hydrolysis, 50 to 90% of the mass used was still present, while with PDLG polymers after 14 days, 14 to 26% was detectable.

It can be stated that by combining physical or covalent shape memory polymer networks with biodegradable polymer segments, biodegradable shape memory polymer networks can be produced. Through targeted selection of the components, the optimal parameters for the respective application, such as the mechanical properties, the deformability, the phase transition temperatures and above all the switching temperature, and the rate of degradation of the polymers can be set.

All of the aforementioned biodegradable shape memory polymers are claimed according to the invention as material for the occlusion device.

With regard to the shape of the medical occlusion instrument according to the invention, it is advantageously provided that the second predetermined shape of the occlusion instrument is designed to close an abnormal tissue opening in the heart of the patient, with the occlusion instrument in its expanded state of proximal retention area, a distal retention area and has an intermediate area, the occlusion device having a smaller diameter at the central area than at the proximal and / or distal retention area. The advantage of this embodiment can be seen in particular in the fact that an intravascular occlusion instrument is specified which is particularly suitable for the treatment of septum defects, patent foramen ovale defects and persistent ductus arteriosus defects, the occlusion device being suitable for delivery via a catheter system suitable for the defect to be sealed.

Among the septal defects are atrial septal defects (ASD), i.e. a hole in the atrial septum of the heart, and ventricular septal defects (VSD), i.e. a hole in the chamber septum to understand.

A patent foramen oval defect (PFO) is an oval opening (slit) in the atrial septum of the heart, which usually closes by gluing the backdrop-like edges after the birth, although in about 25% of the births an imperfect gluing (Persistence) is present, so that an open oval foramen remains.

The term "persistent ductus arteriosus defect" (PDA) is to be understood as an open duct between the aorta and pulmonary artery, which normally closes after birth.

The primary object of the present invention is to produce a reliable, simple heart occlusion device which is shaped to include perforating ovary (PFO), atrial septal defect (ASD), ventricular septal defect (VSD) and patent duct Arteriosus (PDA) can be treated in such a way that the braid, which - as already described - is made up of a shape memory polymer or a biodegradable shape memory polymer, is replaced.

When the second pre-definable shape of the medical occlusion device is formed from the braid made of a polymer composition, there are a large number of flexible strands or threads, the threads being braided in such a way that an elastic material results therefrom. This braided fabric is then deformed to conform to a molded surface of a molded element. The braided fabric is placed on the surface of the molding and is heat-treated at an elevated temperature. The duration and temperature of the heat treatment is chosen so that the braided fabric retains its deformation. After the heat treatment, the braided fabric is removed from the shaped element again and retains it its deformation. The braided tissue treated in this way corresponds to the second predetermined (expanded) form of the medical occlusion device, which, when folded, can be inserted into a path in the patient by means of a catheter system.

Embodiments of the present invention provide special forms for medical devices which can then be made according to the present invention to be used in certain medical cases. The devices have an elongated flat shape and can be provided with retracted clips which can be attached to one end of the introducer or a guidewire to retract the device after insertion. In use, a catheter is inserted and inserted into the patient's body until the distal end of the catheter comes to lie exactly next to the point that requires physiological treatment. A pre-selected medical device according to the present invention in a predetermined second shape is then folded and inserted into the opening of the catheter. The device is pushed through the catheter and exits at its distal end, where, thanks to its memory, it springs back into its original expanded shape next to the area to be treated. The guidewire or guide catheter is then released from the clamp and then retracted.

Preferably, the occlusion device in its second predetermined shape has an elongated shape, with a tube as the central part and an extended diameter part at each end of this central part. The thickness of the middle part corresponds approximately to the wall thickness of the organ to be closed, for example the thickness of the partition.

The center of at least one extended diameter part (proximal or distal retention area) can be offset relative to the center of the middle part. This allows a membranous ventricular septal defect to be closed while using a retainer that is large enough to securely close the abnormal opening in the septum. Each braided end of the device is held by a clip. These clips are drawn into the expanded diameter parts of the device, reducing the overall length of the device and creating a smooth locking mechanism. In another application, the device looks like a bell with an elongated body, a tapered and a larger end piece. The larger end has a disc made of fabric which, when unfolded, generally comes to rest perpendicular to the axis of the channel in which the device is unfolded. The brackets that hold the braided ends together are drawn into the center of the "bell", creating a smooth device with a low overall height.

Because the proximal retention area of the braid in a particularly preferred embodiment has a shape that is open to the proximal end of the occlusion device, it can be achieved in a particularly advantageous manner that the occlusion device - regardless of the proportion of the diameter of the defect to be closed and regardless of the pound Thickness of the septum wall - adjusts itself to the defect in the septum wall, in such a way that on the proximal side of the defect no parts of the occlusion device protrude beyond the plane in which the septum wall with the defect lies. The usual complications associated with this no longer occur. In terms of what is expressed, this means that the occlusion instrument used is completely enclosed by the body's own tissue much faster than in the closing systems known from the prior art. The use of a braid made of thin threads as the starting material for the occlusion device according to the invention derives the further advantage that it has long-term mechanical stability. This largely prevents the occurrence of breaks in the structure of the implant used. The braid also has sufficient rigidity. The shape of the proximal retention area of the braid, which is open towards the proximal end, additionally allows the proximal retention area of the instrument to flatten completely at the edge of the defect in the inserted state, and this is almost independent of the diameter of the defect and the thickness of the septum wall. Accordingly, the occlusion device can be used over a wide range of septum defects of different sizes. Because there is no need for a socket for bundling or summarizing the braid at the proximal retention area, no component of the occlusion device protrudes beyond the septum wall, so that constant blood contact with components of the implant can be prevented. This has the advantage that the body's defense reactions and no trombenboli & cLen complications are to be feared.

