Abstract:
An apparatus and method for coating abluminal surface of a stent is described. A method for coating a stent can include stent mounting, stent movement, and droplet excitation. A method can include applying a coating to a stent, the applying including generating waves in a coating solution to eject droplets of the coating solution from a surface of the coating solution toward the stent, the generating performed by transducers submerged in the coating solution.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a divisional of application Ser. No. 11/442,005, filed May 26, 2006, which is incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates a method for coating a stent. More particularly, this invention provides a method to generate uniform and controllable droplets that can be used to rapidly coat the abluminal surface (selective areas or entire outside surface) of a stent. 
       BACKGROUND 
       [0003]    Percutaneous transluminal coronary angioplasty (PTCA) has revolutionized the treatment of coronary arterial disease. A PTCA procedure involves the insertion of a catheter into a coronary artery to position an angioplasty balloon at the site of a stenotic lesion that is at least partially blocking the coronary artery. The balloon is then inflated to compress against the stenosis and to widen the lumen to allow an efficient flow of blood through the coronary artery. However, restenosis at the site of angioplasty continues to hamper the long term success of PTCA, with the result that a significant proportion of patients have to undergo repeated revascularization. 
         [0004]    Stenting has been shown to significantly reduce the incidence of restenosis to about 20 to 30%. On the other hand, the era of stenting has brought a new problem of in-stent restenosis. As shown in  FIG. 1 , a stent  2  is a scaffolding device for the blood vessel and it typically has a cylindrical configuration and includes a number of interconnected struts  4 . The stent is delivered to the stenosed lesion through a balloon catheter. Stent is expanded to against the vessel walls by inflating the balloon and the expanded stent can hold the vessel open. 
         [0005]    Stent can be used as a platform for delivering pharmaceutical agents locally. The inherent advantage of local delivery the drug over systematic administration lies in the ability to precisely deliver a much lower dose of the drug to the target area thus achieving high tissue concentration while minimizing the risk of systemic toxicity. 
         [0006]    Given the dramatic reduction in restenosis observed in these major clinical trials, it has triggered the rapid and widespread adoption of drug-eluting stents (DES) in many countries. A DES consisting of three key components, as follows: (1) a stent with catheter based deployment device, (2) a carrier that permits eluting of the drug into the blood vessel wall at the required concentration and kinetic profile, and (3) a pharmaceutical agent that can mitigate the in-stent restenosis. Most current DES systems utilize current-generation commercial stents and balloon catheter delivery systems. 
         [0007]    The current understanding of the mechanism of restenosis suggests that the primary contributor to re-narrowing is the proliferation and migration of the smooth muscle cells from the injured artery wall into the lumen of the stent. Therefore, potential drug candidates may include agents that inhibit cell proliferation and migration, as well as drugs that inhibit inflammation. Utilizing the synergistic benefits of combination therapy (drug combination) has started the next wave of DES technology. 
         [0008]    Strict pharmacologic and mechanical requirements must be fulfilled in designing the drug-eluting stents (DES) to guarantee drug release in a predictable and controlled fashion over a time period. In addition, a high speed coating apparatus that can precisely deliver a controllable amount of pharmaceutical agents onto the selective areas of the abluminal surface of a stent is extremely important to the DES manufactures. 
         [0009]    There are several conventional coating methods have been used to apply the drug onto a stent, e.g. by dipping the stent in a coating solution containing a drug or by spraying the drug solution onto the stent. Dipping or spraying usually results in a complete coverage of all stent surfaces, i.e., both luminal and abluminal surfaces. The luminal side coating on a coated stent can have negative impacts to the stent&#39;s deliverability as well as the coating integrity. Moreover, the drug on the inner surface of the stent typically provides for an insignificant therapeutic effect and it get washed away by the blood flow. While the coating on the abluminal surface of the stent provides for the delivery of the drug directly to the diseased tissues. 
         [0010]    The coating in the lumen side may increase the friction coefficient of the stent&#39;s surface, making withdrawal of a deflated balloon more difficult. Depending on the coating material, the coating may adhere to the balloon as well. Thus, the coating may be damaged during the balloon inflation/deflation cycle, or during the withdrawal of the balloon, resulting in a thrombogenic stent surface or embolic debris. 
         [0011]    Defect formation on the stents is another shortcoming caused by the dipping and spraying methods. For example, these methods cause webbing, pooling, or clump between adjacent stent struts of the stent, making it difficult to control the amount of drug coated on the stent. In addition, fixturing (e.g. a mandrel) used to hold the stent in the spraying method may also induce coating defects. For example, upon the separation of the coated stent from the mandrel, it may leave some excessive coating material attached to the stent, or create some uncoated areas at the interface between the stent struts and mandrel. The coating weight and drop size uniformity control is another challenge of using aforementioned methods. 
