JP2007507278A - Method and apparatus for coating medical implants - Google Patents

Abstract

A method of coating a non-rotating object with an electrospun coating, wherein the charged liquefied polymer is discharged into the electric field through at least one emitting element to form a jet of polymer fibers, the emitting element being applied to the object Moving and coating the object with an electrospun film.
[Selection figure] None

Description

  The present invention relates to a method and apparatus for coating an object, and more particularly, the present invention relates to a method and apparatus for coating an object using electrospinning. The present invention is particularly useful for coating medical implants.

  In particular, the production of fibrous products using techniques of electrospinning liquefied polymers to obtain products composed of polymer fibers is described in the literature. Electrospinning is a method for producing ultrafine synthetic fibers that reduces the number of technical operations and increases the stability of the properties of the product being produced.

  The electrospinning method produces a thin stream or jet of liquid that forms a nonwoven structure when the solvent is properly evaporated to a solid transition state. A thin stream of liquid is created by pulling a small amount of polymer solution through the space using electrical force. More specifically, in the electrospinning method, a substance such as a liquefied polymer is introduced into an electric field, and the liquid is drawn toward an electrode by electric force and further cured to produce a fiber. In the case of a liquid that is usually solid at room temperature, the curing method may be simply a cooling method, but other methods such as a chemical curing method (polymerization method) or a solvent evaporation method can also be used. The produced fibers are collected in a suitably installed precipitation device and then peeled off. This deposition apparatus is usually made according to the desired shape of the final product, which can be, for example, tubular, flat or any shape.

  Examples of tubular fiber products that can be produced by electrospinning are vascular prostheses, especially tubes that can be passed or inserted through instruments or structures such as synthetic blood vessels and wires. Tubular fiber products can also be used as various artificial conduits, such as ureters, air tubes or bile ducts.

  Electrospinning methods can also be used to coat various objects, such as medical implants such as stents. Stents are widely used to place radial supports in coronary arteries to prevent the arteries from constricting. However, clinical data indicate that late restenosis usually starting about 3 months after angioplasty cannot be prevented. Stents having a mechanical barrier designed to prevent biological material from migrating from the lesion site through the stent and into the lumen while the stent is in place are known in the art.

  Utilizing electrospinning to coat stents can yield durable coatings with a wide range of fiber thicknesses (tens of nanometers to tens of micrometers), with exceptional uniformity, smoothness and coating The desired porosity distribution along the thickness of the film is achieved. Since the stent itself does not promote normal cell invasion, cells may grow irregularly within the stent's metal mesh, resulting in cell hyperplasia. When a stent is coated with a porous graft, the tissue of the graft component penetrates into the pores of the graft component from the region of the artery surrounding the stent graft. In addition, diversified polymers with various biochemical and physicomechanical properties can be used for coating.

  For mechanical barriers, coated stents with mechanical barriers can prevent tissue from over-proliferating and occluding blood vessels. US Pat. No. 5,916,264 discloses a stent graft comprising a sheet of PTFE sandwiched between two metal stents. The contents of this patent are incorporated herein by reference. Although this device has been successful in sealing aneurysms and perforations, it is a bulky device that has a much larger cross-sectional area and less flexibility than modern stents.

  Examples of electrospinning methods for producing stent grafts include US Pat. Nos. 5,639,278, 5,723,004, 5,948,018, 5,632,772, No. 5,855,598, International Patent Application No. WO249535 and Australian Patent No. AU2249402.

  Electrospinning has been found to be quite sensitive to changes in the electrophysical and rheological parameters of the solutions used in the coating process. Furthermore, incorporation of a sufficient concentration of drug in the polymer to achieve a therapeutic effect usually reduces the efficiency of the electrospinning process and causes various disadvantages of the coating. Furthermore, the introduction of a drug into the polymer reduces the mechanical properties of the resulting coating. This disadvantage is somewhat negligible for relatively thick coatings, but is detrimental for submicron fibers.

  It is desirable for the stent coating to have excellent adhesion to the metal base of the stent in body fluids so that it does not separate after or during implantation. Furthermore, the elasticity and strength of the stent coating must be able to accommodate the large expansion (about 300-500%) when the stent metal is opened. In addition, it is desirable that the stent coating promote better implantation, reduce the risk of restenosis, and optimize drug release to the tissue adjacent to the implantation site.

  With respect to the above requirements, the properties of prior art stent coatings are far from sufficient. For example, in an electrospinning device having an elongated electrode system, the electric field is critically asymmetric and the fibers are predominantly oriented in the longitudinal direction. Such a coating structure is known to have highly anisotropic mechanical properties in which the axial strength (along the fiber orientation direction) is greater than the radial strength. Radial strength has been found to be an important parameter, particularly for stent coatings, which must be adapted to the substantial expansion of the stent metal as described above. Furthermore, in the prior art electrospinning apparatus, repulsion due to static electricity between fibers increases the opening angle of the jet, enlarges the deposition area and decreases the breaking strength.

  Percutaneous coronary intervention (PCI), including balloon angioplasty and stent expansion, risks damaging blood vessels during stent implantation. As the stent is radially expanded at the defect site, the plaque on the arterial wall breaks and its sharp edges cut into the surrounding tissue. As a result, internal bleeding can occur and local infections can occur, which if not adequately treated, can spread to other parts of the body and have an adverse effect.

  Treatment of local infections in the area of an arterial defect by injecting antibiotics into the patient's bloodstream is useless because such treatments are usually ineffective against localized infections. A more general approach to this problem is to coat the stent wire mesh with a therapeutic agent that contacts the infected area. However, such a one-time treatment is not enough to remove the infection, so antibiotics and / or other therapeutic drugs need to be administered for hours, days or months There are many.

  The risk of vascular damage during implantation of the stent is reduced by using a soft stent that serves to improve the biological interface between the stent and the artery and reduce the risk of damage to the stent during implantation. be able to. Examples of polymeric stents or biocompatible fiber stent coatings are described, for example, in US Pat. Nos. 6,001,125, 5,376,117, and 5,628,788. All of these patents are incorporated herein by reference.

U.S. Pat. No. 5,948,018 discloses a graft composed of an expensive stent element that is coated with an elastic polymer graft component that is stretchable and does not interfere with stent expansion. The graft component is made by electrospinning so that porosity is obtained to promote normal cell growth. However, US Pat. No. 5,948,018 cannot treat the damage caused by the stent during the process of implanting the stent into the delicate tissue of the artery. These injuries can result in local infection of the transplant site or other disorders that can negate the benefits of the transplant if not effectively treated.
Other interesting prior art includes Murphy et al. , “Percutaneous Polymeric Stents in Porcine Coronary Arts”, Circulation 86: 1596-1604, 1992; Jeong et al. , “Does Heparin Release Coating of the Wallstent Limit Thrombosis and Platelet Deposition?”, Circulation 92: 173A, 1995; and Wiedermann S. C. “Intercoronary Irradiation Markedly Reduces Necessary Proliferation after Ballon Angioplasty in Swin” Amer. Col. Cardiol. 25: 1451-1456, 1995.

  However, the prior art methods have low radial strength or are not adequately porous for implantation in the body. Furthermore, the prior art methods cannot provide a method for coating a medical implant while attached to a guidance system such as a catheter balloon.

