Antibacterial metal device and its preparation method and application

Abstract

The present application relates to the technical field of alloy preparation, and discloses an antibacterial metal device and its preparation method and application, including a metal matrix and an antibacterial metal layer obtained by adding antibacterial metal to the surface of the metal matrix; the mass of the antibacterial metal layer is 0.02%-0.06% of the weight of the metal matrix; the extremely small amount of antibacterial metal added to the surface of the cobalt-chromium-molybdenum alloy gives the metal matrix excellent antibacterial properties, and makes the metal matrix have good biocompatibility. The preparation method uses an acidic solution to treat the surface of the metal matrix, so that its surface is chemically corroded into nano-micropores, and after loading antibacterial metal ions, the antibacterial metal ions in the chemically corroded pores are in situ reduced to nano-metal simple substances, so that the nano-metal simple substances are solidified to the surface of the cobalt-chromium-molybdenum alloy, so that it has lasting antibacterial properties. Impurities are not easily mixed in the preparation process, and the cost is low, the operation is simple, and it is suitable for large-scale production.

Description

Technical Field

[0001] The present application relates to the technical field of medical device preparation, and in particular to an antibacterial metal device and a preparation method and application thereof. Background Art

[0002] Medical cobalt-chromium-molybdenum alloy, as a high-performance biomedical cobalt-based alloy casting, has stood out as a leader in medical device materials due to its extraordinary biocompatibility, long-lasting wear and corrosion resistance, as well as its outstanding strength and rigidity. It is especially suitable for orthopedic implant materials and is used to prepare high-end medical devices such as artificial joints and artificial spines.

[0003] Although cobalt-chromium-molybdenum alloy has many advantages as an orthopedic implant material, it is prone to bacterial infection during its transfer into the body, which may pose a serious threat to the patient's health. Summary of the invention

[0004] In view of this, the present application provides a method for preparing an antibacterial metal device and its preparation method and application, so as to solve the problem in the prior art that metal devices are prone to bacterial infection during transfer into the body.

[0005] In a first aspect, the present application provides an antimicrobial metal device.

[0006] The antibacterial metal device comprises a metal substrate and an antibacterial metal layer obtained by doping the antibacterial metal on the surface of the metal substrate;

[0007] The mass of the antibacterial metal layer is 0.02%-0.06% of the mass of the metal substrate.

[0008] In an optional embodiment, the metal matrix includes one of a medical cobalt-chromium-molybdenum alloy, a medical titanium alloy, and a medical steel plate;

[0009] and / or, the antimicrobial metal comprises one or more of silver, zinc or copper;

[0010] And / or, the mass of the antibacterial metal layer is 0.02%-0.03% of the mass of the metal substrate.

[0011] In an optional embodiment, the metal substrate is a nanoporous cobalt-chromium-molybdenum alloy plate with a thickness of 0.1 mm to 100 mm;

[0012] And / or, the antibacterial metal is silver.

[0013] In a second aspect, the present application provides a method for preparing an antibacterial metal device.

[0014] The method for preparing the antibacterial metal device comprises the following steps:

[0015] (1) Immersing the metal substrate in an acidic solution for surface treatment to form a microporous metal substrate;

[0016] (2) The microporous metal substrate is loaded with antibacterial metal ions, and the loaded antibacterial metal ions are then reduced into nano-metal elements to form an antibacterial metal device.

[0017] In an optional embodiment, in step (2), the microporous metal matrix is ​​immersed in a medium containing antibacterial metal ions at 50-100° C., so that the antibacterial metal ions are adsorbed on the surface of the microporous metal matrix, and then taken out and dried until the surface is free of water to obtain a metal matrix loaded with antibacterial metal ions;

[0018] The salt solution containing antibacterial metal ions includes one or more of a nitrate aqueous solution, a nitrate ethanol solution, and a nitrate ammonia aqueous solution containing antibacterial metal ions;

[0019] and / or, the concentration of the salt solution containing antibacterial metal ions is 0.5 mol / L-8 mol / L; the immersion time is 25-35 min;

[0020] And / or, the antibacterial metal ions include one or more of silver ions, zinc ions, and copper ions.

[0021] In an optional embodiment, the metal substrate loaded with antibacterial metal ions is immersed in a solution containing a reducing agent and heated to 50°C-100°C and refluxed for 25-35 minutes, and then taken out and heat-treated to form an antibacterial metal device;

[0022] The reducing agent includes one or more of formaldehyde, acetaldehyde, propionaldehyde, glucose, and vitamin C;

[0023] and / or, the concentration of the solution containing the reducing agent is 5wt%-30wt%;

[0024] And / or, the heat treatment temperature is 200°C-300°C, and the heat treatment time is 8-12 minutes.

