Patent Application
20070191926
The invention relates to vascular repair devices, and in particular intravascular stents, which are adapted to be implanted into a patient's body lumen, such as an artery or coronary artery, or bile duct, to maintain the patency thereof. It is an important feature of the present invention to provide a stent structure that can be crimped onto a catheter to form a high degree of stent retention so that during delivery of the stent to a coronary artery or other vessel or duct the stent remains on the catheter.
Stents are generally tubular-shaped devices which function to hold open a segment of a blood vessel or other body lumen such as a renal or coronary artery. At present, there are numerous commercial stents being marketed throughout the world. While some of these stents are flexible and have the appropriate radial rigidity needed to hold open a vessel or artery, there typically is a tradeoff between flexibility and radial strength and the ability to tightly compress or crimp the stent onto a catheter so that it does not move relative to the catheter or dislodge prematurely prior to controlled implantation in a vessel.
What has been needed and heretofore unavailable is a stent pattern which has a high degree of flexibility so that it can be advanced through tortuous passageways and can be readily expanded, remain tightly crimped onto a balloon catheter during delivery, and yet have the mechanical strength to hold open the body lumen or artery into which it is implanted and provide adequate vessel wall coverage. The present invention satisfies this need. That is, the stent of the present invention has a pattern that increases stent retention on the catheter.
The present invention is directed to a stent that has a pattern or configuration that permits the stent to be tightly compressed or crimped onto a catheter to provide an extremely high stent retention on the catheter. The stent of the present invention generally includes a plurality of cylindrical rings that are interconnected to form a plurality of cells. In one embodiment, there are less cells in the distal end rings than in the remaining rings, for example, there are two cells in the distal end rings and three cells in all other rings. The two cell pattern allows more balloon material to protrude into the cells during crimping thereby increasing stent retention relative to the catheter balloon.
In another embodiment, each of the cylindrical rings making up the stent have a proximal end and a distal end and a cylindrical plane defined by a cylindrical outer wall surface that extends circumferentially between the proximal end and the distal end of the cylindrical ring. Generally the cylindrical rings have a serpentine or undulating shape which includes at least one U-shaped element, and typically each ring has more than one U-shaped element. The cylindrical rings are interconnected by links which attach one cylindrical ring to an adjacent cylindrical ring. The links are highly flexible and allow the stent to be highly flexible along its longitudinal axis. In this embodiment, all of the connecting links are substantially straight and substantially parallel to the longitudinal axis of the stent. Since the links are substantially straight and the struts that connect the U-shaped elements or undulations are substantially straight, the stent can be compressed or crimped to a much tighter or smaller diameter onto the catheter which permits low profile delivery as well as a tight gripping force on the catheter to reduce the likelihood of movement between the stent and the catheter during delivery and prior to implanting the stent in a vessel or a bile duct. In order to further improve stent retention on the expandable member (or balloon), the gap between adjacent rings on the distal end of the stent is greater than the gap between the rings on the main body of the stent. Further, one or more distal end rings have two cells per ring while the main body of the stent has three cells per ring. Each of these structural features increases stent retention on the catheter balloon since the balloon can protrude into the gap and into the larger two cell structure to hold the stent onto the balloon.
In yet another embodiment, each of the cylindrical rings making up the stent have a proximal end and a distal end and a cylindrical plane defined by a cylindrical outer wall surface that extends circumferentially between the proximal end and the distal end of the cylindrical ring. Generally the cylindrical rings have a serpentine or undulating shape which includes at least one U-shaped element, and typically each ring has more than one U-shaped element. The cylindrical rings are interconnected by at least one connecting link which attaches one cylindrical ring to an adjacent cylindrical ring. The links are highly flexible and allow the stent to be highly flexible along its longitudinal axis. In order to further improve stent retention on the expandable member, the gap between adjacent rings on the distal end of the stent is greater than the gap between adjacent rings on the main body of the stent. Further, the two distal end rings are connected together with undulating links having a straight portion and a U-shaped bend (like a hinge). The undulating links may take various configurations but in general have at least one U-shaped bend. The undulating links can include bends connected by substantially straight portions wherein the substantially straight portions are substantially perpendicular to the stent longitudinal axis. The undulating links provide greater flexibility and more space between rings for better crimping onto the catheter expandable member. The U-shaped portion of the undulating links are perpendicular to the longitudinal axis of the stent thereby increasing stent retention relative to the balloon.
