JP2024537713A - Metal alloys, medical devices and methods - Google Patents

Abstract

High melting point metal alloys with reinforced coating materials. [Selection diagram] None

Description

(Cross Reference)
This disclosure is a continuation-in-part of U.S. Patent Application No. 17/586,270, filed January 27, 2022, and claims priority to U.S. Provisional Application No. 63/226,270, filed July 28, 2021, which is incorporated herein by reference.

This disclosure claims priority to U.S. Provisional Application No. 63/389,281, filed July 14, 2022, which is incorporated herein by reference.

This disclosure claims priority to U.S. Provisional Application No. 63/347,337, filed May 31, 2022, which is incorporated herein by reference.

This disclosure claims priority to U.S. Provisional Application No. 63/247,540, filed September 23, 2021, which is incorporated herein by reference.

This disclosure claims priority to U.S. Provisional Application No. 63/316,077, filed March 3, 2022, which is incorporated herein by reference.

(Technical field)
The present disclosure relates generally to refractory metal alloys, such as, but not limited to, protective coatings for refractory metal alloys, and even more specifically to medical devices formed at least in part from refractory metal alloys.

Stainless steels, cobalt-chromium alloys, and TiAlV alloys are some of the common metal alloys used in medical devices. Although these alloys have been successful in forming a variety of medical devices, they do have some drawbacks.

The present disclosure relates to refractory metal alloys, particularly rhenium-containing refractory metal alloys, that are partially or completely coated with a material that improves one or more properties of the refractory metal alloy.

The present disclosure relates to protective coatings for refractory metal alloys, such as refractory metal alloys comprising rhenium, and more particularly to medical devices formed at least in part from refractory metal alloys and including protective coatings. As defined in this disclosure, a refractory metal alloy is a metal alloy comprising at least 20% by weight of one or more of Mo, Re, Nb, Ta, or W. Non-limiting refractory metal alloys include MoRe alloys, ReW alloys, MoReCr alloys, MoReTa alloys, MoReTi alloys, WCu alloys, ReCr alloys, Mo alloys, Re alloys, W alloys, Ta alloys, Nb alloys, and the like. In one non-limiting embodiment, the refractory metal alloy comprises at least 20% by weight of rhenium. Non-limiting examples of refractory metal alloys containing rhenium include, but are not limited to, MoRe alloys, ReW alloys, MoReCr alloys, MoReTa alloys, MoReTi alloys, and ReCr alloys.

According to one non-limiting aspect of the present disclosure, the medical device may be an orthopedic device, a PFO (patent foramen ovale) device, a stent, a valve (e.g., heart valve, TAVR valve, mitral valve replacement, tricuspid valve replacement, pulmonary valve replacement, etc.), a spinal implant, a spinal disc, a frame and other structures used in spinal implants, a vascular implant, a graft, a guidewire, a sheath, a catheter, a needle, a stent catheter, an electrophysiology catheter, a hypotube, a staple, a cutting device, an implant of any type, a pacemaker, a dental implant, a dental crown, an orthodontic appliance, a wire used in a medical procedure, a bone implant, an artificial disc, an artificial spinal disc, a prosthetic implant, or a device bone (e.g., acromion , atlas, shaft, calcaneus, carpal bones, clavicle, coccyx, epicondyle, supraliscus, femur, fibula, frontal bone, greater trochanter, humerus, ilium, ischium, mandible, maxilla, metacarpals, metatarsals, occipital bone, olecranon, parietal bone, patella, phalanges, radius, ribs, sacrum, scapula, sternum, talus, tarsus, temporal bone, tibia, ulna, zygomatic bone, etc.) and/or cartilage, bone plates, knee replacements, hip replacements, shoulder replacements, ankle replacements, nails, rods, screws, posts, cages, plates, pedicle screws, caps, hinges, joint systems, anchors, spacers, shafts, anchors, discs, balls, tension bands, locking connectors and other structural assemblies. Locking connectors and other structure assemblies are used within the body to support structures, attach structures, or repair structures within the body (including, but not limited to, the human body, animal body, etc.).

According to another and/or alternative non-limiting aspect of the present disclosure, a medical device is provided that is partially or completely formed of a refractory metal alloy. In one non-limiting embodiment, 50-100% (and all values and ranges therebetween) of the medical device is formed of a refractory metal alloy. In another non-limiting embodiment, at least 30% by weight (e.g., 30-100% by weight and all values and ranges therebetween) of the medical device is formed of a refractory metal alloy that includes rhenium (e.g., MoRe alloy, ReW alloy, MoReCr alloy, MoReTa alloy, MoReTi alloy, ReCr alloy, etc.).

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy used to form at least a portion of the medical device has one or more improved properties (e.g., strength, durability, hardness, biostability, bendability, coefficient of friction, radial strength, flexibility, tensile strength, tensile elongation, longitudinal elongation, stress-strain properties, reduced recoil, radiopacity, thermal sensitivity, biocompatibility, improved fatigue life, crack resistance, crack propagation resistance, reduced magnetic susceptibility, etc.), improved bending compliance, reduced recoil, increased yield strength, improved fatigue ductility, improved durability, improved fatigue life, reduced adverse tissue reactions, reduced metal ion release, reduced corrosion, reduced allergic reactions, improved hydrophilicity, reduced toxicity, reduced thickness of the metal component, improved bone integration, and/or reduced ion release into tissue. These one or more improved physical properties of the refractory metal alloy may be achieved in a medical device without the need to increase the bulk, volume, and/or weight of the medical device, and in some cases, these improved physical properties may be obtained even when the volume, bulk, and/or weight of the medical device is reduced as compared to medical devices formed, at least in part, from conventional stainless steel, titanium alloy, or cobalt-chromium alloy materials.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy used to at least partially form the medical device may therefore: 1) increase the radiopacity of the medical device; 2) increase the radial strength of the medical device; 3) increase the yield strength and/or ultimate tensile strength of the medical device; 4) improve the stress-strain characteristics of the medical device; 5) improve the compression and/or expansion characteristics of the medical device; 6) improve the flexure and/or flexibility of the medical device; 7) improve the strength and/or durability of the medical device; 8) increase the hardness of the medical device; 9) improve the recoil characteristics of the medical device; 10) improve the biostability and/or biocompatibility characteristics of the medical device; 11) improve the fatigue resistance of the medical device; 12) resist cracking and resist crack propagation of the medical device; 13) enable a smaller, thinner, and/or lighter medical device; 14) reduce the outer diameter of the compressed medical device; 15) increase the durability and/or longevity of the medical device when used and maintained within the treatment area; 16) improve the ability of the medical device to conform to the shape of the treatment area as the medical device is expanded and/or recoiled from the shape of the treatment area as the medical device is expanded within the treatment area; 17) increase the yield strength of the medical device; 18) improve the fatigue ductility of the medical device; 18) improve the durability of the medical device; 19) improve the fatigue life of the medical device; 20) reduce adverse tissue reactions after implantation of the medical device; 21) reduce metal ion release after implantation of the medical device; 22) reduce corrosion of the medical device after implantation of the medical device; 23) reduce allergic reactions after implantation of the medical device; 24) improve hydrophilicity of the medical device; 25) reduce the thickness of the meta-component of the medical device; 26) improve bone union by the medical device; and/or 27) reduce ion release from the medical device to tissue; 28) reduce the magnetic susceptibility of the medical device implanted in a patient; and/or 29) reduce toxicity of the medical device after implantation of the medical device.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device is optionally subjected to one or more manufacturing processes, including, but not limited to, expanding, laser cutting, etching, compressing, annealing, drawing, pilge ring, electroplating, electropolishing, machining, plasma coating, 3D printing, 3D print coating, chemical vapor deposition, chemical polishing, cleaning, pickling, ion beam deposition or implantation, sputter coating, vacuum deposition, and the like. In one non-limiting embodiment, a portion or all of the medical device is formed by a 3D printing process.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy used to at least partially form the medical device optionally has a substantially uniform density throughout the refractory metal alloy and provides the desired yield strength and ultimate tensile strength of the refractory metal alloy. The density of the refractory metal alloy is generally at least about 5 gm/cc (e.g., 5 gm/cc to 21 gm/cc and all values and ranges therebetween, such as 10 to 20 gm/cc), and typically at least about 11 to 19 gm/cc. This substantially uniform high density refractory metal alloy can optionally improve the radiopacity of the refractory metal alloy.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy optionally includes, but is not required to include, a certain amount of carbon and oxygen. These two elements have been found to affect the forming properties and brittleness of the refractory metal alloy. A controlled atomic ratio of carbon to oxygen in the refractory metal alloy can also be used to minimize the tendency of the refractory metal alloy to form microcracks during at least partial formation of the refractory metal alloy into a medical device and/or during use and/or expansion of the medical device within a body passageway. Controlling the atomic ratio of carbon to oxygen in the refractory metal alloy allows for a redistribution of oxygen in the refractory metal alloy, which can minimize the tendency of microcracks in the refractory metal alloy during at least partial formation of the refractory metal alloy into a medical device and/or during use and/or expansion of the medical device within a body passageway. It is believed that the atomic ratio of carbon to oxygen in the refractory metal alloy promotes minimizing the tendency of microcracks in the refractory metal alloy and enhancing the degree of elongation of the refractory metal alloy. Any of these may affect one or more physical properties of the refractory metal alloy that are useful or desirable in forming and/or using a medical device. The atomic ratio of carbon to oxygen can be as low as about 0.2:1 (e.g., 0.2:1 to 50:1 and all values and ranges therebetween). In one non-limiting formulation of the refractory metal alloy, the atomic ratio of carbon to oxygen in the refractory metal alloy is generally at least about 0.3:1. Typically, the carbon content of the refractory metal alloy is less than about 0.2% by weight (e.g., 0% to 0.1999999% by weight and all values and ranges therebetween). Too much carbon content can adversely affect the physical properties of the refractory metal alloy. Generally, the oxygen content is kept at a very low level. In a non-limiting formulation of the refractory metal alloy, the oxygen content is less than about 0.1% by weight of the refractory metal alloy (e.g., 0% to 0.0999999% by weight and all values and ranges therebetween). It is believed that the refractory metal alloy has a very low tendency to form microcracks during formation of the medical device and after the medical device is inserted into the patient by tightly controlling the carbon to oxygen ratio when the oxygen content exceeds a certain amount in the refractory metal alloy. In one non-limiting configuration, when the oxygen content in the refractory metal alloy is greater than about 100 ppm, the atomic ratio of carbon to oxygen in the refractory metal alloy is at least about 2.5:1.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy optionally includes a controlled amount of nitrogen, but this is not required. Including a large amount of nitrogen in the refractory metal alloy can adversely affect the ductility of the refractory metal alloy. This can adversely affect the elongation properties of the refractory metal alloy. If the nitrogen content in the refractory metal alloy is too high, the ductility of the refractory metal alloy begins to decrease unacceptably, which can adversely affect one or more physical properties of the refractory metal alloy that are useful or desirable in forming and/or using a medical device. In one non-limiting formulation, the refractory metal alloy includes less than about 0.001% nitrogen by weight (e.g., 0% to about 0.0009999% by weight and all values and ranges therebetween). It is believed that the nitrogen content in the refractory metal alloy should be less than the carbon or oxygen content. In one non-limiting formulation of the refractory metal alloy, the atomic ratio of carbon to nitrogen is at least about 1.5:1 (e.g., from 1.5:1 to 400:1 and all values and ranges therebetween). In another non-limiting formulation of the refractory metal alloy, the atomic ratio of oxygen to nitrogen is at least about 1.2:1 (e.g., from 1.2:1 to 150:1 and all values and ranges therebetween).

In another and/or alternative non-limiting aspect of the present disclosure, the medical device is generally designed to include at least about 5% by weight of a refractory metal alloy (e.g., 5-100% by weight and all values and ranges therebetween). In one non-limiting embodiment of the present disclosure, the medical device includes at least about 50% by weight of a refractory metal alloy. In another non-limiting embodiment of the present disclosure, the medical device includes at least about 95% by weight of a refractory metal alloy. In one particular configuration, when the medical device includes an expandable frame, the expandable frame is formed of 50-100% by weight (and all values and ranges therebetween) of a refractory metal alloy, typically 75-100% by weight of a refractory metal alloy.

In another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy used to form all or a portion of the medical device is 1) optionally not clad, metal sprayed, plated, and/or formed (e.g., cold worked, hot worked, etc.) onto another metal, or 2) optionally not sprayed, plated, clad, and/or formed with another metal or metal alloy metal onto the refractory metal alloy.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy used to form all or part of the medical device may be: 1) clad, metal sprayed, plated, and/or formed (e.g., cold worked, hot worked, etc.) onto another metal; or 2) have another metal or alloy metal sprayed, plated, clad, and/or formed onto the refractory metal alloy.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device may optionally be formed at least partially or completely from a tube or rod of a refractory metal alloy and formed into a shape that is at least 80% of the final net shape of the medical device.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device can be formed at least partially or completely by 3D printing.

According to another and/or alternative non-limiting aspect of the present disclosure, when a medical device is at least partially formed from the refractory metal alloy of the present disclosure, the refractory metal alloy has several physical properties that positively impact the medical device. In one non-limiting embodiment of the present disclosure, the average Vickers hardness of the refractory metal alloy of the present disclosure used to at least partially form the medical device is optionally at least about 150 Vickers (e.g., 150-300 Vickers and all values and ranges therebetween), typically 160-240 Vickers, but this is not required. The refractory metal alloy of the present disclosure generally has a higher average hardness than stainless steel (e.g., grade 304, grade 316). In another and/or alternative non-limiting embodiment of the present disclosure, the average ultimate tensile strength of the refractory metal alloy of the present disclosure is optionally at least about 100 ksi (e.g., 100-350 ksi and all values and ranges therebetween), but this is not required. In yet another and/or alternative non-limiting embodiment of the present disclosure, the average yield strength of the refractory metal alloy of the present disclosure is optionally, but not required to be, at least about 80 ksi (e.g., 80-300 ksi and all values and ranges therebetween). In yet another and/or alternative non-limiting embodiment of the present disclosure, the average grain size of the refractory metal alloy of the present disclosure used to at least partially form the medical device is optionally about 4 ASTM or less (e.g., 4 ASTM-20 ASTM, e.g., 0.35 microns-90 microns, using ASTM E112 and all values and ranges therebetween). The small grain size of the refractory metal alloy of the present disclosure allows the medical device to have desirable elongation and ductility properties useful for enabling the formation, compression, and/or expansion of the medical device.

In another and/or alternative non-limiting embodiment of the present disclosure, the average tensile elongation of the refractory metal alloy of the present disclosure used to at least partially form the medical device is optionally at least about 25% (e.g., 25% to 50% average tensile elongation and all values and ranges therebetween). An average tensile elongation of at least 25% refractory metal alloy is useful in facilitating proper expansion of the medical device when placed in the treatment area of the body passage. Medical devices that do not have an average tensile elongation of at least about 25% may be susceptible to the formation of microcracks and/or breakage during formation, compression, and/or expansion of the medical device.

In accordance with another and/or alternative non-limiting aspect of the present disclosure, the unique combination of metals in the refractory metal alloys of the present disclosure, in combination with achieving a desired purity and composition of the refractory metal alloy and a desired grain size of the refractory metal alloy, can provide: 1) a medical device having a desired high ductility at about room temperature; 2) a medical device having a desired amount of tensile elongation; 3) a homogenous solution or solid solution of the refractory metal alloy having high radiopacity; 4) reducing or preventing the formation of microcracks and/or breakage of the refractory metal alloy of the disclosed tubing when sizing and/or cutting the tubing to form the medical device; 5) reducing or preventing the formation of microcracks and/or breakage of the medical device when the medical device is compressed; 6) a medical device having a desired high ductility at about room temperature; 7) a medical device having a desired amount of tensile elongation at about room temperature; 8) a medical device having a desired amount of tensile elongation at about room temperature; 9) a medical device having a desired amount of tensile elongation at about room temperature; 10) a medical device having a desired amount of tensile elongation at about room temperature; 11) a medical device having a desired amount of tensile elongation at about room temperature; 12) a medical device having a desired amount of tensile elongation at about room temperature; 13) a medical device having a desired amount of tensile elongation at about room temperature; 14) a medical device having a desired amount of tensile elongation at about room temperature; 15) a medical device having a desired amount of tensile elongation at about room temperature; 16) a medical device having a desired amount of tensile elongation at about room temperature; 7) a medical device having a desired ultimate tensile strength and yield strength; 8) a medical device having a very thin wall thickness and still having the desired radial force required to hold the medical device open when expanded; 9) a medical device that exhibits reduced recoil when the medical device is compressed onto a delivery system and/or expanded within a body passage; 10) a medical device that exhibits improved conformance to the shape of the treatment area within the body passage when the medical device is expanded within the body passage; 11) a medical device that exhibits improved fatigue ductility; and/or 12) a medical device that has increased durability.

According to another and/or alternative non-limiting aspect of the present disclosure, at least 30 wt. % (e.g., 30-100 wt. % and all values and ranges therebetween) of the refractory metal alloy comprises one or more of molybdenum, niobium, rhenium, tantalum, or tungsten. In another non-limiting embodiment, at least 40 wt. % of the refractory metal alloy comprises one or more of molybdenum, niobium, rhenium, tantalum, or tungsten. In another non-limiting embodiment, at least 50 wt. % of the refractory metal alloy comprises one or more of molybdenum, niobium, rhenium, tantalum, or tungsten.

In another non-limiting embodiment, the refractory metal alloy comprises at least 50% by weight (e.g., 50-100% by weight and all values and ranges therebetween) of one or more of molybdenum, niobium, rhenium, tantalum, or tungsten, and 0-40% by weight (and all values and ranges therebetween) of a refractory metal alloy. The refractory metal alloy comprises one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, nickel, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, technetium, titanium, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide. In another non-limiting embodiment, the refractory metal alloy comprises at least 50% by weight (e.g., 50-99.9% by weight and all values and ranges therebetween) of one or more of molybdenum, niobium, rhenium, tantalum, or tungsten, and 0.1-40% by weight (and all values and ranges therebetween) of a refractory metal alloy comprising one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, nickel, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, technetium, titanium, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide. In another non-limiting embodiment, the refractory metal alloy comprises at least 50 weight percent (e.g., 50-100 weight percent and all values and ranges therebetween) of one or more of molybdenum, niobium, rhenium, tantalum, or tungsten, and 0-40 weight percent (and all values and ranges therebetween) of a refractory metal alloy comprising one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, nickel, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, technetium, titanium, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy comprises 0-2 weight percent (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, the refractory metal alloy comprises at least 50% by weight (e.g., 50-99.9% by weight and all values and ranges therebetween) of one or more of molybdenum, niobium, rhenium, tantalum, or tungsten, and 0.1-40% by weight (and all values and ranges therebetween) of a refractory metal alloy comprising one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, nickel, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, technetium, titanium, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy comprises 0-2% by weight (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, at least 55% by weight of the refractory metal alloy includes one or more of molybdenum, niobium, rhenium, tantalum, or tungsten, and 0-40% by weight of the refractory metal alloy including one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, nickel, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, technetium, titanium, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy includes 0-0.1% by weight of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, at least 55% by weight of the refractory metal alloy includes one or more of molybdenum, niobium, rhenium, tantalum, or tungsten, and 0.1 to 40% by weight of the refractory metal alloy, which includes one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, nickel, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, technetium, titanium, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy includes 0 to 0.1% by weight of a combination of other metals, carbon, oxygen, and nitrogen.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy comprises at least 30% by weight (e.g., 30-99% by weight and all values and ranges therebetween) of rhenium and one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, a rare earth metal, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide. In another non-limiting embodiment, the refractory metal alloy includes at least 30% by weight (e.g., 30-99% by weight and all values and ranges therebetween) of rhenium and one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy includes 0-2% by weight (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, the refractory metal alloy includes at least 30% by weight (e.g., 30-99% by weight and all values and ranges therebetween) of rhenium and one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy includes 0-0.1% by weight (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, the refractory metal alloy comprises at least 35% by weight (e.g., 35-99% by weight and all values and ranges therebetween) rhenium and 0.1-65% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide. In another non-limiting embodiment, the refractory metal alloy comprises at least 35 weight percent rhenium (e.g., 35-99 weight percent and all values and ranges therebetween) and 0.1-65 weight percent (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy comprises 0-2 weight percent (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, the refractory metal alloy comprises at least 35 weight percent rhenium (e.g., 35-99.9 weight percent and all values and ranges therebetween) and 0.1-65 weight percent (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy comprises 0-0.1 weight percent (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, the refractory metal alloy comprises at least 40% by weight (e.g., 40-99.9% by weight and all values and ranges therebetween) rhenium and 0.1-60% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide. In another non-limiting embodiment, the refractory metal alloy comprises at least 40% by weight rhenium (e.g., 40-99.9% by weight and all values and ranges therebetween) and 0.1-60% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy comprises 0-2% by weight (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen. In another non-limiting embodiment, the refractory metal alloy comprises at least 40% by weight (e.g., 40-99.9% by weight and all values and ranges therebetween) of rhenium and 0.1-60% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, or zirconium oxide, and the refractory metal alloy comprises 0-0.1% by weight (and all values and ranges therebetween) of a combination of other metals, carbon, oxygen, and nitrogen.

According to another and/or alternative non-limiting aspect of the present disclosure, a refractory metal alloy is provided, wherein at least 20 wt. % (e.g., 20-99 wt. % and all values and ranges therebetween) of the refractory metal alloy comprises rhenium. In one non-limiting embodiment, the refractory metal alloy comprises at least 20% by weight (e.g., 20-99.9% by weight and all values and ranges therebetween) of rhenium and 0.1-80% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 20 weight percent rhenium (e.g., 30-99.9 weight percent and all values and ranges therebetween) and 0.1-80 weight percent (and all values and ranges therebetween) of one or more of copper, chromium, hafnium, iridium, manganese, molybdenum, niobium, osmium, rhodium, ruthenium, tantalum, technetium, titanium, tungsten, vanadium, zirconium, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 30% by weight (e.g., 30-99.9% by weight and all values and ranges therebetween) rhenium, and 0.1-70% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 30% by weight (e.g., 30-99.9% by weight and all values and ranges therebetween) of rhenium and 0.1-70% by weight (and all values and ranges therebetween) of one or more of copper, chromium, hafnium, iridium, manganese, molybdenum, niobium, osmium, rhodium, ruthenium, tantalum, technetium, titanium, tungsten, vanadium, zirconium, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 35% by weight (e.g., 35-99.9% by weight and all values and ranges therebetween) rhenium, and 0.1-65% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 35 weight percent rhenium (e.g., 35-99.9 weight percent and all values and ranges therebetween) and 0.1-65 weight percent (and all values and ranges therebetween) of one or more of copper, chromium, hafnium, iridium, manganese, molybdenum, niobium, osmium, rhodium, ruthenium, tantalum, technetium, titanium, tungsten, vanadium, zirconium, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises 35-60% by weight (and all values and ranges therebetween) of rhenium and 40-65% by weight (and all values and ranges therebetween) of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises 35-60 weight percent rhenium (and all values and ranges therebetween) and 40-65 weight percent (and all values and ranges therebetween) of one or more of copper, chromium, hafnium, iridium, manganese, molybdenum, niobium, osmium, rhodium, ruthenium, tantalum, technetium, titanium, tungsten, vanadium, zirconium, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 40% by weight rhenium (e.g., 40-99.9% by weight and all values and ranges therebetween) and 0.1-60% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 40% by weight (e.g., 40-99.9% by weight and all values and ranges therebetween) of rhenium and 0.1-60% by weight (and all values and ranges therebetween) of one or more of copper, chromium, hafnium, iridium, manganese, molybdenum, niobium, osmium, rhodium, ruthenium, tantalum, technetium, titanium, tungsten, vanadium, zirconium, and/or alloys of one or more of these components. In one non-limiting embodiment, the refractory metal alloy comprises at least 50% by weight (e.g., 50-99.9% by weight and all values and ranges therebetween) rhenium and 0.1-50% by weight (and all values and ranges therebetween) of one or more of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components. In another non-limiting embodiment, the refractory metal alloy comprises at least 50% by weight (e.g., 50-99.9% by weight and all values and ranges therebetween) of rhenium and 0.1-50% by weight (and all values and ranges therebetween) of one or more of copper, chromium, hafnium, iridium, manganese, molybdenum, niobium, osmium, rhodium, ruthenium, tantalum, technetium, titanium, tungsten, vanadium, zirconium, and/or alloys of one or more of these components.

