Patent Application
20080255657
This invention generally relates to stents, such as intravascular stents. More particularly, the invention is directed to stents comprising expandable stent segments, such as unconnected expandable stent segments. The invention is also directed to methods for making such stents.
Stents are used to treat a variety of medical conditions. In blood vessels, they have been used to treat, e.g., stenoses and aneurysms. They are also used to treat or correct conditions in body lumens other than blood vessels, such as the ureter, urethra, duodenum, and bile duct. Drug-coated stents are known, for localized delivery of therapeutic agents to a body lumen. See, e.g., U.S. Pat. No. 6,099,562 to Ding et al.
Certain stents comprise a plurality of expandable stent segments interconnected by connectors. Such stents can be manufactured by a variety of methods. For example, they can be manufactured by starting with a hollow cylinder made of a given material. Struts and connectors are formed by removing material from certain parts of the cylinder.
It has been noted that the performance and characteristics of stents can be improved. For example, one aspect of the performance of a stent in a medical application is deliverability, i.e. the ability of the stent to be delivered through sometimes tortuous body lumens. To some degree, deliverability is affected by the number of connectors included in a stent. Reducing the number of connectors tends to make the stent more flexible or bendable, leading to increased deliverability of the stent.
Also, another characteristic of stents is uniformity or non-uniformity of design parameters along the length of the stent. For example, a stent may have a consistent geometric design along its entire length, or the stent may have a geometric design that varies along the length. In part because of current methods of manufacture, it is difficult to make a stent having non-uniform design parameters along its length, as opposed to uniform design parameters along its length.
It is therefore an object of the present invention to provide stents having improved deliverability and more flexibility in the uniformity or non-uniformity of design parameters along the length of the stent.
The present invention seeks to address these objectives by providing a stent comprising individual expandable stent segments not connected to each other whose design parameters can be readily varied along the length of the stent. Also, since the stent segments are unconnected, deliverability of the stent is increased.
In one embodiment, an intravascular stent for implantation in a blood vessel is disclosed comprising a first expandable stent segment comprised of a first material and a second expandable stent segment comprised of a second material that is different from the first material, wherein the first stent segment and the second stent segment may or may not be connected to each other. The first material may have a different radiopacity than the second material. For instance, the second material may have a greater radiopacity than the first material. In some embodiment, the first material may comprise platinum. The first and second materials may each comprise a weight percentage of platinum, and the second material may have a higher weight percentage of platinum than the first material. Also, the second stent segment may be disposed at one end of the stent. In another aspect of this embodiment, the stent may further comprise a third expandable stent segment that is not connected to the first and second stent segments. The third stent segment may comprise the second material and be disposed at the other end of the stent. The third stent segment may comprise a third material that is different from the first and second materials. The stent segments may be configured to be expanded using a balloon.
In another embodiment, an intravascular stent for implantation in a blood vessel is disclosed comprising at least three expandable stent segments that are not connected to each other, wherein the first stent segment comprises a first material and the second and third stent segments comprise a second material that is more radiopaque than the first material, and wherein the first stent segment is disposed between the second and third stent segments and the second and third stent segments are each disposed at an end of the stent.
In yet another embodiment, an intravascular stent for implantation in a blood vessel is disclosed comprising a first expandable stent segment having a first composition comprising a first therapeutic agent disposed thereon, and a second expandable stent segment having a second composition comprising a second therapeutic agent disposed thereon, wherein the first and second stent segments may or may not be connected to each other and wherein the first and second therapeutic agents are different. The first therapeutic agent may comprise an anti-proliferative agent. The first therapeutic agent may comprise an anti-thrombotic agent. The first therapeutic agent may comprise an anti-proliferative agent, and the second therapeutic agent may comprise an anti-thrombotic agent. In a variation, the stent further comprises a third expandable stent segment that is not connected to the first and second stent segments. The first stent segment may be disposed between the second and third stent segments and the third stent segment may comprise the second composition comprising the second therapeutic agent disposed thereon. The second and third stent segments may each be disposed at an end of the stent. The first therapeutic agent may comprise paclitaxel. The first therapeutic agent may comprise rapamycin, and if so the second therapeutic agent may comprise paclitaxel. The first therapeutic agent may comprise an anti-inflammatory agent. The stent may be configured to be expanded using a balloon.
