WO2021218089A1 - 高氮无镍奥氏体不锈钢无缝薄壁管材、 - Google Patents

高氮无镍奥氏体不锈钢无缝薄壁管材、 Download PDF

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WO2021218089A1
WO2021218089A1 PCT/CN2020/125095 CN2020125095W WO2021218089A1 WO 2021218089 A1 WO2021218089 A1 WO 2021218089A1 CN 2020125095 W CN2020125095 W CN 2020125095W WO 2021218089 A1 WO2021218089 A1 WO 2021218089A1
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stent
nickel
metal
nitrogen
deformation
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PCT/CN2020/125095
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English (en)
French (fr)
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李文
白树功
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中科益安医疗科技（北京）股份有限公司
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Priority claimed from CN202010364623.2A external-priority patent/CN111840659B/zh
Priority claimed from CN202010367246.8A external-priority patent/CN111850668A/zh
Priority claimed from CN202010367220.3A external-priority patent/CN111850422B/zh
Application filed by 中科益安医疗科技（北京）股份有限公司 filed Critical 中科益安医疗科技（北京）股份有限公司
Priority to EP20933365.7A priority Critical patent/EP4144387A1/en
Priority to US17/922,109 priority patent/US20230166010A1/en
Publication of WO2021218089A1 publication Critical patent/WO2021218089A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/024—Carbon; Graphite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D1/00—General methods or devices for heat treatment, e.g. annealing, hardening, quenching or tempering
    • C21D1/26—Methods of annealing
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D1/00—General methods or devices for heat treatment, e.g. annealing, hardening, quenching or tempering
    • C21D1/74—Methods of treatment in inert gas, controlled atmosphere, vacuum or pulverulent material
    • C21D1/76—Adjusting the composition of the atmosphere
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D6/00—Heat treatment of ferrous alloys
    • C21D6/002—Heat treatment of ferrous alloys containing Cr
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D6/00—Heat treatment of ferrous alloys
    • C21D6/005—Heat treatment of ferrous alloys containing Mn
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D7/00—Modifying the physical properties of iron or steel by deformation
    • C21D7/02—Modifying the physical properties of iron or steel by deformation by cold working
    • C21D7/10—Modifying the physical properties of iron or steel by deformation by cold working of the whole cross-section, e.g. of concrete reinforcing bars
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D8/00—Modifying the physical properties by deformation combined with, or followed by, heat treatment
    • C21D8/10—Modifying the physical properties by deformation combined with, or followed by, heat treatment during manufacturing of tubular bodies
    • C21D8/105—Modifying the physical properties by deformation combined with, or followed by, heat treatment during manufacturing of tubular bodies of ferrous alloys
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D9/00—Heat treatment, e.g. annealing, hardening, quenching or tempering, adapted for particular articles; Furnaces therefor
    • C21D9/08—Heat treatment, e.g. annealing, hardening, quenching or tempering, adapted for particular articles; Furnaces therefor for tubular bodies or pipes
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/001—Ferrous alloys, e.g. steel alloys containing N
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/002—Ferrous alloys, e.g. steel alloys containing In, Mg, or other elements not provided for in one single group C22C38/001 - C22C38/60
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/02—Ferrous alloys, e.g. steel alloys containing silicon
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
    • C22C38/22—Ferrous alloys, e.g. steel alloys containing chromium with molybdenum or tungsten
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
    • C22C38/38—Ferrous alloys, e.g. steel alloys containing chromium with more than 1.5% by weight of manganese
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
    • C22C38/40—Ferrous alloys, e.g. steel alloys containing chromium with nickel
    • C22C38/42—Ferrous alloys, e.g. steel alloys containing chromium with nickel with copper
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
    • C22C38/40—Ferrous alloys, e.g. steel alloys containing chromium with nickel
    • C22C38/44—Ferrous alloys, e.g. steel alloys containing chromium with nickel with molybdenum or tungsten
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22C—ALLOYS
    • C22C38/00—Ferrous alloys, e.g. steel alloys
    • C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
    • C22C38/40—Ferrous alloys, e.g. steel alloys containing chromium with nickel
    • C22C38/58—Ferrous alloys, e.g. steel alloys containing chromium with nickel with more than 1.5% by weight of manganese
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D2211/00—Microstructure comprising significant phases
    • C21D2211/001—Austenite
    • C—CHEMISTRY; METALLURGY
    • C21—METALLURGY OF IRON
    • C21D—MODIFYING THE PHYSICAL STRUCTURE OF FERROUS METALS; GENERAL DEVICES FOR HEAT TREATMENT OF FERROUS OR NON-FERROUS METALS OR ALLOYS; MAKING METAL MALLEABLE, e.g. BY DECARBURISATION OR TEMPERING
    • C21D2261/00—Machining or cutting being involved

Definitions

  • the invention relates to the field of high-nitrogen steel pipes, in particular to a high-nitrogen nickel-free austenitic stainless steel seamless thin-walled pipe and a preparation method thereof.
  • the preparation method can be applied to the preparation of chromium-manganese-nitrogen stainless steel thin-walled pipes.
  • the present invention relates to the field of medical devices, in particular to a nickel-free metal drug-eluting vascular stent with long service life and high safety and a manufacturing method thereof.
  • Nickel is an essential trace element for the human body, but excessive intake can cause allergies, deformity, cancer and other pathological changes.
  • many countries have become more and more stringent on the nickel content in daily and medical metal materials.
  • the European Parliament standard (94/27/EC) promulgated in 1994 stipulates that the nickel content in materials implanted in the human body should not exceed 0.05%; and alloys that have long-term contact with human skin (jewelry, watches, rings, bracelets, etc.), The amount of nickel that penetrates into the skin every week should not exceed 0.5 ⁇ g/cm 2 .
  • research and development of medical low-nickel and nickel-free austenitic stainless steel has become a major international development trend of medical stainless steel.
  • the chromium-manganese-nitrogen high-nitrogen nickel-free austenitic stainless steel is to increase the solid solubility of nitrogen by increasing the manganese element content in the material, thereby obtaining a stable austenitic stainless steel. It has the characteristics of high strength and toughness, large deformation resistance, good corrosion performance and biological performance.
  • Stent implantation is currently the most effective and safe method for treating vascular stenosis.
  • stent implantation and stent manufacturing technology have basically matured.
  • a drug coating needs to be prepared on the surface of the stent in order to inhibit the excessive proliferation of vascular tissue or achieve rapid endothelialization at the initial stage of implantation.
  • the drug coating on the surface of the stent is generally obtained by ultrasonic atomization spraying.
  • Coronary stents generally adopt a method of preparing a drug coating on the surface of a metal stent.
  • the stent is fixed to the target diseased part of the blood vessel through balloon expansion, which acts as a long-term physical support for the diseased blood vessel and participates in the blood supply of the blood vessel.
  • balloon expansion acts as a long-term physical support for the diseased blood vessel and participates in the blood supply of the blood vessel.
  • some patients will still experience restenosis, thrombosis and late failure of the stent after stent implantation.
  • the reasons may be related to the following factors: (1)
  • the incidence of restenosis in the stent is higher in patients with metal allergy, and nickel allergy is the majority of patients with metal allergy.
  • Patent Document 1 a high-nitrogen nickel-free stainless steel that does not add harmful nickel elements. Its composition is: Cr: 17-22%, Mn: 12-20%, Mo: 1-3% , Cu: 0.5 to 1.5%, N: 0.4 to 0.7%, Ni: ⁇ 0.02%, C: ⁇ 0.03%, Si: ⁇ 0.75%, S: ⁇ 0.01%, P: ⁇ 0.025%, Fe: the balance.
  • the material has the characteristics of high strength, high fatigue strength, high corrosion resistance and stable tissue, and has obvious advantages as an implant material.
  • stent manufacturers use methods such as surface modification and preparation of gradient coatings to make the drug coating on the surface of the stent stronger.
  • Increasing the surface area and increasing the firmness of the bonding between the stent and the coating have certain effects.
  • Electrochemical polishing is a relatively mature and widely used metal polishing technology, especially suitable for the polishing of small samples, special-shaped samples and unstressed samples.
  • small-caliber tube mesh samples such as vascular stents for medical devices and other luminal stents, and small springs for instruments and meters, are electrochemically polished to improve surface quality and control dimensional accuracy.
  • this kind of sample has a hollow structure, and the sample has only part of the metal mesh structure covered, which is called the metal coverage.
  • the metal coverage rate of the small-diameter pipe mesh sample of the present invention is less than 50%, so as to ensure sufficient solution exchange in the pipe during the polishing process.
  • the polishing of the small-diameter pipe mesh sample is generally as shown in Figure 1. Specifically, the anode is used to clamp a part of the sample, and the sample is polished by reciprocating motion.
  • Patent Document 1 CN1519387A
  • Patent Document 2 CN101255593A
  • Patent Document 3 CN103668390A
  • FIG. 1 shows the metallographic photograph of the manganese-poor layer formed on the surface of the pipe.
  • the manganese-poor layer on the surface of the tube becomes thicker, and when the wall thickness reaches a certain ratio to the manganese-poor layer, the tube cracks.
  • Figure 3 shows the metallographic photo of the severely poor manganese cracking on the surface of the pipe.
  • Patent Document 2 and Patent Document 3 mentioned above are difficult to achieve an ideal effect on a pipe mesh stent with a mesh of only 0.08 to 0.1 mm. Therefore, there is an urgent need to find a surface roughening technology that is more suitable for stent manufacturing technology.
  • the existing method for polishing a small-diameter pipe mesh sample as shown in FIG. 1 mainly has the following problems: (1) There will be excessive local current between the sample and the electrode due to contact problems, causing the mesh to break; (2) Point contact causes uneven polishing, especially when the sample is long, there will be a significant difference between the proximal electrode end and the far electrode end. For springs and vascular stents, the above-mentioned problems will directly lead to inconsistencies in the mechanical properties of the product, and may even cause the product to fail.
