WO2011089459A1

WO2011089459A1 - Biodegradable device for occluding an opening in a wall associated with an organ

Info

Publication number: WO2011089459A1
Application number: PCT/IB2010/000079
Authority: WO
Inventors: Alberto Della Martina; Philippe Le Goff
Original assignee: Bioring Sa
Priority date: 2010-01-19
Filing date: 2010-01-19
Publication date: 2011-07-28

Abstract

The invention relates to a device for occluding an opening in the tissue of a wall associated with an organ, in particular the permeable foramen ovale. According to the invention, the device, which is advantageously made of a bioresorbable organic polymer material, includes two opercula (10), each consisting of a self-deploying flexible framework (13) and a membrane (11) supporting the growth of adjacent tissue, suitable for assembling in their deployed configuration such as to close the opening.

Description

BIODEGRADABLE DEVICE FOR OCCLUSION

OF AN ORIFICE IN AN ORGANIC WALL

The present invention relates to the field of devices or prostheses intended to be implanted in the organic tissues and in particular in the heart. More specifically, it relates to a biodegradable occlusion device intended to close an open orifice in an organic wall, the defects of the heart septa in particular. This device is intended in particular for the treatment of certain cardiac conditions of patients with persistence of foramen ovale. The invention aims in particular to allow cardiological practices to mitigate, or as far as possible remedy, such a deficiency and to allow closure of the foramen ovale, and to reduce or even avoid post-interventional treatments, side effects and consequences in the longer term for the patient.

Among the septal defects, the most common is the permeable foramen ovale. It is an embryonic opening in the inter-ventricular wall of the heart, that is to say the cardiac wall separating the two cavities of the auricles.

FIG. 1 shows a view of the heart on which the right atrium 1 is recognized (at the top left of the figure conventionally), the right ventricle 2, the left atrium 3 and the left ventricle 4 from which the lacrosse the aorta 5 and the general arterial circulation 6.

The inter-ventricular wall separating the two ventricles is prolonged in the upper part of the heart by the interatrial wall, or atrial septum, 7, which separates the two atria. This partition is in fact formed of two tissue walls 7 'and 7 "(see Figure 2a).

As illustrated in more detail in Figure 2b, when they form in the embryonic heart, the two tissue walls 7 'and 7 "do not join, thus, returning to Figure 1, the blood returning from the placenta by the lower vena cava 8 'and opening into the right atrium 1 can pass directly into the left atrium 3 and avoids the pulmonary circulation circuit 2' which has no functional activity during intrauterine life.

CONFIRMATION C0PY At birth, the entry into function of the pulmonary circulation, causes the increase of the pressure in the left atrium 3, which presses the two walls 7 'and 7 "together which will eventually merge, preventing communication between the two atria.

Nevertheless, it is possible that the walls T and 7 "do not overlap the oval skylight of the other and respectively, or they may not completely fuse together, and in both cases there remains a communication channel. between the two auricles is the permeable foramen ovale.The existence of such a way of communication could explain some of the diagnosed cases of stroke or heart disease when other established causes (atheromatosis of the trunks) arterial, atrial fibrillation, lacunary state) do not allow it.

Relatively recent work has highlighted the existence of a permeable foramen ovale in large sections of the population. It is commonly accepted that this anomaly affects about a quarter of the population (B. Meier, J. E. Lock "Contemporary management of foramen ovale", Circulation 2003, 107 (1): pp. 5-9).

In most individuals, the existence of a patent foramen ovale remains asymptomatic, non-disabling and the usefulness of an intervention with its risks and associated treatments does not seem justified. However, in cases of diagnosis of paradoxical cerebral (CV) or cardiac embolism in patients with sudden transient ischemic attack (TIA) correlated with the detection of a patent foramen ovale, more and more physicians and Health authorities recommend the closure of the foramen ovale percutaneously permeable (P. Urban, A. Bloch, "Foramen ovale permeable", Swiss Medical Review, 2483) (High Authority of French Health, opinion of July 6, 2005).

Indeed, there are today percutaneously implantable occlusion devices introduced and introduced into the heart through a catheter and deployed in situ.

A series of foramen ovale occlusion devices are thus known formed of two flasks of various shapes (hats, hemispheres, spherical caps, strainer) which fold within the narrow lumen of a catheter and himself deploy out of its end. Once in place on both sides of the inter-ear wall, the two flanges are connected by an interconnection rod whose two ends are fixed to the two vertices or to the opposite poles of the two flanges, by screwing, so that they are held together on either side of the orifice of the foramen ovale, resting on the flanks of the inter-auricular wall. Each flange consists of a grid (or lattice) metal formed of fine metal son following the volumetric envelope curves of the flange. These son are made of nickel and titanium alloys known as "shape memory". This reinforcement grid of the flange is filled with a polyester woven insert to form a solid flange capable of plugging the orifice.

These occlusion devices have the disadvantages that the entire metal structure is particularly troublesome. The two strand-shaped twisted wire structures occupy part of the heart volume, and have attachment ends at the hemispherical apices that protrude into the cavities of the atria.

The disadvantage especially, is that the metal structures of these implants are incompatible with living tissues and can lead to risks of thrombosis (clot formation on the grids) which is precisely against the stated objective of these devices, that is to say, to avoid the risks of a new embolism due to circulating thrombi, originating from the left heart.

