WO2007140797A1

WO2007140797A1 - Occlusion instrument for closing a cardiac auricle

Info

Publication number: WO2007140797A1
Application number: PCT/EP2006/005292
Authority: WO
Inventors: Hans-Reiner Figulla; Susann Klebon; Katrin Schmidt; Rüdiger OTTMA; Friedrich Moszner; Robert Moszner; Florian Krizanic
Original assignee: Occlutech Gmbh
Priority date: 2006-06-02
Filing date: 2006-06-02
Publication date: 2007-12-13

Abstract

The invention relates to an occlusion instrument for closing a cardiac auricle (100), with a self-expanding occlusion body (1) which is composed of a braid (10) of thin wires or filaments and whose braid (10) is given a suitable configuration by means of a shaping and heating method, wherein the occlusion body (1) has a rear proximal retention area (2) and a front distal retention area (3). The ends of the wires or filaments of the braid (10) run together in a holder (4) in the distal retention area (3), and the occlusion body (1) also has a central area (5) between the proximal and distal retention areas (2, 3), wherein the occlusion body (1) in the collapsed state can be introduced minimally invasively into the body of a patient by means of a catheter and can be positioned in the cardiac auricle (100) of the patient. The object of the invention is to make available an occlusion instrument designed in such a way that it can be anchored in a particularly stable and fixed manner in the cardiac auricle (100). The object is achieved, according to the invention, by the fact that the occlusion instrument also comprises a fixing means (20) with a polymer network which is formed by means of a polyreaction mechanism, preferably taking place in the patient's cardiac auricle (100), and which establishes a force-fit connection between the braid (10) of the occlusion body (1) and the wall of the cardiac auricle.

Description

"Occlusion device for closing a cardiac ear"

description

The present invention relates to an occlusion device for closing a cardiac ear. The occlusion device comprises a self-expandable occlusion body consisting of a mesh of thin wires or filaments, the mesh of which is given a suitable shape by means of a deformation and heat treatment process, wherein in particular the occlusion body has a back proximal retention area and a front distal retention area in which the ends the wires or threads of the braid converge in a socket. Furthermore, the occlusion body has a central region between the proximal and the distal retention region, wherein the occlusion body is designed such that it can be inserted minimally invasively into the body of a patient in the collapsed state by means of a catheter and positioned in the patient's atrial appendage. Furthermore, the invention relates to a use of a fixing means for forming a frictional connection between the mesh of an occlusion body and a Herzohrwandung.

Such Occlusionsinstrument is at least partially known in principle from medical technology. For example, in DE 10 338 702 of 22 August 2003 an occlusion device for the treatment of septal defects is known, which consists of a mesh of thin wires or threads and receives a suitable shaping by means of a forming and heat treatment process. The known occlusion device has a proximal retention area, which is particularly flat, a distal retention area and a cylindrical bridge between the proximal and distal retention area. At the distal retention area, the ends of the braid-forming wires converge in a socket. It is provided that the two retention areas of the known occlusion device come into abutment by a mostly intravascular surgical intervention on both sides of a shunt to be closed in a septum, while the bridge passes through the shunt.

There has long been an effort in medical technology to close catheter-interventional non-surgical septic defects, such as defects of the atrial septum, by means of a transvenous, interventional approach, ie without surgery in the actual sense. Various occlusion systems with different advantages and disadvantages were proposed, without which a particular closure system could prevail. In the following, the various systems are called "occluder" or "occlusion devices". In all interventional occlusion systems, a self-expanding umbrella system is inserted transvenously via a defect to be occluded in a septum. For example, such a system could consist of two umbrellas, each positioned on the distal side (ie, on the side farther from the body center or from the heart) or on the proximal side (ie, nearer to the body center) of the septum in which case the two shield prostheses in the septal defect are subsequently screwed together to form a double umbrella. The closure system is thus then in the assembled state usually consists of two clamped Schirmchen, which are connected to each other via a short, passing through the defect pin.

In such known from the prior art occlusion, however, it turns out to be disadvantageous that the implantation procedure is relatively complicated, difficult and expensive. Apart from the complicated implantation of the closure system in the septal defect to be closed, the umbrellas used generally have the risk of material fatigue with fracture of the branch. Furthermore, thrombembolic complications are likely.

In order to achieve that the occlusion device according to the invention can be introduced by means of an introducer or a guidewire, it is provided that the end of the distal retention area has a socket which can be brought into engagement with the introducer or guide wire. It is envisaged that the procedure after the positioning of the occlusion device in the defect can be easily solved again. For example, it is possible to remove the braid at the end of the distal retina. tion range of Occlusionsinstruments such that in the socket, an internal thread is made, with which the introducer comes into engagement. Of course, other forms of implementation are also conceivable here.

In particular, when a patient suffers from a so-called atrial fibrillation of the heart, embolization-related problems may appear. This is a frequent excitation of the atria of the heart, which does not lead to a contraction of the atria. The consequence of this contractile loss of the atria of the heart is that there is no effective turbulence and mixing of the blood and that trannies can form in the atrium. A significant risk of atrial fibrillation due to atrial fibrillation is that such trunks can be entrained with the bloodstream and enter the arterial circulation. The consequences of this embolization are, in particular, strokes, which occur in approximately 5% per year in patients with atrial fibrillation, unless hemolytic inhibition of the blood with so-called dicumerols is performed by chronic treatment. However, it is also not without risk to bring about the inhibition of the inhibition of the blood with so-called dicumerols. Adverse reactions to dicumerol treatment include increased bleeding so that contraindications to this treatment are present in approximately 20% of patients with atrial fibrillation and patients are at risk of stroke due to risk of bleeding / stroke.

Trombes in the atrium of the heart arise in the overwhelming majority in the so-called heart ears. The heart ears are protuberances on the atria of the human heart. The right ear of the heart is next to the ascending aorta, the left next to the large pulmonary artery. In the case of patients with atrial fibrillation, the left ear of the heart is the common place of origin for blood clots, which can lead to a stroke.