In another non-limiting aspect of the present disclosure, the metals used to form the refractory metal alloy include, but are not limited to, rhenium, tungsten, and optionally one or more alloying agents such as calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iron, lanthanum oxide, lead, magnesium, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhenium, silver, tantalum, technetium, titanium, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components (e.g., WRe, WReMo, etc.). Although the refractory metal alloy is described as including one or more metals and/or metal oxides, it may be understood that a portion of the metals and/or metal oxides in the refractory metal alloy may be replaced with one or more materials selected from the group of ceramics, plastics, thermoplastics, thermosets, rubbers, laminates, nonwovens, etc. In one non-limiting formulation, the refractory metal alloy includes 1-40 wt. % rhenium (and all values and ranges therebetween) and 60-99 wt. % tungsten (and all values and ranges therebetween). In one non-limiting embodiment, the combined weight percentage of tungsten and rhenium in the tungsten-rhenium alloy is at least about 95 wt. %, typically at least about 99 wt. %, more typically at least about 99.5 wt. %, and even more typically at least about 99.9 wt. % and even more typically at least about 99.99 wt. %. In another non-limiting formulation, the refractory metal alloy includes 1-47.5 wt. % rhenium (and all values and ranges therebetween), 20-80 wt. % tungsten (and all values and ranges therebetween), and 1-47.5 wt. % molybdenum (and all values and ranges therebetween). The combined weight percentage of tungsten, rhenium and molybdenum is at least about 95 weight percent, typically at least about 99 weight percent, more typically at least about 99.5 weight percent, even more typically at least about 99.9 weight percent, and even more typically at least about 99.99 weight percent. In one non-limiting specific tungsten-rhenium-molybdenum alloy, the weight percentage of tungsten is greater than the weight percentage of rhenium and is also greater than the weight percentage of molybdenum. In another non-limiting specific tungsten-rhenium-molybdenum alloy, the weight percentage of tungsten is greater than 50 weight percent of the tungsten-rhenium-molybdenum alloy. In another non-limiting specific tungsten-rhenium-molybdenum alloy, the weight percentage of tungsten is greater than the weight percentage of rhenium but less than the weight percentage of molybdenum. In another non-limiting specific tungsten-rhenium-molybdenum alloy, the weight percentage of tungsten is greater than the weight percentage of molybdenum, but less than the weight percentage of rhenium. In another non-limiting specific tungsten-rhenium-molybdenum alloy, the weight percentage of tungsten is less than the weight percentage of rhenium and also less than the weight percentage of molybdenum.

In another non-limiting aspect of the present disclosure, the metals used to form the refractory metal alloy include rhenium, molybdenum, and one or more alloying metals selected from the group consisting of bismuth, chromium, copper, hafnium, iridium, manganese, niobium, osmium, rhodium, ruthenium, tantalum, technetium, titanium, tungsten, vanadium, yttrium, and zirconium. In one non-limiting embodiment, the combined weight percentage of rhenium and alloying metals in the refractory metal alloy is equal to or greater than the weight percentage of molybdenum in the refractory metal alloy. In another non-limiting embodiment, the combined weight percentage of rhenium and alloying metals in the refractory metal alloy is greater than the weight percentage of molybdenum in the refractory metal alloy. In another non-limiting embodiment, the weight percentage of molybdenum in the refractory metal alloy is at least 10% by weight and less than 60% by weight (and all values and ranges therebetween). In another non-limiting embodiment, the weight percentage of rhenium in the refractory metal alloy is 35-60 weight percent (and all values and ranges therebetween). In another non-limiting embodiment, the weight percentage of rhenium in the refractory metal alloy is 5-45 weight percent (and all values and ranges therebetween) of the refractory metal alloy. In another non-limiting embodiment, the weight percentage of rhenium in the refractory metal alloy is greater than the combined weight percentage of the alloying metals. In another non-limiting embodiment, the combined weight percentage of rhenium, molybdenum, and the one or more alloying metals in the refractory metal alloy is at least 99.9 weight percent. In another non-limiting embodiment, the alloying metal comprises chromium. In another non-limiting embodiment, the alloying metal comprises chromium and one or more metals selected from the group consisting of bismuth, zirconium, iridium, niobium, tantalum, titanium, and yttrium. In another non-limiting embodiment, the alloying metal comprises chromium and one or more metals selected from the group consisting of bismuth, zirconium, iridium, niobium, tantalum, titanium, and yttrium, where the atomic ratio of chromium to each or all of the metals selected from the group consisting of bismuth, chromium, iridium, niobium, tantalum, titanium, and yttrium is from 0.4:1 to 2.5:1 (and all values and ranges therebetween). In another non-limiting embodiment, the alloying metal comprises chromium and one or more metals selected from the group consisting of zirconium, niobium, and tantalum. In another non-limiting embodiment, the alloying metals include a first metal selected from the group consisting of bismuth, chromium, iridium, niobium, tantalum, titanium, yttrium, and zirconium, and a second metal selected from the group consisting of bismuth, chromium, iridium, niobium, tantalum, titanium, yttrium, and zirconium, and the first metal and the second metal are distinct from each other, and the atomic ratio of the first metal to the second metal is 0.4:1 to 2.5:1 (and all values and ranges therebetween). In another non-limiting embodiment, the alloying metals include a first metal selected from the group consisting of chromium, niobium, tantalum, and zirconium, and a second metal selected from the group consisting of chromium, niobium, tantalum, and zirconium, and the first metal and the second metal are distinct from each other, and the atomic ratio of the first metal to the second metal is 0.4:1 to 2.5:1 (and all values and ranges therebetween).

According to another and/or alternative non-limiting aspect of the present disclosure, the weight percentage of rhenium and the total weight percentage of bismuth, niobium, tantalum, tungsten, titanium, vanadium, chromium, manganese, yttrium, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper and iridium is greater than the weight percentage of molybdenum in the refractory metal alloy. In one particular non-limiting formulation, the sum of the weight percentage of rhenium and the total weight percentage of bismuth, chromium, iridium, niobium, tantalum, titanium, yttrium and zirconium is greater than the weight percentage of molybdenum in the refractory metal alloy. In another particular non-limiting formulation, the sum of the weight percentage of rhenium and the total weight percentage of chromium, niobium, tantalum and zirconium is greater than the weight percentage of molybdenum in the refractory metal alloy. In another non-limiting specific non-limiting formulation, the weight percentage of molybdenum in the refractory metal alloy is at least 10 weight percent and less than 50 weight percent (and all values and ranges therebetween). In another non-limiting specific non-limiting formulation, the weight percentage of rhenium in the refractory metal alloy is 41-58.5 weight percent (and all values and ranges therebetween), the weight percentage of molybdenum in the refractory metal alloy is at least 15-45 weight percent (and all values and ranges therebetween), and the combined weight percentage of bismuth, niobium, tantalum, tungsten, titanium, vanadium, chromium, manganese, yttrium, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, and iridium in the refractory metal alloy is 11-41 weight percent (and all values and ranges therebetween). In another non-limiting specific non-limiting formulation, the weight percentage of rhenium in the refractory metal alloy is 41-58.5 weight percent (and all values and ranges therebetween), the weight percentage of molybdenum in the refractory metal alloy is at least 15-45 weight percent (and all values and ranges therebetween), and the combined weight percentage of bismuth, chromium, iridium, niobium, tantalum, titanium, yttrium, and zirconium in the refractory metal alloy is 11-41 weight percent (and all values and ranges therebetween). In another non-limiting specific non-limiting formulation, the weight percentage of rhenium in the refractory metal alloy is 41-58.5 wt.% (and all values and ranges therebetween), the weight percentage of molybdenum in the refractory metal alloy is at least 15-45 wt.% (and all values and ranges therebetween), and the combined weight percentage of chromium, niobium, tantalum, and zirconium in the refractory metal alloy is 11-41 wt.% (and all values and ranges therebetween). In another non-limiting embodiment of the present invention, the weight percentage of rhenium in the refractory metal alloy is greater than the combined weight percentage of bismuth, chromium, iridium, niobium, tantalum, titanium, yttrium, and zirconium in the refractory metal alloy. In another non-limiting specific non-limiting formulation, the weight percentage of rhenium in the refractory metal alloy is greater than the combined weight percentage of chromium, niobium, tantalum, and zirconium in the refractory metal alloy.

According to another and/or alternative non-limiting aspect of the present disclosure, the atomic weight ratio of rhenium to the atomic weight ratio of the combination of bismuth, niobium, tantalum, tungsten, titanium, vanadium, chromium, manganese, yttrium, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, and iridium in the refractory metal alloy is 0.7:1 to 1.5:1 (and all values and ranges therebetween), typically 0.8:1 to 1.4:1, more typically 0.8:1 to 1.25:1, and even more typically about 0.9:1 to 1.1:1 (e.g., 1:1). In one particular non-limiting formulation, the atomic weight ratio of rhenium to the atomic weight ratio of the combination of bismuth, chromium, iridium, niobium, tantalum, titanium, yttrium, and zirconium is 0.7:1 to 5.1:1 (and all values and ranges therebetween), typically 0.8:1 to 1.5, more typically 0.8:1 to 1.25:1, and even more typically about 0.9:1 to 1.1:1 (e.g., 1:1). In one particular non-limiting formulation, the atomic weight ratio of rhenium to the atomic weight ratio of the combination of chromium, niobium, tantalum, and zirconium is 0.7:1 to 5.1:1 (and all values and ranges therebetween), typically 0.8:1 to 1.5:1, more typically 0.8:1 to 1.25:1, and even more typically about 0.9:1 to 1.1:1 (e.g., 1:1).

According to another and/or alternative non-limiting aspect of the present disclosure, when the refractory metal alloy comprises two of bismuth, niobium, tantalum, tungsten, titanium, vanadium, chromium, manganese, yttrium, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, and iridium, the atomic ratio of the two metals is 0.4:1 to 2.5:1 (and all values and ranges therebetween), typically 0.5:1 to 2:1. In one particular non-limiting formulation, when the refractory metal alloy comprises two of bismuth, chromium, iridium, niobium, tantalum, titanium, yttrium, and zirconium, the atomic ratio of the two metals is 0.4:1 to 2.5:1 (and all values and ranges therebetween), typically 0.5:1 to 2:1. In another specific non-limiting formulation, when the refractory metal alloy includes two of chromium, niobium, tantalum, and zirconium, the atomic ratio of the two metals is 0.4:1 to 2.5:1 (and all values and ranges therebetween), typically 0.5:1 to 2:1.

According to another and/or alternative non-limiting aspect of the present disclosure, at least 35 wt. % of the refractory metal alloy (e.g., 35-75 wt. % and all values and ranges therebetween) comprises rhenium, and the refractory metal alloy also comprises chromium. In one non-limiting embodiment, at least 25 wt. % of the refractory metal alloy (e.g., 25-49.9 wt. % and all values and ranges therebetween) comprises chromium. In another non-limiting embodiment, at least 30 wt. % of the refractory metal alloy comprises chromium. In another non-limiting embodiment, at least 33 wt. % of the refractory metal alloy comprises chromium. In another non-limiting embodiment, at least 50 wt. % of the refractory metal alloy (e.g., 50-74.9 wt. % and all values and ranges therebetween) comprises rhenium, at least 25 wt. % of the refractory metal alloy (e.g., 25-49.9 wt. % and all values and ranges therebetween) comprises chromium, and 0.1-25 wt. % (and all values and ranges therebetween) of the refractory metal alloy comprises one or more of molybdenum, bismuth, niobium, tantalum, titanium, vanadium, tungsten, manganese, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, yttrium, zirconium, and/or iridium. In another non-limiting embodiment, at least 55 wt. % (e.g., 55-69.9 wt. % and all values and ranges therebetween) of the refractory metal alloy comprises rhenium, at least 30 wt. % (e.g., 30-44.9 wt. % and all values and ranges therebetween) of the refractory metal alloy comprises chromium, and 0.1-15 wt. % (and all values and ranges therebetween) of the refractory metal alloy comprises one or more of molybdenum, bismuth, niobium, tantalum, titanium, vanadium, tungsten, manganese, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, yttrium, zirconium, and/or iridium. In another non-limiting embodiment, at least 60 weight percent of the refractory metal alloy (e.g., 60-69.9 weight percent and all values and ranges therebetween) comprises rhenium, at least 30 weight percent of the refractory metal alloy (e.g., 30-39.9 weight percent and all values and ranges therebetween) comprises chromium, and 0.1-10 weight percent (and all values and ranges therebetween) of the refractory metal alloy comprises one or more of molybdenum, bismuth, niobium, tantalum, titanium, vanadium, tungsten, manganese, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, yttrium, zirconium, and/or iridium. In another non-limiting embodiment, at least 62 wt. % (e.g., 62-67.9 wt. % and all values and ranges therebetween) of the refractory metal alloy comprises rhenium, at least 32 wt. % (e.g., 32-32.9 wt. % and all values and ranges therebetween) of the refractory metal alloy comprises chromium, and 0.1-6 wt. % (and all values and ranges therebetween) of the refractory metal alloy comprises one or more of molybdenum, bismuth, niobium, tantalum, titanium, vanadium, tungsten, manganese, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, yttrium, zirconium, and/or iridium.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy includes less than about 5 wt. % (e.g., 0-4.999999 wt. % and all values and ranges therebetween) of other metals and/or impurities. High purity levels of the refractory metal alloy result in a more homogeneous alloy. This results in a more uniform density throughout the refractory metal alloy, as well as the desired yield strength and ultimate tensile strength of the refractory metal alloy. In one non-limiting embodiment, the refractory metal alloy includes less than about 0.5 wt. % of other metals and/or impurities. In another non-limiting embodiment, the refractory metal alloy includes less than about 0.2 wt. % of other metals and/or impurities. In another non-limiting embodiment, the refractory metal alloy includes less than about 0.1 wt. % of other metals and/or impurities. In another non-limiting embodiment, the refractory metal alloy includes less than about 0.05 wt. % of other metals and/or impurities. In another non-limiting embodiment, the refractory metal alloy contains less than about 0.01% by weight of other metals and/or impurities.

Some non-limiting examples of refractory metal alloys according to the present disclosure are described below.

In Examples 1-146, all of the ranges above can be understood to include any value between that range and any other range between the ranges above. Any value above that includes the symbol ≦ includes a range from 0 to the specified value and all values and ranges therebetween.

In the above refractory metal alloy, the average grain size of the refractory metal alloy is about 4-20 ASTM, the tensile elongation of the refractory metal alloy is 25-50%, the average density of the refractory metal alloy is at least about 5 gm/cc, the average yield strength of the refractory metal alloy is about 70-250 (ksi), the average ultimate tensile strength of the refractory metal alloy is about 80-550 UTS (ksi), the average Vickers hardness is 234 DPH-700 DPH, and the Rockwell C hardness is 19-60 at 77°F, but these are not required.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is optionally at least partially formed by a swaging process, but this is not required. In one non-limiting embodiment, a swaging process is performed on the refractory metal alloy to at least partially or completely achieve the final dimensions of one or more portions of the medical device. The swaging die can be shaped to match the final dimensions of the medical device, but this is not required. If the medical device has an undercut of the hollow structure (which is not required), a separate metal piece can be placed in the undercut to at least partially fill the gap. The separate metal piece (when used) can be designed to be later removed from the undercut, but this is not required. The swaging operation can be performed on the medical device in the area to be hardened. In the case of round or curved portions of the medical device, the swaging can be rotary. In the case of non-circular portions of the medical device, the swaging of the non-circular portions of the medical device can be performed by a non-rotating swaging die. The die can be made to oscillate radially and/or longitudinally instead of or in addition to rotating. The medical device can be swaged in multiple directions, either in a single operation or in multiple operations, to achieve hardness in a desired location and/or direction of the medical device. The swaging temperature for a particular refractory metal alloy may vary. For refractory metal alloys (such as MoRe alloys, ReW alloys, ReCr alloys, etc.), the swaging temperature can be from room temperature (RT) (e.g., 10-27°C and all values and ranges therebetween) to about 400°C (e.g., 10-400°C and all values and ranges therebetween) if the swaging is performed in air or in an oxidizing environment. If the swaging is performed in a controlled neutral or non-reducing environment (e.g., an inert environment), the swaging temperature can be increased up to about 1500°C (e.g., 10-1500°C and all values and ranges therebetween). The swaging process can be performed by repeatedly hitting the medical device at the location to be hardened with a hammer at the desired swaging temperature. In one non-limiting embodiment, during the swaging process, boron and/or nitrogen ions bombard the rhenium atoms in the rhenium-containing refractory metal alloy to form ReB ₂ , ReN ₂ and/or ReN ₃ , although this is not required. ReB ₂ , ReN ₂ and/or ReN 3 have been found to be superhard compounds. As will be appreciated, other refractory metal alloys containing Re and undergoing swaging can also form ReB ₂ , ReN ₂ and/or ReN 3. In one non-limiting process, the refractory metal alloy for the medical device can be machined and shaped to at least partially form the medical device when the refractory metal alloy is in a less hardened state, although this is not required. Thus, the raw material can first be annealed to soften it and then machined into the desired shape. After forming the refractory metal alloy, the refractory metal alloy can be rehardened. Hardening the refractory metal alloy of the medical device can improve the wear resistance and/or shape retention of the medical device. Medical refractory metal alloys generally cannot be rehardened by annealing and therefore require special rehardening treatment. Such rehardening can be achieved by the swaging process of the present disclosure.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy can be optionally, but not necessarily, nitrided. The nitride layer on the refractory metal alloy can act as a lubricating surface during any drawing of the refractory metal alloy in partially or completely forming the medical device. After the refractory metal alloy is nitrided, it is typically, but not necessarily, washed. During the nitriding process, the surface of the refractory metal alloy is modified by the presence of nitrogen. The nitriding process can be performed by gas nitriding, salt bath nitriding, or plasma nitriding. In gas nitriding, nitrogen diffuses into the surface of the refractory metal alloy, thereby forming a nitride layer. The thickness and phase composition of the resulting nitride layer can be selected to optimize the process for the specific properties required. During gas nitriding, the refractory metal alloy is generally nitrided for at least 10 seconds in the presence of nitrogen gas or a nitrogen gas mixture (e.g., 90-99% volume % nitrogen and 1-10% volume % hydrogen, etc.). The refractory metal alloy is nitrided at a temperature of at least about 400° C. (e.g., 400-1000° C. and all values and ranges therebetween). In one non-limiting nitriding process, the refractory metal alloy is heated in the presence of nitrogen or a mixture of nitrogen and hydrogen to a temperature of at least 400° C., generally about 400-800° C. (and all values and ranges therebetween), for at least 10 seconds (e.g., from 10 seconds to 60 minutes and all values and ranges therebetween), generally about 1-30 minutes. In salt bath nitriding, a nitrogen-containing salt, such as a cyanide salt, is used. During salt bath nitriding, the refractory metal alloy is generally exposed to a temperature of about 520-590° C. In plasma nitriding, the gas used for plasma nitriding is usually pure nitrogen. Plasma nitriding is often performed in combination with a physical vapor deposition (PVD) process, although this is not required. Plasma nitriding is generally performed at a temperature of 220-630° C. (and all values and ranges therebetween). The refractory metal alloy may be optionally exposed to argon and/or hydrogen gas prior to the nitriding process to clean and/or preheat the refractory metal alloy. These gases may be optionally used to remove oxide layers and/or solvents from the surface of the refractory metal alloy. The refractory metal alloy may be optionally exposed to hydrogen gas during the nitriding process to inhibit or prevent the formation of oxides on the surface of the refractory metal alloy. The nitrided surface layer has a thickness of less than about 1 mm. In one non-limiting embodiment, the nitrided surface layer has a thickness of at least about 50 nanometers and less than about 1 mm (and all values and ranges therebetween). In another non-limiting embodiment, the nitrided surface layer has a thickness of at least about 50 nanometers and less than about 0.1 mm. In general, the weight percentage of nitrogen in the nitrided surface layer is 0.0001 to 5 weight percent nitrogen (and all values and ranges therebetween). In one non-limiting embodiment, the weight percentage of nitrogen in the nitrided surface layer is generally less than one of the major components of the refractory metal alloy, and typically less than each of the two major components of the refractory metal alloy. For example, when a refractory metal alloy in the form of a MoRe alloy is nitrided, the weight percentage of nitrogen in the nitrided surface layer is less than the weight percentage of molybdenum in the nitrided surface layer. Also, the weight percentage of nitrogen in the nitrided surface layer is less than the weight percentage of rhenium in the nitrided surface layer. In one non-limiting composition of a nitrided surface layer on a MoRe alloy (e.g., 40-99 wt. % Mo, 1-40 wt. % Re), the nitrided surface layer includes 40-99 wt. % molybdenum (and all values and ranges therebetween), 1-40 wt. % rhenium (and all values and ranges therebetween), and 0.0001-5 wt. % nitrogen (and all values and ranges therebetween). In another non-limiting composition of the nitrided surface layer, the nitrided surface layer includes 40-99 wt. % molybdenum, 1-40 wt. % rhenium, and 0.001-1 wt. % nitrogen. As will be appreciated, other refractory metal alloys can also be nitrided. For such other refractory metal alloys, the nitrided surface layer typically includes 0.001-5 wt. % nitrogen (and all values and ranges therebetween) and the refractory metal alloy (e.g., refractory metal alloy). The major component of the refractory metal alloy (metal constituting at least 5% by weight of the refractory metal alloy) is present in the nitride surface layer in a weight percentage greater than the nitrogen content in the refractory metal alloy. Nitriding for refractory metal alloys can be used to increase the hardness and/or wear resistance of the surface of a medical device and/or to inhibit or prevent discoloration (e.g., oxidative discoloration, etc.) of the refractory metal alloy. For example, nitriding can be used to increase the life of a medical device, to improve the wear resistance of articulating surfaces or surfaces of refractory metal alloys used in medical devices, and/or to increase the wear life of mating surfaces on medical devices (such as polyethylene liners for joint implants in the knee, hip, shoulder, etc.), to reduce particle generation from use of the medical device, and/or to maintain the appearance of the surface of the refractory metal alloy on the medical device.

According to another and/or alternative non-limiting aspect of the present disclosure, the surface of the refractory metal alloy is optionally nitrided prior to at least one drawing step of the refractory metal alloy.

According to another and/or alternative non-limiting aspect of the present disclosure, after the refractory metal alloy is annealed, the refractory metal alloy is optionally nitrided prior to drawing.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is optionally cleaned to remove nitride compounds on the surface of the refractory metal alloy prior to annealing the refractory metal alloy. The nitride compounds can be removed by various steps including, but not limited to, grit blasting, polishing, and the like. After annealing the refractory metal alloy, the refractory metal alloy can be nitrided again prior to one or more drawing steps, but this is not required. As will be appreciated, the entire outer surface of the refractory metal alloy can be nitrided, or only a portion of the outer surface of the refractory metal alloy can be nitrided.