In yet another embodiment, a stent for implantation in a blood vessel is disclosed comprising a first expandable stent segment having a first composition comprising a first amount of a therapeutic agent disposed thereon, and a second expandable stent segment having a second composition comprising a second amount of the therapeutic agent disposed thereon, wherein the second amount is different from the first amount, and wherein the first and second stent segments may or may not be connected to each other. The first amount may be less than the second amount. The first composition may comprise a first polymer, and the second composition may comprise a second polymer. In a variation, the stent further comprises a third expandable stent segment that may or may not be connected to the first and second stent segments. A third composition comprising a third amount of the therapeutic agent may be disposed thereon. The third amount may be different from the first amount and the second amount. The first stent segment may be disposed between the second and third stent segments. The stent may be configured to be expanded using a balloon.
In yet another embodiment, a stent for implantation in a blood vessel is disclosed comprising at least three stent segments that may or may not be connected to each other, wherein the first stent segment is disposed between the second and third stent segments and the second and third stent segments are each disposed at an end of the stent, and wherein the first stent segment comprises a first amount of a composition comprising a therapeutic agent disposed thereon and the second and third stent segments each comprise a second amount of the composition comprising the therapeutic agent disposed thereon in which the first amount is less than the second amount.
In yet another embodiment, a stent for implantation in a blood vessel is disclosed comprising a first expandable stent segment having an outer surface having a first surface area, and a second expandable stent segment having an outer surface having a second surface area, wherein the first and second stent segments may or may not be connected to each other, and wherein the first surface area and second surface area are different. The first expandable stent segment may comprise struts having a first undulation length and the second expandable stent segment may comprises struts having a second undulation length. The first undulation length may be less than the second undulation length.
In yet another embodiment, a stent for implantation in a blood vessel is disclosed comprising a first expandable stent segment having a first strut thickness, and a second expandable stent segment having a second strut thickness, wherein the first and second stent segment may or may not be connected to each other. The second strut wall thickness may be greater than the first strut wall thickness.
In yet another embodiment a stent for implantation in a blood vessel is disclosed comprising at least three stent segments that may or may not be connected to each other and are disposed about a longitudinal axis, wherein the first stent segment is disposed between the second and third stent segments and the second and third stent segments are each disposed at an end of the stent, and wherein the first stent segment comprises a plurality of struts having a first strut thickness, and wherein the second and third stent segments each comprises a plurality of struts having a second strut thickness, and wherein the second strut thickness is greater than the first strut thickness.
In another embodiment, a stent for implantation in a blood vessel comprises a first expandable stent segment having a plurality of struts. These struts include at least a first strut that has an abluminal surface, a luminal surface, an upstream surface, and a downstream surface. The stent also includes a second expandable stent segment having a plurality of struts. These struts of the second stent segment include at least a second strut that has an abluminal surface, a luminal surface, an upstream surface, and a downstream surface. A first coating is disposed on at least one of the abluminal, luminal, upstream or downstream surfaces of the first strut. A second coating is disposed on at least one of the abluminal, luminal, upstream or downstream surfaces of the second strut. The first and second coatings are disposed on different surfaces or on a different combination of surfaces of the first and second strut. Also, the first and second stent segments are not connected to each other.
Preferred features of the present invention are disclosed in the accompanying drawings, wherein similar reference characters denote similar elements throughout the several views, and wherein:
In one embodiment, the unconnected stent segments comprising a stent may be made of different materials. In the exemplary embodiment depicted in
In some variations, each stent segment may comprise a different material from every other stent segment. In other variations, at least some of the stent segments may comprise the same material. Also, these stent segments of different materials can include a coating comprising a polymer and/or therapeutic agent such as those discussed below.