  • the purpose of the present invention is to provide a high-manganese (Mn ⁇ 10 wt%) high-nitrogen (N: 0.7-1.3 wt%) nickel-free (Ni ⁇ 0.05 wt%) austenitic It is a stainless steel seamless thin-walled pipe, and provides a method for preparing the high-nitrogen nickel-free austenitic stainless steel seamless thin-walled pipe with high dimensional accuracy and controllable nitrogen content and manganese content.
  • the purpose of the present invention is to provide a blood vessel stent with longer service life and higher safety and a method for manufacturing the same.
  • the present inventors conducted in-depth research on the surface treatment method of the high-nitrogen nickel-free austenitic stainless steel seamless thin-walled pipe used for the stent pipe and the stent metal platform, and for the first time obtained the following (1) ⁇ ( 5) Discovery.
  • the surface layer of the pipe can be achieved without manganese volatilization, and the nitrogen content in the material and the comprehensive performance of the pipe can be controlled by applying the nitrogen partial pressure.
  • the contact between the electrode and the small-diameter pipe network sample (for example, the metal platform of the bracket) is realized by the method of rolling line contact, and the contact force and contact time of all points on the small-diameter pipe network sample with the electrode are Uniformity, so as to ensure the uniform polishing of the small-diameter pipe mesh sample, thereby realizing the surface finishing of the small-diameter pipe mesh sample and accurately controlling the mesh size.
  • the surface micro-patterning of the small-diameter pipe network sample can be synchronously realized during the polishing process. Therefore, under the premise that no foreign matter is introduced and the overall performance of the sample is not affected, the surface micro-patterning can improve the bonding firmness of the small-diameter pipe network sample and the drug coating.
  • the present invention was completed based on the above findings, that is, the gist of the present invention is as follows.
  • a high-nitrogen nickel-free austenitic stainless steel seamless thin-walled pipe characterized in that:
  • the N content is 0.7-1.3% by weight, and it is a single austenite structure in the solid solution state and the cold deformed state below 66%, and the grain size is ⁇ 7 grade,
  • the wall thickness of the pipe is 60 ⁇ 200 ⁇ m, the outer diameter dimension deviation is ⁇ 0.03mm, the wall thickness dimension deviation is ⁇ 0.02mm, the yield strength is ⁇ 600MPa, the tensile strength is ⁇ 1000MPa, the axial elongation is ⁇ 50%, and the pitting potential is ⁇ 1000mV .
  • the heat treatment is carried out after 2 to 3 cold deformations with the decreasing gradient in each pass, the heat treatment temperature is 1000-1150°C, and the treatment time is 5 to 90 minutes.
  • the preparation method according to 7 or 8 characterized in that, when the outer diameter of the pipe is ⁇ 3.0mm, cold deformation is performed 3 times per pass, and the amount of deformation each time is 45-50% of the deformation amount of the pass. , 30 to 35% and 20 to 25%; when the outer diameter of the pipe is less than 3.0mm, cold deformation is performed twice per pass, and the amount of deformation each time is 55-60% and 40-45% of the deformation of the pass.
  • a nickel-free metal drug-eluting vascular stent characterized in that:
  • the metal platform material of the stent is high-nitrogen nickel-free austenitic stainless steel, and the composition of the metal platform material is calculated by weight %: Cr: 17-20%, Mn: 14-18%, Mo: 1-3% , N: 0.8 ⁇ 1.2%, Si: ⁇ 0.75%, Cu: ⁇ 0.25%, C: ⁇ 0.03%, Si: ⁇ 0.01%, P: ⁇ 0.025%, Ni: ⁇ 0.05%, Fe: the balance,
  • the tensile strength of the metal platform material is 1100 MPa or more, the fatigue strength in the solid solution state is 570 MPa or more, and the fatigue strength at 20% cold deformation is 750 MPa or more,
  • the pitting potential of the metal platform material in physiological saline and PBS buffer is above 1000 mV
  • the metal platform material still has a single austenite structure, and the grain size is greater than or equal to 7 grades.
  • the nickel-free metal drug-eluting vascular stent according to any one of 11 to 13 above, which is used for cardio-cerebral blood vessels.
  • a method for manufacturing a nickel-free metal drug-eluting vascular stent characterized in that, during the preparation of the stent tube, a high-nitrogen nickel-free austenitic stainless steel tube blank with a nitrogen content of less than 0.7% by weight is subjected to cold deformation and heat treatment
  • the combined method can increase the nitrogen content of the pipe to 0.8-1.2% and achieve no manganese volatilization on the surface layer while the pipe is formed and the dimensional accuracy is controlled.
  • the heat treatment is carried out after 2 to 3 cold deformations with the decreasing gradient in each pass, the heat treatment temperature is 1000-1150°C, and the treatment time is 5 to 90 minutes.
  • the metal electrode selects a dissimilar inert metal material different from the support metal platform, so that the metal electrode and the support metal platform are connected in a continuous rolling linear contact manner, and the metal electrode and the support metal
  • the micro potential difference between the platforms makes the surface of the metal platform of the support form a micron-level convex-concave structure through crystal grains of different orientations, and the height difference between the crystal grains is 0.1-0.5 ⁇ m.
  • the present invention it is possible to provide a high-manganese, high-nitrogen, nickel-free austenitic stainless steel thin-walled pipe with high dimensional accuracy, high surface quality and excellent comprehensive performance, and a preparation method thereof.
  • the stent metal platform material adopts a high-nitrogen nickel-free stainless steel material with high fatigue performance and high corrosion performance obtained by nitriding step by step, thereby making the stent metal platform have high mechanical properties and Fatigue strength, so that the bracket has a higher fatigue life.
  • the metal platform of the stent is made of high-nitrogen nickel-free austenitic stainless steel.
  • the material does not actively add harmful nickel elements with sensitizing and carcinogenic effects, and the material has excellent corrosion resistance, thereby reducing the drug coating on the surface of the stent.
  • the risk of restenosis may be caused by the dissolution of metal ions or nickel allergy after the layer is degraded.
  • the fatigue strength of the stent is further improved, and the service cycle of the stent is longer.
  • the rolling line contact electrochemical polishing By adopting the rolling line contact electrochemical polishing, the surface finishing of the small-diameter pipe network metal sample such as the support metal platform can be quickly realized, thereby greatly improving the surface polishing efficiency and surface polishing quality of the support metal platform. Moreover, through the rolling line contact electrochemical polishing method of the present invention, the precise control rule of the metal platform of the support can be realized, and the method can greatly reduce the scrap rate of such precision metal samples.
  • the surface of the metal platform of the stent is roughened by rolling line contact electrochemical polishing, and the micron-level convex-concave structure is formed by crystal grains of different orientations, which increases the binding force between the metal platform of the stent and the drug coating, and makes the drug coating on the surface of the stent.
  • the layer can better resist deformation and damage that may be caused by fatigue. Therefore, the coating is not easy to fall off during the deformation, transportation and service of the stent, which reduces the risk of thrombosis in the initial stage of stent implantation.
  • the surface roughening method of the present invention does not require the introduction of foreign substances, and therefore has higher safety.
  • the surface roughening method of the present invention does not have the problem of reduced fatigue life caused by physical surface roughening methods such as texturing and sandblasting.
  • the high-safety nickel-free metal drug-eluting vascular stent of the present invention has the characteristics of long life and low risk, it is expected to improve the quality of life of implanted patients and benefit the society.
  • Fig. 1 is a schematic diagram showing a conventional polishing method of a small-diameter pipe mesh sample.
  • Figure 2 is a metallographic photograph of a manganese-poor layer formed on the surface of a pipe.
  • Figure 3 is a metallographic photo of severely manganese-poor cracks on the surface of the pipe.
  • FIG. 4 is a photo of the metallographic structure showing the axial section of the ⁇ 3.0 ⁇ 0.11 mm pipe of Example 1.
  • FIG. It is a photo of the metallographic structure taken with a Zeiss Observer Z1M metallographic microscope with a magnification of 100 times according to the GB/T 6397-2017 metal average grain size measurement method.
  • Fig. 5 is a photo of the metallographic structure showing the axial section of the ⁇ 1.8 ⁇ 0.09 mm pipe of Example 2.
  • Figs. It is a photo of the metallographic structure taken with a Zeiss Observer Z1M metallographic microscope with a magnification of 100 times according to the GB/T 6397-2017 metal average grain size measurement method.
  • FIG. 6 is a photo of the metallographic structure showing the axial section of the ⁇ 4.5 ⁇ 0.19 mm pipe of Example 3.
  • FIG. It is a photo of the metallographic structure taken with a Zeiss Observer Z1M metallographic microscope with a magnification of 100 times according to the GB/T 6397-2017 metal average grain size measurement method.
  • FIG. 7 is a diagram showing the structure of a stent with a nominal diameter of 2.5 mm in Example 4.
  • FIG. 8 is a schematic diagram showing the rolling type line contact type electrochemical polishing apparatus of the present invention.
  • Fig. 8A is a front view of the polishing device.
  • Fig. 8B is a top view of the polishing device.
  • FIG. 9 is a diagram showing the macroscopic and microscopic morphology of the surface of the high-nitrogen nickel-free stainless steel vascular stent after surface modification by the method of the present invention in Example 4.
  • FIG. 9A and 9B are the macroscopic morphology of the surface of the high-nitrogen nickel-free stainless steel vascular stent, wherein, FIG. 9B is a partial enlarged view of FIG. 9A.
  • Figure 9C is a microscopic image of the surface of a high-nitrogen nickel-free stainless steel vascular stent.
  • FIG. 10 is a diagram showing the morphology of the 316L stainless steel vascular stent of Example 5 after surface finishing, precision molding and surface micro-patterning.
  • Figure 10A is a stent surface topography of a 316L stainless steel blood vessel stent under a metallurgical microscope.
  • Fig. 10B is a microscopic image of the surface of a 316L stainless steel vascular stent.
  • FIG. 11 is a diagram showing the structure of a stent with a nominal diameter of 2.5 mm in Example 6.
  • FIG. 12 is a diagram showing the structure of a stent with a nominal diameter of 3.0 mm in Example 7.
  • FIG. 12 is a diagram showing the structure of a stent with a nominal diameter of 3.0 mm in Example 7.