There are other implants that work in much the same way. These implants are permanent, and among them, only one has a bioabsorbable fraction. Therefore implantation of this type of known occlusion device requires constant medical monitoring and forces the patient to follow a permanent treatment with anticoagulant or antithrombotic drugs and antirejection treatments with all their side effects. If the implant proves to be poorly tolerated, rejected by the heart tissue or triggers an immune response, then it should be removed, if necessary, by open heart surgery. Even if in such a case, the surgeon could then take advantage of the operation to suture the opening, ie the foramen ovale, for example, or any abnormal orifice appearing in the tissues of this organic wall, to definitively close such abnormal communications, this operation remains heavy and undesirable. The ideal would be to obtain an implant whose membranes intended to fill the defect in the organic wall would promote the regrowth on their surfaces of the endothelial tissue so that the implant is quickly isolated from contact with the blood. This would therefore avoid any problem of long-term treatment with anticoagulant and anti thrombotic drugs. This implant would more ideally consist of only perfectly biocompatible and biodegradable material, which, after recovery by the endothelial tissue and therefore the restoration of organic function, would disappear entirely, thus leaving no foreign body, which would limit the duration of possible use of anti-rejection or immunosuppressive therapy and preclude the need for surgical removal of the device.

Such a device must also be implanted percutaneously, that is to say in this case by means of a catheter of sufficiently fine diameter to be able to cross the blood passages and the defect to be closed. This implant must also be able to be deployed and fixed in situ, so as to maintain mechanically on the walls at the edge of the orifice to be closed, by simple operations that can be controlled by an external manipulator. It must occupy little space in the implantation vector while having sufficient mechanical strength when deployed and fixed in situ

The object of the present invention is a device, which can be implanted percutaneously by means of a catheter, to close off an abnormal orifice open in an organic wall, among which it is possible to mention interauricular communications, such as foramen ovale. , inter-ventricular communications or any other abnormal orifice in the tissues of an organic wall, cardiac or other, such as a wound, an arterial wound or simply occluding a permeable wall, while overcoming the aforementioned drawbacks.

The device is in the form of two umbrella-shaped or bell-shaped covers provided with a relatively rigid but flexible self-unfolding structure or frame. These two lids are assembled in-situ by means of an axial fastening system. The device is designed to be implanted by a technique and equipment similar to those used for the installation of conventional sealing devices and therefore does not disturb the practitioner. The particularly innovative nature of the present invention lies in the fact that the entire device consisting of the caps, with their self-expanding armature and the fixation system, is made entirely of perfectly biocompatible, bioabsorbable and non-thrombogenic materials which thus allow as much as possible, to avoid taking long-term treatments based, for example, on anticoagulants, antithrombotics, antirejects, immunosuppressants and / or anti-inflammatories. The entirely bioabsorbable nature of the device of the invention has the additional advantage of ruling out, as a first approach, the possibility of a heavy surgical operation to remove the device.

Another particularly innovative feature of the device of the invention is the use, for the closure of the orifice, of operculas consisting of a not only biocompatible, bioresorbable and non-thrombogenic membrane, but also promoting tissue growth. . The device is therefore no longer simply a prosthesis for life, but, in addition to its initial function of closing the orifice, it allows self-repair or regeneration of neighboring tissues to the device, thereby restoring the deficient organic function of the device. patient's organ, then it disappears entirely.

The present invention relates to a bioabsorbable device for producing in humans, percutaneously, the occlusion of defects or orifices in organic walls. The device of the invention applies in particular to the occlusion of the foramen ovale permeable.

Briefly, the invention is an occlusion device for closing an open orifice in organic tissue, implantable minimally invasively by means of a catheter system provided with a manipulator. The device is formed of two structures or more precisely two self-expanding armatures (such as an umbrella), at least one of which has a rigid, relatively rigid but flexible diaphragm and made of biodegradable polymer material, and provided with fastening means complementary axial, to assemble against each other.

This or these organic polymeric materials, of which examples of chemical formulation will be detailed below, are resorbed in a time period independent of the metabolic activity of the target organ, including enzymatic mechanisms existing in vivo, and moreover according to a predetermined period of time corresponding at least to the time required for healing, a consolidation and / or regeneration of the deficient function, ie a period of the order of one week to ten years, preferably between one month and one year or two years. In addition, these biodegradable polymeric materials can even induce self-repair of the tissues and, moreover, degrade or resorb over time in the living tissues of the organs of the body and disappear with the restoration of the normal functions of the organ. and the patient.

Thus, the occlusion device according to the invention advantageously provides, in addition to its primary function of prosthesis, that is to say in this case, implant for sealing or sealing an opening or a foramen, on the one hand a function of induction of healing of the target organ and, on the other hand, a natural self-elimination function, avoiding as far as possible, any new surgical operation, including heavy surgical operations of removal of this device implanted.

The aforementioned objectives are achieved, therefore, according to the invention, by producing an occlusion device for a foramen or an open orifice in organic tissues, composed of at least two elements able to be assembled against each other. other: a first operculum and a second operculum, each operculum comprising a diaphragm membrane provided with a self-expanding flexible armature integral with the membrane, characterized in that the two flexible armatures are made of bioabsorbable organic polymer material.

Other features, objects and advantages of the present invention are listed in the dependent claims and will become apparent on reading the following detailed description, with reference to the appended drawing sheets, of a particular embodiment, given by way of example. non-limiting.

