Abstract:
A nozzle for use in a coating apparatus for the application of a coating substance to a stent is provided. Method for coating a stent can include discharging a coating composition out from a needle of a nozzle assembly, and atomizing the coating composition as the coating composition is discharged. The needle can be positioned in a chamber of the nozzle assembly, and gas can be introduced into the chamber for atomizing the coating composition.

Description:
This application is a divisional of U.S. patent application Ser. No. 10/322,255, filed Dec. 17, 2002 now U.S. Pat. No. 7,338,557, the entire disclosure of which is incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     This invention relates to an apparatus used in the process of coating a stent, and more particularly provides a nozzle for use in drug eluting stent spray coating. 
     BACKGROUND 
     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. 
     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. 
     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. 
     A shortcoming of the above-described method of medicating a stent is the potential for coating defects and the lack of uniformity of the amount of composition material sprayed onto stents. While some coating defects can be minimized by adjusting the coating parameters, other defects occur due the shot to shot variation leading to excess composition being sprayed onto the stent. One cause of this shot to shot variation is the type of spray coater used. For example, a conventional EFD N1537 (EFD Inc. East Providence R.I.) spray coater uses a valve mechanism to dispense fluid and is most suitable for dispensing large amounts of composition (i.e., grams) and not small amounts (e.g., milligrams per spray cycle) as used in stent coating applications. Accordingly, conventional spray coaters tend to spray excess coating onto stents, which may stick to the stent, thereby leaving excess coating as clumps or pools on the struts or webbing between the struts. 
     Accordingly, a new nozzle for spraying coating is needed to minimize coating defects. 
     SUMMARY 
     The present invention is generally directed to a method of coating a stent. In some aspects of the present invention, the method comprises positioning a nozzle assembly having a needle disposed therein next to a stent, wherein the needle is in fluid communication with a reservoir containing a coating composition, discharging the coating composition from the reservoir out from the needle, and atomizing the coating composition into droplets as the coating composition is discharged out from the needle. In further aspects, the method additionally comprises rotating the stent about the longitudinal axis of the stent. In detailed aspects, the composition is atomized within the nozzle assembly. The composition is, in other detailed aspects, atomized external to the nozzle assembly. 
     In other aspects of the present invention, the method further comprises positioning the needle within a chamber of the nozzle assembly, and atomizing the coating composition includes introducing a gas into the chamber. In further aspects, the method comprises coupling the needle to the chamber such that an outlet of the needle extends through an outlet of the chamber to form an annular aperture through which gas introduced into the chamber exits. In other further aspects, the method comprises coupling the needle to the chamber such that an outlet of the needle does not extend through an outlet of the chamber. Positioning the needle within the chamber, in other aspects of the invention, includes adjusting the position of an outlet of the needle relative to an outlet of the chamber. Adjusting, in other some, includes threading a needle centering body of the nozzle assembly to the chamber, the needle centering body holding the needle. In other aspects, positioning the needle within the chamber includes holding the needle with a needle centering body of the nozzle assembly, and positioning the needle centering body in the chamber to form a cavity between the needle centering body and the chamber, the cavity in fluid communication with an inlet of the chamber for receiving a gas and an outlet of the chamber for discharging the gas introduced into the chamber. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       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. 
         FIG. 1  is a block diagram illustrating a coating system for coating a stent with a composition; 
         FIG. 2  is a disassembled perspective view illustrating the nozzle assembly of the coating system of  FIG. 1  in accordance with an embodiment of the invention; 
         FIG. 3  is a schematic cross section illustrating a portion of the nozzle assembly with the hypodermic needle at a first position for external mixing; 
         FIG. 4  is a schematic cross section illustrating a portion of the nozzle assembly with the hypodermic needle at a second position for internal mixing; and 
         FIG. 5  is a cross section illustrating one embodiment of the nozzle assembly. 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1  is a block diagram illustrating a coating system  100  for coating a stent  10  with a composition. The coating system  100  comprises a pump  120 ; a pump control  110 ; a reservoir  125 ; a nozzle assembly  140 ; an atomizer  160 ; an atomizer control  150 ; a mandrel fixture  180  and a mandrel fixture control  170 . The pump control  110  is communicatively coupled to the pump  120  and controls the amount of fluid (also referred to interchangeably as coating substance or composition) dispensed by the pump  120  from the reservoir  125 . The pump control  110  may include mechanical and/or electrical control mechanisms. In an embodiment of the invention, the pump control  110  is integrated with the pump  120 . 
