Patent Application
20070281072
Referring to the drawings, which form a part of this disclosure:
a shows a metering device that may be employed in accord with the present invention;
b shows another metering device that may be employed in accord with the present invention;
c shows another metering device that may be employed in accord with the present invention;
d shows another metering device that may be employed in accord with the present invention;
a is a cross-sectional view of a portion of a coated strut from a medical device that has been coated in accord with the present invention;
b is a cross-sectional view showing the coated strut of
c is a side-view of an arterial stent, which is a medical device that may be coated in accord with the present invention;
a shows a meyer bar and a rotating member that may be employed in accord with the present invention;
b is an enlarged view of the meyer bar of
a shows a system of coating a workpiece with a roller and a metering device that may be employed in accord with the present invention;
b shows another system of coating a workpiece with a roller, a metering device, and a doctor blade that may be employed in accord with the present invention;
c shows still another system of coating a workpiece with a roller and a metering device that may be employed in accord with the present invention; and
The present invention regards coating one or more surfaces of a workpiece while not coating other surfaces of the workpiece. In some embodiments this may include coating the outside or side surfaces of the workpiece while not coating the inside surfaces of the workpiece. By coating in this fashion the amount of coating resident on the workpiece may be reduced. For example, if the workpiece is a medical implant and the coating contains therapeutic a reduction in coating may allow the therapeutic to be delivered in a more targeted fashion after the stent is implanted at a target site. The limited use of coating can also conserve coating materials, which themselves may be valuable.
A desired uniform thickness of coating may be applied to a target surface of a workpiece using a roller and a metering device in accord with the present invention. For example, the metering device may contact a roller to regulate the thickness of the coating. Each of the workpiece, the roller, and the metering device may be rotated to facilitate the coating of one or more surfaces of the workpiece. The roller may be rotated within a coating reservoir or otherwise positioned in communication with a coating source. A plurality or combination of metering devices may also be used. For example, a meyer rod may be used in combination with a smooth rod.
The meyer rod is a rod with wire wrapped around an outside surface. The meyer rod is generally used to regulate coating solution by controlling the weight and/or thickness of the coating. The meyer rod may improve the accuracy of achieving predetermined coating thicknesses and may also improve the uniformity of resulting coating thicknesses. The meyer bar rod and wire may be any suitable size. For example, the wire can be between about 2 and 150 mils. There are spaces or interstices formed between adjacent wire turns. The thickness of these spaces is determined by the thickness or diameter of the wire. The thickness of the wire, in turn, determines the thickness of the coating transferred from the roller to the target surface of the workpiece.
The rods and wires discussed herein may be any suitable metallic and/or polymeric material such as stainless steel. The outer surface of the rods and wires may also be coated with a non-stick material. For instance, PTFE and Teflon™ may be used. Further, the outer surface of the rods and wires may also be plated. For example, the rods and wires may be plated with chrome, nickel, or titanium nitride. Plating the rod and wire may facilitate coating by providing a relatively smooth contact surface. Further, plating the rod and wire may also reduce wear, by reducing abrasion, and increase the life span of the metering device.
a shows a metering device 100 that may be employed in accord with the present invention. Evident in
b shows another metering device 112 that may be employed in accord with the present invention. In
d shows another metering device 124 that may be employed in accord with the present invention. Evident in
In other embodiments, which are not shown, a plurality of additional wires may be wrapped around the rod of the metering device in a variety of other ways. For example, a second wire may be wound around the rod. Further, the second wire may be of a smaller diameter and wrapped around the grooves of the first rod. The multiple wire wrapped rods may be used, for example, in applications that apply a relatively thick coating. Additionally, any combinations of the above-identified metering devices may be plausible.
