Silver-free surface coating

Abstract

An object is provided, the object has particles on its surface, and the amount of particles is 0.041 to 6 μg / cm 2 Between 0.02 and 2 μg / cm 2 Palladium in an amount equivalent to 0.001-2 μg / cm 2 Neodymium equivalent to 0.02 to 2 μg / cm 2 100 ppm of gold and the particles contain less than 30 ppm of silver, which is considered silver-free. The coating is both biocompatible and antibacterial, and because the coating is silver-free it does not suffer from the disadvantages associated with silver. The coating shows an improving effect against thrombosis.

Description

[Technical field]

[0001] The present invention relates to a surface coating comprising particles of palladium, gold and neodymium, which coating is silver-free. [Background technology]

[0002] Antimicrobial and biocompatible surfaces are important in many applications. Examples of surfaces for which such properties are important include surfaces intended for contact with the human and animal body, such as skin and contact with body cavities and internal bodies. Medical devices intended for contact with human or animal blood should preferably have properties that avoid clot formation and thrombosis.

[0003] US 6,224,983 discloses an article comprising a layer of silver stabilized by exposure to one or more salts of one or more metals selected from the group consisting of platinum, palladium, rhodium, iridium, ruthenium and osmium, having an adhesive, antibacterial and biocompatible coating. The thickness of the silver layer is between 2 and 2000 Å (Å, angstroms, 10 -10 m), with further disclosed ranges being 2-350 Å and 2-50 Å. Example thicknesses for the silver layer also include 50 Å, 350 Å, 500 Å, and 1200 Å. The substrate may be latex, polystyrene, polyester, polyvinyl chloride, polyurethane, ABS polymer, polycarbonate, polyamide, polytetrafluoroethylene, polyimide, or synthetic rubber.

[0004] WO2007 / 117191, WO2007 / 117213 and WO2007 / 117214 disclose a substrate having an electron donating surface, on which are located metal particles, the metal particles consisting of palladium and at least one metal selected from the group consisting of gold, ruthenium, rhodium, osmium, iridium and platinum, the amount of the metal particles being from about 0.001 to 8 μg / cm 2 The present invention discloses a substrate characterized in that

[0005] Kris NJ Stevens et al. in Biomaterials 30(2009) pp. 3682-3690 disclose the incorporation of silver nanoparticles to render surface coatings of medical devices antimicrobial. Due to the very large surface area to volume ratio, the silver particles act as a reservoir for the sustained release of silver ions, despite the fact that silver is not easily oxidized. The study specifically addresses the question of how the release of silver nanoparticles (exposed at the coating surface) and / or silver ions affect the coagulation of the contacting blood. It is concluded that the observed activation of blood platelets can best be explained by a collision mechanism. The results suggest that platelets colliding with the surface exposed silver are activated without adhering to the surface. These new results, rather unexpectedly, show a dual effect of silver nanoparticles in the coating, i.e. a strong antimicrobial effect, which is accompanied by the promotion of coagulation of the contacting blood.

[0006] WO 2007 / 142579 discloses a polymer matrix comprising: a. an electron donating component; and b. metal particles comprising at least one metal selected from the group consisting of palladium, gold, ruthenium, rhodium, osmium, iridium and platinum.

[0007] WO 2019 / 206950 discloses a method for reducing leakage of a substance from an object into the environment, the object being coated with a coating applied to at least a portion of the object, the coating comprising at least a portion of a coating layer comprising silver, the object optionally including areas without the layer, the coating comprising metal particles applied to the layer and optionally to the areas without the layer, the metal particles comprising palladium and at least one metal selected from the group consisting of gold, ruthenium, rhodium, osmium, iridium, niobium, neodymium and platinum, the amount of metal particles being between 0.01 and 8 μg / cm 2It has been disclosed that blood clotting can be reduced when the surface is exposed to blood of human or animal origin if the metal particles include palladium and neodymium. Silver is always present in the coating.

[0008] Although the amount of silver released from coatings such as those described in WO 2019 / 206950 is minimal, silver can be a drawback in some cases. When applied to certain materials, silver, according to prior art such as WO 2019 / 206950, causes discoloration even when applied in relatively small amounts. Furthermore, the application of silver requires several steps during manufacturing. Silver is usually applied in a bath form that must be replaced periodically.