The materials comprising stent segments 110-150 may be chosen to have different properties, such as radiopacity, tensile strength, malleability, density, porosity, hardness, heat conductivity, electrical conductivity, magnetic susceptibility, coefficient of thermal expansion, length change on expansion, heat capacity, melting point, hoop strength, radial resistive force, flexibility, stiffness, elastic recoil or shape memory properties. For example, a stent segment that is located at the end of the stent (i.e., an end stent segment), such as stent segment 110, may be chosen to have a greater radiopacity than a stent segment, such as stent segment 120, that is not an end stent segment. This may permit the ends of the stent to be readily identified using X-ray photography or fluoroscopy. As another example, stent segments 120, 130, and 140 may be chosen to have high flexibility to improve delivery of the stent through tortuous passages, while stent segments 110 and 150 may be chosen to have high hoop strength in order to prevent stent collapse. Other variations and combinations are expressly contemplated, and will be appreciated by those of skill in the art.
In another embodiment, the stent segments comprise different therapeutic agents. For instance, in the exemplary embodiment depicted in
For example, stent segment 210 may be coated with an anti-thrombotic drug, and stent segment 220 may be coated with an anti-proliferative drug. Stent segment 210 may be coated with rapamyacin or a rapamyacin derivative. Stent segment 220 may be coated with paclitaxel. Stent segment 210 may be coated with an anti-inflammatory. Various other therapeutic agents including but not limited to those described herein may be placed on the stent segments. A more comprehensive (though not exhaustive) listing of therapeutic agents with which the stent segments of stent 200 may be coated appears infra.
In some variations, each stent segment 210-250 may be coated with a different therapeutic agent, such as a drug. In other embodiments, at least some of the stent segments may be coated with the same therapeutic agent. In some embodiments, such as that of
In the exemplary stent of
In another variation, the stent segments are coated with three or more different therapeutic agents in a repeating pattern. For example, stent segment 310 may be coated with a first therapeutic agent, stent segment 320 may be coated with a second therapeutic agent, stent segment 330 may be coated with a third therapeutic agent, stent segment 340 may be coated with the first therapeutic agent, stent segment 350 may be coated with the second therapeutic agent, and a sixth stent segment (not shown) adjacent to stent segment 350 may be coated with the third therapeutic agent.
Many other variations are possible. For example, if the numerals 1, 2, 3, . . . represent a first therapeutic agent, a second therapeutic agent, and a third therapeutic agent, a series of stent segments might be coated with therapeutic agents in the pattern 1-2-2-1-1-2-2-1, or in the pattern 1-2-3-3-3-1-2-3-3-3, or in any other pattern. In another embodiment, stent segments having different therapeutic agents disposed thereon are not arranged in a repeating pattern. Such an embodiment may be advantageous for an application in which a stent must have some certain number of stent segments coated with a given therapeutic agent, but for which the relative placement of such stent segments along the stent is unimportant. In general, stent segments having different therapeutic agents disposed thereon can be arranged in any order, depending on the needs of the application.
Also, the therapeutic agent disposed on the stent segments can be contained in a coating. The coating can contain in addition to the therapeutic agent a polymer, such as those discussed below. In the exemplary embodiment depicted in
In the embodiment shown in
In another embodiment, shown in
Many other variations are possible. For example, if the numerals 1, 2, 3, . . . represent a first amount, a second amount, and a third amount of therapeutic agent, a series of stent segments might be coated with different amounts of therapeutic agent in the pattern 1-2-2-1-1-2-2-1, or in the pattern 1-2-3-3-3-1-2-3-3-3, or in any other pattern. This may allow delivery of specific amounts of therapeutic agent to specific tissue areas based on, for example, the specific configuration of a particular obstruction within a lumen.
Patterns that load more drug near the ends of the stent may be advantageous in achieving uniform delivery, considering that the vessel beyond an end of the stent may act as a “sink,” absorbing more of the drug, whereas the segments in the middle are surrounded by adjacent drug-eluting segments. Such configurations may be represented by patterns such as 2-1-1-1-1-2, 2-2-1-1-1-2-2, 3-2-1-1-1-2-3, or 5-4-3-2-1-2-3-4-5, where higher numbers indicate relatively larger amounts of drug or therapeutic agent.
In another variation, the therapeutic agent amount of the unconnected stent segments comprising a stent may vary randomly, subject to the constraints that no single stent segment has a therapeutic agent amount of greater than M1 grams or less than M2 grams, and the total therapeutic agent amount of all the stent segments in the stent taken together is no greater than M3 grams and no less than M4 grams, where M1, M2, M3, and M4 are variables that can be assigned particular numeric values. This variation may have the advantage that less precise, less costly drug application methods may be used in making the stent while still delivering the correct overall amount of therapeutic agent to the stented area.
