Patent Application
20150374485
It is well known to employ various intravascular endoprostheses delivered percutaneously for the treatment of diseases of various body vessels. These types of endoprosthesis are commonly referred to as stents. A stent is a generally formed longitudinal tubular device of biocompatible material, such as stainless steel, cobalt-chromium, nitinol or biodegradable materials, having holes or slots cut therein so they can be radially expanded, by a balloon catheter or the like, or alternately self-expanded within the vessel. Stents are useful in the treatment of stenosis, strictures or aneurysms in body vessels such as blood vessels. These devices are implanted within the vessel to reinforce collapsing, partially occluded, weakened or abnormally dilated sections of a vessel. Stents are typically employed after angioplasty of a blood vessel to prevent restenosis of the diseased vessel. While stents are most notably used in blood vessels, stents may also be implanted in other body vessels such as the urogenital tract and bile duct.
Stents generally include an open flexible configuration. This configuration allows the stent to be inserted through curved vessels. Furthermore, the stent configuration allows the stent to be configured in a radially compressed state for intraluminal catheter implantation. Once properly positioned adjacent the damaged vessel, the stent is radially expanded so as to support and reinforce the vessel. Radial expansion of the stent can be accomplished by inflation of a balloon attached to the catheter, or alternatively using self-expanding materials such as nitinol within the stent. Examples of various stent constructions are shown in U.S. Pat. No. 4,733,665 filed by Palmaz on Nov. 7, 1985, which is hereby incorporated herein by reference.
Recently, there has been a desire to place a covering of biocompatible material over expandable stents. The covering for the stent can provide many benefits. For example, the covered stent could act as a stent-graft. Intraluminal vascular stent-grafts can be used to repair aneurysmal vessels, particularly aortic arteries, by inserting an intraluminal vascular graft within the aneurysmal vessel so that the prosthetic withstands the blood pressure forces responsible for creating the aneurysm.
Applicant notes that there are at least two down-sides to usage of the graft or a combined stent-graft in the vasculature: (a) the graft is believed to occlude side-branches across the length of the treated vasculature and (b) the graft leads to focal edge restenosis, i.e., focalized restenosis at proximal and distal ends of the graft. In fact, edge restenosis is the primary cause of failure of stent grafts. For instance, 87% of stent graft failures in the VIBRANT trial (from the August 2012 publication of “Endovascular Today”) were via focalized edge restenosis. In contrast, 93% of the failures in bare nitinol stents (BNS) exhibited diffused restenosis. The VIBRANT trial is a multicenter, randomized study of the prior GORE® VIABAHN® Device (without heparin, contoured proximal edge; 5-mm device sizes available) versus BNS (multiple brands) in 148 patients (Rutherford classes 1-5), with a primary endpoint of primary patency at 3 years. The mean lesion lengths were 19 and 18 cm, 40% were CTOs, and 62.5% of lesions demonstrated moderate to severe calcification (primarily TASC C and D lesions). Both groups had disappointing primary patency rates of 53% and 58%, respectively, but there were important differences in the patterns of restenosis: 93% of failed BNS had diffuse ISR versus focal edge restenosis in 87% of the failed GORE® VIABAHN® Devices.
Therefore, applicant has recognized that certain improvements can be made to a prosthetic such as a stent-graft to achieve restenotic response at targeted regions. In short, the present invention is an endovascular prosthetic in the form of a graft or stent-graft (and variations thereof) that prevents focalized edge (or end) restenosis. In particular, these improvements would mitigate or prevent focalized restenosis at graft ends. The designed-in restenotic regions would be circumferentially and axially distributed so that graft patency is not compromised.
One embodiment of the present invention may include: an expandable frame having a plurality of hoops disposed about a longitudinal axis extending through the plurality of hoops from a first frame end to a second frame end; a generally cylindrical graft material disposed generally coaxial to the expandable frame about the longitudinal axis from a first graft end to a second graft end, the graft material being connected to the frame at a plurality of locations; and wherein the graft material is configured to include perforations formed on the graft material so that the perforations proximate the first and second graft ends are equal or larger than the perforations that are disposed away from the first or second graft end. The expandable frame may be enclosed by graft material on its outside surface, inside surface or both surfaces.