  Accordingly, it is widely known that there is a need for a method and apparatus for coating a medical implant without the above limitations, and it would be highly advantageous to have such a method and apparatus.

  According to one aspect of the present invention, the charged liquefied polymer is discharged into the electric field through at least one dispensing element to form a jet of polymer fibers, and then the emitting element is moved relative to the non-rotating object. A method of coating a non-rotating object with an electrospun coating comprising coating the object with an electrospun coating.

  According to still further features in the following preferred embodiments of the invention, the method further comprises translating the object relative to a jet of polymer fibers to uniformly distribute the polymer fibers on the object. .

  According to still further features in the described preferred embodiments the translation is a harmonic movement.

  According to still further features in the described preferred embodiments the translation is a reciprocation.

  According to still further features in the described preferred embodiments the object is an expandable tubular support element.

  According to still further features in the described preferred embodiments the expandable tubular support element includes a deformable mesh made of metal wire.

  According to still further features in the described preferred embodiments the expandable tubular support element includes a deformable mesh made of stainless steel wire.

  According to still further features in the described preferred embodiments the object is a stent.

  According to still further features in the described preferred embodiments the object is a stent assembly having at least one coating.

  According to still further features in the described preferred embodiments the object is a stent attached to a stent guidance system.

  According to still further features in the described preferred embodiments the object is an implantable medical device.

  According to still further features in the described preferred embodiments the object is an implantable medical device attached to a stent guidance system.

  According to still further features in the described preferred embodiments the method further comprises mounting an expandable tubular support element on the mandrel prior to releasing the charged liquefied polymer.

  According to still further features in the described preferred embodiments the method further includes discharging the charged liquefied polymer into the electric field through the at least one emitting element and then coating the mandrel so that the emitting element is against the mandrel. Moving and providing an expandable tubular support element with an inner coating.

  According to still further features in the described preferred embodiments the method further comprises providing at least one adhesive layer on the expandable tubular support element.

  According to still further features in the described preferred embodiments the at least one adhesive layer is an impermeable adhesive layer.

  According to another aspect of the invention, there is provided an apparatus for coating a non-rotating object with an electrospun coating, the apparatus having a potential difference with respect to the object, and within the electric field formed by the potential difference, It comprises at least one release element that can move relative to the object while discharging the charged liquefied polymer, thereby creating a jet of polymer fibers and coating the object.

  According to still further features in the described preferred embodiments of the invention the at least one discharge element is movable along a circular path.

  According to still further features in the described preferred embodiments the at least one release element is movable along a helical path.

  According to still further features in the described preferred embodiments the at least one discharge element is movable along a zigzag path.

  According to still further features in the described preferred embodiments the at least one emitting element is designed and configured such that the electric field can move in synchronism with the movement of the at least one emitting element.

  According to still further features in the described preferred embodiments the movement of the at least one discharge element is selected such that the polymer fiber jet establishes helical movement around the object, the helical movement gradually increasing in radius. It is a feature that becomes smaller.

  According to still further features in the described preferred embodiments the at least one emitting element comprises an array of electrodes.

  According to still further features in the described preferred embodiments the at least one discharge element comprises a rotatable ring having at least one capillary.

  According to still further features in the described preferred embodiments the rotatable ring is made of a dielectric material.

  According to still further features in the described preferred embodiments the rotatable ring is made of a conductive material.

  According to still further features in the described preferred embodiments the apparatus further comprises a bath containing the liquefied polymer, the bath being in fluid communication with the at least one discharge element.

  According to still further features in the described preferred embodiments the apparatus further comprises a pump for transferring the liquefied polymer from the bath to the at least one discharge element.

  According to still further features in the described preferred embodiments the apparatus further comprises a mechanism for moving the object parallel to the polymer fiber jet to uniformly distribute the polymer fiber on the object. ing.

  According to still further features in the described preferred embodiments the device further comprises a charged liquefied polymer, and further the drug is mixed with the charged liquefied polymer and then simultaneously with the liquefied polymer through at least one release element. Once released, the object is coated with an electrospun drug loaded coating.

  According to still further features in the described preferred embodiments the device further comprises a nebulizer that disperses the compact object comprising the drug between the polymer fibers.

  According to still another aspect of the present invention, (a) a stent assembly is provided, (b) the charged liquefied polymer is discharged into the electric field through at least one emitting element to form a jet of polymer fibers; A method of treating a stenotic vessel is provided that includes moving the release element relative to the stent assembly, coating the stent assembly with an electrospun coating, and then (c) placing the stent assembly within a stenotic vessel.

  According to still further features in the described preferred embodiments of the invention, the method further expands the stent assembly in a manner such that the flow constriction is substantially cleared. Inflating.

  According to still further features in the described preferred embodiments the movement of the at least one release element is selected to effect helical movement characterized by a gradually decreasing radius of the polymer fiber jet around the stent assembly. Is done.

  According to still further features in the described preferred embodiments the method further comprises the step of moving the stent assembly parallel to the jet of polymer fibers to uniformly distribute the polymer fibers over the stent assembly. Contains.

  According to still further features in the described preferred embodiments the drug is mixed with the charged liquefied polymer and simultaneously released with the liquefied polymer through at least one release element and the object is coated with an electrospun drug additive coating. .

  According to still further features in the described preferred embodiments the drug is dissolved in the charged liquefied polymer.

  According to still further features in the described preferred embodiments the drug is suspended in the charged liquefied polymer.

  According to still further features in the described preferred embodiments the drug is composed of particles embedded in polymer fibers.

  According to still further features in the described preferred embodiments the method further comprises constructing the drug into a dense object and dispersing the dense object between the polymer fibers.

  According to still further features in the described preferred embodiments the drug is heparin.

  According to still further features in the described preferred embodiments the drug is a radioactive compound.

  According to still further features in the described preferred embodiments the drug is silver sulfadiazine.

  According to still further features in the described preferred embodiments the high density object is a capsule.

  According to still further features in the described preferred embodiments the high density object is in powder form.

  According to still further features in the described preferred embodiments the dispersing of the high density object is effected by spraying.

  According to still further features in the described preferred embodiments the method further comprises providing at least one additional coating over the electrospun coating.

  The present invention succeeds in addressing the shortcomings of presently known configurations by providing a method and apparatus for coating a non-rotating object with an electrospun coating.

  Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

The present invention is described herein by way of example only with reference to the accompanying drawings. Referring now in particular to the detailed drawings, the details set forth are merely illustrative and are intended to illustrate the preferred embodiments of the present invention and provide what is deemed most useful. It is emphasized that the principles and conceptual aspects of the present invention can be readily understood by the description thereof. In this regard, the details of the structure of the present invention are not intended to be shown in more detail than is necessary for a basic understanding of the present invention. It will be apparent to those skilled in the art how to implement this form.
FIG. 1 is a schematic view of a prior art electrospinning apparatus.
FIG. 2a is a flow chart of a method for coating a non-rotating object with an electrospun coating according to a preferred embodiment of the present invention.
Figures 2b-e are schematic views of the movable path of the discharge element according to a preferred embodiment of the present invention.
FIG. 2f is a schematic illustration of a helical trajectory of a polymer fiber according to a preferred embodiment of the present invention.
FIG. 3 is a cross-sectional view of a stent assembly according to a preferred embodiment of the present invention.
FIG. 4a is an end view of a stent assembly according to a preferred embodiment of the present invention.
FIG. 4b is an end view of a stent assembly further having at least one adhesive layer according to a preferred embodiment of the present invention.
FIG. 5 shows a tubular support element designed and constructed to dilate a stenotic vessel of the body vasculature according to a preferred embodiment of the present invention.
FIG. 6 shows a portion of the tubular support element of FIG. 5 composed of a deformable mesh of metal wire, according to a preferred embodiment of the present invention.
FIG. 7 illustrates a stent assembly manufactured in accordance with the teachings of the present invention that occupies a defect site in an artery.
FIG. 8 shows a portion of a non-woven web of polymer fibers made according to a preferred embodiment of the present invention.
FIG. 9 shows a portion of a non-woven web of polymer fibers comprising a drug composed of high density objects and dispersed between electrospun polymer fibers.
FIG. 10 is a schematic diagram of an apparatus for coating a non-rotating object with an electrospun coating, according to a preferred embodiment of the present invention.
FIG. 11 is a flowchart of a method for treating a stenotic blood vessel according to a preferred embodiment of the present invention.

  The present invention is an invention of a method and apparatus for coating an object that can be an implantable medical device. Specifically, the present invention relates to an implantable medical device, such as, but not limited to, a non-rotating object, such as but not limited to a guidance system (eg, a stent guidance system) or a portion thereof. Can be used to apply electrospun films. The present invention is further an invention of a method for treating stenotic blood vessels.

  In order to better understand the invention illustrated in FIGS. 2-11, the structure and operation of the conventional (ie, prior art) electrospinning apparatus shown in FIG. 1 will first be described.

Before describing at least one embodiment of the present invention in detail, it is to be understood that the present invention is not limited to the details of the structure and arrangement of elements set forth in the following description or illustrated in the drawings. Should. The invention has other embodiments or can be practiced or carried out in other ways. It should also be understood that the terminology and terminology employed herein is for the purpose of explanation and should not be considered limiting.
Referring now to the drawings, FIG. 1 illustrates a conventional electrospinning device for producing nonwoven materials, generally referred to herein as device 1.

  The device 1 comprises a dispenser 2, for example a bath having one or more capillary openings 4. The discharger 2 serves to store the liquid (dissolved or melted) spun polymer. The emitter 2 is arranged at a predetermined distance from the deposition electrode 6 and a first axis 5 is defined between them. The deposition electrode 6 serves to form a structure on it. The deposition electrode 6 is usually manufactured according to the shape characteristics of the final product to be manufactured. For example, the deposition electrode 6 may be a mandrel having a longitudinal axis 3 that can be used when manufacturing a tubular structure.

  The emitter 2 is normally grounded, while the deposition electrode 6 is preferably connected to a negative voltage high voltage source (not shown in FIG. 1), between the emitter 2 and the deposition electrode 6. An electric field is formed. Alternatively, the deposition electrode 6 may be grounded and the emitter 2 may be connected to a positive voltage high voltage source.

  To produce a non-woven material, the liquefied polymer is extruded through the capillary opening 4 of the emitter 2, for example, under the action of static pressure or using a pump (not shown in FIG. 1). As soon as the extruded liquefied polymer meniscus is formed, the process of solvent evaporation or cooling is initiated, resulting in a capsule having a semi-rigid envelope or crust. Due to the potential difference between the emitter 2 and the deposited electrode 6, the electric field may cause a monopolar corona discharge in the region of the emitter 2. Since the liquefied polymer has a certain degree of conductivity, the capsule becomes charged. The repulsive electrical force in the capsule dramatically increases the static pressure. The semi-rigid envelope is stretched, a number of micro-break points are formed on the surface of each envelope, and a very thin jet of liquefied polymer is sprayed from the emitter 2.

  Due to the action of the Coulomb force, the jet moves away from the emitter 2 towards the opposite polarity electrode or deposition electrode 6. The jet travels at high speed through the space between the electrodes and is cooled or the solvent therein evaporates to form a polymer fiber jet that is collected on the surface of the deposited electrode 6 and is non-woven on the surface. A structure is formed. Tubular nonwoven structures are conventionally manufactured by rotating the deposition electrode 6 about the longitudinal axis 3 during the electrospinning process to coat the deposition electrode 6 into a tubular shape.

  A typical electrospinning process (for example, a process employed in the apparatus 1) is subject to a number of limitations.

  First, as will be appreciated by those skilled in the art, when the radius of curvature of the deposition electrode 6 is small, the polymer fibers tend to be arranged along the longitudinal axis 3 in the axial direction. In such a case, the generated structure has an axial strength that is greater than the radial strength. Therefore, when a small diameter product is manufactured by a conventional electrospinning method, the radial strength is limited.

  Second, conventional electrospinning methods for producing nonwoven tubular structures are limited to the production of hollow tubes. This is done by coating the deposition electrode 6 with an electrospun coating or by attaching a tubular member to the deposition electrode 6 before starting the electrospinning process. In any case, the final product removed from the deposition electrode 6 is hollow. However, while it is often required to produce a structure with additional members designed to engage the internal volume of the structure, in prior art electrospinning methods such internal members are It has been found that after removing the structure from the deposition electrode 6, it can simply be inserted into the non-woven structure. For example, conventional electrospinning techniques cannot coat a stent when it is already attached to a stent guidance system.

  Third, in the normal electrospinning method, the electric field generated between the emitter 2 and the deposition electrode 6 is an electrostatic electric field, so that the charged polymer fibers tend to be aligned by a field line, Move along the electrostatic path. This therefore limits the ability to control the fiber orientation and hence the strength of the final product.

  We hypothesized and anticipated the present invention that the object could be coated by moving the discharge element of the electrospinning device along a predetermined path while holding the object in a non-rotating or stationary state. And realized. The advantage of this embodiment where the object is in a non-rotating state is that the object does not need to be attached to the rotating electrode before being subjected to the electrospinning process, and not only hollow objects but also non-hollow objects can be coated. For example, using this embodiment, an electrospinning method can be used to attach a medical implantable device such as a stent, alone or while attached to a suitable guidance system, such as, but not limited to, a stent guidance system such as a catheter balloon. You can coat with. This embodiment improves strength and is usually sold by the seller as a “one unit product” where the medical implantable device is attached to or integral with the additional member or device. It is useful when it is desired to form a mechanical barrier and / or incorporate a drug into a commercially available medical implantable device that is being supplied.

  Reference is now made to FIG. 2a, which is a flow chart of a method of coating a non-rotating object of a preferred embodiment of the present invention. In the first step of this method, shown in block 7 in FIG. 2a, the charged liquefied polymer is released into the electric field through at least one emitting element to form a jet of polymer fibers. In the second step of the method, indicated by block 8, the emitting element is moved relative to the object to coat the object with the electrospun coating. Single or multiple emitting elements can change the direction and / or magnitude of the electric field while moving along a predetermined path. These changes can be adjusted according to the polymer fiber orientation required on the object, as detailed above.

