Abstract:
A system for forming a coating on a stent has a hub for holding a plurality of cartridges. Each cartridge has a plurality of mandrels, each mandrel capable of supporting a stent. A chamber has a drying section and a spray coating section, and is configured to receive a cartridge from the hub. An arm moves a cartridge from the hub to the chamber. A spray applicator applies a coating composition to a stent in the spray coating section.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a division of application Ser. No. 11/690,100, filed Mar. 22, 2007, which is a division of U.S. application Ser. No. 10/315,457, filed Dec. 9, 2002, now U.S. Pat. No. 7,211,150, the entire contents of which applications are incorporated herein by reference. 
     
    
     TECHNICAL FIELD 
       [0002]    This invention relates to a system used in the process of manufacturing a stent, and more particularly provides a system for coating and drying stents. 
       BACKGROUND 
       [0003]    Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a stent. Stents act as scaffolding, functioning to physically hold open and, if desired, to expand the wall of affected vessels. Typically stents are capable of being compressed, so that they can be inserted through small lumens via catheters, and then expanded to a larger diameter once they are at the desired location. Examples in the patent literature disclosing stents include U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor. 
         [0004]    Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. Local delivery of a therapeutic substance is a preferred method of treatment because the substance is concentrated at a specific site and thus smaller total levels of medication can be administered in comparison to systemic dosages that often produce adverse or even toxic side effects for the patient. 
         [0005]    One method of medicating a stent involves the use of a polymeric carrier coated onto the surface of the stent. A composition including a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend is applied to the stent by spraying the composition onto the stent. The solvent is allowed to evaporate, leaving on the stent surfaces a coating of the polymer and the therapeutic substance impregnated in the polymer. In order to quicken the process, the stents may be baked so that the solvent evaporates quickly. 
         [0006]    Shortcomings of the above-described method of medicating a stent is the potential for shot to shot variation of the coating weight and the need for baking or otherwise drying each stent after the coating application. These two shortcomings limit production throughput. Specifically, after each coating process (e.g., primer, drug coat, topcoat), the stent must be weighed to calculate the amount of drug and polymer deposited onto the stent. In addition, up to two hours bake time can be required to evaporate the solvent from the stent. 
         [0007]    Accordingly, a new apparatus for spraying coating is needed to increase production throughput. 
       SUMMARY OF THE INVENTION 
       [0008]    Briefly and in general terms, the present invention is directed to a system for forming a coating on a stent. In aspects of the present invention, a system comprises a hub, a chamber, an arm, and a spray applicator. The hub is for holding at least one cartridge. The is cartridge capable of having a plurality of stents supported thereon. The chamber is capable of receiving the cartridge for the application of a coating substance to the stents. The arm is capable of moving the cartridge between the hub and the chamber. The spray applicator is capable of applying a coating composition to the stent. 
         [0009]    In aspects of the present invention, a system comprises a hub configured to hold a plurality of cartridges having stent mandrels for supporting stents, a chamber configured to receive a cartridge among the plurality of cartridges, an arm configured to move a cartridge among the plurality of cartridges from the hub to the chamber and from the chamber to the hub, and a spray applicator configured to apply a coating composition in the chamber to coat a stent on a stent mandrel of a cartridge received within the chamber. 
         [0010]    The features and advantages of the invention will be more readily understood from the following detailed description which should be read in conjunction with the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0011]    Non-limiting and non-exhaustive embodiments of the present invention are described with reference to the following figures, wherein like reference numerals refer to like parts throughout the various views unless otherwise specified. 
           [0012]      FIG. 1  is a diagram illustrating a multiple stent coater/dryer apparatus; 
           [0013]      FIG. 2  is a diagram illustrating a cross section of the multiple stent coater/dryer apparatus; 
           [0014]      FIG. 3  is a diagram illustrating a cross section of a portion the coating/drying chamber; 
           [0015]      FIG. 4  is a block diagram illustrating controlling electronics in accordance with one embodiment of the present invention; 
           [0016]      FIG. 5  is a diagram illustrating a profile of the cartridge; 
           [0017]      FIG. 6  is a diagram illustrating the coating/drying chamber holding a cartridge; and 
           [0018]      FIG. 7  is a diagram illustrating the coating/drying chamber holding a cartridge with a coating applicator. 