Varying the amount of the coating along the stent can achieve a more uniform distribution of the therapeutic agent to tissues along the stent, or, alternatively, can achieve a deliberately non-uniform distribution of the therapeutic agent. For example, if the therapeutic agent is soluble or suspendable in blood, sorting the stent segments such that the stent segment with the smallest amount of therapeutic agent is at the downstream end of the stent may achieve a more uniform distribution of drug to the tissue surrounding the stent, since the amounts of therapeutic agent contributed by the stent segments will tend to be additive in the downstream direction.
In another embodiment, each of the unconnected stent segments comprising a stent may be coated with a composition comprising a therapeutic agent having a different release rate. The release rate may be affected by, for example, the matrix or polymers in which the therapeutic agent is disposed. In a variation, the release rates may vary from unconnected stent segment to unconnected stent segment within a stent according to a pattern. In another variation, the release rates may vary from unconnected stent segment to unconnected stent segment within a stent randomly.
In another embodiment, each of the unconnected stent segments comprising a stent may be coated with a therapeutic agent (or a composition comprising a therapeutic agent) having a different duration of release. In a variation, the release durations may vary from unconnected stent segment to stent segment within a stent according to a pattern. In another variation, the release durations may vary from unconnected stent segment to stent segment within a stent randomly.
In one embodiment, the stent comprises unconnected stent segments that vary in total undulation length, or vary in the total surface area of an outer surface, or in both total undulation length and total surface area. In one embodiment, a stent comprises end stent segments having a relatively large number of struts per segment, such as stent segment 510, as shown in
In some embodiments, the stent segments that make up the stent can each have struts in which different surfaces or a different combination of surfaces of the struts are coated with a coating composition.
In this embodiment, the struts of at least two stent segments, 710 and 720, have coatings disposed on a different combination of their respective strut surfaces. Specifically, a first coating 750 is disposed on all four surfaces, 710A, 710L, 710U and 710D of strut 710s of segment 710 and a second coating 752 is only disposed on the abluminal surface 720A of strut 720s of segment 720. Thus, in this embodiment, the first and second coatings are disposed on a different combination of surfaces of the two struts, i.e., four surfaces of strut 710s are coated while one surface of strut 720s is coated. Although the coatings in this embodiment are different, they can be the same. Similarly, a first coating 750 is disposed on all four surfaces, 730A, 730L, 730U and 730D of strut 730s of segment 730 and a second coating 752 is only disposed on the abluminal surface 740A of strut 740s of segment 740.
In another embodiment, the inventive stent comprises unconnected stent segments disposed about a longitudinal axis, wherein the thickness of each stent segment is different. For example,
In a variation of this embodiment, the wall thickness tapers from the center to the ends (i.e. the central stent segment has the greatest wall thickness and the end stent segments have the least wall thickness). This configuration makes the stent as flexible as possible at the ends, and stiffest in the center. It also tends to maximize laminar flow through the stent. In another variation, wall thickness tapers from the ends toward the center (i.e. the end segments have the greatest wall thickness and the central stent has the least wall thickness in order to position thinner segments centrally). This may provide for more flexible stent segments near the center in order to facilitate delivery through tortuous passages.
Although the exemplary stents described herein and depicted in the above figures generally comprise 4 or 5 stent segments, the inventive stent may comprise other numbers of stent segments, for example 2, or 3, or more than 5 stent segments. In general, a stent segment may have a length less than that of the area to be stented, so that a stent will comprise at least two stent segments. Fewer stent segments may be needed when treating a relatively short section of tissue, and more stent segments may be needed to treat a longer section of tissue. The number of stent segments required will also depend on the length of each individual stent segment.
Even though, in the exemplary stents described herein no stent segment is rigidly connected to any other stent segment, in other variations at least some of the stent segments may be connected to other stent segments. This allows combining the advantages of unconnected stent segments (described supra) with advantages of conventional, connected stent segments, such as greater rigidity. Stent segments may be connected with at least one connecting member.