In a further embodiment, each of the cylindrical rings making up the stent have a proximal end and a distal end and a cylindrical plane defined by a cylindrical outer wall surface that extends circumferentially between the proximal end and the distal end of the cylindrical ring. Generally the cylindrical rings have a serpentine or undulating shape which includes at least one U-shaped element, and typically each ring has more than one U-shaped element. The cylindrical rings are interconnected by at least one connecting link which attaches one cylindrical ring to an adjacent cylindrical ring. The links are highly flexible and allow the stent to be highly flexible along its longitudinal axis. In this embodiment all of the connecting links are substantially straight and substantially parallel to the longitudinal axis of the stent. Since the links are substantially straight and the struts that connect the U-shaped elements or undulations are substantially straight, the stent can be compressed or crimped to a much tighter or smaller diameter onto the catheter which permits low profile delivery as well as a tight gripping force on the catheter to reduce the likelihood of movement between the stent and the catheter during delivery and prior to implanting the stent in the vessel or into a duct. In order to further improve stent retention on the expandable member (or balloon), the gap between adjacent rings on the distal end of the stent is greater than the gap between the rings on the main body of the stent. Further, one or more distal end rings have two cells per ring while the main body of the stent has three cells per ring. Each of these structural features increases stent retention on the catheter balloon. In this embodiment, the links connecting the distal end rings extend from a peak of one ring to a peak of an adjacent ring. By connecting the distal end rings peak to peak, the gap between the end rings is greater than the gap between adjacent rings on the body of the stent. Thus, the distal end ring structure increases stent retention on the catheter balloon since the balloon can more easily protrude into the gaps to hold the stent in place.
In one embodiment, each of the cylindrical rings making up the stent have a proximal end and a distal end and a cylindrical plane defined by a cylindrical outer wall surface that extends circumferentially between the proximal end and the distal end of the cylindrical ring. Generally the cylindrical rings have a serpentine or undulating shape which includes at least one U-shaped element, and typically each ring has more than one U-shaped element. The cylindrical rings are interconnected by at least one connecting link which attaches one cylindrical ring to an adjacent cylindrical ring. The links are highly flexible and allow the stent to be highly flexible along its longitudinal axis. The undulating portion of the link has an S-shape to further increase the gap between the distal end rings and the main body rings. The S-shaped link includes bends and straight portions, the straight portions being substantially perpendicular to the longitudinal axis of the stent. Both the increased gap between the distal end rings and the main body rings, and the straight portions of the S-shaped links being perpendicular to the longitudinal axis increase the stent retention on the balloon portion of the catheter. More specifically, the balloon can protrude into the increased gap area, and the straight portions that are perpendicular to the longitudinal axis of the stent resist longitudinal movement of the stent relative to the balloon. Further, the S-shaped portion of the undulating links act like a hinge to further increase longitudinal flexibility.
The present invention stent improves on existing stents by providing a stent pattern that greatly increases the retention force between the stent and the balloon on which it is mounted. The design of highly flexible interconnecting members and their placement relative to cylindrical rings provides for a tightly compressed stent onto a catheter thereby maintaining a high degree of stent retention on the balloon during delivery of the stent to a vessel or duct for implantation.
Turning to the drawings,
Catheter assembly 12 as depicted in
As shown in
In a typical procedure to implant prior art stent 10, the guide wire 18 is advanced through the patient's vascular system by well known methods so that the distal end of the guide wire is advanced past the plaque or diseased area 26. Prior to implanting the stent, the cardiologist may wish to perform an angioplasty procedure or other procedure (i.e., atherectomy) in order to open the vessel and remodel the diseased area. Thereafter, the stent delivery catheter assembly 12 is advanced over the guide wire so that the stent is positioned in the target area. The expandable member or balloon 22 is inflated by well known means so that it expands radially outwardly and in turn expands the stent radially outwardly until the stent is apposed to the vessel wall. The expandable member is then deflated and the catheter withdrawn from the patient's vascular system. The guide wire typically is left in the lumen for post-dilatation procedures, if any, and subsequently is withdrawn from the patient's vascular system. As depicted in
The prior art stent 10 serves to hold open the artery after the catheter is withdrawn, as illustrated by
In keeping with the present invention,
As shown in
Each cylindrical body ring 40 defines a cylindrical plane which is a plane defined by the proximal and distal ends of the ring and the circumferential extent as the cylindrical ring travels around the cylinder. Each cylindrical ring includes a cylindrical outer wall surface which defines the outermost surface of the stent, and a cylindrical inner wall surface which defines the innermost surface of the stent. The cylindrical plane follows the cylindrical outer wall surface.
