Patent Application
20100106234
This invention relates generally to biomedical devices. More specifically, the invention relates to implantable stents and other medical devices having prolonged delivery of therapeutic agents.
Implantable devices often include a therapeutic agent as part of a therapeutic agent coating or as part of the material forming the implantable device. With these devices, the therapeutic agent contained in the coating begins to elute or diffuse from the device surface soon after implantation resulting in a burst of therapeutic agent at the treatment site. In some situations an initial burst of therapeutic agent may be useful. However, in other situations a sustained, controlled release of the therapeutic agent from the device surface is desired.
Polymers, mixed with the therapeutic agent, have been used to control the release rate of the therapeutic agent from the device surface. Where a polymer is used, an initial burst of therapeutic agent occurs immediately after implantation followed by a slow sustained release over a predetermined length of time. The length of time that a therapeutic agent elutes is often critical to successful treatment of the patient's condition. In many cases a slow release over an extended period of time is desirable. However, the length of time that the therapeutic agent is eluted often depends on factors such as the presence of a polymer in the coating, the type of polymer(s) used and the thickness of the drug or drug/polymer coating and the amount of drug in the coating.
In the case of diffusion from a therapeutic coating including a polymer, delivery of drug to a surrounding matrix is regulated by the effective diffusion coefficient of the drug in the polymer and the length of the mean diffusion path that a molecule must take to exit the polymer. The mean diffusion path may be considered to be half the thickness of the coating. In the case of drug dissolution into solution from a coating without a polymer, the diffusion path may be extremely short since rapid hydration of an applied drug formulation may quickly render the entire drug load soluble and subject to convective transport into the surrounding matrix.
In an effort to increase the mean diffusion path of the drug or drugs contained within the coating, thicker therapeutic agent coatings have been applied to medical device surfaces, thereby extending the duration of elution. Factors to consider when applying a thicker coat include the device to be coated, the size and/or crossing profile of the device to be coated and the pathway the device must traverse to reach the treatment site. A thicker coating may be applied as one layer or in multiple layers as best suited for the particular application. However, thicker coatings have an increased chance of damage during every stage of the implantation procedure. Therefore, the effectiveness of the increase of the mean diffusion path of the drug by increasing the coating thickness is limited.
Some coating procedures provide barrier layers between drug or drug-polymer layers to separate layers having different drugs. Barrier layers also may be used to increase the elution time and to effectively increase the mean diffusion path by slowing down the degradation of the coating. One drawback to this is that the barrier layers may not be suitable due to an unwanted increase in thickness of the coating and, thus, the crossing profile. Another drawback is that the barrier layer may not keep the different drugs from comingling prior to elution from the device.
It would therefore be desirable, to provide an implantable therapeutic agent eluting medical device that would overcome the limitations and disadvantages described above.
One aspect of the present invention provides a system for treating a vascular condition. The system includes a catheter, a stent disposed on the catheter, the stent having a stent framework including a stent wire and at least one stent foil attached to and wrapped around the stent wire, and a therapeutic agent coating disposed on an inner surface of the at least one stent foil.
Another aspect of the invention provides a stent for treating a vascular condition. The stent includes a stent framework including a stent wire and at least one stent foil attached to and wrapped around the stent wire and a therapeutic agent coating disposed on an inner surface of the at least one stent foil.
Another aspect of the invention provides a method of manufacturing a stent for treating a vascular condition. The method includes securing a first edge of at least one stent foil to a stent wire, applying a therapeutic agent coating to an inner surface of the at least one stent foil and wrapping the therapeutic agent coated stent foil around an outer surface of the stent wire to encase the therapeutic agent coating between the inner surface of the stent foil and the outer surface of the stent wire. The method further includes securing a second edge of the wrapped stent foil to the stent wire, forming at least one exit port along the secured second edge and forming the wrapped stent wire into a stent framework.
The present invention is illustrated by the accompanying drawings of various embodiments and the detailed description given below. The drawings should not be taken to limit the invention to the specific embodiments, but are for explanation and understanding. The detailed description and drawings are merely illustrative of the invention rather than limiting, the scope of the invention being defined by the appended claims and equivalents thereof. The drawings are not to scale. The foregoing aspects and other attendant advantages of the present invention will become more readily appreciated by the detailed description taken in conjunction with the accompanying drawings.