According to another and/or alternative non-limiting aspect of the present disclosure, only selected portions of the outer surface of the refractory metal alloy can be optionally nitrided to obtain different surface properties of the refractory metal alloy, but this is not required.

According to another and/or alternative non-limiting aspect of the present disclosure, the final formed refractory metal alloy can optionally include a nitride outer surface.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy can be optionally cleaned, polished, sterilized, nitrided, etc., immediately before or immediately after being partially or completely formed into the desired medical device for final processing of the refractory metal alloy. In one non-limiting embodiment of the present disclosure, the refractory metal alloy is optionally electropolished. In one non-limiting aspect of this embodiment, the refractory metal alloy is cleaned before being exposed to the polishing solution, but this is not required. The cleaning process (when used) can be performed by a variety of techniques, including, but not limited to, 1) using a solvent (e.g., acetone, methyl alcohol, etc.) and wiping the refractory metal alloy with a Kimwipe or other suitable towel, and/or 2) at least partially dipping or immersing the refractory metal alloy in a solvent and then ultrasonically cleaning the refractory metal alloy, etc. As can be appreciated, the refractory metal alloy can be cleaned in other or additional ways. According to another and/or alternative non-limiting aspect of this embodiment, the polishing solution may include one or more acids. A non-limiting formulation of the polishing solution includes about 10 to 80 volume percent sulfuric acid (and all values and ranges therebetween). As will be appreciated, other polishing fluid compositions may be used. In yet another and/or alternative non-limiting aspect of this embodiment, about 5 to 12 volts (and all values and ranges therebetween) are applied to the refractory metal alloy during the electropolishing process, although other voltage levels may be used. In yet another and/or alternative non-limiting aspect of this embodiment, the refractory metal alloy is rinsed with water and/or a solvent and dried to remove the polishing fluid on the refractory metal alloy.

According to another and/or alternative non-limiting aspect of the present disclosure, the use of refractory metal alloys to partially or completely form a medical device can be used to increase the strength, hardness, and/or durability of the medical device compared to stainless steel, chromium-cobalt alloys, or titanium alloys, and thus a lesser amount of refractory metal alloy can be used in the medical device to achieve comparable strength compared to a medical device formed of a different metal. Thus, the resulting medical device can be made smaller and less bulky by using refractory metal alloys without sacrificing the strength and durability of the medical device. Such medical devices can have a smaller profile and therefore can be inserted into smaller areas, openings, and/or passages. The refractory metal alloy can also increase the radial strength of the medical device. For example, the thickness of the walls of the medical device and/or the wire used to at least partially form the medical device can be reduced and achieve comparable or improved radial strength compared to a thicker walled medical device formed of stainless steel, titanium alloy, or alloy of cobalt and chromium. The high melting point alloy can also improve the stress-strain properties, bendability and flexibility of the medical device, thereby increasing the lifespan of the medical device. For example, the medical device can be used in areas where the medical device is bent. The improvement in the physical properties of the medical device by the high melting point metal alloy increases the fracture resistance of the medical device in such frequent bending environments. Additionally or alternatively, the improved bendability and flexibility of the medical device due to the use of the high melting point metal alloy can allow the medical device to be more easily inserted into various areas of the body. The high melting point metal alloy can also reduce the degree of recoil during compression and/or expansion of the medical device. For example, the medical device better maintains its compressed shape and/or better maintains its expanded shape after expansion due to the use of the high melting point metal alloy. Thus, when the medical device is compressed, when the medical device is mounted on the delivery device, the medical device better maintains its smaller profile during insertion of the medical device into various areas of the body. The medical device also better maintains its expanded profile after expansion, promoting the success of the medical device in the treatment area. In addition to improving the physical properties of the medical device through the use of refractory metal alloys, refractory metal alloys have improved radiopacity compared to standard materials such as stainless steel or cobalt-chromium alloys, thereby reducing or eliminating the need for marker materials on the medical device. For example, refractory metal alloys are believed to be at least about 10-20% more radiopaque than stainless steel or cobalt-chromium alloys.

In accordance with another and/or alternative non-limiting aspect of the present disclosure, the medical device may include, contain, and/or be coated with one or more agents that enhance the success of the medical device and/or therapeutic area. The term "agent" includes, but is not limited to, substances, pharmaceuticals, biologics, veterinary products, drugs, and analogs or derivatives that are otherwise formulated and/or designed to prevent, inhibit, and/or treat one or more clinical and/or biological events and/or promote healing. Non-limiting examples of clinical events that may be addressed by one or more agents include viral, fungal and/or bacterial infections, vascular diseases and/or disorders, digestive diseases and/or disorders, reproductive diseases and/or disorders, lymphatic system diseases and/or disorders, cancer, implant rejection, pain, nausea, swelling, arthritis, bone diseases and/or disorders, organ failure, immune diseases and/or disorders, cholesterol problems, blood diseases and/or disorders, lung diseases and/or disorders, heart diseases and/or disorders, brain diseases and/or disorders, nerve pain diseases and/or disorders, kidney diseases and/or disorders, ulcers, liver diseases, The therapeutic effects of the present invention include, but are not limited to, diseases and/or disorders, intestinal diseases and/or disorders, gallbladder diseases and/or disorders, pancreatic diseases and/or disorders, psychiatric disorders, respiratory diseases and/or disorders, glandular diseases and/or disorders, skin diseases and/or disorders, hearing diseases and/or disorders, oral diseases and/or disorders, nasal diseases and/or disorders, eye diseases and/or disorders, fatigue, genetic diseases and/or disorders, burns, scars and/or scars, trauma, weight diseases and/or disorders, addiction diseases and/or disorders, hair loss, convulsions, muscle spasms, tissue repair, nerve repair, nerve regeneration, and the like. Non-limiting examples of agents that can be used include 5-fluorouracil and/or derivatives thereof, 5-phenylmethimazole and/or derivatives thereof, ACE inhibitors and/or derivatives thereof, acenocoumarol and/or derivatives thereof, acyclovir and/or derivatives thereof, actilyse and/or derivatives thereof, adrenocorticotropic hormone and/or derivatives thereof, adriamycin and/or derivatives thereof, agents that modulate intracellular Ca2+ transport such as L-type (e.g., diltiazem, nifedipine, verapamil, etc.) or T-type Ca2+ channel blockers (e.g., amiloride, etc.), α-adrenergic blockers and/or derivatives thereof, alteplase and/or derivatives thereof, aminoglycosides and/or derivatives thereof (e.g., gentamicin, tobramycin, etc.), angiopeptin and/or derivatives thereof, angiogenic antisteroids and/or derivatives thereof, angiotensin II receptor antagonists and/or derivatives thereof, anistreplase and/or derivatives thereof, vascular epithelium. Antagonists of growth factors and/or derivatives thereof, antibiotics, anticoagulant compounds and/or derivatives thereof, antifibrotic compounds and/or derivatives thereof, antifungal compounds and/or derivatives thereof, anti-inflammatory compounds and/or derivatives thereof, anti-invasion factors and/or derivatives thereof, antimetabolic compounds and/or derivatives thereof (e.g., staurosporine, trichothecenes, modified diphtheria and ricin toxins, pseudomonas exotoxins, etc.), anti-matrix compounds and/or derivatives thereof (e.g., colchicine, tamoxifen, antimicrobial agents and/or derivatives thereof, antimigratory agents and/or derivatives thereof (e.g., caffeic acid derivatives, nilvadipine, etc.), antimitotic compounds and/or derivatives thereof, antitumor compounds and/or derivatives thereof, antioxidants and/or derivatives thereof, antiplatelet compounds and/or derivatives thereof, antiproliferative agents and/or derivatives thereof, antithrombotic agents and/or derivatives thereof, argatroban and/or derivatives thereof, ap-1 inhibitors and/or derivatives thereof (e.g., tyrosine kinase, protein kinase C, myoglobin, scin light chain kinase, Ca2+/calmodulin kinase II, casein kinase II, etc.), aspirin and/or derivatives thereof, azathioprine and/or derivatives thereof, β-estradiol and/or derivatives thereof, β-1-anticollagenase and/or derivatives thereof, calcium channel blockers and/or derivatives thereof, calmodulin antagonists and/or derivatives thereof (e.g., H7, etc.), captopril and/or derivatives thereof, cartilage derived inhibitors and/or derivatives thereof, Ch IMP-3 and/or derivatives thereof, cephalosporins and/or derivatives thereof (e.g., cefadroxil, cefazolin, cefaclor, etc.), chloroquine and/or derivatives thereof, chemotherapeutic compounds and/or derivatives thereof (e.g., 5-fluorouracil, vincristine, vinblastine, cisplatin, doxorubicin, adriamycin, tamosifen, etc.), chymostatin and/or derivatives thereof, cilazapril and/or derivatives thereof, clopidigrel and/or derivatives thereof, clopidogrel and/or derivatives thereof, Trimazole and/or derivatives thereof, colchicine and/or derivatives thereof, cortisone and/or derivatives thereof, coumadin and/or derivatives thereof, curacin-A and/or derivatives thereof, cyclosporine and/or derivatives thereof, cytochalasin and/or derivatives thereof (e.g., cytochalasin A, cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E, cytochalasin F, cytochalasin G, cytochalasin H, cytochalasin J, cytochalasin K, cytochalasin cytochalasin L, cytochalasin M, cytochalasin N, cytochalasin O, cytochalasin P, cytochalasin Q, cytochalasin R, cytochalasin S, chetoglobosin A, chetoglobosin B, chetoglobosin C, chetoglobosin D, chetoglobosin E, chetoglobosin F, chetoglobosin G, chetoglobosin J, chetoglobosin K, deoxaphomin, proxyphomin, protophomin, zygosporin D, zygosporin E, zygosporin F, zygosporin G, aspochalasin B, aspochalasin C, aspochalasin D, etc.), cytokines and/or derivatives thereof, desirudin and/or derivatives thereof, dexamethasone and/or derivatives thereof, dipyridamole and/or derivatives thereof, eminase and/or derivatives thereof, endothelin and/or derivatives thereof, endothelial growth factor and/or derivatives thereof, epidermal growth factor and/or derivatives thereof, epothilone and/or derivatives thereof, estramustine and/or derivatives thereof, estrogen and/or derivatives thereof, fenoprofen and and/or derivatives thereof, fluorouracil and/or derivatives thereof, flucytosine and/or derivatives thereof, forskolin and/or derivatives thereof, ganciclovir and/or derivatives thereof, glucocorticoids and/or derivatives thereof (e.g., dexamethasone, betamethasone, etc.), glycoprotein IIb/IIIa platelet membrane receptor antibodies and/or derivatives thereof, GM-CSF and/or derivatives thereof, griseofulvin and/or derivatives thereof, growth factors and/or derivatives thereof (e.g., VEGF, TGF, IGF, PDGF, FGF, etc.), growth hormone and/or derivatives thereof, heparin and/or derivatives thereof, hirudin and/or derivatives thereof, hyaluronate and/or derivatives thereof, hydrocortisone and/or derivatives thereof, ibuprofen and/or derivatives thereof, immunosuppressants and/or derivatives thereof (e.g., corticosteroids, cyclosporine, etc.), indomethacin and/or derivatives thereof, inhibitors of sodium/calcium antiporters and/or derivatives thereof (e.g., amiloride, etc.), inhibitors of IP3 receptors and/or derivatives thereof, inhibitors of sodium/hydrogen antiporters and/or derivatives thereof (e.g., amiloride and derivatives thereof), insulin and/or derivatives thereof, interferon α-2-macroglobulin and/or derivatives thereof, ketoconazole and/or derivatives thereof, lepirudin and/or derivatives thereof, lisinopril and/or derivatives thereof, lovastatin and/or derivatives thereof, marevane and/or derivatives thereof, mefloquine and/or and derivatives thereof, metalloproteinase inhibitors and/or derivatives thereof, methotrexate and/or derivatives thereof, metronidazole and/or derivatives thereof, miconazole and/or derivatives thereof, monoclonal antibodies and/or derivatives thereof, mutamycin and/or derivatives thereof, naproxen and/or derivatives thereof, nitric oxide and/or derivatives thereof, nitroprusside and/or derivatives thereof, nucleic acid analogs and/or derivatives thereof (e.g., peptide nucleic acids, etc.), nystatin and/or derivatives thereof, oligonucleotides and/or derivatives thereof, paclitaxel and/or derivatives thereof, penicillin and/or derivatives thereof, pentamidine isethionate and/or derivatives thereof, phenindione and/or derivatives thereof, phenylbutazone and/or derivatives thereof, phosphodiesterase inhibitors and/or derivatives thereof, plasminogen activator inhibitor-1 and/or derivatives thereof, plasminogen activator inhibitor-2 and/or derivatives thereof, platelet factor 4 and/or derivatives thereof, platelet derived growth factor and/or derivatives thereof, Plavix and/or derivatives thereof, POSTMI75 and/or its derivatives, prednisone and/or derivatives thereof, prednisolone and/or derivatives thereof, probucol and/or derivatives thereof, progesterone and/or derivatives thereof, prostacyclin and/or derivatives thereof, prostaglandin inhibitors and/or derivatives thereof, protamine and/or derivatives thereof, protease and/or derivatives thereof, protease inhibitors ... Kinase inhibitors and/or derivatives thereof (e.g., staurosporine, etc.), quinine and/or derivatives thereof, radioactive substances and/or derivatives thereof (e.g., Cu-64, Ca-67, Cs-131, Ga-68, Zr-89, Ku-97, Tc-99m, Rh-105, Pd-103, Pd-109, In-111, I-123, I-125, I-131, Re-186, Re-188, Au-198, Au-199, Pb-203, At-211, Pb-212, Bi-212, H ₃ P ₃₂ O ₄ , etc.), rapamycin and/or derivatives thereof, receptor antagonists of histamine and/or derivatives thereof, refludan and/or derivatives thereof, retinoic acid and/or derivatives thereof, revasc and/or derivatives thereof, rifamycin and/or derivatives thereof, sense or antisense oligonucleotides and/or derivatives thereof (e.g., DNA, RNA, plasmid DNA, plasmid RNA, etc.), theramine and/or derivatives thereof, steroids, theramine and/or derivatives thereof, serotonin and/or derivatives thereof, serotonin blockers Car and/or derivatives thereof, streptokinase and/or derivatives thereof, sulfasalazine and/or derivatives thereof, sulfonamides and/or derivatives thereof (e.g., sulfamethoxazole, etc.), sulfated chitin derivatives, sulfated polysaccharide peptidoglycan complexes and/or derivatives thereof, TH1 and/or derivatives thereof (e.g., interleukin-2, -12, and -15, gamma interferon, etc.), thioprotease inhibitors and/or derivatives thereof, taxol and/or derivatives thereof (e.g., taxotere, baccatin, 10-deacetylase, etc.), cephalomannine, 10-deacetyl-7-epitaxol, 7-epitaxol, 10-deacetylbaccatin III, 10-deacetylcephaormannine, etc.), ticlide and/or derivatives thereof, ticlopidine and/or derivatives thereof, tick anticoagulant peptide and/or derivatives thereof, thioprotease inhibitors and/or derivatives thereof, thyroid hormone and/or derivatives thereof, tissue inhibitors of metalloproteinase-1 and/or derivatives thereof, metalloproteinase-2 and/or including, but not limited to, tissue inhibitors and derivatives thereof, tissue plasma activators, TNF and/or derivatives thereof, tocopherol and/or derivatives thereof, toxins and/or derivatives thereof, tranilast and/or derivatives thereof, transforming growth factors alpha and beta and/or derivatives thereof, trapidil and/or derivatives thereof, triazolopyrimidines and/or derivatives thereof, bapiprost and/or derivatives thereof, vinblastine and/or derivatives thereof, vincristine and/or derivatives thereof, zidovudine and/or derivatives thereof. As will be appreciated, the agent may include derivatives of one or more of the compounds listed above and/or other compounds. In one non-limiting embodiment, the agent is trapidil, a trapidil derivative, taxol, a taxol derivative (e.g., taxotere, baccatin, 10-deacetyltaxol, 7-xylosyl-10-deacetyltaxol, cephalomannine, 10-deacetyl-7-epitaxol, 7-epitaxol, 10-deacetylbaccatin III, 10-deacetylcephaormannine, etc.), cytochalasin, a cytochalasin derivative (e.g., cytochalasin A, cytochalasin B, cytochalasin C, cytochalasin D, cytochalasin E, cytochalasin F, cytochalasin G, cytochalasin H, cytochalasin J, cytochalasin K, cytochalasin L, cytochalasin M, cytochalasin N, cytochalasin O, cytochalasin P, cytochalasin Q, cytochalasin R, cytochalasin S, chetoglobosin A, chetoglobosin B, chetoglobosin C, chetoglobosin D, chetoglobosin E, chetoglobosin F, chetoglobosin G, chetoglobosin J, chetoglobosin K, deoxafomin, proxyfomin, protofomin, zygosporin D, zygosporin E, zygosporin F, zygosporin G, aspochalasin B, aspochalasin C, aspochalasin D, etc.), paclitaxel, paclitaxel derivatives, rapamycin, rapamycin derivatives, 5-phenylmethimazole, 5-phenylmethimazole derivatives, GM-CSF (granulocyte macrophage colony stimulating factor), GM-CSF derivatives, HMG-CoA reductase inhibitors forming a type of statin or hyperlipidemic drug, combinations thereof, or analogs thereof, or combinations thereof. The types and/or amounts of agents included in and/or coated on a medical device can vary. When more than one agent is included in and/or coated on a medical device, the amounts of the two or more agents can be the same or different. The types and/or amounts of agents included on, within and/or used with a medical device are generally selected to address one or more clinical events.

According to another and/or alternative non-limiting aspect of the present disclosure, the amount of agent contained on, contained within, and/or used with the medical device when the agent is in use is about 0.01-100 μg per ^mm2 (and all values and ranges therebetween) and/or at least about 0.00001% by weight of the device, although other amounts can be used. The amounts of two or more agents on, in, and/or used with the medical device can be the same or different. One or more agents can be coated on and/or impregnated into the medical device by a variety of mechanisms, including, but not limited to, spraying (such as, for example, atomized spray techniques), flame spray coating, powder deposition, dip coating, flow coating, dip spin coating, roll coating (direct and reverse), sonication, brushing, plasma deposition, deposition by evaporation, MEMS techniques, and spin mold deposition. When more than one agent is used, the amounts of the two or more agents used on, in and/or with the medical device may be the same or different.

According to another and/or alternative non-limiting aspect of the present disclosure, one or more agents on and/or within the medical device may be released in a controlled manner on the medical device when in use, thereby providing a desired dose of the agent over a sustained period of time to the area of interest being treated. As can be appreciated, controlled release of one or more agents on and/or within the medical device is not necessarily necessary and/or desirable. Thus, one or more agents on and/or within the medical device may be released uncontrolled from the medical device during and/or after insertion of the medical device into the treatment area. It can also be appreciated that one or more agents on and/or within the medical device may be controllably released from the medical device and one or more agents on and/or within the medical device may be released uncontrolled from the medical device. It can also be appreciated that one or more agents on and/or within one area of the medical device may be controllably released from the medical device and one or more agents on and/or within the medical device may be released uncontrolled from another area of the medical device. Thus, a medical device can be designed such that: 1) all of the agents on and/or within the medical device are controllably released; 2) some of the agents on and/or within the medical device are controllably released and some of the agents on the medical device are not controllably released; or 3) no agents on and/or within the medical device are controllably released. A medical device can also be designed such that the release rates of one or more agents from the medical device are the same or different. A medical device can also be designed such that the release rates of one or more agents from one or more regions on the medical device are the same or different. Non-limiting configurations that can be used to control the release of one or more agents from a medical device include: 1) at least partially coating one or more agents with one or more polymers; 2) at least partially incorporating and/or at least partially encapsulating one or more agents in and/or with one or more polymers; and/or 3) inserting one or more agents into pores, passages, cavities, etc. of the medical device and at least partially coating or covering such pores, passages, cavities, etc. with one or more polymers. As will be appreciated, other or additional configurations can be used to control the release of one or more agents from the medical device.

According to another and/or alternative non-limiting aspect of the present disclosure, the one or more polymers used to at least partially control the release of one or more agents from the medical device may be porous or non-porous. The one or more agents may be inserted and/or applied to one or more surface structures and/or microstructures on the medical device and/or may be used to at least partially form one or more surface structures and/or microstructures of the medical device. Thus, the one or more agents on the medical device may be 1) coated on one or more surface regions of the medical device, 2) inserted and/or impregnated into one or more surface structures and/or microstructures, etc. of the medical device, and/or 3) formed at least a portion of the structure of the medical device or included in at least a portion of the structure of the medical device. When one or more agents are coated on a medical device, the one or more agents may be 1) coated directly onto one or more surfaces of the medical device, 2) mixed with one or more coating polymers or other coating materials and then at least partially coated onto one or more surfaces of the medical device, 3) at least partially coated onto another coating material that is at least partially coated onto the medical device, and/or 4) at least partially encapsulated between a) an exterior surface or region of the medical device and one or more other coating materials, and/or b) two or more other coating materials. As can be appreciated, many other coating configurations can additionally or alternatively be used. When one or more agents are inserted and/or impregnated into one or more internal structures, surface structures, and/or microstructures of the medical device, 1) one or more other coating materials can be at least partially applied onto one or more internal structures, surface structures, and/or microstructures of the medical device, and/or 2) one or more polymers can be combined with the one or more agents. Thus, the one or more agents may be 1) embedded in the structure of the medical device, 2) disposed on one or more internal structures of the medical device, 3) encapsulated between two polymer coatings, 4) encapsulated between the base structure and the polymer coating, and/or 5) admixed with the base structure of the medical device including at least one polymer coating. Additionally or alternatively, the one or more coatings of the one or more polymers on the medical device may include 1) one or more coatings of a non-porous polymer, 2) one or more coatings of a combination of one or more porous polymers and one or more non-porous polymers, and/or 3) one or more coatings of a porous polymer.

According to another and/or alternative non-limiting aspect of the present disclosure, different agents can be optionally disposed in and/or between different polymer coating layers and/or on and/or structures of the medical device. As will also be appreciated, many other and/or additional coating combinations and/or configurations can be used. The concentration of one or more agents, the type of polymer, the type and/or shape of the internal structures of the medical device, and/or the thickness of the coating of one or more agents can be used to control the release time, release rate, and/or dosage of one or more agents, although other or additional combinations can also be used. Thus, there can be many combinations of agents and polymer systems and locations on the medical device. As will also be appreciated, one or more agents can be deposited on the top surface of the medical device to provide an initial uncontrolled burst effect of one or more agents prior to 1) a controlled release of one or more agents through one or more layers of one or more polymer systems including one or more non-porous polymers, and 2) an uncontrolled release of one or more agents through one or more layers of the polymer system. One or more agents and/or polymers can be coated onto the medical device by a variety of mechanisms, including, but not limited to, spraying (e.g., atomized spray techniques), dip coating, roll coating, sonication, brushing, plasma deposition, and/or vapor deposition deposition.

According to another and/or alternative non-limiting aspect of the present disclosure, the thickness of each polymer layer and/or agent layer is generally at least about 0.01 μm and generally less than about 150 μm (e.g., 0.01 to 149.9999 μm and all values and ranges therebetween). In one non-limiting embodiment, the thickness of the polymer layer and/or agent layer is about 0.02 to 75 μm, more specifically about 0.05 to 50 μm, and even more specifically about 1 to 30 μm. As will be appreciated, other thicknesses may be used.