[0025] In an optional embodiment, in step (1), the metal substrate is immersed in an acidic solution, taken out, washed and dried at 60°C-100°C to form a microporous metal substrate;

[0026] And / or, the temperature of the acidic solution is 50°C-150°C, and the soaking time is 8min-12min;

[0027] and / or, the concentration of the acidic solution is 0.5 mol / L-8 mol / L;

[0028] And / or, the acidic solution is one or more of hydrochloric acid solution, nitric acid solution, and sulfuric acid solution.

[0029] In an optional embodiment, step (1) further comprises a pretreatment step of the metal substrate: the metal substrate is cleaned, dried, and stored in nitrogen for later use;

[0030] And / or, repeat step (2) 1-15 times.

[0031] In a third aspect, the present application provides an application of an antibacterial metal device.

[0032] In an optional embodiment, the antibacterial metal device is used to prepare a medical device.

[0033] In an alternative embodiment, the medical device comprises a surgical implant;

[0034] The surgical implants include artificial joints or artificial spines.

[0035] Compared with the prior art, the beneficial effects of this application are:

[0036] The present application provides an antibacterial metal device, comprising a metal substrate and an antibacterial metal layer obtained by doping antibacterial metal on the surface of the metal substrate; the mass of the antibacterial metal layer is 0.02%-0.06% of the weight of the metal substrate. By modifying the surface of the metal substrate, the added antibacterial metal layer gives the metal substrate excellent antibacterial properties, and a small amount of antibacterial metal not only reduces the cost, but also makes the metal substrate have good biocompatibility. After testing, the antibacterial metal device has a good antibacterial effect on Staphylococcus aureus, Escherichia coli and Candida albicans, and the toxicity rating is level 0.

[0037] The present application provides a method for preparing an antibacterial metal device, comprising the following steps: immersing a metal substrate in an acidic solution for surface treatment, loading antibacterial metal ions, and then reducing the loaded antibacterial metal ions into nano-metal elements to form an antibacterial metal device. The surface of the metal substrate is treated with an acidic solution so that the surface is chemically corroded into nano-micropores. After loading the antibacterial metal ions, the antibacterial metal ions in the chemically corroded pores are in situ reduced into nano-metal elements, and the nano-metal elements are solidified onto the surface of the cobalt-chromium-molybdenum alloy, thereby giving it a lasting antibacterial property. The use of the metal substrate at a very low level on the surface of the cobalt-chromium-molybdenum alloy has a good antibacterial effect, so that the cobalt-chromium-molybdenum alloy has good biocompatibility. Impurities are not easily mixed into the preparation process, and the cost is low, the operation is simple, and it is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0039] Figure 1 is a scanning electron microscope image of the medical cobalt-chromium-molybdenum alloy casting in Example 1 of the present application;

[0040] Figure 2 This is a scanning electron microscope image of the nanosilver-loaded medical antibacterial surgical implant metal instrument casting in Example 1 of the present application;

[0041] Figure 3 The in vivo antibacterial test results in Test Example 3 of the present application, wherein (a) is the test result of the metal instrument implanted in Comparative Example 1; (1a) is the colony count result of the metal instrument implanted in Comparative Example 1; (b) is the test result of the antibacterial surgical implant metal instrument implanted in Example 3, (2b) is the colony count result of the antibacterial surgical implant metal instrument implanted in Example 3; (c) is the test result of the antibacterial surgical implant metal instrument implanted in Example 6, (3c) is the colony count result of the antibacterial surgical implant metal instrument implanted in Example 6; (d) is the test result of the antibacterial surgical implant metal instrument of Example 3 implanted after 200 wet wipes, (4d) is the colony count result of the antibacterial surgical implant metal instrument of Example 3 implanted after 200 wet wipes; (e) is the test result of the antibacterial surgical implant metal instrument of Example 6 implanted after 200 wet wipes, (5e) is the colony count result of the antibacterial surgical implant metal instrument of Example 6 implanted after 200 wet wipes. DETAILED DESCRIPTION

[0042] The following examples are provided for a better understanding of the present application, but are not limited to the best implementation mode described, and do not limit the content and protection scope of the present application. Any product identical or similar to the present application obtained by anyone under the inspiration of the present application or by combining the features of the present application with other prior arts shall fall within the protection scope of the present application.