  As previously mentioned, the discharge element can be moved along a predetermined path. The path is preferably selected to coat the entire object or a selected portion as desired. If the shape of the object is tubular (eg, cylindrical), the emitter can be a spiral path (FIG. 2b), circular path (FIG. 2c), zigzag path (FIG. 2d-), for example, as shown in FIG. 2b-d. e) and so on. The path and the parameters characterizing the path are preferably selected according to the desired orientation of the fibers on the object. Several transfer element sweeps moving along the object can be employed to improve the uniformity of the electrospun coating. The number of migration curves employed is selected depending on the porosity required for the coating, and the average pore size decreases as the number of migration curves increases. In addition, the density of the fibers and / or the type of liquefied polymer can be changed from the first transfer curve to the subsequent transfer curve to provide a multilayer coating as described in detail below.

  The movement of the discharge element can be supplemented by translation of the object relative to the polymer fiber jet (eg, reciprocation, harmonic movement, etc.). This embodiment is particularly useful when the discharge element travel path is a planar path (eg, a circular path), for example, when the object reciprocates relative to the ejection element travel plane, the fibers move along the object. Re-dispersion improves coating uniformity.

  According to the electrospinning principle, an electric field is generated by the potential difference between the emitting element and the object. A typical potential difference is about 20 kV to about 50 kV. Such a potential difference can be achieved, for example, by grounding the emitting element and placing the object at a negative potential, or by other electrostatic configurations that ensure that the charged liquefied polymer moves from the emitting element toward the object. When the object has a conductive portion (eg, a metal mesh of a stent), the conductive portion can be preferably connected to a negative polarity voltage source. If the object is non-conductive, or if desired, the object can be attached to a deposition electrode (eg, a mandrel) and connected to a voltage source.

  As the fiber travels through space, it experiences a frictional force caused by a collision between the medium (usually air) molecules around the object and the fiber molecules. The higher the density of the surrounding medium, the greater the friction force. In a preferred embodiment of the present invention, the velocity of the discharge element is selected so that the polymer fiber obtains a sufficient lateral velocity with respect to the axis defined by the discharge element and the object (see, for example, axis 5 shown in FIG. 1). Is done. Typical linear velocities of the emitting element are from about 100 cm / sec to about 3000 cm / sec. When the discharge element is rotationally moved (e.g., helical movement, circular movement, etc.), the normal rotational speed is about 100 rpm to about 1200 rpm.

  The term “about” as used herein means ± 10%.

  Thus, the path of the polymer fiber in the media around the object is determined by (i) the electrical force applied by the electric field, (ii) the frictional force applied by the molecules of the surrounding media, and (iii) the transverse velocity of the fiber. As will be appreciated by those skilled in the art, when the electrospinning process is performed in a vacuum, there is no frictional force and the polymer fiber trajectory is determined solely by the electrical force and the lateral velocity. Therefore, when the electrospinning method is performed in a gaseous medium, the trajectory of the polymer fiber becomes a curve, whereas when it is performed in a vacuum, the trajectory of the polymer fiber becomes substantially straight because there is no friction.

  Besides the lateral velocity of the fiber, the fiber also accelerates in the direction of the electric field line due to the influence of the electric field. Thus, the direction of movement of the fiber at a given time is the (vector) sum of the velocity achieved in the transverse direction and the velocity in the electric field direction. For example, as the discharge element moves along a circular path, the fiber jet moves in a helical motion characterized by a gradually decreasing radius. A representative example of a helical path is shown in FIG.

  Polymer fibers have a relatively small mass per unit length, but the amount of movement they acquire due to tangent movement is sufficient to stabilize the movement of the fiber in space against the perturbation of the electric field. The inventors of the present invention have discovered this. If the object is tubular and the discharge element is moving in a circle, the amount of movement that the fiber acquires at the rotational speed of the circle movement is sufficient to provide a coating in which the fiber has a dominant orientation space orientation. Something has been discovered. In this regard, the higher the rotational speed, the higher the degree of orientation. According to a preferred embodiment of the present invention, the movement characteristics (e.g., path, linear speed, rotational speed) of the release element are at least 60%, more preferably at least 80%, most preferably at least 90% of the polymer fibers. , Selected to be oriented with respect to the longitudinal axis of the object. Additionally or alternatively, the movement characteristics (e.g., path, linear speed, rotational speed) of the emitting element are such that the electrospun coating is at least 300%, more preferably at least 400%, most preferably without breaking. Selected to be at least 500% radially expandable.

  The inventors of the present invention further discovered that movement of the discharge element substantially reduces the spray angle of the jet, thus creating a more concentrated jet and reducing the average pore size of the final coating. It was. The jet angle can be further reduced by judicious selection of the geometry of the emitting element and hence the magnitude and direction of the electric field in the vicinity of the object and along the fiber trajectory. According to a preferred embodiment of the present invention, the movement and / or shape of the discharge element is selected such that the spray angle is at least 10%, more preferably at least 30%, most preferably at least 60%. Thus, by combining electrical force, friction force, lateral velocity and preferably translation of the object, not only the density of the final coating but also the orientation and porosity can be controlled.

  For example, in applications where an electrospun coating is applied to a stent or other medical tubular implant, the properties of the coating need to be suitable for implantation. Specifically, in order to obtain a high radial strength, it is preferred that the fiber has a high azimuthal orientation, which can be obtained by selecting a circular movement of the emitting element, as already mentioned. . Furthermore, in the case of vascular grafts such as stents and vascular prostheses, the porosity is such that cells can migrate from the surrounding tissue and proliferate while the stent or vascular prosthesis is in place. It is selected to be easy and at the same time prevent unwanted chemicals and plaque fragments from entering the vessel lumen.

  Furthermore, the controllable porosity of this embodiment allows the design of a drug local delivery element that can incorporate a drug or another medicament into the coating. In such devices, the porosity of the coating can preferably be designed to have an independent drug load and act as a barrier to control the drug release rate.

  This embodiment of the present invention can be used to coat stent expandable tubular support elements as well as stent assemblies that already have a pre-coating. In any event, the above method can be used to provide a single coating as well as a multilayer coating such as the coating disclosed in International Patent Application No. PCT / IL01 / 01171. The contents of this patent application are incorporated herein by reference.

  Reference is now made to FIG. 3, which is a schematic cross-sectional view of a stent assembly coated using selected steps of the method of the present invention. The stent assembly includes an expandable tubular support element 10 and at least one coating 12 having a predetermined porosity. The coating 12 includes an inner coating 14 that lines the inner surface of the element 10 and an outer coating 16 that covers the outer surface of the element 10. FIG. 4 a is an end view of the stent assembly showing element 10 coated on the inside with an inner coating 14 and on the outside with an outer coating 16. Turning to FIG. 4b, the coating 12 further has at least one adhesive layer 15 for adhering the elements of the stent assembly, as will be described in more detail below.

  Inner coating 14 and outer coating 16 can each be provided utilizing the above method by moving the release element relative to expandable support element 10. Inner coating 14 and outer coating 16 preferably have a predetermined porosity that may be made of different liquefied polymers and may be different or the same, as desired. According to a preferred embodiment of the present invention, the liquefied polymer of the inner coating 14 and / or outer coating 16 may be mixed with a drug or medicament prior to the electrospinning process. The drug may be dissolved or suspended in the liquefied polymer.