The exemplary stents described herein may have a tubular or cylindrical-like configuration. However, these stents need not be completely cylindrical. For instance, the cross-section of the stent, or of any of the stent segments of which it is comprised, can be substantially triangular, rectangular, oval-shaped, polygonal, or variable-shaped. The cross-section of a stent can be varied to depend on the shape of a body lumen.
Stent segments are depicted in
The stent segments of which each stent depicted in the various figures is comprised are shown as disposed along a longitudinal axis, for example the axis A-A of
The stent segments depicted in each of
Alternatively, the unconnected stent segments comprising stent 10 may be delivered individually (one at a time) or in groups, by balloon or other delivery mechanism.
When stent 10 is inserted into a desired location within a patient, balloon 14 may be inflated, which may thereby expand stent 10. At least one strut element 50 of stent 10 may thereby be brought into contact with at least a portion of the surface 40 of the obstruction 42 and/or the inner wall 72 of a vessel 70. Vessel 70 may be expanded slightly by the expansion of stent 10 to provide volume for the expanded lumen. As a result, interference of blood flow by stent 10 may be minimized, in addition to preventing unwarranted movement of stent 10 once the expansion is complete.
The coating suitable for use with the stents can include a therapeutic agent and/or polymer.
The term “therapeutic agent” as used in the present invention encompasses drugs, genetic materials, and biological materials and can be used interchangeably with “biologically active material”. Non-limiting examples of suitable therapeutic agent include heparin, heparin derivatives, urokinase, dextrophenylalanine proline arginine chloromethylketone (PPack), enoxaprin, angiopeptin, hirudin, acetylsalicylic acid, tacrolimus, everolimus, rapamycin (sirolimus), pimecrolimus, amlodipine, doxazosin, glucocorticoids, betamethasone, dexamethasone, prednisolone, corticosterone, budesonide, sulfasalazine, rosiglitazone, mycophenolic acid, mesalamine, paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, methotrexate, azathioprine, adriamycin, mutamycin, endostatin, angiostatin, thymidine kinase inhibitors, cladribine, lidocaine, bupivacaine, ropivacaine, D-Phe-Pro-Arg chloromethyl ketone, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, dipyridamole, protamine, hirudin, prostaglandin inhibitors, platelet inhibitors, trapidil, liprostin, tick antiplatelet peptides, 5-azacytidine, vascular endothelial growth factors, growth factor receptors, transcriptional activators, translational promoters, antiproliferative agents, 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, agents which interfere with endogenous vasoactive mechanisms, antioxidants, probucol, antibiotic agents, penicillin, cefoxitin, oxacillin, tobranycin, angiogenic substances, fibroblast growth factors, estrogen, estradiol (E2), estriol (E3), 17-beta estradiol, digoxin, beta blockers, captopril, enalopril, statins, steroids, vitamins, paclitaxel (as well as its derivatives, analogs or paclitaxel bound to proteins, e.g. Abraxane™) 2′-succinyl-taxol, 2′-succinyl-taxol triethanolamine, 2′-glutaryl-taxol, 2′-glutaryl-taxol triethanolamine salt, 2′-O-ester with N-(dimethylaminoethyl) glutamine, 2′-O-ester with N-(dimethylaminoethyl) glutamide hydrochloride salt, nitroglycerin, nitrous oxides, nitric oxides, antibiotics, aspirins, digitalis, estrogen, estradiol and glycosides. In one embodiment, the therapeutic agent is a smooth muscle cell inhibitor or antibiotic. In a preferred embodiment, the therapeutic agent is taxol (e.g., Taxol®), or its analogs or derivatives. In another preferred embodiment, the therapeutic agent is paclitaxel, or its analogs or derivatives. In yet another preferred embodiment, the therapeutic agent is an antibiotic such as erythromycin, amphotericin, rapamycin, adriamycin, etc.
The term “genetic materials” means DNA or RNA, including, without limitation, of DNA/RNA encoding a useful protein stated below, intended to be inserted into a human body including viral vectors and non-viral vectors.