  • FIG. 13 is a diagram showing a scanning electron micrograph of the surface of the metal platform of the stent after the roughening treatment in Example 7.
  • FIG. 13 is a diagram showing a scanning electron micrograph of the surface of the metal platform of the stent after the roughening treatment in Example 7.
  • FIG. 14 is a diagram showing a laser confocal photograph of the surface of the metal platform of the stent after the roughening treatment in Example 7.
  • FIG. 14 is a diagram showing a laser confocal photograph of the surface of the metal platform of the stent after the roughening treatment in Example 7.
  • Example 15 is a diagram showing a scanning electron micrograph of the stent surface coating of Example 7 after fatigue.
  • Figure 16 shows the ⁇ 12 ⁇ 1.1mm high-nitrogen nickel-free stainless steel solid solution pipe (N: 0.92 wt%) obtained after the seventh pass of cold deformation and heat treatment in Example 3 and its cooling process at 21%, 43%, and 66% X-ray diffraction spectrum of the deformed high-nitrogen nickel-free stainless steel pipe.
  • Fig. 17 is a graph showing the comparison results of the coating firmness on the surface of the metal platform of the stent after different surface treatments.
  • Fig. 17A shows the surface morphology of the sprayed drug coating after the stent metal platform surface is roughened and modified by the present invention after the stent is crimped and expanded.
  • Figure 17B shows the surface morphology of the stent's metal platform surface after conventional electrochemical polishing and no roughening modification but directly sprayed with a drug coating after the stent is crimped and expanded.
  • the present invention provides a high-nitrogen nickel-free austenitic stainless steel seamless thin-walled pipe, which is characterized in that the N content is 0.7-1.3% by weight, and it is a single austenite in a solid solution state and a cold deformed state below 66% Structure, with a grain size above grade 7 (including grade 7) (measured according to GB/T6394-2002 metal average grain size measurement method), wall thickness 60 ⁇ 200 ⁇ m, outer diameter dimension deviation ⁇ 0.03mm, wall thickness dimension Deviation ⁇ 0.02mm, yield strength ⁇ 600MPa, tensile strength ⁇ 1000MPa, axial elongation ⁇ 50%, pitting potential ⁇ 1000mV.
  • the above-mentioned high-nitrogen nickel-free austenitic stainless steel seamless thin-walled pipe of the present invention preferably has the following composition in weight %: Cr: 17-20%, Mn: 14-18%, Mo: 1-4%, N: 0.7-1.3%, Si: ⁇ 0.75%, Cu: ⁇ 0.25%, C: ⁇ 0.03%, Si: ⁇ 0.01%, P: ⁇ 0.025%, Ni: ⁇ 0.05%, and the balance is Fe.
  • the above-mentioned high-nitrogen nickel-free austenitic stainless steel seamless thin-walled tube of the present invention is suitable for use in the fields of medical equipment, food and drug equipment, jewelry, instrumentation, etc., and is preferably used in surgical implants.
  • the surgical implant is preferably a human luminal stent, more preferably a blood vessel stent.
  • the present invention also provides a method for preparing the above-mentioned high-nitrogen nickel-free austenitic stainless steel seamless thin-walled tube, which is characterized in that the high-nitrogen nickel-free austenitic stainless steel tube blank with a nitrogen content of less than 0.7% by weight is subjected to cold deformation and The combination of heat treatment realizes no manganese volatilization on the surface layer while forming the pipe and controlling the dimensional accuracy, and increases the nitrogen content in the pipe.
  • 2 to 3 times of cold deformation with decreasing gradient are implemented in a single pass, the cumulative deformation of the pass is less than or equal to 50%, and the single cold deformation is less than or equal to 30%, thereby controlling the dimensional accuracy of the pipe. .
  • the heat treatment is carried out after 2 to 3 cold deformations with the decreasing gradient in each pass.
  • the heat treatment temperature is 1000-1150°C.
  • the treatment time depends on the amount of furnace installed and the wall thickness of the pipe, and is between 5 and 90 minutes. between.
  • a positive pressure atmosphere of mixed gas of argon and nitrogen is applied during the heat treatment, the total cold state pressure is 0.12 to 0.30 MPa, and the partial pressure of nitrogen is 5% to 30%.
  • the nitrogen content of the pipe can be controlled within the range of 0.7-1.3% by weight, while preventing the volatilization of surface manganese.
  • the outer diameter of the pipe is ⁇ 3.0mm, cold deformation is performed 3 times per pass, and the deformation amount each time is 45-50% and 30-35% of the deformation amount of the pass. And 20-25%; when the outer diameter of the pipe is less than 3.0mm, cold deformation is performed twice per pass, and each deformation is 55-60% and 40-45% of the deformation of the pass.
  • the pipe material is subjected to the next cold deformation after mechanically removing the nitrogen-rich hard layer on the inner and outer surfaces after the heat treatment. As a result, it is possible to prevent cracking of the pipe material and introduction of foreign matter during the re-cold deformation.
  • the metal platform material of the high-safety nickel-free metal drug-eluting vascular stent of the present invention adopts high-nitrogen nickel-free austenitic stainless steel with high strength, high fatigue strength and high corrosion resistance, and its component composition is calculated by weight%: Cr: 17-20%, Mn: 14-18%, Mo: 1-3%, N: 0.8-1.2%, Si: ⁇ 0.75%, Cu: ⁇ 0.25%, C: ⁇ 0.03%, Si: ⁇ 0.01 %, P: ⁇ 0.025%, Ni: ⁇ 0.05%, the rest is Fe.
  • the stent metal platform material of the present invention In order to obtain the stent metal platform material of the present invention with high nitrogen content and at the same time suppressing the volatilization of manganese in the material, in the preparation process of the stent tube, heat treatment is used to eliminate the cold deformation stress and achieve solid solution, and at the same time, it is improved by stepwise pressure nitriding. Nitrogen content in the pipe.
  • the tensile strength of the metal platform material of the stent obtained in the present invention can reach more than 1100 MPa, and the fatigue strength is more than 570 MPa, which is much higher than the fatigue strength of the mainstream stent materials currently used in clinical practice.
  • the deformation of all the mesh wires of the stent during compression and expansion deformation is 15-25%, so that the fatigue strength of the deformed part (long-term fatigue) of the stent is increased to more than 750MPa.
  • the risk of late fracture and collapse of the stent is reduced, the long-term safety and effectiveness of the stent in the body are maximized, the stent has a longer fatigue life, and the safe service cycle of the stent is prolonged.
  • the corrosion potential of the stent metal platform material of the present invention in physiological saline and PBS buffer can reach more than 1000 mV, without the need for passivation treatment to improve its surface corrosion resistance. Because the stent metal platform material of the present invention has excellent corrosion resistance and no harmful nickel elements with sensitizing or carcinogenic effects are added to the material, after the drug coating on the surface of the stent is degraded, the metal material has high biological safety, and the stent section The risk of late restenosis is reduced.
  • the stent tube After the stent tube is formed by laser cutting, it adopts rolling line contact electrochemical polishing to realize the surface finishing and size control of the metal platform of the stent.
  • the metal platform of the support and the metal electrode are continuously rolling and linearly contacted, and the polishing liquid on the surface of the metal platform of the support is controlled by controlling the rolling speed.
  • the thinning and breaking speed of the membrane enables rapid and uniform surface finishing of the metal platform of the stent.
  • the metal electrode is selected from a dissimilar inert metal material different from the metal platform of the support, so that the metal electrode and the metal platform of the support to be polished are continuously rolling linearly.
  • the contact is conducted, and the micro-potential difference between the metal electrode and the support metal platform is used to cause the surface of the support metal platform to have a difference in the polishing amount between crystal grains, and micro-patterning is realized on the inner surface of the support metal platform.
  • the present invention changes the surface treatment (surface polishing and surface roughening) technology of the existing small-diameter pipe mesh metal sample, changing from the traditional single-point and local clamping to the rolling line contact electrochemical polishing.
  • contact rolling polishing is used to accelerate the thinning and breaking of the polishing liquid film on the surface of the sample to accelerate the smoothing and polishing of the surface of the protrusion, so as to realize the rapid surface finishing of the metal sample.
  • the rolling line contact electrochemical polishing is used to avoid the unevenness of the metal sample caused by single-point and local clamping and polishing, and the phenomenon that the structure of the metal sample after polishing deviates from the target sample structure.
  • the metal electrode selects dissimilar inert metal materials and conducts it in continuous rolling linear contact with the small-diameter pipe mesh metal sample to be polished. It is matched with an appropriate polishing voltage and uses the micro The potential difference makes the surface of the small-diameter pipe network metal sample have a difference in the polishing amount between the crystal grains, thereby realizing the micro-patterning of the inner surface of the pipe network metal sample, and improving the coating bonding strength in the subsequent coating treatment process.
  • the rolling line contact electrochemical polishing of the present invention is suitable for hollow small-diameter pipe mesh metal samples including brackets, the length of which is less than 80mm, the pipe diameter is less than 5mm, and the metal coverage rate is less than 50%.
  • the metal sample material includes stainless steel, titanium alloy, cobalt-based alloy, magnesium alloy, iron alloy, and zinc alloy, but is not limited to the foregoing alloys.
  • the dissimilar inert metal material may be platinum or tantalum, preferably platinum.
  • the current density is controlled to 0.8-1.0 A/cm 2 and the polishing temperature is 10-40°C.
  • the polishing temperature is 10-40°C.
  • the reaction speed can be reduced, and the controllability of the precision structure size can be improved, thereby facilitating the uniform polishing.
  • the volume ratio of perchloric acid to glacial acetic acid that is, perchloric acid/glacial acetic acid, is preferably 1:4 to 1:20.
  • the volume ratio of the corrosion inhibitor in the polishing liquid is preferably 2-8%, more preferably 5%.
  • the rolling speed it is preferable to control the rolling speed to 2 to 2.5 cm/s.
  • the rolling line contact electrochemical polishing of the present invention can also be applied to the surface modification of the peripheral stent, the surface modification of the digestive tract stent, and the surface modification of the urinary system stent.
