WO2019175888A1

WO2019175888A1 - Expandable endo prosthesis with low crimp profile

Info

Publication number: WO2019175888A1
Application number: PCT/IN2018/050298
Authority: WO
Inventors: Deveshkumar Mahendralal KOTHWALA; Rajnikant Gandalal Vyas; Pramod Kumar Minocha
Original assignee: Meril Life Sciences Pvt Ltd
Priority date: 2018-03-16
Filing date: 2018-05-12
Publication date: 2019-09-19

Abstract

An expandable endo prosthesis with low crimp profile is disclosed. The expandable endo prosthesis is implantable in a human blood vessel. The expandable endo prosthesis includes an expandable stent with an outer surface, an inner surface, a proximal end, a distal end and a crimp profile of 0.9 mm. The expandable endo prosthesis includes a tissue graft which covers the outer surface of the expandable stent and has a thickness within a range of 0.08 mm to 0.12mm. The tissue graft is anti- calcified. The crimp profile of the expandable stent and the tissue graft assembly is within a range of 1.2mm to 1.3mm.

Description

EXPANDABLE ENDO PROSTHESIS WITH LOW CRIMP PROFILE

FIELD OF INVENTION

[001] The present invention relates to an expandable endo prosthetic device. More particularly, the invention relates to a stent-graft assembly forming an expandable endo prosthesis implantable in tortuous and/or low diameter blood vessels.

BACKGROUND

[002] Stents are used to treat atherosclerosis, a condition where the coronary arteries become narrowed and hardened resulting in disruption of blood flow in the body. Atherosclerosis may also become a precursor of more complicated conditions like lesion perforation and aneurysm. Moreover, atherosclerosis may create aneurysm in sephanous vein grafts (SVGs) used as bypass conduits for coronary artery disease.

[003] Stents may be referred to as endo prostheses which are implantable in such diseased blood vessels. These stents may have two profiles; one is an expandable profile to support and open narrow blood vessels. The second profile is a reduced crimp profile which helps in navigating or deploying the stent into a narrowed blood vessel using for example, percutaneous transluminal coronary angioplasty (PTCA) catheter.

[004] In case of treating aneurysm, surgeons recommend covered stents over the conventional bare metal stents. Aneurysm is a condition in which a sac is formed in the wall of the lumen or vessel due to its dilation. The blood may clot or fill in the sac hence may create an emergency situation. In this case, conventional stent only open up the narrowed blood vessel while in case of a covered stent, the cover also expands with the stent and reduces the aneurysm sac size, thereby heals the blood vessel. Therefore, covered stent re-establish blood flow in the diseased vessel or lumen without emboli. [005] However, covered stents use either polytetrafluoroethylene (PTFE) grafts or other biological grafts as cover that results in increase in diameter of the crimped profile of the stents and thus, may pose a problem in introduction in blood vessels that are generally narrow. Further, these covered stents with bulky crimped profile have major drawbacks like difficulty in rapid deployment and high rate of restenosis. The bulky crimped profile of covered stents is unavoidable in such covered stents as the cover thickness also adds up to the compressed crimp profile of the stent at the time of deployment.

[006] Moreover, most of the blood vessels also taper from the proximal to distal direction. In such cases, uniform diameter of covered stent along the entire length may increase the risk of restenosis. For example, on using these covered stents with uniform diameter into a tortuous blood vessel, stenting the proximal segment of a vessel may result in over-dilation of the distal segment and increases the risk of dissection/perforation. Whereas in case of stenting the distal segment of the vessel, under-dilation of the proximal segment may occur and leave significant residual stenosis. Therefore, to treat aneurysm and other medical conditions like perforations and lesions in degenerated saphenous venous grafts (SVGs), an endo prosthesis or covered stent overcoming the drawbacks of existing covered stents is recommended to be devised.