On the attached drawing plates:

Figure 1A is an open heart sectional view;

• detail view 2A shows the normal configuration of a closed foramen ovale;

• detail view 2B schematizes abnormal interauricular flow via a permeable foramen ovale (PFO) with the risk of passing emboli or thrombi (bubbles or clot) through this orifice;

FIG. 3A is a view of the deployed membrane of one of the two lids of the occlusion device, according to the invention; FIG. 3B is a view through the membrane (here represented by its only contour) of the flexible structure with its arcuate radial edges;

FIG. 4 shows in an axial sectional view, the two lids of the occlusion device according to the invention mounted at the end and folded inside the cannulas of a catheter allowing its introduction into an organ. like the heart;

FIGS. 5, 6 and 7 are sectional views schematizing a sequence of steps for placing two lids of the occlusion device according to the invention, using a catheter, on the one hand and on the other. another of an open orifice through an organic wall, such as, for example, a permeable foramen ovale (PFO);

FIG. 5 shows the beginning of the deployment of the first seal of the occlusion device according to the invention outside the catheter and on the other side of the orifice of the wall to be closed;

FIG. 6 shows the deployment of the second cap leaving the end of the catheter during the placement of the occlusion device according to the invention on the orifice of the wall to be closed;

FIG. 7 shows the assembly of the two lids of the occlusion device according to the invention and the removal of the catheter, at the end of its placement on the closed orifice;

• Figure 8 shows an alternative embodiment of the assembly system of the two covers.

Referring to FIGS. 3 and 4, it appears that the occlusion device 100 consists essentially of two lids 10 and 10 'having generally an umbrella shape or more precisely a bell shape, intended to be assembled against one another. the other, the concave contact face b of the first cap 10 being turned towards the concave contact face b of the second cap 10 ", by means of axial fixing means such as those designated by 21 and 22. Each cap 10/10 ' as shown in FIG. 3 comprises a flexible membrane 11 of variable thickness integral with a flexible structure 13 or more exactly of a reinforcement 13 of ribs 15, that is to say radial edges 15 having an arched shape . As illustrated in the embodiment of FIGS. 3A to 7, each lid 10 may comprise a flexible membrane 11 of circular shape, symmetrical of revolution about a central axis AA, acting as a diaphragm mounted integrally on a flexible frame 13 formed of several radiating ridges like the whales of an umbrella. The radial edges of the armature may be three to sixteen, preferably between four and twelve.

Alternatively, the covers 10 may have an oblong shape, in particular elliptical or oval, in order to adapt to an orifice of particular shape. The two lids 10 and 10 'can moreover be symmetrical with respect to a transverse plane, such as a plane perpendicular to the axis of revolution A-A. Alternatively, the two lids 10-10 'can be asymmetrical, one of the lids being smaller than the other or the axial mechanical connection can be oblique to fit a bias communication path (opening whistle or oblique bevel), especially to fit a gap between wall plates forming a valve valve, such as septa primum and secundum of the interauricular wall. Alternatively, only one of the two covers 10 may comprise a diaphragm diaphragm 1 1, the other element of the device 100 being reduced to a holding frame 13-15 adapted to be assembled with this single cover 10 which comprises an armature 13 provided with a diaphragm diaphragm 11.

More specifically, each edge 15 extends radially from a central zone or hub 17 to near the periphery 19 of the diaphragm diaphragm 11, over a length substantially corresponding to the radius or at least a major part of the half. transverse dimension of the deployed membrane 11.

Each flexible edge 15 has a slightly arcuate shape at rest, extending in an axial plane A or radial and has, in this plane, a curved profile C-C. The profile may follow a regular curve, in an arc, ellipse or oval, so that the cap 10 takes an extended form, at rest, similar to the simple shape of a flared cut or a umbrella deployed.

Alternatively, the profile can follow a curve CC having at least one point of inflection I, in particular a curve CC substantially corresponding to the profile of a bell or to a portion of sinusoid, ie with a portion of curvature between the axial vertex 17 ( where the curve can be perpendicular to the axis) and the point of inflection I, then an inverted curvature, until the curvature CC becomes again, at the periphery 19 of the cover 10, tangent or close to the perpendicular to the axis AA of the device 100 in order to present a profile CC similar to the skirt of a bell or a corolla, so as to present a surface of maximum peripheral support 19 on the tissues 7 and reduce the shear or blunt force of the end of the edges 15 at the periphery 19 of the cover 10 on the walls 7 -7 "of the organic tissues.

According to the principle of the device 100 according to the invention, it is provided that the edges 15 of the armature 13 are flexible and, as illustrated in FIG. 6, can be bent, in the direction B of the concavity b, for close like a corolla or a closed umbrella when the lids 10-10 'are enclosed in the sheath 33 of a catheter 30. Once released from the sheath 33, the edges 15 of the flexible frame 13 of each lid 10, he allow to unfold itself, to take its neutral configuration, in the form of corolla or campaniforme. The edges 15 of the flexible armature 13 thus exert a self-expanding force D or extension which allows the cap 10 to reach an expanded service configuration. However, preferably, the deployed configuration does not reach a disk-shaped maximum expansion configuration E, but stops at the arcuate, campaniform C-C configuration.

By campaniforme, is meant in the present a family of shapes comprising flared shapes, inflected, such as bell shapes, corolla or flared cut and also regular shapes, without inflection, such as forms of basket, umbrella or umbrella.

When the edges 15 of the flexible armature of each lid 10 are biased beyond E of their campaniform service CC configuration, their own flexibility tends to exert a restoring force F in the opposite direction tending to bring back or refold the lid 10 towards the CC campaniform configuration, like a sucker. The flexible armature 13 of the cap 10 therefore opposes a resistance F to an extension force E which tends to extend beyond its campaniform neutral configuration C-C, including flipping or flattening it.