In a particularly preferred embodiment it is provided that the center of the proximal and / or distal retention area is offset relative to the center of the center area is. This allows a membranous ventricular septal defect to be closed using a restraint device that is large enough to safely close the abnormal opening in the septum. It can be provided that each braided end of the occlusion device is held by a clip. This clip is inserted into the expanded diameter parts (proximal and distal retention area) of the occlusion device, reducing the overall length of the occlusion device and creating a smooth locking mechanism.

In an advantageous further development of the second shape of the occlusion device that can be predetermined, it is provided that in the expanded state the inner surface of the proximal and / or distal retention area has a concave shape. This allows the expanded occlusion instrument to be positioned particularly well in the defect to be closed. It is particularly preferably provided that the braid from which the occlusion device according to the invention is made can be tapered in the first form which can be determined in advance to the diameter of a catheter system used in the intravascular surgical procedure. This makes it possible to insert the occlusion device to close the defect by inserting the catheter, for example through a vein, so that an operation in the actual sense is no longer necessary. If the braid is made of the shape memory polymer material, as explained above, the occlusion instrument, which is tapered to the diameter of the catheter, is a "self-expanding instrument", which unfolds automatically after exiting the catheter, so that it unfolds The construction of the occlusion device according to the invention from the coherent mesh also makes it possible for the occlusion device to have a self-expanding and self-positioning closure system in which the occurrence of permanent occurs mechanical tensions between the occlusion instrument used and the septum wall can be prevented, as a possible realization that the proximal retention area of the braid has an open tulip-shaped shape towards a proximal end.

It would also be conceivable that the proximal retention area has a bell-shaped shape that is open toward the proximal end. Accordingly, the occlusion device can be used to treat various defects, in particular the ventricular septal defect (VSD), atrial septal defect (ASD) and persistent patients Ductus Arteriosus Butali (PDA) can be used, whereby an optimal shaping of the proximal retention area can be chosen for a variety of defects of different sizes and types. Of course, other shapes are also conceivable here, such as a dumbbell-like shape. In order to enable the retention areas of the expanded occlusion device to be put on particularly well, it is advantageously provided that the length of the central part is dimensioned such that the peripheral edge of the distal or proximal retention area overlaps the peripheral edge of the other retention area.

In a particularly preferred further development of the occlusion instrument according to the invention it is provided that the proximal and / or distal retention area has a recess in which the holder is arranged, in which the ends of the braid converge. By arranging the holder in the depression provided at the proximal or distal end of the occlusion device, no components of the occlusion device protrude beyond the septum wall, so that constant blood contact with components of the implant can be prevented. This has the advantage that the body's defense reactions and no trombebolic complications are to be feared. In particular, because the occlusion device is positioned and fixed independently in the defect, whereby the distal and proximal retention area can be prestressed in the radial direction, the occlusion device can be used over a wide area under differently sized defect openings.

In a particularly preferred further development of the occlusion instrument according to the invention, in which the distal retention area has a depression, it is further provided that a connection element is further arranged in the depression at the distal end of the occlusion instrument, the connection element being engageable with a catheter. With this connecting element, which is arranged on the occlusion device in such a way that it does not protrude beyond the septum wall, as a result of which constant blood contact with components of the implant can be prevented, the occlusion device according to the invention also has the functionality of retrievability. On the other hand, a connecting element, which can be brought into engagement with a catheter, facilitates the implantation and positioning of the occlusioflsin instrument (folded during the implantation process) in the defect to be closed. Different devices can be used as connecting elements. For example, latching links or hooks would be conceivable or eyelets that can be non-positively connected with correspondingly complementary connecting elements of a catheter.

In a further advantageous development, it is provided that the occlusion device is designed to be reversibly foldable and unfoldable, so that the expanded state of the instrument can be folded, for example with the aid of an explantation catheter. It is conceivable that for explantation, a catheter engages, for example, on a connecting element formed at the distal end of the occlusion device, and the occlusion device is folded up by external manipulation with the aid of the catheter. The occlusion device is thus completely reversibly retractable into the catheter, which enables the instrument to be removed completely.

Finally, it is particularly preferably provided that the occlusion device has at least one tissue insert, which is arranged in or on the distal retention area or in the center area of the occlusion device to completely close the defect. This tissue insert serves to close the gaps in the defect in the middle area and in the widening diameters of the occlusion device after the insertion and expansion of the instrument. For example, the tissue insert is attached to the braid of the occlusion device at the distal retention area in such a way that it can be stretched over the distal retention area like a cloth. The advantage of this construction is that the edge of the distal retention area lies flush against the septum opening and less foreign material is introduced into the patient's body. The fabric inserts can be made from Dacron, for example. Of course, other materials and other positions of the tissue insert in or on the occlusion device are also conceivable here.