[0043] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0044] In this application, regarding the “first aspect”, “second aspect”, “third aspect”, “fourth aspect”, etc., the terms “first”, “second”, “third”, “fourth”, etc. are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features.

[0045] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0046] The temperature parameters in this application, unless otherwise specified, are allowed to be either constant temperature treatment or to vary within a certain temperature range. It should be understood that the constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. Fluctuations within the range of ±5°C, ±4°C, ±3°C, ±2°C, and ±1°C are allowed.

[0047] In this application, when it comes to percentage concentration, unless otherwise specified, it refers to the final concentration. The final concentration refers to the proportion of the added component in the system after the addition of the component.

[0048] In the present application, wt% means weight percentage, and vol% means volume percentage.

[0049] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0050] In order to eliminate or reduce bacterial infections caused by the implantation of antibacterial surgical metal implants into the human body, the applicant tried to coat silver on the surface of the cobalt-chromium-molybdenum alloy plate. However, the silver coating was thick and easy to fall off. The applicant also tried to electroplate antibacterial metal on the surface of the cobalt-chromium-molybdenum alloy plate. This not only easily introduced impurities, but also made the electroplating layer thicker. At the same time, electroplating was affected by various factors such as temperature, current, and voltage, which would cause uneven thickness in some areas, spots on the electroplating layer, easy detachment, etc., and the yield rate was low.

[0051] In a first aspect, the present application provides an antimicrobial metal device.

[0052] The antibacterial metal device comprises a metal substrate and an antibacterial metal layer obtained by adding antibacterial metal to the surface of the metal substrate;

[0053] The weight of the antibacterial metal layer is 0.02%-0.06% of the weight of the metal substrate.

[0054] The present application modifies the surface of the metal substrate, and the added antibacterial metal layer gives the metal substrate excellent antibacterial properties. Moreover, by adding a small amount of antibacterial metal to the surface, not only the cost is reduced, but also the metal substrate has good biocompatibility. According to the test, the antibacterial metal device has a good antibacterial effect on Staphylococcus aureus, Escherichia coli and Candida albicans, and the toxicity rating is 0-1.

[0055] In antibacterial metal products, the mass proportion of the antibacterial metal layer is critical. If the proportion is too small, it may affect the antibacterial properties, while if the proportion of the antibacterial metal layer is too large, it will affect the biocompatibility of the product.

[0056] In some embodiments, the metal matrix includes one of a medical cobalt-chromium-molybdenum alloy, a medical titanium alloy, and a medical steel plate;

[0057] and / or, the antimicrobial metal comprises one or more of silver, zinc or copper;

[0058] And / or, the mass of the antibacterial metal layer is 0.02%-0.03% of the mass of the metal substrate.

[0059] Preferably, the metal substrate is a nanoporous cobalt-chromium-molybdenum alloy plate with a thickness of 0.1 mm to 100 mm;

[0060] And / or, the antibacterial metal is silver.

[0061] In a second aspect, the present application provides a method for preparing an antibacterial metal device.

[0062] In some embodiments, a method for preparing an antimicrobial metal device comprises the following steps:

[0063] (1) Immersing the metal substrate in an acidic solution for surface treatment to form a microporous metal substrate;

[0064] (2) The microporous metal substrate is loaded with antibacterial metal ions, and the loaded antibacterial metal ions are then reduced into nano-metal elements to form an antibacterial metal layer.

[0065] The present application uses an acidic solution to treat the surface of a metal substrate, so that the surface is chemically corroded into nano-micropores, and after antibacterial metal ions are loaded, the antibacterial metal ions in the chemically corroded pores are in situ reduced to nano-metal elements, so that the nano-metal elements are solidified on the surface of the cobalt-chromium-molybdenum alloy, thereby giving it a lasting antibacterial property. The cobalt-chromium-molybdenum alloy surface has a good antibacterial effect at a very low usage, which improves the stability and durability of the product, thereby giving the cobalt-chromium-molybdenum alloy good biocompatibility. Moreover, it is not easy to mix with impurities, and the operation is simple.

[0066] In some embodiments, in step (2), the antibacterial metal ions include one or more of silver ions, zinc ions, and copper ions.

[0067] Silver ions are preferred antibacterial metal ions. Compared with zinc ions and copper ions, silver has the highest antibacterial activity and is used in the least dosage. Nanosilver is more efficient in antibacterial activity than silver alloys and silver coatings.