Thus, advantageously, the two lids 10 and 10 'of the device 100 according to the invention can be clamped and folded B to be inserted into a sleeve 33 of the catheter 30 and introduced via this percutaneously to the localization orifice 9 to be sealed, which is particularly advantageous for reaching otherwise inaccessible places without tissue dissection. The catheter by its transverse flexibility and its axial inelasticity allows the manipulator to bring the device 100 to the wound, the foramen 8 or more generally the orifice 9 to be closed. The manipulator can then bring the end of the catheter 30 through or near the orifice 9 as illustrated in FIG.

FIG. 4 shows that the first lid 10 of the occlusion device 100 according to the invention is advantageously mounted at the end of a rod 31 or small diameter inner cannula inserted in the outer sleeve 33 of the catheter 30, which allows the manipulator to extract the cap 10 of the sheath by pushing the lid or by retracting the sheath. As soon as the first cap 10 is entirely outside the end 33a of the catheter 30, the self-expanding flexible armature 13 of the cap 10 allows its deployment D to its campaniform configuration C-C.

As can be seen in FIGS. 4 to 7, it is provided that the second cap 10 'of the device 100 according to the invention is arranged coaxially A with the first cap 10 inside the sleeve 33 of the catheter 30. For this purpose , the central zone 17 'of the second cap 10', which preferably forms a central hub, is pierced with a hole 20 for the passage of the axial rod 31 or inner cannula which advantageously has a reduced diameter, in any case the most small diameter of 31-32-33 concentric and coaxial cannulas of the catheter 30. The second lid 10 'is thus pierced with a hole 21 through its central zone, while the first lid is hollowed in its central zone or hub 17 , a cavity 23, to preferably form a non-through cavity 23. The blind cavity 23 is advantageously threaded to form an internal thread, to be screwed to the end of the axial rod 31 or inner cannula of the catheter 30 q he carries a screw at its end or a complementary thread. Alternatively, the cavity 23 may be provided with a neck or a ring of internal radial shrinkage to form a snap-fitting system with the rod 31 which then bears a point provided with a flange or projecting collar. like an arrow, for example, to come into the cavity. Other complementary support means of the male and female type, retractable, can be arranged at the end of the rod 31 and in the axial hub 17 of the first cap 10 to support, guide and position it at the tip 31 of the catheter 30. Thus, the first cap 10 can be mounted on the axial rod 31 of the catheter 30 by other means, for example by snapping, clipping etc.

In addition, it is expected that the two lids 10 and 10 'of the device 100 according to the invention are able to be assembled against each other in their deployed service configuration, in order to be fixed and held in place permanently on the orifice by resting on the limb 7'-7 "of the orifice 9, that is to say on the walls 7 of the organic tissues surrounding the orifice 9, by sandwiching them or enclosing on both sides like two suckers or in the manner of a crimp or a rivet.

Thus, as illustrated by FIGS. 5 and 6, the manipulator may, after having deployed the first lid 10 on the other side of the orifice 9, deploy the second lid 10 'out of the sleeve 33 or outer cannula of the catheter 30 of the first side of the orifice 9, or by further retracting the outer sheath 33 of the catheter relative to the second cannula 32, or intermediate cannula, or by pushing the latter. The intermediate cannula 32 contains the axial rod 31 or inner cannula which carries at its threaded end the first lid 10 and is contained in the sleeve 33 or the last outer cannula of the catheter device 30. This intermediate cannula 32 preferably has an end 32a provided with a flange flared outwardly and forming a transverse bearing surface 32a extending transversely, flat or concave, to push or retain the second cap 10 '.

In the example, the two lids 10 and 10 'are assembled against each other by means of an axial mechanical connection 21-22. FIGS. 3A to 7 show an example of device 100 provided with a single-click clipping assembly system. Alternatively, Figure 8 shows an example of device 100 provided with a multi-notch assembly system.

Indeed, it is expected that the two lids 10-10 'of the occlusion device 100 according to the invention, are maintained clipped to each other in their deployed service configuration CC and even beyond this configuration neutral so as to exert a force F of return and support, as two suckers face to face. More exactly, the two lids 10 and 10 'are respectively plated on one face and the opposite face of the organic wall 7, by clasping the latter in the manner of a rivet or sandwich, so as to support and anchor above. The two lids 10 and 10 'are then fixed and remain supported on the tissues 7 'and 7' on each side of the wall 7. Thus, the occlusion device is assembled and secured on the organic wall 7 until it is completely degraded or resorbed.

According to the exemplary embodiment illustrated in FIGS. 3A to 7, the two lids 10 and 10 'comprise complementary fixing means 21 and 22 advantageously located in the central zone 17 and preferably at the central hub from which the radiating edges 15 of the armature 13. The fastening means 21 and 22 project towards each other, axially, on the side of the concave contact face b of each cap 10/10 ', towards the inside of the assembled device 100. According to the embodiment of Figures 4 to 7, the first cap 10 comprises a pin male 21, axial, mushroom-shaped protruding inside the contact face b. In the present, "pin" designates a small protrusion generally of revolution about the axis A-A mechanical assembly link.

The male stud 21 has a cylindrical body forming a foot, anchored at its base in the central zone 17 of the cap 10 or in the axial hub 17 of the armature 13 and provided with an annular flange 25 protruding transversely or radially towards the spigot. outside or preferably, a collar 25 at its free end on the inner side of the entire device 100.