[0009] Although it is shown in WO 2019 / 206950 that blood clotting can be reduced to a significant and useful extent when the surface is exposed to blood of human or animal origin, there is still room for further improvement of the effect against thrombosis.

[0010] Another problem in the prior art is how to provide a non-silver containing coating that is still antibacterial and biocompatible. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] U.S. Patent No. 6,224,983 [Patent Document 2] International Publication No. 2007 / 117191 [Patent Document 3] International Publication No. 2007 / 117213 [Patent Document 4] International Publication No. 2007 / 117214 [Patent Document 5] International Publication No. 2007 / 142579 [Patent Document 6] International Publication No. 2019 / 206950 [Patent Document 7] U.S. Patent No. 5,320,908 [Non-patent literature]

[0012] [Non-Patent Document 1] Kris NJ Stevens et al. in Biomaterials 30(2009) 3682-3690 Summary of the Invention [Problem to be solved by the invention]

[0013] SUMMARY OF THE PRESENT EMBODIMENT It is an object of the present invention to obviate at least some of the disadvantages of the prior art and to provide an improved surface coating.

[0014] In the first embodiment, the particles are present on the surface of the object, and the amount of the particles is 0.04 to 6 μg / cm 2 Between 0.02 and 2 μg / cm 2 Palladium in an amount equivalent to 0.001-2 μg / cm 2 Neodymium equivalent to 0.02 to 2 μg / cm 2 and particles containing less than 30 ppm silver.

[0015] Further provided is the use of such an object for preventing thrombosis.Also provided is the use of a coating for preventing thrombosis.

[0016] Further embodiments of the present invention are defined in the appended dependent claims, which are expressly incorporated into this specification.

[0017] One advantage is improved antithrombotic effects.

[0018] Additionally, the surface has improved antimicrobial activity compared to similar surfaces containing silver.

[0019] Fabrication of the surface is simpler since no silver needs to be deposited during fabrication. [Means for solving the problem]

[0020] Before the present invention is disclosed and described in detail, it is understood that the invention is not limited to the particular configurations, steps, and materials disclosed herein, and that such configurations, steps, and materials may vary somewhat.

[0021] It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly indicates otherwise.

[0022] The following terms are used throughout the description and claims.

[0023] The "amount" of particles or other material on a surface herein is often expressed in μg / cm 2 This is an appropriate way to express the amount since the applied layers are very thin. To calculate the amount, the covered area of ​​the object is measured and the amount per covered area is calculated.

[0024] "Antimicrobial" as used herein is the property of inhibiting or eliminating microbial growth, including but not limited to bacterial growth.

[0025] "Biocompatibility," as used herein, is the ability of a material to elicit an appropriate host response in a particular application.

[0026] As used herein, an "object" is a substrate that is treated and at least partially surface-coated according to the present invention.

[0027] As used herein, "silver-free" is understood to mean that the coating is substantially free of silver and that the particles in the coating contain less than 30 ppm of silver.

[0028] According to the present invention, a surface coating is applied to an object to impart desired properties. Particles on the surface of the object may be viewed as a surface coating. The object may be made of a wide range of materials.

[0029] In the first embodiment, the particles are present on the surface of the object, and the amount of the particles is 0.041 to 6 μg / cm 2 Between 0.02 and 2 μg / cm 2 Palladium in an amount equivalent to 0.001-2 μg / cm 2 Neodymium equivalent to 0.02 to 2 μg / cm 2 and particles containing less than 30 ppm silver. The object is at least partially coated with metal particles on its surface. The metal particles are deposited on the surface of the object. The object may be at least partially coated with particles and have areas on the object that are free of particles. In one embodiment, the entire object is coated with particles. Areas that are not coated with particles are characterized by a distance of more than 1 mm to the nearest particle on the surface. In the case of a coating, the particles on the surface are very numerous and the distance between the particles is much less than 1 mm, and the distance between the particles on the surface is several orders of magnitude less than 1 mm. Areas without coating can be identified as being free of particles in this case. To determine the exact boundary where the coating ends, a criterion of 1 mm to the nearest particle can be used. This criterion makes it easy to distinguish between coated and uncoated areas, since the distance between the particles in the coated areas is much lower than 1 mm and there are practically no particles in the uncoated areas. Uncoated areas are usually not immersed or covered in some way.