It is an object of the present invention to provide an occlusion device with which the left atrial appendage can be occluded to substantially reduce thrombus formation with the risk of stroke due to the risks and problems associated with the atrial truncation described above. In particular, an occlusion device is to be specified with which the risk of stroke can be reduced even in those patients in whom anticoagulation is inhibited by dicumerols because of bleeding tendencies. In particular, the occlusion device should be designed such that it is particularly stable and firmly anchored in the atrial appendage. These objects are achieved with a self-expandable Occlusionsinstrument of the type mentioned in particular according to the invention that the Occlusionsinstrument next to the occlusion further a fixative with a polymerizable by means of a preferably in the atrial of the patient polyreaction mechanism formed polymer network for forming a frictional connection between the braid of the occlusion body and the Has Herzohrwandung. It is provided that, after the positioning of the occlusion body, the fixing agent described in more detail below, in particular as a low-viscous liquid, which is curable by cannula and controlled to form a flexible insoluble product is filled into the atrial appendage of the patient, thus the occlusion body in the atrial appendage can be firmly anchored.

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

The solution according to the invention has a number of significant advantages over the occlusion instruments known from the prior art and mentioned above. On the one hand, the occlusion body is a self-expandable body which can be implanted in a particularly simple manner with, for example, a suitable insertion catheter. For this purpose, it would be conceivable to puncture a vein in the region of the groin of the patient and to show the Einführkathetersystem to the septum of the right atrium. By means of a puncture of the septum of the atrium, which may be, for example, a known transseptal puncture, the left atrium of the heart is reached, so that subsequently from the inguinal vein from the Einführkathetersystem can be introduced into the left auricle. The self-expandable occlusion body for closing the atrial appendage can then be introduced via the introducer catheter system. Subsequently, i. After the positioning of the occlusion body in the atrial appendage, the fixative can be applied through a cannula and at least partially filled into the atrial appendage. In this case, the fixing agent is designed to harden after application, in particular in a controlled manner to a flexible insoluble product, thus providing a permanent and firm anchoring between the braid of the occlusion body and the Herzohrwandung.

In a further embodiment of the occlusion device according to the invention, provision is further made for the proximal retention area of the occlusion body to have at least one brim area, which in the expanded state of the occlusion body in the atrial appendage to be occluded abuts the inner walls of the atrial appendage and forms a frictional connection with the inner walls of the atrial appendage to retain the implanted and expanded occlusion device in the atrial appendage, wherein the distal retention region of the occlusion device occludes the opening of the atrial appendage. Here, the anchoring function of the fixative supports the frictional connection between the brim area and the atrial appendage.

The occlusion body, which is in the folded state during implantation, preferably has a diameter of 6 to 10 frenches, so that the procedure for closing the atrial appendage is minimally invasive.

After the collapsed occlusion body is positioned in the atrial appendage catheter by means of, for example, the introducer catheter, the occlusion body is released from the catheter, which unfolds due to its self-expandable nature and which exhibits pronounced styling by means of the forming and annealing process used in fabrication. In this expanded state, the rear proximal retention area is completely unfolded with the brim area formed thereon and abuts the inner walls of the atrial appendage to be closed. The proximal retention area with the brim area formed thereon serves for fastening and positioning the expanded occlusion body in the atrial appendage. The central area extending from the proximal retention area in the direction of the atrial appendage and the distal retention area provided at the distal end of the central area almost completely fill the opening area of the atrial appendage, so that the entire expanded occlusion body in the inserted state serves as a closure plug for closing the atrial appendage. In this way, thrombus formation with the risk of stroke can be considerably reduced in a particularly simple and minimally invasive manner.

On the other hand, after the positioning of the occlusion body in the atrial appendage, the fixative is applied so as to improve the anchoring of the occlusion body in the atrial appendage. After curing of the fixative in the atrial appendage, the implementation process of the occlusion device is completed.

In particular, the fact that in the solution according to the invention, the fixing is provided, can be dispensed with attachment hooks or other anchoring means in the occlusion, which usually in such Occlusionsinstrumenteen used for fixation and positioning of the instrument in the tissue. It should be noted in particular that due to the extremely thin-walled design of the tissue in the vicinity of the atrial appendix usually used Befestigungshäkchen can not provide permanent attachment and positioning of Occlusionsinstrumentes. With the solution according to the invention and in particular by the provision of the fixation means, which is preferably applied after positioning the occlusion body in the auricle, the problem of attaching the occlusion device to the extremely thin-walled and easily damaged cardiac ear tissue can be circumvented by means of check marks. The fixative is used for complete and permanent positioning of the occlusion body in the atrial appendage.

In one case, if the occlusion body additionally has at least one brim area, positioning and fixation of the occlusion body can be achieved at least partially with the aid of the brim area which comes into contact with the inner walls of the atrial appendage; This is in particular to the advantage that even before applying the fixing a relatively secure hold of the occlusion body can be provided in the atrial appendage. After reaching the end position of the occlusion body in the blind hole of the atrial appendage in the form of a low-viscosity liquid, which is applied by a cannula, introduced for fixing the distal retention area and finally cured to a flexible, insoluble product controlled.

Hereinafter, preferred embodiments of the configuration of the occlusion body and the design of the fixative will be discussed with reference to the accompanying drawings. Furthermore, preferred embodiments of the occlusion device according to the invention will be explained.

Show it:

1 shows a possible initial shape for a funnel-shaped hollow braid of the occlusion body;

FIG. 2 shows a possible starting shape for a spherical, pear-shaped or drop-shaped hollow braid of the occlusion body; FIG.

3a shows an embodiment of an occlusion body with funnel shape according to FIG. 1 in side view with half section; FIG. 3b shows the occlusion body according to FIG. 3a in plan view; FIG.

FIG. 3c shows the occlusion body according to FIG. 3a in a spatial representation; FIG.

FIG. 4a shows a further embodiment of an occlusion body with spherical shape according to FIG. 2; FIG.

FIG. 4b shows the occlusion body according to FIG. 4a in plan view; FIG.

FIG. 4c shows the occlusion body according to FIG. 4a in a spatial representation; FIG.

FIG. 5a shows a further embodiment of an occlusion body with multiply set rim regions with a ball basic shape according to FIG. 2; FIG.

FIG. 5b shows the occlusion body according to FIG. 5a in a spatial representation; FIG.

6 shows a spatial representation of a human atrial appendage in the left atrium in stylized representation;

7a is a sectional view, simplified for the left atrial appendage, with an inserted occlusion body according to FIG. 3a of a funnel shape;

FIG. 7b is a sectional view, simplified for the left atrial appendage, with the occlusion body according to FIG. 7a and with an applied fixative; FIG.