  • Ultrasonic atomization spraying is used to prepare a drug coating that inhibits the proliferation of smooth muscle cells on the surface of the stent.
  • the drug coating on the surface of the stent is combined with the substrate with high strength.
  • the drug is preferably rapamycin and its derivatives.
  • the coating of the stent will not be damaged or peeled off during assembly, delivery and expansion.
  • the coating will not be severely damaged due to the fatigue of the stent and the erosion of blood flow, thereby reducing This reduces the risk of thrombosis in the initial stage of stent implantation.
  • the high-safety nickel-free metal drug-eluting vascular stent of the present invention can be used for cardiovascular and cerebrovascular and other arteries, venous vessels, etc., and is preferably used for coronary arteries.
  • a high-nitrogen nickel-free stainless steel forged bar with a nitrogen content of 0.62% by weight and a manganese content of 15.4% by weight is taken and processed by a deep hole drill to obtain a tube blank with a size of ⁇ 30 ⁇ 6mm.
  • the designed finished pipe size is ⁇ 3.0 ⁇ 0.11mm.
  • the number of cold deformation passes is 17, and the deformation per pass is 40-50%. Each pass is divided into three cold deformations, and the deformation of a single pass is 45-50%, 30-35% and 20-25% of the deformation of the pass.
  • the surface of the pipe is ultrasonically cleaned to remove surface lubricant. After drying, it is put into a heat treatment furnace that can be vacuumed and pressurized.
  • the material of the furnace is 2520 high temperature alloy. There are three temperature measuring thermocouples inside to monitor the temperature in real time. After the furnace is evacuated to 10 -1 Pa, continue to evacuate for more than 10 minutes, and then close the vacuum system valve. Fill the furnace bladder with a mixed gas of nitrogen and argon, the total pressure is 0.15MPa, the ratio of nitrogen to argon is 1:9, that is, the partial pressure of nitrogen is 10%. When the temperature of the heating furnace reaches 1100°C, send the furnace bladder into the tubular heating furnace. When the temperature of the furnace reaches 1100°C and is stable, the time will be counted. The holding time depends on the amount of furnace installed and the wall thickness of the pipe. The range is 5-60 minute. After each heat treatment, the inner and outer surfaces of the pipe are mechanically polished and polished.
  • the inspection results of the finished pipe are as follows: the outer diameter is 3.0 ⁇ 0.02mm, the wall thickness is 0.11 ⁇ 0.01mm, the nitrogen content is 0.81% by weight, the manganese content is 15.42% by weight, the yield strength is 608MPa, the tensile strength is 1019MPa, and the axial elongation is 51%.
  • the corrosion potential is 1000mV.
  • the measuring methods of yield strength, tensile strength and elongation are as follows: According to GB/T 228.1-2010 Metallic Material Tensile Test Part 1: Room Temperature Test Method, the metal pipe is subjected to tensile test with Z150 mechanical testing machine .
  • the metallographic structure of the axial section of the pipe is shown in Figure 4, which is a single austenite structure with a grain size ⁇ 7.
  • Figure 4 is a single austenite structure with a grain size ⁇ 7.
  • a high-nitrogen nickel-free stainless steel forged bar with a nitrogen content of 0.62% by weight and a manganese content of 15.4% by weight is taken and processed by a deep hole drill to obtain a tube blank with a size of ⁇ 30 ⁇ 6mm.
  • the designed finished pipe size is ⁇ 1.8 ⁇ 0.09mm.
  • the number of cold deformation passes is 21, and the deformation per pass is 40-50%.
  • each pass is divided into three cold deformations, and the deformation of each pass is 45-50%, 30-35% and 20-25% of the deformation of the pass; when the outer diameter of the pipe is less than 3.0mm , Each pass is divided into two cold deformations, and each deformation is 55-60% and 40-45% of the deformation of the pass.
  • the surface of the pipe is ultrasonically cleaned to remove surface lubricant. After drying, it is put into a heat treatment furnace that can be vacuumed and pressurized.
  • the material of the furnace is 2520 high temperature alloy. There are three temperature measuring thermocouples inside to monitor the temperature in real time.
  • the furnace After the furnace is evacuated to 10 -1 Pa, continue to evacuate for more than 10 minutes, and then close the vacuum system valve. Fill the furnace bladder with a mixed gas of nitrogen and argon, the total pressure is 0.25 MPa, and the ratio of nitrogen to argon is 1:4, that is, the partial pressure of nitrogen is 20%.
  • the temperature of the heating furnace reaches 1050°C
  • the furnace bladder is fed into the tubular heating furnace.
  • the time is counted. The holding time depends on the furnace load and the wall thickness of the pipe, ranging from 5 to 60 minute. After each heat treatment, the inner and outer surfaces of the pipe are mechanically polished and polished.
  • the inspection results of the finished pipe are as follows: outer diameter 1.8 ⁇ 0.02mm, wall thickness 0.09 ⁇ 0.01mm, nitrogen content 1.15% by weight, manganese content 15.45% by weight, yield strength 781MPa, tensile strength 1215MPa, axial elongation 56%, pitting corrosion The potential is 1090mV.
  • the methods for measuring yield strength, tensile strength, and elongation are the same as in Example 1.
  • the metallographic structure of the axial section of the pipe is shown in Figure 5, which is a single austenite structure with a grain size ⁇ 7.
  • a high-nitrogen nickel-free stainless steel forged bar with a nitrogen content of 0.62% by weight and a manganese content of 15.4% by weight is taken and processed by a deep hole drill to obtain a tube blank with a size of ⁇ 30 ⁇ 6mm.
  • the size of the designed finished pipe is ⁇ 4.5 ⁇ 0.19mm.
  • the number of cold deformation passes is 15, and the deformation per pass is 40-50%. Each pass is divided into three cold deformations, and the deformation of each pass is 45-50%, 30-35% and 20-25% of the deformation of the pass.
  • the surface of the pipe is ultrasonically cleaned to remove surface lubricant. After drying, it is put into a heat treatment furnace that can be vacuumed and pressurized.
  • the material of the furnace is 2520 high temperature alloy. There are three temperature measuring thermocouples inside to monitor the temperature in real time. After the furnace is evacuated to 10 -1 Pa, continue to evacuate for more than 10 minutes, and then close the vacuum system valve. Fill the furnace bladder with a mixed gas of nitrogen and argon, the total pressure is 0.30 MPa, and the ratio of nitrogen to argon is 1:3, that is, the partial pressure of nitrogen is 25%. When the temperature of the heating furnace reaches 1100°C, send the furnace bladder into the tubular heating furnace. When the temperature of the furnace reaches 1100°C and is stable, the time will be counted. The holding time depends on the furnace load and the wall thickness of the pipe, ranging from 15 to 60 minute. After each heat treatment, the inner and outer surfaces of the pipe are polished and polished.
  • the inspection results of the finished pipe are as follows: the outer diameter is 4.5 ⁇ 0.02mm, the wall thickness is 0.19 ⁇ 0.01mm, the nitrogen content is 1.08% by weight, the manganese content is 15.41% by weight, the yield strength is 711MPa, the tensile strength is 1112MPa, and the axial elongation is 55%.
  • the corrosion potential is 1040mV.
  • the methods for measuring yield strength, tensile strength, and elongation are the same as in Example 1.
  • the metallographic structure of the axial section of the pipe is shown in Figure 6, which is a single austenite structure with a grain size ⁇ 7.
  • the high-nitrogen nickel-free austenitic stainless steel seamless thin-walled tube of Example 2 was cut with a laser to form a coronary stent.
  • the structure of the stent is shown in FIG. 7.
  • the crimping diameter of the stent on the balloon is 0.9mm, and the expansion diameter of the stent is 2.5mm.
  • the stent needs to be pretreated by pickling before polishing to remove the oxide layer on the surface of the stent due to laser processing.
  • the goal of pretreatment is to completely remove the oxide layer on the surface of the stent and avoid the barrier of the oxide layer to the polishing liquid exchange during the electrochemical polishing process.
  • the pickling liquid is a solution with sulfuric acid and hydrogen peroxide as the main components. During the pickling process, the temperature of the pickling liquid is controlled at 10 ⁇ 50°C. After pickling, rinse the stent with a large amount of running water to remove the remaining pickling solution on the surface of the stent.
  • the surface finishing and precise shaping of the stent are realized by the electrochemical polishing of the present invention.
  • the schematic diagram of the electrochemical polishing device is shown in FIG. 8. As shown in the figure, the electrochemical polishing device of the present invention is shown in Figure 8A (front view of the polishing device) and Figure 8B (top view of the polishing device).
  • the device is mainly composed of five parts: (1) Polishing tank, which is made of polypropylene or glass, and the size can be adjusted appropriately according to the size of the polishing piece; (2) Cathode plate, which is made of stainless steel disc, is located in the polishing tank Bottom; (3) Limit cotton, made of polypropylene sponge or melamine sponge, used to limit the distance between the polishing piece and the cathode; (4) Polishing pendant or polishing fixture, made of platinum filaments, with a size of 0.8 ⁇ 1.2mm, the size depends on the inner diameter of the polishing pipe; (5) The polishing liquid, the polishing liquid immerses the cathode plate, the limit cotton and the polishing pendant, and the polishing part is completely immersed in the polishing liquid during the rolling polishing process.
  • the polishing liquid is a mixture of perchloric acid, glacial acetic acid and corrosion inhibitor.
  • the volume ratio of perchloric acid and glacial acetic acid is 1:4
  • the corrosion inhibitor accounts for 2% to 8% of the total polishing solution volume
  • the polishing temperature is 15°C
  • the cathode plate material is stainless steel
  • the metal electrode material is platinum.
  • the polishing voltage is 15V, depending on the size of the bracket.
  • the specific polishing operation is as follows: the cathode is placed at the bottom of the container containing the electrochemical polishing solution, the porous sponge-like limit plate is placed on the cathode, the platinum wire with a diameter of 0.9mm passes through the support, and the platinum wire is moved to make the support 20mm/s The linear speed rolls on the limit plate at a constant speed, and stops when the preset polishing effect is reached. After the stent is cleaned with pure water, the residual acid polishing solution on the surface of the stent is neutralized with NaOH solution.