In the embodiment noted above, the perforations proximate the first and second graft ends generally define respective hoops of perforations proximate the first and second graft ends. Alternatively, the perforations of the graft material define a helical path from the first graft end to the second graft end and a width of such helical path is progressively smaller as the helical path moves away from the first graft end or the second graft end. Further, the expandable frame is disposed on an inner surface of the graft material that is facing the longitudinal axis. Alternatively, the expandable frame can be disposed on the outside surface of the graft; the expandable frame can be sandwiched between two graft materials; or two expandable frames can sandwich graft material.
In such embodiment, the perforations proximate the first graft end or the second graft end comprise a plurality of perforations wherein each perforation defines an opening having an open area AP that has a first aspect ratio range from about 0.1 through about 0.5 of AO1 or AO2, where AO1 or AO2 is end section area one of the first and second graft end perpendicular to the longitudinal axis. Another range for the first aspect ratio could be from about 0.2 to about 0.4. As used herein, AO1 denotes the surface area orthogonal to the longitudinal axis L-L of the first opening of the endovascular prosthetic and AO2 denotes the surface area of the second opening, in which AO1˜AO2 or AO1≠AO2. Alternatively, each of the perforations disposed away from one of the first and second graft ends defines an open area that is progressively smaller from about 0.4 to about 0.9 and could be from about 0.5 to about 0.8 than the open area of the perforations proximate one of the first and second graft ends to define the second aspect ratio range. For example, the ratio of the area AP3/AP2 can be from about 0.4 to about 0.9 and likewise, the ratio of AP4/AP3 is from about 0.4 to about 0.9. The perforations can be of any suitable configuration including but not limited to circular, elliptical, dog-boned or alternate patterns, as long as such configuration complies with the first and second aspect ratios described herein.
In yet another embodiment, perforations may include at least a slit through the graft material and extending generally parallel to the longitudinal axis. It is noted that the at least one slit may be two slits disposed diametrically with respect to the longitudinal axis and spaced apart longitudinally or more than two slits disposed diametrically and staggered longitudinally. Width in circumferential direction of longitudinal slits can be from about 0.1 to about 0.5 times the proximal or distal graft diameter.
The expandable frame may be one of a self-expanding frame or a balloon expandable frame which frame can be of at least a bioresorbable material. The frame may include a series of hoops connected to each other via connectors of the same material as the frame. Alternatively, the frame may include a series of hoops independent from each other so that the hoops are connected indirectly through the graft material. The graft materials may be composed of various polymeric formulations including PET (polyester), Fluoro-polymers such as PTFE and FEP, spun PTFE, and HDPE.
In the case of a graft where no internal or external frame is needed, a thin-film graft made from nitinol can be utilized with either or both of the aspect ratios noted earlier. The “thin-film” material for the graft can be made from well-known chemical deposition or physical deposition techniques. Chemical deposition can be by plating, chemical solution deposition, spin coating, chemical vapor deposition, plasma enhanced vapor deposition, or atomic layer deposition. Physical deposition for thin film manufacturing can be by thermal evaporator, laser deposition, cathodic arc deposition, sputtering, vapor deposition, ion-beam assisted evaporative deposition or electrospray deposition.
These and other embodiments, features and advantages will become apparent to those skilled in the art when taken with reference to the following more detailed description of the exemplary embodiments of the invention in conjunction with the accompanying drawings that are first briefly described.
The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate presently preferred embodiments of the invention, and, together with the general description given above and the detailed description given below, serve to explain features of the invention (wherein like numerals represent like elements), in which:
The following detailed description should be read with reference to the drawings, in which like elements in different drawings are identically numbered. The drawings, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of the invention. The detailed description illustrates by way of example, not by way of limitation, the principles of the invention. This description will clearly enable one skilled in the art to make and use the invention, and describes several embodiments, adaptations, variations, alternatives and uses of the invention, including what is presently believed to be the best mode of carrying out the invention.
As used herein, the terms “about” or “approximately” for any numerical values or ranges indicate a suitable dimensional tolerance that allows the part or collection of components to function for its intended purpose as described herein. More specifically, “about” or “approximately” may refer to the range of values ±10% of the recited value, e.g. “about 90%” may refer to the range of values from 81% to 99%. In addition, as used herein, the terms “patient,” “host,” “user,” and “subject” refer to any human or animal subject and are not intended to limit the systems or methods to human use, although use of the subject invention in a human patient represents a preferred embodiment.
