Patent Application
20090192593
Described herein are implantable medical devices, such as implantable or intravascular stents, for delivering a therapeutic agent, and methods for making such medical devices. In one embodiment, the medical device comprises a stent having a plurality of struts, at least one of which has a cavity disposed therein. A therapeutic agent is delivered from the cavity through an opening in a strut surface. In another embodiment, the medical device is a stent having a coating disposed on the side surface(s) of at least one strut for deliver of a therapeutic agent from the coating.
Medical devices have been used to deliver therapeutic agents locally to the body tissue of a patient. For example, stents having a coating containing a therapeutic agent, such as an anti-restenosis agent, have been used in treating or preventing restenosis. Currently, such medical device coatings include a therapeutic agent alone of a combination of a therapeutic agent and a polymer. Some polymer coating compositions, however, do not actually adhere to the surface of the medical device. In order to ensure that the coating compositions remain on the surface, the area of the medical device that is coated, such as a stent strut, is encapsulated with the coating composition. However, since the polymer does not adhere to the medical device, the coating composition is susceptible to deformation and damage during loading, deployment and implantation of the medical device. Any damage to the polymer coating may alter the therapeutic agent release profile and can lead to an undesirable increase or decrease in the therapeutic agent release rate.
Furthermore, by encapsulating a stent strut with a coating comprising a therapeutic agent, an amount of the therapeutic agent greater than the desired amount may be delivered. For instance, if the therapeutic agent is an anti-restenosis agent, by applying a coating containing such an agent to all surfaces of the strut, including the luminal surface, may result in the unnecessary delivery of the anti-restenosis agent to the bloodstream.
Accordingly, there is a need for medical devices that can release an effective amount of a therapeutic agent in a desired manner while avoiding the disadvantages of current medical devices for delivering a therapeutic agent. Additionally, there is a need for methods of making such medical devices.
These and other objectives are addressed by the medical devices described herein. In one embodiment, the medical device comprises an implantable stent, which comprises a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure. At least one strut comprises an abluminal surface, a luminal surface, and a first side surface. The strut comprises a first material. Also, the at least one strut comprises at least one cavity disposed therein. The cavity has a first opening that is in fluid communication with the abluminal surface and a second opening that is in fluid communication with the first side surface. A therapeutic agent can be disposed in the cavity. Furthermore, a coating is disposed over at least a portion of the first opening of the cavity that is in fluid communication with the abluminal surface. The second opening of the cavity, which is in fluid communication with the side surface, is at least partially exposed.
In another embodiment, the medical device comprises an implantable stent that comprises a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure. At least one strut comprises an abluminal surface, a luminal surface, and a first side surface. Also, the at least one strut comprises at least one cavity disposed therein, in which the cavity has a first opening that is in fluid communication with the first side surface and the first opening of the cavity is at least partially exposed. The cavity does not have any opening that is in fluid communication with the abluminal surface or the luminal surface. Also a therapeutic agent is disposed in the cavity.
In addition, in one embodiment, the medical device comprises an implantable stent that comprises a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure. At least one of the struts comprises an abluminal surface, a luminal surface, and a first side surface. A first coating is disposed on at least a portion of the first side surface and the abluminal and luminal surfaces are substantially free of any coating.
Also described herein are methods for making medical devices. In one embodiment, the method is one for making an implantable stent. The method comprises the step of providing a tube having a tubular wall having a longitudinal axis, in which the tubular wall comprises an abluminal surface and luminal surface. There is at least one groove disposed in the abluminal surface of the tubular wall and the groove does not extend through the tubular wall to the luminal surface. A therapeutic agent is disposed in at least a portion of the groove. A coating is disposed over at least a portion of the abluminal surface such that at least a portion of the therapeutic agent disposed in the groove is covered by the coating. A stent is formed from the tube that has the coating disposed on the abluminal surface. The stent has a stent sidewall structure comprising a plurality of struts and gaps, wherein at least one of the struts comprises an abluminal surface, a luminal surface, and a first side surface. Also, the strut has a cavity that comprises a portion of the groove containing the therapeutic agent, and the cavity that comprises a portion of the groove containing the therapeutic agent, and the cavity has an opening, which is at least partially exposed, that is in fluid communication with the first side surface. Alternatively, instead of disposing a therapeutic agent in the groove, a filler material is disposed in the groove. After the stent is formed, the filler material is removed from the cavity and a therapeutic agent is disposed in the cavity.