8a shows a sectional view, simplified for the left atrial appendage, with an inserted occlusion body according to FIG. 4a of spherical form;

FIG. 8b is a sectional view, simplified for the left atrial appendage, with the occlusion body according to FIG. 8a and with an applied fixative; FIG.

9a shows a sectional view, simplified for the left atrial appendage, with an inserted occlusion body according to FIG. 5a; FIG. 9b shows a sectional view, simplified for the left atrial appendage, with the occlusion body according to FIG. 8a and with an applied fixative; FIG.

10 shows an example of components of a fixative based on tailored polymer networks;

Fig. 11 shows an example of the radical formation of a redox initiator system of DBPO and DEPT;

12 shows an example of a polymerizable peroxide (a) and a polymerizable accelerator amine (b);

Fig. 13 is an example of radically polymerizable groups;

Fig. 14 is an example of structural variations in dimethacrylates;

Fig. 15 is an example of a synthesis scheme for an Ormocer polymer network;

Fig. 16 is an illustration of a dendrimer and hyperbranched oligomer;

17 shows an example of monomer components for a simple peptide adhesive;

Fig. 18 shows an example of biodegradable poly (lactic acid (PLA), polyglycolic acid (PGA) or polyarsuccinic anhydride (PAB) polymer structures;

19 shows an example of the synthesis, the polymerization and the degradation of a diacrylate reaction resin; and

Fig. 20 is an example of inhibitors of radical polymerization resins.

Fig. 1 shows a possible embodiment of a funnel-shaped hollow braid 10, which can serve as a base body for an occlusion body 1 of the occlusion device. FIG. 2 shows an alternative embodiment of this basic body, in which case a spherical, pear-shaped or drop-shaped hollow braid 10 is used. From the funnel-shaped hollow braid 10 (FIG. 1) or the spherical or bulbous and teardrop-shaped hollow braiding according to FIG. 2, the most important but also very specific occlusion bodies 1 of the occlusion body 1 can be produced, as will be described below.

In particular, it can be seen in FIG. 1 that the braid 10 shown here, which serves as the basic body for the occlusion body 1, is designed in the form of a funnel-shaped braid 10 which is open at the proximal retention area 2 and which is provided with a socket 4 only at the distal retention area 3 which converge the ends of the wires or thread of the braid 10. As an alternative to the funnel-shaped hollow braid 10 according to FIG. 1, it would also be conceivable to use the spherical braid 10 according to FIG. 2 as the basic body of the occlusion body 1. The essential difference between the two hollow braids 10 shown in FIGS. 1 and 2 can be seen in particular in that the proximal retention region 2 of the hollow braid 10 according to FIG. 2 has a closed surface, wherein the entire braid is in the form of an upwardly closed tubular or braided structure sack-shaped braid is designed.

A possible embodiment of an occlusion body 1 is shown in FIGS. 3 a to 3 c, which is formed from a base braid 10 according to FIG. 1. On the other hand, FIGS. 4a to 4c show an alternative embodiment for the occlusion body 1, this occlusion body being formed from a base braid 10 according to FIG.

As already indicated, the occlusion body 1 of the illustrated embodiments consists of a braid 10 of thin wires or thread, which is given a suitable shape by a shaping and / or heat treatment process. The shapes of the occlusion body 1 illustrated in FIGS. 3 and 4 are in each case an essentially dumbbell-shaped shaping consisting of a front-side distal retention area 3, a middle area 5 and a rear proximal retention area 2. The ends run in the distal retention area 3 the wire or thread of the braid 10 in a socket 4 together. The proximal retention area 2 of the occlusion body 1 according to FIG. 3 has an open form towards the proximal end, while the proximal retention area 2 of the occlusion body 1 according to FIG. 4 is closed at the proximal end. In FIGS. 3 and 4, the occlusion body 1 is shown in its expanded state. As already indicated, the occlusion body 1 has a proximal retention area 2, a distal retention area 3 and a waisted cylindrical center area 5. As can be seen from the figures, the proximal retention area has at least one brim area 6, which is formed by at least partial retraction of the proximal and / or distal retention area 2, 3 towards the respective end. The proximal retention area 2 with the rim area 6 formed thereon primarily serves for the provisional fixing and holding of the occlusion body 1 already inserted in the heart ear in the implantation process. The final fixation of the occlusion body 1 is effected by subsequent application of a fixation means described below.

FIGS. 5a and 5b show a further exemplary embodiment of an occlusion body 1 which has a plurality of rim areas 6 in order to ensure better retention of the occlusion body 1 used in the heart of a patient.

6 shows a spatial representation of a human atrial appendage 100 in the left atrium. In particular, a heart ear is shown here in a stylized representation.

FIG. 7 a shows a sectional view in which the occlusion body 1 shown in FIG. 3 a is inserted in the atrial appendage 100. FIG. 7 shows the occlusion body 1 used in the atrial appendage 100 in accordance with FIG. Fig. 7a, but with already applied fixer 20th

In an analogous manner, FIGS. 8 a, b and 9 a, b show the occlusion body according to FIGS. 4 a and 5 a respectively without and with applied fixing means 20. The mode of operation of the fixing means 20 can be clearly seen from these figures. In particular, it can be seen that first the occlusion body 1 is inserted into the atrial appendage 100 and positioned there. This positioning is advantageously carried out automatically during the expansion of the occlusion body 1 folded during implantation. Because of the rim area 6 coming into abutment against the inner wall of the atrial appendage 100, a provisional fixation of the occlusion body 1 in the atrial appendage 100 is ensured.

After reaching the end position of the occlusion body 1, the fixing means 20 is introduced into the blind hole of the atrial appendage 100. The fixing agent 20 is preferably a low-viscous liquid which can be applied by a cannula. By the hardening of the fixing agent 20 in a controlled manner and thereby forming a polymer network, a force-locking sige connection between the braid 10 of the occlusion body 1 and the Herzohrwandung be achieved.