[0030] The particles always contain palladium, neodymium and gold. The amount of different metals in the particles is calculated based on the weight of metal per area of ​​the object. The total amount of particles is also calculated based on the weight of particles per area of ​​the object. The total amount of particles includes the three essential metals plus additional additives. However, it should be noted that the coating is intended for a medical product and the impact of additional impurities can be difficult to determine, so in general the amount of impurities should be kept as low as possible.

[0031] The surface coating is silver-free, which is interpreted as the particles in the coating containing less than 30 ppm of silver. Any avoidable silver should not be added to either the particles or the surface of the object. Even if no silver is added to the coating, other metals in the surface coating contain small amounts of various impurities, including silver. Therefore, when other metals are added, it is not negligible to have a small amount of silver as an impurity. Due to impurities in the metal, a very small amount of silver is unavoidable. For example, if gold is added, there may be a small amount of silver as an impurity in the gold. Therefore, even if no silver is intentionally added, a very small amount of silver is difficult to avoid. The amount of silver should be kept as low as practically possible. Since the amount of silver in the commercially available high purity grades of the metals palladium, gold and neodymium is around 10-30 ppm, it may be difficult to reach low amounts of silver in commercial scale. Therefore, it has come to mean that the surface is silver-free when the amount of silver in the particles is less than 30 ppm. By using high quality grades of metal, it is possible to reach silver levels within the grains of less than 20 ppm, or even less than 10 ppm, and even less than 5 ppm.

[0032] The object to which the particles are applied should also not contain silver, or at least should be as free of silver as possible, otherwise the idea of ​​a silver-free coating is not valid. The outermost 10 μm of this object contains less than 30 ppm of silver. The distance from the surface is measured perpendicular to the surface and 10 μm inside the object. In this part of the object the amount of silver is calculated by mass. The amount of silver in the outermost 10 μm is measured or calculated after the application of the particles.

[0033] In one embodiment, the object prior to coating with particles does not contain more than 30 ppm silver. This embodiment takes into account the entire uncoated object, which must not contain more than 30 ppm silver by weight.

[0034] The article to which the particles are attached does not include a coating that contains silver.

[0035] In one embodiment, the entire object containing the particles, i.e., the coating, contains less than 30 ppm silver, preferably less than 20 ppm silver, more preferably less than 10 ppm silver, In one embodiment, the object containing the particles on the surface of the object contains less than 30 ppm silver.

[0036] The amount of silver is measured in ppm (parts per million) by mass. -6 As used herein, 1 ppm is equivalent to 0.0001 wt %.

[0037] In one embodiment, the particles contain at least one metal selected from ruthenium and rhodium. Rhodium has the effect of further reducing leakage of substances from the object. Examples of substances that may leak include allergens and ions from the coated object. Adding rhodium to the metal particles can increase this effect. The effect of reducing leakage of substances is a chemical effect, not a physical barrier. This is evident from the fact that the coating cannot form a physical barrier due to the distance between the particles. Rhodium gives very good results in preventing leakage of substances. In one embodiment, the amount of rhodium in the particles is 0.05-2 μg / cm 2 In an embodiment with a high amount of rhodium in the particles, the amount of particles on the object is 6 μg / cm 2 In one embodiment of particles containing rhodium, the amount of particles is 0.091 to 8 μg / cm 2 It is between.

[0038] Regarding ruthenium, the effect of ruthenium is to reduce leakage of material over time. The addition of ruthenium reduces leakage of material over time. In one embodiment, 0.05 to 2 μg / cm 2 In an embodiment where the amount of rhodium and / or ruthenium in the particles is high, the amount of particles on the object is 6 μg / cm 2 In one embodiment, the particles include ruthenium, the amount of particles is 0.091 to 8 μg / cm 2 In one embodiment, the particles include ruthenium and rhodium, the amount of the particles is between 0.141 and 8.2 μg / cm2 It is between.

