The present invention generally relates to the application of coating materials, comprising coating materials including therapeutic agent, to medical devices such as implantable stents. More specifically, the present invention includes coating systems and methods that transfer coating from an applicator to a medical device during the coating process.
The positioning and deployment of medical devices within a target site of a patient is a common, often repeated procedure of contemporary medicine. These devices, which may be implantable stents and other devices that may be deployed for short or sustained periods of time, may be used for many medical purposes. These can include the reinforcement of recently re-enlarged lumens, the replacement of ruptured vessels, and the treatment of disease, such as vascular disease by local pharmacotherapy, i.e., delivering therapeutic drug doses to target tissues while minimizing systemic side effects. The targeted delivery areas may include body lumens such as the coronary vasculature, peripheral vasculature, cerebral vasculature, esophagus, trachea, colon, biliary tract, urinary tract, prostate, and the like.
Coatings may be applied to the surfaces of these medical devices to increase their effectiveness. These coatings may provide a number of benefits including reducing the trauma suffered during the insertion procedure, facilitating the acceptance of the medical device into the target site, and improving the post-procedure effectiveness of the device.
Coated medical devices may also provide for the localized delivery of therapeutic agents to target locations within the body. Such localized drug delivery avoids the problems of systemic drug administration, producing unwanted effects on parts of the body that are not to be treated, or not being able to deliver a high enough concentration of therapeutic agent to the afflicted part of the body. Localized drug delivery may be achieved, for example, by coating portions of the medical devices that directly contact the inner vessel wall. This drug delivery may be intended for short and sustained periods of time.
The present invention is directed to methods and systems for aligning a medical device during a coating process. For example, a method in accordance with embodiments of the present invention may comprise providing a stent having a lattice portion comprised of a plurality of struts and positioning the stent on a mandrel. The method may include providing an applicator having first and second sections forming an offset. The method may further include aligning the struts via a contact force applied by the first section and delivering coating to the struts from the second section. This method may also include repeating the procedure, performing more or other steps, and adding additional layers of coating.
Embodiments of the present invention may also regard a system for coating a medical device. The system may include a mandrel to support and align the medical device, an applicator having first and second sections which form an offset, and a fluid source communicating with the second section. The first and second sections may form an offset. In the system, either or both the applicator and the medical device can be moved with respect to one another so that the first section applies a contact force to the medical device while the second section applies coating.
Embodiments of the present invention may still further regard a system for coating a medical device which includes a mandrel to support and align the medical device, an applicator having first and second sections along an edge, and a fluid source communicating with the second section. The first section may comprise a contact surface and the second section may comprise a plurality of recesses. In the system, either or both the applicator and the medical device can be moved with respect to one another so that the first section applies a contact force to the medical device while the second section applies coating.
The invention may be embodied by numerous methods and systems. The description provided herein, which, when taken in conjunction with the annexed drawings, discloses examples of the invention. Other embodiments, which incorporate some or all steps and systems as taught herein, are also possible.
Referring to the drawings, which form a part of this disclosure:
a-b show enlarged cross-sectional views of an applicator of the system of
a-b show cross-sectional views of stent struts and
The present invention generally relates to methods and systems for aligning a medical device during a coating process.
These medical devices, which can be stents or other devices sized to be inserted into a patient, may be cut using a laser, injection molded, and/or assembled from wire. Stent production may result in surface misalignment and/or irregularities. Misalignment and/or irregularities of medical device surfaces may impact the coating process.
For example, in the case of an implanted stent, which are comprised of a plurality of stent struts which form a scaffolding structure, some of the struts may be burred, bowed, bent, and/or otherwise misaligned during production. Strut misalignment may limit the effectiveness of coating processes, such as in a roll coating process.
Methods and systems that embody the present invention may include an applicator configured to align and apply coating to a medical device in a single coating cycle.
Referring initially to
In this example, the system 100 includes a mandrel 106 configured to support and align the medical device 104, an applicator 108 having first and second sections 110, 112, which may form an offset along an edge of the applicator 108, and a fluid source 114 communicating with the second section 112.
As seen in
For instance, a steel core may be wound with aluminum and/or tungsten.
The outer diameter of the mandrel 106 may be slightly greater than the inner diameter of the medical device 104, thus, forming an interference fit. Therefore, during coating, the mandrel 106 can be placed under tension, thus imparting linear rigidity to the medical device 104, and therefore facilitating the axial alignment of the medical device 104 and mandrel 106.