       
    
    
     DETAILED DESCRIPTION 
       [0019]    The following description is provided to enable any person having ordinary skill in the art to make and use the invention, and is provided in the context of a particular application and its requirements. Various modifications to the embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments and applications without departing from the spirit and scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown, but is to be accorded the widest scope consistent with the principles, features and teachings disclosed herein. 
         [0020]      FIG. 1  is a diagram illustrating a multiple stent coater/dryer apparatus  100 . The multiple stent coater/dryer apparatus  100  enables the coating and simultaneous drying of stents, thereby increasing throughput. Bare stents are manually loaded onto a circular cartridge  500  ( FIG. 5 ), which can hold twelve to eighteen stents in one embodiment of the invention. The cartridge  500  is then manually placed in a loading bay on a circular-shaped hub  105 . An engine  110  rotates the hub  105  in a counter clockwise direction such that a handle  510  of the cartridge  500  passes through a gate  115 , thereby indicating that the cartridge  500  is oriented correctly so that an arm  120  can pick up the cartridge  500 . 
         [0021]    After the cartridge  500  passes through the gate  115 , the arm  120  picks up the cartridge  500  via the handle  510  and carries the cartridge  500  to a secondary chamber for coating and drying stents on the cartridge  500 . The arm  120  then securely places the cartridge  500  into a base  125  of a coating/drying chamber  600  ( FIG. 6 ). After placement, a lever  135  lowers a cap  140  onto the base  125  so as to form the coating/drying chamber  600 . The lever  135  also lowers an anvil  145  onto the handle  510  of the cartridge  500 . As will be discussed further below, the cartridge  500  rotates within the coating/drying chamber  600  such that while one stent is being coated by a coating applicator  740 , other stents mounted on the cartridge  500  are dried (and/or preheated for coating). In an embodiment of the invention, a dryer  130  is in communication with the coating/drying chamber  600  to supply heated air to dry the stents mounted on the cartridge  500 . 
         [0022]      FIG. 2  is a diagram illustrating a cross section of the multiple stent coater/dryer apparatus  100 . The apparatus includes a shaft  200  coupled to the engine  110  and the hub  105  that is used to rotate the hub  105 . Engines  210  and  220  rotate an inner shaft  320  and an outer shaft  330 , respectively. As will be discussed further below, the outer shaft  330  rotates the cartridge  500  and the inner shaft  320  rotates stent mandrels  520  ( FIG. 5 ) of the cartridge  500 . 
         [0023]      FIG. 3  is a diagram illustrating a cross section of a portion the coating/drying chamber  600 . The chamber  600  includes the base  125  and the cap  140 . The base  125  includes an air inlet  300  for receiving heated air and an air outlet  310  for exhausting heated air, thereby enabling the circulation of heated air within the chamber  600 . The outer shaft  330  is coupled to the cartridge  500  via an outer clutch  550  ( FIG. 5 ) and the components engage by the pressure applied by the anvil  145 . Accordingly, lifting of the lever  135  will enable the decoupling of the cartridge  500  from the outer shaft  330 . Coupled to the outer shaft  330  is gear  340 , which is interlocked with the outer shaft  330  such that rotation of the gear  340  causes outer shaft  330  to rotate. The inner shaft  320  is also coupled to the cartridge  500  via an inner clutch  540  ( FIG. 5 ) via pressure applied by the anvil  145 . Rotation of the inner shaft  320  causes the mandrels  520  to rotate during spraying and drying, as will be discussed further below. 
         [0024]      FIG. 4  is a block diagram illustrating controlling electronics  400  in accordance with an embodiment of the present invention. In an embodiment of the invention, the controlling electronics  400  controls substantially all aspects of the multiple stent coater/dryer apparatus  100 . Specifically, the controlling electronics  400  controls rotation of the hub  105 ; linear movement of the arm  120 ; vertical movement of the lever  135 ; temperature and pressure of air produced by the dryer  130 ; rotation of the outer shaft  330 ; rotation of the inner shaft  320 ; and the coating applicator  740 . 