In another embodiment, the method for making an implantable stent comprises providing a flat sheet of a material having a sheet wall. The sheet wall comprises a first surface and second surface. The method comprises disposing at least one groove in the first surface of the sheet wall, wherein the groove does not extend through the sheet wall to the second surface. A therapeutic agent is then disposed in at least a portion of the groove. A coating is disposed over at least a portion of the first surface such that at least a portion of the therapeutic agent disposed in the groove is covered by the coating. A sidewall structure is formed from the sheet, having the coating disposed on the first surface, by removing portions of the coated sheet. The a sidewall structure comprising a plurality of struts and gaps, wherein at least one of the struts comprises a top surface, a bottom surface, a first side surface and a cavity. The cavity comprises a portion of the groove containing the therapeutic agent, and an opening that is in fluid communication with the first side surface. The opening is at least partially exposed. Instead of disposing a therapeutic agent in the groove, a filler material can be disposed in the groove. After the sidewall structure is formed, the filler material is removed from the cavity and a therapeutic agent is disposed in the cavity.
In another method for making an implantable stent, the method comprises providing a stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure. There is at least one strut comprises an abluminal surface, a luminal surface, and a first side surface. Also, at least one vacity is disposed in the strut and the cavity has a first opening that is in fluid communication with the first side surface and a second opening that is in fluid communication with the abluminal surface or the luminal surface. The method further comprises disposing a therapeutic agent in the cavity and applying a material over the second opening and any other opening so that the cavity is not in fluid communication with the abluminal surface or luminal surface. However, the first opening is at least partially exposed.
In a further embodiment, the method for making an implantable stent comprises providing a stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure. At least one strut comprises an abluminal surface, a luminal surface, and a first side surface. There is at least one cavity disposed in the strut that has a first opening that is in fluid communication with the first side surface. The cavity is not in fluid communication with the abluminal surface or the luminal surface. The method further comprises disposing a therapeutic agent in the cavity and allowing the first opening to be at least partially exposed.
Moreover, in another embodiment, the method for making an implantable stent comprises providing a stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure, wherein at least one strut comprises an abluminal surface, a luminal surface, and a first side surface. The stent is disposed on a mandrel. A coating composition comprising a therapeutic agent is applied onto a flat surface. The stent disposed on the mandrel is rolled in the coating composition applied to the flat surface to apply the coating composition to the first side surface of the strut. Steps are taken to ensure that the abluminal surface and the luminal surface are substantially free of the coating composition.
The embodiments described herein will be explained with reference to the following drawings.
In one embodiment, the medical device is a stent comprising a stent sidewall structure, which comprises a plurality of struts and gaps in the sidewall structure. At least one strut comprises a first material. Also, the at least one strut comprises an abluminal surface, a luminal surface, and a first side surface. The abluminal surface of the strut is the surface that faces away from the lumen or towards the lumen wall, e.g., a wessel wall, when the stent is implanted in a lumen. The luminal surface of the strut is the surface that faces toward the lumen or away from the lumen wall when the stent is implanted in a lumen. The side surface of the strut is a surface that is disposed between the abluminal and luminal surfaces of the strut. In some instances, where the strut is formed by being cut from a material, such as a metal tube, the side surface can be cut-surface, i.e. the surface that is formed when the strut is cut from the material. Furthermore, there is at least one cavity disposed in the at least one strut, wherein the cavity comprises an opening that is in fluid communication with a side surface of the strut. A therapeutic agent can be disposed in the cavity. This agent can be released from the cavity through the opening.