  • the polished stent should have a smooth surface, a uniform stent mesh structure, and meet the nominal weight requirements of the stent, so as to realize the surface finishing and precise shaping of the stent.
  • the surface morphology of the high-nitrogen nickel-free stainless steel blood vessel stent after surface finishing and precise molding of this embodiment is shown in FIG. 9. It can be seen from the figure that the surface modification method of the present invention can uniformly polish the surface of the high-nitrogen nickel-free stainless steel blood vessel stent, and is therefore suitable for surface finishing and precision molding of the blood vessel stent.
  • the 316L stainless steel vascular stent needs to be pretreated by pickling before polishing to remove the oxide layer on the surface of the stent due to laser processing.
  • the goal of pretreatment is to completely remove the oxide layer on the surface of the stent to avoid the barrier of the oxide layer to the exchange of polishing liquid during the electrochemical polishing process.
  • the pickling liquid is a solution with nitric acid and hydrofluoric acid as the main components. During the pickling process, the temperature of the pickling liquid is controlled at 10 ⁇ 50°C. After pickling, rinse the stent with a large amount of running water to remove the remaining pickling solution on the surface of the stent.
  • the surface finishing and precise shaping of the stent are achieved by electrochemical polishing, and the specific electrochemical polishing method is the same as that of Example 4.
  • the polishing conditions such as the composition of the polishing liquid, the rolling speed, and the polishing time are the same as those in Example 4.
  • the polishing temperature is 15°C
  • the cathode plate is made of stainless steel
  • the metal electrode material is platinum
  • the polishing voltage is 25V, depending on the size of the bracket.
  • the polishing process adopts the continuous line contact rolling polishing method.
  • the polished stent should meet the nominal weight of the stent, and the surface of the stent should have a grain-oriented micropattern, so as to realize the surface finishing, precise molding and surface micro-patterning of the stent.
  • the surface morphology of the 316L stainless steel vascular stent after surface finishing and precise molding of this embodiment is shown in FIG. 10. It can be seen from the figure that the surface modification method of the present invention can make the surface of the 316L stainless steel blood vessel stent be uniformly polished while achieving micro-patterning, so it is suitable for surface finishing, precision molding and micro-patterning of the blood vessel stent.
  • the high-nitrogen steel bar with the composition shown in Table 1 was used to prepare the stent tube by the nitriding method described in Example 2, and the size of the tube blank was ⁇ 30 ⁇ 6mm.
  • the number of cold deformation passes is 21 times, the furnace pressure during heat treatment is 0.25MPa, the nitrogen partial pressure is 20%, the heat treatment temperature is 1050°C, and the holding time is 30 to 5 minutes.
  • the inner and outer surfaces of the pipe are mechanically polished and polished.
  • the nitrogen content in the pipe was measured with the TCH600 nitrogen, hydrogen and oxygen analyzer, and the nitrogen content of the finished pipe was 1.10% by weight.
  • the tube is cut into a coronary stent with a laser, and its structure is shown in Figure 11.
  • the crimping diameter of the stent on the balloon is 0.9mm, and the expansion diameter of the stent is 2.5mm.
  • the mesh deformation of the stent during compression and expansion is 15-25%.
  • the fatigue safety factor of the stent is 3.77.
  • the fatigue performance of the stent was tested with the RDTL-0200 stent fatigue test system. Release the stent into a semi-compliant silicone tube that matches the size of the stent.
  • the working medium in the tube is 37 ⁇ 2°C PBS buffer.
  • Pressure is pulsating inside the tube.
  • the lowest pressure is 75-80mmHg and the highest pressure is 160-165mmHg.
  • the pulsation frequency is 45Hz. After 570 million fatigue cycles (service life of 15 years), no fracture or collapse of the stent was found.
  • the stent tube was prepared by the nitriding method under the following conditions, and the size of the tube blank was ⁇ 30 ⁇ 6mm.
  • the number of cold deformation passes is 21 times, the furnace pressure during heat treatment is 0.25MPa, the nitrogen partial pressure is 20%, the heat treatment temperature is 1050°C, and the holding time is 30 to 5 minutes.
  • the inner and outer surfaces of the pipe are mechanically polished and polished.
  • the nitrogen content of the finished pipe was 1.12% by weight, the yield strength measured by the same method as in Example 6 was 782MPa, the tensile strength was 1190MPa, the axial elongation was 54%, and the pipe pitting potential was 1060mV.
  • the tube is cut into a coronary stent metal platform with a laser, and its structure is shown in Figure 12.
  • the metal platform of the obtained coronary stent is electrochemically modified as follows: the cathode is placed at the bottom of the container containing the electrochemical polishing solution, the porous sponge-like limiting plate is placed on the cathode, and the platinum wire with a diameter of 0.9mm passes through the stent and moves through the stent.
  • the platinum wire makes the stent roll on the limit plate at a linear speed of 20mm/s, and stops after reaching the preset polishing effect.
  • the residual acid polishing solution on the surface of the stent is neutralized with NaOH solution to make the stent
  • the surface of the metal platform is slightly roughened.
  • the composition of the electrochemical polishing solution is perchloric acid and glacial acetic acid, the component ratio is 1:10, the temperature of the electrochemical polishing solution is 35 ⁇ 2°C, and the electrochemical current density is 2.3A/cm 2 .
  • Figures 13 and 14 respectively show a scanning electron microscope photograph and a laser confocal photograph of the surface of the metal platform of the stent after the roughening treatment. After measurement, the height difference of the metal platform surface of the stent after the roughening treatment is about 0.2 ⁇ m. Then, rapamycin was sprayed on the surface of the stent by ultrasonic atomization.
  • Table 3 summarizes the mechanical properties of pipes under different nitrogen contents. From the results, it can be seen that as the nitrogen content increases, the strength of the material increases, and there is no essential change in plasticity. That is, Examples 1 to 3 of the present invention obtained high-manganese, high-nitrogen, nickel-free austenitic stainless steel thin-walled pipes with high dimensional accuracy, high surface quality, and excellent overall performance.
  • the high-nitrogen nickel-free stainless steel pipes are measured by X-ray diffraction spectroscopy.
  • the specific measurement method is based on JY/T 009-1996 general rules of multi-crystal X-ray diffraction method for rotating target, using Rigaku D/max 2500PC X-ray diffractometer Measure the metal pipe sample.
  • Figure 16 shows the X-ray diffraction spectrum of the high-nitrogen nickel-free stainless steel (N: 0.92% by weight) in the solid solution state and the above-mentioned three cold deformed states.
  • the (111) crystal plane, (200) crystal plane The X-ray diffraction spectrum of the (220) crystal plane is a standard austenite X-ray diffraction spectrum, and all diffraction peaks have not shifted, indicating that the material remains stable in the solid solution state and the cold deformation state of less than 66%
  • the austenitic structure That is, the high-nitrogen nickel-free austenitic stainless steel thin-walled tube obtained in the present invention is used in a cold deformed state of less than 66%, and will not affect the stability of the austenite structure.
  • the firmness index of the coating on the surface of the stent is an important evaluation index for the drug coating.
  • the coating fastness evaluation method adopted in the present invention is as follows:
  • Group I is the stent after conventional electrochemical polishing (that is, the high-nitrogen nickel-free stainless steel vascular stent after the pre-polishing surface in Example 4 is directly sprayed after conventional electrochemical polishing)
  • Drug coating conventional electrochemical polishing refers to: clamping a part of the sample with an anode, and polishing the sample by reciprocating motion
  • group II is the stent after surface roughening by rolling line contact electrochemical polishing of the present invention (That is, the high-nitrogen nickel-free stainless steel vascular stent obtained in Example 4 after surface finishing and precision molding) is directly sprayed with a drug coating. After the stent was dried for 1 day, it was sterilized by ethylene oxide and analyzed for 7 days.
  • the stent system-specific assembly equipment—vascular stent crimping machine is used to crimp and assemble the drug stents of group I and group II to form a stent system.
  • Figure 17 shows the surface morphology of the stent after being compressed and expanded after spraying a drug coating on the surface of the metal platform of the stent after different surface treatments.
  • Figure 17B when the drug coating is sprayed directly after conventional electrochemical polishing, the stent will partially fall off after expansion.
  • the coating has very good bonding performance after the surface modification of the present invention. Even after large reciprocating deformation, the coating still maintains good shape characteristics.