         [0025]    The controlling electronics  400  includes a central processing unit (CPU)  405 ; working memory  410 ; persistent memory  420 ; input/output (I/O) interface  430 ; display  440  and input device  450 , all communicatively coupled to each other via system bus  460 . CPU  405  may include an Intel Pentium® microprocessor, a Motorola PowerPC® microprocessor, or any other processor capable to execute software to control the multiple stent coater/dryer apparatus  100  that is stored in persistent memory  420 . Working memory  410  may include random access memory (RAM) or any other type of read/write memory devices or combination of memory devices. Persistent memory  420  may include a hard drive, read only memory (ROM) or any other type of memory device or combination of memory devices that can retain data after controlling electronics  400  is shut off. I/O interface  430  is communicatively coupled, via wired or wireless techniques, to the components of the multiple stent coater/dryer apparatus  100  that the controlling electronics  400  controls. Display  440  may include a liquid crystal display or other display device. Input device  450  may include a keyboard, mouse, or other device for inputting data, or a combination of devices for inputting data. 
         [0026]    One skilled in the art will recognize that the controlling electronics  400  may also include additional devices, such as network connections, additional memory, additional processors, LANs, input/output lines for transferring information across a hardware channel, the Internet or an intranet, etc. One skilled in the art will also recognize that the programs and data may be received by and stored in the system in alternative ways. 
         [0027]      FIG. 5  illustrates a profile of the cartridge  500 . The cartridge includes a plurality of stent mandrels  520  and associated knobs  530 , the handle  510 , the inner clutch  540 , and the outer clutch  550 . The arm  120  picks up the cartridge  500  via the handle  510  and moves it between the hub  105  and the base  125 . Specifically, before coating and drying, the arm  120  moves the cartridge  500  via the handle  510  from the hub  105  to the base  125 . After coating and drying, the arm  120  removes the cartridge  500  from the base  125  and returns it to the hub  105 . The stent mandrels  520  hold stents during coating and drying processes. In an embodiment, the stent mandrels  520  includes up to eighteen stent mandrels  520  distributed around the periphery of the cartridge  500 . The inner clutch  540  is coupled to the stent mandrels  520  such that rotation of the inner clutch  540  causes rotation of the stent mandrels  520 . This allows rotation of the stents along the longitudinal axis of the stents. Rotational forces applied to the outer clutch  550  causes rotation of the entire cartridge  500 . 
         [0028]      FIG. 6  is a diagram illustrating the coating/drying chamber  600  holding the cartridge  500 . The drying chamber  600  comprises the base  125  and the cap  140  and holds the cartridge  500 , which rotates counter clockwise within the drying chamber  600  in an embodiment. The base  125  and cap  140  both have open cylinder shapes that when combined form a closed cylindrical shape. 
         [0029]    The coating/drying chamber  600  also includes a spray chamber  670 , which exposes a single stent mandrel  520  to spray coating from the coating applicator  740  ( FIG. 7 ). The spray chamber  670  is formed by an open section of the cap  140  with gates  640   a  and  640   b  (also referred to as flaps) sectioning off the remainder of the spray chamber  670  from the coating/drying chamber  600 . The gates  640   a  and  640   b  are coupled to the top of cap  140  with hinges such that pressure applied to the gates  640   a  and  640   b  (e.g., via knobs  530 ) cause them to rotate upwards from a vertical position to a horizontal position thereby enabling the stent mandrels  520  to pass through the gates  640   a  and  640   b.    
         [0030]    The remainder of the coating/drying chamber  600  forms a drying chamber within which circulates heated air to preheat stents before coating and to dry stents after coating. A tubing  660  couples dryer  130  to the drying chamber section of the coating/drying chamber  600  via inlet  300  for receiving heated air. The heated air rotates through the coating/drying chamber  600  in a counter clockwise direction and exits via outlet  310 , which is coupled to a tubing  650 . The tubing  650  can be coupled to a filtering device (not shown) or other device for collecting and/or filtering the heated air, which may contain chemicals (e.g., solvents and drugs) from the coating process. 