Shown is
In this embodiment, a coating 140 is disposed over at least a portion of the opening of the cavity 130a that is in fluid communication with the abluminal surface 112. In some embodiments, the coating is disposed over the entire opening of the cavity that is in fluid communication with the abluminal surface. In others, the coating is disposed over less than the entire opening. In addition, in this embodiment, the coating 140 is disposed over a portion of the abluminal surface 112 of the strut 110, at for example position X.
The coating can comprise the same material as the strut. Alternatively, the coating can comprise a material that is different from the material of the strut. In certain embodiments, the coating comprises a polymer, a metal, an oxide, a ceramic, or different combination or composites of such materials (e.g., a composite of a ceramic and a polymer). In certain embodiments, the coating can comprise a radiopaque material.
In some instances, the coating is substantially free of any polymer, i.e., no polymer is intentionally added to the coating material. In other embodiments, the coating can comprise a polymer that modulates release of the therapeutic agent from the cavity through the coating. Also, in some embodiments, the coating comprises a material that prevents the release of the therapeutic agent from the cavity through the coating. In the alternative, the coating comprises a material have a plurality of pores therein that allows for the release of the therapeutic agent from the cavity through the coating. In the alternative, the coating comprises a material have a plurality of pores therein that allows for the release of the therapeutic agent from the cavity through the coating. Moreover, in come embodiments, the coating can comprise a therapeutic agent, which can be the same as or different from the therapeutic agent disposed in the cavity or cavities. For example, the coating can comprise a polymer and a first therapeutic agent. In such an embodiment, the first therapeutic agent is released from the abluminal surface of the strut while a second therapeutic agent in the cavity is released from the cut face.
A cavity 305 can also have an opening 360 that is in fluid communication with the luminal surface 330 of the strut 300 as shown in
The openings of the cavities may have various shapes and sizes.
The cavities may have various shapes and sizes.
The embodiment shown in
In yet another embodiment, the medical device comprises a stent having a sidewall structure 700 comprising a plurality of struts 710 and gaps 720 in the sidewall structure 700. In certain embodiments, the stent is self-expanding stent. At least one of the struts 710, such as strut 710a, has an abluminal surface 712, a luminal surface (not shown) and a first side surface 714 and a second side surface 716. A coating 730, which can comprise a polymer and/or a therapeutic agent, is disposed on at least a portion of one or more of the side surfaces 714, 716 of the strut 710. The abluminal surfaces 712 and luminal surfaces of the struts are substantially free of the coating, i.e., no coating is intentionally disposed on these surfaces. In some embodiments, the abluminal and luminal surfaces are substantially free of any coating.
Medical devices suitable for the present embodiments, but are not limited to, those that have a tubular or cylindrical like portion. For example, the tubular portion of the medical device need not be completely cylindrical. The cross-section of the tubular portion can be any shape, such as rectangle, a triangle, etc., not just a circle. Such devices include, but are not limited to, stents, balloon catheters, and grafts. A bifurcated stent is also included among the medical devices which can be fabricated by the methods described herein.
In addition, the tubular portion of the medical device may be a sidewall that may comprise a plurality of struts defining a plurality of openings. The sidewall defines a lumen. The struts may be arranged in any suitable configuration. Also, the struts do not all have to have the same shape or geometric configuration. When the medical device is a stent comprising a plurality of struts, the surface is located on the struts. Each individual strut has an outer surface adapted for exposure to the body tissue of the patient, an inner surface, and at least one side surface between the outer surface and the inner surface.
Medical devices that are particularly suitable for the embodiments described herein include any kind of stent for medical purposes which is known to the skilled artisan. The stents can be intravascular stents that are designed for permanent implantation in a blood vessel of a patient. In certain embodiments, the stent comprises an open lattice sidewall stent structure. In exemplary embodiments, a stent suitable is a coronary stent. Other suitable stents include, for example, vascular stents such as self-expanding stents and balloon expandable stents. Examples of self-expanding stents that can be used are illustrated in U.S. Pat. Nos. 4,655,771 and 4,954,126 issued to Wallsten and U.S. Pat. No. 5,061,275 issued to Wallsten et al. Examples of appropriate balloon-expandable stents are shown in U.S. Pat. No. 5,449,373 issued to Pinchaski et al.
