Stent for implantation

Abstract

The present invention relates to a biodegradable, resorbable stent, comprising a structure consisting of a metal alloy of magnesium with transition metals and / or rare earths, wherein the structure is encased by a polymer and the encased structure has struts of stent elements, wherein the stent can be a valve-bearing stent. The present invention also relates to the use of the disclosed stent without valves, or of a system comprising a corresponding stent for implantation in the case of congenital heart defects for opening a pulmonary artery, for keeping open a ductus arteriosus Botalli, for keeping open an aortic isthmus stenosis for incentivising growth in hypoplastic pulmonary arteries, or as an oesophagus stent, or as a ureter support.

Description

STENT FOR IMPLANTATION DESCRIPTION Field of the invention

[0001] The present invention relates to stents for implantation, also comprising a heart valve-carrying stent, intended in particular for implantation in children. Brief description of the background of the invention

[0002] Congenital heart defects affect an estimated one in every 100 newborns. These heart defects can vary in severity and therefore affect different structures of a newborn's heart. Treatment for congenital heart defects depends on the type and severity of the defect. Some affected infants and children may require one or more surgeries to ensure their heart or blood vessels function properly.

[0003] For example, it may be necessary to insert so-called stents. The term "stent" refers to vascular prostheses or "supports" that are inserted through intervention, for example, to widen narrowed vessels. Stents are also used to anchor heart valves in the vascular system. Currently, due to a lack of pediatric-friendly products, permanent, non-absorbable stents developed for adult patients are used.

[0004] A particular problem with the implantation of stents in children, and especially in newborns, is due to the fact that the stents cannot “grow”, which hinders the physiological growth of surrounding structures, such as vessels.

[0005] Two main types of permanent stents are known from the current state of the art: balloon-expandable and self-expanding stents. Balloon-expandable, permanent stents are currently the most commonly used to treat vascular stenosis. Balloon-expandable stents are usually made of deformable metals or metal alloys. Self-expanding stents are usually made of a nickel-titanium mixture (nitinol). Nitinol exhibits pseudoelasticity and a shape-memory effect as characteristic properties. Balloon-expandable stents can be re-dilated after implantation in a growing child, thereby achieving an increase in diameter. Re-dilation is not always possible (depending on the ingrowth behavior and the location of the stent). Re-dilation can sometimes damage or tear the surrounding structures during re-dilation.Self-expanding stents are not dilated; they usually open almost to their predetermined final diameter depending on their radial force and the ambient pressure of the vessel counteracting the radial force.

[0006] The published international patent application with the file number WO 2011 / 000354 A2 discloses a stent into which a heart valve has been sewn. The stent consists of a plurality of coaxially arranged crown elements, each formed from several U-shaped arches with at least one base and two ends. According to the invention, the bases of a crown element are connected to the ends of a crown element via connecting webs. To manufacture this valve stent, a 3D droplet dosing technique is used to form a thin-walled sandwich structure. The invention further relates to a device suitable for applying a stent, comprising positioning wires having clamps at their ends that can be force-fitted to the fixing hooks of the ends of the crown elements.

[0007] The published international patent application with the file number WO 2016 / 071357 A1 relates to an intraluminal vascular implant, comprising a first hollow cylindrical vessel body and at least one second hollow cylindrical vessel body, wherein the first and the second vessel body are two structurally separate vessel bodies. The vessel bodies each have a first end, a second end and a longitudinal axis, wherein the first and the second vessel body each have vessel sections. The vessel section of the first vessel body and the vessel section of the second vessel body are designed such that they can be at least partially inserted into each other to form a common stent section free of prosthetic material.

[0008] The published international patent application with the file number WO 2016 / 055564 A1 describes a vascular prosthesis system for introducing into and supporting a blood vessel of a patient, wherein the vascular prosthesis system comprises (i) a stent graft element with a hollow cylindrical body, wherein the stent graft element has meandering circumferential supports and a prosthetic material attached to and connecting the supports to form a circumferentially covered stent graft element, and (ii) a stent element with a hollow cylindrical body, wherein the stent element has a stent support structure that is free of prosthetic material, to form an uncovered stent element.Furthermore, a strip-shaped prosthetic material section is provided, via which the stent graft element and the stent element are connected to one another, such that the strip-shaped prosthetic material section is fixed with a first end only to the first, proximal stent graft element end and with its second end to the first, proximal stent element end to form a prosthetic material bridge.