According to another and/or alternative non-limiting aspect of the present disclosure, various polymers can be coated onto and/or used to form at least a portion of a medical device. When one or more polymer layers are coated onto at least a portion of a medical device, the one or more coatings can be applied by a variety of techniques, including, but not limited to, vapor deposition and/or plasma deposition, spraying, dip coating, roll coating, sonication, atomization, brushing, and the like, although other or additional coating techniques can be used. The one or more polymers that can be coated onto and/or used to form at least a portion of a medical device can be polymers that are considered to be biodegradable, bioresorbable or bioerodible, polymers that are considered to be biostable, and/or polymers that can be modified to be biodegradable and/or bioabsorbable. Non-limiting examples of polymers that are considered to be biodegradable include bioabsorbable or bioerodible aliphatic polyesters, with or without additives (e.g., calcium phosphate glass), poly(glycolic acid) and/or copolymers thereof (e.g., poly(glycolide trimethylene carbonate), poly(caprolactone glycolide)), poly(lactic acid) and/or its isomers (e.g., poly-L (lactic acid) and/or poly-D lactic acid) and/or copolymers thereof (e.g., DL-PLA), and/or other copolymers (e.g., poly(caprolactone lactide), poly(lactide glycolide), poly(ethylene glycol lactate)), polyethylene glycol), poly(ethylene glycol) diacrylate, poly(lactide), polyalkylene succinates, polybutylene diglycolate, polyhydroxybutyrate (PHB), polyhydroxyvalerate (PHV), polyhydroxybutyrate/polyhydroxyvalerate copolymers (P Poly(hydroxybutyrate-co-valerate), polyhydroxyalkaoates (PHAs), polycaprolactones, poly(caprolactone-polyethylene glycol) copolymers, poly(valerolactone), polyanhydrides, poly(orthoesters) and/or blends with polyanhydrides, poly(anhydride-co-imides), polycarbonates (aliphatic), poly(hydroxyl-esters), polydioxanones, polyanhydrides, polyanhydride esters, polycyanoacrylates, poly(alkyl 2-cyanoacrylates), poly(amino acids), poly(phosphazenes), poly(propylene fumarate), poly(propylene fumarate-co-ethylene glycol), poly(fumaric anhydride), fibrinogen, fibrin, gelatin, cellulose and/or cellulose derivatives and/or cellulosic polymers (e.g. cellulose acetate, cellulose acetate butyrate, cellulose butyrate, cellulose ethers, cellulose nitrate, cellulose propionate, cellophane), chitosan and/or chitosan derivatives (e.g., chitosan NOCC, chitosan NOOC-G), alginates, polysaccharides, starches, amylases, collagen, polycarboxylic acids, poly(ethyl ester-co-carboxylate carbonate) (and/or other tyrosine-derived polycarbonates), poly(iminocarbonates), poly(BPA-iminocarbonate), poly(trimethylene carbonate), poly(iminocarbonate-amide) copolymers and/or other pseudo poly(amino acids), poly(ethylene glycol), poly(ethylene oxide), poly(ethylene oxide)/poly(butylene terephthalate) copolymers, poly(ε-caprolactone-dimethyltrimethylene carbonate), poly(ester amides), poly(amino acids) and conventional synthetic polymers thereof, poly(alkylene oxalates), poly(alkylcarbonates), poly(adipic anhydride), nylon. Examples of suitable polymeric materials include, but are not limited to, poly(propylene glycol), poly(amino acid), poly(propylene glycol)-co-ethylene glycol ... Non-limiting examples of polymers that are considered to be biostable include parylene, parylene c, parylene f, parylene n, parylene derivatives, maleic anhydride polymers, phosphorylcholine, poly n-butyl methacrylate (PBMA), polyethylene-co-vinyl acetate (PEVA), PBMA/PEVA blends or copolymers, polytetrafluoroethene (Teflon®) and its derivatives, polyparaphenylene terephthalamide (Kevlar®), poly(ether ketone) (PEEK), poly(styrene-b-isobutylene-b-styrene) (Transroute™), tetramethyldisiloxane, ... polyimide polysulfides, polyethylene terephthalate), polymethyl methacrylate), poly(ethylene-co-methyl methacrylate), styrene-ethylene/butylene-styrene block copolymers, ABS, SAN, acrylic polymers and/or copolymers (e.g., n-butyl acrylate, n-butyl methacrylate, 2-ethylhexyl acrylate, lauryl acrylate, 2-hydroxypropyl acrylate, polyhydroxyethyl, methacrylate/methyl methacrylate copolymers), glycosaminoglycans, alkyd resins, elastin, polyethersulfones, ethylene Poly(oxymethylene), polyolefins, polymers of silicone, polymers of methane, polyisobutylene, ethylene-alphaolefin copolymers, polyethylene, polyacrylonitrile, fluorosilicones, poly(propylene oxide), polyvinyl aromatics (such as polystyrene), poly(vinyl ethers) (e.g., polyvinyl methyl ether), poly(vinyl ketone), poly(vinylidene halides) (e.g., polyvinylidene fluoride, polyvinylidene chloride), poly(vinylpyrrolidone), poly(vinylpyrrolidone)/vinyl acetate copolymers, polyvinyl propylene glycol, polyvinyl propylene glycol terpolymers ... Examples of polymers that may be modified to be biodegradable and/or bioabsorbable include, but are not limited to, styren or silk elastin polymers (SELP), silicones, silicone rubbers, polyurethanes (polycarbonate polyurethanes, silicone urethane polymers) (e.g., Chronoflex, Bionate), vinyl halide polymers and/or copolymers (e.g., polyvinyl chloride), polyacrylic acid, ethylene acrylic acid copolymers, ethylene vinyl acetate copolymers, polyvinyl alcohol, poly(hydroxyl alkyl methacrylates), polyvinyl esters (e.g., polyvinyl acetate), and/or copolymers, mixtures, and/or composites of the above. Non-limiting examples of polymers that may be modified to be biodegradable and/or bioabsorbable include, but are not limited to, hyaluronic acid (hyanluronic), polycarbonates, polyorthocarbonates, copolymers of vinyl monomers, polyacetals, biodegradable polyurethanes, polyacrylamides, polyisocyanates, polyamides, and/or copolymers, mixtures, and/or composites of the above. As will be appreciated, other and/or additional polymers and/or derivatives of one or more of the above listed polymers may be used. The one or more polymers can be coated onto the medical device by a variety of mechanisms, including, but not limited to, spraying (e.g., atomized spray techniques), dip coating, roll coating, sonication, brushing, plasma deposition, and/or deposition by vapor deposition. In one non-limiting embodiment, the medical device comprises and/or is coated with Parylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan, and/or one or more derivatives of these polymers. In another and/or alternative non-limiting embodiment, the medical device comprises and/or is coated with a non-porous polymer, including, but not limited to, polyamide, Parylene C, Parylene N, and/or Parylene derivatives. In yet another and/or alternative non-limiting embodiment, the medical device comprises and/or is coated with poly(ethylene oxide), poly(ethylene glycol), and poly(propylene oxide), polymers of silicone, methane, tetrafluoroethylene (including Teflon™ brand polymers), tetramethyldisiloxane, and the like.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device can include and/or be coated with one or more agents, where the one or more agents are the same or different in different regions of the medical device and/or have different amounts and/or concentrations in different regions of the medical device. For example, the medical device can be: 1) coated with and/or containing one or more biological agents at least one portion of the medical device and at least another portion of the medical device is not coated with and/or does not contain the agent; 2) coated with and/or containing one or more biological agents on at least one portion of the medical device that are different from the one or more biological agents on at least another portion of the medical device; and/or 3) coated with and/or containing one or more biological agents at a concentration in at least one portion of the medical device that is different from the concentration of the one or more biological agents in at least another portion of the medical device.

According to another and/or alternative non-limiting aspect of the present disclosure, one or more portions of the medical device optionally 1) contain the same or different agents, 2) contain the same or different amounts of one or more agents, 3) contain the same or different polymer coatings, 4) contain the same or different coating thicknesses of the one or more polymer coatings, 5) one or more portions of the medical device controllably release and/or uncontrolled release one or more agents, and/or 6) one or more portions of the medical device controllably release one or more agents and one or more portions of the medical device uncontrolled release one or more agents.

According to another and/or alternative non-limiting aspect of the present disclosure, one or more surfaces of the medical device can be optionally treated to achieve the desired coating properties of the one or more agents and one or more polymers coated on the medical device. Such surface treatment techniques include, but are not limited to, cleaning, buffing, smoothing, nitriding, annealing, swaging, cold working, etching (chemical etching, plasma etching, etc.), and the like. As will be appreciated, other or additional surface treatment processes can be used prior to coating the one or more agents and/or polymers on the surface of the medical device. Once one or more surface regions of the medical device have been treated, one or more coatings of polymers and/or agents can be applied to one or more regions of the medical device. One or more layers of agent can be applied to the medical device by a variety of techniques (e.g., dipping, rolling, brushing, spraying, particle atomization, etc.). One non-limiting coating technique is by ultrasonic mist coating process, which uses ultrasound to break up droplets of agent to form a mist of very fine droplets. The average droplet diameter of these fine droplets is about 0.1 to 3 microns. The fine droplet mist promotes the formation of a uniform coating thickness and can increase the coverage area on the medical device.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device can optionally include a marker material that facilitates proper placement of the medical device within a body passageway (e.g., blood vessel, heart valve, etc.). The marker material is typically designed to be visible to electromagnetic radiation (e.g., x-ray, microwave, visible light, infrared, ultraviolet, etc.), sound waves (e.g., ultrasound, etc.), magnetic waves (e.g., MRI, etc.), and/or other types of electromagnetic radiation (e.g., microwave, visible light, infrared, ultraviolet, etc.). In one non-limiting embodiment, the marker material is visible to x-rays (i.e., radiopaque). The marker material can form all or part of the medical device and/or can be coated on one or more portions of the medical device (e.g., the flared portion and/or the body portion, the end of the medical device, at or near the transition between the body portion and the flared portion, etc.). The location of the marker material is at one or more locations on the medical device. The size of the one or more areas containing the marker material can be the same or different. The marker material can form ruler-like markings on the medical device at a predetermined distance apart to facilitate positioning of the medical device within the body passageway. The marker material can be a rigid or flexible material. The marker material can be a biostable or biodegradable material. When the marker material is a rigid material, it is typically formed of a metallic material (e.g., metal bands, metal plating, etc.), although other or additional materials can be used. The metal that at least partially forms the medical device can function as the marker material, but this is not required. When the marker material is a flexible material, it is typically formed of one or more polymers that are themselves marker materials and/or contain one or more metal powders and/or metal compounds. In one non-limiting embodiment, the flexible marker material includes one or more metal powders in combination with parylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan, and/or one or more derivatives of these polymers. In another and/or alternative non-limiting embodiment, the flexible marker material includes one or more metals and/or metal powders thereof, including aluminum, barium, bismuth, cobalt, copper, chromium, gold, iron, stainless steel, titanium, vanadium, nickel, zirconium, niobium, lead, molybdenum, platinum, yttrium, calcium, rare earth metals, rhenium, zinc, silver, depleted radioactive elements, tantalum and/or tungsten, and/or compounds thereof. The marker material can be coated with a polymeric protective material, but this is not required. When the marker material is coated with a polymeric protective material, the polymeric coating can be used to 1) at least partially isolate the marker material from bodily fluids, 2) facilitate retention of the marker material on the medical device, 3) at least partially protect the marker material from damage during a medical procedure, and/or 4) provide a desired surface configuration on the medical device. As can be appreciated, the polymeric coating can have other or additional uses. The polymeric protective coating can be a biostable polymer or a biodegradable polymer (e.g., decomposed and/or absorbed). When used, the protective coating polymeric material typically has a coating thickness of less than about 300 microns (e.g., 0.001 to 299.999 microns and all values and ranges therebetween), although other thicknesses can be used. In one non-limiting embodiment, the protective coating material comprises parylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan, and/or derivatives of one or more of these polymers.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device or one or more regions of the medical device can be constructed using one or more microelectromechanical manufacturing (MEMS) techniques (e.g., micromachining, laser micromachining, micromolding, 3D printing, etc.), although other or additional manufacturing techniques can also be used.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device can optionally include one or more surface structures (e.g., pores, channels, pits, ribs, slots, notches, bumps, teeth, needles, wells, holes, grooves, etc.) that can be formed at least in part by MEMS (e.g., micromachining, etc.) techniques and/or other types of techniques (e.g., 3D printing, etc.).

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device may optionally include one or more microstructures (e.g., microneedles, micropores, microcylinders, microcones, micropyramids, microtubes, microcuboids, microprisms, microhemispheres, teeth, ribs, ridges, ratchets, hinges, zippers, cable ties, similar structures, etc.) on the surface of the medical device. As defined in this disclosure, a "microstructure" is a structure having at least one dimension (e.g., average width, average diameter, average height, average length, average depth, etc.) of about 2 mm or less, typically about 1 mm or less. As can be understood, when a medical device includes one or more surface structures, 1) all of the surface structures can be microstructures, 2) all of the surface structures can be non-microstructures, or 3) some of the surface structures can be microstructures and some can be non-microstructures. Non-limiting examples of structures that can be formed on a medical device are shown in US Patent Application Publication Nos. 2004/093076 and 2004/0093077, which are incorporated by reference in this disclosure. Typically, the microstructures (when formed) extend no more than about 400 microns (0.01 to 400 microns and all values and ranges therebetween) from or into the outer surface, more typically less than about 300 microns, and more typically about 15 to 250 microns, although other sizes can be used. The microstructures can be clustered together or dispersed throughout the surface of the medical device. Microstructures and/or surface structures of the same shape and/or size can be used, or microstructures of different shapes and/or sizes can be used. If one or more surface structures and/or microstructures are designed to extend from the surface of the medical device, the one or more surface structures and/or microstructures can be formed in the extended position and/or can be designed to extend from the medical device during and/or after deployment of the medical device in the treatment area. The microstructures and/or surface structures can be designed to include and/or be fluidly connected to passageways, cavities, etc., but this is not required. The one or more surface structures and/or microstructures can be used to engage and/or penetrate surrounding tissues or organs once the medical device is placed on and/or in a patient, but this is not required. The one or more surface structures and/or microstructures can be used to facilitate the formation of a shape-retaining medical device. In one non-limiting embodiment, the one or more surface structures and/or microstructures can be at least partially formed of an agent and/or can be formed of a polymer. One or more of the surface structures and/or microstructures can include one or more internal passageways that can include one or more materials (e.g., agents, polymers, etc.), but this is not required. The one or more surface structures and/or microstructures can be formed by a variety of processes (e.g., machining, chemical modification, chemical reaction, MEMS (e.g., micromachining, etc.), etching, laser cutting, 3D printing, photoetching, etc.). The one or more coatings and/or the one or more surface structures and/or microstructures of the medical device can be used for a variety of purposes, including, but not limited to, 1) increasing the binding and/or adhesion of one or more agents, adhesives, marker materials and/or polymers to the medical device, 2) modifying the appearance or surface properties of the medical device, and/or 3) controlling the release rate of one or more agents. The one or more microstructures and/or surface structures can be biostable, biodegradable, etc. One or more regions of the medical device formed at least in part by MEMS techniques can be biostable, biodegradable, etc. The medical device or one or more regions of the medical device can be at least partially covered or filled with a protective material to at least partially protect the one or more regions of the medical device and/or the one or more microstructures of the medical device and/or the surface structures on the medical device from damage. One or more regions of the medical device and/or one or more microstructures and/or surface structures on the medical device may be damaged when the medical device is 1) packaged and/or stored in a storage tube, 2) unpackaged, 3) connected to and/or secured to and/or placed on another medical device, 4) inserted into a treatment area, and/or 5) handled by a user. As will be appreciated, the medical device may be damaged in other or additional ways. Protective materials may be used to protect the medical device and/or one or more microstructures and/or surface structures from such damage. Protective materials may include one or more polymers already identified above. Protective materials are 1) biostable and/or biodegradable, and/or 2) porous and/or non-porous. In alternative and/or additional non-limiting designs, the protective material includes sugars (e.g., glucose, fructose, sucrose, etc.), carbohydrate compounds, salts (e.g., NaCl, etc.), parylene, PLGA, POE, PGA, PLLA, PAA, PEG, chitosan, and/or derivatives of one or more of these materials, although other and/or additional materials can be used. In yet alternative and/or additional non-limiting designs, the thickness of the protective material is generally less than about 300 microns (e.g., 0.01 microns to 299.9999 microns and all values and ranges therebetween), typically less than about 150 microns, although other thicknesses can be used. The protective material can be coated by one or more mechanisms previously described in this disclosure.

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device may be an expandable device that can be expanded by using some other device (e.g., a balloon, etc.).

According to another and/or alternative non-limiting aspect of the present disclosure, the medical device can optionally be fabricated from a material that has no or substantially no shape memory properties.

According to another and/or alternative non-limiting aspect of the present disclosure, a near-net process is optionally provided for frames and/or other metal components of medical devices. In one non-limiting embodiment of the present disclosure, a method is provided for powder pressing a material and, optionally, applying additional cold work to increase the strength after sintering. In one non-limiting embodiment, the green part is pressed and then sintered. The sintered part is then pressed again to apply cold work to the sintered part to increase its mechanical strength. Generally, the temperature during the pressing process after the sintering treatment is 20-100°C (and all values and ranges therebetween), typically 20-80°C, and more typically 20-40°C. As defined in the present disclosure, cold working is performed at a temperature of 150°C or less (e.g., 10-150°C and all values and ranges therebetween). The change in shape of the re-pressed sintered part needs to be determined so that the final part (pressed, sintered, and re-pressed) meets the dimensional requirements of the final molded part. For Mo47.5Re, MoRe, ReW, ReCr, and other high melting point metal alloys, a pre-press pressure of 1-300 tsi (tons per square inch) (and all values and ranges therebetween) can be used, followed by a sintering process at at least 1600°C (e.g., 1600-2600°C and all values and ranges therebetween) and a post-sintering press at a pressure of 1-300 tsi (and all values and ranges therebetween) at a temperature of at least 20°C (e.g., 20-100°C and all values and ranges therebetween, 20-40°C, etc.). Also provided is an optional process for re-pressing a part after sintering to add additional cold work to the material, thereby increasing the mechanical strength of the pressed metal part. Also provided is an optional process for powder pressing using metal powder into a near net or final part. In one non-limiting embodiment, the metal powder used to form the near net or final part includes a minimum of 40% by weight rhenium and at least 25% by weight molybdenum, with the balance optionally including one or more of the following elements: tungsten, tantalum, chromium, niobium, zirconium, iridium, titanium, bismuth, and yttrium. In another non-limiting embodiment, the metal powder used to form the near net or final part includes 20-80% by weight rhenium (and all values and ranges therebetween), 20-80% by weight molybdenum (and all values and ranges therebetween), and optionally one or more of the following elements: tungsten, tantalum, chromium, niobium, zirconium, iridium, titanium, bismuth, and yttrium. In another non-limiting embodiment, the metal powder used to form the near net or final part includes tungsten (20-60 wt. % and all values and ranges therebetween), rhenium (20-80 wt. % and all values and ranges therebetween), and 0-5 wt. % (and all values and ranges therebetween) of one or more other elements. In another non-limiting embodiment, the metal powder used to form the near net or final part includes tungsten (20-80 wt. % and all values and ranges therebetween), rhenium (20-80 wt. % and all values and ranges therebetween), molybdenum (0.01-15 wt. % and all values and ranges therebetween), and 0-5 wt. % (and all values and ranges therebetween) of one or more other elements.

In another non-limiting embodiment, the metal powder used to form the near net or final part includes 35-65 wt.% rhenium (and all values and ranges therebetween) and two or more elements of tungsten, tantalum, molybdenum, chromium, niobium, zirconium, iridium, titanium, bismuth, and yttrium. In another non-limiting embodiment, the metal powder used to form the near net or final part includes 35-65 wt.% rhenium (and all values and ranges therebetween) molybdenum powder and 11-41 wt.% chromium powder (and all values and ranges therebetween), optionally in combination with powders of one or more metals selected from the group consisting of bismuth, tungsten, tantalum, molybdenum, chromium, niobium, zirconium, iridium, niobium, tantalum, titanium, bismuth, and yttrium. In another non-limiting embodiment, the metal powder used to form the near net or final part includes 35-65 wt.% rhenium (and all values and ranges therebetween), chromium, and 0.1-25 wt.% (and all values and ranges therebetween) of one or more of the following elements: molybdenum, bismuth, niobium, tungsten, tantalum, titanium, vanadium, tungsten, manganese, zirconium, technetium, ruthenium, rhodium, hafnium, osmium, copper, iridium, and yttrium. In another non-limiting embodiment, the metal powder used to form the near net or final part comprises 25-95 wt.% rhenium (and all values and ranges therebetween) and one or more of calcium, carbon, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, zinc, zirconium, and/or alloys of one or more of these elements.

According to another and/or alternative non-limiting aspect of the present disclosure, optionally, pressing of near-net or finished part composites is provided. The process of pressing metal to near-net of finished parts is well established. However, pressing composite structures formed of metal powder and polymer for the purpose of creating complex part shapes and foam-like structures is novel. Similarly, the use of pressing processes to impart specific biological materials to metal matrices is novel. In one non-limiting embodiment, a process is provided for creating metal parts with predefined voids, creating trabecular or foam structures composed of a mixture of metal and polymer powder, then pressing the powder into a finished part or semi-finished green part, and then sintering the part under conditions where the polymer leaves the metal through a pyrolysis process of the polymer. The resulting part is related to the porosity related to the size of the polymer particles and the homogeneity of the mixture during pressing before sintering. In another non-limiting embodiment, a process is provided in which a polymer residue is left behind (on the metal substrate) after pyrolysis, and the polymer residue exerts some desired biological effect (e.g., masking the metal from the body by encapsulation, promoting cell attachment and growth). The polymer and metal powder can create a large number of voids of various sizes; some large ones create pathways for cell growth, and some small ones create a rough surface that promotes cell attachment.

According to another and/or alternative non-limiting aspect of the present disclosure, the polymer can be optionally uniformly or non-uniformly dispersed with the metal powder. For example, if the final molded part is required to have a uniform density and pore structure, the polymer material can be uniformly dispersed with the metal powder, and then the polymer and metal powder are consolidated and pressed together, followed by sintering the metal powder together to form the metal part or medical device. Alternatively, when the formed metal part or medical device will have one or more channels, passages and/or voids in and/or on the exterior surface of the formed part or medical device, at least a portion of the polymer is not uniformly dispersed with the metal powder, but instead is concentrated in or forms the entire area of what will become the one or more channels, passages and/or voids in and/or on the exterior surface of the molded part or medical device, such that when the polymer and metal powder are sintered, some or all of the polymer is decomposed and removed from the part or medical device, thereby forming such one or more channels, passages and/or voids on and/or within the exterior surface of the formed part or medical device. A portion or all of the polymer is decomposed and removed from the part or medical device, thereby forming one or more such channels, passages and/or voids on the exterior surface and/or within the formed part or medical device. Thus, a combination of metal powder and polymer, followed by pressing and sintering, can be used to form novel customized shapes of medical devices or near net forms of medical devices. Generally, the polymer comprises about 0.1-70% by volume (and all values and ranges therebetween) of the consolidated and pressed material prior to the sintering step, typically the polymer comprises about 1-60% by volume of the consolidated and pressed material prior to the sintering step, more typically the polymer comprises about 2-50% by volume of the consolidated and pressed material prior to the sintering step, and even more typically the polymer comprises about 2-45% by volume of the consolidated and pressed material prior to the sintering step. Thus, if the polymer constitutes about 5% by volume of the solidified and pressed material prior to the sintering step, after the sintering step, at least 95% (e.g., 95-100% and all values and ranges therebetween) of the polymer will have degraded and when removed from the part or medical device, the part may contain up to about 5% by volume of cavities and/or passageways within the medical device.