In one embodiments, the intravascular stent is generally cylindrical in shape. The stent includes a sidewall structure which comprises a plurality of struts and at least one gap in the sidewall structure. Generally, the gap is disposed between adjacent struts. Also, the sidewall structure may have a first sidewall surface and an opposing second sidewall surface. The first sidewall surface can be an outer or abluminal sidewall surface, which faces a body lumen wall when the stent is implanted, or an inner or luminal sidewall surface, which faces away from the body lumen surface. Likewise, the second sidewall surface can be an abluminal sidewall surface or a luminal sidewall surface. At least one strut comprises an abluminal surface, which forms part of the abluminal surface of the stent, and at least one strut comprises a luminal surface opposite the abluminal surface of the strut, which forms part of the luminal surface of the stent.
In some embodiments, the abluminal surface of the stent sidewall structure comprises at least on cavity and the luminal surface is free of cavities. In other embodiments, the cavity or cavities can be located on a low-stress bearing part of the stent sidewall structure.
When the coatings described herein are applied to a stent having openings in the stent sidewall structure, in certain embodiments, in come embodiments, the coatings conform to the surface of the stent so that the openings in the sidewall stent structure are preserved. e.g. the openings are not entirely or partially occluded with coating material.
The framework of suitable stents may be formed through various methods as known in the art. The framework may be welded, molded, laser cut, electro-formed, or consist of filaments or fibers which are wound or braided together in order to form a continuous structure.
The medical devices may be fabricated from a metallic material, ceramic material, polymeric or non-polymeric material, or a combination thereof (see Sections 5.1.1.1 to 5.1.1.3 infra.). Preferably, the materials are biocompatible. The material may be porous or non-porous, and the porous structural elements can be microporous or nanoporous. Further the coating may be a different material from the substrate or the same material as the substrate.
In certain embodiments, the medical device comprises a substrate or coating that is metallic. Suitable metallic materials useful for making the substrate or the coating include, but are not limited to, metals and alloys based on titanium (such as nitinol, nickel titanium alloys, thermo memory alloy materials), stainless steel, gold, platinum, iridium, molybdenum, niobium, palladium, chromium, tantalum, nickel, nickel chrome, cobalt, tungsten, or alloys thereof and/or combinations thereof. Examples of alloys include platinum iridium alloys, cobalt-chromium alloys, including cobalt chromium nickel alloys such as Elgiloy® and Phynox®, MP35N alloy, and nickel-titanium alloys, for example, Nitinol. Other metallic materials that can be used to make the medical device include clad composite filaments, such as those disclosed in WO 94/16646.
In some embodiments, the metal is a radiopaque material that makes the medical device visible under X-ray or fluoroscopy. Suitable materials that re radiopaque include, but are not limited to, gold, tantalum, platinum, bismuth, iridium, zirconium, iodine, titanium, barium, silver, tin, alloys of these metals, or a combination thereof.
Furthermore, although a single type of metal can be used to form the substrate, various combinations of metals can also be employed. The appropriate mixture of metals can be coordinated to produce desired effects when incorporated into a substrate.
In certain embodiments, the medical device comprises a substrate or a coating which is ceramic. Suitable ceramic materials used for making the substrate or coating include, but are not limited to, oxides, carbides, or nitrides of the transition elements such as those containing titanium, hafnium, iridium, chromium, aluminum, zirconium, transition metals, platinum, tantalum, niobium, tungsten, rhodium, iron, vanadium, nickel, or a combination thereof. Silicon based materials, such as silica, may also be used. Furthermore, although a single type of ceramic can be used to form the substrate, various combinations of ceramics can also be employed. The appropriate mixture of ceramics can be coordinated to produce desired effects when incorporated into a substrate.