SUMMARY

[007] The present invention discloses an expandable endo prosthesis having a low crimp profile within a range of 1.2 mm to 1.3 mm and is implantable into a human blood vessel. In an embodiment, of the present invention the expandable endo prosthesis is provided with a cylindrical configuration. In another embodiment the expandable endo prosthesis is provided with a tapered cylindrical configuration compatible to the tapered profile of blood vessels. The expandable endo prosthesis includes a stent and a tissue graft mounted on an outer surface of the stent. The expandable endo prosthesis is compatible to a 6F percutaneous transluminal coronary angioplasty (PTCA) delivery catheter.

BRIEF DESCRIPTION OF THE DRAWINGS

[008] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the appended drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those in the art will understand that the drawings are not to scale.

[009] FIG la illustrates an exemplary embodiment of an expandable endo prosthesis (stent-graft) in a cylindrical configuration in accordance with an embodiment of the present invention. [0010] FIG lb illustrates tapered cylindrical configuration of the expandable endo prosthesis (stent-graft) depicted in FIG. la crimped onto a delivery catheter in accordance with an embodiment of the present invention.

[0011] FIG lc illustrates the hybrid open-closed stent design of the stent present in the expandable endo prosthesis (stent-graft) depicted in FIGs la and lb in accordance with an embodiment of the present invention.

[0012] FIG 2 illustrates an exemplary flow-chart of a process of preparation of a tissue graft for an expandable endo prosthesis (stent-graft) depicted in FIGs la and lb in accordance with an embodiment of the present invention. [0013] FIG 3 illustrates exemplary steps employed in preparation of a tissue graft in accordance with an embodiment of the present invention.

[0014] FIG 4 illustrates an exemplary flow-chart of a process of manufacturing an expandable endo prosthesis (stent-graft) depicted in FIG. la and lb in accordance with an embodiment of the present invention. [0015] FIG 5 illustrates an exploded view of stitching of the tissue-graft and knotting of a stent- graft pattern present on the expandable endo prosthesis (stent-graft) depicted in FIGs la and lb in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0016] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have a property of, or the like; Definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases. [0017] Wherever possible, same reference numbers will be used throughout the drawings to refer to same or like parts. Moreover, references to various elements described herein are made collectively or individually when there may be more than one element of the same type. However, such references are merely exemplary in nature. It may be noted that any reference to elements in the singular may also be construed to relate to the plural and vice-versa without limiting the scope of the disclosure to the exact number or type of such elements unless set forth explicitly in the appended claims.

[0018] Particular embodiments of the present disclosure are described herein below with reference to the accompanying drawings, however, it is to be understood that the disclosed embodiments are merely examples of the disclosure, which may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure. In the present description and claims, the term proximal end refers to an end of an element that is closer to a user while the distal end refers to an end of the element which is farther from the user.

[0019] The present invention discloses an expandable endo prosthesis having a low crimp profile. In various embodiments, the present invention pertains to improved treatment of aneurysm, stenting SVGs and/or perforation by providing a crimp profile which is easy to deploy. An embodiment of the present invention provides a tapered configuration of the expandable endo prosthesis for easy deployment of endo prosthesis in tapered blood vessels without trauma.