         [0031]    During rotation of the cartridge  500  within the coating/drying chamber  600 , the knobs  530 , which are metallic, push open the gate  640   a  so that the a stent mandrel  520  can enter the spray chamber  670 . In addition, the knobs  530  push open gate  640   b  so that a recently coated stent on a stent mandrel  520  can enter the drying chamber. A sensor (not shown) comprising a metal detector or other device detects and determines the position of at least one of the knobs  530  and provides feedback to control electronics  400 , which then controls rotation of the cartridge  500  such that a stent mandrel  520  is positioned correctly in the spray chamber  670 . 
         [0032]    Adjacent to the spray chamber  670  are circular vents  620   a  and  620   b  located in the rim of the cap  140 . Additionally, rectangular vents  610   a  and  610   b  are located on the top of the cap  140  adjacent to the spray chamber  670 . The base  125  also includes two circular vents  630   a  and  630   b  located beneath vents  620   a  and  620   b  respectively. These vents enable excess heated air to vent from the drying section of the coating/drying chamber  600  without interfering with a coating process. 
         [0033]    The coating process, as will be described in further detail in conjunction with  FIG. 7 , sprays a coating substance onto stents mounted on the stent mandrels  520 . The coating substance can include a solvent and a polymer dissolved in the solvent and optionally a therapeutic substance or a drug added thereto. Representative examples of polymers that can be used to coat a stent include ethylene vinyl alcohol copolymer (commonly known by the generic name EVOH or by the trade name EVAL), poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone; poly(lactide-co-glycolide); poly(hydroxybutyrate); poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester; polyanhydride; poly(glycolic acid); poly(D,L-lactic acid); poly(glycolic acid-co-trimethylene carbonate); polyphosphoester; polyphosphoester urethane; poly(amino acids); cyanoacrylates; poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether esters) (e.g. PEO/PLA); polyalkylene oxalates; polyphosphazenes; biomolecules, such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid; polyurethanes; silicones; polyesters; polyolefins; polyisobutylene and ethylene-alphaolefin copolymers; acrylic polymers and copolymers; vinyl halide polymers and copolymers, such as polyvinyl chloride; polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidene halides, such as polyvinylidene fluoride and polyvinylidene chloride; polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics, such as polystyrene; polyvinyl esters, such as polyvinyl acetate; copolymers of vinyl monomers with each other and olefins, such as ethylene-methyl methacrylate copolymers, acrylonitrilestyrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers; polyamides, such as Nylon 66 and polycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes; polyimides; polyethers; epoxy resins; polyurethanes; rayon; rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate; cellulose acetate butyrate; cellophane; cellulose nitrate; cellulose propionate; cellulose ethers; and carboxymethyl cellulose. 
         [0034]    “Solvent” is defined as a liquid substance or composition that is compatible with the polymer and is capable of dissolving the polymer at the concentration desired in the composition. Examples of solvents include, but are not limited to, dimethylsulfoxide, chloroform, acetone, water (buffered saline), xylene, methanol, ethanol, 1-propanol, tetrahydrofuran, 1 -butanone, dimethylformamide, dimethylacetamide, cyclohexanone, ethyl acetate, methylethylketone, propylene glycol monomethylether, isopropanol, isopropanol admixed with water, N-methyl pyrrolidinone, toluene, and mixtures and combinations thereof. 
         [0035]    The therapeutic substance or drug can be for inhibiting the activity of vascular smooth muscle cells. More specifically, the active agent can be aimed at inhibiting abnormal or inappropriate migration and/or proliferation of smooth muscle cells for the inhibition of restenosis. The active agent can also include any substance capable of exerting a therapeutic or prophylactic effect in the practice of the present invention. For example, the agent can be for enhancing wound healing in a vascular site or improving the structural and elastic properties of the vascular site. Examples of agents include antiproliferative substances such as actinomycin D, or derivatives and analogs thereof (manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin D include dactinomycin, actinomycin IV, actinomycin I 1 , actinomycin X 1 , and actinomycin C 1 . The active agent can also fall under the genus of antineoplastic, antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and antioxidant substances. Examples of such antineoplastics and/or antimitotics include paclitaxel (e.g. TAXOL® by Bristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g. Taxotere®, from Aventis S.A., Frankfurt, Germany) methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. Adriamycin® from Pharmacia &amp; Upjohn, Peapack N.J.), and mitomycin (e.g. Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, and thrombin inhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examples of such cytostatic or antiproliferative agents include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. Prinivil and Prinzide® from Merck &amp; Co., Inc., Whitehouse Station, N.J.); calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name Mevacor® from Merck &amp; Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which may be appropriate include alpha-interferon, genetically engineered epithelial cells, dexamethasone, and rapamycin. 