         [0012]    Another coating method involves the use of inkjet or bubble-jet technology. The drop ejection is generated by the physical vibration through an piezoelectric actuation or by thermal actuation. In an example, single inkjet or bubble jet nozzle head can be devised as an apparatus to precisely deliver a controlled volume coating substance to the entire or selected struts over a stent, thus it mitigates some of the shortcomings associated with the dipping and spraying methods. Typically, this operation involves moving an ejector head along the struts of a stent to be coated, but its coating speed is inherently much slower than, for example, an array coating system which consists of many transducers and each transducer can generate droplets to coat a stent simultaneously. This coating apparatus enables to generate droplets at single or multiple locations simultaneously on demand, thus it allows to coat stent in a much faster and versatile way (e.g. line printing rather than dot printing). 
         [0013]    Furthermore, nozzle clogging, which may adversely affect coating quality, is a common problem to spraying, inkjet, and bubble-jet methods. Cleaning the nozzles results in a substantial downtime, decreased productivity, and increased maintenance cost. 
         [0014]    It has been shown that focused and high intensity sound beams can be used for ejecting droplets. It is based on a constructive interference of acoustic waves—the acoustic waves will add in-phase at the focal point. Droplet formation using a focused acoustic beam is capable of ejecting liquid drop as small as a few microns in diameter with good reliability. It typically requires an acoustic lens to focus the acoustic waves. 
         [0015]    The present invention provides a stent coating apparatus and method that overcome the aforementioned shortcomings from the conventional coating methods. The stent coating apparatus of the present invention can coat the abluminal surface of a stent at a high speed, and it can deliver a precise amount of coating material to the specific stent surfaces. Furthermore, the present invention does not use a nozzle, thus it eliminates the potential nozzle clogging issues. 
         [0016]    According to the present invention, the stent coating apparatus includes a stent support, a coating device, and an imaging system. The stent support provides the mechanisms to hold a stent in place on a mandrel and to control the rotational and circumferential movement of the stent during the coating. 
         [0017]    The coating apparatus includes a reservoir, a transducer assembly, and an ejection logic controller. The reservoir is used to hold a coating solution; a transducer assembly is used to generate acoustic energy to actuate the drop ejection from the surface of the coating solution; the ejection logic provides a control can over the position of droplet ejection. Transducers can be differentially turned on or off to steer the excitation of the droplets, and the droplet formation can be controlled only at the areas of the stent that need be coated. The advantage of this technique is it provides a reliable ejection of the fluids “on demand” without clogging the ejection aperture because the area of each ejection focal point is a relatively small region to the aperture. 
         [0018]    The transducer assembly includes a plurality of transducers, RF drive device, and an ejection controller. Each transducer (e.g. piezoelectric transducer) can convert electrical energy into waves, such as ultrasonic waves. The transducer assembly generates acoustic waves and they propagate in the solution toward the liquid/air interface. Those waves are constructively interfered at a focal point of the solution surface, i.e., the waves will add in-phase at the focal point. The focused energy causes a droplet to be ejected from the surface of the coating solution. The wave frequency or amplitude can be used to adjust the droplet volume or droplet velocity. 
         [0019]    In an embodiment of the invention, the constructively interfered waves are generated in certain patterns by controlling only portion of the transducers from the transducer arrays. Preferably, a switching system (or an ejection logic control) is linked to an imaging system to energize the transducers according to the stent strut position. 
         [0020]    In an embodiment of the invention, the controller commands the transducer arrays to simultaneously eject droplets at multiple ejection points on the surface of the coating solution so that the stent can be coated simultaneously. 
         [0021]    In an embodiment of the invention, the stent is preferably positioned above the ejector to receive the droplets generated from the surface of coating solution. In another embodiment, stent can be placed beneath the ejector. It will be appreciated by one of the ordinary skill in the art that embodiments of the invention enable to position the stent or the ejector in any orientation. 
         [0022]    In an embodiment of the invention, the stent coating apparatus includes at least one assisted device, an imaging device. The image system is to track the stent strut location, to control the stent movement, and to communicate the information to the ejection logic controller. Accordingly, an imaging device with a feedback control is used to communicate to the stent holder controller to orient the stent to a particular position to receive the droplets generated by the corresponding coating device. 
