Method and system for coating a surface of a medical device with a therapeutic agent and drug eluting medical devices made thereby

#This invention relates generally to medical devices intended for implant in a mammal and, more particularly to a method and system for forming a drug eluting coating on a medical device avoiding the necessity of using a polymer matrix to retain the drug or control its elution properties.

#Medical devices intended for implant into the body or bodily tissues of a mammal (including a human), as for example medical prostheses or surgical implants, may be fabricated from a variety of materials including various metals, metal alloys, plastic or polymer materials, solid resin materials, glassy materials and other materials including various biodegradable materials as may be suitable for the application and appropriately biocompatible. As examples, certain stainless steel alloys and cobalt-chrome alloys have been used. Such devices include for example, without limitation, vascular stents and artificial joint prostheses, etc. It has often been found beneficial to coat the surfaces of such devices with a therapeutic agent such as a medicine or drug to increase the likelihood of a successful outcome for the surgical implant treatment.

#For example, in the case of an implantable vascular stent, it is often desirable to apply drugs to the surface of the stent prior to its introduction into a vascular vessel. Implantable vascular stents may be fabricated from metal materials or may be fabricated from biodegradable materials. In the past, it has been the experience that therapeutic drugs, when applied directly to an expandable vascular stent, are not as effective as intended. Sometimes, the therapeutic agent is released (elutes) from the surface too rapidly (perhaps even washing off almost entirely during implantation of the stent. Other times the stent-drug combination does not withstand the mechanical stresses imposed during compression, expansion, or flexing of the stent required before and during implantation and the drug coat cracks, flakes, or delaminates during mechanical deformation—this generally results in either loss of the drug, or an undesirable change in the rate at which it elutes, following implantation. Especially when larger drug loads requiring thicker coatings are indicated, the problem of retaining an undamaged drug coating on the stent during and following mechanical strains has been problematical. It has become a common practice to use a polymer matrix to bond the therapeutic agent to such stents or to encapsulate the drug both to improve the durability and ductility of the coating and to help control the in-situ drug elution rate. It is now believed that such polymers have undesirable side effects that can result in unfavorable outcomes. There is a need for a drug-coated expandable vascular stent that doesn't employ a polymer or other binder matrix to control mechanical and elution properties, but where a robust and durable drug coating is applied directly on the bare stent in a manner that provides a suitable elution rate and which withstands the normal mechanical activities necessary to implant the stent without shedding or unacceptably compromising the coating.

#FIG. 1 is a schematic view of a vacuum spray coating system for medical devices according to an embodiment of the invention;

#FIG. 2 is a schematic view of a vacuum spray coating system for medical devices according to an alternate embodiment of the invention;

#FIG. 3 is a timing diagram showing timing details for controlling pulse spray coating of a medical device according to the invention;

#Reference is made to FIG. 1 of the drawings, which shows a system 200 for vacuum spray coating of a medical device according to an embodiment of the invention. FIG. 1 is a schematic view and dimensions are not drawn to scale. This system has two modes of use according to separate methods of the invention and is able to produce drug coatings on medical devices that are either smooth or textured coatings. The system includes a vacuum coating chamber 202 with multiple ports having flanges sealed by component mounting plates 208, 216, 230, and 288. The chamber 202 preferably has a volume of about 200 to 400 cubic inches. One of the ports has a component mounting plate 208 that mounts a motor 204 having a rotary shaft 206, which attaches a mandrel 210 so that the mandrel can be rotated about its axis with a rotary motion 212. The mandrel is adapted to hold cylindrical medical devices, as for example expandable vascular stents 246, 248, and 250 by passing through the bore of the stents and retaining them by friction fit or by means of clips or collars not shown. Although, for simplicity, a mandrel supporting the stents or other tubular or cylindrical medical devices by the inside diameter, it will be immediately understood by those skilled in the arts that other rotating supports are readily provided that will support an expandable mesh vascular stent in such a way that the inside diameter surfaces of the, stent can also be coated if necessary, by spraying through the mesh of the stent to impact the inside surface. It will also be appreciated that flat or otherwise shaped surfaces can also be spray coated by the apparatus by substituting appropriate holders for the medical devices using techniques well known in the arts. Using the rotating mandrel 210, the stents 246, 248, and 250 can be rotated about their axes by the rotary motion 212 provided by motor 204 to facilitate spray coating of the entire outer surface of the stents. The motor may rotate at any suitable rate, for example about 6 RPM.

#A vacuum system operates the coating chamber 202 at a reduced pressure. Vacuum pump 226 may be a rough vacuum pump such as for example a Leybold D65B having a pumping speed of 54 CFM, for example. A high pumping speed of 50 CFM or more with an ultimate pressure capability below 35 mtorr is preferred. Vacuum pump 226 is coupled to the coating chamber 202 through a filter 224, a pumping line 222, a vacuum reservoir 220, additional pumping line 218, and a control valve (V5) 214. The vacuum reservoir may be a separate volume as indicated or may be formed assuring that pumping lines 218 and 222 have adequate volume to act as a reservoir to improve the rate of evacuating the coating chamber 202 when it receives a pressure burst (as will be discussed below. It is preferable that the reservoir should have a volume greater than the volume of the coating chamber 202, preferably 2 to 6 times the volume of the chamber 202. The control valve 214 is preferably a valve of a type that can be remotely actuated, preferably electrically or electro-pneumatically actuated.

#One of the ports in the chamber 202 has a component mounting plate 288 with an opening through a gate valve 286, provided for connecting the chamber with other equipment as will be discussed hereinafter.