In the following preferred embodiments of the inventive occlusion device are explained in more detail with reference to the drawings.

Show it:

Fig. 1 is a schiiiiiüsclie DäisLellung the shape memory effect; 2 shows a schematic representation of the molecular mechanisms taking place during the shape memory transition of a partially crystalline polymer network;

3 is a synthesis scheme of thermoplastic polyurethane multiblock

Copolymers;

4 shows a chemical structure of monomer components for thermoplastic polyurethane multiblock copolymers;

5 shows a structure of diblock or triblock copolymers with

Shape memory effect;

6 is a representation of monomers for covalent shape memory

Polymer networks;

7 shows an example of biodegradable polyesters;

Fig. 8 examples of biodegradable polyanhydrides, poly (amino acid) or

Polyamides;

9 monomer components for amorphous polyurethane copolyester

Polymer networks with shape memory properties;

Fig. 10 monomer components for covalent biodegradable networks;

11 polymer segments in biodegradable poly (p-dioxanone) polyurethane

Multiblock copolymers;

Fig. 12a, b is a side view and a spatial view of a PFO occlusion device from. Type 1;

13a, b show a spatial representation of a PFO occlusion instrument of type I;

14 is a side view of a PFO type 2 occlusion device; 15 is a side view of a Type 3 PFO occlusion device;

16 is a top view of a Type 3 PFO occlusion device;

17a, b show a stylized side view and sectional illustration of a PFO occlusion device of type 4;

18a shows an enlarged partial view of a section through an occlusion instrument for closing an atrium septal defect (ASD) of type 1 (ASD occlusion instrument type 1); the occlusion device is stretched and partially protrudes from the opening of an insertion catheter;

18b is an enlarged partial view of a section through an ASD

Type 2 occlusion device in a classic design;

18c is an enlarged partial view of a section through an ASD

Type 3 occlusion device, the polymer fibers are thermally bundled in the left atrial arch;

18d is an enlarged partial view of a section through an ASD

Type 4 occlusion device, with a type of braiding comparable to type 1 (FIGS. 19 to 21);

FIG. 19a shows a front view of the type 1 ASD occlusion instrument according to FIG. 18a in its preformed shape; FIG.

FIG. 19b shows the ASD occlusion instrument according to FIG. 19a in a slightly elongated shape;

19c shows a side view of the ASD occlusion instrument according to FIG. 19a in a further elongated form;

20a shows a front view of an ASD occlusion instrument of type 2 according to FIG. 18b in its preformed shape; FIG. 20b shows the ASD occlusion instrument according to FIG. 20a in a slightly elongated form;

20c shows the ASD occlusion instrument according to FIG. 20a in a further extended shape;

FIG. 21a shows a front view of the type 3 ASD occlusion instrument according to FIG. 18c in its preformed shape; FIG.

FIG. 21b shows the side view of the ASD occlusion instrument according to FIG. 21a in a slightly elongated shape;

FIG. 21c shows a side view of the ASD occlusion instrument according to FIG. 21a in a further slightly elongated form;

FIG. 22a shows a front view of the type 4 ASD occlusion instrument according to FIG. 18d in its preformed shape; FIG.

FIG. 22b shows a side view of the ASD occlusion instrument according to FIG. 22a in a slightly elongated shape;

FIG. 22c shows a side view of the ASD occlusion instrument according to FIG. 22a in a further slightly elongated form;

23 is a partial view of a section from the side through the ASD

21 in the ASD of a heart;

24 is an enlarged front view of an occlusion device for the

Sealing a VSD in its preformed shape;

FIG. 25 shows a side view of the VSD occlusion instrument according to FIG. 24;

26 is a partial view of a section from the front through the VSD

Occkisicnsinstrαmcnt according to FIG. 24;

27 shows a flat view from above of the VSD occlusion device according to FIG

Fig. 24; 28 shows a flat view from below of the VSD occlusal device according to FIG

Fig. 24;

29 is an enlarged front view of another VSD.

Occlusion instruments in its preformed shape;

30 is a partial view of a section from the side through the VSD

Occlusion instrument according to FIG. 29;

31 is an enlarged front view of another VSD.

Occmsioßsmstniments in its preformed shape;

32 is a partial view of a section from the side through the VSD

Occlusion instrument according to FIG. 31;

33 is an enlarged front view of another VSD or PDA.

Occlusion device in its preformed shape;

Fig. 34 is a partial view of a section from the side through the VSD or

PDA occlusion device according to FIG. 33;

Fig. 35 is a perspective view of a medical

Occlusion device according to the present invention;

36 shows a side view of the occlusion instrument according to FIG. 35;

37 shows a top view of the occlusion instrument according to FIG. 35;

Fig. 38 is a partial view of a section through a shaped element, as for

35 of the occlusion device is used;

39 is a perspective view of a medical

Occlusion instrument according to the present invention, the corresponding sleeve being omitted in the proximal region compared to the occlusion instrument according to FIG. 35; FIG. 40 shows a perspective partial view of a section through the heart with the occlusion instrument according to FIG. 35, which was deployed in a central shunt in the patient's blood vessel;

41 is an enlarged front view of an occlusion device used in occluding a PDA;

42 is a partial view of a section through the PDA

Occlusion instrument according to FIG. 41;

43 shows a top view of the PDA occlusion instrument according to FIG. 41;

FIG. 44 shows a plan view from below of the PDA occlusion instrument according to FIG. 41; and

45 shows a PDA occlusion instrument in the insertion catheter.