[0068] In some embodiments, the microporous metal substrate is immersed in a solution containing antibacterial metal ions at 50-100° C., so that the antibacterial metal ions are adsorbed on the surface of the microporous metal substrate, and then taken out and dried at 100-200° C. to obtain a metal substrate loaded with antibacterial metal ions;

[0069] The salt solution containing antibacterial metal ions includes one or more of a nitrate aqueous solution, a nitrate ethanol solution, and a nitrate ammonia aqueous solution containing antibacterial metal ions;

[0070] And / or, the concentration of the salt solution containing antibacterial metal ions is 0.5 mol / L-8 mol / L.

[0071] In some embodiments, the metal substrate loaded with antibacterial metal ions is immersed in a solution containing a reducing agent and heated to 50°C-100°C and refluxed for 25-35 minutes, and then taken out and heat-treated to form an antibacterial metal device;

[0072] The reducing agent includes one or more of formaldehyde, acetaldehyde, propionaldehyde, glucose, and vitamin C;

[0073] and / or, the concentration of the solution containing the reducing agent is 5wt%-30wt%;

[0074] And / or, the heat treatment temperature is 200°C-300°C, and the heat treatment time is 10 minutes.

[0075] In some embodiments, in step (1), the metal substrate is immersed in an acidic solution for 8-12 minutes, taken out, washed and dried to form a microporous metal substrate;

[0076] If the immersion time is too short, the corrosion holes on the surface of the metal substrate will be too small, the amount of metal ions loaded will be small, and the antibacterial property of the antibacterial metal device formed will be poor. If the immersion time is too long, pits will easily form on the surface and the surface will not be smooth.

[0077] And / or, the drying temperature is 60°C-100°C.

[0078] In some embodiments, the acidic solution is one or more of a hydrochloric acid solution, a nitric acid solution, and a sulfuric acid solution;

[0079] And / or, the concentration of the acidic solution is 0.5 mol / L-8 mol / L.

[0080] The selection of the acidic solution, its concentration and immersion time determine the pore size of the nanopores and the loading amount of metal ions, thereby affecting the antibacterial properties of the antibacterial metal device.

[0081] In some embodiments, step (1) further includes a pretreatment step of the metal substrate: cleaning and drying the metal substrate and storing it in nitrogen for later use;

[0082] And / or, repeat step (2) 1-15 times.

[0083] In a third aspect, the present application provides an application of an antibacterial metal device.

[0084] In some embodiments, the antimicrobial metal device is used to prepare a medical device.

[0085] In some embodiments, the medical device comprises a surgical implant;

[0086] The surgical implants include artificial joints or artificial spines.

[0087] Medical cobalt-chromium-molybdenum alloy was purchased from Jinchuan Group Co., Ltd.

[0088] The present application is further described in detail below in conjunction with specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in the present application.

[0089] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0090] Example 1

[0091] This embodiment provides an antibacterial surgical implantable metal device, and the preparation method thereof is as follows:

[0092] (1) Soaking the medical cobalt-chromium-molybdenum alloy casting in an 8 mol / L hydrochloric acid solution (temperature of 50°C) for 8 min, taking it out, washing it, and drying it in an oven at 60°C to prepare a nanoporous medical cobalt-chromium-molybdenum alloy casting;

[0093] (2) Soaking the surface-treated cobalt-chromium-molybdenum alloy casting in an 8 mol / L silver nitrate ethanol solution for 30 min to allow silver ions to be adsorbed onto the surface of the medical cobalt-chromium-molybdenum alloy casting;

[0094] (3) immersing the medical cobalt-chromium-molybdenum casting loaded with silver ions in step (2) into an acetaldehyde solution with a mass concentration of 5%, heating to 50° C. and reflux for 30 min to reduce the silver ions to single nanosilver;

[0095] (4) Repeat steps (2) and (3) 3 times;

[0096] (5) washing with clean water and heat treating at 200°C for 10 min to obtain a medical antibacterial surgical implant metal device casting;

[0097] The loading amount of antibacterial metal was calculated by the formula:

[0098]

[0099] Among them, B is the quality of medical antibacterial surgical implant metal device castings, and A is the quality of nanoporous medical cobalt-chromium-molybdenum alloy castings;

[0100] It was concluded that the loading amount of the antibacterial metal layer in this embodiment was 0.06%.