The second cap 10 'has a fixing means 22 complementary to the previous one. According to the embodiment of Figures 4 to 7, the second cap 10 'has a female nipple 22 in the form of a receptacle projecting axially on the side of the concave face b of contact of the second cap 10'.

The female stud 22 is hollowed out axially and forms a receptacle 24 having tubular walls 22 of revolution and an internal chamber 24 provided at its end with a bottleneck 26, that is to say a transverse rib 26 or an annular narrowing 26 facing inwards. Conveniently and advantageously, it is the second cap 10 'which carries such a female nipple 22 hollowed out 24 axially and it is the first cap 10 which carries the male pin 21 complementary attachment. Thus, the through-hole 20 or bore for the passage of the rod 31 of the second support of the second seal 10 'is drilled axially in the center of the hub 17 of the armature 13 of the second cap 10' and opens into the recess 24 of the female nipple 22, then crosses this obviously 24, while the blind cavity 23 is threaded into the body of the male stud 21. This allows to have a thick axial dimension for arranging the length of the thread in the body of the male stud 21 and to avoid over-thickening the diaphragm diaphragm 11 or the hub 17 in the center of the cap 10 to do this.

Thus, the two lids 10 and 10 'can be assembled one against the other, inner face against inner face, the elastic collar 25 of the male stud 21 to snap or "clipping" and permanently subject to the interior of such complementary fastening means 22-24-26, this in a simple, almost automatic manner, the manipulator having just to pull the rod 31 or inner cannula, in the retracted position, relative to the second intermediate cannula 32 of the catheter 30, as illustrated in FIG. 7, to engage the complementary fastening means 21 and 22 and to engage them, which makes it possible to assemble the two caps 10 and 10 'by snap-fastening, by enclosing the wall 7 between the membranes 11-11' deployed lids 10 and 10 '. The manipulator can finally turn the axial rod 31 or inner cannula on itself to unscrew its end and detach it from the first lid 10.

Such an embodiment of fastening means 21 and 22 complementary and axial is particularly advantageous, economical in volume of material, arranged along the axis AA of the most favorable mechanical connection, is housed in the communication via the orifice 9 to be closed and assumes several functions: that of cooperation with the support means 31, supply and placement of the two lids 10 and 10 'with the aid of a catheter 30, in addition to its functions of assembly means 21- They are simple, compact and easy to operate, which is crucial for its maneuverability, its use by a surgeon and its ease of catheterization to locations that are generally particularly difficult to access and inaccessible manually.

Alternatively, the exemplary embodiment illustrated in FIG. 8 has a multiple-click clipping system. The modification with respect to the system shown in FIGS. 3A to 7 only holds in the male stud 21 which elongates to carry a plurality of elastic collars and the adapted cavity 24 sees its passage orifice 20 of the axial rod 31 widen to let the entire width of the male stud 21 lying down. This system advantageously allowing one side to offer greater freedom of adaptation to the organic wall thickness 7 and, on the other hand, greater security of clipping, several notches to be unclipped so that the two lids 10 and 10 'are disconnected. Given the enlargement of the passage opening 20 of the axial rod 31, the self-centering of the two parts of the assembly system can only be ensured by adding a movable centering shuttle 41, of the shape a shell, initially positioned in the cavity 24 and slidable along the axial rod 31. The latter would be seen in this second advantageous system with a small rim 42 just below its threaded end, so that during its unscrewing then from its extraction, it carries with it the movable centering shuttle 41. The handling, positioning and assembly of the exemplary reciprocating system device illustrated in FIG. 8 is exactly the same. way as for the exemplary device shown in FIGS. 3A through 7.

To complete the occlusion device 100 according to the invention, a diaphragm diaphragm 1 1 is disposed on the self-expanding flexible frame 13 of at least one lid 10, and preferably on each frame 13 of the two covers 10 and 10 of the device 100.

The diaphragm diaphragm 1 1 is advantageously formed of a veil or sheet of circular or oblong shape, in particular oval or elliptical, similar to a piece of dressing or a closet (or "patch"), flexible and thin. This membrane 1 1 has, as an indication, a thickness of the order of a tenth of a millimeter to a millimeter, or even of a fraction less than a tenth of a millimeter to a few millimeters, while the dimensions of the diaphragm 1 1 of the The operculum 10 deployed can reach on the order of one or several millimeters to several centimeters or to a decimetre. More specifically, the thickness of the wall of this diaphragm diaphragm 11 may be between fifty micrometers (50 μπή and two millimeters (2 mm), while the radius of a diaphragm 11 1 circular 10 operculum deployed can reach between two millimeters (2 mm) and five centimeters (5 cm).

Although not excluding the eventuality, if the realization of the device necessitated, other materials, for a fraction as small as possible of the device, provided that they are at least perfectly biocompatible, it is provided according to the The lids 10 and 10 'of this device 100 are advantageously made exclusively of biocompatible, bioresorbable and non-thrombogenic organic polymer material. The adjective 'organic' used to qualify a material or a polymer, is used herein, in the chemical sense of the term, that is to say that it is materials or polymers consisting of a or of a plurality of chemical compounds essentially based on carbon, hydrogen, oxygen and / or nitrogen (C, H, O, N), with optionally one or more heteroatoms such as sulfur (S), or even the chlorine (Cl) and / or phosphorus (P) or trace elements, in extremely minor proportions.