         [0036]      FIG. 7  is a diagram illustrating the coating/drying chamber  600  holding the cartridge  500  with the coating applicator  740  positioned adjacent thereto. The coating applicator  740  includes a nozzle  710 , reservoir  730  and tubing  720  that places the nozzle  710  in fluid communication with the reservoir  730 . The coating applicator  740  is communicatively coupled to controlling electronics  400 , which controls movement of the coating applicator  740  as well as dispensation of a coating substance, stored in the reservoir  730 , via nozzle  710  onto a stent in the spray chamber  670 . During a spray coating process, the coating applicator  740  can move back and forth along the length of the stent to spray the stent. In addition, the stent mandrel  520  holding the stent also rotates during the spray coating process to ensure that the stent is equally coated with the coating substance. 
         [0037]    After spraying, the controlling electronics  400  causes the cartridge  500  to rotate in a counter clockwise direction such that one of the knobs  530  pushes open gate  640   b  so that the coated stent can enter the drying portion of coating/drying chamber  600 . The cartridge  500  can make a full 360-degree revolution so that the stent can go through a subsequent spray coating process, thereby enabling multiple layers of a coating substance or multiple layers of a plurality of different coating substances to be formed on a stent. 
         [0038]    In an embodiment of the invention, the coating/drying chamber  600  includes a plurality of spray chambers  670  and coating applicators  740  so that a plurality of different coating substances can be dispensed onto a stent during a coating/drying cycle. In an example coating/drying process, the dryer  130  supplies heated air having a temperature of, for example, 50 to 80 degrees celsius. The heated air can circulate within the drying section of the coating/drying chamber  600  at a speed of up to about  20  meters/second. The cartridge  500  makes  20  to  60  revolutions per process, leading to 20 to 60 coating layers applied to each stent mounted on the stent mandrels  520 . The coating applicator can spray a stent mounted on the stent mandrel  520  for about five to ten seconds at a rate of about 50 cubic millimeters per minute. The nozzle  710  can use about 15 psi atomization air pressure to atomize the composition dispensed from the nozzle  710 . 
         [0039]    Accordingly, the multiple stent coater/dryer apparatus  100  enables elimination of a long final oven bake of the stents because the solvent is removed after application of each thin layer. Further, the multiple stent coater/dryer apparatus  100  minimizes drug-solvent interaction because the solvent is removed from each layer immediately after the composition is applied. In addition, the multiple stent coater/dryer apparatus  100  enables minimization of extraction of the drug in a lower layer into an upper layer because the solvent is removed immediately for each layer after coating. Another benefit is that the multiple stent coater/dryer apparatus  100  enables minimal handling between applications of layers. For example, the stents do not need to be weighed between applications of layers. An additional benefit is that the multiple stent coater/dryer apparatus  100  enables deposition of a higher coating weight per layer/coating cycle by drying off substantially all of the solvent after each spray coating cycle. Finally, the multiple stent coater/dryer apparatus  100  enables preheating of each stent prior to each cycle for better wetting. 
         [0040]    The foregoing description of the illustrated embodiments of the present invention is by way of example only, and other variations and modifications of the above-described embodiments and methods are possible in light of the foregoing teaching. Components of this invention may be implemented using a programmed general purpose digital computer, using application specific integrated circuits, or using a network of interconnected conventional components and circuits. Connections may be wired, wireless, modem, etc. The embodiments described herein are not intended to be exhaustive or limiting. The present invention is limited only by the following claims.