[0009] The published international patent application with the file number WO 2000 / 062708 A1 relates to a multi-part stent comprising a connecting structure that allows the stent sections to move and bend relative to one another. For deployment and positioning, the connecting structure connects the multiple stent sections and keeps the stent sections substantially stationary relative to one another. After deployment, the connecting structure allows the multiple stent sections to move relative to one another. The movable stent sections enable the stent to bend during deployment within a body lumen. This flexible structure enables a better conformation of the stent to the shape of the body lumen and exerts less overall pressure on the lumen wall, thereby reducing the risk of trauma. After deployment, the various stent sections can be completely detached from one another.Alternatively, the stent sections can remain partially connected so that they can move largely independently of each other. The connecting structure can be designed to separate upon deployment, e.g., due to rupture or degradation within the body lumen in which the stent is positioned.

[0010] The published international patent application with the file number WO 2019 / 052610 A1 relates to an implantable valve prosthesis, in particular for preventing blood backflow from an atrium into a vein flowing into the atrium. The object of the present invention is to provide an alternative to the currently available means for treating mitral or tricuspid valve insufficiency.To achieve the object, the invention provides an implantable valve prosthesis, comprising - a generally tubular stent, which can be branched or unbranched and has at least a first end section with a first end opening and a second end section with a second end opening, and - a flexible tube, which can be branched or unbranched and has at least a first end section with a first end opening and a second end section with a second end opening that can be closed by collapsing the tube, which flexible tube is arranged at least in a partial region of the second end section of the stent on its outer peripheral surface such that the tube with its second end section and the second end opening projects beyond the second end opening of the stent, wherein the second end opening of the tube is open in the unpressurized state.

[0011] The published German patent application with the file number DE 4222 610 A1 describes a stent for valve and closing devices, in particular for heart valve prostheses, which stent has a base ring which carries at least two posts which are symmetrically offset from one another and point essentially in the ring axis direction and are connected to one another via arched strips which serve to attach at least two flexible leaflets, with which stent a valve or closing device, in particular a heart valve prosthesis, can be produced which works reliably even with different closing pressure differences, i.e. in particular also with varying physiological load conditions, the stent is kept flexible only in certain areas and to a limited extent, namely by a rigid design of the free post ends and / or a limit-limited flexibility of the post bases and / or a limit-limited flexibility of the strips.

[0012] The published US patent application US 2009 / 0312834 A1 relates to stent structures with improved migration resistance. In particular, US 2009 / 0312834 A1 relates to Mesh stents, such as braided or twisted stents, in which at least a portion of the stent is folded back upon itself to form a multi-layered stent device. Such multi-layered sections provide migration resistance, among other advantages.

[0013] Published US patent application US 2012 / 0290073 A1 discloses a bioabsorbable scaffold composed at least partially of a poly(L-lactide)-based composite. The composite contains poly(4-hydroxybutyrate) or poly(L-lactide)-b-polycaprolactone block copolymer, which increases the fracture toughness or fracture strength of the scaffold. The composite may also contain bioceramic particles, L-lactide monomer, or both distributed throughout the composite. The bioceramic particles improve the radial strength and stiffness of the scaffold. The L-lactide monomer is used to control the scaffold's absorption rate.

[0014] The published international application WO 2016 / 127542 A1 discloses a multilayer, expandable vascular scaffold comprising at least two layers of lattice-like scaffold walls made of a magnesium alloy and a scaffold interior cavity. An expandable balloon is disposed within the scaffold interior. During expansion of the multilayer, expandable vascular scaffold, the scaffold wall near the outer layer exceeds its strain rate and fractures due to the relatively large expansion. By providing the multilayer, lattice-like scaffold wall according to WO 2016 / 127542 A1, the vascular scaffold is prevented from fracture and loss of scaffold function caused by fracture of the outer layer during expansion, and safety is also improved.