[0039] In one embodiment, the object comprises at least one metal. Since the coating is silver-free, the object being coated should also be as silver-free as possible, and therefore the metal of the object cannot be silver. As noted above, silver with a maximum amount of 30 ppm silver in the object is a suitable limit.

[0040] In one embodiment, the at least one metal is selected from the group consisting of iron, titanium, cobalt, nickel, chromium, and mixtures thereof.

[0041] In one embodiment, the at least one metal is selected from the group consisting of steel, stainless steel, and nitinol.

[0042] In one embodiment, the at least one metal is selected from the group consisting of medical grade titanium, medical grade stainless steel, and medical grade nitinol. The term medical grade indicates that the metal or alloy is intended for medical use, e.g., as an implant or in contact with humans or animals. Examples of medical grade stainless steel include, but are not limited to, SAE316, SAE440, SAE420 manufactured according to ASTM F138 / F139.

[0043] In one embodiment, the body comprises at least one ceramic material, which is a material made by firing inorganic, non-metallic materials.

[0044] In one embodiment, the article comprises at least one metal selected from the group consisting of silicon nitride and zirconium dioxide.

[0045] In one embodiment, the body comprises at least one selected from apatite and hydroxyapatite.

[0046] In one embodiment, the article comprises at least one polymer.

[0047] In one embodiment, the object comprises at least one polymer composite, which is a mixture of short or continuous fibers bound together by a matrix of organic polymers, in which the polymer is combined with a variety of continuous and non-continuous reinforcing materials / fibers, typically added to the polymer to improve the performance of the material.

[0048] In one embodiment, the polymer is selected from the group consisting of latex, vinyl, polymers containing vinyl groups, polyurethane urea, silicone, polyvinyl chloride, polypropylene, styrene, polyurethane, polyester, ethylene vinyl acetate copolymer, polytetrafluoroethylene (PTFE), polyether ether ketone (PEEK), polystyrene, polycarbonate, polyethylene, polyacrylate, polymethacrylate, acrylonitrile butadiene styrene (ABS), polyamide, polyimide, and mixtures thereof, which become part of the polymer composite or form the object.

[0049] In one embodiment, the object comprises at least one textile material. A textile is a material made of intertwined fibers.

[0050] It should be noted that the particles are essentially uniformly composed, i.e., the particles have essentially the same composition of metal throughout the particle. The amount of particles on the surface is between 0.041 and 6 μg / cm 2 However, if additional metals are used in addition to the three required metals, the particle amount may be up to 8 μg / cm 2 or up to 10μg / cm 2 In one embodiment, the amount of particles is 0.05 to 2 μg / cm 2 This quantity refers to the total mass of particles associated with the coated part of the object.

[0051] In one embodiment, the particles are isolated particles that are not in contact with each other, i.e., slightly dispersed particles, and are not in contact with each other. In another embodiment, some of the particles are in contact with each other to form particle aggregates. In such aggregates, many particles are in contact to form the aggregate. Nevertheless, the surface of the object is still accessible to the aqueous solution because the coating of the particles is permeable and permeable to the aqueous solution.

[0052] In one embodiment, the particles have a size between 10 and 500 nm. The particle size is measured by scanning electron microscopy according to ISO 19749:2021. The skilled artisan will recognize that there are other methods of characterizing the surface, such as an electron probe microanalyzer (EPMA) with a WDX detector and calculating the particle size by simulation of the measurement data. However, the particle size defined in the present specification and claims is as defined in ISO 19749:2021. In one embodiment, the particles have a size between 10 and 200 nm. In one embodiment, the particles have a size between 10 and 60 nm. The skilled artisan will recognize that the particle size can be in different intervals from about 10 to about 500 nm. Examples of each interval include, but are not limited to, 10 to 400 nm, 10 to 300 nm, 10 to 100 nm, 10 to 80 nm, 10 to 70 nm, 10 to 60 nm, 15 to 150 nm, 15 to 100 nm, 15 to 60 nm, 20 to 80 nm, 20 to 60 nm, 25 to 50 nm, and 30 to 40 nm.

[0053] Examples of objects comprising the substrate according to the present invention include, but are not limited to, medical devices, medical implements, and medical disposables. In one embodiment, the object is selected from medical devices, medical implements, and medical disposables. Medical devices are devices intended for medical use. Medical implements are devices intended for medical use. Medical disposables are disposable products not intended for medical use.

