A metallic composite coating, and methods for forming same, for an implantable medical device is disclosed. The composite coating comprises at least one metal or metallic tie layer formed on the surface of the device, followed by an electroless electrochemical cladding of one or more additional layers over the tie layer. One or more therapeutic or biologically active agents are co-deposited with at least one of the electroless electrochemical claddings.

BRIEF SUMMARY OF THE INVENTION

The present invention provides a thin metal coating and coating process for coating implantable medical devices. In addition, the invention provides a relatively passive, or relatively non-reactive, external surface coating on implantable medical devices lessening the reaction to the device and improving the device-tissue interface.

One aspect of the invention is to improve adherence of the coating to the surface of the underlying implantable device.

It is also an object of the invention to incorporate one or more therapeutic agents into the coating.

In another aspect of the invention the implantable medical device is coated without signficantly increasing its bulk.

Where the implantable device is fabricated from a metal or metal alloy, another object of the invention is to provide a coating which possesses properties more compatible with the underlying substrate.

It is a further aspect of the invention to provide an improved coating on the surface of an implantable endolumenal prosthesis for maintaining lumen patency.

As previously described, certain implantable medical devices, such as stents, are limited in their material choices due to the desire to have a passive surface. For example, it is a reason why balloon-expandable stents have been fabricated from stainless steel, and, more recently, cobalt-chromium. Therefore, an additional object of the invention is to alleviate this material limitation by having a relatively passive coating encasing the stent.

It is even a further object of the invention to provide an improved thin metal coating process for deposition onto implantable endolumenal devices. Another aspect of this object is to also co-deposit therapeutic agents with and within the coating for subsequent elution from the implantable medical device.

The invention comprises forming multiple layers on the surface of a device to form a composite matrix. In a particular embodiment, a first layer is applied or struck on the surface by contacting the surface with an electrolytic solution containing metal ions, and subsequently electrodepositing a thin metal film onto the surface. This is followed by contacting the surface with a second electrochemical bath containing metal ions and one or more therapeutic agents to form a second layer on the surface of the device. The agents are co-deposited with the metal ions on the surface of the device to form a composite, bioactive, metallic matrix on the device.

In a further embodiment of the invention, the first layer is electroplated onto the surface of the device and the second layer is deposited through an electroless electrochemical co-deposition process. The invention further contemplates the application of more or more electroplated layers, and one or more layers deposited through an electroless electrochemical process. In another embodiment of the invention, the electroless electrochemical deposition steps are performed with out any pre-sensitizing of the surface nor any pre-deposition of a catalyst on the surface to be coated.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a thin metal coating and a process depositing the thin metal coating on implantable endolumenal medical devices. The following description is presented to enable one of ordinary skill in the art to make and use the invention and is provided in the context of a patent application and its requirements. Various modifications to the preferred embodiment will be readily apparent to those skilled in the art and the generic principles herein may be applied to other embodiments. Thus, the present invention is not intended to be limited to the embodiment shown but is to be accorded the widest scope consistent with the principles and features described herein.

This invention introduces an improved method for depositing a thin metal matrix onto the surface of an implantable device. The multiple step process deposits a composite thin metal matrix onto the device's surface. This multiple step process also includes one or more steps where a therapeutic or biologically active agent, or agents, is co-deposited with and within one or more thin metal films. The process is quite controllable and variable based on such parameters as temperature, pH, relative concentration of solution constituents, other additives or agents present in solution and time.

Specifically, the present invention makes use of the process of electroless electrochemical deposition to apply one or more layers of thin metal film, incorporating one or more biologically active agents, onto the surface of an implantable device. Electroless electrochemical deposition is a self-assembling or autocatalytic process.

More specifically, in a further embodiment, the invention combines the processes of electroplating and electroless electrochemical deposition, in a multi-step approach, to provide better adherence of the metallic matrix to the surface of the underlying device while also incorporating one or more biologically active agents with and within the coating matrix.

By one aspect of the invention, two solutions are prepared. The first being an electroplating or electrolytic solution or bath, and the second being an electroless deposition solution or bath. The first bath is formed with a cathode (the device to be coated), and an electrolytic solution containing metal ions. The second bath is formed using metal salts, a solvent, a reducing agent, and more or more biologically active agents to be incorporated into the coating matrix.

Prior to subjecting the device to the electrochemical processes described, the surface of the device must be appropriately prepared. This is done by contacting or immersing the device in a pre-treatment bath. This bath can include organic or inorganic acids. For example, with regard to alloys such as stainless steel, nickel-titanium, or cobalt-chromium an acid bath including an one or combination of inorganic acids such as hydrochloric acid (HCl), nitric acid (HNO.sub.3, or hydroflouric acid (HF). Other methods of cleaning the surface can include molten salts, mechanical removal, alkaline cleaning, or any other suitable method that provides a clean, coatable surface. This initial step serves to clean the surface and etch the surface thereby removing any resident oxide layers on the structure and pitting the surface to improve subsequent adherence of the coating to the device.