In certain embodiments, the medical device comprises a substrate or a coating which is polymeric. In other embodiments, the material can be a non-polymeric material. The polymer(s) useful for forming the components of the medical devices should be ones that biocompatible and avoid irritation to body tissue. The polymers can be biostable or bioabsorbable. Suitable polymeric materials useful for making the substrate include, but are not limited to, isobutylene-based polymers, polystyrene-based polymers, polyacrylates, and polyacrylate derivatives, vinyl acetate-based polymers and its copolymers, polyurethane and its copolymers, silicone and its copolymers, ethylene vinyl-acetate, polyethylene terephtalate, thermoplastic elastomers, polyvinyl chloride, polyolefins, cellulosics, polyamides, polyesters, polysulfones, polytetrafluorethylenes, polycarbonates, acrylonitrile butadiene styrene copolymers, acrylics, polylactic acid, polyglycolic acid, polycaprolactone, polylactic acid-polyethylene oxide copolymers, cellulose, collagens, chitins, or a combination thereof.
Other polymers that are useful as materials for making the substrate include, but are not limited to, Dacron polyester, poly(ethylene terephthalate), polycarbonate, polymethylmethacrylate, polypropylene, polyalkylene oxalates, polyvinylchloride, polyurethanes, polysiloxanes, nylons, poly(dimethyl siloxane), polycyanoacrylates, polyphosphazenes, poly(amino acids), ethylene glycol I dimethacrylate, poly(methyl methacrylate), poly(2-hydroxyethyl methacrylate), polytetrafluoroethylene poly(HEMA), polyhydroxyalkanoates, polytetrafluorethylene, polycarbonate, poly(glycolide-lactide) co-polymer, polylactic acid, poly(ε-caprolactone), poly(β-hydroxybutyrate), polydioxanone, poly(γ-ethyl glutamate), polyiminocarbonates, poly(ortho ester), polyanhydrides, styrene isobutylene styrene, polyetheroxides, polyvinyl alcohol, polyglycolic acid, polylactic acid, polyamides, poly-2-hydroxy-butyrate, polycaprolactone, poly(lactic-co-clycolic)acid, Teflon, alginate, dextran, chitin, cotton, polyglycolic acid, polyurethane, derivatized versions thereof, (i.e., polymers which have been modified to include, for example, attachment sites or cross-linking groups, e.g. arginine-glycine-aspartic acid RGD, in which the polymers retain their structural integrity while allowing for attachment of cells and molecules, such as proteins and/or nucleic acids), or a combination thereof.
The polymers may be dried to increase their mechanical strength. The polymers may then be used as the base material to form a whole or part of the substrate.
Furthermore, although a single type of polymer can be used to form the substrate, various combinations of polymers can also be employed. The appropriate mixture of polymers can be coordinated to produce desired effects when incorporated into a substrate.
The term “therapeutic agent” as used herein encompasses drugs, genetic materials, and biological materials and can be used interchangeably with “biologically active material”. The term “genetic material” means DNA or RNA, including, without limitation, 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, bacterial, 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, transferring, cytotactin, cell binding domains (e.g., RGD), and tenascin. Examplary 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 suitable therapeutic agents include:
Other therapeutic agents include nitroglycerin, nitrous oxides, nitric oxides, antibiotics, aspirins, digitalis, estrogen, estradiol and glycosides. Exemplary therapeutic agents include anti-proliferative drugs such as steroids, vitamins, and restenosis-inhibiting agents. Exemplary restonosis-inhibiting agents include microtubule stabilizing agents such as Taxol®, paclitaxel (i.e., paclitaxel, paxlitaxel analogs, or paclitaxel derivatives, and mixtures thereof). For example, derivatives suitable for use in the medical devices 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 exemplary therapeutic agents include tacrolimus; halafuginone; inhibitors of HSP90 heart shock proteins such as geldanamysin; microtubule stabilizing agents such as epothilone D; phosphodiesterase inhibitors such as cliostazole; Barkct inhibitors; phospholamban inhibitors; and Serca 2 gene/proteins. In yet another embodiment, the therapeutic agent is an antibiotic such as erythromycin, amphotericin, rapamycin, adriamycin, etc.
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 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.
Provided herein are methods of making the medical devices described herein.
