US20070032856A1 - Drug eluting stent - Google Patents

Abstract

Stents having struts with narrowed portions are described. The narrowed portions have a coating disposed thereon for the local delivery of a drug.

Description

CROSS REFERENCE TO RELATED APPLICATION
• This is a divisional application of U.S. patent application Ser. No. 10/262,150, which was filed on Sep. 30, 2002.
BACKGROUND
• This invention relates to implantable medical devices, such as stents. More particularly, this invention relates to a stent having drug delivery capabilities.
• Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radially compress against the atherosclerotic plaque of the lesion to remodel the lumen wall. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient's vasculature.
• A problem associated with the procedure includes formation of intimal flaps or torn arterial linings that can collapse and occlude the conduit after the balloon is deflated. Moreover, thrombosis and restenosis of the artery can develop over several months after the procedure, which can require another angioplasty procedure or a surgical bypass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis, an intraluminal prosthesis, an example of which includes an expandable stent, is implanted in the lumen to maintain the vascular patency. Stents are scaffolding structures, usually cylindrical or tubular in shape, functioning to physically hold open, and if desired, to expand the wall of the passageway. Typically stents are capable of being compressed for insertion through small cavities via small catheters, and then expanded to a larger diameter once at the desired location.
• To treat the damaged vasculature tissue and further fight against thrombosis and restenosis, there is a need to administer therapeutic substances to the treatment site. For example, anticoagulants, antiplatelets and cytostatic agents are commonly used to prevent thrombosis of the coronary lumen, to inhibit development of restenosis, and to reduce post-angioplasty proliferation of the vascular tissue. To provide an efficacious concentration to the treated site, systemic administration of medication can produce adverse or toxic side effects for the patient. Local delivery is a highly suitable method of treatment in that smaller levels of medication, as compared to systemic dosages, are concentrated at a specific site. Local delivery produces fewer side effects and achieves more effective results.
• One commonly applied technique for the local delivery of the drugs is through the use of medicated stents. One method of medicating stents involves the use of a polymeric carrier coated onto the body of the stent. A polymer dissolved in a solvent and a drug added thereto can be applied to the stent. Once the solvent evaporates, a coating of the polymer containing the drug remains on the stent. The embodiments of the present invention provide various stent structures for containing a coating, such as a polymeric coating, for the local delivery of a drug.
SUMMARY
• In accordance with one embodiment, a stent is disclosed comprising a strut having a first segment, a second segment and a third segment located between the first and second segments, wherein the transverse cross sectional area of the third segment is less than the transverse cross sectional area of the first segment and the second segment; and a coating disposed on the third segment of the strut, wherein the first and second segments of the strut are free of any coating. In one embodiment, the coating is disposed all the way around the third segment of the strut. The outer surface of the coating should not extend beyond the outer surface of the first or second segment of the strut. The coating can be made from a polymeric material containing a therapeutic substance. In accordance with one embodiment, the strut includes a linear segment extending into a curved segment, wherein the first, second and third segments define a part of the linear segment of the strut. The curved segment can include a notch or can be smaller in thickness or width than the first or second segment of the strut.
• In accordance with another embodiment of the invention, a radially expandable stent is provided comprising a strut, at least a segment of the strut having a circumference smaller than the circumference of a remaining portion of the strut; and a coating supported by the segment of the strut having the smaller circumference. The strut can include four sides, wherein the width of the segment of the strut having the smaller circumference is less than the width of the remaining portion of the strut. Alternatively, the thickness of the segment of the strut having the smaller circumference is less than the thickness of the remaining portion of the strut. The coating can, for example, surround the segment of the strut having the reduced circumference. The remaining portion of the strut having the larger circumference can be free from any coating.
• In accordance with another embodiment of the invention, a method of manufacturing a drug eluting stent is provided, comprising depositing a coating on a first segment of a strut of the stent, the stent including a second segment and a third segment, wherein the first segment is positioned between the second segment and the third segment, the first segment having a smaller transverse cross sectional area than the transverse cross sectional area of the second or third segment.
• In accordance with another embodiment of the invention, a method of manufacturing a drug eluting stent is provided, comprising depositing a coating on a stent, the stent including a strut having a first segment, a second segment, and a third segment located between the first and second segments, wherein the transverse cross sectional area of the third segment is less than the transverse cross sectional area of the first segment and the second segment; and removing the coating off of the first and second segments so that the coating remains on the third segment.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 illustrates an embodiment of a conventional stent;
• FIG. 2 is an enlarged perspective view of the stent strut ofencircled region2 ofFIG. 1;
• FIGS. 2A and 2B are transverse cross sectional views along theline2A-2A and2B-2B, respectively, ofFIG. 2; and
• FIGS. 3, 4,5,6A, and6B are perspective views of a stent strut according to other embodiments of the invention.
DETAILED DESCRIPTION