By bioabsorbable is meant herein, a chemical body capable of degrading and resorbing in the organic body medium, that is to say, to disappear almost completely in the presence of the tissues and organic fluids of the body that eliminate the products degradation, and this at body temperature. According to the invention, the device is degraded, globally or progressively, over a period of time corresponding to that required for healing and preferably for consolidation or even complete restoration of the natural functions of the patient's target organ. . Such a length of time can be of the order of a week to ten years, more precisely between one month and one year, typically around two to six months.

One or more bioabsorbable organic polymer materials may be used to produce part or parts, preferably all or, failing that, the largest possible part of each cap 10 of the occlusion device 100 and its attachment means 21 -22 axial.

Thus, it is possible either to make the diaphragm membrane 1 of each lid 10, in whole or in part, in one or more bioresorbable organic polymer materials, or to make the self-expanding flexible armature 13 of each lid 10, in whole or in part. part, in one or more bioabsorbable organic polymeric materials. Similarly, the axial fastening means 21-22 may also be made of one or more bioabsorbable organic polymer materials. Preferably, all or, failing that, the largest possible part of the device 100 is composed or constituted of one or more bioabsorbable polymer organic materials.

A single polymeric material may be used to make each portion, membrane 11, armature 13, hub 17 and / or fastening means 21 or 22 and possibly a single polymer material may be substantially the all of the two lids 10 and 10 'of the device 100. Preferably and particularly advantageously, it is provided according to the invention that a plurality of organic polymeric materials having different resorption periods are used to respectively perform each part of the occlusion device 100 , membrane 11, armature 13, flexible radiating edges, hub 17 and / or connecting means 21-22, which will make it possible in a particularly advantageous manner, as described hereinafter, to gradually deteriorate and resorption in successive steps, modulated and differed from the different parts of the device 100 while having adequate mechanical properties required by these different parts.

To achieve the caps 10 of biodegradable polymer material of the occlusion device 100, according to the invention, the two main parts of each cap 10, that is to say the two flexible armatures 13-15 with the hub 17 and its fastening element 21 for the first or 22 for the second, can be formed and obtained by molding in a single operation, which leads to an embodiment of monolithic seal.

Preferably, the flexible armature 13-15, with its hub 17 and its fastening element 21 or 22, each lid 10 and the flexible diaphragm diaphragm 11 are made separately. The self-expanding flexible armature 13-15, with its hub 17 and its fastening element 21 or 22, can advantageously be obtained by molding a bioresorbable organic polymer material, which makes it possible to obtain an edge structure conveniently. Flexible radiant pattern assuming a flared, campaniform, flared DC configuration, at rest, out of stress.

The diaphragm 11 of the seal 10 is preferably produced by a process for obtaining films, membranes or thin layers. The membranes 11 obtained can be porous or non-porous. Ideally, the process should make it possible in particular to obtain a polymer membrane 1 whose microstructure comprises a porosity calibrated so that the endothelial cells are deposited and grow in the interstices of porosity. In this kind of material, the porosity interstices are colonized and occluded by the cells of the organic tissues in a few days. Preferably, the porosity is controlled to be between one micrometer (1 μm) and one hundred micrometers (100 μm), typically between five micrometers (5 μm) and fifty micrometers (50 μm), preferably between ten micrometers ( 10 μm) and 45 micrometers (45 μm). The membrane of the operculum could be obtained with a single polymer compound or with a mixture of several different polymer compounds, preferably chemically close, but having different degradation rates.

The lid is formed by joining said membrane biodegradable organic polymer with the flexible armature deployed and solidarisant, the cohesion between these two parts forming the seal can be obtained by autogenous welding or using a biocompatible adhesive preferably composed of another biodegradable organic polymer.

Biocompatible and biodegradable polymer materials are like the biological molecules of organic compounds. Preferably, the biodegradable and / or bioabsorbable polymers contemplated for the invention are chosen from those that degrade without being directly involved in the metabolic processes and in particular are not sensitive to enzymatic activity. These polymers only bioabsorb under the effect of physicochemical processes, especially hydrolysis, independently of the metabolic or enzymatic activity. However, the products of this resorption, they can be and will be involved in the activity of cells and enzymes to be degraded, excreted and eliminated.

The chemical natures of the main polymers known to be bioabsorbable include polyesters, polyorthoesters, polyanhydrides, poly (ether) esters, polyamino acids and polydepsipeptides (see, for example: B. Buchholz J Mater Sci Mater Med 1993, 4: 381 - 388).

In a schematic, but not exhaustive manner, the bioresorbable organic polymers can be described by a basic unit corresponding to the following semi-developed general formula:

- [- X ^ CiOJ-R Y S H-Xz-CiOJ-Rz-Ya-Sz -] - in which:

C (O) denotes a group> C = O, ie a ketone group or a part of a carboxylic acid X ₁ and X ₂ denote an oxygen atom (-O-) or a secondary amino group (-NH-), which can become an amide bond

Yi (respectively Y ₂ ) denotes an oxygen atom (-O-), a group (- NH-), or a single or double chemical bond directly connecting Ri to Si (respectively F¾ to S2)

R ₂ ; Si and S ₂ denote linear or branched carbon chains of 0 to 10 carbon atoms, saturated or partially unsaturated, bearing or not heteroatoms. In a particular case, if X ₁ and X ₂ , i and R ₂ , Y ₁ and Y _{2 as} well as Si ₂ S ₂ are identical two by two, then the first monomer (the one whose indices are 1) is identical to the second (the one whose the indices are 2) and it is a homopolymer. In the opposite cases, they are copolymers.