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Abstract

一种高氮无镍奥氏体不锈钢无缝薄壁管材、由其制得的高安全性无镍金属药物洗脱血管支架以及它们的制造方法。通过逐级渗氮的方式在制备支架管材时进一步提高材料的氮含量，得到氮含量达到0.8～1.2％的高氮无镍奥氏体不锈钢无缝薄壁管材作为支架金属平台材料。通过采用滚动线接触式电化学抛光，使支架的表面通过不同取向的晶粒形成微米级凸凹结构，提高了支架金属材料与药物涂层的结合力。该血管支架具有高疲劳寿命、高生物安全性和高药物涂层与基体结合力的特性。

Description

高氮无镍奥氏体不锈钢无缝薄壁管材、
由其制得的高安全性无镍金属药物洗脱血管支架以及它们的制造方法
技术领域
本发明涉及高氮钢管材领域，尤其涉及一种高氮无镍奥氏体不锈钢无缝薄壁管材及其制备方法，该制备方法可应用于铬-锰-氮类不锈钢薄壁管材制备。此外，本发明涉及医疗器械领域，尤其涉及具有长使用寿命和高安全性的无镍金属药物洗脱血管支架及其制造方法。
背景技术
镍是一种人体必需的微量元素，但过多摄入，会引发过敏、导致畸形、癌变和其它病变。针对镍的危害，许多国家对日用和医用金属材料中的镍含量限制越来越严格。1994年颁布的欧洲议会标准(94/27/EC)规定，植入人体内的材料中，镍含量不应超过0.05％；而长期接触人体皮肤的合金(首饰、手表、戒指、手镯等)，镍每周渗入皮肤的数量不应超过0.5μg/cm 2。鉴于镍对人体的危害，研究开发医用低镍和无镍奥氏体不锈钢已经成为国际上医用不锈钢的一个主要发展趋势。
铬-锰-氮类高氮无镍奥氏体不锈钢，是通过增加材料中锰元素含量提高氮的固溶度，从而获得稳定的奥氏体不锈钢。具有高强高韧、变形抗力大、腐蚀性能与生物学性能好等特点。
支架植入术是目前治疗血管狭窄的最有效且安全的手段，经过30多年的发展，支架植入术和支架制造技术已基本成熟。对于血管支架等产品，为取得更好的临床效果，需在支架表面制备一层药物涂层，以期在植入初期抑制血管组织的过度增生或实现快速内皮化。支架表面的药物涂层一般用超声雾化喷涂的方式获得。冠脉支架一般采用在金属支架表面制备药物涂层的方法，通过球囊扩张，使支架固定于血管靶病变部位，对病变血管起长期物理支撑的作用，参与血管的血运。 但支架植入后仍会有部分患者出现支架段再狭窄、血栓和支架晚期失效。其原因可能与下面因素有关：(1)支架植入过程和植入初期，支架表面的药物涂层脱落产生血栓；(2)支架的长期疲劳导致的支架断裂或塌陷(目前支架设计寿命为10年)；(3)金属过敏患者支架内再狭窄的发生率较高，而金属过敏者以镍过敏居多。
为进一步提高支架植入后的安全性和使用寿命，同时为了避免镍过敏引发的支架段再狭窄，材料研究者一直致力于开发更高生物安全性、更好力学性能的支架金属材料。中国科学院金属研究所自主研发了不添加有害镍元素的高氮无镍不锈钢(专利文献1)，其成分组成为：Cr：17～22％，Mn：12～20％，Mo：1～3％，Cu：0.5～1.5％，N：0.4～0.7％，Ni：≤0.02％，C：≤0.03％，Si：≤0.75％，S：≤0.01％，P:≤0.025％，Fe：余量。该材料具有高强度、高疲劳强度、高耐腐蚀和组织稳定等特点，作为植入材料具有明显的优势。
在支架结构设计和制造技术方面，人们也都在不断追求支架的支撑强度等力学性能的合理匹配，使支架具有更好的临床操作性和临床安全性。在提高药物涂层与基体的结合强度方面，支架制造者们通过表面改性、制备梯度涂层等方法，以求使支架表面的药物涂层更牢固。东北大学的“一种金属材料表面毛化处理的方法”(专利文献2)、四川大学的“具有微米-纳米粗糙结构表面的钛或钛合金材料及制备方法”(专利文献3)等技术对于提高表面积、增加支架与涂层结合牢固度均具有一定的作用。
电化学抛光是较为成熟且普遍应用的金属抛光技术，尤其适用于小型样件、异形样件和不可受力样件的抛光。目前，小口径管网状样件如医疗器械的血管支架及其它管腔支架、仪器仪表用的小型弹簧等，均采用电化抛光的方式来提高表面质量和控制尺寸精度。一般这种样件为镂空结构，样件只有部分金属网丝结构覆盖，称为金属覆盖率。本发明所说的小口径管网状样件的金属覆盖率低于50％，以保证抛光 过程中管内充分的溶液交换。小口径管网状样件的抛光一般采用图1所示的方法，具体而言，用阳极夹持样件局部，通过往复运动实现样件的抛光。
现有技术文献
专利文献
专利文献1：CN1519387A
专利文献2：CN101255593A
专利文献3：CN103668390A
发明内容
发明所要解决的问题
对于铬-锰-氮类高氮无镍奥氏体不锈钢而言，由于锰的饱和蒸气压很高，材料在进行高温热处理时，锰会从约束力较低的自由表面挥发，在表面形成贫锰层。图2示出了管材表面形成贫锰层的金相照片。在用于血管支架的薄壁管材的制备过程中，随着热处理次数的增加，管材表面贫锰层不断变厚，当壁厚与贫锰层达到一定比例时，管材开裂。图3示出了管材表面严重贫锰发生开裂的金相照片。
另外，薄壁管材的制备中必然经历形变和热处理这两个过程。由于材料变形抗力大，常规工艺制备的管材难以实现高尺寸精度且易产生裂纹。而且，普通热处理工艺会导致管材表面形成贫锰层，改变表面材料成分、表面不能形成稳定奥氏体且会导致变形过程中的开裂。由此，产品难以满足血管支架领域对不锈钢管材高精度、高稳定性的要求。鉴于上述方面，专利文献1的高氮无镍不锈钢仍存在改善的余地。
上述专利文献2和专利文献3记载的表面处理工艺对于网丝只有0.08～0.1mm的管网状支架难以得理想的效果。因此，迫切需要寻求更适用于支架制造技术的表面粗糙技术。
此外，对于上述图1所示的现有的小口径管网状样件的抛光方法，主要存在如下问题：(1)样件与电极间由于接触问题会发生局部电流过大导致网丝断裂；(2)点接触导致抛光不均匀，尤其是样件较长时会发生近电极端与远电极端的明显区别。对于弹簧和血管支架等，上述问题会直接导致产品力学性能的不一致，甚至可能造成产品的失效。
鉴于现有技术所存在的上述问题，本发明的目的在于，提供一种高锰(Mn≥10重量％)高氮(N：0.7～1.3重量％)无镍(Ni≤0.05重量％)奥氏体不锈钢无缝薄壁管材，并且，提供该高氮无镍奥氏体不锈钢无缝薄壁管材的尺寸精度高、氮含量及锰含量可控的制备方法。此外，本发明的目的还在于提供具有更长使用寿命和更高安全性的血管支架及其制造方法。
用于解决问题的方法
为解决上述问题，本发明人对于用于支架管材的高氮无镍奥氏体不锈钢无缝薄壁管材以及支架金属平台的表面处理方法进行了深入研究，首次得到了以下的(1)～(5)的发现。
(1)针对材料高强高变形抗力的特点，采用单道次梯度递减多次冷变形可在控制管材尺寸精度的同时避免形成微裂纹。
(2)在热处理过程中，通过施加炉内保护气氛正压可实现管材表面层无锰挥发，同时通过施加氮分压可调控材料中的氮含量及管材综合性能。
(3)在管材热处理后机械清除热处理所带来的内外表面富氮硬质层后再进行下一道次冷变形，可以防止冷变形过程中管材开裂和外来物引入。
(4)通过采用滚动线接触的方式实现电极与小口径管网状样件(例如，支架金属平台)的导通，小口径管网状样件上的所有点与电极的接触力和接触时间均匀一致，从而能够保证小口径管网状样件的均匀抛光，由此实现小口径管网状样件的表面精整、精准控制网丝尺寸。
(5)进而，通过利用电极材料与小口径管网状样件的微电位差，能够在抛光过程中同步实现小口径管网状样件的表面微图案化。由此，在不引入外来物质和不影响样件整体性能的前提下，通过表面微图案化，提高小口径管网状样件与药物涂层的结合牢固度。
由此，利用高氮无镍不锈钢材料的高疲劳强度、高耐腐蚀性能、高组织稳定性以及不含有害镍元素的特性，并进一步通过支架结构设计以及支架金属平台表面的抛光、粗糙化处理工艺，能够得到具有更长使用寿命和更高安全性的血管支架。
本发明是基于以上的发现而完成的，即，本发明的主旨如下。
1.一种高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，
N含量为0.7～1.3重量％，在固溶状态和66％以下冷变形状态下为单一奥氏体组织，晶粒度≥7级，
所述管材的壁厚60～200μm，外径尺寸偏差±0.03mm，壁厚尺寸偏差±0.02mm，屈服强度≥600MPa，抗拉强度≥1000MPa，轴向延伸率≥50％，点蚀电位≥1000mV。
2.根据上述1所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，以重量％计，具有如下成分组成：Cr：17～20％、Mn：14～18％、Mo：1～4％、N：0.7～1.3％、Si：≤0.75％、Cu：≤0.25％、C：≤0.03％、Si：≤0.01％、P：≤0.025％、Ni：≤0.05％，余量为Fe。
3.根据上述1或2所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，该管材用于医疗器械、食品药品器械、首饰、仪器仪表领域。
4.根据上述1～3中任一项所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，该管材用于外科植入物。
5.根据上述4所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，所述外科植入物为人体管腔支架。
6.根据上述5所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，所述人体管腔支架为血管支架。
7.上述1～6中任一项所述的高氮无镍奥氏体不锈钢无缝薄壁管材的制备方法，其特征在于，将氮含量＜0.7重量％的高氮无镍奥氏体不锈钢管坯，通过冷变形和热处理相结合的方式，在管材成型和控制尺寸精度的同时实现表面层无锰挥发，并提高管材中的氮含量，
在单道次内，实施梯度递减的2～3次冷变形，道次累计变形量≤50％，单次冷变形量≤30％，