[0020] The expandable endo prosthesis prevents over-dilation and/or under-dilation of the tortuous blood vessels. Further, the endo prosthesis of the present invention applies a homogenous radial force on the walls of a vessel and has adequate mechanical stress upon expansion. The endo prosthesis has optimized stent-arterial wall ratio along its entire length. Moreover, the expandable endo prosthesis of the present invention balances flexibility and vessel wall coverage as well as provides for an accurate and safe deployment. [0021] As represented in FIGs. la and lb, the present invention describes an expandable endo prosthesis 100 having a proximal end 102, a distal end 104, a deployed profile and a crimp profile. In an embodiment, the expandable endo prosthesis 100 may be cylindrical in configuration (FIG. la) for implantation in human blood vessels. The deployed profile of the expandable endo prosthesis 100 varies between 2.00 mm to 4.50 mm. In another embodiment, the expandable endo prosthesis 100 may have a tapered cylindrical configuration (FIG. lb) compatible with a tortuous profile of human blood vessels. The endo prosthesis 100 with tapered cylindrical configuration may have a deployed profile within a range of 2.25 mm to 3.00 mm at the distal end 104 and 2.75 mm to 3.50 mm at the proximal end 102. In both the cylindrical and tapered cylindrical configurations, the expandable endo prosthesis 100 may have a crimp profile within a range of 1.2 mm to 1.3 mm compatible with small dimensioned delivery catheters like a 6F delivery catheter or less. The length of the expandable endo prosthesis may vary between 30 mm to 60 mm for cylindrical and/or tapered cylindrical configurations. The expandable endo prosthesis 100 includes a stent 110 and a tissue graft 140.

[0022] The stent 110 includes a proximal end, a distal end, an outer surface, a deployed profile and a crimp profile. In an embodiment of the present invention, the stent 110 may have a cylindrical configuration with a deployed profile within a range of 2.00 mm to 4.50 mm. In another embodiment of the present invention, the stent 110 may have a tapered cylindrical configuration. In the tapered cylindrical configuration, the stent 110 may have a deployed profile within a range of 2.25 mm to 3.00 mm at the distal end and 2.75 mm to 3.50 mm at the proximal end. The stent 110 may have a crimp profile of 0.9 mm and a length within a range of 30 mm to 60 mm for cylindrical and/or tapered cylindrical configuration.

[0023] In an embodiment, the stent 110 may be manufactured from different sizes of tubes and made from nitinol, cobalt chromium or stainless steel. In an exemplary embodiment of the present invention, the stent 110 may be fabricated from a L605 cobalt chromium tube having a plurality of rows of open and closed cells (hybrid open-closed cell design FIG lc). The hybrid open-closed cell design of the stent 110 may be obtained by laser cutting of a tube having a diameter of 1.4mm to 1.8mm and can be expanded to a diameter within a range of 2.00mm to 4.50mm and length up to 48mm. In an embodiment, the strut thickness of hybrid cells may vary from 50pm to 65pm. The hybrid cell design provides excellent expansion and minimal recoil features to the stent 110. Moreover, the presence of multiple 'S links' on the stent 110 to link open and closed cells grants required flexibility to the expandable endo prosthesis 100 for safe delivery and expansion.

[0024] In an embodiment, to obtain the expandable endo prosthesis 100, the tissue graft 140 is mounted onto the outer surface of the stent 110. The tissue graft 140 may cover the outer surface of the stent partially or completely between the proximal and distal end of the stent 110. In an exemplary embodiment, the tissue graft 140 covers the entire stent 110 starting from the proximal end to the distal end. The coverage of the outer surface of the entire stent 110 by the tissue graft 140 creates barrier between the blood vessel wall and lumen, thereby, prevents emboli and traps plaque debris caused by aneurysm and perforation. [0025] The tissue graft 140 may have a proximal end, a distal end, an inner surface, an outer surface and a thickness (not shown). The thickness of the tissue graft extends from the inner surface to the outer surface of the tissue graft 140. The thickness of the tissue graft 140 may vary between 0.08 mm to 0.12mm. In an embodiment, the tissue graft 140 may be 60 mm long. In an embodiment, the tissue graft 140 is prepared from a biological tissue from one or more of autogenous, homologous or heterologus category. In the present invention, biological tissue can be harvested from various animal parts like arteries, pericardium, collagen, peritoneum etc. The tissue graft 140 may be obtained from the animal origin like bovine, porcine, equine or ovine species. In an embodiment, the tissue graft 140 is harvested from a bovine source having an upper age limit of 24 months. In an exemplary embodiment, the pericardium of a bovine source, a 12 day old neo natal calf is used to obtain the tissue graft 140.