In particular, in order to avoid being exposed to the mechanisms of protein degradation by the enzymes that attack the proteins and lyse the amide or peptide bonds (proteases, peptidases), it is preferable to choose polymeric materials that have no amide function or same amino function. The bioabsorbable polymer materials are therefore preferably polymerized from monomers having no amine function (-NH ₂ , - NH- or = N-) and therefore no nitrogen (N). Therefore, in the above synthetic general formula, all the cases in which the groups Xi, Υι, X ₂ , Y ₂ are amino groups will be excluded. The X ₁ and X _{2 groups} therefore consist of an oxygen atom or ether bond -O- (which becomes an ester bond since forming -O-C (O) -R).

Thus, among the vast class of the preceding families, appeared an advantageous structure taking the following form:

C (O) -Ri-Yi-Si-H-O-C (O) -R ₂ -Y ₂ -S eq ₂ in which:

-OC (O) - denotes a polymer bond formed by a group -OC = O, that is to say an ester bond R 1 and R ₂ denote a carbon chain, linear or branched, having from 0 to 5 carbon atoms (C) and preferably from 0 to 3 C

Yi (respectively Y ₂ ) denotes an oxygen atom (ie an ether bond or alcohol function) or a single or double chemical bond connecting Ri to Si (or R ₂ to S ₂ )

Si and S ₂ denote a carbon chain, linear or branched, having from 0 to 5 carbon atoms (C) and preferably from 0 to 3 C. Among these types of polymers two appear more particularly interesting. The first type is obtained when Y1 or Y2 is an oxygen atom, respectively giving the structures ~ [-O-C (O) -Ri-O-Si-] ~ and ~ [-O-C (O) -R ₂ - O-Sr -] - that is to say ester-ether. The other, simpler type is obtained when Yi or Y ₂ is a direct chemical bond (single or double), respectively giving the structures ~ [-O-C (O) -Ri-] ~ or ~ [-0- C (O) -Rn-] ~ in which R 1 or Rn is a carbon chain containing from 0 to 10 carbon atoms, preferably from 0 to 6 C.

Thus, among these two last types of polymers, corresponding to the two large families of poly (ester-ethers) and polyesters, all or part of the device of the invention should advantageously consist of homopolymers that are polylactides (where Ri = Rn and is a group -CH (CH ₃ ) -), polyglycolides (where R 1 = R n and is a group -CH ₂ -) and polydioxanones (where

and is a group -CHr- and where Si = S ₂ is a -CHr-CHr- group, as well as their copolymers or mixtures. However, other homopolymers and copolymers of the series or their mixtures may be used.

Alternatively, another type of bioabsorbable organic polymer of interest for the realization of all or part of the device of the invention is that corresponding to the cases where, in the equation 2, R 1 and / or R ₂ disappears replaced by a simple chemical bond or double giving the following semi-developed formula:

~ [-O-C (O) -Y ₁ -S ₁ -H-O-C (O) -Y ₂ -S ₂ -] ~ eq.3 In this case, if Y1 and Y2 respectively designate an oxygen atom and Si and S2 linear or branched carbon chains, then the resulting polymer ~ [-O-C (O) -O-Si-] ~ [-0- C (O) -O-S2-] - is a poly (alkylenecarbonate) (if S = S ₂ ) or a poly (co-alkylenecarbonate) (if Si ≠ S2>.

These polymers have the ability to be resorbed in vivo according to established and predictable resorption modes, especially in their duration, independent of the organic activity of the tissue, and whose rate of chemical degradation is mainly related to the temperature, the latter being substantially constant in human tissues. It thus becomes possible to defer and modulate the resorption of the occlusion device according to the invention as a function of the polymeric material (s) chosen from such families of bioabsorbable organic polymeric materials.

Particularly advantageously, it is provided according to the invention to produce each occlusion device seal from several bioresorbable polymeric materials having respectively distinct and staggered resorption times (deferred and modulated), depending on the constituent part. of the device 100 in which they integrate. Advantageously, it is thus possible to obtain that the different portions of the device gradually disintegrate, in turn, as and when the organic tissues resume and occupy their place, so depending on their replacement by organic functions.

The chosen / selected polymeric materials for producing each part of the occlusion device 100 according to the invention, ie respectively the flexible membrane 1 1, the flexible armature 13 and the connection means 21-22 of each lid 10 or 10 ', In addition to resorption times that are staggered and compatible with the tissue reconstruction times and the restoration of the organic function, intrinsic mechanical properties compatible with the expected mechanical properties of each part of the device must be provided. Here, for example, the expected mechanical properties of each part:

• for the membrane: a relative flexibility compared to the frame and a degradation in a few weeks or a few months; • for reinforcement: flexibility, ie absence of plasticity and relative rigidity and a relatively long resorption time, greater than the membrane and of the order of one month to one or two years, typically between 2 and 6 months ;

• for the assembly system: elastically deformable and long resorption time, equal to or greater than the reinforcement.

Thus, if the membrane can degrade quickly, it is most important that the self-expanding frame is flexible and relatively rigid while being durable, i.e. lasts much longer or lasts at least as long as the flexible membrane. The resorption time periods of the various elements of the device of the invention are provided so as to correspond to the time required for the regeneration of the organic tissues surrounding the sealed orifice or the restoration of the deficient organic function, which makes it possible to obtain a healing and a complete consolidation of the patient's condition.