• FIG. 1 illustrates one embodiment of astent10 that can be used with the practice of the present invention.Stent10 can be generally cylindrical and radially self- or balloon-expandable. Stent10 can be inserted and deployed in a patient with an appropriate delivery device such as a balloon dilatation catheter.Stent10 can be made, for example, from a plurality of wave-like or serpentine-like struts12 having curved segments and generally linear segments.Struts12 are connected to theadjacent struts12 via connectingelements14. The embodiments of the present invention, however, should not be limited to the structure ofFIG. 1. A variety of other scaffolding designs can also be used, such as “V” shaped struts or Struts having a “zigzag” formation.
• Referring toFIG. 2, the linear section ofstrut12 includes a segment, referred to byreference number16, wherein any transverse cross sectional portion ofsegment16 has a smaller cross sectional surface area than the remaining segment ofstrut12.FIG. 2A illustrates a transverse cross sectional view ofstrut12 ofFIG. 2 taken along theline2A-2A.FIG. 2B illustrates a transverse cross sectional view ofstrut12 ofFIG. 2 taken along theline2B-2B. As illustrated byFIGS. 2A and 2B,segment16 has a reduced thickness and width, which provides for a smaller circumference, as compared to the remaining portions ofstrut12.
• FIGS. 2, 2A and2B illustrate a four-sided strut12 whereinsegment16 has a reduced width W as well asthickness T. Struts12 need not be four-sided, however, and can have any suitable transverse cross sectional geometry, such as a three sided, oval or circular struts. The reduced circumferential size ofsegment16 defines arecessed volume18 in which acoating20 can be deposited.Coating20 can be a drug or a therapeutic composition or can contain the drug.Coating20 can be made from any suitable biocompatible polymer, examples of which are disclosed below. As best illustrated byFIG. 2, the remaining segments ofstrut12 can be free from any substances or coatings.Coating20 can be disposed all the way aroundsegment16 as coating20 can completely encapsulate the narrowedsegment16 ofstrut12. Recessedvolume18 can be fully filled with the coating substance such that the outer surfaces ofcoating20 are “flush” with their respective outer surfaces ofstrut12. In other words, the outer dimensions ofcoating20 can equal the outer dimensions ofstrut12, thereby creating a smooth transition between the surfaces ofcoating20 and the surfaces ofstrut12, thus minimizing intravascular flow turbulence aroundstent10.
• In accordance with another embodiment of the invention, as illustrated inFIG. 3, strut12 can have a variable thickness T, but a constant width W. As best illustrated byFIG. 3, width W ofstrut12 is the same, but thickness T is reduced alongsegment16 ofstrut12. The reduced thickness T provides recessedvolume18 containingcoating20 on the outer surface or tissue-contacting surface ofstrut12. Although not illustrated, a recessedvolume18 can also be provided in the inner or lumen surface ofstrut12.
• In accordance with another embodiment, as illustrated byFIG. 4, a variable width W forstrut12 can be provided, while maintaining the thickness T constant. As best illustrated byFIG. 4, thickness T of strut is the same, but width W is reduced alongsegment16 ofstrut12.FIG. 4 illustrates recessedvolumes18 on opposing sides ofstrut12. However, as is the case withFIG. 3, recessedvolume18 can be about only one of the two sides ofstrut12.
• Transition zones leading intosegment16 can be gradual, with a slight slop, as illustrated byFIG. 2 or can be a relatively sharp drop-off, as illustrated byFIG. 3 or4. The smallest transverse cross sectional area insegment16 can be up to about 50% smaller than the transverse cross sectional area of the remaining portions ofstrut12. One having ordinary skill in the art should be cautious of mechanical fatigue and failure that could be caused if the circumference ofsegment16 is too small or if the transition zone is sloped too non-compliant. Exemplary dimensions and design ofstrut12 depend, of course, on an variety of factors including the material from which strut12 is made, the length ofsegment16, and the application for whichstent10 will be used. Accordingly, there is a tradeoff between trying to maximizerecess volume18 for maximizing drug delivery capabilities and eliminating mechanical failure that can be caused by radial expansion and use ofstent10.
• In accordance with yet another embodiment, as illustrated inFIG. 5, any number ofsuitable segments16 having a reduced circumferential area can be included instrut12. Having a multitude ofsegments16 allows for the incorporation of more than one type of therapeutic substance in different areas ofstent10. Accordingly, a variety of cocktail combinations of drugs can be delivered viastent10. The longitudinal span of eachsegment16 depends on the number ofsegments16 that are to be incorporated intostrut12 and the length ofstrut12, among other factors.
• In accordance with yet another embodiment of the invention,FIG. 6A illustratesstrut12 having a thinned section, in either thickness or width, in the curved portion (as designated by reference number22) ofstrut12. Alternatively, as illustrated inFIG.6B notches24 can be provided incurved portion22 ofstrut12. The thinned section and/or pivotnotches24 incurved portion22 ofstrut12 can produce a weakened bending region forstent10. The weakened bending region can maximize bending alongcurved region22 or atpivot notches24 and minimize stress along the linear portion ofstrut12. This is advantageous in preserving the structural integrity ofcoating20 so as to prevent or reduce fragmentation of coating during the radial expansion ofstent10.
• Struts12 can be made from a metallic material or an alloy such as, but not limited to, cobalt chromium alloy (ELGILOY), stainless steel (316L), “MP35N,” “MP20N,” ELASTINITE (nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or combinations thereof “MP35N” and “MP20N” are trade names for alloys of cobalt, nickel, chromium and molybdenum available from Standard Press Steel Co., Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum.Struts12 can also be made fiom bioabsorbable or biostable polymers.