在每道次实施所述梯度递减的2～3次冷变形后实施热处理，所述热处理温度为1000～1150℃，处理时间为5～90分钟。
8.根据上述7所述的制备方法，其特征在于，在所述热处理过程中施加氩气和氮气混合气体的正压气氛，冷态总气压为0.12～0.30MPa，氮气分压为5％～30％。
9.根据上述7或8所述的制备方法，其特征在于，管材外径≥3.0mm时，每道次实施3次冷变形，每次变形量依次为该道次变形量的45～50％、30～35％和20～25％；管材外径＜3.0mm时，每道次实施2次冷变形，每次变形量依次为该道次变形量的55～60％和40～45％。
10.根据上述7～9中任一项所述的制备方法，其特征在于，管材在热处理后机械清除内外表面富氮硬质层后再进行下一道次冷变形。
11.一种无镍金属药物洗脱血管支架，其特征在于，
所述支架的金属平台材料为高氮无镍奥氏体不锈钢，该金属平台 材料的成分组成以重量％计为：Cr：17～20％，Mn：14～18％，Mo：1～3％，N：0.8～1.2％，Si：≤0.75％，Cu：≤0.25％，C：≤0.03％，Si：≤0.01％，P：≤0.025％，Ni：≤0.05％，Fe：余量，
所述金属平台材料的抗拉强度为1100MPa以上，固溶态时的疲劳强度为570MPa以上，20％冷变形时的疲劳强度为750MPa以上，
所述金属平台材料在生理盐水和PBS缓冲液中的点蚀电位为1000mV以上，
并且，所述金属平台材料在冷变形量达50％时，仍具有单一奥氏体组织，晶粒度≥7级。
12.根据上述11所述的无镍金属药物洗脱血管支架，其中，所述支架的所有变形点在压握和扩张变形时的变形量为15～25％，所述支架变形部位的疲劳强度为750MPa以上。
13.根据上述11或12所述的无镍金属药物洗脱血管支架，其中，在所述支架金属平台的表面，不同取向的晶粒形成微米级凸凹结构，晶粒间的高度差为0.1～0.5μm。
14.根据上述11～13中任一项所述的无镍金属药物洗脱血管支架，其用于心脑血管。
15.根据上述14所述的无镍金属药物洗脱血管支架，其用于冠状动脉。
16.一种无镍金属药物洗脱血管支架的制造方法，其特征在于，在支架管材制备时，将氮含量＜0.7重量％的高氮无镍奥氏体不锈钢管坯，通过冷变形和热处理相结合的方式，在管材成型和控制尺寸精度的同时，提高管材中的氮含量至0.8～1.2％并实现表面层无锰挥发，
在单道次内，实施梯度递减的2～3次冷变形，道次累计变形量≤50％，单次冷变形量≤30％，
在每道次实施所述梯度递减的2～3次冷变形后实施热处理，所述热处理温度为1000～1150℃，处理时间为5～90分钟。
17.根据上述16所述的无镍金属药物洗脱血管支架的制造方法，其中，所述热处理温度为1045～1055℃，施加的气氛中的氮分压为5～30％，其余为惰性气体，炉内压力为1.5～3atm。
18.根据上述16或17所述的无镍金属药物洗脱血管支架的制造方法，其中，管材外径≥3.0mm时，每道次实施3次冷变形，每次变形量依次为该道次变形量的45～50％、30～35％和20～25％；管材外径＜3.0mm时，每道次实施2次冷变形，每次变形量依次为该道次变形量的55～60％和40～45％。
19.根据上述16～18中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，用激光将所述管材切割成支架金属平台，采用滚动线接触式电化学抛光，将所述支架金属平台与金属电极连续滚动线性接触，通过控制滚动速度，控制支架金属平台表面凸起处的抛光液膜的减薄和破膜速度，对该支架金属平台进行表面精整，
同时，所述金属电极选择不同于所述支架金属平台的异种惰性金属材料，使所述金属电极与所述支架金属平台以连续滚动线性接触的方式导通，利用所述金属电极与该支架金属平台之间的微电位差，使该支架金属平台的表面通过不同取向的晶粒形成微米级凸凹结构，晶粒间的高度差为0.1～0.5μm。
20.根据上述19所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，电流密度控制在0.8～1.0A/cm 2。
21.根据上述19或20所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，电化学处理温度控制在10～40℃。
22.根据上述19～21中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，电化学抛光液的成分包括高氯酸、冰乙酸以及缓蚀剂，高氯酸与冰乙酸的体积比、即高氯酸/冰乙酸为1：4～1：20，缓蚀剂在抛光液中的体积比例为2～8％。
23.根据上述19～22中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，抛光滚动速度控制在2～2.5cm/s。
24.根据上述19～23中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，所述异种惰性金属材料为铂金或钽。
25.根据上述19～24中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，所述异种惰性金属材料为铂金。
发明效果
根据本发明，可以提供高尺寸精度、高表面质量的综合性能优良的高锰高氮无镍奥氏体不锈钢薄壁管材及其制备方法。
此外，根据本发明，支架金属平台材料采用了具有高疲劳性能和高腐蚀性能的通过逐级渗氮的方式得到的高氮无镍不锈钢材料，由此，使支架金属平台具有高的力学性能和疲劳强度，从而使支架具有更高的疲劳寿命。
而且，支架金属平台材料采用高氮无镍奥氏体不锈钢，材料中不主动添加具有致敏、致癌作用的有害镍元素，且材料具有优异的耐腐蚀性能，由此，降低了支架表面药物涂层降解后金属离子溶出或镍过敏可能引发的再狭窄风险。
通过控制支架变形点的变形量的结构设计，进一步提高了支架的疲劳强度，使支架的服役周期更长。
通过采用滚动线接触式电化学抛光，可以快速实现支架金属平台这样的小口径管网状金属样件的表面精整，由此，可以大大提高支架金属平台的表面抛光效率以及表面抛光品质。而且，通过本发明的滚动线接触式电化学抛光方法，可以实现支架金属平台的精准控尺，该方法可以大大降低这种精密金属样件的废品率。
此外，通过滚动线接触式电化学抛光对支架金属平台表面进行粗糙化，通过不同取向的晶粒形成微米级凸凹结构，增加了支架金属平台与药物涂层的结合力，使支架表面的药物涂层能够更好的抵抗变形及疲劳可能导致的破坏。由此，支架在变形、输送和服役过程中涂层不易脱落，降低了支架植入初期产生血栓的风险。而且，与利用腐蚀的化学方式的表面粗糙化方法相比，由于本发明的表面粗糙化方法无需引入外来物质，因此安全性更高。此外，本发明的表面粗糙化方法还不存在如毛化、喷砂等物理方式的表面粗糙化方法导致的疲劳寿命降低的问题。
本发明的高安全性无镍金属药物洗脱血管支架由于具有如上高寿命、低风险的特性，因此有望提高植入患者的生存质量，造福社会。
附图说明
图1是示出现有的小口径管网状样件的抛光方法的示意图。
图2是管材表面形成贫锰层的金相照片。
图3是管材表面严重贫锰发生开裂的金相照片。
图4是示出实施例1的Φ3.0×0.11mm管材轴向剖面的金相组织照片。其为依据GB/T 6397-2017金属平均晶粒度测量方法，用Zeiss Observer Z1M金相显微镜拍摄的放大倍数为100倍的金相组织照片。
图5是示出实施例2的Φ1.8×0.09mm管材轴向剖面的金相组织照 片。其为依据GB/T 6397-2017金属平均晶粒度测量方法，用Zeiss Observer Z1M金相显微镜拍摄的放大倍数为100倍的金相组织照片。
图6是示出实施例3的Φ4.5×0.19mm管材轴向剖面的金相组织照片。其为依据GB/T 6397-2017金属平均晶粒度测量方法，用Zeiss Observer Z1M金相显微镜拍摄的放大倍数为100倍的金相组织照片。
图7是示出实施例4的标称直径2.5mm的支架结构的图。
图8是示出本发明的滚动式线接触式电化学抛光装置的示意图。图8A为该抛光装置的主视图。图8B为该抛光装置的俯视图。
图9是示出实施例4中采用本发明的方法进行表面修饰后的高氮无镍不锈钢血管支架表面的宏观与微观形貌的图。图9A和图9B为高氮无镍不锈钢血管支架表面的宏观形貌图，其中，图9B为图9A的局部放大图。图9C为高氮无镍不锈钢血管支架表面的微观形貌图。
图10是示出实施例5的316L不锈钢血管支架的表面精整、精准成型和表面微图案化后的形貌的图。图10A为316L不锈钢血管支架在金相显微镜下的支架表面形貌图。图10B为316L不锈钢血管支架表面的微观形貌图。
图11是示出实施例6的标称直径2.5mm的支架结构的图。
图12是示出实施例7的标称直径3.0mm的支架结构的图。
图13是示出实施例7的经粗糙化处理后的支架金属平台表面的扫描电镜照片的图。
图14是示出实施例7的经粗糙化处理后的支架金属平台表面的激光共聚焦照片的图。
图15是示出实施例7的支架表面涂层疲劳后的扫描电镜照片的图。
图16是实施例3中第七道次冷变形及热处理后得到的Φ12×1.1mm高氮无镍不锈钢固溶态管材(N：0.92重量％)及其经21％、43％、66％冷变形后的高氮无镍不锈钢管材的X射线衍射谱。
图17是示出经不同表面处理后的支架金属平台表面的涂层牢固度对比结果的图。图17A示出了支架金属平台表面经本发明的粗糙化修饰后喷涂的药物涂层在支架压握扩张后的表面形貌。图17B示出了 支架金属平台表面经常规电化学抛光后不经粗糙化修饰而直接喷涂的药物涂层在支架压握扩张后的表面形貌。
具体实施方式
本发明提供一种高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，N含量为0.7～1.3重量％，在固溶状态和66％以下冷变形状态下均为单一奥氏体组织，具有7级以上(含7级)的晶粒度(依据GB/T6394-2002金属平均晶粒度测定方法测得)，壁厚60～200μm，外径尺寸偏差±0.03mm，壁厚尺寸偏差±0.02mm，屈服强度≥600MPa，抗拉强度≥1000MPa，轴向延伸率≥50％，点蚀电位≥1000mV。