  There are two or more ways to provide the outer coating 16. In one embodiment, element 10 is attached to a deposition electrode (eg, a mandrel) prior to performing the electrospinning process. In this embodiment, the deposition electrode functions as a carrier for the element 10 and as a conductive element that applies a high voltage to create an electric field. As a result, the polymer fibers emerging from the release element are released toward the deposition electrode, forming an outer coating 16 on the tubular support element 10. This coating covers both the metal wires of element 10 and the gaps between these wires.

  In another embodiment, element 10 serves as a deposition electrode. In this embodiment, the polymer fibers are exclusively attracted to the wire of the tubular support element 10 that exposes the interstices present therebetween. Thus, the resulting coated stent has pores that facilitate delivery of the drug from the stent assembly into the body vasculature.

  According to a preferred embodiment of the present invention, the inner coating 14 is installed as follows. First, the mandrel is directly coated using an electrospinning method, and the inner coating 14 is formed on the mandrel. Once the mandrel has been coated, the electrospinning process is temporarily stopped and the element 10 is slid over the mandrel and pulled onto the inner coating 14. The outer coating 16 is provided on the element 10 by restarting the electrospinning process.

  Since the operation of providing the inner coating 14 needs to stop the process for a specific period, most of the solvent contained in the inner coating 14 can be evaporated. As a result, when the process is resumed, the adhesion between the elements of the stent assembly is reduced and the coating is layered after the stent-graft is opened.

  The present invention successfully handles the above constraints with two optimization methods. According to one method, the outer sublayer of the inner coating 14 and the inner sublayer of the outer coating 16 are each manufactured by electrospinning with an increased capacity. Typical capacity increases are in the range of about 50% to about 100%. This method produces a dense adhesive layer made of thick fibers and having a significantly increased solvent content. The typical thickness of the adhesive layer is in the range of about 20 μm to about 30 μm and is small compared to the overall diameter of the stent assembly, so it does not significantly affect the general parameters of the coating. According to another method, the adhesive layer contains another polymer that has a lower molecular weight than the main polymer and is more elastic and reactive.

  Other ways of improving the adhesion between the layer and the tubular support element 10 can also be employed. For example, a method of putting various adhesives, primers, welding agents, and chemical binders in a solvent fume can be used. Examples of suitable materials are silanes such as aminoethylaminopropyltriacetoxysilane.

  The advantage of using an electrospinning method to produce the inner coating 14 and outer coating 16 is the flexibility to select the type of polymer and the fineness of the fiber, so that strength as described herein The end product is provided with the requisite combination of properties, such as elasticity. Furthermore, the alternating sequence of sub-layers formed in the coating 12, each made of fibers of different orientation, determine the nature of the dispersion of porosity along the wall thickness of the stent assembly. In addition, the electrospinning method has the advantage that various components, such as pharmaceuticals, can be incorporated into the fiber by mixing them into the liquefied polymer prior to electrospinning.

  Reference is now made to FIG. 5, which is a schematic illustration of a tubular support element 10 designed and constructed to dilate a constricted blood vessel of the body vasculature. Element 10 expands radially to dilate the stenotic blood vessel. According to a preferred embodiment of the present invention, the expandability of the stent assembly can be optimized by the appropriate structure of the element 10 and the coating 12. First, the structure of the element 10 will be described with reference to FIG. 6, and then the structure of the coating 12 will be described.

  Thus, FIG. 6 shows a portion of the element 10 made of a deformable mesh made of metal wire 18, for example made of stainless steel wire. When the stent assembly is positioned at a desired location within the artery, the element 10 can be radially expanded to substantially expand the arterial tissue around the stent assembly to eliminate arterial stenosis. The expansion can be done by any method known in the art, for example using a balloon catheter, or by making the element 10 of a material that exhibits shape memory properties that are activated at a temperature, such as Nitinol. Can be implemented. In this preferred embodiment of the invention, the polymer fibers forming the coating 12 are elastomeric polymer fibers that stretch when the element 10 is radially expanded. In a preferred embodiment of the invention, the inner coating 14 and the outer coating 16 expand simultaneously with the element 10. That is, the tubular support element 10 is substantially coated. Alternatively, the inner coating 14 and / or the outer coating 16 may be shorter than the element 10, in which case at least one end of the element 10 is exposed.

  Reference is now made to FIG. 7 illustrating a stent assembly that occupies an arterial defect site 20. The outer diameter of the unexpanded stent assembly including the outer coating 16 is sized to ensure that the stent assembly is moved through the artery to the defect site 20, for example by a catheter. The expansion range of the stent assembly is the range having a maximum diameter that, when the expanded assembly is in place at the defect site 20, expands the arterial tissue around the stent assembly to such an extent that the flow site constriction is cleared. It is.

  When a stent assembly is implanted in a blood vessel, disorders such as damage, restenosis, in-stent stenosis, and cell overgrowth that are added to the tissue of the vessel at the time of implantation may occur in the vessel. To treat disorders such as injury, a drug that delivers a drug to the body vasculature may be included. Thus, the coating 12 not only serves to implant the assembly into the artery, but also serves as a reservoir for storing the drug to be delivered over an extended period of time. Within the diameter limit, the greater the total volume of the coating 12, the greater the capacity of the coating that stores the drug.

  Reference is now made to FIG. 8, which illustrates a portion of a non-woven web of polymer fibers made according to a preferred embodiment of the present invention. The fibers 22, 24 and 26 intersect and join at the intersection, and the resulting gap makes the web highly porous. Electrospun fibers are extremely thin and have an extraordinarily large surface area, allowing large amounts of drugs and drugs to be incorporated onto the surface. Since the surface area of the electrospun polymer fiber is close to the surface area of the activated carbon, the non-woven web of the polymer fiber is an effective device for delivering the drug locally.

  The preferred mechanism for releasing the drug from the coating is the mechanism by diffusion, regardless of the method employed to embed the drug in the coating. The period of release of the therapeutic drug at a predetermined concentration depends on a number of variables that can be controlled during the manufacturing process. One variable is the chemistry of the carrier polymer and the chemical means to attach the drug to it. This variable can be controlled by appropriate selection of one or more polymers used in the electrospinning process. Another variable is the contact area between the body and the drug. This contact area can be controlled by changing the free surface of the electrospun polymer fiber. Also, the method used to incorporate the drug within the at least one coating 12 affects the duration of drug release, as further described herein.

  According to a preferred embodiment of the invention, the coating has a number of sublayers. Depending on their purpose, these sublayers can be distinguished by fiber orientation, polymer type, drug incorporated therein and the desired rate of drug release. Thus, the release of drugs for the first hours and days after implantation incorporates solid solutions containing drugs such as anticoagulants and antithrombotic agents into a sublayer of readily soluble biodegradable polymer fibers. Can be achieved. Drugs released during the first period after transplantation include anticoagulants and antithrombotic agents.

  Referring now again to FIG. 8, the drug may be composed of particles 28 embedded in electrospun polymer fibers that form at least one sublayer of the coating 12. This method is useful for releasing the drug during the first days and weeks after surgery. Drugs for this purpose include antibacterial or antibiotics, thrombolytic drugs, vasodilators and the like. The duration of the delivery method is affected by the type of polymer used to produce the corresponding sublayer. Specifically, the optimum release rate is ensured by using a reasonably stable biodegradable polymer.