[0101] Example 2

[0102] This embodiment provides an antibacterial surgical implantable metal device, and the preparation method thereof is as follows:

[0103] (1) Take a medical cobalt-chromium-molybdenum alloy plate (such as Figure 1 ), soaked in 0.5mol / L nitric acid solution (temperature is 80℃) for 10min, taken out, washed and dried in an oven at 100℃ to prepare a nanoporous medical cobalt-chromium-molybdenum alloy plate;

[0104] (2) Soaking the surface-treated cobalt-chromium-molybdenum alloy plate in a 0.5 mol / L silver nitrate aqueous solution for 30 min to allow silver ions to be adsorbed onto the surface of the medical cobalt-chromium-molybdenum alloy plate;

[0105] (3) immersing the medical cobalt-chromium-molybdenum loaded with silver ions in step (2) into a formaldehyde solution with a mass concentration of 30%, heating to 100° C. and reflux for 30 min to reduce the silver ions to single nano-silver;

[0106] (4) Repeat steps (2) and (3) 3 times;

[0107] (5) Wash with clean water and heat-treat at 280°C for 10 min to obtain a medical antibacterial surgical implant metal device plate. Figure 2 ;

[0108] The loading amount of antibacterial metal was calculated by the formula:

[0109]

[0110] Among them, B is the mass of the medical antibacterial surgical implant metal device plate, and A is the mass of the nanoporous medical cobalt-chromium-molybdenum alloy plate;

[0111] It was concluded that the loading amount of the antibacterial metal layer in this embodiment was 0.03%.

[0112] Example 3

[0113] This embodiment provides an antibacterial surgical implantable metal device, and the preparation method thereof is as follows:

[0114] (1) The cobalt-chromium-molybdenum casting was cleaned, dried, and stored in nitrogen for later use; the medical cobalt-chromium-molybdenum alloy casting was immersed in a 4 mol / L sulfuric acid solution (temperature: 100°C) for 12 min, taken out, cleaned, and dried in an oven at 80°C to prepare a nanoporous medical cobalt-chromium-molybdenum alloy casting;

[0115] (2) Soaking the surface-treated cobalt-chromium-molybdenum alloy casting in a 4 mol / L silver nitrate-ammonia aqueous solution for 30 min to allow silver ions to be adsorbed onto the surface of the medical cobalt-chromium-molybdenum alloy casting;

[0116] (3) immersing the medical cobalt-chromium-molybdenum loaded with silver ions in step (2) into a propionaldehyde solution with a mass concentration of 15%, heating to 80° C. and reflux for 30 min to reduce the silver ions to single nanosilver;

[0117] (4) Repeat steps (2) and (3) 3 times;

[0118] (5) washing with clean water, and heat treating at 300°C for 10 min to obtain a medical antibacterial surgical implant metal device casting;

[0119] The loading amount of antibacterial metal was calculated by the formula:

[0120]

[0121] Among them, B is the quality of medical antibacterial surgical implant metal device castings, and A is the quality of nanoporous medical cobalt-chromium-molybdenum alloy castings;

[0122] It was concluded that the loading amount of the antibacterial metal layer in this embodiment was 0.02%.

[0123] Example 4

[0124] This embodiment is basically the same as embodiment 1, except that, in step (3), the medical cobalt-chromium-molybdenum loaded with silver ions is immersed in a glucose aqueous solution with a mass concentration of 15%, the temperature is raised to 80° C. and heated under reflux for 30 min to reduce the silver ions to single nano-silver;

[0125] The loading amount of antibacterial metal was calculated by the formula:

[0126]

[0127] Among them, B is the quality of medical antibacterial surgical implant metal device castings, and A is the quality of nanoporous medical cobalt-chromium-molybdenum alloy castings;

[0128] It was concluded that the loading amount of the antibacterial metal layer in this embodiment was 0.02%.

[0129] Example 5

[0130] This embodiment is basically the same as embodiment 1, except that, in step (3), the medical cobalt-chromium-molybdenum loaded with silver ions is immersed in a 15% vitamin C aqueous solution, heated to 80° C. and refluxed for 30 min to reduce the silver ions to single nano-silver.

[0131] The loading amount of antibacterial metal was calculated by the formula:

[0132]

[0133] Among them, B is the quality of medical antibacterial surgical implant metal device castings, and A is the quality of nanoporous medical cobalt-chromium-molybdenum alloy castings;

[0134] It was concluded that the loading amount of the antibacterial metal layer in this embodiment was 0.02%.