The grooves can be formed by various methods, which include without limitation grinding, scoring, or using a laser to remove tube material. Also, the grooves can be formed by any other method known to one skilled in the art, including, but not limited to, sintering, co-deposition, micro-roughing, drilling, chemical etching or a combination thereof. For example, the grooves can be made by a deposition process such as sputtering with adjustments to the deposition condition, by micro-roughening using reactive plasmas, by ion bombardment electrolyte etching, or a combination thereof. Other methods include, but are not limited to, alloy plating, physical vapor deposition, chemical vapor deposition, sintering, or a combination thereof. In addition to material removal techniques, other methods may include incorporating protrusions into a mold used by one skilled in the art for forging the tube or stent. The protrusions create grooves or cavities in the forge tube or stent. Other methods include extruding a tube with grooves already incorporated into the tube.
In the embodiment shown in
As shown in
As shown in
The coating may comprise any of the materials listed herein. In certain embodiments, the coating comprises a material that prevents the release of the therapeutic agent through the coating. In other embodiments, the coating comprises a material having a plurality of pores therein that allows for the release of the therapeutic agent through the coating.
Also, the coating can be disposed on the abluminal surface by methods such as spray-coating, dip-coating, roll coating, or vapor deposition.
As shown in
Another embodiment of a method for making an implantable stent is similar to the one described above. However, instead of disposing a therapeutic agent in the groove, a filler material is disposed in at least a portion of the groove. After or during the formation of the stent from the tube, at least a portion of the filler material is removed from the cavity of the strut. The filler material can be removed by dissolving the filler material in a solvent. For instance, in one embodiment, the filler material can be dissolved by submerging the stent in a solvent. After at least a port of the filler material is removed, a therapeutic agent is then disposed in the cavity.
The therapeutic agent is disposed in the cavity in one embodiment by using a mandrel and a tube having an inner wall. In particular, the stent that is formed from the tube, is disposed on an expandable mandrel. The stent disposed on the mandrel is placed in a tube having an inner wall. The mandrel is expanded so that at least a portion of the stent contacts the inner wall of the tube. The stent is then exposed to a therapeutic agent and the therapeutic is allowed to enter the cavity.
In an alternative embodiment, the stent is disposed on a rigid mandrel. The stent disposed on the mandrel is placed in a tube having an inner wall. Instead of expanding the mandrel, the tube is moved towards or closed around the stent so that at least a portion of the stent contacts the inner wall of the tube. The stent is then exposed to a therapeutic agent and the therapeutic agent is allowed to enter the cavity.
In some instances, the therapeutic agent is contained in a composition that is capable of becoming solid and the stent is exposed to such composition and the composition is allowed to enter the cavity. The composition can be allowed to enter by being pressure forced into the cavity. Also, in some embodiment, the method comprises the step of allowing the composition to solidify or harden.
Furthermore, in some embodiments, the method further comprises removing any excess therapeutic agent from the stent. Such excess therapeutic agent can be removed by laser-cutting, mechanical cutting or water-jet cutting.
Another embodiment of a method is shown in
In the embodiment shown in
As shown in
As shown in
As shown in
As shown in
Another embodiment of a method for making an implantable stent is similar to the one described above in connection with
In addition, the therapeutic agent can be disposed in the cavity in one embodiment by using two flat surfaces. In particular, the sidewall structure that is formed from the sheet, is disposed between two flat surfaces. The sidewall structure is then exposed to a therapeutic agent and the therapeutic is allowed to enter the cavity.
In another embodiment of a method for making an implantable stent, a therapeutic agent is disposed in the cavity of a strut of a stent after the strut has been formed. The method comprises providing a stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure. At least one strut comprises an abluminal surface, a luminal surface, a first side surface, and at least one cavity disposed in the strut. The cavity has a first opening that is in fluid communication with the first side surface and second opening that is in fluid communication with the abluminal surface or the luminal surface. A therapeutic agent is disposed in the cavity. Thereafter, a material is applied over the second opening and any other opening so that the cavity is not in fluid communication with the abluminal surface or luminal surface. The first opening which is in fluid communication with the side surface, remains at least partially exposed.