Also seen in
The first section 110 may contact the medical device 104 during the coating process to apply a contact force. The contact force applied by the first section 110 can act to axially align and straighten out struts or other portion of the medical device 104. As a result, misaligned surfaces and/or irregularities on surfaces of the medical device 104 may be removed or limited prior to the coating of the medical device 104. As can best be seen in
As seen in
As best seen in
The system 100 of
a-b show an enlarged view of a medical device being coated with an applicator as may be employed with embodiments of the present invention. As illustrated in
a is a side sectional view of a stent strut 416 as may be coated in accordance with embodiments of the present invention. The stent strut 416 shown in
b shows another example of how coatings 402 may be applied in accordance with embodiments of the invention. In
c shows a side view of a stent 404 as may be aligned and coated in accordance with embodiments of the present invention. A coating or coatings may be applied to portions of or along the entire length of the stent 404. The struts shown in
The stent 404 of
While the workpiece shown in this figure is a stent, many other medical devices may be coated in accord with the methods of the present invention. For example, other medical devices that may be coated include filters, grafts, and other devices used in connection with therapeutic coatings.
The applicator 508 may be disposed at any suitable angle, for instance, acute angles between 1-5° degrees may be used. In this example, since the applicator 508 may be disposed at an angle, the second section 512 of the applicator 508 may apply coating 502 in a helical pattern to the medical device 504. In addition, in some instances, a regulating wheel (not shown) can also be provided. The medical device 504 may be positioned between the applicator 508 and the regulating wheel. The medical device 504 may be rotated about its axis between the applicator 508 and the regulating wheel due to the inclination of the applicator 508 relative to the regulating wheel. For example, such an arrangement may be similar to that used in a conventional centerless grinding operation.
As shown in
The mandrel 706 may be rotated and moved linearly across the applicator 708. As the mandrel 706 is moved, the first section 710 may apply a contact force to surfaces of the medical device 704 while the second section 712 may apply coating 702. As may also be seen in this example, the applicator 708 may be arranged on a work surface at an angle, however, other arrangements are possible.
In alternative embodiments, not shown, the sequence of steps may be reordered and steps may be added or removed. The steps may also be modified.
While various embodiments have been described, other embodiments are plausible. It should be understood that the foregoing descriptions of various examples of the applicator are not intended to be limiting, and any number of modifications, combinations, and alternatives of the examples may be employed to facilitate the effectiveness of aligning and application of coating to the medical device.
Coatings that may be used with embodiments of the present invention, may comprise a polymeric and/or therapeutic agent formed, for example, by admixing a drug agent with a liquid polymer, in the absence of a solvent, to form a liquid polymer/drug agent mixture. The coatings may also be polymer free. A suitable list of drugs and/or polymer combinations is listed below. The term “therapeutic agent” as used herein includes one or more “therapeutic agents” or “drugs.” The terms “therapeutic agents” or “drugs” can be used interchangeably herein and include pharmaceutically active compounds, nucleic acids with and without carrier vectors such as lipids, compacting agents (such as histones), viruses (such as adenovirus, adenoassociated virus, retrovirus, lentivirus and α-virus), polymers, hyaluronic acid, proteins, cells and the like, with or without targeting sequences.
Specific examples of therapeutic agents used in conjunction with the present invention include, for example, pharmaceutically active compounds, proteins, cells, oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compacting agents, gene/vector systems (i.e., any vehicle that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector or in a viral vector and which further may have attached peptide targeting sequences; antisense nucleic acid (RNA or DNA); and DNA chimeras which include gene sequences and encoding for ferry proteins such as membrane translocating sequences (“MTS”) and herpes simplex virus-1 (“VP22”)), and viral liposomes and cationic and anionic polymers and neutral polymers that are selected from a number of types depending on the desired application. Non-limiting examples of virus vectors or vectors derived from viral sources include adenoviral vectors, herpes simplex vectors, papilloma vectors, adeno-associated vectors, retroviral vectors, and the like. Non-limiting examples of biologically active solutes include anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, and PPACK (dextrophenylalanine proline arginine chloromethylketone); antioxidants such as probucol and retinoic acid; angiogenic and anti-angiogenic agents and factors; anti-proliferative agents such as enoxaprin, everolimus, zotarolimus, angiopeptin, rapamycin, angiopeptin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, acetyl salicylic acid, and mesalamine; calcium entry blockers such as verapamil, diltiazem and nifedipine; antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; antimicrobials such as triclosan, cephalosporins, aminoglycosides, and nitrofurantoin; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors such as linsidomine, molsidomine, L-arginine, NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NO adducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, enoxaparin, hirudin, Warfarin sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet factors; vascular cell growth promoters such as growth factors, growth factor receptor antagonists, transcriptional activators, and translational promoters; vascular cell growth inhibitors such as 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 vascoactive mechanisms; survival genes which protect against cell death, such as anti-apoptotic Bcl-2 family factors and Akt kinase; and combinations thereof. Cells can be of human origin (autologous or allogenic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at the insertion site. Any modifications are routinely made by one skilled in the art.