[0015] Published US patent application US 2021 / 0338422 A1 discloses valve prostheses with mechanically coupled leaflets. The embodiments described in this document are directed to centrally opening valve prostheses with a valve frame and a mechanically coupled valve. The described valve frames have projections configured to connect to a valve attachment region of a valve. Some embodiments include a valve retention device that engages the projections of the valve frame and serves to secure the valve to the valve frame. Furthermore, a method for manufacturing and using such valve prostheses is described.

[0016] The published German patent application DE 10 2008 040 786 A1 describes an implant with a base body which consists entirely or in part of a biocorrodible, metallic material, wherein the material is such that it decomposes into an alkaline product in an aqueous environment and wherein the base body has a coating or a cavity filling which comprises a polymer matrix and at least one active ingredient embedded in the polymer matrix, characterized in that at least one polymer of the matrix and the at least one active ingredient are coordinated with one another in such a way that the release rate of the active ingredient from the matrix is ​​increased with increasing pH.

[0017] The published American patent application US 2011 / 060401 A1 relates to a tubular, growth-capable supporting prosthesis with a mesh structure, wherein the mesh structure consists of at least two structural rings which are connected to one another via connecting elements and are arranged point-symmetrically around the longitudinal axis of the prosthesis, wherein the structural rings and / or the connecting elements have at least one predetermined breaking point.

[0018] Published American patent application US 2013 / 325102 A1 discloses an absorbable blood vessel stent having a proximal end and a distal end. A tubular structure with a pattern is formed between the proximal end and the distal end. The patterned structure includes a plurality of support and connecting rods. The support rod or the connecting rod has a straight, U-shaped, or S-shaped section, and at least one through-groove or through-hole is provided in at least one support rod. Due to the special structure of the blood vessel stent, the performance of an iron blood vessel stent can be improved, and blood vessel stents made of other absorbable materials can degrade more quickly.

[0019] With absorbable stents, as described above, the problem is adjusting or setting the absorption time so that the stented heart and vascular segments are not hindered from growing. The foreign material (stent, occluder, etc.) grows into the tissue. The adhesion fixes the stent in its position, and the tissue takes on the shape of the stent and also remains in this position. This The use of conventional stents hinders the growth of the supplied heart and vascular sections.

[0020] A permanent stent is particularly disadvantageous for heart valve implantation in children, as the valve itself makes it even more difficult to post-dilate than a non-valved balloon-expandable stent. The heart valve could be damaged during post-dilation because the valve tissue would be crushed between the high-pressure balloon and the stent.

[0021] In 2007, Zartner et al. described the first application of a magnesium stent in children with hypoplastic pulmonary arteries (Zartner, P., et al. Catheterization and Cardiovascular Interventions, 2007, 69(3), 443-446). However, the disadvantage of the stent described in this publication was that it dissolved so quickly that no long-term results could be achieved.

[0022] Also in 2007, Waksman published a review of bioresorbable stent options (Waksman, R, Catheterization and Cardiovascular Interventions, 2007, 70(3), 407-414). The stents described in this publication have a resorption time of 6 to 24 months, which is considered too long for use in growing infants.

[0023] Therefore, there is still a need for a stent that can be used especially in children. Object of the invention

[0024] The object of the present invention therefore concerns the provision of a stent for vascular care in which the absorption time of the biodegradable stent can be adjusted so that vascular growth is not hindered. Such a stent is intended for use in particular in newborns and children. Summary of the invention

[0025] The present invention discloses a biodegradable, resorbable stent comprising a scaffold consisting of a metal alloy of magnesium with transition metals and / or rare earths, wherein the scaffold is coated with a polymer and the coated scaffold has struts of stent elements.

[0026] In one embodiment, the stent elements are diamond-shaped.

[0027] One embodiment of the stent relates to a stent in which the struts are flattened.

[0028] According to the invention, it is further provided that the struts of the stent elements are slotted.

[0029] In a further embodiment of the stent, it is provided that the rare earths are selected from the group of lanthanides, comprising gadolinium, disprosium, yttrium.