[0135] Example 6

[0136] This embodiment is basically the same as embodiment 1, except that in step (2), a copper nitrate aqueous solution is used for soaking;

[0137] The loading amount of antibacterial metal was calculated by the formula:

[0138]

[0139] Among them, B is the quality of medical antibacterial surgical implant metal device castings, and A is the quality of nanoporous medical cobalt-chromium-molybdenum alloy castings;

[0140] It was concluded that the loading amount of the antibacterial metal layer in this embodiment was 0.02%.

[0141] Example 7

[0142] This embodiment is basically the same as embodiment 1, except that in step (2), a zinc nitrate aqueous solution is used for soaking;

[0143] The loading amount of antibacterial metal was calculated by the formula:

[0144]

[0145] Among them, B is the quality of medical antibacterial surgical implant metal device castings, and A is the quality of nanoporous medical cobalt-chromium-molybdenum alloy castings;

[0146] It was concluded that the loading amount of the antibacterial metal layer in this embodiment was 0.03%.

[0147] Comparative Example 1

[0148] This comparative example provides a method for preparing an antibacterial surgical implantable metal device, which is the same as step (1) of Example 1 to prepare a nanoporous medical cobalt-chromium-molybdenum alloy casting.

[0149] Comparative Example 2

[0150] This comparative example provides a method for preparing a cobalt-chromium-molybdenum alloy, which is different from Example 1 in that step (3) is omitted, the medical cobalt-chromium-molybdenum loaded with silver ions is washed with water, and heat-treated at 960° C. for 10 min to form a cobalt-chromium-molybdenum alloy loaded with silver ions.

[0151] Test Example 1

[0152] The antibacterial properties and toxicity of the antibacterial surgical implant metal instruments of Examples 1-7, the medical cobalt-chromium-molybdenum alloy casting of Comparative Example 1, and the cobalt-chromium-molybdenum alloy loaded with silver ions of Comparative Example 2 were compared.

[0153] According to ISO 22196-2011 "Evaluation method for antimicrobial properties of plastic products surface";

[0154] Conduct relevant biological evaluation according to the national standard GB / T16886.5-2017 "Biological Evaluation of Medical Devices Part 5 In Vitro Cytotoxicity Test";

[0155] The antibacterial surgical implant metal instruments of Examples 1-7, the medical cobalt-chromium-molybdenum alloy castings of Comparative Example 1, and the cobalt-chromium-molybdenum alloy loaded with silver ions of Comparative Example 2 were evaluated for cytotoxicity to L929 (mouse fibroblasts) at 1-7 days. Among them, grades 0 and 1 meet the requirements of biomedical materials. The test results are shown in Table 1.

[0156] Table 1 Test results of antibacterial properties and antiviral activities

[0157]

[0158] It can be seen from the test results in Table 1 that the antibacterial medical cobalt-chromium-molybdenum alloys prepared in Examples 1-7 can effectively kill and inhibit Staphylococcus aureus and Escherichia coli, and at the same time pass the cytotoxicity test and have good biocompatibility.

[0159] Compared with Example 1, Example 6 loaded with nano copper element, the antibacterial rate was 98.6% and 97.6%, indicating that copper also has a good antibacterial effect, but the antibacterial effect is not as good as the nano silver element in Example 1. The biocompatibility is also not as good as the nano silver element in Example 1.

[0160] Compared with Example 1, Example 7 loaded with nano zinc element, and the antibacterial rate was 98.5% and 96.7%, indicating that copper also has a good antibacterial effect, but the antibacterial effect is not as good as the nano silver element in Example 1. The biocompatibility is also not as good as the nano silver element in Example 1.

[0161] Compared with Example 1, the antibacterial metal layer was not added to the surface of the silver-cobalt-chromium-molybdenum alloy in Comparative Example 1, and the antibacterial effect was poor, only 45.5% and 38.6%.

[0162] Compared with Example 1, the cobalt-chromium-molybdenum alloy loaded with silver ions in Comparative Example 2 also has poor antibacterial effect.

[0163] Test Example 2

[0164] In order to further verify the long-term effectiveness of medical antibacterial, the cobalt-chromium-molybdenum alloys of Examples 1-7 and Comparative Examples 1-2 were subjected to antibacterial durability tests.

[0165] According to the national standard GB / T31410-2015, the coating was wet scrubbed 200 times and then subjected to antibacterial and cytotoxicity tests. The test data are shown in Table 2.