  FIG. 9 illustrates another method of incorporating a drug into the coating that ensures drug release for the first days or weeks after surgery. Thus, according to a preferred embodiment of the present invention, the drug consists of high density objects 30 dispersed between the electrospun polymer fibers of the coating. The dense object 30 may be any known shape, such as, but not limited to, a capsule of a reasonably stable biodegradable polymer.

  The present invention can also provide a method of drug release that can last for months to years. According to a preferred embodiment of the invention, the drug is dissolved or encapsulated in a sublayer made of biologically stable fibers. Since the rate of diffusion from within the biologically stable sublayer is substantially low, the duration of drug release is reliably extended. Drugs suitable for extending such release periods include, but are not limited to, antiplatelet substances, growth factor antagonists and free radical scavengers.

  Thus, the order of drug release and the lifetime of action of a particular specific drug is determined by the type of polymer in which the drug is incorporated, the method by which the drug is introduced into the electrospun polymer fibers, the order of the layers forming the coating, each layer Determined by the specificity of the form of the matrix and the concentration of the drug.

  Reference is now made to FIG. 10, which is a schematic illustration of an apparatus 50 for coating a non-rotating object 52 with an electrospun coating, according to a preferred embodiment of the present invention. The apparatus 50 comprises at least one discharge element 37 that has a potential difference with respect to the object 52, which discharge element 37 moves relative to the object 52 while discharging the charged liquefied polymer, as will be described in detail below. it can. Arranged in the discharge element 37 is, for example, an electrode or a rotatable ring 45 with at least one capillary 46 which is preferably oriented radially. The ring 45 can be made of an insulating material or a conductive material as required. The capillaries 46 are made of a conductive material and they are in electrical communication. The number of capillaries is preferably 1-10 or more, more preferably 2-4, and most preferably 3. The diameter of the ring 45 and the length of the capillary 46 is such that the distance between the object 52 and the tip 51 of the capillary 46 is preferably about 100 mm to about 250 mm, more preferably about 120 mm to about 180 mm, and most preferably about 150 mm. Selected to be.

  In a preferred embodiment of the invention, the discharge element 37 is connected to a shaft 47 having at least one arm 48. Arm 48 and shaft 47 are preferably hollow elements through which the liquefied polymer can flow. Alternatively, a flexible tube system can be used to achieve fluid communication between the discharge element 37 and the bath 41 holding the liquefied polymer. The shaft 47 is preferably disposed between one or more bearings 58 and serves to mechanically connect the discharge element 37 to the motor 54.

  The device 50 further comprises a mandrel 42 that can be connected to a power source 43 in embodiments where the mandrel 42 acts as a conductive electrode. The mandrel 42 or object 52 (in the embodiment that does not use the mandrel 42) is preferably operatively associated with a mechanism 56 that translates the object 52 as described in detail above.

  In a preferred embodiment of the invention, the device 50 further comprises a pump 40, which is connected to a bath 41 for drawing the liquid polymer stored therein into the discharge element 37. The device 50 further comprises one or more filters 49 through which the liquefied polymer is transported into the element 37 through the shaft 47 and the arm 48.

  Optionally and preferably, the device 50 comprises a nebulizer 57 for dispersing a dense object made of drug (eg, object 30) between polymer fibers, as described in detail above. .

  Reference is now made to FIG. 11, which is a flowchart of a method for treating a stenotic blood vessel according to a preferred embodiment of the present invention. In the first step of the method, indicated by block 60 in FIG. 11, a stent assembly is provided. In a second step, indicated by block 62, the charged liquefied polymer is released through the moving release element as described in detail above. In the third step of the method, indicated by block 64, the stent assembly is placed in a stenotic vessel using, for example, a catheter balloon or other stent guidance system. In the fourth step of this method, indicated by block 66, the stent assembly is preferably expanded to expand the arterial tissue around the stent assembly to the extent that it clears the stenosis of the vessel flow.

  Although the present invention has been described in combination with a medical implant, it should be understood that other medical implants that are not necessarily tubular structures can be coated using the method of the present invention. For example, grafts and patches can be coated prior to implantation or application, so that they can be loaded with drugs and enjoy the benefits described above.

  The coating can be made from any known biocompatible polymer. The polymer fiber of the drug containing layer is preferably a combination of a biocompatible polymer and a biologically stable polymer.

  Representative examples of biologically stable polymers with relatively small chronic tissue reactions include, but are not limited to, polycarbonate-based aliphatic polyurethanes, siloxane-based aromatic polyurethanes, silicone rubbers such as polydimethylsiloxane , Polyesters, polyolefins, polymethyl methacrylate, vinyl halide polymers and copolymers, polyaromatic vinyls, polyvinyl esters, polyamides, polyimides, polyethers and suitable solvents and on the stent There are many other polymers that can be electrospun.

  Biodegradable fiber-forming polymers that can be used include poly (L-lactic acid), poly (lactide-co-glycolide), polycaprolactone, polyphosphate ester, poly (hydroxybutyric acid), poly (glycolic acid), poly (DL -Butyric acid), poly (amino acids), cyanoacrylates, several copolymers and biomolecules such as DNA, silk, chitosan and cellulose.

  These hydrophilic polymers and hydrophobic polymers that are easily degraded by microorganisms and enzymes are suitable as materials for encapsulating drugs. In particular, polycaprolactone is particularly suitable for controlling drug release over an extended period of time in the range of about 2 years to about 3 years because it has a slower degradation rate than most other polymers.

  Suitable medicaments that can be incorporated into at least one coating 12 include heparin, tridodecylmethylammonium heparin, epothilone A, epothilone B, rotomycin, ticlopidine, dexamethasone, caumadin, and antithrombotic. Drugs, estrogens, corticosteroids, cytostatics, anticoagulants, vasodilators, antiplatelet drugs, thrombolytics, antibacterial or antibiotics, mitotic inhibitors, anticell proliferative drugs, antisecretory There are other drugs that usually fall in the category of drugs, non-steroidal anti-inflammatory drugs, growth factor antagonists, free radical scavengers, antioxidants, radiopaque drugs, immunosuppressive drugs and radioisotope labeling drugs.

  Many related implantable medical devices will be developed during the lifetime of this patent, but the scope of the term “implantable medical device” includes all such new technologies a priori. Conceivable.

  Additional objects, advantages and novel features of the present invention will become apparent to those skilled in the art upon examination of the following examples, which are not intended to be limiting. Furthermore, the various embodiments and aspects of the present invention described above and claimed in the claims section of this application are each supported by the tests of the following examples.

  The following examples will be described together with the above description to illustrate the present invention without limiting it.

Materials, Equipment and Methods Carbothane PC-3575A was purchased from Thermedics Polymer Products and used for coating. This polymer has satisfactory fiber-forming performance, is biocompatible and can incorporate lipophilic drugs. A mixture of dimethylformamide and toluene in a ratio ranging from 1: 1 to 1: 2 was used as the solvent for all experiments.