In
a is a side sectional view of a strut 228 of a stent 226 that may be coated in accord with the present invention. The strut 228 in
b shows another example of how a coating may be applied in accord with the invention. In
c is a side view of an implantable aortic stent 226 including a lattice portion that may be coated in accord with the invention. The stent 226 may be porous or have portions thereof that are porous. The struts 228 shown in
a shows a meyer bar 300 which may be employed with the embodiments of the present invention. In this example, the meyer bar 300 may be connected to supports 340 and also may be in contact with a portion of a roller 310. The meyer bar 300 may include a rod 302 with wire 304 wound around the circumference from one end of the rod to the other end. The rod 302 and wire 304 may be made of any suitable material such as stainless steel. For example, the rod 302 may be 3′ 1/16″ inch stainless steel. The meyer bar 300 may be rotated and the rod 302 of the meyer bar 300 may even be rotatably connected to a drive mechanism 342. The drive mechanism 342 can use an electrical, mechanical, or hydraulic drive source, and may use combinations thereof. For example, motors, endless belts, gearing, or hand cranks may be used.
The roller 310 may also be rotatable and may fluidly communicate with a coating source (not shown). The coating source may supply coating to the roller 310 to a coat portion of the roller. Then, the coated portion of the roller 310 may contact the meyer bar 300 prior to the roller 310 contacting a target surface of the workpiece. The meyer bar 300 may act as a squeegee to remove or control the amount of coating 344 located on a portion of the roller 310.
As illustrated in
As stated above, the wet thickness of the coating may be substantially controlled by selecting a desired thickness or gauge of the wire. For example, the wet thickness of the coating may be about 0.1 times the wire diameter. Numerous wire sizes may
be available to produce a desired wet film thickness. Wet thickness may be controlled within about 0.1 mils or 2.5 microns. For example, the following table provides exemplary wire sizes and wet film thicknesses in both U.S. standard and metric units of measure which may be suitable.
Comparatively, the dry thickness of the coating may be determined in part by the solids concentration and evaporation rate of the coating solution. The characteristics of the coating (e.g. viscosity) may also be relatively important in determining the dry thickness of the coating solution.
a shows a system for coating a target surface of a workpiece 401 using a roller 410 and a metering device 400 that may be employed in accord with the present invention. In this example, the metering device 400 may be stationary. The roller 410 may be at least partially positioned in a reservoir 448 having coating 444. Also evident in
b shows another a system for coating a target surface of a workpiece 401 using a roller 410, a plurality of metering devices 400, 403, and a doctor blade 450 that may be employed in accord with the present invention. In this example, the roller 410 may be at least partially positioned within a reservoir 448 having coating 444. Additionally, in this instance, the roller 410 may rotate in the clockwise direction, one metering device 400 and the workpiece 401 may be rotated in the counterclockwise direction, and the other metering device 403 may be stationary. However, other suitable arrangements may be plausible.
c shows still another system of coating a target surface of a workpiece 401 using a roller 410 and a metering device 400 that may be employed in accord with the present invention. In this embodiment, the metering device 400 may be at least partially positioned within a reservoir 448 having coating 444. In this example, the metering device 400 and workpiece 401 may be rotated counterclockwise. The roller 410 may be rotated clockwise. In this embodiment, the roller 410 may be located outside of the reservoir 448 and may be coated by the metering device 400. However, other arrangements are possible.
Other suitable examples not shown in
Moreover, any combination of metering devices 400, 403, 450, not limited to those shown, may also be used.
While various embodiments have been described, other embodiments are plausible. It should be understood that the foregoing descriptions of various examples of the metering device and roller 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 the coating of target surfaces of the workpiece.
The coating, in accord with the 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. 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, andenoassociated 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, 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 promotors such as growth factors, growth factor receptor antagonists, transcriptional activators, and translational promotors; 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 ∀ and ∃, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor ∀, 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 (“BMP's”). 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 BMP's 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 DNA's encoding them.
As stated above, coatings used with the exemplary embodiments of the present invention may comprise 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. In the case of a balloon catheter, the thickness is preferably about 1 to 10 microns thick, and more preferably about 2 to 5 microns. Very thin polymer coatings, e.g., of about 0.2-0.3 microns and much thicker coatings, e.g., more than 10 microns, are also possible. 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 (BAYHDROL®, etc.) and acrylic latex dispersions are also within the scope of 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 of the invention, 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 of the invention, 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.