The present invention includes a percutaneous catheter-guided occlusion device ("occlusion device"), which serves to close abnormal openings, such as, for example, atrial septal defects (ASD, PFO), ventricular septal defects (VSD), patent ductus arteriosus (PDA) and the like. The present invention further provides a method for forming a medical device with a flat or tubular plastic or polymer fabric.

Both the flat and tubular fabrics are composed of a plurality of strands of wire, with a predetermined relative orientation between the strands. The tubular fabric has plastic strands that delimit two sets of substantially parallel spiral strands, the strands of one set having a direction of rotation opposite to that of the other strand. This fabric is also called tubular mesh in industry.

The braided form is primarily used for the device forms PFO, type 2 (FIG. 14) and type 3 (FIG. 15), the wires or threads of the proximal arches being thermally grasped at the proximal end 2, in one element, which is referred to as a "thermal socket". The wires are welded together under the influence of thermal energy. Likewise, tubular fabric 10 is used in the device forms ASD, type 2 (FIG. 18b, and FIGS. 20a to 20c) and type 3 (FIG. 18c, FIGS. 21a to 21c), furthermore for the device forms VSD (Fig. 24, Fig. 25, Fig. 26), the device form according to Fig. 35 and Fig. 39 and finally for the PDA device according to Fig. 41.

Using the braiding method developed by JEN.meditec GmbH in accordance with the German patent application No. 10 338 702 from August 22, 2003 mentioned at the outset, further preferred device forms result, which in particular show material savings and the material braided by this method has flatter end forms in the PFO- and ASD devices. The medical devices made with this braiding method include the device forms PFO, Type 1 (Figures 12a, b and 13a, b) and Type 4 (Figures 17a, b) and ASD Type 1 (Figures 18a, 19a) to 19c) and type 4 (Fig. 18d, Fig. 22a to 22c).

The slope of the plastic strands and the weft (i.e. the number of bends per length) as well as other factors such as the number of wires used in the tubular braid are essential for determining a number of important properties of the device. The denser the weft and the inclination of the fabric 10, that is, the denser the plastic strands are interwoven, the stiffer the device. A larger wire density means a larger wire surface, which increases the sealing capacity of the device. This thrombogenesis can either be increased, e.g. by a thrombolytic coating, or reduced, e.g. thanks to an anti-thrombolytic coating that increases lubricity.

When forming a device 1 according to the invention presented here, a correspondingly large piece of tubular or flat plastic fabric 10 is inserted into a press mold, the fabric 10 adapts to the cavities in the shape. These cavities are shaped so that the plastic fabric 10 takes the shape of the desired device. The ends of the plastic strands of the tubular or flat plastic fabric 10 should be secured to prevent separation. For this purpose, a clip can be used (e.g. PFO and ASD devices of type 2, as described above) or the ends of the plastic strands are thermally treated or welded (e.g. PFO and ASD devices Type 3). In the case of a tubular braid, a shaped element can be inserted into the tube of the braid before the braid is inserted into the press mold. This defines the mold surface even more precisely. If the ends of the tubular plastic fabric have already been clamped or welded, the shaped element can be inserted manually into the tube by bending the plastic strands of the fabric 10 apart. The final size and shape of the device can be controlled quite accurately with the help of such a molding element, by ensuring that the tissue conforms to the cavity of the shape.

A material that can be comminuted or removed from the interior of the plastic fabric can be selected for the shaped element. The shaped element can e.g. be made of a brittle or crumbly material. After the heat treatment of the material in the mold cavity with the molding element, the molding element is broken up into small pieces that can be easily removed from the plastic fabric.

As a rule, however, tools (form elements) can be used for all of the medical devices described here, which precisely define the shape of the medical devices by means of an outer shell (which can be broken down into various individual parts). Since the medical devices consist of plastics which have a melting point below 350 ° C., the mold elements can be made of aluminum, tool steel, non-ferrous metal or also titanium or titanium alloys.

However, it should be noted that the specific shape of a particular feature creates a specific shape, and that other features with other configurations can be used as desired. If a complex shape is desired, the shaped element and the mold can have additional parts, including a cam connection. The mold may have fewer parts for simpler shapes. The number of parts in a given mold and their shape depend almost exclusively on the shape of the desired device, to which the plastic fabric will adapt. In their relaxed form, the plastic strands of the tubular braid assume a predetermined relative orientation to one another. If the Röhrcagεflecht zusäiriineiigtprcsat along bcinci A _^ HSE, the tissue tends to expand away from the axis corresponding to the shape of the mold. The relative orientation of the wire strands of the plastic fabric changes in the deformed fabric. When assembling the press mold fits the plastic fabric on the mold surface of the cavity. The device has a predetermined expansion configuration and a collapsed configuration so that it can be inserted through a catheter or similar guiding device. The expansion configuration is determined by the shape of the fabric after it has been formed by the surface of the die.