Polynucleotide sequences useful in practice of the invention include DNA or RNA sequences having a therapeutic effect after being taken up by a cell. Examples of therapeutic polynucleotides include anti-sense DNA and RNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA to replace defective or deficient endogenous molecules. The polynucleotides can also code for therapeutic proteins or polypeptides. A polypeptide is understood to be any translation product of a polynucleotide regardless of size, and whether glycosylated or not. Therapeutic proteins and polypeptides include as a primary example, those proteins or polypeptides that can compensate for defective or deficient species in an animal, or those that act through toxic effects to limit or remove harmful cells from the body. In addition, the polypeptides or proteins that can be injected, or whose DNA can be incorporated, include without limitation, angiogenic factors and other molecules competent to induce angiogenesis, including acidic and basic fibroblast growth factors, vascular endothelial growth factor, hif-1, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin like growth factor; growth factors; cell cycle inhibitors including CDK inhibitors; anti-restenosis agents, including p15, p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase (“TK”) and combinations thereof and other agents useful for interfering with cell proliferation, including agents for treating malignancies; and combinations thereof. Still other useful factors, which can be provided as polypeptides or as DNA encoding these polypeptides, include monocyte chemoattractant protein (“MCP-1”), and the family of bone morphogenic proteins (“BMPs”). The known proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMPs are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a BMP can be provided. Such molecules include any of the “hedgehog” proteins, or the DNAs encoding them.
Coatings used with embodiments of the present invention may comprise a drug agent or a polymeric material/drug agent matrix formed, for example, by admixing a drug agent with a liquid polymer, in the absence of a solvent, to form a liquid polymer/drug agent mixture. Curing of the mixture typically occurs in-situ. To facilitate curing, a cross-linking or curing agent may be added to the mixture prior to application thereof. Addition of the cross-linking or curing agent to the polymer/drug agent liquid mixture must not occur too far in advance of the application of the mixture in order to avoid over-curing of the mixture prior to application thereof. Curing may also occur in-situ by exposing the polymer/drug agent mixture, after application to the luminal surface, to radiation such as ultraviolet radiation or laser light, heat, or by contact with metabolic fluids such as water at the site where the mixture has been applied to the luminal surface. In coating systems employed in conjunction with the present invention, the polymeric material may be either bioabsorbable or biostable. Any of the polymers described herein that may be formulated as a liquid may be used to form the polymer/drug agent mixture.
The polymer used in the exemplary embodiments of the present invention is preferably capable of absorbing a substantial amount of drug solution. When applied as a coating on a medical device in accordance with the present invention, the dry polymer is typically on the order of from about 1 to about 50 microns thick. It is also within the scope of the present invention to apply multiple layers of polymer coating onto a medical device. Such multiple layers are of the same or different polymer materials.
The polymer of the present invention may be hydrophilic or hydrophobic, and may be selected from the group consisting of polycarboxylic acids, cellulosic polymers, including cellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone, polyanhydrides including maleic anhydride polymers, polyamides, polyvinyl alcohols, copolymers of vinyl monomers such as EVA, polyvinyl ethers, polyvinyl aromatics, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters including polyethylene terephthalate, polyacrylamides, polyethers, polyether sulfone, polycarbonate, polyalkylenes including polypropylene, polyethylene and high molecular weight polyethylene, halogenated polyalkylenes including polytetrafluoroethylene, polyurethanes, polyorthoesters, proteins, polypeptides, silicones, siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxybutyrate valerate and blends and copolymers thereof as well as other biodegradable, bioabsorbable and biostable polymers and copolymers.
Coatings from polymer dispersions such as polyurethane dispersions (BAYHYDROLR®, etc.) and acrylic latex dispersions may also be used with the present invention. The polymer may be a protein polymer, fibrin, collagen and derivatives thereof, polysaccharides such as celluloses, starches, dextrans, alginates and derivatives of these polysaccharides, an extracellular matrix component, hyaluronic acid, or another biologic agent or a suitable mixture of any of these, for example. In one embodiment, the preferred polymer is polyacrylic acid, available as HYDROPLUS® (Boston Scientific Corporation, Natick, Mass.), and described in U.S. Pat. No. 5,091,205, the disclosure of which is hereby incorporated herein by reference. U.S. Pat. No. 5,091,205 describes medical devices coated with one or more polyisocyanates such that the devices become instantly lubricious when exposed to body fluids. In another preferred embodiment, the polymer is a copolymer of polylactic acid and polycaprolactone.
The examples described herein are merely illustrative, as numerous other embodiments may be implemented without departing from the spirit and scope of the exemplary embodiments of the present invention. Moreover, while certain features of the invention may be shown on only certain embodiments or configurations, these features may be exchanged, added, and removed from and between the various embodiments or configurations while remaining within the scope of the invention. Likewise, methods described and disclosed may also be performed in various sequences, with some or all of the disclosed steps being performed in a different order than described while still remaining within the spirit and scope of the present invention.
The present application claims priority to U.S. provisional application Ser. No. 60/916,583 filed May 8, 2007, the disclosure of which is incorporated herein by reference in its entirety.
Number | Date | Country | |
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60916583 | May 2007 | US |