       SUMMARY 
       [0023]    Briefly and in general terms, the present invention is directed to a method of coating a surface of a stent. In aspects of the invention, a method comprises applying a coating to a stent. The applying includes generating waves in a coating solution to eject droplets of the coating solution from a surface of the coating solution toward the stent. The generating is performed by transducers submerged in the coating solution. In detailed aspects, the generated waves are in-phase with each other at an ejection point at which a droplet is ejected from the surface of the coating solution. 
         [0024]    In other aspects of the present invention, a method comprises powering a plurality of transducers to produce acoustic waves in a coating solution that eject droplets from the coating solution toward a stent, and using an image of the stent to align a strut of the stent and one of the ejected droplets with each other. In detailed aspects, the transducers are submerged in the coating solution. In other aspects, the acoustic waves are in-phase with each other. 
         [0025]    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 
         [0026]      FIG. 1  is a drawing to show a typical stent design. 
           [0027]      FIG. 2  is a schematic view of a stent coating apparatus according to an embodiment of the present invention. 
           [0028]      FIG. 3  is a schematic diagram of a transducer assembly. 
           [0029]      FIG. 4  is an example of generating single droplet using a transducer array according to an embodiment of the present invention. 
           [0030]      FIG. 5  is a schematic view of a stent coating apparatus includes more than one coating device. 
           [0031]      FIG. 6  is a schematic diagram of external transducer arrays containing a single reservoir. 
           [0032]      FIG. 7  is a schematic diagram of external transducer arrays containing multiple individual reservoirs. 
       
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0033]      FIG. 2  illustrates a stent coating apparatus  10 . The apparatus  10  includes a stent handling  12 , a coating device  14 , and an imaging system,  56  and  58 . The stent handling system  12  is to provide the supports to a stent  16  which is connected to motor  26  and motor  27  so as to control stent&#39;s circumferential and translational movements. The coating device  14  applies a coating to the stent  16 . 
         [0034]    In the embodiment shown in  FIG. 2 , the stent support  12  includes a shaft  20 , a mandrel  22 , and an optional lock member  24 . The lock member  24  is optional if the mandrel  22  by itself can support the stent  16 . The support member  20  is connected to a motor  26  to rotate the stent in the circumferential direction, so as motor  27  to translate the stent in the longitudinal direction of the stent  16 , as depicted by the arrows  28  and  29 . 
         [0035]    In this embodiment, the support member  20  includes a conical end portion  30  and a bore  32  for receiving a first end of the mandrel  22 . The first end can be threaded to screw into the bore  32  or can be retained within the bore  32  by a friction fit. The bore  32  should be deep enough to allow the mandrel  22  to mate securely with the support member  20 . The depth of the bore  32  can also be further extended to allow a significant length of the mandrel  22  to penetrate or screw into the bore  32 . The bore  32  can also extend completely through the support member  20 . This would allow the length of the mandrel  22  to be adjusted to accommodate stents of various sizes. The mandrel  22  may also include a plurality of ridges  34  that add rigidity to and support to the stent  16  during coating. The ridges  34  may have a diameter of slightly less than the inner diameter of the stent  16 . While three ridges  34  are shown, it will be appreciated by one of ordinary skill in the art that additional, fewer, or no ridges may be present, and the ridges may be evenly or unevenly spaced. 
         [0036]    The lock member  24  also may include a conical end portion  36 . A second end of the mandrel  22  can be permanently affixed to the lock member  24  if the first end is disengageable from the support member  20 . Alternatively, the mandrel  22  can have a threaded second end for screwing into a bore  38  of the lock member  24 . The bore  38  can be of any suitable depth that would provide the lock member  24  incremental movement with respect to the support member  20 . The bore  38  on the lock member  24  can also be made as a through hole. Accordingly, stents of any length can be secured between the support member  20  and the lock members  20  and  24 . In accordance with this embodiment, the second end lock member  24  contains a through hole  38  enabling the second end lock member to slide over the mandrel  22  to keep the stent  16  on the mandrel  22 . 
         [0037]    The coating device  14  shown in  FIG. 2  includes a reservoir  40  and a transducer assembly  42 . The reservoir  40  is used to hold a coating substance  44  to be applied to the stent  16 . The transducer assembly  42  is submerged in the reservoir  40 . The transducer assembly  42  generates acoustic energy to eject droplets from the surface  46  of the coating solution  44  to coat the stent  16 . Preferably, the locations of the ejection points on the surface  46  of the coating substance  44  are matched to the stent strut areas that need to be coated. 
         [0038]    The reservoir  40  may have any suitable configuration and may be disposed at any suitable location. For example, the reservoir  40  may have a cylindrical, elliptical or parallelepiped configuration. Preferably, the reservoir  40  encompasses the entire stent  16  so that droplets ejected from the surface  46  can reach all areas of the stent  16 . Alternatively, the reservoir  40  may cover only an area of the stent to be coated. In a preferred embodiment, the reservoir  40  is positioned directly underneath the stent. Also, a short distance between the stent and the surface of reservoir  46  is maintained to ensure a stable droplet ejection. 