[0054] In one embodiment, the object is an object intended to come into contact with human or animal blood. This use is particularly beneficial as it reduces the formation of blood clots compared to other materials. It reduces the risk of thrombosis. Objects intended to come into contact with the human or animal body or with human or animal blood are suitable for coating according to the invention. For example, objects in devices intended to come into contact with human or animal blood are coated. Such objects are included in machines and devices that process human or animal blood and return it to the human or animal. In such a procedure, it reduces the risk of thrombosis.

[0055] In one embodiment, the object is at least one selected from the group consisting of a catheter, a central venous catheter, a peripheral venous catheter, a urinary catheter, a Foley catheter, an intermittent catheter, an implant, a dental implant, a dental abutment, a dental aligner, a dental prosthetic device, a bone replacement implant, an orthopedic implant, a tissue replacement implant, a stent, a biliary stent, a tracheal stent, a peripheral stent, a glove, a pacemaker, a rupture net, a surgical instrument, a blood bag, an artificial heart valve, a vascular port, a hemodialysis machine, a peritoneal dialysis machine, a plasmapheresis machine, an ECMO machine, a cardiopulmonary bypass machine, an inhalation drug delivery device, a vascular graft, an arterial vascular graft, a venous vascular graft, a cardiac assist device, a wound dressing, an ECG electrode, an orthopedic device, an intraocular lens, a suture, a needle, a staple, a mesh, a drug delivery device, an endotracheal tube, a shunt, a drain, a suction device, a hearing aid, a urinary medical device, and an artificial blood vessel.

[0056] In accordance with the present invention, catheters may be coated. Examples of catheters include, but are not limited to, central venous catheters, peripheral venous catheters, urinary catheters, Foley catheters, and intermittent catheters.

[0057] Articles of the present invention that are intended for dental use can be coated. Examples of such articles include, but are not limited to, dental implants, dental abutments, dental aligners, and dental prosthetic devices.

[0058] According to the present invention, implants can be coated. Implants for both dental applications and all other applications can be coated. Examples of implants include, but are not limited to, bone replacement implants, orthopedic implants, and tissue replacement implants.

[0059] Stents according to the present invention may be covered. Examples of stents include, but are not limited to, biliary stents, tracheal stents, and peripheral stents.

[0060] According to the present invention, objects intended to come into contact with human or animal blood during at least a portion of the intended use can be coated. Such objects include parts of devices and equipment, which are intended to be exposed to blood. Examples of such objects include, but are not limited to, hemodialysis machines, peritoneal dialysis machines, plasmapheresis machines, ECMO (extracorporeal membrane oxygenation), and cardiac bypass machines. It is understood that such objects are suitable for coating parts intended to come into contact with blood.

[0061] Articles intended to come into contact with human or animal blood are suitable for coating, further examples of which include, but are not limited to, vascular grafts, arterial grafts, venous grafts, artificial blood vessels, artificial heart valves, blood bags, and vascular ports.

[0062] Additional objects are also suitable for the coatings of the present invention, including, but not limited to, gloves, cardiac assist devices, pacemakers, rupture nets, surgical instruments, inhaled drug delivery devices, wound dressings, ECG electrodes, orthopedic devices, intraocular lenses, sutures, needles, staples, meshes, drug delivery devices, endotracheal tubes, shunts, drains, suction devices, hearing aids, and urinary medical devices.

[0063] The present invention is an improvement / derivative of the material defined in, for example, US Patent 5,320,908. Differences include, but are not limited to, the absence of the silver layer of US Patent 5,320,908. Instead, the present invention has particles containing neodymium, gold and palladium. The metals in the particles are also different compared to the metals in the layer of US Patent 5,320,908. In short, it is an improvement of the material described in US Patent 5,320,908.

[0064] The amount of metal in the particles and the amount of coating on the particles are expressed in μg / cm 2 It is calculated as the mass of the particle relative to the area covered, and the mass of the metal relative to the area covered.