The device is then rinsed, preferably deionized water and more preferably, deionized and distilled water. Although, any suitable suitable liquid or gas could be used to remove any possible impurities from the surface. After rinsing, the implantable structure to be coated is immersed in the first bath. A current is then applied across the device causing the metal ions to move to the device and plate the surface. This electroplating step causes an intermediate or "strike" layer to be formed on the surface of the device. Metal ions for this first bath are chosen to be compatible with the material making up the device itself. For example, if the underlying structure is made of cobalt chrome, cobalt ions are preferred. It has been found that this strike layer improves overall adherence of the coating to the implantable device as well as increasing the rate of deposition or efficiency of the second, electroless film. The device is subsequently removed from the first bath and rinsed again with water prior to immersion into the second bath.

The device is then immersed in the second, electroless bath at a controlled temperature and pH value. In this step, metal ions, the reducing agent, and the one or more therapeutic agents are simultaneously and substantially uniformly, co-deposited on the struck surface of the device. After immersion in this second bath, a bioactive composite metallic matrix has been formed on the surface of the device. The device is removed from the second bath and allowed to dry.

By this deposition process, any suitable structure can be coated. The device can be porous or solid, flexible or rigid, have a planar or non-planar surface. Accordingly, in some embodiments the device could be stent, a pellet, a pill, a seed, an electrode, a coil, etc. The device to be coated may be formed of any suitable material such as, metal, metal alloy, ceramic, polymer, glass, etc.

Any suitable source of metal ions can be used for the first electrolytic bath. Typically, such metal ions are derived from metal salts which dissociate from one another in solution. Such salts, and therefore ions, are well known in the field of electrolytic deposition and can be chosen by those of ordinary skill in this art. Examples of suitable metal ions depends on the underlying device to be coated, but does include ions of nickel, copper, gold, cobalt, silver, palladium, platinum, etc., and alloys thereof. Different types of salts can be used if it is desired to strike a metal alloy matrix on the surface of the device.

Similarly, any suitable source of metal ions can be used for the second electroless electrochemical deposition bath. And are also typically derived from metal salts. Examples of such suitable sources depends on the underlying device to be coated and are well known in the field of electroless electrochemical deposition and can be selected by those of ordinary skill in this art.

The electroless electrochemical solution also includes a reducing agent and may include complexing agents, buffers and stabilizers. The reducing agent reduces the oxidation state of the metal ions in solution such that the metal ions deposit on the surface of the device as metal. Complexing agents are used to hold the metal in solution. Buffers and stabilizers are used to increase bath life and improve stability of the bath. Buffers are also used to control the pH of the solution. Stabilizers are also used to keep the solution homogeneous. Examples of such complexing agents, buffers and stabilizers are well known in the field of electroless electrochemical deposition and can be selected by those of ordinary skill in this art.

Concerning the therapeutic agents to be co-deposited, any such agent, agents, or combinations thereof can be deposited within the coating depending on the condition to be treated, response desired, or tissue into which the device is to be introduced. Agents which can be coated onto the surface of the device in accordance with the invention include the following compounds; organic, inorganic, water soluble, water insoluble, hydrophobic, hydrophilic, lipophilic, large molecules, small molecules, proteins, anti-proliferatives, anti-inflammatory, anti-thrombogenetic, anti-biotic, anti-viral, hormones, growth factors, immunosuppressants, chemotherapeutic, etc.

These therapeutic agents which are co-deposited or captured within the electroless electrochemically deposited layer, diffuse out or are released from the coating via pores formed in the coating by the coating process itself. The metal composite matrix forms pores between self-assembling grains as they meet and grow on the surface being coated. This porosity, or the extent and nature of these pores, is a property that is readily manipulated according to proven methods well known to those of ordinary skill in this art.

With regard to the first electroplating bath, in another embodiment of the invention, one or more intermediate layers can be struck on the surface of the device. This can improve the efficiency of the subsequent electroless electrochemical coating step.

Likewise, with regard to the second electroless electrochemical bath, one or more films can be coated onto the surface of the device. Furthermore, multiple electroless electrochemical baths can be used such that not all these baths co-deposit one or more therapeutic agents. For example, after the electroplating step, a first electroless electrochemical bath without any therapeutic agents can be employed to place a first electroless coating onto the surface of the device. The device can then be transferred to a second electroless bath containing one or more therapeutic agents in solution. This can improve the efficiency of the step involving co-deposition of the metal ions, reducing agent and one or more therapeutic agents.

Moreover, multiple electroless baths can be prepared containing and co-depositing different biologically active agents in each coating layer. In addition, an electroless bath, not containing any therapeutic agents, can be applied as a top coat to modify or control the release of therapeutic agents from an inner layer or layers.

The invention will now be described in additional detail by way of working examples of the metallic bioactive matrix deposited on stents. The scope of the present invention, however, is not at all limited by these working examples. Nor is the implantable device limited to a stent. Rather, these examples are illustrative of a manner in which the invention can be practiced.

 

Claim 1 of 10 Claims

1. A medical device comprising: a substrate having an outer surface; and a composite coating on said outer surface including a plurality of layers which are comprised of: a first metal layer; and a second metallic composite layer comprising a metal and at least one therapeutic material wherein said therapeutic material is selected from the group consisting of rapamycin (sirolimus), rapamycin (sirolimus) analogs, paclitaxel, paclitaxel derivatives, growth factors, heparin, aspirin, tetracycline, dexamethasone, des-aspartate angiotensin I, tachykinins, sialokinins, apocynin, siRNA, pleiotrophin, exochelins, and combinations thereof.
 

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