  A PHD 2000 syringe pump was purchased from Harvard Apparatus and used to feed the polymer solution to the electrospinning apparatus. The discharge element comprises a hollow ring made of stainless steel tube and having a diameter of 400 mm. Three capillaries with a length of 25 mm and an inner diameter of 0.5 mm are arranged symmetrically on the inner surface of the ring. The flow rate in each capillary is 1 ml / min to 5 ml / min. The discharge element was connected to the pump with a flexible polytetrafluoroethylene tube and grounded. A polished stainless steel rod having a diameter of 1.05 mm and a length of 60 mm was used as a mandrel and held at a potential of 30 kV. The mandrel was placed at the geometric center of the ring about 175 mm away from the end of the capillary.

  The ring was rotated at a rotational speed of 60-1000 rpm, and the mandrel was reciprocated longitudinally with an amplitude of 30-40 mm and a rotational speed of 12-13 times / minute.

Example 1
A 16 mm long stent assembly was manufactured using a stainless steel stent with a expanded diameter of 3.4 mm and an unexpanded diameter of 1.1 mm as the tubular support element. The stainless steel stent used is usually used for angioplasty with a catheter and a balloon. To increase adhesion when coating the polymer, the stent was exposed to a 160-180 kJ / m ² corona discharge, rinsed with ethyl alcohol and deionized water, and then dried in a stream of nitrogen gas. The solution parameters were 8% concentration, 560 cP viscosity and 0.8 mS conductivity. As a medicine, a solution in which heparin was dissolved in tetrahydrofuran at a concentration of 250 U / ml was used. The ratio of polymer: heparin solution was 100: 1. The rotational speed of the discharge element was 60 rpm.

  A two-step coating method was employed. In the first step, the mandrel was coated with a layer of polymer fibers having a thickness of about 20 μm by electrospinning. Once this first step was performed, a tubular support element was placed over the first coating to obtain an inner coating of the tubular element. In the second step, an outer coating was applied to the outer surface of the tubular support element. The thickness of the outer coating was about 40 μm.

  The stent assembly was removed from the mandrel and placed in a 45 ° C. saturated dimethylformamide (DMF) vapor atmosphere for about 30 seconds to ensure increased adhesion between the inner and outer coatings. To remove residual solvent, the stent was partially vacuum treated for approximately 24 hours. Once the coating process was complete, the elasticity was tested by radially expanding the coated stent.

  The resulting coated fibers were randomly oriented. The coating could expand 320% in the radial direction without rupturing.

Example 2
The stent assembly was manufactured as described in Example 1 with the rotational speed increased to 600 rpm. About 80% of the fibers of the resulting coating were oriented. The coating was able to expand 410% in the radial direction without rupturing.

Example 3
The stent assembly was manufactured as described in Example 1 with the rotational speed increased to 1000 rpm. The resulting coating was more uniform and the fibers were mostly azimuthally oriented, i.e. about 95% of the fibers were azimuthally oriented and the coating could expand 550% in the radial direction without rupturing. .

Example 4
A stent assembly was prepared as described in Example 2 using a 380 U / ml heparin solution mixed with a 15% solution obtained by dissolving poly (DL-lactide-CD-glycolide) in chloroform. . Thus, changing the drug did not affect the properties of the coating.

Example 5
A stent assembly having a 60 μm thick inner coating of heparin-loaded biodegradable polymer and an outer coating of polyurethane fibers and a total coating thickness of 100 μm was manufactured using the materials described in Example 1. Rotational speeds of 60 rpm and 1000 rpm were used to provide the inner and outer coatings, respectively. The resulting inner coating was dominated by axial (longitudinal) orientation, while the outer coating was dominated by azimuthal orientation. Thus, it has been demonstrated that the fiber orientation can be controlled and determined by the rotational speed of the release element.

  It will also be appreciated that the features of the invention described in separate embodiments for clarity can be combined and provided in a single embodiment. Conversely, the various features of the invention described in a single embodiment for the sake of brevity can also be provided separately or in appropriate subcombinations.

  While the invention has been described in specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, the present invention is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents, and patent applications cited herein are as complete as if each individual publication, patent or patent application was specifically and individually cited herein. Is incorporated herein by reference. Further, citation or mention of a document in this application shall not be construed as an admission that such document is available as the prior art of the present application.

1 is a schematic view of a prior art electrospinning apparatus. FIG. 2 is a flow chart of a method for coating a non-rotating object with an electrospun coating according to a preferred embodiment of the present invention. Figures 2b-e are schematic views of the movable path of the discharge element according to a preferred embodiment of the present invention. FIG. 2f is a schematic illustration of a helical trajectory of a polymer fiber according to a preferred embodiment of the present invention. 1 is a cross-sectional view of a stent assembly according to a preferred embodiment of the present invention. FIG. 4a is an end view of a stent assembly according to a preferred embodiment of the present invention. FIG. 4b is an end view of a stent assembly further having at least one adhesive layer according to a preferred embodiment of the present invention. Fig. 3 shows a tubular support element designed and constructed for dilating a stenotic vessel of the body vasculature according to a preferred embodiment of the present invention. FIG. 6 shows a portion of the tubular support element of FIG. 5 composed of a deformable mesh of metal wire according to a preferred embodiment of the present invention. Fig. 4 illustrates a stent assembly manufactured in accordance with the teachings of the present invention that occupies a defect site in an artery. Figure 2 shows a portion of a nonwoven web of polymer fibers made according to a preferred embodiment of the present invention. Figure 3 shows a portion of a non-woven web of polymer fibers comprising a drug composed of high density objects and dispersed between electrospun polymer fibers. 1 is a schematic diagram of an apparatus for coating a non-rotating object with an electrospun coating, in accordance with a preferred embodiment of the present invention. 2 is a flowchart of a method for treating a stenotic blood vessel according to a preferred embodiment of the present invention.

Claims (92)