[0030] The struts of a stent according to the present disclosure may have barbs.

[0031] Furthermore, it can be provided that the circumference has 24, 21, 18, 15 or 12 stent elements.

[0032] The invention also relates to an embodiment of the stent, wherein the barbs have a diameter of up to 20 to 50 pm.

[0033] The barbs of a stent according to the present invention may be bent inwardly at an angle between 45° to 90° with respect to the struts of the stent.

[0034] In a further embodiment of a stent according to the present invention, it is provided that the polymer of the sheath is biodegradable, wherein the polymer is poly(DL-lactide-co-glycolide).

[0035] According to the invention, one embodiment is a valve-bearing stent.

[0036] In the case of a valve-bearing stent, the circumference of the framework is provided with a number of stent elements divisible by 3, with the framework having 24, 21, 18, 15 or 12 stent elements.

[0037] In one embodiment of the valve-bearing stent, the heart valves are attached to the barbs of the struts.

[0038] A further object of the present invention relates to a system for implanting a stent comprising a device for implanting a stent as described above.

[0039] Furthermore, the present invention relates to the use of a stent as described above without valves, or of a system as described above, for implanting the stent in cases of congenital heart defects to open a pulmonary artery, to keep open a ductus arteriosus Botalli, to keep open an aortic isthmus stenosis to create a growth stimulus in hypoplastic pulmonary arteries, or as an esophageal stent, or as a ureteral support. Summary of figures

[0040] The invention is described with reference to figures. It will be apparent to those skilled in the art that the embodiments and aspects of the invention described in the figures are only examples and do not limit the scope of the claims in any way. The invention is defined by the claims and their equivalents. It is understood that features of one aspect or embodiment of the invention may be combined with a feature of another aspect or aspects of other embodiments of the invention.

[0041] FIG. 1 shows a schematic overview of an embodiment of the structure of a stent according to the invention.

[0042] FIG. 2 schematically shows a tubular stent.

[0043] FIG. 3 schematically shows an embodiment of the barbs. Detailed description of the invention

[0044] The technical problem is solved by the independent claims. The dependent claims address further embodiments of the invention.

[0045] For the purposes of the present invention, the term “biodegradable” is understood to mean a property of the metal alloy, polymers or polymer mixtures that they can be biologically degraded in the human or animal body without endangering the health of humans or animals.

[0046] The problem described above and underlying the invention is solved by a valve-bearing, biodegradable, resorbable stent made of a metal alloy of magnesium and rare earths in combination with a coating made of a polymer mixture. The entire stent made of metal alloy and polymer coating is biodegradable, which, in the context of the present disclosure, refers to chemical decomposition into smaller molecules, compounds, or even elements through biological processes. An example of a biodegradable polymer within the meaning of the present disclosure is poly(DL-lactide-co-glycolide).

[0047] The structure of the stent is based on continuously arranged struts, which form so-called stent elements. These stent elements can, for example, be rhombus-shaped, which in the context of the present invention can also be referred to as diamond shape. In one embodiment, the struts of the stent can serve to attach heart valves. Thus, the same number of Diamonds are available. The number of diamonds around a stent is therefore a number divisible by 3, preferably 24 or 21, and 18, 15, or 12 for stents with a smaller target diameter. The number of strut elements divisible by 3 results from the fact that a three-leaflet valve must be sewn / attached, point-symmetrical to the center of the stent, with all valve leaflets being the same size. Each of the three leaflets therefore requires the same number of attachment struts.

[0048] The stent, cut from a tube, is manufactured with barbs (spikes) that serve to fix a heart valve (heart valve holder). According to the invention, a stent may comprise only one row of diamonds around its circumference, several rows of diamonds may be arranged directly adjacent to one another and connected to one another, or the diamonds may be connected to one another around its circumference via struts.

[0049] Another element of the present invention are, in one embodiment, integrated barbs (so-called spikes), with the aid of which, for example, the heart valve consisting of pericardium is fixed in the stent.