[0166] Table 2 Antibacterial and antiviral activity test results after 2200 wet scrubbing cycles

[0167]

[0168] It can be seen from the test results in Table 2 that, compared with Example 1-2, after 200 wet scrubbing cycles, the antibacterial effect of the prepared metal instruments in Example 1-7 decreased significantly, while the antibacterial effect of Example 1-7 only decreased slightly, but still showed good antibacterial effect, indicating that the antibacterial surgical implant metal instruments prepared in Example 1-7 have the property of not being able to tolerate water, thereby giving the antibacterial medical cobalt chromium molybdenum a long-lasting antibacterial property.

[0169] Test Example 3

[0170] A subcutaneous infection model was established by selecting healthy rats weighing 200-220 g, and the antibacterial surgical implant metal instruments of Comparative Example 1, Example 3, and Example 6 were implanted respectively to evaluate the antibacterial performance in vivo.

[0171] Experimental animals: 20 healthy rats weighing 200-220g were selected for this experiment and divided into 5 groups, 4 rats in each group, half male and half female. The rats were allowed to adapt to the environment for 5 days before the experiment. During this period, they were fed SPF rat pellet feed and had free access to sterilized tap water. The room temperature was 20-26℃, the relative humidity was 40%-70%, and the lighting was 12 hours light / 12 hours dark.

[0172] Model establishment: 2% sodium pentobarbital was intraperitoneally injected at a dose of 30 mg / kg to anesthetize the rats in 5 groups. The skin was prepared and routinely disinfected. The skin of the rats was incised along the lateral side of the femur of the left hind limb. The muscles were separated layer by layer and the bone marrow cavity was drilled with Kirschner pins. 10 μL of 1×10 5cfu / mL of Staphylococcus aureus solution was injected into the medullary cavity, and then the metal instruments of Comparative Example 1, Example 3, and Example 6 (all metal rods with a diameter of 2 mm) were implanted into the left femoral medullary cavity of rats in Groups 1-3, respectively. The wounds were sutured layer by layer, and the rats were housed in single cages.

[0173] The antimicrobial surgical implantable metal instruments (all metal rods with a diameter of 2 mm) of Example 3 and Example 6 were wet scrubbed for 200 cycles and then implanted into the left femoral medullary cavity of rats in Group 4 and Group 5, respectively. The wounds were sutured layer by layer, and the rats were housed in single cages.

[0174] Test results:

[0175] Seven days after the subcutaneous infection model was established, the implantation site was observed, bacteria around the implanted metal device were sampled, and the bacterial contamination in the bone marrow cavity was detected by gradient dilution and plate counting method, and its antibacterial activity was evaluated. The test results are as follows: Figure 3 As shown, (a) is the test result of the metal instrument implanted in comparative example 1, and obvious infection appeared around the wound; (1a) is the colony count result of the metal instrument implanted in comparative example 1; (b) is the test result of the antibacterial surgical implanted metal instrument implanted in example 3, and it can be seen that the inflammation around the wound is small and is gradually healing, (2b) is the colony count result of the antibacterial surgical implanted metal instrument implanted in example 3; (c) is the test result of the antibacterial surgical implanted metal instrument implanted in example 6, and it can be seen that the inflammation around the wound is gradually healing, (3c) is the colony count result of the antibacterial surgical implanted metal instrument implanted in example 6 Colony count results of surgical implanted metal instruments; (d) is the test result of the antibacterial surgical implanted metal instrument of Example 3 after being wet wiped 200 times, (4d) is the colony count result of the antibacterial surgical implanted metal instrument of Example 3 after being wet wiped 200 times; (e) is the test result of the antibacterial surgical implanted metal instrument of Example 6 after being wet wiped 200 times, (5e) is the colony count result of the antibacterial surgical implanted metal instrument of Example 6 after being wet wiped 200 times; the inflammation in Figure (a) is the most serious, and the inflammation around the wound in Figures (d) and (e) is gradually healing, but the range of inflammation is larger than that in Figure (b). Among the in vivo implants, the colony count of group (1a) is the largest, while the colony counts of the remaining groups are reduced to varying degrees, and the colony counts of Figures (2b) and (3c) are the least.

[0176] The above experimental results indicate that the antibacterial surgical implant metal instrument prepared by the present application has obvious antibacterial effect in vivo as an implant, can kill bacteria at an early stage in vivo, and still has significant antibacterial effect after 200 wet scrubbing cycles.

[0177] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection created by this application.