The type of polymer and the type of metal powder are not limited. The polymer and metal powders can be of various sizes to create multiple voids/passages/channels. The multiple voids/passages/channels can be used to create pathways for cell growth, create rough surfaces to promote cell attachment, insert biological agents into one or more of the voids/passages/channels, insert biological materials into one or more of the voids/passages/channels, etc. In one non-limiting embodiment, the average particle size of the polymer is larger than the average particle size of the metal powder before sintering.

In another non-limiting aspect of the present disclosure, after the sintering process, at least 95% by volume (95% to 100% and all values and ranges therebetween) of the polymer is pyrolyzed and/or removed from the sintered material, typically at least 99% by volume of the polymer is pyrolyzed and/or removed from the sintered material, more typically at least 99.5% by volume of the polymer is pyrolyzed and/or removed from the sintered material, even more typically at least 99.9% by volume of the polymer is pyrolyzed and/or removed from the sintered material, and even more typically at least 99.95% by volume of the polymer is pyrolyzed and/or removed from the sintered material. The resulting part or medical device has a porosity related to the size of the polymer particles and the homogeneity of the mixture during pressing prior to sintering.

In another non-limiting aspect of the present disclosure, after the sintering process, a portion of the polymer may optionally remain in the sintered part or medical device. The polymer remaining in the sintered part or medical device may optionally have some desired biological effect (e.g., masking metal from the body by encapsulation, promoting cell attachment and growth, etc.). The remaining polymer may optionally include one or more biological agents that remain active after the sintering process. In one non-limiting embodiment, if the polymer is designed to remain in the sintered part, after the sintering process, about 5-99.9% by volume (and all values and ranges therebetween) of the polymer is pyrolyzed and/or removed from the sintered material, typically about 10-95% by volume of the polymer is pyrolyzed and/or removed from the sintered material, and more typically about 10-80% by volume of the polymer is pyrolyzed and removed from the sintered material.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy used to at least partially form the medical device may be first formed into a near net part, blank, rod, tube, or the like, and then finished to a final shape by one or more finishing processes (e.g., centerless grinding, turning, electrolytic polishing, drawing, grinding, laser cutting, shaving, polishing, EDM cutting, micromachining, laser micromachining, microforming, machining, drilling (e.g., gun drilling, etc.), 3D printing, cold wording, swaging, cleaning, buffing, smoothing, nitriding, annealing, plug drawing, etching (e.g., chemical etching, plasma etching, etc.), chemical modification, chemical reaction, photoetching, chemical coating, etc.).

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy near-net parts, blanks, rods, tubes, etc. can be formed by a variety of techniques, including, but not limited to, 1) melting the refractory metal alloy and/or the metals forming the refractory metal alloy (e.g., vacuum arc melting, etc.), and then extruding and/or casting the refractory metal alloy into a near-net part, blank, rod, tube, etc.; 2) melting the refractory metal alloy and/or the metals forming the refractory metal alloy and forming a metal strip, and then rolling and welding the strip into a near-net part, blank, rod, tube, etc.; 3) consolidating (e.g., pressing, pressing and sintering, etc.) a metal powder of the refractory metal alloy and/or a metal powder of the metals forming the refractory metal alloy into a near-net part, blank, rod, tube, etc.; and/or 4) 3D printing the metal alloy into a near-net part, blank, rod, tube, etc. When the refractory metal alloy is formed into a blank, the shape and size of the blank are not limited. When the refractory metal alloy is formed into a rod or tube, the rod or tube generally has a length of about 48 inches or less (e.g., 0.1 to 48 inches and all values and ranges therebetween), although longer lengths can be formed. In one non-limiting configuration, the length of the rod or tube is about 8 to 20 inches. The average outer diameter of the rod or tube is generally less than about 2 inches (i.e., less than about 3.14 square inches of cross-sectional area), more typically less than about 1 inch, and even more typically about 0.5 inch or less, although larger diameter rods or tubes can be formed. In one non-limiting configuration for the tube, the tube has an inner diameter of about 0.31 inches ± about 0.002 inches and an outer diameter of about 0.5 inches ± about 0.002 inches. The wall thickness of the tube is about 0.095 inches ± about 0.002 inches. As can be appreciated, this is just one example of the various sizes of tubes that can be formed. In one non-limiting process, near-net frames, blanks, rods, tubes, etc. of medical devices. In one non-limiting process, near-net medical devices, blanks, rods, tubes, etc. can be formed from one or more ingots of metal or high melting point alloy. In one non-limiting process, an arc melting process (e.g., a vacuum arc melting process, etc.) can be used to form near-net medical devices, blanks, rods, tubes, etc. In another non-limiting process, rhenium powder, tungsten powder, and optionally molybdenum powder can be placed in a crucible (e.g., a silica crucible, etc.) and heated in an induction melting furnace under a controlled atmosphere (e.g., a vacuum environment, a carbon monoxide environment, a hydrogen and argon environment, helium, argon, etc.) to form near-net medical devices, blanks, rods, tubes, etc. As can be appreciated, other metal particles can be used to form other refractory metal alloys (e.g., refractory metal alloys, MoRe alloys, MoReCr alloys, WRe alloys, ReCr alloys, MoReTa alloys, MoReTi alloys, ReCr alloys, etc.) by various processes such as melting, sintering, compressing particles and heating, etc. It can be appreciated that other or additional processes can be used to form the refractory metal alloy. When forming a tube of a refractory metal alloy, a snug-fitting rod can be used during the extrusion process to form the tube, but this is not required. In another and/or additional non-limiting process, a tube of a refractory metal alloy can be formed from a strip or sheet of a refractory metal alloy. A strip or sheet of a refractory metal alloy can be formed into a tube by rolling the ends of the sheet or strip and then welding the ends of the sheet or strip. Welding the edges of the sheet or strip can be done in a number of ways, including but not limited to: a) holding the edges together and electron beam welding the edges in a vacuum; b) placing thin strips of refractory metal alloys over and/or under the edges of the rolled strip or sheet to be welded, then welding one or more strips along the edges of the rolled strip or sheet, and then grinding the outer strips; or c) laser welding the edges of the rolled sheet or strip in a vacuum, reduced oxygen atmosphere, or inert atmosphere. In yet another and/or additional non-limiting process, near-net frames of medical devices, blanks, rods, tubes, and the like of refractory metal alloys are formed by consolidating metal powders. In this process, fine particles of metals (e.g., Re, W, Mo, Ti, Cu, Ni, Cr, and the like) are mixed with additives to form a homogenous mixture of particles. Typically, the average particle size of the metal powder is less than about 200 mesh (e.g., less than 74 microns, 2-74 microns and all values and ranges therebetween). A large average particle size may prevent proper mixing of the metal powder and/or adversely affect one or more physical properties of the near-net frame, blank, rod, tube, etc. of the medical device formed from the metal powder. In one non-limiting embodiment, the average particle size of the metal powder is less than about 230 mesh (e.g., less than 63 microns). In another and/or alternative non-limiting embodiment, the average particle size of the metal powder is about 2-63 microns, more specifically about 5-40 microns. As can be appreciated, smaller average particle sizes can be used. The purity of the metal powder should be selected so that the metal powder contains very low levels of carbon, oxygen, and nitrogen. Typically, the metal powders used to form the refractory metal alloys have a carbon content of less than about 100 ppm, an oxygen content of less than about 50 ppm, and a nitrogen content of less than about 20 ppm. Typically, the metal powders used to form the refractory metal alloys have a purity grade of at least 99.9, more typically at least about 99.95. The mixture of metal powders is then pressed together to form a solid solution of the refractory metal alloy to form a near-net medical device, blank, rod, tube, etc. Typically, the pressing process is performed by an isostatic process (i.e., uniform pressure is applied from all sides of the metal powder), although other processes can be used. When the metal powders are pressed together isostatically, cold isostatic pressing (CIP) is typically used to consolidate the metal powders, although this is not required. The pressing process can be performed under an inert atmosphere, an oxygen-reduced atmosphere (e.g., hydrogen, argon, and hydrogen mixtures, etc.), and/or a vacuum, although this is not required. The average density of the near-net medical device, blank, rod, tube, etc. achieved by pressing the metal powders together is about 80-95% (and all values and ranges therebetween) of the final average density of the near-net medical device, blank, rod, tube, etc., or about 70-99% (and all values and ranges therebetween) of the minimum theoretical density of the refractory metal alloy. A pressing pressure of at least about 300 MPa (e.g., 300-800 MPa and all values and ranges therebetween) is typically used. Typically, the pressing pressure is on the order of 400-700 MPa, although other pressures can be used. After the metal powders are pressed together, the pressed metal powders are sintered at a temperature of at least 1600° C. (e.g., 1600-3500° C. and all values and ranges therebetween) to partially or fully fuse the metal powders to form a near-net medical device, blank, rod, tube, etc. Sintering of the consolidated metal powder can be performed in an oxygen-reduced atmosphere (e.g., helium, argon, hydrogen, argon and hydrogen mixtures, etc.) and/or under vacuum, although this is not required. At high sintering temperatures, a high hydrogen atmosphere reduces both the amount of carbon and oxygen in the formed near-net medical device, blank, rod, tube, etc. The sintered metal powder generally has an average density after sintering of about 90-99.9% (and all values and ranges therebetween) of the minimum theoretical density of the refractory metal alloy. Typically, the sintered refractory metal alloy has a final average density of at least about 5 gm/cc (e.g., 5-20 gm/cc and all values and ranges therebetween), typically at least about 8.3 gm/cc, and may be up to or greater than about 16 gm/cc, but this is not required. The density of the formed near-net medical device, blank, rod, tube, etc. generally depends on the type of refractory metal alloy used.

According to another and/or alternative non-limiting aspect of the present disclosure, when a solid rod of refractory metal alloy is formed, the rod is formed into a tube prior to reducing the outer cross-sectional area or diameter of the rod. The rod can be formed into a tube by a variety of processes, including, but not limited to, by cutting or drilling (e.g., gun drilling, etc.), or cutting (e.g., EDM, EDM sinker, wire EDM, etc.) or 3D printing. The cavity or passage formed in the rod is typically formed completely through the rod, although this is not required.

In further and/or alternative non-limiting aspects of the present disclosure, the near-net medical device, blank, rod, tube, etc. may be optionally cleaned and/or polished after the near-net medical device, blank, rod, tube, etc. is formed, but this is not required. Typically, the near-net medical device, blank, rod, tube, etc. is cleaned and/or polished before being further processed, but this is not required. When a rod of a refractory metal alloy is formed into a tube, the formed tube is typically cleaned and/or polished before being further processed, but this is not required. When resizing and/or annealing the near-net medical device, blank, rod, tube, etc., the near-net medical device, blank, rod, tube, etc., is typically cleaned and/or polished before and/or after each or a series of resizing and/or annealing processes, but this is not required. Cleaning and/or polishing the near-net medical device, blank, rod, tube, etc. is used to remove impurities and/or contaminants from the surface of the near-net medical device, blank, rod, tube, etc. Impurities and contaminants can be introduced into the refractory metal alloy during processing of the near-net medical device, blank, rod, tube, etc. The inadvertent introduction of impurities and contaminants into the near-net medical device, blank, rod, tube, etc. can result in undesirable amounts of carbon, nitrogen, oxygen, and/or other impurities in the refractory metal alloy. The inclusion of impurities and contaminants in the refractory metal alloy can cause premature microcracking in the refractory metal alloy and/or adversely affect one or more physical properties of the refractory metal alloy (e.g., decreased tensile elongation, increased ductility, increased brittleness, etc.). Cleaning of the refractory metal alloy can be accomplished by a variety of techniques, including, but not limited to, 1) using a solvent (e.g., acetone, methyl alcohol, etc.) and wiping the refractory metal alloy with a Kimwipe or other suitable towel, 2) at least partially dipping or submerging the refractory metal alloy in the solvent and then ultrasonically cleaning the refractory metal alloy, and/or 3) by at least partially dipping or submerging the refractory metal alloy in an acid pickling solution. As can be appreciated, the refractory metal alloy can be cleaned in other or additional ways. When polishing a refractory metal alloy, the refractory metal alloy is generally polished using a polishing solution that includes an acid solution, although this is not required. In one non-limiting example, the polishing solution includes sulfuric acid, although other or additional acids can be used. In one non-limiting polishing solution, the polishing solution can include 60-95% sulfuric acid and 5-40% deionized water (DI water) by volume. Generally, the polishing solution that includes an acid increases in temperature during preparation of the solution and/or during the polishing step. Thus, the polishing solution is typically stirred and/or cooled during preparation of the solution and/or during the polishing step. The temperature of the polishing solution is typically about 20-100° C. (and all values and ranges therebetween), and is typically greater than about 25° C. One non-limiting polishing technique that can be used is an electropolishing technique. When using electropolishing techniques, a voltage of about 2-30V (and all values and ranges therebetween), typically about 5-12V, is applied to the near net frame, blank, rod, tube, etc. of the medical device during the polishing process, although it will be appreciated that other voltages may be used. The time it takes to polish the refractory metal alloy depends on both the size of the near net frame, blank, rod, tube, etc. of the medical device and the amount of material that needs to be removed from the near net frame of the medical device. The near net frame, blank, rod, tube, etc. of the medical device may be processed in a two-stage polishing process, where the refractory metal alloy piece is at least partially immersed in the polishing solution for a period of time (e.g., 0.1-15 minutes, etc.), rinsed (e.g., in deionized water, etc.) for a short period of time (e.g., 0.02-1 minute, etc.), and then turned over and at least partially immersed in the solution again for the same or a similar period of time as the first, although this is not required. The refractory metal alloy may be rinsed (e.g., deionized water, etc.) for a period of time (e.g., 0.01-5 minutes, etc.) before rinsing with a solvent (e.g., acetone, methyl alcohol, etc.), but this is not required. The refractory metal alloy may be allowed to dry (e.g., exposed to air, maintained in an inert gas environment, etc.) on a clean surface. These polishing steps may be repeated until a desired amount of polishing of the medical device near-net frame, blank, rod, tube, etc. is achieved. The medical device near-net frame, blank, rod, tube, etc. may be uniformly electropolished or selectively electropolished. When selectively electropolishing the medical device near-net frame, blank, rod, tube, etc., selective electropolishing may be used to obtain different surface characteristics of the medical device near-net frame, blank, rod, tube, etc. and/or to selectively expose one or more areas of the medical device near-net frame, blank, rod, tube, etc., but this is not required.

In yet further and/or alternative non-limiting aspects of the present disclosure, the near-net medical device, blank, rod, tube, etc. can be resized to the desired dimensions of the medical device. In one non-limiting embodiment, the cross-sectional area or diameter of the blank, rod, tube, etc. is reduced in a single step or by a series of steps to the dimensions of the final near-net medical device, blank, rod, tube, etc. The reduction in the outer cross-sectional area or diameter of the near-net medical device, blank, rod, tube, etc. can be achieved by centerless grinding, turning, electropolishing, drawing, grinding, laser cutting, shaving, polishing, EDM cutting, etc. The size of the outer cross-sectional area or diameter of the near-net medical device, blank, rod, tube, etc. can be reduced by using one or more drawing processes, but this is not required. Care should be taken to avoid the formation of microcracks in the near-net medical device, blank, rod, tube, etc. during the drawing process during the reduction in the outer cross-sectional area or diameter of the near-net medical device, blank, rod, tube, etc.

In another and/or alternative non-limiting aspect of the present disclosure, the near-net medical device, blank, rod, tube, etc. is generally reduced in size upon drawing each time the cross-sectional area is not reduced by about 25% or more (e.g., 0.1-25% and all values and ranges therebetween). If the near-net medical device, blank, rod, tube, etc. optionally includes a nitride layer, the nitride layer can optionally act as a lubricating surface during drawing to facilitate drawing of the near-net medical device, blank, rod, tube, etc. Generally, the near-net medical device, blank, rod, tube, etc. is reduced in cross-sectional area by about 0.1-20% each time the near-net medical device, blank, rod, tube, etc. is drawn through a reduction mechanism. In another and/or alternative non-limiting process step, the near-net medical device, blank, rod, tube, etc. is reduced in cross-sectional area by about 1-15% each time the near-net medical device, blank, rod, tube, etc. is drawn through a reduction mechanism. In yet another and/or alternative non-limiting process step, the near net medical device, blank, rod, tube, etc., reduces in cross-sectional area by about 2-15% each time the near net medical device, blank, rod, tube, etc. is drawn through a reduction mechanism. In yet another non-limiting process step, the near net medical device, blank, rod, tube, etc., reduces in cross-sectional area by about 5-10% each time the near net medical device, blank, rod, tube, etc. is drawn through a reduction mechanism. In another and/or alternative non-limiting embodiment of the present disclosure, the near net medical device, blank, rod, tube, etc., is drawn through a die to reduce the cross-sectional area of the near net medical device, blank, rod, tube, etc. Generally, one end of the near net medical device, blank, rod, tube, etc. is drawn (nose) and fed through the die prior to passing the near net medical device, blank, rod, tube, etc. through the die, although this is not required. The drawing of the tube is typically a cold drawing or plug drawing through a die. When cold drawing or mandrel drawing is used, typically a lubricant (molybdenum paste, grease, etc.) is coated on the outer surface of the near-net medical device, blank, rod, tube, etc., and the near-net medical device, blank, rod, tube, etc. is then drawn through a die. Typically, little or no heat is used in cold drawing. After the near-net medical device, blank, rod, tube, etc. is drawn through the die, the outer surface of the near-net medical device, blank, rod, tube, etc. is typically washed with a solvent to remove the lubricant and limit the amount of impurities incorporated into the refractory metal alloy, but this is not required. This cold drawing process can be repeated several times until the desired outer cross-sectional area or diameter, inner cross-sectional area or diameter, and/or wall thickness of the near-net medical device, blank, rod, tube, etc. is achieved. A plug drawing process can also be used in addition to or instead to size the near-net medical device, blank, rod, tube, etc. In plug drawing, typically no lubricant is used during the drawing process. The plug drawing process typically includes a heating step in which the near-net medical device, blank, rod, tube, etc. is heated prior to and/or during drawing through the die. Eliminating the use of lubricants can reduce the incidence of impurities being introduced into the refractory metal alloy during the drawing process. During the plug drawing process, the near-net medical device, blank, rod, tube, etc. can be protected from oxygen by using a vacuum environment, a non-oxygen environment (e.g., hydrogen, a mixture of argon and hydrogen, nitrogen, nitrogen, etc., and hydrogen, etc.), or an inert environment. One non-limiting protective environment includes argon, hydrogen, or argon and hydrogen, although other or additional inert gases can be used. As indicated above, the near-net medical device, blank, rod, tube, etc. is typically cleaned after each drawing process to remove impurities and/or other undesirable materials from the surface of the near-net medical device, blank, rod, tube, etc., although this is not required. Typically, when the temperature of the near-net medical device, blank, rod, tube, etc. is raised to 500° C. or higher, typically 450° C. or higher, more typically 400° C. or higher, the near-net medical device, blank, rod, tube, etc. needs to be protected from oxygen and nitrogen, although this is not required. When the near-net medical device, blank, rod, tube, etc. is heated to temperatures above about 400-500° C., the near-net medical device, blank, rod, tube, etc. tends to begin to form nitrides in the presence of nitrogen and oxygen. In such high temperature environments, hydrogen environments, argon and hydrogen environments, etc. are generally used. When the near-net medical device, blank, rod, tube, etc. is drawn at temperatures below 400-500° C., there is little or no adverse effect from exposure to air, although an inert or slightly reducing environment is generally preferred.

In another and/or alternative non-limiting aspect of the present disclosure, the near-net medical device, blank, rod, tube, etc. is cooled after annealing, but this is not required. Generally, the near-net medical device, blank, rod, tube, etc. is cooled at a fairly rapid rate after annealing to inhibit or prevent the formation of sigma phase in the refractory metal alloy, but this is not required. Generally, near-net medical devices, blanks, rods, tubes, etc. are cooled at a rate of at least about 50°C/min (e.g., 50-500°C/min and all values and ranges therebetween) after annealing, typically at least 75°C/min after annealing, more typically at least about 100°C/min after annealing, even more typically at about 100-400°C/min after annealing, even more typically at about 150-350°C/min after annealing, even more typically at about 200-300°C per minute after annealing, and even more typically at about 250-280°C per minute after annealing, although this is not required.

In another and/or alternative non-limiting aspect of the present disclosure, the near-net medical device, blank, rod, tube, etc. is annealed after one or more drawing operations. The refractory metal alloy blank, rod, tube, etc. can be annealed after each drawing operation or after multiple drawing operations. The refractory metal alloy blank, rod, tube, etc. is typically annealed before reducing the cross-sectional size of the refractory metal alloy blank, rod, tube, etc. by about 60%. In other words, the near-net medical device, blank, rod, tube, etc. should not be reduced in cross-sectional area by more than 60% before annealing (e.g., 0.1-60% reduction and all values and ranges therebetween). Too much reduction in cross-sectional area of the refractory metal alloy blank, rod, tube, etc. during drawing operations prior to annealing the near-net medical device, blank, rod, tube, etc. may result in microcracks in the near-net medical device, blank, rod, tube, etc. In one non-limiting processing step, the refractory metal alloy blank, rod, tube, etc. is annealed prior to reducing the cross-sectional size of the refractory metal alloy blank, rod, tube, etc. by about 50%. In another and/or alternative non-limiting processing step, the refractory metal alloy blank, rod, tube, etc. is annealed prior to reducing the cross-sectional size of the refractory metal alloy blank, rod, tube, etc. by about 45%. According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy blank, rod, tube, etc. is annealed prior to reducing the cross-sectional size of the refractory metal alloy blank, rod, tube, etc. by about 1-45%. In yet another and/or alternative non-limiting processing step, the refractory metal alloy blank, rod, tube, etc. is annealed prior to reducing the cross-sectional size of the refractory metal alloy blank, rod, tube, etc. by about 5-30%. In yet another and/or alternative non-limiting processing step, the refractory metal alloy blank, rod, tube, etc. is annealed prior to reducing the cross-sectional size of the refractory metal alloy blank, rod, tube, etc. by about 5-15%.

According to another and/or alternative non-limiting aspect of the present disclosure, when annealing the near-net medical device, blank, rod, tube, etc., the near-net medical device, blank, rod, tube, etc. is typically heated at a temperature of about 500-1700°C (and all values and ranges therebetween) for a period of about 1-200 minutes (and all values and ranges therebetween), although other temperatures and/or times may be used. In one non-limiting processing step, the near-net medical device, blank, rod, tube, etc. is annealed at a temperature of about 1000-1600°C for about 2-100 minutes. In another non-limiting processing step, the near-net medical device, blank, rod, tube, etc. is annealed at a temperature of about 1100-1500°C for about 5-30 minutes. The annealing process is typically performed in an inert or oxygen-reduced environment to limit the amount of impurities that may become embedded in the refractory metal alloy during the annealing process. One non-limiting oxygen reducing environment that can be used during the annealing process is a hydrogen environment. However, it can be understood that a vacuum environment can be used or one or more other or additional gases can be used to create the oxygen reduced environment. At the annealing temperature, the hydrogen-containing atmosphere further reduces the amount of oxygen in the near-net medical device, blank, rod, tube, etc. The chamber in which the near-net medical device, blank, rod, tube, etc. is annealed should be substantially free of impurities (such as carbon, oxygen, and nitrogen) (e.g., 0-50 ppm, and all values and ranges therebetween) to limit the amount of impurities that may become embedded in the near-net medical device, blank, rod, tube, etc. during the annealing process. The annealing chamber is typically formed of a material that does not impart impurities to the near-net medical device, blank, rod, tube, etc. as the near-net medical device, blank, rod, tube, etc. is annealed. Non-limiting materials that can be used to form the annealing chamber include, but are not limited to, molybdenum, rhenium, tungsten, molybdenum TZM alloy, cobalt, chromium, ceramics, and the like. When constraining a near-net medical device, blank, rod, tube, etc. in an annealing chamber, the restraining device used to contact the near-net medical device, blank, rod, tube, etc. is typically formed of a material that will not introduce impurities into the refractory metal alloy during processing of the near-net medical device, blank, rod, tube, etc. Non-limiting examples of materials that can be used to at least partially form the restraining device include, but are not limited to, molybdenum, titanium, yttrium, zirconium, rhenium, cobalt, chromium, tantalum, and/or tungsten. In one non-limiting embodiment, when the refractory metal alloy is exposed to temperatures in excess of 150° C. during process steps including annealing, materials that contact the refractory metal alloy during processing of the refractory metal alloy are typically made from chromium, cobalt, molybdenum, rhenium, tantalum, and/or tungsten. When the refractory metal alloy is processed at low temperatures (i.e., below 150° C.), materials made of Teflon™ parts can also be used or can be used instead.