[0050] The invention is based on a fluoridated or non-fluoridated compound (alloy) of magnesium, transition metals, rare earths, for example from the group of lanthanides such as gadolinium, disprosium, yttrium, etc., in combination with a mixture of polymers. Magnesium has a short resorption time. For this reason, a stent according to the present disclosure proposes a combination of a small amount of polymer on a framework consisting of magnesium and rare earths as the material in order to achieve a precisely adjustable resorption time. The combination of magnesium and rare earths has proven advantageous with regard to the adjustability of the resorption time. The stent consists of a framework formed by a net-like, for example, diamond-shaped, structure made of a mesh of the metal-rare earth alloy, which is coated with a polymer.In one embodiment, flattened metal struts are connected to each other in a diamond shape.

[0051] It is obvious to the expert that the advantages of adjusting the resorption time allow for better synchronization with the growth of the vessels.

[0052] In one embodiment, it can be provided that the struts of the stent elements are flattened and have recesses in the surface; the struts, which Stent elements are therefore slitted. One section of the honeycomb-like mesh structure made of struts is connected via lateral struts to another section of a diamond-shaped honeycomb-like mesh structure, for example. This design allows the stent to be adjusted in both width and length depending on the intended application.

[0053] The stent structure is coated with a polymer coating. This coating ensures that the stent's resorption time can be adjusted to a defined period (targeted at 3-6 months).

[0054] The stent struts can have barbs with a diameter ranging from 20 to 50 μm. After cutting, polishing, and coating the magnesium alloy polymer stent, the spikes are bent luminally (inwardly into the stent) at an angle of 45-90° and now extend into the stent interior.

[0055] After forming a heart valve from the patient's own tissue, the stent can be pulled over the valve in a suitable design. The barbs pierce the pericardium and anchor themselves there. The heart valve is thus anchored in the stent without any additional sutures, except for a few safety stitches. Since sewing a heart valve into a stent normally takes up a large portion of the manufacturing time for a heart valve stent (experience shows that this takes between 40 and 60 minutes), the invention of the barbs saves valuable intervention time and thus anesthesia time for the patient.

[0056] A heart valve stent is delivered using a delivery system that includes a balloon catheter through which the Mg / rare earth / polymer stent can be anchored in children with congenital heart valve defects.

[0057] The stent according to the invention is a balloon-expandable stent whose struts can be slit and filled with polymer. It is envisaged that the polymer-coated struts can be designed as double-T beams to achieve greater mechanical stability.

[0058] The shape of the stent is chosen depending on the location of use: For use in a pulmonary valve position, the stent is shaped in length and circumference For example, they can consist of diamond-shaped diamonds, although this shape is not mandatory. Each diamond is connected to the neighboring diamonds at its four corners. This means that all diamonds have a closed configuration (see FIG. 1 and FIG. 2). For use in the aortic valve position, an upper ring of diamonds is created (crown), followed by long, longitudinal, curved struts in the commissure area and a conical skirt consisting of two rows of diamonds in the left ventricular outflow tract area.

[0059] According to the invention, applications without the use of a heart valve are also conceivable: For use in a hypoplastic aortic segment (coarctation of the aorta), a stent with a large number of short struts, thus creating small diamonds, is manufactured. All struts are connected to each other by a connector. This provides the stent with high radial force and low longitudinal shortening.

[0060] For use in pulmonary arteries, a smaller number of longer struts are used. Not every diamond (= diamond; a square surrounded by struts) is connected to every other diamond via connectors. This allows for greater longitudinal deformability for improved maneuverability and to prevent stent fractures.

[0061] For applications outside the cardiovascular system, the stent according to the invention can be designed according to specific requirements, including, for example, the need for radial force, planned indwelling time, and the required diameter. One advantage of the invention is that the stent can be adapted to different requirements.

[0062] Further advantages and improvements over known state-of-the-art stents include the time-controlled dissolution behavior of the stent due to the alloy of magnesium and rare earths used. This allows for the treatment of vascular constrictions over a precisely defined period of time, thus enabling the treated vascular and cardiac segments to continue to grow. This is particularly advantageous for newborns, infants, and small children, as their heart and vascular growth rates are rapid. Experience has shown that treatment with conventional stents and prostheses frequently leads to stenosis in children and newborns within a short period of time. The biodegradable stent according to the invention, on the other hand, allows normal growth of the vessels of children and newborns.