The term “biological materials” include cells, yeasts, bacteria, proteins, peptides, cytokines and hormones. Examples for peptides and proteins include vascular endothelial growth factor (VEGF), transforming growth factor (TGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), cartilage growth factor (CGF), nerve growth factor (NGF), keratinocyte growth factor (KGF), skeletal growth factor (SGF), osteoblast-derived growth factor (BDGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), cytokine growth factors (CGF), platelet-derived growth factor (PDGF), hypoxia inducible factor-1 (HIF-1), stem cell derived factor (SDF), stem cell factor (SCF), endothelial cell growth supplement (ECGS), granulocyte macrophage colony stimulating factor (GM-CSF), growth differentiation factor (GDF), integrin modulating factor (IMF), calmodulin (CaM), thymidine kinase (TK), tumor necrosis factor (TNF), growth hormone (GH), bone morphogenic protein (BMP) (e.g., BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (PO-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-14, BMP-15, BMP-16, etc.), matrix metalloproteinase (MMP), tissue inhibitor of matrix metalloproteinase (TIMP), cytokines, interleukin (e.g. IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-15, etc.), lymphokines, interferon, integrin, collagen (all types), elastin, fibrillins, fibronectin, vitronectin, laminin, glycosaminoglycans, proteoglycans, transferrin, cytotactin, cell binding domains (e.g., RGD), and tenascin. Currently preferred BMP's are BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. 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 transplant site. The delivery media can be formulated as needed to maintain cell function and viability. Cells include progenitor cells (e.g., endothelial progenitor cells), stem cells (e.g., mesenchymal, hematopoietic, neuronal), stromal cells, parenchymal cells, undifferentiated cells, fibroblasts, macrophage, and satellite cells.
Other non-genetic therapeutic agents include:
Preferred biological materials include anti-proliferative drugs such as steroids, vitamins, and restenosis-inhibiting agents. Preferred restenosis-inhibiting agents include microtubule stabilizing agents such as Taxol®, paclitaxel (i.e., paclitaxel, paclitaxel analogs, or paclitaxel derivatives, and mixtures thereof). For example, derivatives suitable for use in the present invention include 2′-succinyl-taxol, 2′-succinyl-taxol triethanolamine, 2′-glutaryl-taxol, 2′-glutaryl-taxol triethanolamine salt, 2′-O-ester with N-(dimethylaminoethyl) glutamine, and 2′-O-ester with N-(dimethylaminoethyl) glutamide hydrochloride salt.
Other suitable therapeutic agents include tacrolimus; halofuginone; inhibitors of HSP90 heat shock proteins such as geldanamycin; microtubule stabilizing agents such as epothilone D; phosphodiesterase inhibitors such as cliostazole; Barkct inhibitors; phospholamban inhibitors; and Serca 2 gene/proteins.
Other preferred therapeutic agents include nitroglycerin, nitrous oxides, nitric oxides, aspirins, digitalis, estrogen derivatives such as estradiol and glycosides.
In one embodiment, the therapeutic agent is capable of altering the cellular metabolism or inhibiting a cell activity, such as protein synthesis, DNA synthesis, spindle fiber formation, cellular proliferation, cell migration, microtubule formation, microfilament formation, extracellular matrix synthesis, extracellular matrix secretion, or increase in cell volume. In another embodiment, the therapeutic agent is capable of inhibiting cell proliferation and/or migration.
In certain embodiments, the therapeutic agents for use in the medical devices of the present invention can be synthesized by methods well known to one skilled in the art. Alternatively, the therapeutic agents can be purchased from chemical and pharmaceutical companies.
Polymers useful in the coating composition should be ones that are biocompatible, particularly during insertion or implantation of the device into the body and avoids irritation to body tissue. Examples of such polymers include, but not limited to, polyurethanes, polyisobutylene and its copolymers, silicones, and polyesters. Other suitable polymers include polyolefins, polyisobutylene, 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, copolymers of vinyl monomers and olefins such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides such as Nylon 66 and polycaprolactone, alkyd resins, polycarbonates, polyoxyethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, collagens, chitins, polylactic acid, polyglycolic acid, and polylactic acid-polyethylene oxide copolymers.