  A method of coating a non-rotating object with an electrospun coating, wherein the charged liquefied polymer is discharged into the electric field through at least one emitting element to form a jet of polymer fibers, the emitting element being applied to the object Moving and coating the object with an electrospun film.   The method of claim 1, wherein the movement of the at least one discharge element is at least in part a helical path.   The method of claim 1, wherein the movement of the at least one discharge element is at least in part a circular path.   The method of claim 1, wherein the movement of the at least one emitting element is at least in part a zigzag path.   The method of claim 1, further comprising moving the electric field in synchronization with the movement of the at least one emitting element.   2. The movement of the at least one emitting element is selected to establish a helical movement of the jet of the polymer fiber around an object, the helical movement being characterized by a gradually decreasing radius. The method described.   The method of claim 1, further comprising translating the object relative to the jet of polymer fibers to uniformly disperse the polymer fibers on the object.   The method according to claim 7, wherein the translation of the object is a reciprocating movement.   The method according to claim 7, wherein the translation of the object is a harmonic movement.   The method of claim 1, wherein the object has a tubular shape.   The method of claim 1, wherein the object is an expandable tubular support element.   The method of claim 11, wherein the expandable tubular support element comprises a deformable mesh made of metal wire.   The method of claim 11, wherein the expandable tubular support element comprises a deformable mesh made of stainless steel wire.   The method of claim 1, wherein the object is a stent.   The method of claim 1, wherein the object is a stent assembly having at least one coating.   The method of claim 1, wherein the object is a stent attached to a stent guidance system.   The method of claim 1, wherein the object is an implantable medical device.   The method of claim 1, wherein the object is an implantable medical device attached to a stent guidance system.   The method of claim 1, wherein a drug is mixed with the charged liquefied polymer and simultaneously released through the at least one release element with the liquefied polymer, and the object is coated with an electrospun drug additive coating.   20. The method of claim 19, wherein the drug is dissolved in the charged liquefied polymer.   20. The method of claim 19, wherein the drug is suspended in the charged liquefied polymer.   20. The method of claim 19, wherein the drug is comprised of particles embedded in the polymer fiber.   20. The method of claim 19, wherein the drug is heparin.   20. The method of claim 19, wherein the drug is a radioactive compound.   20. The method of claim 19, wherein the drug is silver sulfadiazine.   The method of claim 1, further comprising configuring a drug into a high density object and dispersing the high density object between the polymer fibers.   27. The method of claim 26, wherein the drug is heparin.   27. The method of claim 26, wherein the drug is a radioactive compound.   27. The method of claim 26, wherein the drug is silver sulfadiazine.   27. The method of claim 26, wherein the high density object is a capsule.   27. The method of claim 26, wherein the high density object is in powder form.   27. The method of claim 26, wherein the dispersion of the dense object is performed by spraying.   The method of claim 11, further comprising mounting the expandable tubular support element on a mandrel prior to releasing the charged liquefied polymer.   In order to release the charged liquefied polymer into the electric field through the at least one emitting element and then coat the mandrel, the emitting element is moved relative to the mandrel to coat the expandable tubular support element with an inner coating. 34. The method of claim 33, further comprising: providing.   The method of claim 11, further comprising providing at least one adhesive layer on the expandable tubular support element.   36. The method of claim 35, wherein the at least one adhesive layer is an impermeable adhesive layer.   37. The method of claim 36, wherein the at least one adhesive layer is an impermeable adhesive layer.   The method of claim 1, further comprising providing at least one additional coating over the electrospun coating.   An apparatus for coating a non-rotating object with an electrospun film, having a potential difference with respect to the object, and moving relative to the object while discharging a charged liquefied polymer into the electric field formed by the potential difference An apparatus comprising at least one discharge element capable of creating a polymer fiber jet and coating an object.   40. The apparatus of claim 39, wherein the at least one discharge element is movable along a helical path.   40. The apparatus of claim 39, wherein the at least one discharge element is movable along a circular path.   40. The apparatus of claim 39, wherein the at least one discharge element is movable along a zigzag path.   40. The apparatus of claim 39, wherein the at least one emitting element is designed and configured such that the electric field moves synchronously with the movement of the at least one emitting element.   40. The movement of the at least one discharge element is selected such that the jet of the polymer fiber establishes a helical movement around an object, the helical movement being progressively smaller in radius. The device described.   40. The apparatus of claim 39, wherein the at least one emitting element comprises an array of electrodes.   40. The apparatus of claim 39, wherein the at least one discharge element comprises a rotatable ring having at least one capillary.   The apparatus of claim 45, wherein the rotatable ring is made of a dielectric material.   46. The apparatus of claim 45, wherein the rotatable ring is made of a conductive material.   40. The apparatus of claim 39, further comprising a bath containing a liquefied polymer, wherein the bath is in fluid communication with the at least one discharge element.   50. The apparatus of claim 49, further comprising a pump that transfers the liquefied polymer from the bath to the at least one discharge element.   40. The apparatus of claim 39, further comprising a mechanism for moving the object parallel to the jet of polymer fibers to uniformly disperse the polymer fibers on the object.   52. The apparatus of claim 51, wherein the translation of the object is a reciprocating movement.   52. The apparatus of claim 51, wherein the translation of the object is a harmonic movement.   The charged liquefied polymer is further included, and a drug is further mixed with the charged liquefied polymer and simultaneously released through the at least one release element together with the liquefied polymer, and the object is coated with an electrospun drug additive coating. 40. The apparatus of claim 39.   55. The device of claim 54, wherein the drug is dissolved in the charged liquefied polymer.   55. The device of claim 54, wherein the drug is suspended in the charged liquefied polymer.   55. The device of claim 54, wherein the drug is comprised of particles embedded in the polymer fiber.   55. The device of claim 54, wherein the drug is heparin.   55. The device of claim 54, wherein the drug is a radioactive compound.   55. The device of claim 54, wherein the drug is silver sulfadiazine.   40. The apparatus of claim 39, further comprising a nebulizer that disperses a high density object comprising a drug therein between the polymer fibers.   62. The device of claim 61, wherein the drug is heparin.   62. The device of claim 61, wherein the drug is a radioactive compound.   62. The device of claim 61, wherein the drug is silver sulfadiazine.   62. The apparatus of claim 61, wherein the high density object is a capsule.   62. The apparatus of claim 61, wherein the high density object is in powder form. (A) preparing a stent assembly;
(B) discharging the charged liquefied polymer into an electric field through at least one emitting element to form a jet of polymer fibers and moving the emitting element relative to the stent assembly to electrospun the stent assembly; And (c) treating the stenotic vessel comprising placing the stent assembly within the stenotic vessel.   68. The method of claim 67, further comprising expanding the stent assembly to expand tissue around the stent assembly in a manner such that flow constriction is substantially cleared.   68. The method of claim 67, wherein the movement of the at least one release element is at least in part a helical path.   68. The method of claim 67, wherein the movement of the at least one discharge element is at least in part a circular path.   68. The method of claim 67, wherein the movement of the at least one discharge element is at least in part a zigzag path.   68. The method of claim 67, further comprising moving the electric field synchronously with the movement of the at least one emitting element.   The movement of the at least one release element is selected to establish a helical movement of the jet of the polymer fiber around the stent assembly, the helical movement being progressively smaller in radius. 68. The method according to 67.   68. The method of claim 67, further comprising moving the stent assembly parallel to the jet of polymer fibers to uniformly distribute the polymer fibers over the stent assembly.   75. The method of claim 74, wherein the translation of the stent assembly is a reciprocal movement.   75. The method of claim 74, wherein the translation of the stent assembly is a coordinated movement.   68. The method of claim 67, wherein the stent assembly is attached to a stent guidance system.   68. The method of claim 67, wherein a drug is mixed with the charged liquefied polymer and simultaneously released through the at least one release element with the liquefied polymer, and the object is coated with an electrospun drug additive coating.   79. The method of claim 78, wherein the drug is dissolved in the charged liquefied polymer.   79. The method of claim 78, wherein the drug is suspended in the charged liquefied polymer.   79. The method of claim 78, wherein the drug is composed of particles embedded in the polymer fiber.   79. The method of claim 78, wherein the drug is heparin.   79. The method of claim 78, wherein the drug is a radioactive compound.   79. The method of claim 78, wherein the drug is silver sulfadiazine.   68. The method of claim 67, further comprising configuring a drug into a high density object and dispersing the high density object between the polymer fibers.   86. The method of claim 85, wherein the drug is heparin.   86. The method of claim 85, wherein the drug is a radioactive compound.   86. The method of claim 85, wherein the drug is silver sulfadiazine.   86. The method of claim 85, wherein the high density object is a capsule.   86. The method of claim 85, wherein the high density object is in powder form.   86. The method of claim 85, wherein the dispersion of the dense object is performed by spraying.   68. The method of claim 67, further comprising providing at least one additional coating over the electrospun coating.

Images