In
In addition, the method can further comprise forming the stent sidewall structure by providing a tube having a tubular wall and a longitudinal axis, in which the tubular wall comprises an abluminal surface and a luminal surface, such as the one shown in
The method can further comprise forming the stent sidewall structure by providing a flat sheet having a sheet wall and longitudinal axis, in which the sheet wall comprises a first surface and second surface, such as the one shown in
Moreover, another method for making an implantable stent, in which a therapeutic agent is disposed in the cavity of a strut after the strut has been formed, comprises providing a stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure.
Another embodiment of a method for making an implantable stent comprises disposing a coating on at least one side surface of a stent strut while keeping the abluminal and luminal surfaces of the strut substantially free of the coating composition. This method comprises providing a stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure, wherein at least one strut comprises an abluminal surface, a luminal surface, and a first side surface. The stent is disposed on a mandrel. A coating composition comprising a therapeutic agent is applied onto a flat surface. The stent disposed on the mandrel is rolled in the coating composition applied to the flat surface to apply the coating composition to the first side surface of the strut.
Steps are taken to ensure that the abluminal surface and the luminal surface are substantially free of the soating composition. In some embodiments, the stent is rolled with sufficient pressure such that the coating composition is applied to the first side surface while the abluminal surface is made substantially free of the coating composition. In other embodiments, the abluminal surface and luminal surface are made substantially free of the coating composition by removing any coating composition disposed on the abluminal surface or luminal surface after the coating composition is applied to the first side surface. The coating composition can be removed by mechanical grinding, laser-ablation, masking and etching, or chemical dissolution of the coating.
The therapeutic agent of the coating composition can be, but are not limited to, those described herein. Also, the coating composition can comprise a polymer, such as but not limited to those described above for forming medical devices. Furthermore, the coating composition can include a solvent for suspending or dissolving the therapeutic agent and/or polymer.
Some exemplary embodiments of medical devices and methods for making same in accordance with the present invention are described in the following numbered paragraphs:
Paragraph 1. A method for making an implantable stent comprising:
a. providing a stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure, wherein at least one strut comprises an abluminal surface, a luminal surface, a first side surface, and at least one cavity disposed in the strut, wherein the cavity has a first opening that is in fluid communication with the first side surface and wherein the cavity is not in fluid communication with the abluminal surface or the luminal surface;
b. disposing a therapeutic agent in the cavity; and
c. allowing the first opening to be at least partially exposed.
Paragraph 2. A method for making an implantable stent comprising:
a. providing a flat sheet of a material having a sheet wall, in which the sheet wall comprises a first surface and a second surface, and at least one groove disposed in the first surface of the sheet wall, wherein the groove does not extend through the sheet wall to the second surface;
b. disposing a therapeutic agent in at least a portion of the groove;
c. disposing a coating over at least a portion of the first surface such that at least a portion of the therapeutic agent disposed in the groove is covered by the coating;
d. forming from the sheet, having the coating disposed on the first surface, a sidewall structure comprising a plurality of struts and gaps, wherein at least one of the struts comprises an top surface, a bottom surface, a first side surface and a cavity, wherein the cavity comprises a portion of the groove containing the therapeutic agent, and an opening that is in fluid communication with the first side surface, and wherein the opening is at least partially exposed.
Paragraph 3. The method of paragraph 2 further comprising forming the sidewall structure into a tubular shape before or after the sidewall structure is form.
Paragraph 4. The method of Paragraph 2 further comprising forming the sidewall structure into a tubular shape before or after the sidewall structure is form.
Paragraph 5. A method for making an implantable stent comprising:
a. providing a flat sheet of material having a sheet wall, in which the sheet wall comprises a first surface and a second surface, and at least one groove disposed in the first surface of the sheet wall, wherein the groove does not extend through the sheet wall to the second surface;
b. disposing a filler material in at least a portion of the groove;
c. disposing a coating over at least a portion of the first surface such that at least a portion of the filler material disposed in the groove is covered by the coating;
d. forming from the sheet, having the coating disposed on the first surface, a sidewall structure comprising a plurality of struts and gaps, wherein at least one of the struts comprises a top surface, a bottom surface, a first side surface and a cavity, wherein the cavity comprises a portion of the groove containing the filler material, and an opening that is in fluid communication with the first side surface, and wherein the opening is at least partially exposed.
e. removing at least a portion of the filler material from the cavity; and
f. disposing a therapeutic agent in the cavity.