The occlusion body 1 has, in particular, a rim region 6, the proximal retention region 2 preferably being designed with its rim region 6 such that it bulges outward during expansion of the occlusion body 1 in order to abut with the inner walls of the heart ear 100 in the implanted state come. With this embodiment, it is therefore possible that the self-expandable occlusion body 1 can be advanced particularly deeply into the cardiac ear 100 to be closed by means of an introducer catheter system. The distal retention area 3, which is advantageously designed, for example, as a distal screen, is subsequently, i. after the occlusion body 1 has been inserted with the aid of the catheter system in the atrial appendage 100 to be closed, brought to unfolding and positioned, wherein the Schirmchen rests on the edge of the opening of the atrial appendage 100 to the entrance of the atrial appendage 100. At the same time, the proximal region 2 of the occlusion body 1 also expands, i. the proximal shield, wherein in the expansion process of the proximal Schirmchens the proximal retention area 2 of the occlusion body 1 is further drawn into the atrial appendage 100 and so over the central region 5 a tensile force is exerted on the distal Schirmchen. As a direct consequence of this, the distal screen or the distal retention area is held at least provisionally under a permanent tension at the entrance of the atrial appendage 100, with subsequent solid anchoring of the occlusion body 1 with the fixing means 20 being realized.

The proximal retention area 2 of the occlusion body 1 can have a completely closed proximal wall which has a continuous area which forms the proximal end of the occlusion body 1. In this case, the proximal wall can have as a continuous surface a curved surface that, for example, coincides with the surface of a section of a spherical, pear-shaped or drop-like body.

By the concern of the at least one brim area 6 on the inner wall of the atrial appendage 100, it can further be achieved that the occlusion instrument used can be completely enclosed by the body's own tissue much faster than in the closure systems known from the prior art.

The use of a braid 10 constructed of thin wires or filaments as the starting material for the occlusion body 1 derives the further advantage that it has long-term mechanical stability. In particular, the occurrence of breaks in the structure or other type of material fatigue of the implant used can be largely prevented. Furthermore, the braid has sufficient rigidity

In a particularly advantageous embodiment of the occlusion body 1, provision can be made for the rim region 6, which is formed, for example, on the proximal retention region 2, to be formed by pushing back the proximal retention region 2 toward the distal end 3. This is a particularly easy to implement and effective way to form the brim area 6 in the occlusion body 1. In particular, it is thus possible to form the entire occlusion body 1 from a one-piece mesh 10, so that on the one hand no mechanical connection elements between the brim area 6 and the proximal end 2 are necessary, and on the other hand minimizes the dimension of the occlusion body 1 further in the folded state Of course, other embodiments for forming the at least one brim area 6 are also conceivable here.

In order to achieve that the distal retention area 3 of the occlusion body 1 in the implanted and expanded state completely flattens on the edge margin of the Herzohroffnung, almost independent of the diameter of the Herzohroffnung, can be provided in a further development of the Occlusionskorpers 1 that the distal retention area 3 has a recess in which the socket 4 is arranged. By arranging the socket 4 in the recess provided at the distal end 3 of the occlusion body 1, no components of the occlusion body 1 protrude beyond the atrial appendage, so that a continuous blood contact with components of the implant can be prevented. This has the advantage that defense reactions of the body and no thrombebolic complications are to be feared. In particular, by the fact that the Occlusionskorper 1 self-expanding in the opening of the atrial appendage 100, positioned and at least temporarily fixed, the distal and proximal retention area 3, 2 are biased in the radial direction, the Occlusionskorper 1 can be used over a wide range of different sized Herzohroffnungen become.

In a further development of the last-mentioned embodiment of the occlusion body 1, in which the distal retention area 3 has a depression, it can further be provided that a connecting element is also arranged in the depression at the distal end 3 of the occlusion body 1, the connecting element being arranged with a catheter in FIG Intervention can be brought. With this connecting element, which preferably On Occlusionskorper 1 is arranged such that it does not protrude beyond the Herzohrwandung, whereby a constant blood contact with components of the implant can be prevented, the Occlusionskorper 1 also has the functionality of the Ruckhol- ability. On the other hand, a connecting element, which can be brought into engagement with a catheter, facilitates the implantation and positioning of the occlusion body 1 (folded during the implantation process) in the atrial appendage 100 to be closed. Different devices are possible as connecting elements. Conceivable elements were, for example, catching elements or also hooks or eyelets which can be frictionally connected with correspondingly complementary connection elements of a catheter.

In a further development, provision may be made for the occlusion body 1 to be folded and unfolded in a reversible manner, so that the body 1 can be folded in its expanded state, for example with the aid of an explant catheter, the provisional, force-locking connection between, for example, the proximal retention area 2 formed, at least one brim area 6 and the inner walls of the atrial appendage 100 is solved. It is conceivable that for explantation, a catheter engages, for example, on a connecting element formed on the distal end 3 of the occlusion body 1, and the external body is caused to fold over the occlusion body 1 by external manipulation with the aid of the catheter. Thus, the occlusion body 1 is completely reversible retractable into the catheter, which allows the complete removal of the body 1.

In order to achieve that the braid 10 of the occlusion body 1 can obtain its suitable shape by means of a shaping and heat treatment method, it would be conceivable for the braid 10 to be formed from a shape memory material, in particular nitinol or polymer plastic. The use of nitinol in occlusion instruments is known. Shape memory polymers belong to the group of smart polymers and are polymers that exhibit a shape memory effect, i. under the action of an external stimulus, e.g. a temperature change, their external shape can change.

The polymer is first brought into its permanent form by conventional processing methods, such as extrusion or extrusion. Subsequently, the plastic is deformed and fixed in the desired temporary shape, which is also called "programming." On one hand, this process can be carried out in such a way that the sample is heated, deformed, and then cooled Polymer or the plastic are also deformed at low temperature, which is referred to as "cold stretching" .Thus the permanent shape is stored, while the temporary shape is currently present.When the polymer molding is heated to a temperature higher than the switching temperature, it comes to trigger the shape memory effect and thus to restore the stored permanent shape. By cooling the sample, the temporary shape is not reversible, which is why one speaks of a so-called one-way shape memory effect.

Compared to the known shape memory materials such as e.g. The shape memory alloy nitinol, an equiatomic alloy of nickel and titanium, are shape memory polymers with their memory powers many times superior. Only a small amount of effort (heating or cooling) is required to program the temporary shape or to restore the permanent shape. In addition, in Nitinol the maximum deformation between permanent and temporary form is only 8%. Shape memory polymers have significantly higher ductility of up to 1100%. All of the aforementioned shape memory polymers and materials are claimed by the present invention for the biomedical application of the occlusion body 1.