         [0039]    As shown in  FIG. 2 , the transducer assembly  42  includes a plurality of transducers  48  and a controller  50  that is programmed to control the transducers  48 . Each transducer  48  is used to generate the acoustic energy in the form of sound or ultrasound waves. Each transducer  48  preferably is a piezoelectric device, although it can be any other device suitable for generating ultrasound waves. The use of focused acoustic beam to eject droplets of controlled diameter and velocity from a free-liquid surface are well known in the art.  FIG. 3  is a schematic diagram to show the mechanism of generating the droplet on demand using transducer arrays. 
         [0040]    The controller  50  may be used to control the frequency, amplitude, and phase of the waves generated by each transducer  48  and to turn on or off the power supplied to the transducer  48 . To generate a droplet at a predetermined point on the surface  46 , the controller  50  controls the transducers  48  to generate waves that constructively interfere at this predetermined point. The focused acoustic energy causes a droplet to be ejected from the surface  46  of the coating substance  44  to coat the stent  16 . Adjusting the frequency and amplitude of the ultrasound waves allows control over the ejection speed and volume of the droplet. 
         [0041]      FIG. 4  depicts the mechanism of generating a droplet from the surface of a coating substance. As illustrated in  FIG. 4 , a coating substance  44  is contained in a reservoir (not shown); also, there are nine transducers  48  submerged in the coating substance  44 . The transducers  48  are used to generate focused in-phase waves at a predetermined ejection point  54  on the surface  46  of the coating substance  44 . In other words, the waves are coherently constructed (in phase) at the ejection point (focal point)  54 . The focused (through the acoustic lens) acoustic energy creates the required pressure at the ejection point  54 , to eject a droplet  52  from the surface  46  onto the stent surface. In order for the waves to arrive at the ejection point  54  in phase, the transducers  48  should generate the waves at different times. In the example shown in  FIG. 4 , each of the first and ninth transducers, which are farthest from the ejection point  54 , should first generate a wave. The fifth transducer, which is the closest to the ejection point  54 , is the last to generate a wave. The precise timing for progressively generating the waves can be determined by a person of ordinary skill in the art and will not be discussed herein. 
         [0042]    According to the present embodiment, as illustrated in  FIG. 2 , stent  16  is coated line by line as the stent rotates. The droplet ejection is controlled in a linear fashion and the droplet is generated only in the section that stent strut is detected. Preferably, these ejection points are aligned to stent&#39;s longitudinal direction, and the coating substance is received only on the stent&#39;s outside surfaces. The ejection points are determined through the image controllers to verify if a stent strut is present. Thus, the ejection can be excited accordingly. Excitation of drops can start from one end and ending at the other end, or the droplets can be fired in segment or in all. 
         [0043]    The droplet formation can be generated by singe or combination of any number of transducers  48  in the reservoir  40 . In some embodiments, the number of transducers used to generate each droplet may be seven. For example, the first droplet may be generated by transducers Nos. 1 to 7, the second droplet by Nos. 2 to 8, the third droplet by Nos. 3 to 9, . . . and so on. In some other embodiments, the number of transducers for generating a droplet may vary from droplet to droplet. For example, the first droplet may be generated by nine transducers, the second droplet by five, the third droplet by 15, . . . and so on. Preferably, the transducers used to generate a droplet are symmetrically arranged about the ejection point from which the droplet is ejected. Non-symmetrically arranged transducers tend to eject a droplet in a direction oblique to the surface of the coating substance. But one of ordinary skill in the art recognizes that an asymmetrical arrangement of the transducers can also be utilized to generate any specific ejection patterns by adjusting the timing, amplitude, or frequency of waves. 
         [0044]    One preferred embodiment as shown in  FIG. 2 , the transducers  48  are arranged linearly and evenly spaced. In general, however, the transducer array can be arranged in any suitable manner. For example, instead of being arranged in a single row as shown in  FIG. 2 , the transducers may be arranged in two or multiple parallel rows. Additionally, the total required number of transducers  48  included in the transducer assembly  42  can vary depending on the application. For example, the number of transducers may range from 5 to 10,000, from 10 to 2,000, from 20 to 1,000, from 30 to 600, or from 40 to 400. 