According to another and/or alternative non-limiting aspect of the present disclosure, the annealing parameters may be varied depending on the cross-sectional area or diameter of the near-net medical device, blank, rod, tube, etc., and/or depending on the wall thickness of the near-net medical device, blank, rod, tube, etc. It has been found that varying the annealing parameters depending on the parameters of the near-net medical device, blank, rod, tube, etc., can achieve good grain size characteristics of the near-net medical device, blank, rod, tube, etc. For example, the annealing temperature can be decreased as the wall thickness decreases, but the annealing time can be increased. As will be appreciated, the annealing temperature of the near-net medical device, blank, rod, tube, etc. can be decreased as the wall thickness decreases, but the annealing time can remain the same or be decreased as the wall thickness decreases. After each annealing process, the grain size of the metal of the near-net medical device, blank, rod, tube, etc. should be 4 ASTM or less. Generally, the grain size range is about 4 to 20 ASTM (and all values and ranges therebetween). It is believed that the smaller grain size is achieved as the annealing temperature decreases as the wall thickness decreases. The grain size of the metal in the near-net medical device, blank, rod, tube, etc. should be as uniform as possible. Also, the sigma phase of the metal in the near-net medical device, blank, rod, tube, etc. should be reduced as much as possible. Sigma phase is a spherical, elliptical or tetragonal crystal form in refractory metal alloys. After the final drawing of the near-net medical device, blank, rod, tube, etc., a final anneal of the near-net medical device, blank, rod, tube, etc. can be performed to provide final consolidation of the near-net medical device, blank, rod, tube, etc., but this is not required. If this final annealing process is used, it is generally performed at a temperature of about 500-1600°C (and all values and ranges therebetween) for at least about 1 minute, although other temperatures and/or durations can be used.

According to another and/or alternative non-limiting aspect of the present disclosure, the near-net medical device, blank, rod, tube, etc., can be cleaned before and/or after annealing. The cleaning process is designed to remove impurities, lubricants (nitride compounds, molybdenum paste, grease, oxides, carbides, etc.) and/or other materials from the surfaces of the near-net medical device, blank, rod, tube, etc. Impurities on one or more surfaces of the near-net medical device, blank, rod, tube, etc., can become permanently embedded in the near-net medical device, blank, rod, tube, etc., during the annealing process. These embedded impurities can adversely affect the physical properties of the refractory metal alloy as the near-net medical device, blank, rod, tube, etc., is formed into the medical device, and/or can adversely affect the operation and/or life of the medical device. In one non-limiting embodiment of the present disclosure, the cleaning process includes a de-lubricant or degreasing process, typically followed by a pickling process, although this is not required. The delubricating or degreasing process followed by a pickling process is typically used when a lubricant was used on the near-net medical device, blank, rod, tube, etc. during drawing. Lubricants typically include carbon compounds, nitride compounds, molybdenum paste, and other types of compounds that may adversely affect the refractory metal alloy if such compounds and/or elements therein are bonded and/or embedded in the refractory metal alloy during the annealing process. The delubricating or degreasing process may be performed by a variety of techniques, including but not limited to: 1) using a solvent (e.g., acetone, methyl alcohol, etc.) and wiping the refractory metal alloy with a Kimwipe or other suitable towel; 2) by at least partially dipping or submerging the refractory metal alloy in a solvent and then ultrasonically cleaning the refractory metal alloy; 3) sandblasting the refractory metal alloy; and/or 4) chemically etching the refractory metal alloy. As can be appreciated, the refractory metal alloy may be delubricated or degreased in other or additional ways. After de-lubricating or degreasing the near-net medical device, blank, rod, tube, etc., the near-net medical device, blank, rod, tube, etc. may be further cleaned using an acid pickling process, but this is not required. The acid pickling process (when used) involves the use of one or more acids to remove impurities from the surface of the near-net medical device, blank, rod, tube, etc. Non-limiting examples of acids that can be used as an acid pickling solution include, but are not limited to, nitric acid, acetic acid, sulfuric acid, hydrochloric acid, and/or hydrofluoric acid. These acids are typically analytical reagent (ACS) grade acids. The acid solution and acid concentration are selected to remove oxides and other impurities on the surface of the near-net medical device, blank, rod, tube, etc. without damaging or excessively etching the surface of the near-net medical device, blank, rod, tube, etc. Surfaces of near-net medical devices, blanks, rods, tubes, etc. that contain large amounts of oxides and/or nitrides typically require stronger acid pickling solutions and/or longer acid pickling treatment times. Non-limiting examples of pickling solutions include: 1) 25-60% deionized water (and all values and ranges therebetween), 30-60% nitric acid (and all values and ranges therebetween) and 2-20% sulfuric acid (and all values and ranges therebetween), 2) 40-75% acetic acid (and all values and ranges therebetween), 10-35% nitric acid (and all values and ranges therebetween) and 1-12% hydrofluoric acid (and all values and ranges therebetween), and 3) 50-100% hydrochloric acid (and all values and ranges therebetween). As can be appreciated, one or more different pickling solutions can be used during the pickling process. During the pickling treatment, the near-net medical device, blank, rod, tube, etc. is fully or partially immersed in the pickling solution for a time sufficient to remove impurities from the surface of the near-net medical device, blank, rod, tube, etc. Typically, the pickling time is about 2-120 seconds (and all values and ranges therebetween), although other time periods can be used. After pickling the near-net medical device, blank, rod, tube, etc., the near-net medical device, blank, rod, tube, etc. is typically rinsed with water (e.g., deionized water, etc.) or a solvent (e.g., acetone, methyl alcohol, etc.) to remove the pickling solution from the near-net medical device, blank, rod, tube, etc., after which the near-net medical device, blank, rod, tube, etc. may be dried. The near-net medical device, blank, rod, tube, etc. may be kept in a protective environment during the rinsing and/or drying process to inhibit or prevent the reformation of oxides on the surface of the near-net medical device, blank, rod, tube, etc. before the near-net medical device, blank, rod, tube, etc. is drawn and/or annealed, but this is not required.

According to another and/or alternative non-limiting aspect of the present disclosure, the near-net medical device, blank, rod, tube, etc., after a) being formed into a desired green shape, b) being formed to have a desired outer cross-sectional area or diameter, and/or c) being formed to have a desired inner cross-sectional area or diameter and/or wall thickness, can subsequently be cut and/or etched to at least partially form the desired configuration of the medical device (e.g., stent, TAV valve, etc.). The near-net medical device, blank, rod, tube, etc., can be cut or otherwise formed by one or more processes (e.g., centerless grinding, turning, electropolishing, drawing, grinding, laser cutting, shaving, polishing, electrodischarge machining, etching, micromachining, laser micromachining, micromolding, machining, etc.). As will be appreciated, some or all of the medical device can be formed by 3D printing. In one non-limiting embodiment of the present disclosure, the refractory metal alloy used to partially or completely form the near-net medical device, blank, rod, tube, etc., is at least partially cut by a laser. The laser typically has a beam intensity capable of heating the refractory metal alloy near-net medical device, blank, rod, tube, etc., to a temperature of at least about 2200-2300° C. In one non-limiting aspect of this embodiment, a pulsed Nd:YAG neodymium doped yttrium aluminum garnet (Nd:Y ₃ Al ₅ O ₁₂ ) or CO ₂ laser is used to at least partially cut the medical device pattern from the refractory metal alloy blank, rod, tube, etc. In accordance with another and/or alternative non-limiting aspect of this embodiment, the laser cutting of the refractory metal alloy used to partially or completely form the near-net medical device, blank, rod, tube, etc. can be, but is not required to be, performed in a vacuum, reduced oxygen, or inert environment. It has been found that laser cutting of near-net medical devices, blanks, rods, tubes, etc. in an unprotected environment can introduce impurities into the cut near-net medical device, blank, rod, tube, etc., which may induce microcracks in the near-net medical device, blank, rod, tube, etc. during cutting of the near-net medical device, blank, rod, tube, etc. One non-limiting oxygen reducing environment includes a combination of argon and hydrogen, although a vacuum environment, an inert environment, or other gases or additional gases may also be used to form the oxygen reducing environment. In yet another and/or alternative non-limiting aspect of this embodiment, the refractory metal alloy used to partially or completely form the near-net medical device, blank, rod, tube, etc. is stabilized to limit or prevent vibration of the near-net medical device, blank, rod, tube, etc. during the cutting process. The devices used to stabilize the near net medical device, blank, rod, tube, etc. can be, but are not required to be, made of molybdenum, rhenium, tungsten, tantalum, cobalt, chromium, molybdenum TZM alloys, ceramics, etc., to prevent contaminants from being introduced into the near net medical device, blank, rod, tube, etc., during the cutting process. Vibration of the near net medical device, blank, rod, tube, etc., during cutting of the near net medical device, blank, rod, tube, etc., can result in the formation of microcracks in the near net medical device, blank, rod, tube, etc. The average amplitude of vibration during cutting of the near net medical device, blank, rod, tube, etc., is generally, but is not required to be, about 150% (0-150% and all values and ranges therebetween) or less of the wall thickness of the near net medical device, blank, rod, tube, etc. In one non-limiting aspect of this embodiment, the average amplitude of vibration is about 100% or less of the wall thickness of the near net medical device, blank, rod, tube, etc. In another non-limiting aspect of this embodiment, the average amplitude of vibration is about 75% or less of the wall thickness of the near net medical device, blank, rod, tube, etc. In yet another non-limiting aspect of this embodiment, the average amplitude of vibration is about 50% or less of the wall thickness of the near net medical device, blank, rod, tube, etc. In yet another non-limiting aspect of this embodiment, the average amplitude of vibration is about 25% or less of the wall thickness of the near net medical device, blank, rod, tube, etc. In yet another non-limiting aspect of this embodiment, the average amplitude of vibration is about 15% or less of the wall thickness of the near net medical device, blank, rod, tube, etc.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy used to partially or completely form the near-net medical device can be optionally cleaned, polished, sterilized, nitrided, etc. after being formed to a final or near-final shape. In one non-limiting embodiment of the present disclosure, the medical device is electropolished. In one non-limiting aspect of this embodiment, the medical device is cleaned before being exposed to the polishing solution, although this is not required. The cleaning process (when in use) can be performed by a variety of techniques, including but not limited to: 1) using a solvent and wiping the medical device with a Kimwipe or other suitable towel, and/or 2) by at least partially dipping or immersing the medical device in a solvent and then ultrasonically cleaning the medical device. As will be appreciated, the medical device can be cleaned in other or additional ways. According to another and/or alternative non-limiting aspect of this embodiment, the polishing solution may include one or more acids. In yet another and/or alternative non-limiting aspect of this embodiment, the medical device is rinsed with water and/or a solvent and dried to remove the polishing liquid on the medical device. In another and/or alternative non-limiting embodiment of the present disclosure, the formed medical device is optionally nitrided. After the medical device is nitrided, it is typically washed, but this is not required. During the nitriding process for the medical device, the surface of the medical device is modified by the presence of nitrogen. The nitriding process can be used to increase the hardness and/or wear resistance of the surface of the medical device and/or to limit or exhibit discoloration of the surface of the frame of the medical device. For example, the nitriding process can be used to increase the wear resistance of the articulating surfaces or surfaces of the medical device to increase the life of the medical device and/or to increase the wear life of the mating surfaces of the medical device and/or to reduce particulate generation from the use of the medical device.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy may be coated with a strengthening coating to improve one or more properties of the refractory metal alloy (e.g., to change the color appearance of the metal alloy, increase the hardness of the coating surface, increase the toughness of the coating surface, reduce the friction of the coating surface, improve the impact wear of the coating surface, improve the corrosion and oxidation resistance, form a non-stick coating surface, improve the biocompatibility of the metal alloy having the coating surface, reduce the toxicity of the metal alloy having the coating surface, etc.). Strengthening coatings that may be applied to a portion or the entire outer surface of the refractory metal alloy include chromium nitride (CrN), diamond-like carbon (DLC), titanium nitride (TiN), zirconium nitride (ZrN), zirconium oxide ( _ZrO2 ), zirconium nitrogen carbon (ZrNC), zirconium oxycarbide (ZrOC), and combinations of such coatings. In one non-limiting embodiment, the one or more strengthening coatings are applied to a portion of the entire outer surface of the refractory metal alloy in a vacuum process that uses an energy source to evaporate material and deposit a thin layer of the strengthening coating material. Such vacuum coating processes include physical vapor deposition (PVD) processes (such as sputter deposition, cathodic arc deposition, or electron beam heating), chemical vapor deposition (CVD) processes, atomic layer deposition (ALD) processes, or plasma enhanced chemical vapor deposition (PE-CVD) processes. In one non-limiting embodiment, the coating process is one or more of PVD, CVD, ALD, and PE-CVD, and the coating process is carried out at a temperature of 200-400° C. (and all values and ranges therebetween) for at least 10 minutes (e.g., 10-400 minutes and all values and ranges therebetween). In another non-limiting embodiment, the coating process is one or more of PVD, CVD, ALD, and PE-CVD, and the coating process is carried out at a temperature of 220-300° C. for 60-120 minutes. The one or more reinforcement coating materials can be combined with one or more metals in the refractory metal alloy and/or can be combined with nitrogen, oxygen, carbon, or other elements present in the refractory metal alloy and/or in the atmosphere surrounding the refractory metal alloy to form a reinforcement coating on the outer surface of the refractory metal alloy that can have enhanced properties (e.g., the reinforcement coating is harder than case hardened steel, the reinforcement coating is less scratch resistant than hardened chrome, the reinforcement coating is more corrosion resistant, etc.). In another non-limiting embodiment, the one or more reinforcement coatings can form a variety of coating colors on the outer surface of the refractory metal alloy (e.g., gold, copper, brass, black, rose gold, chrome, blue, silver, yellow, green, etc.). In another non-limiting embodiment, the thickness of the reinforcement coating is greater than 1 nanometer (e.g., 2 nanometers to 100 microns and all values and ranges therebetween), typically 0.1 to 25 microns, and more typically 1 to 10 microns. In another non-limiting embodiment, the hardness of the reinforced coating is 5 GPa (ASTMC1327-15 or ASTM C1624-05), typically 5 to 50 GPa (and all values and ranges therebetween), more typically 10 to 25 GPa, and even more typically 14 to 24 GPa. In another non-limiting embodiment, the coefficient of friction (COF) of the reinforced coating is 0.04 to 0.2 (and all values and ranges therebetween), typically 0.6 to 0.15. In another non-limiting embodiment, the wear rate of the reinforced coating is 0.5×10 ⁻⁷ mm ³ /N-m to 3×10 ⁻⁷ mm ³ /N-m (and all values and ranges therebetween), typically 1.2×10 ⁻⁷ mm ³ /N-m to 2×10 ⁻⁷ mm ³ /N-m. In another non-limiting embodiment, a silicon-based precursor (e.g., trimethylsilane, tetramethylsilane, hexachlorodisilane, silane, dichlorosilane, trichlorosilane, silicon tetrachloride, tris(dimethylamino)silane, bis(tert-butylamino)silane, trisilylamine, allyltrimethoxysilane, (3-aminopropyl)triethoxysilane, butyltrichlorosilane, n-sec-butyl(trimethylsilyl)amine, chloropentamethyldisilane, 1,2-dichlorotetramethyldisilane, [3-(diethylamino)silane, 1,2-dichlorotetra ... [0033] Examples of suitable silanes that may be used include, but are not limited to, 1,3-dimethyl-1,1,3,3-tetramethyldisilazane, dimethoxydimethylsilane, dodecamethylcyclohexasilane, hexamethyldisilane, isobutyl(trimethoxy)silane, methyltrichlorosilane, 2,4,6,8,10-pentamethylcyclopentasiloxane, pentamethyldisilane, n-propyltriethoxysilane, silicon tetrabromide, silicon tetrabromide, and the like, may be used to facilitate application of the reinforcing coating to one or more portions or to the entire exterior surface of the refractory metal alloy.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, and the reinforcement coating composition includes a chromium nitride (CrN) coating. Some or all of the outer surface of the refractory metal alloy can include a chromium nitride (CrN) coating. The reinforcement coating can be used to improve hardness, improve toughness, reduce friction, improve impact wear resistance, improve corrosion and oxidation resistance, and/or reduce stick surface when in contact with various materials. According to one non-limiting embodiment, the refractory metal alloy is coated with a strengthening coating generally comprising 40-85 wt. % Cr (and all values and ranges therebetween), 15-60 wt. % N (and all values and ranges therebetween), 0-10 wt. % Re (and all values and ranges therebetween), 0-10 wt. % Si (and all values and ranges therebetween), 0-2 wt. % O (and all values and ranges therebetween), and 0-2 wt. % C (and all values and ranges therebetween). In one non-limiting coating process, all or a portion of the outer surface of the refractory metal alloy is first coated with Cr metal. The Cr metal coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The Cr metal coating has a thickness of 0.5-15 microns. The Cr metal coating is then exposed to nitrogen gas and/or a nitrogen-containing gas compound to react the nitrogen with the Cr metal coating to form a layer of CrN on the outer surface of the Cr metal coating and/or the outer surface of the refractory metal alloy. In another non-limiting embodiment, the reinforced coating composition generally comprises 65-80 wt% Cr, 15-30 wt% N, 0-8 wt% Re, 0-1 wt% Si, 0-1 wt% O, and 0-1 wt% C.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, and the reinforcement coating composition generally comprises a diamond-like carbon (DLC) coating. Some or all of the outer surface of the refractory metal alloy can include a diamond-like carbon (DLC) coating. The reinforcement coating can be used to improve hardness, improve toughness, reduce friction, improve impact wear resistance, improve corrosion and oxidation resistance, improve biocompatibility, and/or reduce sticking surfaces when in contact with many different materials. In one non-limiting embodiment, all or a portion of the outer surface of the refractory metal alloy is coated with a reinforced coating composition generally comprising 60-99.99 wt.% C (and all values and ranges therebetween), 0-2 wt.% N (and all values and ranges therebetween), 0-10 wt.% Re (and all values and ranges therebetween), 0-20 wt.% Si (and all values and ranges therebetween), and 0-2 wt.% O (and all values and ranges therebetween). The carbon coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The carbon layer can be applied using methane and/or acetylene gas. However, other or additional carbon sources can also be used. The carbon coating has a thickness of 0.5-15 microns. In another non-limiting embodiment, all or a portion of the outer surface of the refractory metal alloy is coated with a reinforcement coating composition generally comprising 90-99.99 wt.% C, 0-1 wt.% N, 0-8 wt.% Re, 0-1 wt.% Si, and 0-1 wt.% O.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, the reinforcement coating composition generally comprising a titanium nitride (TiN) coating. Part or all of the outer surface of the refractory metal alloy can include a titanium nitride (TiN) coating. The reinforcement coating can be used to increase hardness, increase toughness, increase corrosion and oxidation resistance, reduce friction, and/or reduce stick surfaces when in contact with many different materials. In one non-limiting embodiment, all or a portion of the outer surface of the refractory metal alloy is first coated with titanium metal. The Ti metal coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The Ti metal coating thickness is 0.5 to 15 microns. The Ti metal coating is then exposed to nitrogen gas and/or a nitrogen-containing gas compound to react the nitrogen with the Ti metal coating to form a layer of TiN on the outer surface of the Ti metal coating and/or the outer surface of the refractory metal alloy. In another non-limiting embodiment, the reinforced coating composition generally comprises 20-85 wt% Ti (and all values and ranges therebetween), 5-30 wt% N (and all values and ranges therebetween), 0-10 wt% Re (and all values and ranges therebetween), 0-20 wt% Si (and all values and ranges therebetween), 0-2 wt% O (and all values and ranges therebetween), and 0-2 wt% C (and all values and ranges therebetween). In another non-limiting embodiment, the reinforced coating composition generally comprises 70-80 wt% Ti, 20-25 wt% N, 0-8 wt% Re, 0-1 wt% Si, 0-1 wt% O, and 0-1 wt% C.