[0063] To date, no stent is known in which heart valve tissue is anchored in a stent by means of barbs.

[0064] FIG. 3 schematically shows an embodiment of the barbs of a stent according to the invention.

[0065] A biodegradable stent according to the present invention can be used as a vascular support in various congenital heart defects, e.g. for opening a pulmonary atresia, for keeping a patent ductus arteriosus, for keeping a patent aortic isthmus stenosis, for creating a growth stimulus in hypoplastic pulmonary arteries (“artificial growth”).

[0066] Furthermore, applications of the stent according to the invention outside of cardiovascular medicine are conceivable, for example as esophageal stents, as ureteral supports and in urethral valves.

[0067] The present invention also relates to a system comprising a device for implanting a stent as described above, together with the stent.Such a device is described, for example, in the published German patent application with the file number DE 10 2013 224 298 A1 and comprises a device for the transluminal introduction and placement of a self-expandable stent, in particular a heart valve stent, into a hollow organ, wherein the stent is arranged in a compressed state at the distal end of a tubular, flexible implantation catheter, characterized in that it has a tubular outer catheter, a tubular inner catheter and a tubular ring-shaped helical tension spring arranged at least at the distal end of the implantation catheter between the outer catheter and the inner catheter, which supports the proximal end of the stent with its distal end, which stent unfolds at the implantation site by retracting the outer catheter relative to the helical tension spring to bear against the hollow organ.

[0068] The foregoing description of the preferred embodiment of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the invention. The embodiment was chosen and described in order to explain the principles of the invention and their practical application to enable those skilled in the art to utilize the invention in various embodiments as are suited to the particular application. It is intended that the scope of the invention be defined by the appended claims and their equivalents. The entirety of the foregoing documents is incorporated herein by reference. Reference symbol A Area of ​​the sinus of the semilunar valve B Area of ​​the intervalvular trigone C Barbs D Stent strut E Stent area near the outflow tract F, G, H, I, K, L Slot within a strut J Eyelet for seam fastening M Eye N Device for repositioning using a storage system

Claims

CLAIMS 1. A biodegradable, resorbable stent comprising a scaffold consisting of a metal alloy of magnesium with transition metals and / or rare earths, wherein the scaffold is coated with a polymer and the coated scaffold has struts of stent elements.

2. The stent of claim 1, wherein the stent elements are diamond-shaped.

3. The stent according to any one of claims 1 or 2, wherein the struts are flattened.

4. The stent according to any one of claims 1 to 3, wherein the struts of the stent elements are slotted.

5. The stent according to any one of claims 1 to 4, wherein the rare earths are selected from the group of lanthanums comprising gadolinium, disprosium, yttrium.

6. The stent of any one of claims 1 to 4, wherein the struts have barbs.

7. The stent of claim 5, wherein the barbs have a diameter in the range of 20 to 50 pm.

8. The stent of any one of claims 1 to 6, wherein the barbs are bent inwardly at an angle of between 45° to 90° with respect to the struts of the stent.

9. The stent according to any one of claims 1 to 7, wherein the polymer is poly(DL-lactide-co-glycolide) 10. The stent according to any one of claims 1 to 8, which is a valved stent.

11. The stent of claim 9, wherein the circumference of the framework has a number of stent elements divisible by 3.

12. The stent of claim 11, wherein the framework comprises 24, 21, 18, 15 or 12 stent elements.

13. The stent according to any one of claims 9 to 11, wherein the heart valves are attached to the barbs of the struts 14. A system for implanting a stent, comprising a device for implanting a stent and a stent according to any one of claims 1 to 12.

15. The use of a stent according to any one of claims 1 to 8 or a system according to claim 13 for implanting the stent in cases of congenital heart defects for opening a pulmonary artery, for maintaining patent ductus arteriosus, for maintaining patent coarctation of the aorta, for creating a growth stimulus in hypoplastic pulmonary arteries, or as an esophageal stent, or as a ureteral support.

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