The invention will now be described by reference to the figures wherein like numbers refer to like structures. The terms “distal” and “proximal” are used herein with reference to the treating clinician during the use of the catheter system; “distal” indicates an apparatus portion distant from, or a direction away from the clinician and “proximal” indicates an apparatus portion near to, or a direction towards the clinician.
The present invention is directed to a system for treating abnormalities of the cardiovascular system comprising a catheter and a therapeutic agent-carrying stent disposed on the catheter. Those with ordinary skill in the art will appreciate that the below described invention can be applied to other implantable medical device composed of wire, such as, for example, pacemaker leads.
Catheter 110 may comprise an elongated tubular member having a substantially circular cross-section and inside and outside walls that are substantially smooth. Catheter 110 may be secured at its proximal end to a suitable Luer fitting 122 and may include a distal rounded end to reduce harmful contact with a vessel. Catheter 110 may be manufactured substantially from a material such as a thermoplastic elastomer, urethane, polymer, polypropylene, plastic, ethelene chlorotrifluoroethylene (ECTFE), polytetrafluoroethylene (PTFE), fluorinated ethylene propylene copolymer (FEP), nylon, Pebax®, Vestamid®, Tecoflex®, Halar®, Hyflon®, Pellathane®, combinations thereof, and the like. Catheter 110 may include lumen 114 formed therethrough allowing it to be advanced over a pre-positioned guidewire.
Balloon 112, shown in a collapsed state, may be any variety of balloon capable of expanding stent 120. Balloon 112 may be manufactured from any sufficiently elastic material such as polyethylene, polyethylene terephthalate (PET), nylon, or the like.
Stent 120 includes stent framework 130 forming interior and exterior surfaces of the stent. Stent framework 130 includes an elongated stent wire and at least one foil wrapped around an outer surface of the wire.
Stent foil 234 comprises a biocompatible metal or metal alloy. In one embodiment of the invention, the stent foil 234 comprises one or more of a variety of biocompatible metals such as stainless steel, titanium, magnesium, aluminum, chromium, cobalt, nickel, gold, iron, iridium, chromium/titanium alloys, chromium/nickel alloys, chromium/cobalt alloys, such as MP35N and L605, cobalt/titanium alloys, nickel/titanium alloys, such as nitinol, platinum, and platinum-tungsten alloys. In one embodiment, stent wire 232 and stent foil 234 are composed of the same material. In one embodiment, stent wire 232 and stent foil 234 are composed of nitinol. In another embodiment, stent wire 232 and stent foil 234 are composed of stainless steel.
Stent framework 230 is formed by first attaching a first edge 236 of stent foil 234 along the length of stent wire 232. In one embodiment, first edge 236 is attached to stent wire 232 by welding a continuous weld 237 along the length of stent wire 232. In another embodiment, first edge is attached to stent wire using an adhesive. Those with skill in the art will appreciate that stent foil 234 may be attached to stent wire 232 by any means suitable for providing a continuous attachment.