In a further development of the last-mentioned embodiment of the occlusion body 1, in which the braid 10 is formed from a shape memory material, it can be provided that the material comprises a biodegradable shape memory polymer material. In particular, synthetic, biodegradable implant materials are suitable. Such degradable materials or polymers contain cleavable bonds under physiological conditions. It is said to be "biodegradable" if the material is degraded by loss of mechanical property through or in a biological system, and the external shape and mass of the implant may be retained during degradation By the term "quantifying information" is meant the time at which the complete loss of mechanical property occurs. "Biostable materials" are understood to mean those that are stable in biological systems and at least partially degraded in the long term.

In the case of degradable polymers, a distinction is made between hydrolytically and enzymatically degradable polymers. The hydrolytic degradation has the advantage that the rate of degradation is independent of the site of implantation, since water is everywhere. In contrast, the concentration of enzymes is locally very different. For biodegradable Accordingly, degradation of polymers or materials by pure hydrolysis, enzymatically induced reactions or by their combination can take place. Typical hydrolyzable chemical bonds are amide, ester or acetal bonds. There are two mechanisms involved in degradation. In surface degradation, the hydrolysis of chemical bonds takes place exclusively at the surface. Due to its hydrophobic character, polymer build-up is faster than the diffusion of water into the interior of the material. This mechanism is observed especially in the case of poly (anhydrides) n or poly (orthoesters) n. For the poly (hydroxycarboxylic acids), which are particularly important for the shape memory effect, such as poly (lactic acid) or poly (glycose acid) or corresponding copolymers, polymer degradation takes place in the entire volume. The rate-limiting step here is the hydrolytic bond cleavage, since the diffusion of water in the rather hydrophilic polymer matrix takes place relatively quickly. For the application of biodegradable polymers is crucial that they on the one hand with a Kontrollierbzw, reduce speed and on the other hand, the degradation products are non-toxic.

All of the abovementioned biodegradable shape memory polymers are claimed according to the invention.

With regard to the shaping of the occlusion body 1, it is particularly preferred, as already indicated, for the occlusion body 1 to have a sphere-like shape, with the tapered end of the ball-like shape forming the distal retention area 3. Alternatively, the occlusion body 1 may also have a mushroom-like shape, wherein the cap of the mushroom-like shape forms the proximal or distal retention area 2, 3. It is also conceivable that the occlusion body 1 has a dumbbell-like shape, with the middle part of the dumbbell-like shaping forming the middle area 5 between the proximal and the distal retention area 2, 3 of the occlusion body 1. Of course, other shapes are also conceivable here, which are suitable to select depending on the application.

In a particularly preferred embodiment, the mesh 10 of the occlusion body 1 can be tapered to the diameter of a catheter used in the minimally invasive surgical procedure. The advantage of this embodiment is the fact that the catheter systems to be used for implantation and explantation can have a significantly reduced inside diameter, which significantly increases the maneuverability of the occlusion body 1 to be implanted. Therefore, the Positioning accuracy of the instrument in the atrial appendage 100 can be improved. In an Nitinol occlusion body 1, the inner diameter of the catheter used for implantation or explantation is between 8 to 10 frenches, whereas when using polymer plastic occlusion bodies, the inner diameter must only be between 6 to 8 frenches.

Finally, it is also conceivable for the occlusion body 1 to have at least one tissue insert (not explicitly shown) which is arranged for completely occluding the atrial appendage 100 in or on the distal retention region 3 or in the middle region 5 of the occlusion body 1. This tissue insert serves to close the gaps remaining in the middle region 5 and in the widening diameters of the occlusion body 1 after the insertion and expansion of the body 1 in the atrial appendage 100. The tissue insert is fastened, for example, to the braid 10 of the occlusion body 1 at the distal retention area 3 such that it can be stretched over the distal retention area 3 like a tissue. The advantage of this construction is that the rim of the distal retention area 3 rests flush against the Herzohrόffnung and less foreign material is introduced into the body of the patient. The fabric inserts may for example be made of Dacron. Of course, other materials and other positions of the fabric insert in or on the occlusion body 1 are also conceivable here.

Below is briefly on preferred from export forms of the embodiment of the fixative 20 received. However, before a detailed description of possible polymeric fixing agents 20 based on customized polymer networks is given, a brief assessment of known tissue adhesives should be made for a better understanding.

A per se known tissue adhesive is the so-called fibrin adhesive, which is a 2-component adhesive, one component consisting primarily of fibrinogen and a special blood clotting factor, and the second component of thrombin with the addition of CaCl ₂ . The curing mechanism is the equivalent of blood coagulation, so they are unlikely to be used on the heart.

Furthermore, a tissue adhesive known per se, the so-called gelatin resorcinol-aldehyde adhesive. The base of the gelatin-resorcinol-aldehyde adhesive forms a mixture of gelatin and resorcinol (1, 3-dihydroxybenzene), whereby the hardening by polycondensation with formaldehyde. Formaldehyde is considered to be carcinogenic and mutagenic.

Also known as Gewebekleb fabric so-called gelatin-resorcinol-dialdehyde adhesive, which consists of a mixture of gelatin and resorcinol. The curing takes place by reaction with the less toxic dialdehydes (glyoxal, glutaraldehyde). It achieves only a low strength with moist curing.

Cyanoacrylates which are also known as superglue in the art and are used, for example, as fabric adhesives are also suitable. based on n-butyl-2-cyanoacrylate or ethyl-2-cyanoacrylate. A disadvantage is their extreme sensitivity to moisture, as they cure in contact with traces of water and their toxicity.

In a peptide adhesive, polymerizable groups are introduced into natural products, such as carbohydrates, lipids, amino acids or short-chain peptides, which can then be cured to form polymer networks. With this group of tissue adhesives, good biocompatibilities can be achieved so that analogous monomer systems are also considered below.

In contrast to the tissue adhesives known per se from the prior art and explained above, the fixing means 20 for the occlusion instrument according to the invention, on the other hand, fulfills the following requirement profile:

(i) The fixing means 20 for the occlusion device according to the invention are preferably low-viscosity liquids which can be applied by means of a cannula and harden in a controlled manner to give a flexible, insoluble product.

(ii) The hardening of the fixing agent 20 for the occlusion device according to the invention is preferably completed after about 10 minutes (processing width).