If the tubular or flat plastic fabric is inserted into the selected mold, the fabric laying against the surface of the cavities in the mold, the heat treatment is carried out. The tissue 10 remains in shape. The wire strands of the plastic fabric are realigned and shaped relative to one another by the heat treatment, the fabric adapting to the press mold. The tissue is then removed from the mold and maintains the given shape of the surface of the mold cavity. It now forms the desired device. The heat treatment largely depends on the material from which the wire strands of the plastic fabric are made, but the duration and temperature of the heat treatment should be chosen so that the fabric is consolidated in its new form, i.e. the wire strands assume their relative realignment after the fabric has adapted to the mold surface.

After the heat treatment, the fabric is freed from the shaped element and retains its new shape. If a form element was used, it is now removed as described above. The duration and temperature of the heat treatment depend very much on the material composition of the wire strands and has already been described in detail above.

After the device 1 has been brought into the predetermined shape, it can be used for treatment on the patient. The device that is suitable for the treatment of the respective medical problem is selected. This device can correspond to one of the application forms described above. Once the appropriate device has been selected, a catheter or other insertion device is inserted into the patient and positioned so that the distal end of the guide device lies next to the site to be treated, e.g. right next to (or level with) a shunt of an abnormal opening in an organ.

The guide device can be shaped differently, but should preferably consist of a flexible metal shaft with a thread at the distal end. The Guide device is used to push the medical device through the tube of the catheter and to position it in the patient. If the device is pushed out of the distal end of the catheter, it is still held by it. Only when the device is positioned within the shunt of the abnormal opening is the shaft of the catheter rotated about its axis to unscrew the device from the catheter.

As long as the device is still connected to the catheter, the operator can move the device back and forth relative to the abnormal opening until it is exactly at the desired location in the shunt. With the help of a threaded clip attached to the device, the operator can control how the device is pushed out of the distal end of the catheter. Once the device 1 has emerged from the catheter, it will spring back into the expanded shape which it has assumed through the heat treatment of the tissue. The moment it springs back to its original shape, it may happen that it bumps against the distal end of the catheter and is pushed forward. This can lead to incorrect positioning of the device. This can be critical if it is to be placed in a shunt between two blood vessels. The operator can use the threaded clamp to hold the device in place during insertion, the device does not spring uncontrollably and can be positioned exactly.

The device is folded and inserted into the opening of the catheter. The collapsed shape of the device should be shaped so that it can be easily inserted into the tube of the catheter and properly exited at its distal end. So z. B. an ASD locking device have a relatively elongated folded shape, where the individual components lie along the axis (see Fig. 18a to 18d)). This can be achieved by pulling the device apart on its axis by z. B. manually grips the clamps and pulls them apart so that the extended diameter parts fold inwards towards the axis.

The PDA locking device works similarly. It can also be folded in for insertion into the catheter by pulling on its axis (see Fig. 45). The devices fold when you pull them apart.

If the device is intended to permanently close a channel in the patient, the catheter is simply pulled out. The device remains in the vascular system of the Patient and can close the blood vessel or other desired channel there. In some cases, the device can be attached to an insertion system such that the device is firmly connected to the end of the insertion device. Before the catheter is removed from such a system, it may be necessary to detach the medical device from the delivery device before the catheter and delivery device are removed.

Although the device springs back to its original expanded shape (i.e. the shape it was in before it was folded for insertion into the catheter), it must be made clear here that it does not always return to its original shape. For example, it is desirable that the device have a maximum outer diameter in its expanded shape that is at least as large and preferably larger than the inner diameter of the lumen of the abnormal opening to which it is to be attached. When such a device is placed in a blood vessel or abnormal opening with a small lumen, it expands until it fills the lumen. It can happen that the device does not have to spring back completely into its original expanded shape. Nevertheless, it is properly attached, because it closes with the inner wall of the lumen and settles there.

If the device is placed in the patient, thrombi form on the surface of the wires. With a larger wire density, the total area of the wires increases, so does the thrombotic activity of the device, and the blood vessel in which it is placed closes relatively quickly. If it is desired to speed up the shutter speed, a number of thrombotic agents can be applied to the device.

The devices (occlusion instruments 1) according to FIGS. 12 to 17 are used for the closure of defects such as the so-called patent Foramen Ovale (PFO). With the variants PFO, types 1 to 4 (exclusively plastic fibers) shown here, critical defect locations can also be treated from the location. A detailed description of the PFO occluder, type 1 in the material version with Nitinol can be found in the already mentioned JEN. meditec patent application No. 10 338 702 dated 22.Aυs & υ- st 2003.

18 to 22 show a further application of the present devices (occlusion instruments 1), with which atrial septal defects (ASD) are corrected can. 19 to 22, phase images of the device types ASD type 1 to 4 are shown in their relaxed, non-stretched state up to the partially stretched state.

ASD is a congenital anomaly of the atrial septum due to a structural weakness of the atrial septum. A shunt can be present in the atrial septum, through which blood flows from the right to the left atrium. If the defect is large with significant shunts from left to right due to the defect, the right atrium and right ventricle are overfilled and the excess is emptied into a less resistant lung vessel.

Pulmonary vascular occlusion and pulmonary atrial hypertension develop in adulthood. Patients with secondary ASD with a significant shunt (when the ratio of pulmonary blood flow to system blood flow is greater than 1.5) are preferably operated on at the age of 5 years or as soon as the diagnosis is made later in life. Since two-dimensional echocardiography and Doppler color flow mapping have been available, the exact anatomy of the defect can be illustrated. An ASD device of the appropriate size is selected to match the size of the defect.