Paragraph 6. The method of paragraph 5, wherein the disposing of the therapeutic agent in the cavity comprises:
(1) disposing the sidewall structure between a first flat surface and a second flat surface;
(2) exposing the sidewall structure to a therapeutic agent; and
(3) allowing the therapeutic agent to enter the cavity.
Paragraph 7. The method of paragraph 6, wherein the therapeutic agent is contained in a composition that is capable of becoming solid and the sidewall structure is exposed to the composition and the composition is allowed to enter the cavity.
Paragraph 8. The method of paragraph 6, wherein the therapeutic agent is allowed to enter the cavity by being pressure forced into the cavity.
Paragraph 9. An implantable self-expanding stent comprising:
a. a self-expanding stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure, wherein at least one of the struts comprises an abluminal surface, a luminal surface, and a first side surface; and
b. a first coating, which comprises a polymer or a therapeutic agent, disposed on at least a portion of the first side surface, wherein the abluminal and luminal surfaces are substantially free of any coating.
Paragraph 10. The stent of paragraph 9, wherein the strut further comprises a second side surface opposite the first side surface and second coating disposed on at least a portion of the second side surface.
Paragraph 11. A method for making an implantable self-expanding stent comprising:
a. providing an implantable self-expanding stent having a stent sidewall structure comprising a plurality of struts and gaps in the sidewall structure, wherein at least one strut comprises an abluminal surface, a luminal surface, and a first side surface;
b. disposing the stent on a mandrel;
c. applying a coating composition comprising a therapeutic agent or a
polymer onto a flat surface;
d. rolling the stent disposed on the mandrel in the coating composition applied to the flat surface to apply the coating composition to the first side surface; and
e. ensuring that the abluminal surface and the luminal surface are substantially free of the coating composition.
Paragraph 12. The method of Paragraph 11, wherein the stent is rolled with sufficient pressure such that the coating composition is applied to the first side surface while the abluminal surface is made substantially free of the coating composition.
Paragraph 13. A method for making an implantable stent comprising:
a. providing a tube having a tubular wall having a longitudinal axis, in which the tubular wall comprises an abluminal surface and a luminal surface, and at least one groove disposed in the abluminal surface of the tubular wall, wherein the groove does not extend through the tubular wall to the luminal surface;
b. disposing a therapeutic agent in at least a portion of the groove;
c. disposing a coating over at least a portion of the abluminal surface such that at least a portion of the therapeutic agent disposed in the groove is covered by the coating;
d. forming from the tube, having the coating disposed on the abluminal surface, a stent having a stent sidewall structure comprising a plurality of struts and gaps, wherein at least one of the struts comprises an abluminal surface, a luminal surface, a first side surface and a cavity, wherein the cavity comprises a portion of the groove containing the therapeutic agent, and an opening that is in fluid communication with the first side surface, and wherein the opening is at least partially exposed.
The description contained herein is for purposes of illustration and not for purposes of limitation. The methods and devices described herein can comprise any feature described herein either alone or in combination with any other feature(s) described herein. Changes and modifications may be made to the embodiments of the description. Indeed, various modifications, in addition to those shown and described herein, will become apparent to those skilled in the art from the foregoing description and accompanying drawings using no more than routine experimentation. Such modifications and equivalents are intended to fall within the scope of the appended claims.
All publications, patents and patent applications mentioned in this specification are herein incorporated by reference into specification to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. Citation or discussion of reference herein shall not be construed as an admission that such is prior art.
This application claims priority from Provisional Application No. 61/023,142, filed Jan. 24, 2008, the contents of which is hereby incorporated by reference
| Number | Date | Country | |
|---|---|---|---|
| 61023142 | Jan 2008 | US |