[0065] Hereinafter, one embodiment of the present invention will be described for the preparation of the coating. In one embodiment, the method comprises the following steps: 1. Rinse (optional) 2. Activation 3. Rinse (optional) 4. Particle adhesion 5. Rinse (optional) 6. Drying (optional)

[0066] An initial wash is optional but recommended.

[0067] Activation is carried out with an aqueous solution of stannous salts containing 0.0005-30 g / l of stannous ions. The pH is 1-4 and is adjusted with hydrochloric and / or sulfuric acid. The treatment time is 2-60 minutes at room temperature. After pretreatment, the surface is rinsed with demineralized water but not dried.

[0068] In addition to the above activation, a treatment may be carried out with a stannous salt prior to activation, such additional treatment being in one embodiment selected from the group consisting of treatment with an alkaline solution followed by neutralization with an acid solution, treatment with a NaOH solution followed by neutralization with HCl, treatment with an alkaline solution heated to less than 90° C., treatment with an alcohol, and treatment with isopropanol.

[0069] Some polymeric objects, such as polytetrafluoroethylene (PTFE), are generally known to be difficult to coat. For such difficult objects, including, for example, polytetrafluoroethylene (PTFE), polyetheretherketone (PEEK), polypropylene, and hydroxyapatite, alternative pretreatments can be used to improve adhesion to the object. In one embodiment, the pretreatment is performed before coating. An aliphatic polyisocyanate-based plasticizer is dissolved in a solvent. Suitable solvents include, but are not limited to, n-butyl acetate, isopropanol, and xylene. The dissolved plasticizer is applied to the object to be coated and allowed to dry. The concentration of the plasticizer is, in one embodiment, adapted so that the dried layer of the plasticizer is only a few moles thick. With such thin coatings, there is essentially no change in most of the physical properties of the object. When the surface has hardened, the coating proceeds. By using this pretreatment, good adhesion is obtained for difficult objects including polytetrafluoroethylene (PTFE), carbon composite filled polyetheretherketone (PEEK), polypropylene based nonwoven materials, and hydroxyapatite. After pretreatment, in one embodiment, the object is rinsed with demineralized water.

[0070] In one embodiment, a colloidal suspension of metals is used to obtain particles on a surface. The particles include a mixture of metals to arrive at a desired composition, i.e., all particles contain the desired composition of metals. The particles are deposited from a suspension of the desired particles. The composition of the particles in the suspension is adjusted according to the desired amount of metal in the particles. The object is immersed in the suspension of particles for a period of time ranging from a few seconds to a few minutes or more.

[0071] The substrate is treated with the suspension for a period of time ranging from a few seconds to a few minutes or longer. After treatment, the substrate is rinsed with a solvent or water, e.g. demineralized water, and dried at room temperature.

[0072] In the presence of palladium, together with activation by stannous ions, an autocatalytic effect is obtained such that metal salts of palladium, neodymium, gold, and any other metal are reduced to elemental metal in the particles.

[0073] Other features of the present invention and their associated advantages will be apparent to those skilled in the art upon reading the specification and examples. It is understood that the disclosed embodiments may be freely combined with all other embodiments unless clearly inconsistent.

[0074] It will be understood that the present invention is not limited by the specific embodiments set forth herein. The following examples are provided for illustrative purposes.

[0075] In the following, each of the methods, apparatus, examples and aspects described is not entirely equivalent to the invention defined in the claims and, therefore, is not in accordance with the present invention, but, like the entirety of the following description, is presented for illustrative purposes only or to highlight certain aspects or features of the claims. [Brief description of the drawings]

[0076] Aspects and embodiments are described with reference to the following figures:

[0077] Figure 1 shows an example of the surface of an object according to the invention. The photograph shows Example 2, the coating of a Nitinol tube. The particles contain palladium, neodymium and gold.

[0078] 2 shows at a higher magnification another example of the surface of an object according to the invention. The photograph shows Example 1, i.e. a coating of the alloy Ti-6Al-4V. EXAMPLES

[0079] Example 1 The substrate was coated with the common implant material Ti-6Al-4V, which is an αβ titanium alloy. First, the material was cleaned and rinsed with RO / DI (reverse osmosis demineralized) water. After cleaning, the material was treated with Sn as a sensitization step. 2+ The bath contained an aqueous solution of tin(II) chloride. After rinsing with RO / DI water, the specimen was subsequently immersed in a bath containing a mixture of Pd, Au and Nd ions. The metal ions were present as chlorides. Due to the autocatalytic action of palladium, the metal formed particles and was deposited on the object. The metal deposition on the titanium alloy surface was 0.6 μg / cm of Pd. 2 , Au 0.2μg / cm 2 and Nd 0.04μg / cm 2 It was.