(in) The solidification time of the fixing agent 20 for the occlusion device according to the invention is preferably about 10 to 20 minutes (curing time). (iv) The fixing agent 20 for the occlusion device according to the invention preferably has an adhesive property on the occlusion body 1 and on the tissue of the atrial appendage.

(v) The fixing means 20 for the occlusion device according to the invention preferably has the choice between a non-degradable or a biodegradable fixation agent 20.

(vi) The fixing agent 20 for the occlusion device according to the invention is preferably non-toxic or of little toxicological concern and does not produce any undesired reactions in the case of blood contact.

This requirement profile can be achieved, in particular, by custom-tailored network polymers obtained by a controlled polyreaction (network formation) of a liquid multicomponent mixture of selected monomers or oligomers, an initiator system and additional additives, such as. e.g. Stabilizers are accessible.

FIG. 10 in this context shows an example of components of a fixing agent 20 for the occlusion device according to the invention on the basis of tailor-made polymer networks. As shown, the solidification of the applied liquid fixing agent 20 can be achieved in a targeted manner by the addition of suitable substances, a so-called initiator system, in which e.g. by a chemical reaction of two compounds (initiator and coinitiator), the poly-inducing species is formed. The relevant initiator components together are not storage-stable. This results in that the desired fixative can only be prepared by mixing two liquid compositions before application.

Other additives include, for example, stabilizers that prevent premature poly-reaction and thus uncontrolled curing of polymerizable mixtures. The viscosity of the fixing agent can be adjusted, above all, by the targeted selection of low-viscosity monomers, it also being possible to achieve structurally viscous properties, ie low viscosity when tiling, but stability after leaving the cannula, by adding suitable additives. Furthermore, the structure and functionality of the components can influence the density and polarity of the polymer network formed and thus such properties as extensibility, swelling, substrate adhesion.

Biodegradability can be achieved by using biodegradable monomers. Through polymer network formation, the multifunctional monomer or oligomer components, assuming nearly complete conversion, are highly likely to be incorporated into the network, which contributes to improving biocompatibility.

Finally, the use of non-water-soluble or non-polar substances allows a substantial prevention of the mixing of the curing agent with tissue or blood fluid. Likewise, to dispense with the use of hydrolysis-sensitive components or water-reactive compounds.

Due to the contact with blood, the highest demands are placed on such so-called "class III materials", which lead to a significant restriction of the components in question Accordingly, potentially suitable fixatives are described below, which on the one hand non-biodegradable or biodegradable are largely in line with the above requirement profile.

In the following, polymerchemical aspects or potentially possible components of non-biodegradable biocompatible fixing agents based on tailor-made polymer networks will now be described. The components or fixing means described below are claimed as fixing means 20 for the occlusion device according to the invention.

The known polyreaction mechanisms for polymer network formation are polycondensation, polyaddition and polymerization. Since in polycondensations low molecular weight substances are split off and these usually take many hours, such polyreactions are unsuitable for fixing agents. Likewise, the polyadditions frequently used in the art are eliminated because the monomer components used, such as diisocyanates or diepoxides, are very toxic. In addition, isocyanates can react with water to form gaseous CO ₂ . Thus, only the polymerization is suitable as a polyreaction in which form from unsaturated or cyclic compounds, the so-called monomers, polymer chains The polymerization can be triggered by radicals or ions. Due to a possible blood contact no ionic, but only a radical polymerization in question

The formation of polymer chains is triggered by radical free radical polymerization. Radical highly reactive species, which are formed from stable substances called initiators. It is known that the radical formation and thus the radical polymerization u. a. by irradiation of light (photoinitiators), by the action of heat (thermal initiators) or by redox reaction of an oxidizing agent with a reducing agent (redox initiator systems) are triggered. For radical polymerizable fixing agents, for obvious reasons, only redox initiator systems are suitable. Redox initiator systems are, for example, combinations of a peroxide, e.g. Dibenzoyl peroxide (DBPO) and a tertiary amine, e.g. N, N-diethanol-p-toluidine (DEPT), which form the polymerization-releasing radicals R- at room temperature as a result of a redox reaction

In this regard, reference is also made to Fig. 11, which shows an example of the radical formation of a redox initiator system of DBPO and DEPT.

Although redox initiator systems are not untoxic, their biocompatibility can be significantly improved by using polymerizable initiator components. For example, a polymerizable DBPO is 4.4 ^N -divinylbenzoyl peroxide. Figure 12 also shows an example of a polymerizable peroxide (a) and a polymerizable accelerator amine (b)

The components of the redox initiator systems together are not storage-stable and can only be brought into contact with one another before use as 2-component systems. The advantage of such redox initiator systems, however, is that the choice of the concentration of the initiator constituents and variation of the ratio of peroxide and amine accelerator, the so-called processing width (ie, the time from mixing the component together until the onset of curing) and the curing time ( ie the period from the beginning to the end of the curing) can be set in the desired manner within wide limits. Free-radically polymerizable compounds (monomers) contain at least one reactive C =C double bond to which the polymerization-initiating radicals add. The thus initiated chain reaction then leads within a short time (seconds to minutes) to form linear polymers in monofunctional monomers or a polymer network in the case of multifunctional monomers, ie of monomers containing several polymerizable C = C double bonds. In this case, the reactivity of the monomers, ie the rate of polymerization or aging, increases with the functional group F, ie. the number of polymeπsa- tionable groups per monomer molecule, wherein F varies in commercial monomers usually between 1 to 4

Typical free-radically polymerizable monomers are styrenes (a), dienes (b), vinyl monomers (c), allyl compounds (d), acrylates (e) or methacrylates (f), as shown in FIG. 13, in which examples of radically polymerizable groups are shown

For the applications as a fixer especially methacrylates have been preserved, since on the one hand styrenes, dienes or allyl compounds are too less reactive and on the other hand, the reactive acrylates show high cytotoxicity and sometimes mutagenicity. Conceivable here were different methacrylates, especially di-, tri- or tetrafunctional methacrylates whose radical polymerization leads to a polymer network.

The polymer network properties can be adjusted by the structure of the methacrylates used. Thus, tri- or tetramethacrylates give denser polymer networks compared to dimethacrylates. In the case of the dimethacrylates, the structure of the spacer group, that is to say the distance group between the two methacrylate groups, can be used to influence the properties of the polymer networks in a targeted manner. Reference is made to FIG. 14, which shows an example of structural variations in dimethacrylates.