Stent framework also includes at least one therapeutic agent coating 250. Therapeutic agent coating 250 comprises a biologically or pharmacologically active substance. In one embodiment, the biologically or pharmacologically active substance may be suspended in a polymer matrix or carrier. In one embodiment, the polymer matrix or carrier is biodegradable or bioresorbable such that it is absorbed in the body. The polymer matrix may comprise biodegradable polymers such as polylactic acid (PLA), polyglycolic acid, and their copolymers, polyethylene oxide (PEO), caproic acid, polyethylene glycol, polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamides, polyurethanes and other suitable polymers
The term “biologically or pharmacologically active substance” refers to any substance, whether synthetic or natural, that has a pharmacological, chemical, or biological effect on the body or a portion thereof. Suitable biologically or pharmacologically active materials that can be used in embodiments of the present invention include without limitation glucocorticoids (e.g. dexamethasone, betamethasone), antithrombotic agents such as heparin, cell growth inhibitors, hirudin, angiopeptin, aspirin, growth factors such as VEGF, antisense agents, anti-cancer agents, fibrinolytics, antirestenotic agents, and anti-inflammatory agents may be used. Antiplatelet agents can include drugs such as aspirin and dipyridamole. Aspirin is classified as an analgesic, antipyretic, anti-inflammatory and antiplatelet drug. Dipyridamole is a drug similar to aspirin in that it has anti-platelet characteristics. Dipyridamole is also classified as a coronary vasodilator. Anticoagulant agents may include drugs such as heparin, protamine, hirudin and tick anticoagulant protein. Anti-cancer agents may include drugs such as taxol and its analogs or derivatives. Taxol is also classified as a cell-growth inhibitor. Antioxidant agents may include probucol. Antiproliferative agents may include drugs such as amlodipine, doxazosin, and sirolimus or other—limus family compounds. Antimitotic agents and antimetabolite agents may include drugs such as methotrexate, azathioprine, vincristine, vinblastine, 5-fluorouracil, adriamycin and mutamycin. Antibiotic agents can include penicillin, cefoxitin, oxacillin, tobramycin, and gentamicin. Suitable antioxidants include probucol. Also, genes or nucleic acids, or portions thereof may be used. Recombinant DNA products, or other bioactive agents, diagnostic agents, radioactive isotopes, or radiopaque substances may be used depending on the anticipated needs of the targeted patient population. Such genes or nucleic acids can first be packaged in liposomes or nanoparticles. Furthermore, collagen-synthesis inhibitors, such as tranilast, may be used.
The therapeutic agent coating 250 containing the at least one therapeutic agent may additionally contain excipients including solvents or other solubilizers, stabilizers, suspending agents, antioxidants, and preservatives, as needed to deliver an effective dose of the therapeutic agent to the treatment site. The therapeutic agent coating 250 may be applied to the outer surface of stent wire 232 and/or an inner surface 238 of stent foil 234 by any means known in the art such as, for example, by spraying, dipping, and brushing. In one embodiment, the coating is applied as a liquid by brushing or spraying, and then dried to remove solvent using air, vacuum, or heat, and any other effective means of causing the formulation to adhere to the stent framework. In one embodiment, the therapeutic agent coating is applied to the stent foil prior to the attachment of the stent foil to the stent wire.
In one embodiment illustrated in
Referring to
Stent foil 234 is wrapped around stent wire 232 in such a manner as to bring second edge 239 in close proximity to attached first edge 236. As shown in
The foil wrapped wire having an encased therapeutic agent can be formed into a drug eluting medical device such as, for example, stent 120. In one embodiment, stent framework 230 is formed into stent 120 by shaping the foil wrapped metallic wire. The foil wrapped wire may be shaped into a stent by any means known in the art.
In this embodiment, the mean diffusion pathway of the encased therapeutic agent is extended well beyond a mean diffusion pathway provided by a coating disposed directly on a stent surface and exposed to the vessel wall. In an example, a stent wire 0.0050 inches in diameter with a coating of 10 μm in thickness and a foil approximating the circumference of the stent wire, at least a 40-fold increase in the mean diffusion path is provided.
Aspects of stent framework 330 similar to stent framework 130 and 230 will not be discussed further. In this embodiment, stent framework includes three stent foils 334A, 334B and 334C wrapped around stent wire 332 as shown in
Referring to
As shown in
In use, the drug delivery stent mounted at a distal end of a delivery catheter is inserted into a patient's vascular system and delivered to the treatment site. At the treatment site, the stent is positioned across the lesion to be treated and expanded. The catheter is then withdrawn from the body.
In the physiological environment, the therapeutic agents are released from the coating via the exit ports. The length of time for diffusion of the drugs is predetermined by the mean diffusion path of each respective therapeutic agent.
While the invention has been described with reference to particular embodiments for treating a vascular condition, it will be understood by one skilled in the art that variations and modifications may be made in form and detail without departing from the spirit and scope of the invention. In an example, the method of wrapping a wire with foil having a therapeutic agent coating may be applied to wires used for pacemaker leads as well as other leads and devices implanted into a patient's body.