[0080] A control coating of silver was also performed, Pd 0.5 μg / cm 2 , Au 0.4μg / cm 2 , Nd 0.06μg / cm 2 and Ag 1.3 μg / cm 2 was attached.

[0081] An uncoated control sample was also run and no metal was deposited.

[0082] The thrombin-antithrombin complex (TAT) is a complex of thrombin and antithrombin and was used as a marker of net activation of blood coagulation. TAT values ​​were measured after contact with human blood.

[0083] Comparison of the measured TAT values, which indicate a propensity for thrombosis, showed the following results from the TAT combined analysis: [Table 1]

[0084] As can be seen from the results, when Ag was omitted, the TAT value was further decreased.

[0085] Example 2 A coating process similar to that of Example 1 was carried out on a tube of alloyed Nitinol.

[0086] An uncoated control sample with no metal attached was also prepared, as was a control sample containing silver.

[0087] The amount obtained was 1.1 μg / cm of Pd. 2 , Au 0.6μg / cm 2 and Nd 0.06μg / cm 2 The amount of silver in the control sample was 0.7 μg / cm Pd. 2 , Au 0.6 μg / cm 2 , Nd 0.04 μg / cm 2 and Ag 1.1 μg / cm 2 It was.

[0088] TAT values ​​were measured and were as follows: [Table 2]

[0089] As can be seen from the results, when Ag was omitted, the TAT value was clearly decreased.

[0090] Example 3 A coating process similar to that of Example 1 was carried out on medical grade silicone.

[0091] A control sample with no metal attached was also prepared in the same manner. 2 A control sample containing was also prepared.

[0092] The silicone equivalent coating showed the following values: [Table 3]

[0093] As can be seen from these results, when Ag was also removed from the silicone, the TAT value was clearly shown to decrease.

[0094] Example 4 A coating process similar to that of Example 1 was carried out on a polyurethane hemodialysis catheter.

[0095] A control sample was prepared in the same manner, with no metal being deposited, and a control sample containing silver was also prepared.

[0096] Coatings on polyurethane hemodialysis catheters showed the following amounts: Pd 0.6 μg / cm 2 , Au 0.4 μg / cm 2 , Nd 0.05 μg / cm 2 The control sample containing silver had the following amounts: Pd 0.8 μg / cm 2 , Au 0.3 μg / cm 2 , Nd 0.05 μg / cm 2 , and Ag 1.0 μg / cm 2 .

[0097] A control sample with no metal attached was also prepared. [Table 4]

[0098] Again, improvements are seen when silver is omitted.

[0099] Antibacterial properties All tests, with or without Ag, used the Ahearn test to measure the percent reduction in bacterial growth, and the results were within 95-100%. However, additional tests measuring viability showed no reaction with Ag, but up to 50% reaction on the Nd coating. Zone of inhibition tests were performed to determine whether bacterial kill had occurred, and no reaction was observed.

[0100] In conclusion, the Ag-free Nd coating appears to have a higher reduction rate of thrombosis and a stronger effect of reducing bacterial growth.

Claims

1. An object, the object having particles on a surface thereof, the amount of the particles being 0.041-6 μg / cm 2 and the particles are between 0.02 and 2 μg / cm 2 Palladium in an amount equivalent to 0.001-2 μg / cm 2 and 0.02 to 2 μg / cm 2 and the particles contain less than 30 ppm silver, and the outermost 10 μm of the object contains less than 30 ppm silver.

2. 10. The object of claim 1, wherein the object containing particles on a surface of the object comprises less than 30 ppm silver.

3. 3. The article of claim 1 or 2, wherein the particles comprise at least one metal selected from the group consisting of ruthenium and rhodium.

4. 4. The object of any one of claims 1 to 3, wherein the particles contain less than 20 ppm silver.