For example, long-chain spacers (A: decandiol dimethacrylate) give more flexible networks, aromatic spacers (B-propoxy-bisphenol A dimethacrylate) rigid networks, polar spacers (C ethylene glycol dimethacrylate) hydrophilic networks or perfluorinated (D) or dimethylsiloxane-containing spacers (E) water-repellent polymer networks. In addition, further property variations can be achieved by copolymerization with functionalized methacrylates, ie with methacrylates which carry a further functional group in addition to the polymerizable methacrylate group. For example, OH-group-containing methacrylates can improve wetting on moist surfaces, methacrylate-containing methacrylates allow adhesion to metals, or CHO- or SH-group-containing methacrylates impart adhesion to biological tissue.

Accordingly, on the one hand can be realized by a targeted selection of different methacrylates and on the other hand by optimizing the composition of the corresponding methacrylate mixture, the respective desired property profile of the polymer network, which is prepared from the methacrylate mixture by radical polymerization.

The fixative 20 for the occlusion device according to the invention are classified as class III medical devices. These are materials that have contact with the heart or the circulating blood, and therefore require a much higher level of biocompatibility, which is hardly feasible with technical methacrylates. One of the reasons for this is the lack of purity of technical chemicals. Furthermore, the structure of the methacrylates should be optimally adapted to the intended application.

Methacrylates with improved biocompatibility are accessible with the following strategies:

Foremost regarding the accessibility of methacrylates having improved biocompatibility, reference is made to ormocer matrix systems with reference to Figure 15, wherein in Figure 15 an example of a synthetic scheme for an Ormocer polymer network is shown. The term Ormocer derives from the English. These are flowable oligomeric or polymeric polysiloxanes which, starting from trialkoxysilanes containing methacrylate groups, can be prepared by hydrolytic condensation (Fig. 15, step A) in the context of the so-called sol-gel process. Due to the presence of methacrylate groups (MA), the formed Ormocer resin can be polymerized in a second step (step B) with radicals X- to a three-dimensional (3D) Ormocer polymer network, forming a so-called inorganic-organic hybrid material Properties of the Ormocer resins are above all a high biocompatibility and a low polymerization shrinkage. Second, with regard to the accessibility of methacrylates with improved biocompatibility, reference is made to hyperbranched or dendritic oligomers with reference to Figure 16, in which Figure 16 is a representation of a dendrant and hyperbranched oligomer. Ideally branched ohgomers, so-called dendrimers, and more or less regularly structured highly branched structures, so-called hyperbranched oligomers or polymers, are a very promising class of substances for the production of biomedical materials in modern polymer synthesis. Due to their special molecular architecture, high molecular weight products can be obtained as liquids, which are characterized among others by a very good biocompatibility. This makes it possible starting from commercial products, such as hyperbranched polyglycidols or polypropyleneimine Dendnmeren, by their chemical modification with polymerizable methacrylate groups for the fixing agent 20 of the occlusion device according to the invention produce suitable biocompatible reaction resins.

Third, regarding the accessibility of improved biocompatibility bi-methacrylates, reference is made to natural product resins with reference to Figure 17, wherein an example of monomer components for a simple peptide adhesive is shown in Figure 17. This strategy derives from peptide adhesives based on the hypothesis that an improved biocompatibility of tissue adhesives can be achieved with substances that also occur in the body. Accordingly, for example, carbohydrates and their building blocks (ie monosaccharides) or proteins and their building blocks (amino acids) can be used for the preparation of polymerization resins having improved biocompatibility. For example, by dissolving a substituted dipeptide of glycine each containing a radical-polymerizable methacrylic and allyl group in a methacrylated alanine derivative (B), a radically polymerizable resin which is suitable as a biocompatible tissue adhesive after addition of a radical initiator has been obtained. Analogously thereto, by introducing polymerizable methacrylic groups into ohgopetides having 3 to 5 identical or different natural amino acid units or, for example, into natural disaccharides such as sucrose with 7 methacrylic OH groups, higher functionalized and tailor-made reaction resins with improved biocompatibility and on the other hand produce with the optimal adapted properties for each application. While the matrix systems listed above are not biodegradable, it will be briefly discussed below biodegradable radically polymerizable resin systems.

Biodegradable materials, e.g. biodegradable polymerization resins containing cleavable bonds under physiological conditions. Accordingly, biodegradable polymers can be degraded by pure hydrolysis, enzymatically induced reactions or by their combination. Typical hydrolyzable chemical bonds are amide, ester or acetal bonds.

Reference is made to FIG. 18, which shows an example of biodegradable polymer (PLA), polyglycolic acid (PGA) or polyarsinic anhydride (PAB) polymer structures.

There are two mechanisms involved in degradation. In surface degradation, the hydrolysis of chemical bonds takes place exclusively at the surface. Due to the hydrophobic character, the polymer degradation occurs faster than the diffusion of water into the interior of the material.

This mechanism is observed mainly in poly (anhydrides) n. In contrast, in the case of poly (hydroxycarboxylic acids), such as poly (lactic acid) or poly (glycolic acid), polymer degradation occurs throughout the entire volume. For the use of biodegradable polymers is crucial that they degrade on the one hand with a controlled or adjustable speed and on the other hand, the degradation products are non-toxic.

For biodegradable polymerization products, reference is made, for example, to biodegradable hydrogels based on photopolymerized polyester diacrylate resin. 19 shows an example of the synthesis, the polymerization and the degradation of a diacrylate reaction resin. Synthesis of the polymerization resins proceeds stepwise: In the first step, ring-opening polymerization of lactide with polyethylene glycol (PEG) produces a biodegradable oligomer bearing terminal OH groups. In the second step, the OH groups are then converted with acrylic acid chloride into polymerizable acrylate groups. The resulting diacrylate reaction resin can then be radically polymerized in a third step to a polymer network which biodegrades in a fourth step under physiological conditions. Similarly, biodegradable fixing agents 20 can be produced for the occlusion device according to the invention, wherein instead of the acrylate groups methacrylate groups are to be preferred and the desired property profile can be set by selecting suitable comonomers.