When the polymer is being applied to a part of the medical device, such as a stent, which undergoes mechanical challenges, e.g. expansion and contraction, the polymers are preferably selected from elastomeric polymers such as silicones (e.g. polysiloxanes and substituted polysiloxanes), polyurethanes, thermoplastic elastomers, ethylene vinyl acetate copolymers, polyolefin elastomers, and EPDM rubbers. The polymer is selected to allow the coating to better adhere to the surface of the strut when the stent is subjected to forces or stress. Furthermore, although the coating can be formed by using a single type of polymer, various combinations of polymers can be employed.
Generally, when a hydrophilic therapeutic agent is used then a hydrophilic polymer having a greater affinity for the therapeutic agent than another material that is less hydrophilic is preferred. When a hydrophobic therapeutic agent is used then a hydrophobic polymer having a greater affinity for the therapeutic agent is preferred. However, in some embodiments, a hydrophilic therapeutic agent can be used with a hydrophobic polymer and a hydrophobic therapeutic agent can be used with a hydrophilic polymer.
Examples of suitable hydrophobic polymers or monomers include, but not limited to, polyolefins, such as polyethylene, polypropylene, poly(1-butene), poly(2-butene), poly(1-pentene), poly(2-pentene), poly(3-methyl-1-pentene), poly(4-methyl-1-pentene), poly(isoprene), poly(4-methyl-1-pentene), ethylene-propylene copolymers, ethylene-propylene-hexadiene copolymers, ethylene-vinyl acetate copolymers, blends of two or more polyolefins and random and block copolymers prepared from two or more different unsaturated monomers; styrene polymers, such as poly(styrene), poly(2-methylstyrene), styrene-acrylonitrile copolymers having less than about 20 mole-percent acrylonitrile, and styrene-2,2,3,3,-tetrafluoropropyl methacrylate copolymers; halogenated hydrocarbon polymers, such as poly(chlorotrifluoroethylene), chlorotrifluoroethylene-tetrafluoroethylene copolymers, poly(hexafluoropropylene), poly(tetrafluoroethylene), tetrafluoroethylene, tetrafluoroethylene-ethylene copolymers, poly(trifluoroethylene), poly(vinyl fluoride), and poly(vinylidene fluoride); vinyl polymers, such as poly(vinyl butyrate), poly(vinyl decanoate), poly(vinyl dodecanoate), poly(vinyl hexadecanoate), poly(vinyl hexanoate), poly(vinyl propionate), poly(vinyl octanoate), poly(heptafluoroisopropoxyethylene), poly(heptafluoroisopropoxypropylene), and poly(methacrylonitrile); acrylic polymers, such as poly(n-butyl acetate), poly(ethyl acrylate), poly(1-chlorodifluoromethyl)tetrafluoroethyl acrylate, poly di(chlorofluoromethyl)fluoromethyl acrylate, poly(1,1-dihydroheptafluorobutyl acrylate), poly(1,1-dihydropentafluoroisopropyl acrylate), poly(1,1-dihydropentadecafluorooctyl acrylate), poly(heptafluoroisopropyl acrylate), poly 5-(heptafluoroisopropoxy)pentyl acrylate, poly 11-(heptafluoroisopropoxy)undecyl acrylate, poly 2-(heptafluoropropoxy)ethyl acrylate, and poly(nonafluoroisobutyl acrylate); methacrylic polymers, such as poly(benzyl methacrylate), poly(n-butyl methacrylate), poly(isobutyl methacrylate), poly(t-butyl methacrylate), poly(t-butylaminoethyl methacrylate), poly(dodecyl methacrylate), poly(ethyl methacrylate), poly(2-ethylhexyl methacrylate), poly(n-hexyl methacrylate), poly(phenyl methacrylate), poly(n-propyl methacrylate), poly(octadecyl methacrylate), poly(1,1-dihydropentadecafluorooctyl methacrylate), poly(heptafluoroisopropyl methacrylate), poly(heptadecafluorooctyl methacrylate), poly(1-hydrotetrafluoroethyl methacrylate), poly(1,1-dihydrotetrafluoropropyl methacrylate), poly(1-hydrohexafluoroisopropyl methacrylate), and poly(t-nonafluorobutyl methacrylate); polyesters, such a poly(ethylene terephthalate) and poly(butylene terephthalate); condensation type polymers such as and polyurethanes and siloxane-urethane copolymers; polyorganosiloxanes, i.e., polymeric materials characterized by repeating siloxane groups, represented by Ra SiO 4-a/2, where R is a monovalent substituted or unsubstituted hydrocarbon radical and the value of a is 1 or 2; and naturally occurring hydrophobic polymers such as rubber.