Referring now to the figures wherein like numerals indicate the same element throughout the views, there is shown in
As shown in
The embodiment of
Alternatively,
While
In each of the embodiments described herein, frame 102 may be a self-expanding expandable stent or a balloon expandable stent. The frame 102 is a tubular member having a first end 102A and a second end 102B. The frame 102 has an interior surface 110, which is not pointed out in
Frame 102 is preferably made from a suitable biocompatible material such as balloon expandable metal alloy or a superelastic alloy such as Nitinol. Most preferably, frame 102 is made from an alloy comprising from about 50.5% (as used herein these percentages refer to atomic percentages) Ni to about 60% Ni, and most preferably about 55% Ni, with the remainder of the alloy Ti. Preferably, the stent is such that it is superelastic at body temperature. The superelastic design of the expandable frame makes it crush recoverable which, as discussed above, is useful in treating many vascular problems.
Referring back to
The stents can be cut from a tube or wound from a wire on a mandrel. Thereafter, the stents can be expanded in the duct or vessel of a host by a separate mechanism (e.g., balloon) or by utilization of a material that self-expands upon predetermined implantation conditions. The stent can be formed from a suitable biocompatible material such as, for example, polymer metals and other biocompatible materials which may be bioabsorble. Preferably, stents are laser cut from small diameter tubing from biocompatible metals such as shape memory materials or balloon expandable materials. Details of this particular embodiment of the stent can be gleaned from U.S. Pat. No. 8,328,864, which is hereby incorporated by reference herein.
Although the stent frame has been shown and described as being connected via bridges, one embodiment of the stent frame includes a plurality of discrete hoops that are not connected directly to other stent hoops via stent bridges but indirectly by virtue of each hoop being attached to the graft material (e.g., sutured, glued or retained between inner and outer graft materials).
Graft material 108 of prosthetic 100 is preferably made from a suitable material such as, for example, PTFE, ePTFE, Dacron, PET (polyester), Fluoro-polymers such as PTFE and FEP, spun PTFE, HDPE, and combinations thereof. Either or both of the graft and stent can be formed from biodegradable polymers such as polylactic acid (i.e., PLA), polyglycolic acid (i.e., PGA), polydioxanone (i.e., PDS), polyhydroxybutyrate (i.e., PHB), polyhydroxyvalerate (i.e., PHV), and copolymers or a combination of PHB and PHV (available commercially as Biopol®), polycaprolactone (available as Capronor®), polyanhydrides (aliphatic polyanhydrides in the back bone or side chains or aromatic polyanhydrides with benzene in the side chain), polyorthoesters, polyaminoacids (e.g., poly-L-lysine, polyglutamic acid), pseudo-polyaminoacids (e.g., with back bone of polyaminoacids altered), polycyanocrylates, or polyphosphazenes. As used herein, the term “bio-resorbable” includes a suitable biocompatible material, mixture of materials or partial components of materials being degraded into other generally non-toxic materials by an agent present in biological tissue (i.e., being bio-degradable via a suitable mechanism, such as, for example, hydrolysis) or being removed by cellular activity (i.e., bioresorption, bioabsorption, or bioresorbable), by bulk or surface degradation (i.e., bioerosion such as, for example, by utilizing a water insoluble polymer that is soluble in water upon contact with biological tissue or fluid), or a combination of one or more of the bio-degradable, bio-erodable, or bio-resorbable material noted above.
In certain applications where a fabric or a polymeric material is not desired, the graft material 108, 208, 308 or 408 can be formed by a suitable thin-film deposition technique over a substrate such as an expandable frame (self-expanding or balloon expandable stent). In this configuration with the thin-film, the expandable frame can be disposed on the outside surface of the thin-film (acting as a graft); the expandable frame can be sandwiched between two thin-film graft materials (
Alternatively, in applications that may require a very thin graft in the pre-deployment profile, the stent as a substrate is eliminated completely from the prosthetic thereby resulting in a prosthetic formed from a thin-film of materials such as biocompatible metals or pseudometals (
The thin-film graft 608 can also be made by deposition of a thin film onto a sacrificial two-dimensional substrate (i.e., a planar substrate) then thereafter rolled about a three-dimensional form (i.e., a cylindrical form) and welded together along a common seam to form the preferred configuration (e.g., a hollow thin-film open ended cylinder 600 with perforations). Regardless of the techniques to make prosthetic 600, additional processing may be utilized to enhance the surface finish or physical properties of the thin-film graft. Even though such prosthesis does not have a frame, it is believed that the thin-film material for the graft allows for much greater fatigue life than would be possible using a stent to support the graft. Details of various techniques are shown and described in U.S. Pat. No. 8,460,333, which is incorporated by reference as if set forth herein its entirety in this application.