To stabilize polyreaction resins, substances are added to these liquid mixtures, so-called inhibitors, which are capable of trapping spontaneously formed radicals during storage of the resin in such a way that premature polymerization does not occur. Two different stabilizer types can be used: aerobic and anaerobic inhibitors. Aerobic inhibitors are phenols, e.g. BHT (2,6-di-tert-butyl-4-methylphenol) or MEHQ (hydroquinone monomethyl ether) (Figure 20), which exhibit their full effectiveness only in the presence of oxygen, since they react particularly fast only with peroxide radicals. They are usually used in amounts of about 100 to 1000 ppm based on the monomer. In contrast, the effect of the anaerobic inhibitors, e.g. of PTA (phenothiazine) or TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy radical) are not bound to the simultaneous presence of oxygen and react very efficiently directly with primary radicals or growing polymer radicals. Accordingly, usually 20-50 ppm are sufficient for adequate stabilization. In order to avoid that these stabilizers lead to biocompatibility problems, corresponding polymerizable methacrylate derivatives thereof would have to be used, e.g. a methacrylate derivative of BHT (4-methacryloyloxy-2,6-di-tert-butylphenol.

In summary, it should be noted that, as a potential fixing agent 20 for the occlusion device, tailor-made mixtures of liquid, radically polymerizable reaction resins made of biocompatible multimethacrylates based on hyperbranched oligomers, oligopeptides or disaccharides are suitable. In the case of biodegradable materials dimethacrylates are to be used with biodegradable oligoester or oligoanhydride spacer. The desired processing latitude and cure time can be adjusted by selecting the concentration and mixing ratio of the redox initiator system used. An improvement in the biocompatibility through the use of polymerizable initiator components is mögüch. Furthermore, the substrate adhesion (metal or tissue) can be influenced by the addition of suitably functionalized methacrylates. Finally, 20 polymerizable inhibitors should also be used to stabilize the fixative. It should be noted that the embodiment of the invention is not limited to the embodiments described in the figures, but is also possible in a plurality of variants.

Claims

claims

An occlusion device for closing a cardiac ear, comprising a self-expandable occlusion body (1) consisting of a braid (10) of thin wires or threads, whose braid (10) is given a suitable shape by means of a deformation and heat treatment method, the occlusion body (1) a rear proximal retention area (2) and a front distal retention area (3), wherein in the distal retention area (3) the ends of the wires or threads of the braid (10) converge in a socket (4), and wherein the occlusion body (1 ) further comprises a central region (5) between the proximal and distal retention regions (2, 3), wherein the occlusion body (1) in the collapsed state by means of a catheter in the body of a patient minimally invasive insertable and positionable in the heart of the patient characterized in that the occlusion device further comprises a fixing means (20) having a polymer network formed by means of a polyreaktionsmechanismus preferably expiring in the atrial appendage of the patient for forming a frictional connection between the braid (10) of the occlusion body (1) and the Herzohrwandung.

2. Occlusion instrument according to claim 1, wherein in the polyreaction mechanism, a polymerization of unsaturated and / or cyclic monomers or oligomers proceeds, are formed in which polymer chains for the polymer network of the fixing agent (20).

3. occlusion device according to claim 1 or 2, wherein in the polyreaction mechanism is a free radical polymerization, in which the formation of polymer chains of the polymer network is triggered by radicals, which are formed by the action of an external stimulus on a stable initiator composition.

The occlusion device of claim 3 wherein the stable initiator composition comprises redox-type initiators which form the radicals to initiate polymer chain formation by a redox reaction of an oxidant with a reducing agent.

5. Occlusion instrument according to claim 4, wherein the initiators of the redox type polymerizable initiator components, in particular 4,4 'Divinylbenzoylperoxid have.

6. Occlusion instrument according to one of claims 2 to 5, wherein the polymerization or curing rate of the polymer network is adjustable in particular by a suitable choice of the monomers used in the polymerization.

7. Occlusion instrument according to claim 6, wherein the monomers styrenes, dienes, vinyl monomers, allyl compounds, acrylates or methacrylates have.

8. occlusion device according to one of the preceding claims, wherein the fixing agent (20) comprises a composition of liquid, radically polymerizable reaction resins of biocompatible multimethacrylates based on hyperbranched oligomers, oligopeptides or disaccharides.

The occlusion device of claim 8, wherein the composition further comprises dimethacrylates with biodegradable oligoester and / or oligoanhydride spacers.

10. Occlusion instrument according to one of the preceding claims, wherein the fixing agent (20) comprises a initiator composition of the redox type, in particular a combination of a peroxide and a tertiary Armin, wherein the processing width and / or curing time of the polymer network by a suitable choice of concentration and / or the mixing ratio of the components used in the initiator composition is beforehand adjustable.

11. occlusion device according to one of the preceding claims, wherein the fixing means (20) suitably functionalized methacrylates for influencing the stability of the frictional connection between the braid (10) of the occlusion body (1) and the Herzohrwandung.

12. Occlusionsinstrument according to any one of the preceding claims, wherein the fixing means (20) separated from the occlusion body (1) preferably by means of a catheter in the body of the patient minimally invasive insertable and can be introduced into the atrial appendage of the patient.

13. Occlusion instrument according to one of the preceding claims, wherein the proximal retention area (2) of the occlusion body (1) has at least one brim area (6) which in the expanded state of the occlusion body (1) at least partially in the heart ear to be closed on the inner wall of the atrial appendage comes to rest and with the help of the polymer network of the fixative (20) forms a frictional connection with the inner wall of the atrial appendage and thus holds the implanted and expanded Occlusionsinstrument in the atrial appendage, wherein the distal

Retention area (3) of the occlusion body (1) at least partially closes the atrial appendage.

14. Occlusion instrument according to one of the preceding claims, wherein the proximal retention area (2) of the occlusion body (1) with its at least one brim area (6) is designed such that it bulges when expanding the Occlusionskörpers (1) at least partially outwards so come to rest with the inner wall of the atrial appendage.

15. Occlusion instrument according to one of the preceding claims, wherein the proximal retention area (2) of the occlusion body (1) is a complete closed proximal wall having a continuous surface which forms the proximal end of the Occlusionsinstrumentes.

16. occlusion device according to claim 15, wherein the proximal wall has a curved surface as a continuous surface.

17. Occlusion instrument according to claim 16, wherein the curved surface coincides with the surface of a portion of a spherical, pear or teardrop-like body.

18. Use of a fixing means (20) according to one of the preceding claims for forming a frictional connection between the braid (10) of an occlusion body (1) and a Herzohrwandung.