Particularly advantageously, in the case of an application to the closure of the foramen ovale through the cardiac interauricular wall by an occlusion device according to the invention, the two diaphragm diaphragms of the operculum will gradually be absorbed. from the periphery to the center, the thickness of each membrane growing advantageously regularly from the limbs towards the center of the membrane, as and when they are replaced by the growth of the organic tissues which, stimulated by the presence of this support, grow on the membrane of the operculum. Thus the orifice is progressively occupied by the cicatrization of the organic tissues. Once the orifice is closed by the growth of the endothelium of the inter-auricular wall, the armature begins to fall apart and to gradually recover from the periphery towards the center of the operculum. Finally, once the reinforcement resorbed, the central part with the assembly means of the device which are embedded in the organic tissues are degraded and gradually resorb, without external intervention.

For wound closure applications, the lids of the device can be resorbed in much shorter periods of time than occlusion devices for occluding a foramen ovale or a communication port through cardiac walls. For example, a wound occlusion device can be resorbed and disappear in periods of time ranging from a week to a month or a few months, at most a year. Each operculum be made of a single polymeric material or the same type of polymeric materials or in bioabsorbable organic polymeric materials in relatively short periods of time.

In the case of the present invention, the recognized flexibility and shape memory properties of the polydioxanones are particularly advantageous precisely for the realization of the flexible reinforcement which must return to its initial shape, ie its flared campaniform neutral configuration as well as for the realization of the assembly means which must have flexible forms of complementary male and female studs, to be inserted elastically by snapping into a complementary form of receptacle having a flexible tubular wall having a recess with an elastic annular shrink neck.

Similarly, the recognized ability to promote the colonization and multiplication of cells within them porous polydioxanone supports, make this material an advantageous choice for the realization of the membrane of the device of the invention.

In addition, polydioxanones are known to cause almost no inflammatory reaction and, unlike the metals used in the prior art, do not cause the formation or reappearance of emboli or thrombus (clot) resulting from coagulation phenomena on their structure.

Claims

Occlusion device for a foramen or an open orifice in organic tissues, composed of at least two elements capable of being assembled against each other: a first operculum and a second operculum, each operculum comprising a membrane of diaphragm provided with a self-expanding flexible frame integral with the membrane, characterized in that the two flexible frames are made of bioresorbable organic polymer material.

Occlusion device according to claim 1, characterized in that the device is made of one or more bioabsorbable organic polymer material.

Occlusion device according to claim 1 or 2, wherein each cap comprises a flexible diaphragm membrane provided with a self-expanding flexible armature integral with the flexible membrane, the flexible armature being more rigid than the flexible membrane and conferring each covers a campaniform deployed service configuration, the deployment of the flexible armature tending to extend the diaphragm diaphragm towards said campaniform deployed configuration, the flexible armature exerting a force in a direction of deployment if the lid is bent below said configuration, the flexible armature exerting a restoring force and folding in the opposite direction if the cap is biased towards an extension configuration beyond said campaniform deployed configuration.

Occlusion device according to one of claims 1 to 3, wherein the two caps have, preferably in their central part, complementary fixing means for a final assembly against each other and binding the flexible frames to extend beyond their campaniform unfolded configuration, so that both flexible armatures exert restoring forces and support in opposite directions and plating the two deployed membranes towards each other.

Device according to one of claims 1 to 4, wherein the armature comprises a plurality of ridges or whales extending radially around a central zone or hub, preferably of the number of three to sixteen, typically from four to twelve, the edges or ribs of the armature having a radial length substantially corresponding to the radius or transverse half-dimension of the diaphragm diaphragm deployed, the edges or ribs of the armature being flexible and at rest a deployed position in bell or umbrella, position towards which they tend to return when they are biased in an axial direction or in the other axial direction.

Device according to one of claims 1 to 5, wherein the two lids are fixed together against each other by a latching system, crimping, riveting or type 'snap'.

Device according to one of claims 1 to 6, wherein a central portion of each lid comprises a fastening means having a complementary shape and adapted to cooperate with a fastening means complementary to the other lid.

Device according to one of claims 1 to 7, wherein the membrane is made of the same material or materials as the armature.

Device according to one of claims 1 to 8, wherein the armature is obtained by molding.

Device according to one of claims 1 to 9, wherein the membrane of the diaphragm is secured to the armature of the lid by welding, in particular autogenous welding, or by bonding, in particular with a biological adhesive, ie biocompatible and / or biodegradable.

Device according to one of claims 1 to 10, wherein the membrane is microporous, preferably with a porosity of the order of one micrometer to one hundred micrometers, typically between five micrometers and fifty micrometers, preferably between 10 micrometers. pm and 45 pm.

Device according to one of claims 1 to 11, wherein the membrane of each lid has a thickness of between fifty micrometers and two millimeters.

Device according to one of claims 1 to 12, wherein each deployed operculum has a diameter or transverse dimensions of between one millimeter and ten centimeters.

Device according to one of claims 1 to 13, wherein the diaphragm diaphragm of each expanded cap takes the form of a flexible disk or the diaphragm of each cap has a generally circular or oval, revolving or oblong expanded form.

15. Device according to one of claims 1 to 14, wherein one of the bioresorbable organic polymeric materials, known to be the most biocompatible possible, the least thrombogenic possible, is selected from a polylactide, a polyglycolide, a polycaprolactam, a polycaprolactone, a copolymer or mixtures of the aforesaid materials.

The device of claim 15 wherein the material is a polydioxanone.