The size of the ASD flap is proportional to the size of the shunt to be closed. In its relaxed state, the plastic fabric is shaped such that two disc-like members or retention areas 2 and 3 (FIG. 19a) are axially aligned and connected to a short cylindrical segment or central area 4. The length of the cylindrical segment 4 should correspond to the thickness of the atrial septum, that is to say 2 to 20 mm thick. The proximal disc 2 and distal disc 3 have an outer diameter which is so much larger than the shunt that the device 1 cannot slip. The proximal disk 2 is relatively flat, while the distal disk 3 is curved toward the proximal end in such a way that it overlaps somewhat with the proximal disk 2. In this way, the peripheral edge of the distal disc 3 is pressed fully against the side wall of the septum by springing open of the device 1. In the same way, the outer edge of the proximal disc 2 is pressed against the opposite side wall of the septum.

The ends of the device 1 made of tubular braided metal fabric 10 are welded or clamped together with the socket 5, similar to the clamps described above to prevent fraying. The socket 5, which holds the wire strands together at one end, also serves to attach the device the insertion system (see Fig. 18). In the embodiment shown, the socket 5 is generally cylindrical with a recess for the ends of the metal mesh, so that the wires of the braided mesh 10 do not move against each other. The socket 5 has a thread in the recess. This thread is designed to accept and hold the distal end of an insertion system.

The ASD closure device 1 as an embodiment of this invention can advantageously be produced using the above-mentioned method.

FIG. 23 illustrates as a partial view of a section from the side through the ASD occluder of FIG. 21 in the ASD of a heart.

24 to 28 show a closure device in various variants, which is preferably used in membrane VSD. These devices 1 have, in their preset form, two expanded diameter parts (retention area) 2 and 3 and a smaller diameter part (central region) 4 between the two expanded diameter parts 2 and 3. Each expanded diameter part 2 and 3 has a recess that extends from the outer surface of the extended diameter parts 2 and 3 protrudes inwards. A clip 7 is attached to each end of the tubular plastic fabric 10 in the recesses 10 and 12.

The smaller diameter part (central area) 4 has a length which corresponds to the thickness of the abnormal opening in the septum wall. In its extended, preset form, the VSD device can be deformed, thereby achieving a smaller cross-section so that it can be inserted through a channel in the body as described above. The inner surface of the expanded diameter parts can be concave or curved so that the outer periphery of each diameter part contacts the septum.

At least one diameter part 2 or 3 can also be arranged offset relative to the smaller diameter part 4. This prevents an offset opening next to the aorta from enclosing the displaced restraint device or the extended diameter parts 2 and 3 after insertion of the aorta.

29 and 30 show a VS D device 1, in which the center of both extended diameter parts 2 and 3 and the smaller diameter part 4 are in a line. Brackets (not explicitly dated) are fanned at the ends of the plastic fabric 10 and pulled inwards in order to achieve a smooth closure device. The clips can have an internal or external thread for attachment to an introducer or guidewire. Such a VSD device 1 is preferably used to close a muscular ventricular septal defect. This VSD device is inserted as described above.

31 and 32 show another form of application of the device 1 for closing a VSD. The device of FIG. 32 is similar to the VSD device of FIGS. 29 and 30 with a few changes: the length of the smaller diameter part 4 has been reduced and both expanded diameter parts 2 and 3 have been compressed to reduce the thickness of each diameter part.

33 and 34 show a further application form of a device 1 similar to FIGS. 31 and 32. With the device according to FIGS. 33 and 34, a patent ductus arteriosus (PDA) can be closed, in which the patient suffers from high pulmonary pressure. Both expanded diameter parts 2 and 3 are shaped with a thin cross section so as not to impede the flow of fluid through the pulmonary vein or aorta. In addition, the smaller diameter part 4 tapers to enlarge the contact area with the tissue around the defect.

PDA is essentially the condition in which two blood vessels, usually the aorta and pulmonary artery next to the heart, have a shunt between their lumens. Blood flows directly through the shunt from one blood vessel to the other and hinders the patient's normal blood flow. 35 and 36 to 37 has a bell-shaped trunk 3 and an outwardly projecting front part 2. The bell-shaped trunk 3 is adapted for placement in the shunt between the blood vessels, while the front part 2 for positioning in the aorta is adjusted to hold the body of the device in the shunt. The size of fuselage 3 and end 2 can be adjusted to the size of the shunt. So hull 3 e.g. have a diameter of around 10 mm and an axis length of around 25 mm in its generally slim middle part.

In the PDA device, the lower part of the fuselage can expand radially except for the outer diameter of the front part 2, which has a diameter of around 20 mm. The lower part 4 should widen considerably in order to form a shoulder piece which tapers radially away from the center of the trunk 3. If the PDA device is inserted into the blood vessel, the shoulder piece presses against the edge of the treated lumen with greater pressure. The front part 2 is held in the blood vessel and presses on the lower end of the trunk 3 so that the shoulder piece can nestle against the vessel wall. This prevents the device from coming loose from the shunt.