     The pump  120  pumps fluid from the reservoir  125 , for coating the stent  10 , to the nozzle assembly  140  via a tubing  130 . The pump  120  may pump the fluid from the reservoir  125  at a rate of 0.15 cc/min, for example. In one embodiment of the invention, the pump  120  includes a syringe pump. In another embodiment of the invention, the pump  120  includes a gear pump. It will be appreciated that the pump  120  can comprise other types of pumps and/or combinations of pumps such as a positive displacement pump or a green pump. 
     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(glycerol-sebacate); 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. 
     “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-methylpyrrolidinone, toluene, and mixtures and combinations thereof. 
     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. 
     The atomizer  160  supplies high-pressure air to the nozzle assembly  140  via a tubing  170  coupled to an air inlet  280  ( FIG. 2 ). This high-pressure air is used to atomize the composition dispensed from the nozzle assembly  140  onto the stent  10 , as will be discussed in further detail in conjunction with  FIG. 3  and  FIG. 4 . The atomizer control  150  is communicatively coupled to the atomizer  160  and controls the pressure of the air dispensed from the atomizer  160  to the nozzle assembly  140 . The atomizer control  150  can include electrical mechanisms, mechanical mechanisms, or a combination thereof to control the atomizer  160 . In an embodiment of the invention, the atomizer control  150  and the atomizer  160  can be integrated into a single device. 
     The mandrel fixture  180  supports the stent  10  during a coating application process. In addition, the mandrel fixture  180  can include an engine so as to provide rotational motion about the longitudinal axis of the stent  10 , as depicted by the arrow  190 , during the coating process. Another motor can also be provided for moving the stent  10  in a linear direction, back and forth. The mandrel control  170  is communicatively coupled to the mandrel fixture  180  and controls movement of the stent  10 . The type of stent that can be crimped on the mandrel fixture  180  is not of critical significance. The term stent is broadly intended to include self- and balloon-type expandable stents as well as stent-grafts. 
     The nozzle assembly  140 , as will be discussed in further detail in conjunction with  FIG. 2 , receives the coating composition from the reservoir  125  via the tubing  130 . In addition, the nozzle assembly  140  receives high-pressure air from the atomizer  160 . During a stent coating application process, the nozzle assembly  140  dispenses composition onto stent  10 . During the dispensing, high-pressure air from the atomizer  160  atomizes the composition, leading to a more uniform distribution on the stent  10 . 
     It will be appreciated that the multiple control devices, i.e., the pump control  110 , atomizer control  150 , and mandrel control  170  can be combined into a single control device to simplify setting parameters for an operator. 
       FIG. 2  is a disassembled perspective view illustrating the nozzle assembly  140  of the coating system  100  in accordance with an embodiment of the invention. The nozzle assembly  140  includes a coupling  210  having a fluid inlet  200 ; a hypodermic needle  220 , two O-rings  230  and  260 ; a needle centering body  240 ; a needle height locking ring  250 ; and an air chamber  270  having an air inlet  280 . The coupling  210  is in liquid communication with the reservoir  125  via the tubing  130  that is coupled to the fluid inlet  200 . The coupling  210  receives the composition from the reservoir  125  for coating the stent  10 . In an alternative embodiment of the invention, the nozzle assembly  140  includes a barrel connection, which is coupled to a barrel that dispenses fluid, in place of the coupling  210 . In this alternative embodiment, the amount of fluid dispensed is controlled by a valve mechanism in conjunction with variable air pressure in the barrel and/or in the needle  220 . 
     The hypodermic needle  220  is in liquid communication with the coupling  210  and receives the fluid for coating the stent  10  from the coupling  210 . In an embodiment of the invention, the hypodermic needle  220  includes a 28 gauge needle. In an alternative embodiment of the invention, the nozzle assembly  140  includes a hypotube in place of the hypodermic needle  220 . The O-ring  230  is located between the coupling  210  and the needle centering body  240  and forms a tight seal there between. 
     The needle centering body  240  securely centers the hypodermic needle  220  within the nozzle assembly  140 . A portion of the needle centering body  240  is located within the air chamber  270  so as to form an air cavity for receiving air from the atomizer  160  via the air inlet  280  and exiting via an air outlet  300  ( FIG. 3 ), as will be discussed in further detail in conjunction with  FIG. 3  and  FIG. 4 . In an alternative embodiment of the invention, the air chamber  270  has a plurality of air inlets for receiving air from the atomizer  160 . 