In keeping with the invention,
The stent 30 shown in
In another embodiment, as shown in
In the embodiment shown in
In another embodiment, as shown in 8A-8C, the stent 30 can be described more particularly as having U-shaped portions 100, W-shaped portions 102, and Y-shaped portions 104. Although the stent is not divided into separate elements, for ease of discussion references to U-shaped portions 100, W-shaped portions 102, and Y-shaped portions 104 is appropriate. In this embodiment, the cylindrical body rings 40 are interconnected by links 106 that are substantially straight and substantially aligned with the longitudinal axis of the stent. The distal end 108 of the links is attached to valley 110 and form what appears to be W-shaped portion 102. The proximal end 112 of the links 106 is attached to first peaks 114 forming what appears to be the Y-shaped portion 104. The U-shaped portions 100 are unattached to any connecting link 106. In this embodiment, a first distal end ring 116 is attached to an adjacent cylindrical body ring 40 by links 118 that are substantially straight and substantially aligned with the longitudinal axis of the stent. Similarly, a second distal end ring 120 is attached to the first distal end ring by links 118. The proximal end 122 of the links 118 is attached to first peaks 114 and the distal end 124 of the links 118 are attached to second peaks 126 of the first distal end ring. Similarly, the proximal end 122 of links 118 are attached to third peaks 128 of the first distal end ring, and the distal end 124 of link 118 is attached to fourth peaks 130 of the second distal end ring 120. As can be seen, adjacent cylindrical body rings 40 are interconnected by links wherein the links are connected from a peak of one cylindrical ring to a valley of an adjacent cylindrical ring. In this manner, a first gap 132 is formed between adjacent cylindrical rings and is very small, on the order of less than 0.5 mm (0.0197 inch) and can range to as low as 0.1 mm (0.00394 inch). In contrast, the first distal end ring 116 is attached to the adjacent cylindrical body ring 40 by links 118 that are peak to peak, rather than peak to valley as with the body rings. Likewise, the first distal end rings 116 are connected by links 118 in a peak-to-peak pattern with the second distal end ring 120. A second gap 134 is formed between the first distal end ring 116 and the adjacent cylindrical body ring 40 as well as between the first distal end ring 116 and the second distal end ring 120. The second gap 134 is larger than the first gap 132 which, as previously described, provides a greater area for the expandable portion (balloon) of the catheter to protrude into when the stent is crimped onto the expandable portion of the catheter. This increases stent retention and prevents inadvertent stent dislodgment during delivery of the stent to, for example, the renal arteries or the coronary arteries.
In another embodiment, shown in
In another aspect of the invention, as shown in
The stent 30 of the present invention can be mounted on a balloon catheter similar to the catheter shown in the prior art device in
The stent 30 of the present invention can be made in many ways. One method of making the stent is to cut a thin-walled tubular member, such as stainless steel tubing to remove portions of the tubing in the desired pattern for the stent, leaving relatively untouched the portions of the metallic tubing which are to form the stent. The stent also can be made from other metal alloys such as tantalum, nickel-titanium, cobalt-chromium, titanium, shape memory and superelastic alloys, and the nobel metals such as gold or platinum. In accordance with the invention, it is preferred to cut the tubing in the desired pattern by means of a machine-controlled laser as is well known in the art.
The stent of the present invention also can be made from metal alloys other than stainless steel, such as shape memory alloys. Shape memory alloys are well known and include, but are not limited to, nickel-titanium and nickel-titanium-vanadium. Any of the shape memory alloys can be formed into a tube and laser cut in order to form the pattern of the stent of the present invention. As is well known, the shape memory alloys of the stent of the present invention can include the type having superelastic or thermoelastic martensitic transformation, or display stress-induced martensite. These types of alloys are well known in the art and need not be further described here.
Importantly, a stent formed of shape memory alloys, whether the thermoelastic or the stress-induced martensite-type, can be delivered using a balloon catheter of the type described herein, or be delivered via a catheter without a balloon or a sheath catheter.
The present invention stent is ideally suited, for example, for drug delivery (i.e., delivery of a therapeutic agent) since it has a uniform surface area which ensures uniform distribution of drugs. Typically, a polymer is coated onto the stent of the type disclosed in U.S. Pat. Nos. 6,824,559 and 6,783,793 which are incorporated herein by reference.