Examples of suitable hydrophilic polymers or monomers include, but not limited to; (meth)acrylic acid, or alkaline metal or ammonium salts thereof; (meth)acrylamide; (meth)acrylonitrile; those polymers to which unsaturated dibasic, such as maleic acid and fumaric acid or half esters of these unsaturated dibasic acids, or alkaline metal or ammonium salts of these dibasic adds or half esters, is added; those polymers to which unsaturated sulfonic, such as 2-acrylamido-2-methylpropanesulfonic, 2-(meth)acryloylethanesulfonic acid, or alkaline metal or ammonium salts thereof, is added; and 2-hydroxyethyl (meth)acrylate and 2-hydroxypropyl (meth)acrylate.
Polyvinyl alcohol is also an example of hydrophilic polymer. Polyvinyl alcohol may contain a plurality of hydrophilic groups such as hydroxyl, amido, carboxyl, amino, ammonium or sulfonyl (—SO3). Hydrophilic polymers also include, but are not limited to, starch, polysaccharides and related cellulosic polymers; polyalkylene glycols and oxides such as the polyethylene oxides; polymerized ethylenically unsaturated carboxylic acids such as acrylic, mathacrylic and maleic acids and partial esters derived from these acids and polyhydric alcohols such as the alkylene glycols; homopolymers and copolymers derived from acrylamide; and homopolymers and copolymers of vinylpyrrolidone.
Other suitable polymers include without limitation: polyurethanes, silicones (e.g., polysiloxanes and substituted polysiloxanes), and polyesters, styrene-isobutylene-copolymers. Other polymers which can be used include ones that can be dissolved and cured or polymerized on the medical device or polymers having relatively low melting points that can be blended with biologically active materials. Additional suitable polymers include, but are not limited to, thermoplastic elastomers in general, polyolefins, polyisobutylene, 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, copolymers of vinyl monomers and olefins such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS (acrylonitrile-butadiene-styrene) resins, ethylene-vinyl acetate copolymers, polyamides such as Nylon 66 and polycaprolactone, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, polyether block amides, epoxy resins, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, collagens, chitins, polylactic acid, polyglycolic acid, polylactic acid-polyethylene oxide copolymers, EPDM (ethylene-propylene-diene) rubbers, fluoropolymers, fluorosilicones, polyethylene glycol, polysaccharides, phospholipids, and combinations of the foregoing.
The coating composition comprising the therapeutic agent and/or polymer can be formed using a solvent. Solvents that may be used to prepare coating compositions include ones which can dissolve or suspend the polymer and/or therapeutic agent in solution. Examples of suitable solvents include, but are not limited to, tetrahydrofuran, methylethylketone, chloroform, toluene, acetone, isooctane, 1,1,1, trichloroethane, dichloromethane, isopropanol, IPA, and mixture thereof.
The coating composition comprising the therapeutic agent and/or polymer can be applied to the device by any method. Examples of suitable methods include, but are not limited to, spraying such as by conventional nozzle or ultrasonic nozzle, dipping, rolling, electrostatic deposition, and a batch process such as air suspension, pan coating or ultrasonic mist spraying. Also, more than one coating method can be used.
Coating compositions can be applied selectively to certain surfaces of certain stent segments and not to other surfaces. For example, a certain coating composition can be applied to the abluminal surfaces of one stent segment, whereas a different coating composition is applied to the luminal surfaces of another stent segment. Such selective coating of segments can be more easily accomplished if the segments are not connected to each other. Other techniques, such as masking, may also be used.
The description contained herein is for purposes of illustration and not for purposes of limitation. Changes and modifications may be made to the embodiments of the description and still be within the scope of the invention. Furthermore, obvious changes, modifications or variations will occur to those skilled in the art. Also, all references cited above are incorporated herein, in their entirety, for all purposes related to this disclosure.
This application claims the benefit of U.S. Provisional Application No. 60/910,698, filed on Apr. 9, 2007, the entire contents of which are incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 60910698 | Apr 2007 | US |