The PDA closure device as an embodiment of this invention can be produced very well by the method described above, by deforming a tubular metal fabric so that it conforms to the surface of a mold; then the fabric is heat treated to fix its new shape.

The PDA device according to FIG. 39 is simplified in such a way that the sleeve can unfold in the proximal region due to the plastic material used, since at this point the plastic wires were welded flush with one another.

Figure 40 shows the sketch of a PDA device in a patient's heart to occlude a PDA. The sketch shows the device in a shunt which extends from the aorta "A" to the pulmonary artery "P". The device is passed through the PDA by keeping the device folded in the catheter. Then allow the shoulder piece to spring back into its "memory shape" thermally given by the heat treatment by pushing the device out of the distal end of the catheter. The shoulder part should be larger than the lumen of the shunt of the PDA.

Then pull the device slightly so that the shoulder piece attaches to the wall of the pulmonary artery P. If the catheter is pulled in further, then the device attaches itself to the wall of the PDA and thereby pulls its body part 3 out of the catheter. Now body part 3 can expand. Body part 3 should be dimensioned so that it snaps into the lumen of the PDA shunt due to friction. The device is held in place on the one hand by friction between the trunk section 3 and the lumen of the shunt and on the other hand by the blood pressure of the aorta against the shoulder part of the device. Thrombi form in and on the device and in a short time

Another variant of the PDA device is shown in FIGS. 41 to 44. This device has a tapered cylindrical body 3, 4 and a shoulder part 2 which protrudes radially from one end of the body. The ends of the braided fabric are pressed inwards into the cavity of the body part 3. Thus, the clips are located at each end of the tubular tissue in the device, which shortens the overall length of the PDA device and simplifies its handling.

It should be pointed out that the embodiment of the invention is not limited to the exemplary embodiment described in the figures, but is also possible in a large number of variants.

Claims

"Medical self-expandable occlusion device" claims

1. Medical self-expandable occlusion device for the treatment of defects in the rush of a patient, in particular for the closure of tissue openings, the occlusion device (1) being minimally invasively inserted into the body of a patient by means of a catheter system and consisting of a network (10) of thin threads, wherein the braid (10) during insertion of the occlusion device into the patient's head has a first shape that can be defined and in the implanted state of the occlusion device has a second shape that can be determined in advance, the occlusion device in the first shape of the braid (10) in a folded state and in the second shape of the braid (10) is in an expanded state, characterized in that the threads of the braid (10) consist of a shape memory polymer composition, so that the braid (10) under the action of an external stimulus from a temporary For m deformed into a permanent shape, the temporary shape being in the first shape of the braid (10) and the permanent shape being in the second shape of the braid (10).

2. occlusion device according to claim 1, characterized in that the stimulus expressed is a definable switching temperature.

3. Occlusion instrument according to claim 2, characterized in that the switching temperature is in the range between the room temperature and the body temperature of the patient.

4. Occlusion instrument according to claim 2 or 3, characterized in that the polymer composition has polymeric switching elements, the temporary shape of the braid (10) being stabilized below the definable switching temperature with the aid of characteristic phase transitions of the polymeric switching elements.

5. Occlusion instrument according to claim 4, characterized in that the polymer composition has a crystalline or partially crystalline polymer network with crystalline switching segments, the temporary shape of the braid (10) being fixed and stabilized by freezing the crystalline switching segments during the crystallization transition, the switching temperature being determined by the Crystallization temperature or switching temperature of the crystalline switching segments is determined.

6. Occlusion instrument according to claim 4, characterized in that the polymer composition has an amorphous polymer network with amorphous switching segments, the temporary shape of the braid (10) being fixed and stabilized by freezing the amorphous switching segments during the glass transition of the switching segments, the switching temperature being determined by the Glass transition temperature of the amorphous switching segments is determined.

7. Occlusion instrument according to one of the preceding claims, characterized in that the rolyiiifcrkomposidon has a linear, phase-segregated multiblock copolymer network, which can be present in at least two different phases, the first phase being a hard segment-forming phase, in which a multiplicity in the polymer formed by hard segment-forming blocks which serve for the physical crosslinking of the polymer structure and determine and stabilize the permanent shape of the braid (10), and wherein the second phase is a switching segment-forming phase in which a multiplicity of switching segment-forming blocks are formed in the polymer which are used for Fix the temporary shape of the braid (10), wherein the transition temperature of the switching segment-forming phase to the hard segment-forming phase is the switching temperature, and above the transition temperature of the hard segment-forming phase, the shape of the braid (10) by conventional methods, in particular can be adjusted by injection molding or extrusion processes.

8. Occlusion instrument according to claim 7, characterized in that the polymer composition has thermoplastic polyurethane elastomers with a multiblock structure, the hard segment-forming phase by reaction of diisocyanates, in particular methylene bis (4-phenyl isocyanate) or hexamethylene diisocyanate, with diols, in particular 1,4-butanediol is formed, and the switching segment-forming phase of oligomeric polyether or polyester diols, in particular starting from OH-terminated poly (tetrahydrofuran), poly (ε-caprolacetone), poly (ethylene adipate), poly ( ethylene glycol) or poly (propylene glycol).