         [0045]    The stent coating apparatus  10  shown in  FIG. 2  is used to illustrate an example of using only one coating device  14  to coat the stent. This apparatus can be easily expanded to contain a dual-reservoir or multiple-reservoir coating system that will allow to accelerate the coating speed or it will allow to apply different formulations onto a stent. For example, as shown in  FIG. 5 , a stent coating apparatus  110  includes two coating assemblies  114   a  and  114   b  that are laterally arranged next to each other. Each assembly may contain different therapeutic agent. The therapeutic agent can be applied over the stent in sequence (i.e. layer by layer) to achieve a synergist effect. For example, the first coating assembly  114   a  is used to apply a layer of drug A over the stent  16 , while the second assembly  114   b  is used to apply another layer of drug B on top of drug A layer. 
         [0046]    As illustrated in  FIG. 2 , the stent coating apparatus  10  may include a first vision device  56  that images the stent  16  before or after the coating substance  44  has been applied to the stent  16 . The first imaging device  56 , along with a second imaging device  58  located a distance from the stent  16 , are both communicatively coupled to the controller  50  of the transducer assembly  42 . Based on the image provided by the imaging devices  56 ,  58 , the controller  50  actuates the ejection of the droplets to coat only selected areas of the stent  16  accordingly. 
         [0047]    After a section of the stent  16  has been coated, the coating device  14  may be stopped from dispensing the coating substance, and the imaging device  56  may begin to image the stent section to determine if the section has been adequately coated. This determination can be made by measuring the difference in color or reflectivity of the stent section before and after the coating process. If the stent section has been adequately coated, the stent coating apparatus  10  will begin to coat a new section of the stent  16 . If the stent section is not coated adequately, then the stent coating apparatus  10  will recoat the stent section. 
         [0048]    In an embodiment of the invention, the imaging devices  56 ,  58  can include charge coupled devices (CCDs) or complementary metal oxide semiconductor (CMOS) devices. In an embodiment of the invention, the imaging devices can be combined into a single imaging device. Further, it will be appreciated by one of ordinary skill in the art that placement of the imaging devices  56 ,  58  can vary as long as the devices have an acceptable view of the stent  16 . 
         [0049]    During the operation of the stent coating apparatus  10  illustrated in  FIG. 2 , the stent  16  is first mounted on the mandrel  22  of the stent support  12 . The stent  16  is then rotated about its longitudinal axis by the motor  26  of the stent support  12 . Once the stent  16  starts to rotate, the controller  50  of the coating device  14  commands the transducers  48  to generate in phase acoustic waves at one or more predetermined ejection points on the surface  46 . Droplets are ejected at the focal points and get dispensed onto the stent  16 . Additionally, the droplet volume can be tuned by adjusting the frequencies, and the drop velocity can be controlled by changing the wave amplitude. Furthermore, one or two imaging devices  56 ,  58  may be used to generate an image of the stent  16  to be used to direct the droplets to selected areas of the stent  16 . 
         [0050]    Although the transducer assemblies  42  of the above-described embodiments are placed inside the reservoir  40  and submerged in a coating substance during operation, it is possible to place a transducer assembly outside of a reservoir.  FIG. 6  illustrates a stent coating apparatus  110  that includes a reservoir  40  and a transducer assembly  142  that is placed outside of the reservoir  40 . In some embodiments, it may be preferable to place only some, but not all, of the transducers of the transducer assembly outside of the reservoir. The stent coating apparatus  110  may further include an acoustic lens  160  placed preferably between each transducer  148  and the reservoir  40 . Each acoustic lens  160  may have any suitable configuration, such as a concave configuration. The acoustic lenses  160  may be in direct contact with the coating substance or indirectly in contact with the coating substance through a coupling fluid  162  (external to the solution reservoir). The transducer assembly  142  may include (or may be coupled to) drive electronics, such as an ejection control  50 , an RF amplifier, RF switches, and RF drives  164 . 
         [0051]    Furthermore, although the embodiment shown in  FIG. 6  has only one reservoir  40 , one or more additional reservoirs may be added, and each reservoir may have one or more transducers. In the embodiment  210  shown in  FIG. 7 , for example, there is a reservoir  240  for each transducer  148 . 
         [0052]    The present invention offers many advantages over the prior art. For example, the present invention has the ability of coating stent abluminal surface only. A controlled volume of drops are generated and precisely delivered to the selective stent struts, thus it provides a better therapeutic control and it avoids the coating defects that are occurred in spraying and dipping methods. Additionally, the coating speed can be significantly increased through the transducer arrays design that enables coating the stent at multiple locations at a time. Furthermore, the present invention utilizes a nozzleless coating apparatus, thereby it eliminates the nozzle clogging issue which is a common issue to many conventional coating methods. 
         [0053]    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.