[0026] FIG. 2 depicts the steps employed in the preparation of the tissue graft 140. In the first step 210, a flat sheet of biological tissue is subjected to trimming. The pericardium tissue is laser cut in any geometrical shape using parameters described in Table 1.

[0027] For example, a rectangular patch of approximately 80X80mm may be cut from the pericardium tissue. The diameter and length of the rectangular patch may correspond to the diameter and length of the stent 110. For example, for a stent with a diameter of 3.00mm and length 27mm, the width of the rectangular patch may be of 10mm to 11mm while the length may be of 28mm. The rectangular patch is formed in such a way that it is flexible to allow smooth expansion of both the stent 110 and tissue graft 140 (cylindrical form of the rectangular patch).

[0028] At step 220, the rectangular patch obtained from trimming/laser cutting pericardium tissue is subjected to conditioning to enhance the durability of the said patch. The durability is enhanced in conditioning as it reduces the chances of calcification of tissue graft 140 (cylindrical form of the rectangular patch) inside the blood vessel. Further, the process of conditioning includes fixation followed by anti-calcification of the rectangular patch. An exemplary process of conditioning of a tissue may be referred from Indian patent application numbers 201721040401, 201721040399 and 201721040400, incorporated herein by reference.

[0029] During fixation of the rectangular patch, any cross-linking agent including but not limited to glutaraldehyde, formaldehyde, ethanol and glycerol or combination thereof may be used. In an exemplary embodiment, the rectangular patch is fixed by using glutaraldehyde in a concentration within a range of 0.250% to 0.625%. The dry conditioned rectangular patch may provide sufficient basic mechanical properties that are required to be present in a stent cover. For example, the rectangular patch may have a tissue tensile strength varying between lON/mm² and 20N/mm² and a shrinkage temperature varying between 60 °C and 90 °C. Furthermore, the dry conditioned rectangular patch thus obtained has a suture retention varying between 200gf and 300gf and a tissue burst strength varying between 100N and 150N. Further, in an embodiment of the present invention, the rectangular patch may not be subjected to the dehydration process after anti calcification. The dehydration process may not be required in the present invention as the expandable endo prosthesis 100 is designed to be stored in liquid storage conditions to prevent degradation of biological tissue.

[0030] At step 230, to obtain the tissue graft 140, a stainless steel mandrel as depicted in FIG. 3(i) is used to coil the rectangular patch into a cylindrical form. As shown in FIG. 3(i), the stainless steel mandrel has a half portion with a diameter corresponding to the target diameter of the tissue graft

140 and another half portion with a diameter corresponding to the partial expansion diameter of the stent 110. First of all, right and left edges of the rectangular patch are wrapped over the stainless steel mandrel (FIG. 3(H)). In an exemplary embodiment, smooth surface of the rectangular patch is positioned towards the outer surface of the mandrel. Both the edges are wrapped over the mandrel in a way that about 0.5mm to 1.0mm of right edges are covered by the left edges and thereby creating an overlapping region on edges (FIG. 3(iii)).

[0031] At step 240, the overlapping region of the edges is then stitched with the help of an ultrathin monofilament preferably between 8/0 and 10/0 USP suture size as depicted in FIG. 3(iv). The monofilament can be selected either from polyester, nylon, poly-propylene, silk, 8/0 polypropylene monofilament or any non-degradable material. In an exemplary embodiment, the 8/0 polypropylene monofilament is used to stitch the overlapping region of edges with 12" eye needle. The stitching is performed in an upward or one to other direction by right over left pattern having a 0.5mm-1.0mm gap in between two adjacent stitches (FIG. 3(v)). The right over left upward stitching pattern with 0.5-1.0 mm gap will provide sufficient adherence when stent graft is deployed and thus prevents any leakage from the stitching portion. Further, a double knot and a tighten knot of the suture are formed at each end of the rectangular patch with precision (FIG. 3(vi)). Finally, as shown in FIG. 3(vii) the tissue graft 140 is obtained by stitching both the ends of the wrapped rectangular patch. The tissue graft 140 thus obtained may have a cylindrical configuration. The tissue graft 140 is then stored in sterile saline for example, in 0.9% sterile normal saline till further use. [0032] FIG. 4 depicts the flow chart representing a process 400 of manufacturing the expandable endo prosthesis. In an embodiment, the endo prosthesis is manufactured by covering the stent 110 with the tissue graft 140.