• The drug, therapeutic substance or active agent, terms which are used interchangeably, in thecoating20 can inhibit the activity of vascular smooth muscle cells. More specifically, the active agent can be aimed at inhibiting abnormal or inappropriate migration and/or proliferation of smooth muscle cells for the inhibition of restenosis. The active agent can also include any substance capable of exerting a therapeutic or prophylactic effect for a diseased condition. For example, the agent can be for enhancing wound healing in a vascular site or improving the structural and elastic properties of the vascular site. Examples of agents include antiproliferative substances such as actinomycin D, or derivatives and analogs thereof (manufactured by Sigma-Aldrich, Inc., Milwaukee, Wis.; or COSMEGEN available from Merck & Co., Inc., Whitehorse Station, N.J.). Synonyms of actinomycin D include dactinomycin, actinomycin IV, actinomycin I_l, actinomycin X_l, and actinomycin C_l. The active agent can also fall under the genus of antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and antioxidant substances. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g., TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g., Taxotere®, from Aventis S.A., Frankfurt, Germany), 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.). 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, and thrombin inhibitors such as Angiomax ä (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten® and Capozide® from Bristol-Myers Squibb Co.), cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck & Co., Inc.); 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 Mevacor® from Merck & Co., Inc.), 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), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate include alpha-interferon, genetically engineered epithelial cells, rapamycin and its derivatives and analogs, and dexamethasone.
• Coating20 can be made from any suitable biocompatible polymer, examples of which include ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL); poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone; poly(lactide-co-glycolide); poly(hydroxybutyrate); poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester; polyanhydride; poly(glycolic acid); poly(D,L-lactic acid); poly(glycolic acid-co-trimethylene carbonate); polyphosphoester; polyphosphoester urethane; poly(amino acids); cyanoacrylates; poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether-esters) (e.g., PEO/PLA); polyalkylene oxalates; polyphosphazenes; biomolecules, such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid; polyurethanes; silicones; polyesters; polyolefins; polyisobutylene and ethylene-alphaolefin copolymers; acrylic polymers and copolymers; vinyl halide polymers and copolymers, such as polyvinyl chloride; polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidene halides, such as polyvinylidene fluoride and polyvinylidene chloride; polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics, such as polystyrene; polyvinyl esters, such as polyvinyl acetate; copolymers of vinyl monomers with each other and olefins, such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers; polyamides, such as Nylon66 and polycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes; polyinides; polyethers; epoxy resins; polyurethanes; rayon; rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate; cellulose acetate butyrate; cellophane; cellulose nitrate; cellulose propionate; cellulose ethers; and carboxymethyl cellulose.Coating20 can also be silicon foam, neoprene, santoprene, or closed cell foam.
• Stent10 can be constructed, for example, from a tube of a desired strut material. The tube can be mounted onto a mandrel and angular grooves can be cut into the outer surface of the tube by a lathe or a Swiss screw, for example KJR-16Swiss Screw Machine available from STAR CNC Automatic Lathe in Shizuoka, Japan. The shape ofstrut12 can then be radially cut from the tube by a laser. The laser cutting can also produce the thinnedcurved section22 orpivot notches24 illustrated inFIGS. 6A and 6B.Struts12 can be electropolished to reshape or round off sharp comers.
• Stent10 can then be mounted on a Teflon® or paralyne coated mandrel fixed to a two-dimensional actuator controlled by a computer numerical control (CNC) controller, for example a Model DR500available from Aerotek, Inc., Pittsburgh, Pa. The two-dimensional actuator can translate and rotatestent10 about the longitudinal axis ofstent10. A fluid applicator device, for example a Model 1500XL available from EFD, Inc., East Providence, R.I., with a needle tip, can be fixed adjacent to the mountedstent10 and ejection of a coating substance can be controlled by the CNC controller. The needle tip can have an outer diameter of about 0.02 mm (0.0008in.) to about 0.038 mm (0.0015 in.) and an inner diameter from about 0.005 mm (0.0002 in.) to about 0.02 mm (0.0009 in.). The CNC controller then causes ejection ofcoating20 in a liquid state from the needle tip into recessedvolume18 and simultaneously movesstent10 longitudinally to spreadcoating20 evenly in recessedvolume18. Once recessedvolume18 ofsegment16 is coated with a desired volume ofcoating20, ejection of the coating substance ceases andstent10 can be moved until the next uncoated recessedvolume18 is adjacent to the needle tip of the fluid applicator device. The process can repeat until all the recessedvolumes18 are coated. The needle tip should also be capable of being raised and lowered relative tostent10 by the CNC controller particularly when coating small volumes necessitates direct contact between the needle tip andstent10.
• Alternatively, coating20 can be deposited in recessedvolumes18 by crimpingstent10 onto a mandrel covered with a soft material (for examples, having a D hardness rating of about 20 to about 50, such as silicon foam, neoprene, santoprene, or a closed cell foam). In a relaxed state, the soft material can have, for example, a soft material thickness of at least the thickness ofstrut12. The mandrel andstent10 can then be dipped into the coating substance or the coating substance can be sprayed ontostent10. The mandrel andstent10 can then be pulled through an orifice with a clearance aroundstrut12 of less than about 0.003 mm (0.0001 in.), more narrowly less than about 0.001 mm (0.00005 in.).Stent10 can also be pulled over a reamer to scrape off excess coating substance.
• In accordance with another embodiment of the invention, masking techniques as is known to a person having ordinary skill in the art can be used to depositcoating20 in recessedvolumes18 ofsegment16.
• While particular embodiments of the present invention have been shown and described, it will be obvious to those having ordinary skill in the art that changes and modifications can be made without departing from this invention. Therefore, the appended claims are to encompass within their scope all such changes and modifications as they fall within the true spirit and scope of the invention.