These bioactive agents can be any agent, which is a therapeutic, prophylactic, or diagnostic agent. These agents can have anti-proliferative or anti-inflammmatory properties or can have other properties such as antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombonic, antimitotic, antibiotic, antiallergic, antioxidant as well as cytostatic agents. Representative embodiments of the active component include actinomycin D (available from Sigma-Aldrich; or Cosmegen® available from Merck) or derivatives, analogs or synonyms thereof, such as dactinomycin, actinomycin IV, actinomycin I1, actinomycin X1, and actinomycin C1; podophyllotoxins such as etoposide and teniposide (Bristol Myers Squibb and Sigma Chemical); cephalotin (Bristol Myers Squibb); trapidil; ticlopidine (Danbury Pharma, Genpharm); tranilast (SmithKline Beecham and LG Chemical Kissei, Japan); IIb-IIIa inhibitors such as eptifibatide (COR therapeutic); clobetasol (Glaxo Wellcome); COX-2 inhibitors such as celecoxib (CELEBREX) (Searle and Pfizer) and rofecoxib (VIOXX) (Merck); PGE1 or alprostadil (Bedford); bleomycin; ENDOSTATIN (EntreMed); ANGIOSTATIN (EntreMed); thalidomide; 2-methoxyestraidol (EntreMed and Sigma Chemical) curcimin (the major constituent of turmeric power extract from the rhizomes of the plant Curcuma longa L found in south and southeast tropical Asia); cisplatin (Sigma Chemical); dipyridamole; tirofiban; verapamil; vitronectine; argatroban; and carboplatin (Sigma Chemical). Additionally corticosteroids such as anti-inflammatory glucocorticoids including clobetasol, diflucortolone, flucinolone, halcinonide, and halobetasol can also be used. In one embodiment, faster acting non-steroidal anti-inflammatory agents such as naproxen, aspirin, ibuprofen, fenoprofin, indomethacin, and phenylbutazone can be used in conjunction with the glucocorticoids. The use of a non-steroidal anti-inflammatory agent is useful during the early stages of the inflammation in response to a mechanically mediated vascular injury. Examples of suitable therapeutic and prophylactic agents include synthetic inorganic and organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, and DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities. Nucleic acid sequences include genes, antisense molecules which bind to complementary DNA to inhibit transcription, and ribozymes. Some other examples of other bioactive agents include antibodies, receptor ligands, enzymes, adhesion peptides, blood clotting factors, inhibitors or clot dissolving agents such as streptokinase and tissue plasminogen activator, antigens for immunization, hormones and growth factors, oligonucleotides such as antisense oligonucleotides and ribozymes and retroviral vectors for use in gene therapy. Examples of anti-proliferative agents include rapamycin and its functional or structural derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), and its functional or structural derivatives, paclitaxel and its functional and structural derivatives. Examples of rapamycin derivatives include methyl rapamycin, ABT-578, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin. Examples of paclitaxel derivatives include docetaxel. Examples of antineoplastics and/or antimitotics include methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin® from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g. Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, thrombin inhibitors such as Angiomax ä (Biogen, Inc., Cambridge, Mass.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacore® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), nitric oxide or nitric oxide donors, super oxide dismutases, super oxide dismutase mimetic, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), estradiol, anticancer agents, dietary supplements such as various vitamins, and a combination thereof. Examples of anti-inflammatory agents including steroidal and non-steroidal anti-inflammatory agents include tacrolimus, dexamethasone, clobetasol, combinations thereof. Examples of such cytostatic substance include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. Prinivil® and Prinzide® from Merck & Co., Inc., Whitehouse Station, N.J.). An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate include alpha-interferon, bioactive RGD, and genetically engineered epithelial cells. The foregoing substances can also be used in the form of prodrugs or co-drugs thereof. The bioactive agents also include metabolites of the foregoing substances and prodrugs of these metabolites. The foregoing substances are listed by way of example and are not meant to be limiting. Other active agents which are currently available or that may be developed in the future are equally applicable.
While the invention has been illustrated and described herein, in terms of its use as an intravascular stent, it will be apparent to those skilled in the art that the stent can be used in other body lumens. Further, particular sizes and dimensions, number of undulations or U-shaped portions per ring, materials used, shape of the connecting links, and the like have been described herein and are provided as examples only. Other modifications and improvements may be made without departing from the scope of the invention.