[0033] In an exemplary embodiment, the process 400 is initiated at the step 410 relating to preparation of the tissue graft 140 by treating pericardium tissue, for example, a 12 day old neo natal calf pericardium. The detailed process of tissue preparation is described in the description of FIG. 2.

[0034] At the step 420 of the process 400, the tissue graft 140 is mounted on the outer surface of the stent 110. During mounting, the stent 110 is expanded partially with the PTCA balloon dilatation catheter as per the required diameter. For example, if the required diameter is 3.00mm, the stent is partially expanded up to an inner diameter within a range of 2.60mm to 2.70mm. The partially expanded stent 110 is then placed at the stainless steel mandrel (FIG 3 (i)) and afterwards, the tissue graft 140 is stretched onto the outer surface of the stent 110 using micro forceps, to cover the entire stent 110. Once full surface of the stent 110 is covered with the tissue graft 140, the corresponding proximal and distal ends of the stent 110 and tissue graft 140 are secured with a plurality of double knots. In an embodiment, the tissue 140 is secured on each end of the stent 110 with four double knots (Fig 5). Additionally, the tissue graft 140 is secured on the entire outer surface of the stent 110 using right over left stitching pattern (Fig 5). The tissue graft 140 thus secured also maintains the lumen size of the stent 110. [0035] At step 430, the expandable endo prosthesis 100 (tissue graft 140 covered stent 110 or stent-graft) is crimped to a reduced diameter, to allow easy access in body lumens like blood vessels. The expandable endo prosthesis 100 is mounted onto a PTCA balloon catheter and crimped to a reduced diameter within a range of 1.2 mm to 1.3 mm. The expandable endo prosthesis 100 is crimped by using a stent crimping machine. In an embodiment, the crimping of the expandable endo prosthesis 100 is performed in three stages by applying predefined pressure for a specified duration as described in Table 2. The duration of pressure exposure may vary between 180 to 220 seconds in an exemplary embodiment as depicted below:

Table 2

[0036] In an embodiment, the reduction and pressure may vary according to various deployed profiles of expandable endo prosthesis 100. For example, higher pressure may be applied while crimping of larger diameter expandable endo prosthesis 100. The crimped expandable endo prosthesis 100 is further subjected to primary packaging process followed by liquid chemical sterilization. For coronary application, the expandable endo prosthesis 100 with low profile is compatible with for example, 6F guide catheter. [0037] The expandable endo prosthesis 100 is then subjected to various performance tests like trackability, push efficiency and dimensional attributes like recoil, uniformity of expansion, stent foreshortening and radial strength. The basic properties including recoil, foreshortening and radial strength of the expandable endo prosthesis 100 obtained from steps 410 to 430 is within a range of 1.0% to 4.0%, 0.5% to 3.0%, and 20N to 30N respectively. Moreover, there is no change between compacted longitudinal length vs. its deployed longitudinal length of the tissue graft 140. These features enable the expandable endo prosthesis 100 of the present invention to have a design suitable for safe, easy delivery and complete expansion therefore efficient treatment of the diseased blood vessel. [0038] Further, the expandable endo prosthesis 100 of the present invention is ultra-thin due to the thin stent 110 and ultra-thin tissue graft 140 combination, thereby helpful for rapid deployment in human blood vessels. Moreover, as the expandable endo prosthesis 100 uses an anti-calcified tissue graft 140 and tapered and cylindrical configuration stent 110, it is also easy to deploy the same in calcified and tortuous blood vessels. The expandable endo prosthesis 100 of the present invention may be used in treating medical conditions including but not limited to aneurysm, perforation and degenerated SVGs.

