Patent Application
20080058921
The stent substrate 120 is a hollow-tubed structure that can be formed with interconnected or interwoven members that can be referred to as struts. The struts can be, for example, straight, serpentine, sinusoidal, or other shapes that allow the stent substrate 120 to expand from a reduced diameter (i.e., contracted state) to a diameter useful in a particular application (i.e., expanded state). Suitable materials for the stent substrate 120 include, for example, metals and alloys based on titanium (such as nitinol, nickel titanium alloys, thermo-memory allow materials), stainless steel, tantalum, nickel-chrome, clad composite filaments, polymers, co-polymers, or certain cobalt alloys including cobalt-chromium-nickel alloys.
The drug excipient coating 110 can be any type of appropriate combination of one or more biologically active materials (e.g., drug) and/or vehicles for the drug. The drug can be, for example, a genetic material, a pharmaceutical agent, a cell, an inhibitor, a non-genetic therapeutic agent, a polymer matrix having a therapeutic component or any other substance which would be desirable to deliver into a body lumen. The vehicle can be a binder, filler, disintegrant, lubricant, or coating that can include, for example, an inert polymeric material/compound.
Suitable polymeric materials that can serve as the vehicle for the drug within the drug excipient coating 110 include, for example, polyurethane and its copolymers, silicone and its copolymers, ethylene vinyl-acetate, polyethylene terephtalate, thermoplasic elastomers, polyvinyl chloride, polyolefins, cellulosics, polyamides, polyesters, polysulfones, polytetrafluorethylenes, polycarbonates, acrylonitrile butadiene styrene copolymers, acrylics, polylactic acid, polyglycolic acid, polycaprolactone, polylactic acid-polyethylene oxide copolymers, cellulose, collagens, and chitins. In the illustrated embodiment, the drug excipient coating 110 is a styrene-isobutylene-styrene (SIBS) based coating (i.e., excipient) that is applied to the surface 114 of the substrate 120.
The drug excipient coating 110 can be applied to the surface 114 of the stent substrate 120 using any appropriate coating technique. For example, a solvated polymer blend (e.g., polymer blend that includes a solvent) with a therapeutic agent can be used as the drug excipient coating 110 and can be applied through direct spray application (e.g., spray-coating technique) onto the surface 114 of the stent substrate 120 after the surface 114 has been exposed to the UV-ozone process. In some embodiments, the drug excipient coating 110 can be applied to the stent substrate 120 by a micro-drop application technique, a roll-coating technique, and/or by dipping the stent substrate 120 into a solvated form of the drug excipient coating 110.
The surface 114 of the stent substrate 120 has been exposed to a UV-ozone process to promote the adhesion of the drug excipient coating 110 to the surface 114 of the stent substrate 120. The UV-ozone process is employed to modify an adhesive property associated with the surface 114 of the stent substrate 120. For example, the UV-ozone process can modify a chemical property of the stent substrate 120. Specifically, the UV-ozone process can add one or more oxygen-containing functional groups to the surface 114 of the stent substrate 120. These functional groups can modify the surface energy and/or morphology of the surface 114 of the stent substrate 120 to promote adhesion. The UV-ozone process can also remove organic contaminants (e.g., machine oils, human sebum, solder flux, etc.) and/or inorganic compounds (e.g., dusts, metal powder, quartz, etc.) from the surface 114 of the stent substrate 120 that would otherwise decrease and/or prevent adhesion of the drug excipient coating 110 to the surface 114.
The UV-ozone process can remove contaminants that occupy and/or block molecular bonds at the surface 114 that can then be allowed to molecularly bond to the drug excipient coating 110.
In the UV-ozone process, contaminants on the surface 114 of the stent substrate 120 are converted into volatile substances after being decomposed by UV light (e.g., UV rays) and oxidized by an atomic oxygen molecule. UV light of approximately 185 nm and 254 nm can be used to form and decompose ozone molecules, respectively, to produce the atomic oxygen from reactants used in the UV-ozone process. The atomic oxygen and/or ozone used in the UV-ozone process can be derived from an oxygen containing reactant such as oxygen (O2). The UV light can be produced using, for example, a low-pressure quartz-mercury vapor lamp.
In many embodiments, the conditions of the UV-ozone process (e.g., reactant concentrations and/or types, length of exposure, temperature, pressure) can be adjusted and/or determined based on, for example, the type of drug excipient coating being applied to the stent substrate, type of application of the DES, and physical characteristics of the stent substrate. In some embodiments, for example, the stent substrate is exposed to the UV-ozone process at room temperature and pressure, but in several implementations, the UV-ozone process is conducted at different conditions such as, for example, elevated temperatures and/or pressures.