5. 4. The object of any one of claims 1 to 3, wherein the particles contain less than 10 ppm silver.

6. The object according to any one of claims 1 to 5, wherein the object is selected from the group consisting of medical devices, medical implements and medical disposables.

7. The object according to any one of claims 1 to 6, wherein the object is any object intended to come into contact with human or animal blood.

8. 8. The object according to any one of claims 1 to 7, comprising at least one metal.

9. 9. The article of claim 8, wherein the at least one metal is selected from the group consisting of iron, titanium, cobalt, nickel, chromium, and mixtures thereof.

10. 9. The object of claim 8, wherein the at least one metal is selected from the group consisting of steel, stainless steel, and nitinol.

11. 9. The object of claim 8, wherein the at least one metal is selected from the group consisting of medical grade titanium, medical grade stainless steel, and medical grade nitinol.

12. 12. The object according to any one of the preceding claims, comprising at least one ceramic material.

13. The article according to any one of claims 1 to 11, comprising at least one selected from the group consisting of silicon nitride and zirconium dioxide.

14. The object according to claims 1 to 13, comprising at least one selected from the group consisting of apatite and hydroxyapatite.

15. The object according to any one of claims 1 to 14, comprising at least one polymer.

16. 16. An object according to any one of claims 1 to 15, comprising at least one polymer composite material.

17. 17. The article of claim 15 or 16, wherein the polymer is selected from the group consisting of latex, vinyl, polymers containing vinyl groups, polyurethaneurea, silicone, polyvinyl chloride, polypropylene, styrene, polyurethane, polyester, ethylene vinyl acetate copolymer, polytetrafluoroethylene (PTFE), polyether ether ketone (PEEK), polystyrene, polycarbonate, polyethylene, polyacrylate, polymethacrylate, acrylonitrile butadiene styrene (ABS), polyamide, polyimide, and mixtures thereof.

18. 18. An object according to any one of the preceding claims, comprising at least one textile material.

19. The amount of the particles is 0.05 to 2 μg / cm 2 The object according to any one of claims 1 to 18, wherein

20. The object of any one of claims 1 to 19, wherein the particles are separate particles that are not in contact with each other.

21. 20. The object of any one of claims 1 to 19, wherein at least a portion of the particles are in contact with other particles to form particle agglomerates.

22. The neodymium is 0.001 to 0.15 μg / cm 2 The object according to any one of claims 1 to 21, which is present in an amount corresponding to:

23. The object according to any one of claims 1 to 22, wherein the particles have a size between 10 and 500 nm measured according to ISO 19749:2021.

24. The object according to any one of claims 1 to 23, wherein the particles have a size between 20 and 100 nm measured according to ISO 19749:2021.

25. 25. The object of any one of claims 1 to 24, which is at least one selected from the group consisting of a catheter, a central venous catheter, a peripheral venous catheter, a urinary catheter, a Foley catheter, an intermittent catheter, an implant, a dental implant, a dental abutment, a dental aligner, a dental prosthetic device, a bone replacement implant, an orthopedic implant, a tissue replacement implant, a stent, a biliary stent, a tracheal stent, a peripheral stent, a glove, a pacemaker, a rupture net, a surgical instrument, a blood bag, an artificial heart valve, a vascular port, a hemodialysis machine, a peritoneal dialysis machine, a plasma apheresis machine, an ECMO machine, a cardiopulmonary bypass machine, an inhalation drug delivery device, a vascular graft, an arterial vascular graft, a venous vascular graft, a cardiac assist device, a wound dressing, an ECG electrode, an orthopedic device, an intraocular lens, a suture, a needle, a staple, a mesh, a drug delivery device, an endotracheal tube, a shunt, a drain, a suction device, a hearing aid, a urethral medical device, and an artificial blood vessel.

26. Use of an object for preventing thrombosis, the object having particles on its surface, the amount of the particles being 0.041 to 6 μg / cm 2 between 0.02 and 2 μg / cm 2 Palladium in an amount equivalent to 0.001-2 μg / cm 2 and 0.02 to 2 μg / cm 2 Contains an amount of gold equivalent to 30 ppm of silver particles, use.

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