According to another and/or alternative non-limiting aspect of the present disclosure, a refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, the reinforcement coating composition generally comprising a zirconium nitride (ZrN) coating. A portion or all of the outer surface of the refractory metal alloy can include a zirconium nitride (ZrN) coating. The reinforcement coating can be used to increase hardness, increase toughness, increase corrosion and oxidation resistance, reduce friction, and/or reduce stick surfaces when in contact with many different materials. In one non-limiting embodiment, all or a portion of the outer surface of the refractory metal alloy is first coated with Zr metal. The Zr metal coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The Zr metal coating thickness is 0.5 to 15 microns. The Zr metal coating is then exposed to nitrogen gas and/or a nitrogen-containing gas compound to react the nitrogen with the Zn metal coating to form a layer of ZrN on the outer surface of the Zr metal coating and/or the outer surface of the refractory metal alloy. The ZrN coating has been found to produce a gold enhanced coating color. In another non-limiting embodiment, the enhanced coating composition generally comprises 35-90 wt% Zr (and all values and ranges therebetween), 5-25 wt% N (and all values and ranges therebetween), 0-10 wt% Re (and all values and ranges therebetween), 0-20 wt% Si (and all values and ranges therebetween), 0-2 wt% O (and all values and ranges therebetween), and 0-2 wt% C (and all values and ranges therebetween). In another non-limiting embodiment, the reinforced coating composition generally comprises 80-90 wt% Zr, 10-20 wt% N, 0-8 wt% Re, 0-1 wt% Si, 0-1 wt% O, and 0-1 wt% C.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, the reinforcement coating composition generally comprising a zirconium oxide (ZrO ₂ ) coating. A portion or all of the outer surface of the refractory metal alloy can comprise a zirconium oxide (ZrO ₂ ) coating. The reinforcement coating can be used to increase hardness, increase toughness, increase corrosion and oxidation resistance, reduce friction, and/or reduce stick surface when in contact with many different materials. In one non-limiting embodiment, a portion or all of the outer surface of the refractory metal alloy is first coated with Zr metal. The Zr metal coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The Zr metal coating thickness is 0.5 to 15 microns. The Zr metal coating is then exposed to oxygen gas and/or an oxygen-containing gas compound to react the oxygen with the Zn metal coating to form a layer of zirconium oxide (ZrO ₂ ) on the outer surface of the Zr metal coating and/or the outer surface of the refractory metal alloy. The zirconium oxide (ZrO ₂ ) coating has been found to produce a blue enhanced coating color. In another non-limiting embodiment, the enhanced coating composition generally comprises 35-90 wt % Zr (and all values and ranges therebetween), 10-35 wt % O (and all values and ranges therebetween), 0-2 wt % N (and all values and ranges therebetween), 0-10 wt % Re (and all values and ranges therebetween), 0-20 wt % Si (and all values and ranges therebetween), and 0-2 wt % C (and all values and ranges therebetween). In another non-limiting embodiment, the reinforced coating composition generally comprises 70-80 wt.% Zr, 20-30 wt.%, 0-1 wt.% N, 0-8 wt.% Re, 0-1 wt.% Si, and 0-1 wt.% C.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, the reinforcement coating composition generally includes both a zirconium oxide (ZrO ₂ ) coating and a zirconium nitride (ZrN) coating. Some or all of the outer surface of the refractory metal alloy can include a zirconium oxide (ZrO ₂ ) coating and a zirconium nitride (ZrN) coating. The reinforcement coating can be used to increase hardness, increase toughness, increase corrosion and oxidation resistance, reduce friction, and/or reduce stick surface when in contact with many different materials. In one non-limiting embodiment, all or a portion of the outer surface of the refractory metal alloy is first coated with Zr metal. The Zr metal coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The Zr metal coating thickness is 0.5 to 15 microns. The Zr metal coating is then exposed to a) both oxygen gas and/or oxygen-containing gas compounds and nitrogen gas and/or nitrogen-containing gas compounds, b) nitrogen gas and/or nitrogen-containing gas compounds and then oxygen gas and/or oxygen-containing gas compounds, or c) oxygen gas and/or oxygen-containing gas compounds and then nitrogen gas and/or nitrogen-containing gas compounds. The coating compositions of the zirconium oxide ( _ZrO2 ) coating and the zirconium nitride coating (ZrN) are similar or the same as those discussed above.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, the reinforcement coating composition generally comprising a zirconium oxycarbide (ZrOC) coating. Part or all of the outer surface of the refractory metal alloy can include a zirconium oxycarbide (ZrOC) coating. The reinforcement coating can be used to increase hardness, increase toughness, increase corrosion and oxidation resistance, reduce friction, and/or reduce stick surface when in contact with many different materials. In one non-limiting embodiment, all or a portion of the outer surface of the refractory metal alloy is first coated with Zr metal. The Zr metal coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The Zr metal coating thickness is 0.5 to 15 microns. The Zr metal coating is then exposed to a) both oxygen gas and/or oxygen containing gas compounds and carbon and/or carbon containing gas compounds (e.g., methane and/or acetylene gas), b) carbon and/or carbon containing gas compounds and then oxygen gas and/or oxygen containing gas compounds, or c) oxygen gas and/or oxygen containing gas compounds and then carbon and/or carbon containing gas compounds. In another non-limiting embodiment, the reinforced coating composition generally comprises 40-95 wt% Zr (and all values and ranges therebetween), 5-25 wt% O (and all values and ranges therebetween), and 10-40 wt% C (and all values and ranges therebetween), 0-2 wt% N (and all values and ranges therebetween), 0-10 wt% Re (and all values and ranges therebetween), and 0-20 wt% Si (and all values and ranges therebetween). In another non-limiting embodiment, the reinforced coating composition generally comprises 40-65 wt% Zr, 5-25 wt% O, and 25-40 wt% C, 0-1 wt% N, 0-8 wt% Re, and 0-1 wt% Si.

According to another and/or alternative non-limiting aspect of the present disclosure, the refractory metal alloy is coated with a reinforcement coating to improve one or more properties of the refractory metal alloy, the reinforcement coating composition generally comprising a zirconium-nitrogen-carbon (ZrNC) coating. A portion or all of the outer surface of the refractory metal alloy can include a zirconium-nitrogen-carbon (ZrNC) coating. The reinforcement coating can be used to increase hardness, increase toughness, increase corrosion and oxidation resistance, reduce friction, and/or reduce stick surfaces when in contact with many different materials. In one non-limiting embodiment, all or a portion of the outer surface of the refractory metal alloy is first coated with Zr metal. The Zr metal coating can be applied by PVD, CVD, ALD, and PE-CVD in an inert environment. The Zr metal coating thickness is 0.5 to 15 microns. The Zr metal coating is then exposed to nitrogen gas and/or nitrogen-containing gas compounds, followed by carbon and/or carbon-containing gas compounds (e.g., methane and/or acetylene gas). The color of the ZrNCs depends on the amount of C and N in the coating. In one non-limiting embodiment, the reinforced coating composition generally comprises 40-95 wt% Zr (and all values and ranges therebetween), 5-40 wt% N (and all values and ranges therebetween), and 5-40 wt% C (and all values and ranges therebetween), 0-2 wt% O (and all values and ranges therebetween), 0-10 wt% Re (and all values and ranges therebetween), and 0-20 wt% Si (and all values and ranges therebetween). In another non-limiting embodiment, the reinforced coating composition generally comprises 40-80 wt% Zr, 5-25 wt% N, and 5-25 wt% C, 0-1 wt% O, 0-8 wt% Re, and 0-1 wt% Si.

According to another and/or alternative non-limiting aspect of the present disclosure, the use of refractory metal alloys to form all or part of a medical device provides several advantages over medical devices formed from other materials. These advantages include, but are not limited to, the following:

- Because refractory metal alloys have increased strength and/or hardness compared to stainless steel, chromium-cobalt alloys, or titanium alloys, less refractory metal alloys can be used in a medical device to achieve comparable strength compared to a medical device formed of a different metal. Thus, the resulting medical device can be made smaller and less bulky by using refractory metal alloys without sacrificing the strength and durability of the medical device. The medical device can also have a smaller profile, so that it can be inserted into smaller areas, openings, and/or passageways. Thinner struts of refractory metal alloys that form the frame or other portions of the medical device can be used to form the frame or other portions of the medical device that have strength that would require thicker struts or other structures of the medical device when formed of stainless steel, chromium-cobalt alloys, or titanium alloys.

The increased strength of the refractory metal alloy also increases the radial strength of the medical device. For example, the wall thickness of the medical device can be made thinner and achieve the same or improved radial strength compared to thicker walled medical devices made from stainless steel, cobalt and chromium alloys, or titanium alloys.

- Refractory metal alloys provide improved stress-strain, flexural, elongation, and/or flexibility properties of medical devices compared to stainless steels and chromium-cobalt alloys, thereby increasing the lifespan of the medical device. For example, medical devices may be used in areas where the medical device is repeatedly bent. The improved physical properties of the medical device provided by the refractory metal alloys increase the fracture resistance of the medical device in such frequent bending environments. These improved physical properties are attributable, at least in part, to the composition of the refractory metal alloy, the grain size of the refractory metal alloy, the carbon, oxygen, and nitrogen content of the refractory metal alloy, and/or the carbon/oxygen ratio of the refractory metal alloy.

- High melting point metal alloys reduce the degree of recoil during compression and/or expansion of the medical device compared to stainless steel, chromium-cobalt alloys, or titanium alloys. Medical devices formed from high melting point metal alloys better maintain their compressed shape and/or better maintain their expanded shape after expansion due to the use of high melting point metal alloys. Thus, when the medical device is compressed, when the medical device is mounted on the delivery device, the medical device better maintains its smaller profile during insertion of the medical device into the body passageway. Also, the medical device better maintains its expanded profile after expansion, promoting the success of the medical device in the treatment area.

- The use of refractory metal alloys in medical devices allows the medical device to better conform to irregularly shaped body passages when expanded within the body passages, compared to medical devices formed from stainless steel, chromium-cobalt alloys, or titanium alloys.

- Refractory metal alloys have improved radiopacity compared to standard materials such as stainless steel or cobalt-chromium alloys, reducing or eliminating the need for marker materials in medical devices. For example, refractory metal alloys are at least about 10-20% more radiopaque than stainless steel or cobalt-chromium alloys.

- Refractory metal alloys have improved fatigue ductility during cold working compared to cold working of stainless steels, chromium-cobalt alloys, or titanium alloys.

- Refractory metal alloys have improved durability compared to stainless steel, chromium-cobalt alloys or titanium alloys.

-High melting point metal alloys have improved hydrophilicity compared to stainless steel, chromium-cobalt alloys or titanium alloys.

- Refractory metal alloys reduce ion release in body passageways compared to stainless steels, chromium-cobalt alloys, or titanium alloys.

- Refractory metal alloys are less irritating to the body than stainless steel, cobalt-chromium alloys, or titanium alloys, which can reduce inflammation, speed healing, and increase the success rate of medical devices. When a medical device expands within a body passageway, minor damage may occur to the interior of the passageway. As the body begins to heal this minor damage, the body will be less adversely affected by the presence of refractory metal alloys compared to other metals such as stainless steel, cobalt-chromium alloys, or titanium alloys.

- Refractory metal alloys have a lower magnetic susceptibility than CoCr alloys, TiAlV alloys and/or stainless steels, resulting in a lower incidence of potential device defects or patient complications following device implantation when the patient is exposed to MRI or other medical equipment that generates strong magnetic fields.

One non-limiting object of the present disclosure is to provide a refractory metal alloy according to the present disclosure that can be used to partially or completely form a medical device.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device formed partially or completely from the refractory metal alloy of the present disclosure, which improves the success of the procedure.

Another and/or alternative non-limiting object of the present disclosure is to provide methods and processes for forming refractory metal alloys according to the present disclosure that reduce or prevent the formation of microcracks during processing of the refractory metal alloys.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device formed partially or completely from a refractory metal alloy according to the present disclosure, the medical device having improved physical properties.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device formed at least in part from a refractory metal alloy according to the present disclosure, the medical device having increased strength and/or hardness.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device that is at least partially comprised of a refractory metal alloy according to the present disclosure, which allows the medical device to be formed with less material compared to conventional medical devices without sacrificing strength of the medical device.

Another and/or alternative non-limiting object of the present disclosure is to provide methods and processes for forming refractory metal alloys according to the present disclosure to reduce or prevent the formation of microcracks during the process of making the refractory metal alloy into a medical device.

Another and/or alternative non-limiting object of the present disclosure is to provide methods and processes for forming refractory metal alloys according to the present disclosure that inhibit or prevent crack propagation and/or fatigue failure of the refractory metal alloys.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device including a refractory metal alloy having a nitriding process that forms a nitride layer on an outer surface of the refractory metal alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device that includes a refractory metal alloy that has been subjected to a swaging process.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy that has been subjected to a cold working process.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy having greater strength and/or hardness as compared to stainless steel, chromium-cobalt alloys, or titanium alloys.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device that includes a refractory metal alloy, thereby requiring less of the refractory metal alloy to achieve comparable strength as compared to a medical device formed of a different metal.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, the medical device having a smaller compressed profile as compared to a medical device formed of a different metal.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, the medical device having thinner walls and/or struts than a frame of the same shape formed from a stainless steel, a cobalt and chromium alloy, or a titanium alloy, and such a frame formed from a refractory metal alloy has equivalent or increased radial strength when the frame is expanded from a compressed configuration to an expanded configuration, as compared to a frame formed from a stainless steel, a cobalt and chromium alloy, or a titanium alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, the medical device having improved stress-strain, bending, elongation, and/or flexibility properties as compared to medical devices formed from stainless steel, titanium alloys, or chromium-cobalt alloys.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, which has an extended life span as compared to medical devices formed from stainless steel, titanium alloys, or chromium-cobalt alloys.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, which has a reduced degree of recoil during compression and/or expansion of the medical device as compared to a frame of similar size, shape and configuration formed from a stainless steel, a chromium-cobalt alloy, or a titanium alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, which conforms better to irregularly shaped body passages when expanded within the body passage as compared to a frame of similar size, shape and configuration formed from a stainless steel, a chromium-cobalt alloy or a titanium alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, which when subjected to cold working exhibits improved fatigue ductility as compared to cold working of a frame of similar size, shape and configuration formed from a stainless steel, a chromium-cobalt alloy or a titanium alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, the medical device having improved durability as compared to stainless steel, chromium-cobalt alloy, or titanium alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, the medical device having improved hydrophilicity as compared to stainless steel, chromium-cobalt alloy, or titanium alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, which has reduced ion release in a body passageway as compared to stainless steel, a chromium-cobalt alloy, a chromium-cobalt alloy, or a titanium alloy.

Another and/or alternative non-limiting object of the present disclosure is to provide a medical device comprising a refractory metal alloy, which is less irritating to the body than stainless steel, cobalt-chromium alloys, or titanium alloys, resulting in less inflammation, faster healing, and improved success of the medical device.

Another and/or alternative non-limiting object of the present disclosure is to provide a refractory metal alloy including a reinforced coating of chromium nitride (CrN), diamond-like carbon (DLC), titanium nitride (TiN), zirconium nitride (TiN)), zirconium nitride (ZrN), zirconium oxide (ZrO2), or zirconium oxycarbide (ZrOC) that can be used to improve one or more properties of the refractory metal alloy (e.g., change the color appearance of the metal alloy, increase the hardness of the coating surface, increase the toughness of the coating surface, reduce the friction of the coating surface, improve the _impact wear of the coating surface, improve the corrosion and oxidation resistance, form a non-stick coating surface, improve the biocompatibility of the metal alloy having the coating surface, reduce the toxicity of the metal alloy having the coating surface, etc.).

These and other advantages will become apparent to those skilled in the art upon reading this specification and the following.

For clarity, specific terminology is used in the following description, but these terms are intended to refer only to the particular structures of the embodiments selected for illustration in the drawings and are not intended to define or limit the scope of the present disclosure. In the drawings and the following description, it is understood that like number designations refer to components of similar function.

The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

The term "comprising" as used in this disclosure and in the claims can include "consisting of" and "consisting essentially of" embodiments, and the terms "comprising," "including," "having," "having," "can," "having," and variations thereof as used in this disclosure are intended to be open-ended transitional phrases, terms, or words that require the presence of the specified components/steps and permit the presence of other components/steps. However, such descriptions should also be construed as describing the composition or process as "consisting of" and "consisting essentially of" the listed components/steps, thereby permitting the presence of only the specified components/steps, along with any unavoidable impurities that may result, and excluding other components/steps.

Numerical values in the specification and claims of this application should be understood to include the same numerical values when converted to the same significant figures, and numerical values that differ from the stated numerical values by less than the experimental error of conventional measurement techniques of the type described in this application to determine the values.

All ranges disclosed in this disclosure are inclusive of the recited endpoints and are independently combinable (e.g., the range "from 2 grams to 10 grams" includes the endpoints, 2 grams and 10 grams, and all intermediate values).

The terms "about" and "approximately" can be used to include any numerical value that can vary without changing the basic function of that value. When used in conjunction with a range, "about" and "approximately" also disclose the range defined by the absolute values of the two endpoints, for example, "about 2 to about 4" also discloses the range "from 2 to 4." In general, the terms "about" and "approximately" may refer to plus or minus 10% of the indicated numerical value.

Unless expressly stated otherwise, elemental percentages should be assumed to be percentages by weight of the stated element.

Medical devices such as expandable heart valves formed at least in part from refractory metal alloys according to the present disclosure overcome several unmet needs that exist for expandable medical devices formed from CoCr alloys, TiAlV alloys and stainless steels. Such unmet needs addressed by medical devices according to the present disclosure include: 1) eliminating the need to form large holes in large arterial or other vessels to initially insert a compressed medical device into an atrial or other vessel, thereby reducing the incidence of fatal bleeding during treatment; 2) creating a medical device that allows the delivery and implantation of a medical device (e.g., stents, prosthetic heart valves, etc.) in a smaller compressed shape than medical devices formed from CoCr alloys, TiAlV alloys and stainless steels, into or through abnormally shaped heart valves due to sintering in the heart valves and/or sintering in the arterial vessels and/or plaque in the arterial vessels. 3) the use of a frame formed of a refractory metal alloy reduces the incidence of perivalvular leakage and/or other types of leakage around the implanted medical device when the medical device is expanded within the treatment area, and the refractory metal alloy better conforms to the shape of the abnormally shaped heart valve orifice during expansion of the prosthetic heart valve compared to prior art prosthetic heart valves formed of CoCr alloys, TiAlV alloys and stainless steels, thereby reducing the incidence of stroke and/or increasing the success rate of the implanted medical device; 4) the radial strength of the expanded struts, posts and/or strut joints within the expandable frame; and Improve the strength of the expandable frame itself after expansion of the medical device; 5) reduce the compression of the expandable frame of the medical device and/or the amount of recoil of the expandable frame during expansion; 6) allow the medical device to be used in hearts with permanent pacemakers; 7) reduce the incidence of minor strokes during insertion and manipulation of the medical device in the treatment area; 8) reduce the incidence of coronary ostium injury; 9) improve fractional shortening; 10) reduce further aortic valve calcification and/or calcification within the blood vessel after implantation of the medical device; 11) reduce the need for multiple compression cycles when inserting the medical device into a catheter or other type of delivery system; 12) reduce the need for multiple compression cycles when inserting the medical device into a catheter or other type of delivery system; 13) reduce the incidence of frame/stent fracture during vessel compression and/or expansion; 14) reduce the incidence of biofilm endocarditis after implantation of the medical device; 15) improve the hydrophilicity of the medical device to improve tissue growth on and/or around the implanted medical device; 16) reduce the magnetic susceptibility of the medical device; 17) reduce the toxicity of the medical device; 18) reduce the amount of metal ions released from the medical device; and/or 19) increase the lifespan of the leaflets and/or stent/frame and/or other components of the medical device after insertion of the medical device.

In another non-limiting aspect of the present disclosure, a refractory metal alloy is provided that includes rhenium and one or more alloying metals, the refractory metal alloy being used to at least partially form a medical device.

In another non-limiting aspect of the present disclosure, a refractory metal alloy is provided that includes rhenium and one or more alloying metals, the refractory metal alloy being used to at least partially form a medical device, at least one region of the medical device including at least one biological agent.

In another non-limiting aspect of the present disclosure, a refractory metal alloy is provided that includes rhenium and one or more alloying metals, the refractory metal alloy being used to at least partially form a medical device, at least one region of the medical device including at least one polymer.

In another non-limiting aspect of the present disclosure, a refractory metal alloy is provided that includes rhenium and one or more alloying metals, the refractory metal alloy being used to at least partially form a medical device, at least one region of the medical device including at least one polymer, the at least one polymer at least partially coating, encapsulating, or a combination thereof, at least one biological agent.

In another non-limiting aspect of the present disclosure, there is provided a refractory metal alloy comprising rhenium and one or more alloying metals, the refractory metal alloy being used to at least partially form a medical device, and at least one microstructure being disposed on an exterior surface of the medical device, the at least one microstructure being optionally at least partially formed from, including, or being a combination of a material comprising a polymer, an agent, or a combination thereof.

In another non-limiting aspect of the present disclosure, there is provided a refractory metal alloy comprising rhenium and one or more alloying metals, the refractory metal alloy being used to at least partially form a medical device, the medical device including an expandable frame formed from the refractory metal alloy, the expandable frame including a plurality of struts, the expandable frame optionally configured to be compressed to a compressed state such that a maximum outer diameter of the expandable frame when in the compressed state is less than a maximum outer diameter of the expandable frame when fully expanded to an expanded state, the expandable frame being subjected to a first compression process. the expandable frame optionally has less than 5% recoil (e.g., 0.1-4.99 and all values and ranges therebetween) after being expanded from a compressed state to an expanded state, the expandable frame optionally has less than 5% recoil (e.g., 0.1-4.99 and all values and ranges therebetween) after being expanded from a compressed state to an expanded state, the refractory metal alloy optionally has hydrophilicity such that a contact angle of a water droplet on a surface of said refractory metal alloy is 25-45° (e.g., 0.1-4.99 and all values and ranges therebetween), and the refractory metal alloy optionally has a hydrophilicity of 0.5 μg/cm per day when inserted or implanted on or within a patient's body. The refractory metal alloy has a maximum ion release of a major component of the refractory metal alloy of ² or less (e.g., 0.001-0.5 μg/cm ² /day, and all values and ranges therebetween), the major component constituting at least 2% by weight of the refractory metal alloy, and optionally, the refractory metal alloy exhibits an absolute increase in ion release per dose of refractory metal alloy in tissue surrounding the medical device within 50 days of being inserted or implanted on or within a patient's body.

In another non-limiting aspect of the present disclosure, a refractory metal alloy is provided that includes rhenium and one or more alloying metals, the refractory metal alloy being used to at least partially form a medical device, the medical device being an expandable stent or an expandable prosthetic heart valve.

In another non-limiting object of the present disclosure, there is provided a refractory metal alloy comprising rhenium and one or more alloying metals, the refractory metal alloy being optionally used to at least partially form a medical device, the one or more alloying metals being selected from the group consisting of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or one or more alloying components thereof, the combined weight percentage of rhenium, molybdenum, and the one or more alloying metals in the refractory metal alloy being at least 99.9% by weight, and the refractory metal alloy is optionally configured to have a melting point of less than 0.5 μg/cm per day when inserted or implanted on or within a patient's body. The refractory metal alloy has a maximum ion release of the major component of the refractory metal alloy of less than or equal to ² (eg, 0.001-0.5 μg/cm ² per day, and all values and ranges therebetween), and the major component comprises at least 2% by weight of the refractory metal alloy.

It will be seen that the above objects are effectively achieved among the objects made clear from the foregoing description. It is also intended that all matters contained in the above description and shown in the accompanying drawings should be interpreted as illustrative and not in a limiting sense, since certain changes can be made in the described structures without departing from the spirit and scope of the present disclosure. The present disclosure has been described with reference to preferred and alternative embodiments. Modifications and changes will become apparent to those skilled in the art upon reading and understanding the detailed description of the disclosure provided herein. The present disclosure is intended to include all such modifications and changes insofar as they fall within the scope of the present disclosure. It should also be understood that the following claims are intended to cover all of the general and specific features of the disclosure described herein, as well as all statements of the scope of the disclosure that, as a matter of terminology, lie therebetween.

(Additional Note)
(Appendix 1)
A refractory metal alloy,
rhenium and one or more alloying agents selected from the group consisting of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components;
the combined weight percentage of rhenium and one or more alloying agents in said refractory metal alloy is at least 98 weight percent;
At least a portion of the outer surface of the refractory metal alloy comprises a reinforcing coating material.
High melting point metal alloy.

(Appendix 2)
The reinforcement coating material may be a single layer or multi-layer material of the same or different coating layer compositions;
2. The refractory metal alloy of claim 1.

(Appendix 3)
The reinforcement coating material comprises two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
2. The refractory metal alloy of claim 1.

(Appendix 4)
The reinforcement coating material comprises two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
3. The refractory metal alloy of claim 2.

(Appendix 5)
The reinforced coating material comprises nitrides and/or oxides of one or more elements selected from the group consisting of Cr, Ti, Zr and Al;
Refractory metals according to claim 1.

(Appendix 6)
The reinforced coating material comprises nitrides and/or oxides of one or more elements selected from the group consisting of Cr, Ti, Zr and Al;
Attachment 2 to 4. A high-melting point metal according to any one of claims 2 to 4.

(Appendix 7)
The reinforcement coating material comprises two or more of: a) 40-85 wt. % Cr; b) 5-60 wt. % N; c) 60-99.99 wt. % C; d) 20-85 wt. % Ti; e) 35-95 wt. % Zr; f) 0-10 wt. % Re; g) 0-20 wt. % Si; h) 0-35 wt. % O; and i) 0-40 wt. % C.
Refractory metals according to claim 1.

(Appendix 8)
The reinforcement coating material comprises two or more of: a) 40-85 wt. % Cr; b) 5-60 wt. % N; c) 60-99.99 wt. % C; d) 20-85 wt. % Ti; e) 35-95 wt. % Zr; f) 0-10 wt. % Re; g) 0-20 wt. % Si; h) 0-35 wt. % O; and i) 0-40 wt. % C.
7. The high-melting point metal according to any one of claims 2 to 6.