In one embodiment, bio-active agents can be added to the polymer, the metal alloy of the frame or the thin-film material for delivery to the host's vessel or duct. The bio-active agents may also be used to coat the entire graft, the entire stent or only a portion of either. A coating may include one or more non-genetic therapeutic agents, genetic materials and cells and combinations thereof as well as other polymeric coatings. Non-genetic therapeutic agents include anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPack (dextrophenylalanine proline arginine chloromethylketone); antiproliferative agents such as enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine; antineoplastic/antiproliferative/anti-miotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; anti-coagulants, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin anticodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet peptides; vascular cell growth promotors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional activators, and translational promotors; vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents; vasodilating agents; and agents which interfere with endogenous vasoactive mechanisms.
Genetic materials include anti-sense DNA and RNA, DNA coding for, anti-sense RNA, tRNA or rRNA to replace defective or deficient endogenous molecules, angiogenic factors including growth factors such as acidic and basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor alpha and beta, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor alpha, hepatocyte growth factor and insulin like growth factor, cell cycle inhibitors including CD inhibitors, thymidine kinase (“TK”) and other agents useful for interfering with cell proliferation the family of bone morphogenic proteins (“BMPs”), BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-I), BMP-8, BMP-9, BMP-IO, BMP-I, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Desirable BMPs are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the “hedgehog” proteins, or the DNA encoding them.
Cells can be of human origin (autologous or allogeneic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at the deployment site. The cells may be provided in a delivery media. The delivery media may be formulated as needed to maintain cell function and viability.
Suitable polymer coating materials include polycarboxylic acids, cellulosic polymers, including cellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyanhydrides including maleic anhydride polymers, polyamides, polyvinyl alcohols, copolymers of vinyl monomers such as EVA, polyvinyl ethers, polyvinyl aromatics, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters including polyethylene terephthalate, polyacrylamides, polyethers, polyether sulfone, polycarbonate, polyalkylenes including polypropylene, polyethylene and high molecular weight polyethylene, halogenated polyalkylenes including polytetrafluoroethylene, polyurethanes, polyorthoesters, proteins, polypeptides, silicones, siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxybutyrate valerate and blends and copolymers thereof, coatings from polymer dispersions such as polyurethane dispersions (for example, BAYHDROL® fibrin, collagen and derivatives thereof, polysaccharides such as celluloses, starches, dextrans, alginates and derivatives, hyaluronic acid, squalene emulsions. Polyacrylic acid, available as HYDROPLUS® (Boston Scientific Corporation, Natick, Mass.), and described in U.S. Pat. No. 5,091,205, the disclosure of which is hereby incorporated herein by reference, is particularly desirable. Even more desirable is a copolymer of polylactic acid and polycaprolactone. Suitable coverings include nylon, collagen, PTFE and expanded PTFE, polyethylene terephthalate and KEVLAR®, ultra-high molecular weight polyethylene, or any of the materials disclosed in U.S. Pat. No. 5,824,046 and U.S. Pat. No. 5,755,770, which are incorporated by reference herein. More generally, any known graft material may be used including synthetic polymers such as polyethylene, polypropylene, polyurethane, polyglycolic acid, polyesters, polyamides, their mixtures, blends and copolymers.
Referring back to
One method of making the endovascular prosthetic embodiments of
While the invention has been described in terms of particular variations and illustrative figures, those of ordinary skill in the art will recognize that the invention is not limited to the variations or figures described. In addition, where methods and steps described above indicate certain events occurring in certain order, it is intended that certain steps do not have to be performed in the order described but in any order as long as the steps allow the embodiments to function for their intended purposes. Therefore, to the extent there are variations of the invention, which are within the spirit of the disclosure or equivalent to the inventions found in the claims, it is the intent that this patent will cover those variations as well.