Claims

1. An antibacterial metal device, characterized in that: It comprises a metal substrate and an antibacterial metal layer obtained by adding antibacterial metal to the surface of the metal substrate; The mass of the antibacterial metal layer is 0.02%-0.06% of the weight of the metal substrate; The method for preparing the antibacterial metal device comprises the following steps: (1) Immersing the metal substrate in an acidic solution for surface treatment to form a microporous metal substrate; (2) loading the antibacterial metal ions onto the microporous metal substrate, and then reducing the loaded antibacterial metal ions into nano-metal elements to form an antibacterial metal device; Reducing the loaded antibacterial metal ions into nano-metal elements to form an antibacterial metal device comprises the following steps: immersing the metal substrate loaded with antibacterial metal ions in a solution containing a reducing agent and heating the solution to 50°C-100°C and reflux for 25-35 minutes, taking the substrate out and performing heat treatment to form an antibacterial metal device; The reducing agent includes one or more of formaldehyde, acetaldehyde, propionaldehyde, glucose, and vitamin C; and / or, the concentration of the solution containing the reducing agent is 5wt%-30wt%; And / or, the heat treatment temperature is 200°C-300°C.

2. The antibacterial metal device according to claim 1, characterized in that: The metal matrix includes one of medical cobalt-chromium-molybdenum alloy, medical titanium alloy and medical steel plate; and / or, the antimicrobial metal comprises one or more of silver, zinc or copper; And / or, the mass of the antibacterial metal layer is 0.02%-0.03% of the mass of the metal substrate.

3. The antibacterial metal device according to claim 2, characterized in that: The metal substrate is a nanoporous cobalt-chromium-molybdenum alloy plate with a thickness of 0.1 mm to 100 mm; And / or, the antibacterial metal is silver.

4. A method for preparing an antibacterial metal device according to any one of claims 1 to 3, characterized in that: The steps include: (1) Immersing the metal substrate in an acidic solution for surface treatment to form a microporous metal substrate; (2) The microporous metal substrate is loaded with antibacterial metal ions, and the loaded antibacterial metal ions are then reduced into nano-metal elements to form an antibacterial metal device.

5. The method for preparing the antibacterial metal device according to claim 4, characterized in that: In step (2), the microporous metal substrate is immersed in a solution containing antibacterial metal ions at 50-100° C., so that the antibacterial metal ions are adsorbed on the surface of the microporous metal substrate, and then taken out and dried to obtain a metal substrate loaded with antibacterial metal ions; The salt solution containing antibacterial metal ions includes one or more of a nitrate aqueous solution, a nitrate ethanol solution, and a nitrate ammonia aqueous solution containing antibacterial metal ions; and / or, the concentration of the salt solution containing antibacterial metal ions is 0.5 mol / L-8 mol / L; the immersion time is 25-35 min; And / or, the antibacterial metal ions include one or more of silver ions, zinc ions, and copper ions.

6. The method for preparing the antibacterial metal device according to claim 5, characterized in that: The metal substrate loaded with antibacterial metal ions is immersed in a solution containing a reducing agent and heated to 50°C-100°C for reflux for 25-35 minutes, and then taken out and heat treated to form an antibacterial metal device; The reducing agent includes one or more of formaldehyde, acetaldehyde, propionaldehyde, glucose, and vitamin C; and / or, the concentration of the solution containing the reducing agent is 5wt%-30wt%; And / or, the temperature of the heat treatment is 200°C-300°C.

7. The method for preparing the antibacterial metal device according to claim 4, characterized in that: In step (1), the metal substrate is immersed in an acidic solution, taken out, washed and dried at 60°C-100°C to form a microporous metal substrate; And / or, the temperature of the acidic solution is 50°C-150°C, and the soaking time is 8min-12min; and / or, the concentration of the acidic solution is 0.5 mol / L-8 mol / L; And / or, the acidic solution is one or more of hydrochloric acid solution, nitric acid solution, and sulfuric acid solution.

8. The method for preparing the antibacterial metal device according to claim 4, characterized in that: Step (1) also includes a pretreatment step for the metal substrate: cleaning and drying the metal substrate and then storing it in nitrogen for later use; And / or, repeat step (2) 1-15 times.

9. The use of the antibacterial metal device according to any one of claims 1 to 3, characterized in that: The antibacterial metal device is used to prepare medical devices.

10. The use according to claim 9, characterized in that: The medical device comprises a surgical implant; The surgical implants include artificial joints or artificial spines.

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