[0039] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used.

Claims

We claim.

1. An expandable endo prosthesis having a crimp profile and implantable in a human blood vessel, the expandable endo prosthesis comprises: an expandable stent with an outer surface, an inner surface, a proximal end, a distal end and a crimp profile of 0.9 mm; and a tissue graft, covering the outer surface of the expandable stent and having a thickness within a range of 0.08 mm to 0.12mm, wherein the tissue graft is anti-calcified; wherein the crimp profile of the expandable stent and the tissue graft assembly is within a range of 1.2mm to 1.3mm.

2. The expandable endo prosthesis as claimed in claim 1 wherein the expandable stent is a metal stent.

3. The expandable endo prosthesis as claimed in claim 2 wherein the stent metal is a cobalt chromium stent.

4. The expandable endo prosthesis as claimed in claim 1 wherein the expandable stent is

cylindrical in configuration.

5. The expandable endo prosthesis as claimed in claim 1 wherein the expandable stent is

tapered-cylindrical in configuration.

6. The expandable endo prosthesis as claimed in claim 1 wherein the expandable stent

includes a plurality of rows extending circumferentially from the proximal end to the distal end, the plurality of rows including at least one row of open cells and at least one row of closed cells.

7. The expandable endo prosthesis as claimed in claim 6 wherein the open cells and closed cells are made of plurality of struts, each strut having a thickness within a range of 50 pm to 65 pm.

8. The expandable endo prosthesis as claimed in claim 1 wherein the tissue graft is a biological tissue.

9. The expandable endo prosthesis as claimed in claim 8 wherein the biological tissue is a pericardium tissue of 12 day old neo natal calf.

10. The expandable endo prosthesis as claimed in claim 1 wherein the expandable endo

prosthesis is compatible with 6F delivery catheter.

11. A process of manufacturing an expandable endo prosthesis comprising: preparing a tissue graft, the preparing the tissue graft comprises trimming, conditioning, coiling and stitching of a biological tissue, the tissue graft having a thickness within a range of 0.08 mm to 0.12mm; mounting the tissue graft over an outer surface of an expandable stent forming an endo prosthesis; and crimping the endo prosthesis on to a balloon catheter to achieve a crimp profile within a range of 1.2mm to 1.3mm.

12. The process of manufacturing the expandable endo prosthesis as claimed in claim 11

wherein the trimming comprises trimming the biological tissue into a geometrical shape.

13. The process of manufacturing the expandable endo prosthesis as claimed in claim 11

wherein the conditioning includes fixing the biological tissue with glutaraldehyde.

14. The process of manufacturing the expandable endo prosthesis as claimed in claim 11

wherein the conditioning includes performing anti-calcification of the biological tissue.

15. The process of manufacturing the expandable endo prosthesis as claimed in claim 11

wherein the coiling of the biological tissue comprises wrapping the biological tissue over a stitching mandrel.

16. The process of manufacturing the expandable endo prosthesis as claimed in claim 11

wherein the stitching is performed on overlapping right and left edges of the biological tissue wrapped over a stitching mandrel.

17. The process of manufacturing the expandable endo prosthesis as claimed in claim 11

wherein the stitching comprises stitching one side to other side in right over left stitching pattern.

18. The process of manufacturing the expandable endo prosthesis as claimed in claim 11 wherein the mounting of the tissue graft is performed by forming a plurality of double knots at distal and proximal end of the expandable stent.

19. The process of manufacturing the expandable endo prosthesis as claimed in claim 11

wherein the crimping includes crimping the endo prosthesis in three stages with each stage employing a predefined pressure and dwell time.