In many embodiments, the stent substrate 120 is exposed to the UV-ozone process for less than twenty minutes, but in some embodiments, the length of the exposure to the UV-ozone process can be adjusted (e.g., extended or shortened). The length of exposure, in some embodiments, is modified based on measurements of the cleanliness of the surface of the stent substrate. For example, the length of the UV-ozone process can be extended if water contact angles measured on the surface of the stent substrate are, for example, above a specified threshold value. The threshold value can be specified based on, for example, a correlation of adhesion characteristics of the stent substrate and water contact angles. The adhesive characteristics of the stent substrate can be measured using, for example, clinical scrub tests, pulsatile fatigue tests and/or peel adhesion evaluations.
Exposure to the UV-ozone process, in some embodiments, can be conducted in stages and/or at multiple sets of conditions. For example, the UV-ozone process can be conducted first at low temperature and later at high temperature with or without intervening processing such as electropolishing. In some embodiments only a portion or critical portions (e.g., apex regions) of the stent substrate 120 are exposed to the UV-ozone process using, for example, directional UV light and/or a directional introduction of reactants.
In some embodiments, the stent substrate 120 is cleaned using a preliminary cleaning before the surface 114 is exposed to the UV-ozone process. The preliminary cleaning can be conducted using, for example, an ultrasonic bath with a mild detergent or can be accomplished by, for example, scrubbing the surface of the stent substrate 120 with a brush. A primer coating, in some implementations, can be applied to the stent substrate 120 after it has been exposed to the UV-ozone process.
Each of the steps involved in producing the DES 100 can performed in a single chamber and/or multiple chambers. For example, a preliminary cleaning, if included in a particular DES 100 production flow, can be performed in a different chamber than the UV-ozone exposure and/or application of the drug excipient coating 110. Furthermore, the DES 100 can be produced using a process that includes batch processing and/or continuous processing steps.
The DES 200 shown in
As shown in
In many embodiments, the metal stent substrate 222 is coated with the drug excipient coating 226 in the expanded state rather than the contracted state. In some embodiments, the drug excipient coating 226 is applied to the metal stent substrate 222 in an intermediate state of contraction and/or expansion that is the result of the application of some external force (e.g., intentionally applied external force).
Referring now to
After the stent substrate has been manufactured 500, the stent substrate is prepared for UV-ozone processing 520. For example, the surface of the stent substrate can be roughened to promote adhesion of the drug excipient coating that will later be applied to the surface. The stent substrate can also, in several embodiments, be cleaned using, for example, conventional cleaning techniques (e.g., brush scrubbing) to remove compounds and/or residuals such as inorganic salts that may not be effectively removed from the surface of the stent substrate by some UV-ozone processes. In some embodiments for example, the preparation of the stent substrate for UV-ozone processing 520 includes preparing the stent substrate by, for example, cleaning with a detergent. Some of these compounds and/or residuals on the surface can be a result of, for example, handling of the stent substrate or the process used to manufacture the stent substrate at 500.
The stent substrate is then exposed to the UV-ozone process 540 in, for example, a UV-ozone processing chamber. The conditions of the UV-ozone process (e.g., reactant concentrations and/or types, length of exposure, temperature, pressure) can be specified based on the type of drug excipient coating being applied to the stent substrate, type of application of the DES, and the physical characteristics of the stent substrate. The conditions of the preparation of the stent substrate 520 and the exposure to the UV-ozone process 540 can be optimized to produce a particular level of surface cleanliness measured using, for example, water contact angles.
After the stent substrate has been exposed to the UV-ozone process at 540, a drug excipient coating is applied to the stent substrate 560. For example, a solvated polymer blend (e.g., SIBS) with a pharmacological agent can be used as the drug excipient coating and can be applied to the surface of the stent subsrate through direct spray application. In some embodiments, the drug excipient coating can be applied to the stent substrate using, for example, a roll-coating technique, a micro-drop application technique, and/or a dipping technique.
In conclusion, the present invention is related to a DES with a stent substrate that has been exposed to a UV-ozone process. Those skilled in the art can readily recognize that numerous variations and substitutions may be made in the invention, its use and its configuration to achieve substantially the same results as achieved by the embodiments described herein. Accordingly, there is no intention to limit the invention to the disclosed exemplary forms. Many variations, modifications and alternative constructions fall within the scope and spirit of the disclosed invention as expressed in the claims.