     In an embodiment of the invention, both the needle centering body  240  and the air chamber  270  have surfaces that are threaded, thereby enabling them to be coupled together at variable positions so that the tip of the hypodermic needle  220  can extend at variable lengths from the air chamber  270 , as will be discussed in further detail in conjunction with  FIG. 3  and  FIG. 4 . The needle height lock ring  250  locks the air chamber  270  and the needle centering body  240  securely together so as to prevent movement relative to each other during a spray coating process. The O-ring  260  is located between the air chamber  270  and the needle centering body  240  and forms a secure seal there between to prevent pressurized air escaping there from. 
       FIG. 3  is a cross section illustrating a portion of the nozzle assembly  140  with the hypodermic needle  220  at a first position for external mixing. Air from the atomizer  160 , via the air inlet  280 , flows out of the cavity formed by the needle centering body  240  and the air chamber  270  via the air outlet  300 . The atomizer  160  atomizes the fluid dispensed from the hypodermic needle  220  into atomized droplets, such as droplet  310  (not to scale), so that the fluid more evenly coats the stent  10 . In one embodiment of the invention, the air outlet  300  is an annular aperture that circumscribes the needle  220  orifice. 
     Generally, smaller atomized droplets, e.g., a fine mist, is preferable to large droplets so as to ensure an even coating on the stent  10 . Droplet size is directly proportional to the diameter of the hypodermic needle  220  orifice. Accordingly, a smaller needle orifice is superior for atomization than a larger diameter nozzle as used conventionally. More specifically, the standard median droplet diameter 
                 S   ⁢           ⁢   M   ⁢           ⁢   D     ∝       diameter   o     ⁢     U   R     ⁢       Mass   fluid       Mass   air           ⁢           ,     
     ⁢   wherein                   U   R     =       Velocity   fluid       Velocity   air         ,         
and wherein diameter o  is the diameter of the needle  220  orifice. Accordingly, in addition to a small needle diameter, high air velocity and less fluid increases atomization of the fluid and therefore increases the even coating of the stent  10  with the fluid. Conventional nozzle assemblies that are designed to dispense grams of fluid per shot generally dispense large and uneven amounts of fluid per shot and so do not always enable adequate atomization. In contrast, the hypodermic needle  220  can dispense small uniform amounts of fluids via a small diameter orifice, thereby enabling adequate atomization of the fluid to ensure even coating of the stent  10 . Another advantage of the hypodermic needle  220  is that it is disposable. Accordingly, the nozzle assembly  140  can be used for dispensing different fluids without worry of cross contamination by simply replacing the hypodermic needle  220  with a new needle.
 
     The hypodermic needle  220 , in the embodiment illustrated in  FIG. 3 , extends outward from the nozzle assembly  140 , or, more specifically, extends downward from the air chamber  270 , thereby enabling external mixing of the air from the atomizer  160  with the fluid dispensed from the hypodermic needle  220 . In an exemplary embodiment of the invention, the hypodermic needle  220  can extend up to 2 cm from the air chamber  270 . The distance that the needle  220  protrudes should not hinder the atomization of the composition. In one embodiment, the distance that the needle  220  protrudes is adjustable. 
       FIG. 4  is a cross section illustrating a portion the nozzle assembly  140  with the hypodermic needle  220  at a second position for internal mixing. Air from the atomizer  160 , via the air inlet  280 , flows out of the cavity formed by the needle centering body  240  and the air chamber  270  via the air outlet  300 . The atomizer  160  atomizes the fluid dispensed from the hypodermic needle  220  into atomized droplets, such as droplet  310  (not to scale), so that the fluid more evenly coats the stent  10 . The atomization, in this embodiment, is done within the air chamber  270  (i.e., internal mixing). 
       FIG. 5  is a cross section illustrating the nozzle assembly  140 . Composition is fed into the fluid inlet  200  of the coupling  210 . The composition flows into the needle  220  and then exits the nozzle assembly  140 . The atomizer  160  supplies air to the air chamber  270  via the air inlet  280 . The air supplied by the atomizer  160  atomizes composition as it exits the needle  220 . 
     While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects. Therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.