9. Occlusion instrument according to claim 7, characterized in that the polymer composition has phase-segregated diblock copolymers with an amorphous A block and a partially crystalline B block, the glass transition from the amorphous A block forming the hard segment-forming phase, and wherein the melting temperature of the semi-crystalline B blocks serve as switching temperature for the thermal shape memory effect.

10. Occlusion instrument according to claim 9, characterized in that the polymer composition has polystyrene as an amorphous A block and poly (1,4-butadiene) as a Leilkristalliπen B block.

11. Occlusion device according to claim 7, characterized in that the polymer composition has a phase-segregated triblock copolymer with a partially crystalline central B block and with two amorphous terminal A blocks, the A blocks building up the hard segment, and the B block determining the switching temperature.

12. Occlusion instrument according to claim 11, characterized in that the polymer composition has partially crystalline poly (tetrahydrofuran) as the central B block and amorphous poly (2-methyloxazoline) as the terminal A blocks.

13. Occlusion instrument according to one of the preceding claims, characterized in that the polymer composition comprises polynorbornene, polyethylene-nylon-6 graft copolymers and / or crosslinked poly (ethylene-co-vinyl acetate) copolymers.

14. Occlusion instrument according to one of the preceding claims, characterized in that the polymer composition has a covalent cross-linked polymer network which is built up by polymerization, polycondensation and / or polyaddition of difunctional monomers or macromers with the addition of tu- or higher-functional crosslinkers, with a suitable one Selection of the monomers, their functionality and the proportion of the crosslinking, the chemical, thermal and mechanical properties of the polymer network formed can be specifically adjusted.

15. Occlusion instrument according to claim 14, characterized in that the polymer composition is a covalent polymer network which is built up by crosslinking copolymerization of stearyl acrylate and methacrylic acid with N, N'-methylenebisacrylamide as crosslinker, the shape memory effect of the polymer composition being based on crystallizing stearyl side chains.

16. Occlusion instrument according to one of the preceding claims, characterized in that the polymer composition has a covalently cross-linked polymer network, which is formed by a subsequent cross-linking of linear or branched polymers.

17. Occlusion instrument according to claim 16, characterized in that the crosslinking is triggered by ionizing radiation or by thermal cleavage of a radical-forming group.

18. Occlusion instrument according to one of the preceding claims, characterized in that the polymer composition has at least one biodegradable material.

19. Occlusion instrument according to claim 18, characterized in that the polymer composition comprises a hydrolytically degradable polymer, in particular poly (hydroxycarboxylic acids) or corresponding copolymers.

20. Occlusion instrument according to claim 18 or 19, characterized in that the polymer composition comprises enzymatically degradable polymers.

21. Occlusion instrument according to one of claims 18 to 20, characterized in that the polymer composition has a biodegradable thermoplastic amorphous polyurethane copolyester polymer network.

22. Occlusion instrument according to one of claims 18 to 21, characterized in that the polymer composition has a biodegradable elastic polymer network, which are obtained by crosslinking oligomeric diols with diisocyanate.

23. Occlusion instrument according to one of claims 18 to 21, characterized in that the polymer composition is formed on the basis of covalent networks starting from OÜgo (ε-caproiactone) dimethacryate and butyiacrylate.

24. Occlusion device according to one of the preceding claims, characterized in that the second predefinable shape of the occlusion device is designed to close an abnormal tissue opening in the heart of the patient, the occlusion instrument (1) in its expanded state having a proximal retention area (2), a distal retention area (3) and an intermediate central area (4 ), the occlusion device having a smaller diameter at the central area (4) than at the proximal and / or distal retention area (2, 3).

25. Occlusion instrument according to claim 24, characterized in that in the distal retention area (3) the ends of the threads of the braid (10) converge in a holder (5), the proximal retention area (2) having an open shape towards the proximal end .

26. Occlusion instrument according to claim 24 or 25, characterized in that the center of the proximal and / or distal retention area (2, 3) is offset relative to the center of the central area (4).

27. Occlusion instrument according to one of claims 24 to 26, characterized in that the inner surface of the proximal and / or distal retention area (2, 3) has a concave shape.

28. Occlusion instrument according to one of claims 24 to 27, characterized in that the proximal retention area (2) of the braid (10) has a tulip-shaped shape open towards the proximal end.

29. Occlusion instrument according to one of claims 24 to 27, characterized in that the proximal retention area (2) of the braid (10) has a bell-shaped shape open towards the proximal end.

30. Occlusion device according to one of claims 24 to 27, characterized in that the occlusion instrument (1) has a dumbbell-like shape in its expanded state.

31. Occlusion instrument according to one of claims 24 to 30, characterized in that the central region (4) has a smaller diameter compared to the proximal and distal retention region (2, 3), the central region (4) having a length which is the same as the thickness corresponds to an abnormal opening in a fabric wall.

32. Occlusion instrument according to one of claims 24 to 31, characterized in that the length of the central part (4) is dimensioned such that the peripheral edge of the distal or proximal retention area (2, 3) with the peripheral edge of the other retention area (3, 2) overlaps.

33. Occlusion instrument according to one of claims 24 to 32, characterized in that the proximal and / or distal retention area (2, 3) has a recess in which the holder (5) is arranged.

34. Occlusion instrument according to claim 33, characterized in that at least one connecting element is also provided in the recess on the proximal and / or distal retention area (2, 3), the connecting element being engageable with a catheter.