Claims (16)

1. A stent comprising a strut segment including a first recess on an outer surface of the strut and a second recess on an inner surface of the strut, the recesses disposed on opposite sides of the strut segment from each other, wherein the recesses carry a coating substance.

2. The stent ofclaim 1, wherein the coating substance includes a polymeric material.

3. The stent ofclaim 1, wherein a remaining portion of the strut segment is free from any coating.

4. The stent ofclaim 1, wherein the coating substance includes a drug.

5. The stent ofclaim 1, wherein the strut segment has a rectangular, triangular, oval or circular cross-sectional shape.

6. The stent ofclaim 1, wherein an outer surface of the coating substance does not extend beyond the surface of the strut segment.

7. A method of manufacturing a stent, comprising depositing a coating on a stent, the stent including a strut segment having a First recess on an outer surface of the strut and a second recess on an inner surface of the strut, the recesses disposed on opposite sides of the strut segment from each other.

8. The method ofclaim 7, wherein the coating includes a polymeric material.

9. The method ofclaim 7, wherein a remaining portion of the strut segment is free from any coating.

10. The method ofclaim 7, wherein the coating includes a drug.

11. The method ofclaim 7, wherein the strut segment has a rectangular, triangular, oval or circular cross-sectional shape.

12. The method ofclaim 7, wherein an outer surface of the coating does not extend beyond the surface of the strut segment.

13. A method of manufacturing a stent, comprising:

depositing a coating on a stent, the stent including a strut having a first segment, a second segment and a third segment located between the first and second segments, wherein the transverse cross-sectional area of the third segment is less than the transverse cross-sectional area of the first segment and the second segment, and wherein the strut includes a linear segment extending into a curved or bent segment, the first, second and third segments defining a part of the linear segment of the strut, wherein the curved or bent segment includes a notch carved out from the surface of the strut; and

removing the coating off of the first and second segments so that the coating remains on the third segment.

14. The method ofclaim 13, wherein the coating includes a drug.

15. The method ofclaim 13, wherein the strut has a rectangular, triangular, oval or circular cross-sectional shape.

16. The method ofclaim 13, wherein an outer surface of the coating does not extend beyond an outer surface of the strut.

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