(Appendix 9)
The reinforcement coating material comprises two or more of: a) 5-60 wt. % N; b) 35-95 wt. % Zr; f) 0-8 wt. % Re; g) 0-1 wt. % Si; h) 0-35 wt. % O; and i) 0-1 wt. % C.
Refractory metals according to claim 1.

(Appendix 10)
The reinforcement coating material comprises two or more of: a) 5-60 wt. % N; b) 35-95 wt. % Zr; f) 0-8 wt. % Re; g) 0-1 wt. % Si; h) 0-35 wt. % O; and i) 0-1 wt. % C.
9. The high-melting point metal according to any one of claims 2 to 8.

(Appendix 11)
the reinforced coating material includes a first coating layer and a second coating layer;
the first layer comprises 80-90 wt. % Zr, 10-20 wt. % N, 0-8 wt. % Re, 0-1 wt. % Si, 0-1 wt. % O, and 0-1 wt. % C;
a second coating layer is applied on top of the first layer;
The second layer comprises 70-80 wt.% Zr, 20-30 wt.%, 0-1 wt.% N, 0-8 wt.% Re, 0-1 wt.% Si, and 0-1 wt.% C;
Refractory metals according to claim 1.

(Appendix 12)
the reinforced coating material includes a first coating layer and a second coating layer;
the first layer comprises 80-90 wt. % Zr, 10-20 wt. % N, 0-8 wt. % Re, 0-1 wt. % Si, 0-1 wt. % O, and 0-1 wt. % C;
a second coating layer is applied on top of the first layer;
The second layer comprises 70-80 wt.% Zr, 20-30 wt.%, 0-1 wt.% N, 0-8 wt.% Re, 0-1 wt.% Si, and 0-1 wt.% C;
11. The high-melting point metal according to any one of claims 2 to 10.

(Appendix 13)
The reinforcing coating material includes one or more of chromium nitride (CrN), diamond-like carbon (DLC), titanium nitride (TiN), zirconium nitride (ZrN), zirconium oxide ( _ZrO2 ), zirconium nitrogen carbon (ZrNC), zirconium oxycarbide (ZrOC), and combinations of such coatings;
Refractory metals according to claim 1.

(Appendix 14)
The reinforcing coating material includes one or more of (CrN), diamond-like carbon (DLC), titanium nitride (TiN), zirconium nitride (ZrN), zirconium oxide ( _ZrO2 ), zirconium nitrogen carbon (ZrNC), zirconium oxycarbide (ZrOC), and combinations of such coatings;
Attachment 2 to 12. The high melting point metal according to any one of claims 2 to 12.

(Appendix 15)
The reinforced coating material is applied by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
2. The refractory metal alloy of claim 1.

(Appendix 16)
The reinforced coating material is applied by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
15. The refractory metal alloy according to any one of claims 2 to 14.

(Appendix 17)
The enhanced coating material is used to improve one or more properties of the refractory metal alloy selected from the group consisting of: changing the external color of the metal alloy, increasing the hardness of the coating surface, increasing the toughness of the coating surface, reducing friction to the coating surface, improving impact wear of the coating surface, improving corrosion resistance and oxidation resistance, forming a non-stick coating surface, improving the biocompatibility of the metal alloy having the coating surface, and reducing toxicity of the metal alloy having the coating surface.
2. The refractory metal alloy of claim 1.

(Appendix 18)
The enhanced coating material is used to improve one or more properties of the refractory metal alloy selected from the group consisting of: modifying the external color of the metal alloy, increasing the hardness of the coating surface, increasing the toughness of the coating surface, reducing friction to the coating surface, improving impact wear of the coating surface, improving corrosion resistance and oxidation resistance, forming a non-stick coating surface, improving the biocompatibility of the metal alloy having the coating surface, and reducing toxicity of the metal alloy having the coating surface.
17. The refractory metal alloy of any one of claims 2 to 16.

(Appendix 19)
The reinforcement coating material has a coating thickness of 2 nanometers to 100 microns.
2. The refractory metal alloy of claim 1.

(Appendix 20)
The reinforcement coating material has a coating thickness of 2 nanometers to 100 microns.
19. The refractory metal alloy of any one of claims 2 to 18.

(Appendix 21)
The reinforced coating material has a hardness of 5 to 50 GPa.
2. The refractory metal alloy of claim 1.

(Appendix 22)
The reinforced coating material has a hardness of 5 to 50 GPa.
21. The refractory metal alloy of any one of claims 2 to 20.

(Appendix 23)
The reinforced coating material has a coefficient of friction (COF) of 0.04 to 0.2.
2. The refractory metal alloy of claim 1.

(Appendix 24)
The reinforced coating material has a coefficient of friction (COF) of 0.04 to 0.2.
23. The refractory metal alloy of any one of claims 2 to 22.

(Appendix 25)
The wear rate of the reinforced coating material is between 0.5×10 ⁻⁷ mm ³ /Nm and 3×10 ⁻⁷ mm ³ /Nm;
2. The refractory metal alloy of claim 1.

(Appendix 26)
The wear rate of the reinforced coating material is between 0.5×10 ⁻⁷ mm ³ /Nm and 3×10 ⁻⁷ mm ³ /Nm;
25. The refractory metal alloy of any one of claims 2 to 24.

(Appendix 27)
The refractory metal alloy contains less than 0.1% by weight of metals and impurities.
2. The refractory metal alloy of claim 1.

(Appendix 28)
The refractory metal alloy contains less than 0.1% by weight of metals and impurities.
27. The refractory metal alloy of any one of claims 2 to 26.

(Appendix 29)
the refractory metal alloy comprises controlled amounts of nitrogen, oxygen and carbon to reduce microcracking in the refractory metal alloy, the nitrogen content in the refractory metal alloy being less than the combined oxygen and carbon content in the refractory metal alloy;
the refractory metal alloy having an atomic ratio of oxygen to nitrogen of at least about 1.2:1;
The refractory metal alloy has a carbon to nitrogen atomic ratio of at least about 2:1.
2. The refractory metal alloy of claim 1.

(Appendix 30)
the refractory metal alloy comprises controlled amounts of nitrogen, oxygen and carbon to reduce microcracking in the refractory metal alloy, the nitrogen content in the refractory metal alloy being less than the combined oxygen and carbon content in the refractory metal alloy;
the refractory metal alloy having an atomic ratio of oxygen to nitrogen of at least about 1.2:1;
The refractory metal alloy has a carbon to nitrogen atomic ratio of at least about 2:1.
29. The refractory metal alloy of any one of claims 2 to 28.

(Appendix 31)
2. A medical device formed at least in part from the refractory metal alloy of claim 1.

(Appendix 32)
31. A medical device formed at least in part from the refractory metal alloy of any one of claims 2-30.

(Appendix 33)
At least one region of the medical device comprises at least one biological agent;
32. The medical device of claim 31.

(Appendix 34)
At least one region of the medical device comprises at least one biological agent;
33. The medical device of claim 32.

(Appendix 35)
At least one region of the medical device comprises at least one polymer, the at least one polymer optionally at least partially coating, encapsulating, or a combination thereof, at least one biological agent;
32. The medical device of claim 31.

(Appendix 36)
At least one region of the medical device comprises at least one polymer;
the at least one polymer optionally at least partially coats, encapsulates, or a combination thereof, the at least one biological agent;
35. The medical device of any one of appendices 32 to 34.

(Appendix 37)
further comprising at least one microstructure on an exterior surface of the medical device;
the at least one microstructure is at least partially formed from, includes, or is a combination of a material comprising a polymer, an agent, or a combination thereof;
32. The medical device of claim 31.

(Appendix 38)
further comprising at least one microstructure on an exterior surface of the medical device;
The at least one microstructure is at least partially formed from, includes, or comprises a material consisting of a polymer, an agent, or a combination thereof;
37. The medical device of any one of appendices 32 to 36.

(Appendix 39)
The medical device includes an expandable frame formed of a refractory metal alloy;
The expandable frame includes a plurality of struts;
the expandable frame is configured to be compressed to a compressed state such that a maximum outer diameter of the expandable frame in a compressed state is less than a maximum outer diameter of the expandable frame when fully expanded to an expanded state;
the expandable frame has a recoil of less than 5% after undergoing a first compression process;
the expandable frame has a recoil of less than 5% after being expanded from the compressed state to the expanded state;
the high-melting point metal alloy has hydrophilicity such that the contact angle of a water droplet on the surface of the high-melting point metal alloy is 25 to 45°;
the refractory metal alloy, when inserted or implanted on or within a patient's body, has a maximum ion release of a major component of the refractory metal alloy of 0.5 μg/ ^cm2 or less per day;
the major component comprises at least 2 weight percent of the refractory metal alloy;
the refractory metal alloy exhibits an absolute increase in ion release per dose of refractory metal alloy in tissue surrounding the medical device within 50 days of being inserted or implanted on or within the patient's body;
32. The medical device of claim 31.

(Appendix 40)
The medical device includes an expandable frame formed of a refractory metal alloy;
The expandable frame includes a plurality of struts;
the expandable frame is configured to be compressed to a compressed state such that a maximum outer diameter of the expandable frame in the compressed state is less than a maximum outer diameter of the expandable frame when fully expanded to an expanded state;
the expandable frame has a recoil of less than 5% after undergoing a first compression process;
the expandable frame has a recoil of less than 5% after being expanded from the compressed state to the expanded state;
the high-melting point metal alloy has hydrophilicity such that the contact angle of a water droplet on the surface of the high-melting point metal alloy is 25 to 45°;
the refractory metal alloy, when inserted or implanted on or within a patient's body, has a maximum ion release of a major component of the refractory metal alloy of 0.5 μg/ ^cm2 or less per day;
the major component comprises at least 2 weight percent of the refractory metal alloy;
the refractory metal alloy exhibits an absolute increase in ion release per dose of refractory metal alloy in tissue surrounding the medical device within 50 days of being inserted or implanted on or within a patient's body;
39. The medical device of any one of appendices 32 to 38.

(Appendix 41)
2. A method of forming the refractory metal alloy of claim 1, comprising:
providing a powder metal, the powder metal comprising rhenium metal powder and one or more alloying agent powders selected from the group consisting of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, and zirconium oxide;
compressing the powder metal;
sintering the compressed powder metal to form a metal alloy having a combined weight percentage of rhenium and one or more alloying agents in the metal alloy of at least 98 weight percent;
coating an outer surface of the metal alloy with the reinforcing coating material, the reinforcing coating material comprising two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
Including,
The coating step may be performed by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
method.

(Appendix 42)
31. A method of forming the refractory metal alloy of any one of claims 2 to 30, comprising the steps of:
providing a powder metal, the powder metal comprising rhenium metal powder and one or more alloying agent powders selected from the group consisting of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, and zirconium oxide;
compressing the powder metal;
sintering the compressed powder metal to form a metal alloy having a combined weight percentage of rhenium and one or more alloying agents in the metal alloy of at least 98 weight percent;
coating an outer surface of the metal alloy with the reinforcing coating material, the reinforcing coating material comprising two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
The coating step may be performed by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
method.

Claims (42)

A refractory metal alloy,
rhenium and one or more alloying agents selected from the group consisting of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, zirconium oxide, and/or alloys of one or more of these components;
the combined weight percentage of rhenium and one or more alloying agents in said refractory metal alloy is at least 98 weight percent;
At least a portion of the outer surface of the refractory metal alloy comprises a reinforcing coating material.
High melting point metal alloy. The reinforcement coating material may be a single layer or multi-layer material of the same or different coating layer compositions;
The refractory metal alloy of claim 1. The reinforcement coating material comprises two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
The refractory metal alloy of claim 1. The reinforcing coating material comprises two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
The refractory metal alloy of claim 2. The reinforced coating material comprises nitrides and/or oxides of one or more elements selected from the group consisting of Cr, Ti, Zr and Al;
The high melting point metal according to claim 1. The reinforced coating material comprises nitrides and/or oxides of one or more elements selected from the group consisting of Cr, Ti, Zr and Al;
The high melting point metal according to any one of claims 2 to 4. The reinforcement coating material comprises two or more of: a) 40-85 wt. % Cr; b) 5-60 wt. % N; c) 60-99.99 wt. % C; d) 20-85 wt. % Ti; e) 35-95 wt. % Zr; f) 0-10 wt. % Re; g) 0-20 wt. % Si; h) 0-35 wt. % O; and i) 0-40 wt. % C.
The high melting point metal according to claim 1. The reinforcement coating material comprises two or more of: a) 40-85 wt. % Cr; b) 5-60 wt. % N; c) 60-99.99 wt. % C; d) 20-85 wt. % Ti; e) 35-95 wt. % Zr; f) 0-10 wt. % Re; g) 0-20 wt. % Si; h) 0-35 wt. % O; and i) 0-40 wt. % C.
The high melting point metal according to any one of claims 2 to 6. The reinforcement coating material comprises two or more of: a) 5-60 wt. % N; b) 35-95 wt. % Zr; f) 0-8 wt. % Re; g) 0-1 wt. % Si; h) 0-35 wt. % O; and i) 0-1 wt. % C.
The high melting point metal according to claim 1. The reinforcement coating material comprises two or more of: a) 5-60 wt. % N; b) 35-95 wt. % Zr; f) 0-8 wt. % Re; g) 0-1 wt. % Si; h) 0-35 wt. % O; and i) 0-1 wt. % C.
The high melting point metal according to any one of claims 2 to 8. the reinforced coating material includes a first coating layer and a second coating layer;
the first layer comprises 80-90 wt. % Zr, 10-20 wt. % N, 0-8 wt. % Re, 0-1 wt. % Si, 0-1 wt. % O, and 0-1 wt. % C;
a second coating layer is applied on top of the first layer;
The second layer comprises 70-80 wt.% Zr, 20-30 wt.%, 0-1 wt.% N, 0-8 wt.% Re, 0-1 wt.% Si, and 0-1 wt.% C;
The high melting point metal according to claim 1. the reinforced coating material includes a first coating layer and a second coating layer;
the first layer comprises 80-90 wt. % Zr, 10-20 wt. % N, 0-8 wt. % Re, 0-1 wt. % Si, 0-1 wt. % O, and 0-1 wt. % C;
a second coating layer is applied on top of the first layer;
The second layer comprises 70-80 wt.% Zr, 20-30 wt.%, 0-1 wt.% N, 0-8 wt.% Re, 0-1 wt.% Si, and 0-1 wt.% C;
The high melting point metal according to any one of claims 2 to 10. The reinforcing coating material includes one or more of chromium nitride (CrN), diamond-like carbon (DLC), titanium nitride (TiN), zirconium nitride (ZrN), zirconium oxide ( _ZrO2 ), zirconium nitrogen carbon (ZrNC), zirconium oxycarbide (ZrOC), and combinations of such coatings;
The high melting point metal according to claim 1. The reinforcing coating material includes one or more of (CrN), diamond-like carbon (DLC), titanium nitride (TiN), zirconium nitride (ZrN), zirconium oxide ( _ZrO2 ), zirconium nitrogen carbon (ZrNC), zirconium oxycarbide (ZrOC), and combinations of such coatings;
The high melting point metal according to any one of claims 2 to 12. The reinforced coating material is applied by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
The refractory metal alloy of claim 1. The reinforced coating material is applied by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
The high melting point metal alloy according to any one of claims 2 to 14. The enhanced coating material is used to improve one or more properties of the refractory metal alloy selected from the group consisting of: changing the external color of the metal alloy, increasing the hardness of the coating surface, increasing the toughness of the coating surface, reducing friction to the coating surface, improving impact wear of the coating surface, improving corrosion resistance and oxidation resistance, forming a non-stick coating surface, improving the biocompatibility of the metal alloy having the coating surface, and reducing toxicity of the metal alloy having the coating surface.
The refractory metal alloy of claim 1. The enhanced coating material is used to improve one or more properties of the refractory metal alloy selected from the group consisting of: modifying the external color of the metal alloy, increasing the hardness of the coating surface, increasing the toughness of the coating surface, reducing friction to the coating surface, improving impact wear of the coating surface, improving corrosion resistance and oxidation resistance, forming a non-stick coating surface, improving the biocompatibility of the metal alloy having the coating surface, and reducing toxicity of the metal alloy having the coating surface.
The high melting point metal alloy according to any one of claims 2 to 16. The reinforcement coating material has a coating thickness of 2 nanometers to 100 microns.
The refractory metal alloy of claim 1. The reinforcement coating material has a coating thickness of 2 nanometers to 100 microns.
A high melting point metal alloy according to any one of claims 2 to 18. The reinforced coating material has a hardness of 5 to 50 GPa.
The refractory metal alloy of claim 1. The reinforced coating material has a hardness of 5 to 50 GPa.
The high melting point metal alloy according to any one of claims 2 to 20. The reinforced coating material has a coefficient of friction (COF) of 0.04 to 0.2.
The refractory metal alloy of claim 1. The reinforced coating material has a coefficient of friction (COF) of 0.04 to 0.2.
A high melting point metal alloy according to any one of claims 2 to 22. The wear rate of the reinforced coating material is between 0.5×10 ⁻⁷ mm ³ /Nm and 3×10 ⁻⁷ mm ³ /Nm;
The refractory metal alloy of claim 1. The wear rate of the reinforced coating material is between 0.5×10 ⁻⁷ mm ³ /Nm and 3×10 ⁻⁷ mm ³ /Nm;
A refractory metal alloy according to any one of claims 2 to 24. The refractory metal alloy contains less than 0.1% by weight of metals and impurities.
The refractory metal alloy of claim 1. The refractory metal alloy contains less than 0.1% by weight of metals and impurities.
A refractory metal alloy according to any one of claims 2 to 26. the refractory metal alloy comprises controlled amounts of nitrogen, oxygen and carbon to reduce microcracking in the refractory metal alloy, the nitrogen content in the refractory metal alloy being less than the combined oxygen and carbon content in the refractory metal alloy;
the refractory metal alloy having an atomic ratio of oxygen to nitrogen of at least about 1.2:1;
The refractory metal alloy has a carbon to nitrogen atomic ratio of at least about 2:1.
The refractory metal alloy of claim 1. the refractory metal alloy comprises controlled amounts of nitrogen, oxygen and carbon to reduce microcracking in the refractory metal alloy, the nitrogen content in the refractory metal alloy being less than the combined oxygen and carbon content in the refractory metal alloy;
the refractory metal alloy having an atomic ratio of oxygen to nitrogen of at least about 1.2:1;
The refractory metal alloy has a carbon to nitrogen atomic ratio of at least about 2:1.
A refractory metal alloy according to any one of claims 2 to 28. A medical device formed at least in part from the refractory metal alloy of claim 1. A medical device formed at least in part from the high melting point metal alloy according to any one of claims 2 to 30. At least one region of the medical device comprises at least one biological agent;
32. The medical device of claim 31. At least one region of the medical device comprises at least one biological agent;
33. The medical device of claim 32. at least one region of the medical device comprises at least one polymer, the at least one polymer optionally at least partially coating, encapsulating, or a combination thereof, at least one biological agent;
32. The medical device of claim 31. At least one region of the medical device comprises at least one polymer;
the at least one polymer optionally at least partially coats, encapsulates, or a combination thereof, the at least one biological agent;
The medical device according to any one of claims 32 to 34. further comprising at least one microstructure on an exterior surface of the medical device;
the at least one microstructure is at least partially formed from, includes, or is a combination of a material comprising a polymer, an agent, or a combination thereof;
32. The medical device of claim 31. further comprising at least one microstructure on an exterior surface of the medical device;
The at least one microstructure is at least partially formed from, includes, or comprises a material consisting of a polymer, an agent, or a combination thereof;
The medical device according to any one of claims 32 to 36. The medical device includes an expandable frame formed of a refractory metal alloy;
The expandable frame includes a plurality of struts;
the expandable frame is configured to be compressed to a compressed state such that a maximum outer diameter of the expandable frame in a compressed state is less than a maximum outer diameter of the expandable frame when fully expanded to an expanded state;
the expandable frame has a recoil of less than 5% after undergoing a first compression process;
the expandable frame has a recoil of less than 5% after being expanded from the compressed state to the expanded state;
the high-melting point metal alloy has hydrophilicity such that the contact angle of a water droplet on the surface of the high-melting point metal alloy is 25 to 45°;
the refractory metal alloy, when inserted or implanted on or within a patient's body, has a maximum ion release of a major component of the refractory metal alloy of 0.5 μg/ ^cm2 or less per day;
the major component comprises at least 2 weight percent of the refractory metal alloy;
the refractory metal alloy exhibits an absolute increase in ion release per dose of refractory metal alloy in tissue surrounding the medical device within 50 days of being inserted or implanted on or within the patient's body;
32. The medical device of claim 31. The medical device includes an expandable frame formed of a refractory metal alloy;
The expandable frame includes a plurality of struts;
the expandable frame is configured to be compressed to a compressed state such that a maximum outer diameter of the expandable frame in a compressed state is less than a maximum outer diameter of the expandable frame when fully expanded to an expanded state;
the expandable frame has a recoil of less than 5% after undergoing a first compression process;
the expandable frame has a recoil of less than 5% after being expanded from the compressed state to the expanded state;
the high-melting point metal alloy has hydrophilicity such that the contact angle of a water droplet on the surface of the high-melting point metal alloy is 25 to 45°;
the refractory metal alloy, when inserted or implanted on or within a patient's body, has a maximum ion release of a major component of the refractory metal alloy of 0.5 μg/ ^cm2 or less per day;
the major component comprises at least 2 weight percent of the refractory metal alloy;
the refractory metal alloy exhibits an absolute increase in ion release per dose of refractory metal alloy in tissue surrounding the medical device within 50 days of being inserted or implanted on or within the patient's body;
A medical device according to any one of claims 32 to 38. 10. A method of forming the refractory metal alloy of claim 1, comprising:
providing a powder metal, the powder metal comprising rhenium metal powder and one or more alloying agent powders selected from the group consisting of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, and zirconium oxide;
compressing the powder metal;
sintering the compressed powder metal to form a metal alloy having a combined weight percentage of rhenium and one or more alloying agents in the metal alloy of at least 98 weight percent;
coating an outer surface of the metal alloy with the reinforcing coating material, the reinforcing coating material comprising two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
Including,
The coating step may be performed by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
method. A method of forming the refractory metal alloy of any one of claims 2 to 30, comprising the steps of:
providing a powder metal, the powder metal comprising rhenium metal powder and one or more alloying agent powders selected from the group consisting of calcium, carbon, cerium oxide, chromium, cobalt, copper, gold, hafnium, iridium, iron, lanthanum, lanthanum oxide, lead, magnesium, manganese, molybdenum, nickel, niobium, osmium, platinum, rare earth metals, rhodium, ruthenium, silver, tantalum, technetium, titanium, tungsten, vanadium, yttrium, yttrium oxide, zinc, zirconium, and zirconium oxide;
compressing the powder metal;
sintering the compressed powder metal to form a metal alloy having a combined weight percentage of rhenium and one or more alloying agents in the metal alloy of at least 98 weight percent;
coating an outer surface of the metal alloy with the reinforcing coating material, the reinforcing coating material comprising two or more elements selected from the group consisting of chromium, carbon, nitrogen, titanium, zirconium, oxygen, aluminum, chromium and boron;
Including,
The coating step may be performed by a physical vapor deposition (PVD) process, a chemical vapor deposition (CVD) process, an atomic layer deposition (ALD) process, a plasma enhanced chemical vapor deposition (PE-CVD) process, ion implantation, directed energy deposition (DED), and/or thermal spraying techniques such as plasma arc spraying, flame spraying, high velocity oxygen fuel spraying (HVOF), etc.
method.