本发明的上述高氮无镍奥氏体不锈钢无缝薄壁管材优选以重量％计具有如下成分组成：Cr：17～20％、Mn：14～18％、Mo：1～4％、N：0.7～1.3％、Si：≤0.75％、Cu：≤0.25％、C：≤0.03％、Si：≤0.01％、P：≤0.025％、Ni：≤0.05％，余量为Fe。
本发明的上述高氮无镍奥氏体不锈钢无缝薄壁管材适合用于医疗器械、食品药品器械、首饰、仪器仪表等领域，优选用于外科植入物。该外科植入物优选为人体管腔支架，更优选为血管支架。
本发明还提供了上述高氮无镍奥氏体不锈钢无缝薄壁管材的制备方法，其特征在于，将氮含量＜0.7重量％的高氮无镍奥氏体不锈钢管坯，通过冷变形和热处理相结合的方式，在管材成型和控制尺寸精度的同时实现表面层无锰挥发，并提高管材中的氮含量。在该制备方法中，针对材料特性，在单道次内实施梯度递减的2～3次冷变形，道次累计变形量≤50％，单次冷变形量≤30％，由此控制管材尺寸精度。在每道次实施所述梯度递减的2～3次冷变形后实施热处理，所述热处理温度为1000～1150℃，处理时间视装炉量和管材壁厚而定，介于5～90分钟之间。
本发明的上述制备方法中，优选的是，在所述热处理过程中施加氩气和氮气混合气体的正压气氛，冷态总气压为0.12～0.30MPa，氮气分压为5％～30％。通过调节保护气氛的总气压和氮分压，能够在实现管材氮含量在0.7～1.3重量％范围内可控的同时，防止表面锰挥发。
本发明的上述制备方法中，优选的是，管材外径≥3.0mm时，每道次实施3次冷变形，每次变形量依次为该道次变形量的45～50％、30～35％和20～25％；管材外径＜3.0mm时，每道次实施2次冷变形，每次变形量依次为该道次变形量的55～60％和40～45％。
本发明的上述制备方法中，优选的是，管材在热处理后机械清除内外表面富氮硬质层后再进行下一道次冷变形。由此，能够防止再次冷变形时管材开裂和外来物引入。
本发明的高安全性无镍金属药物洗脱血管支架的金属平台材料采用具有高强度、高疲劳强度和高耐腐蚀性能的高氮无镍奥氏体不锈钢，其成分组成以重量％计为：Cr：17～20％，Mn：14～18％，Mo：1～3％，N：0.8～1.2％，Si：≤0.75％，Cu：≤0.25％，C：≤0.03％，Si：≤0.01％，P：≤0.025％，Ni：≤0.05％，其余为Fe。
为了得到氮含量高且同时抑制了材料中锰挥发的上述本发明的支架金属平台材料，在支架管材制备过程中，在热处理消除冷变形应力实现固溶的同时，通过逐级加压渗氮提高管材中的氮含量。由此，得到的本发明的支架金属平台材料的抗拉强度可达1100MPa以上，疲劳强度为570MPa以上，远高于目前临床使用的主流支架材料的疲劳强度。
通过支架结构设计，使支架的所有网丝在压握和扩张变形时的变形量为15～25％，从而使支架变形部位(长期疲劳)的疲劳强度提高至750MPa以上。由此，降低了支架晚期断裂和塌陷的风险，最大限度 的提高了支架在体内的长期安全性和有效性，使支架具有更长的疲劳寿命，延长了支架的安全服役周期。
此外，本发明的支架金属平台材料在生理盐水和PBS缓冲液中的腐蚀电位可达到1000mV以上，无需通过钝化处理提高其表面耐腐蚀性能。由于本发明的支架金属平台材料具有优异的耐腐蚀性能且材料中不添加具有致敏、致癌作用的有害镍元素，在支架表面药物涂层降解后，金属材料具有高的生物安全性，支架段晚期再狭窄的风险得以降低。
支架管材经激光切割成型后采用滚动线接触式电化学抛光的方式实现支架金属平台的表面精整和尺寸控制。本发明的适用于小口径管网状金属样件的滚动线接触式电化学抛光中，支架金属平台与金属电极连续滚动线性接触，通过控制滚动速度，控制支架金属平台表面凸起处的抛光液膜的减薄和破膜速度，对该支架金属平台进行快速均匀地表面精整。更优选的是，本发明的滚动线接触式电化学抛光中，所述金属电极选择不同于所述支架金属平台的异种惰性金属材料，使所述金属电极与待抛光支架金属平台以连续滚动线性接触的方式导通，利用所述金属电极与该支架金属平台之间的微电位差，使该支架金属平台的表面出现晶粒间抛光量差异，在该支架金属平台内表面实现微图案化。
本发明改变了现有小口径管网状金属样件的表面处理(表面抛光和表面粗糙化)技术，由传统的单点、局部夹持，变为滚动式线接触式电化学抛光。首先，采用接触式滚动抛光，通过加速样件表面凸起处的抛光液膜的减薄和破膜，起到加速表面凸起部位平整、抛光的目的，从而实现金属样件的快速表面精整。其次，采用滚动式线接触式电化学抛光，避免因单点、局部夹持抛光引起的金属样件不均匀，以及避免抛光后金属样件结构偏离目标样件结构的现象。
此外，金属电极选择异种惰性金属材料并与待抛光小口径管网状金属样件以连续滚动线性接触的方式导通，以适当的抛光电压相配合，利用金属电极与金属抛光件之间的微电位差，使小口径管网状金属样件的表面出现晶粒间抛光量差异，从而实现管网状金属样件内表面的微图案化，提高后续涂层处理工艺中的涂层结合强度。
本发明的滚动线接触式电化学抛光适用于包括支架在内的镂空的小口径管网状金属样件，其长度小于80mm，管径小于5mm，金属覆盖率低于50％。并且，该金属样件材料包括：不锈钢、钛合金、钴基合金、镁合金、铁合金、锌合金，但不限于上述合金。
本发明的滚动线接触式电化学抛光中，异种惰性金属材料可以为铂金、钽，优选为铂金。
本发明的滚动线接触式电化学抛光中，优选电流密度控制在0.8～1.0A/cm 2、抛光温度为10～40℃。通过在10～40℃这样的低温下进行抛光，能够降低反应速度，提高精密结构尺寸可控性，从而有利于抛光的均匀进行。另外，本发明的滚动线接触式电化学抛光中，优选使用成分包括高氯酸、冰乙酸以及缓蚀剂的抛光液。该抛光液中，高氯酸与冰乙酸的体积比、即高氯酸/冰乙酸优选为1：4～1：20。此外，优选缓蚀剂在抛光液中的体积比例为2～8％，更优选为5％。通过控制抛光液成分、抛光电流密度和反应温度，使支架金属平台表面光滑。同时通过控制电极电位，使不同取向的晶粒具有不同的抛光量，实现支架金属平台表面的微粗糙化，形成0.1～0.5μm的高度差，由此增加了支架金属平台与药物涂层的结合力。
此外，本发明的滚动线接触式电化学抛光中，优选将滚动速度控制在2～2.5cm/s。
本发明的滚动线接触式电化学抛光除了可以应用于血管支架的表 面修饰之外，还可以应用于外周支架的表面修饰、消化道支架的表面修饰、泌尿系统支架的表面修饰，尺寸较大的金属导管的表面修饰，以及骨填充用骨笼的表面修饰等。
采用超声雾化喷涂的方式在支架表面制备具有抑制平滑肌细胞增生的药物涂层，通过控制喷涂工艺和前述支架金属平台表面粗糙化，使支架表面的药物涂层与基体以高强度结合。药物优选雷帕霉素及其衍生物。由此，支架在装配、输送和扩张过程中涂层不会发生破坏或脱落，而且，支架在内皮包覆前，不会因支架的疲劳和血流的冲刷而发生涂层严重破坏，从而降低了支架植入初期产生血栓的风险。
本发明的高安全性无镍金属药物洗脱血管支架可用于心脑血管和其它动脉、静脉血管等，优选用于冠状动脉。
以下，基于实施例对本发明进行详细说明。但实施例只不过是本发明的例示，不对本发明的范围进行限定。
实施例1 高氮无镍奥氏体不锈钢无缝薄壁管材1
取氮含量为0.62重量％、锰含量为15.4重量％的高氮无镍不锈钢锻造态棒材，经深孔钻机加工制得管坯，管坯尺寸为Φ30×6mm。设计成品管材尺寸为Φ3.0×0.11mm。冷变形道次为17，每道次变形量为40～50％。每道次分三次冷变形，单次变形量依次为该道次变形量的45～50％、30～35％和20～25％。每道次冷变形后对管材表面进行超声清洗，去除表面润滑剂。干燥后装入可抽真空和加压的热处理炉胆内，炉胆材料为2520高温合金，内有三个测温热偶实时监测温度。炉胆内抽真空至10 -1Pa后持续抽气10分钟以上，关闭抽真空系统阀门。向炉胆内充入氮气与氩气的混合气体，总气压为0.15MPa，氮气与氩气比例为1:9，即氮分压为10％。当加热炉温度达到1100℃时，将炉胆送入管式加热炉内，待炉胆温度达到1100℃并稳定时计时，保温时间根据装炉量和管材壁厚而定，范围为5～60分钟。在每道次热处理后，对管材 进行内外表面机械磨抛处理。
成品管材检验结果如下：外径3.0±0.02mm，壁厚0.11±0.01mm，氮含量为0.81重量％，锰含量15.42重量％，屈服强度608MPa、抗拉强度1019MPa、轴向延伸率51％，点蚀电位1000mV。其中，屈服强度、抗拉强度以及延伸率的测定方法如下所述：依据GB/T 228.1-2010金属材料拉伸试验第1部分：室温试验方法，用Z150力学试验机对金属管材进行拉伸试验。管材轴向剖面金相组织如图4所示，为单一奥氏体组织，晶粒度≥7级。并且，依据“GB/T3505-2009、GB/T1031-2009、GB/T10610-2009”标准，用Alpha-Step IQ接触式表面形貌仪，对管材的内、外表面粗糙度进行测定，测定结果分别为Ra 内＝0.046μm、Ra 外＝0.039μm。
实施例2 高氮无镍奥氏体不锈钢无缝薄壁管材2
取氮含量为0.62重量％、锰含量为15.4重量％的高氮无镍不锈钢锻造态棒材，经深孔钻机加工制得管坯，管坯尺寸为Φ30×6mm。设计成品管材尺寸为Φ1.8×0.09mm。冷变形道次为21，每道次变形量为40～50％。管材外径≥3.0mm时，每道次分三次冷变形，每次变形量依次为该道次变形量的45～50％、30～35％和20～25％；管材外径＜3.0mm时，每道次分两次冷变形，每次变形量依次为该道次变形量的55～60％和40～45％。每道次冷变形后对管材表面进行超声清洗，去除表面润滑剂。干燥后装入可抽真空和加压的热处理炉胆内，炉胆材料为2520高温合金，内有三个测温热偶实时监测温度。炉胆内抽真空至10 -1Pa后持续抽气10分钟以上，关闭抽真空系统阀门。向炉胆内充入氮气与氩气的混合气体，总气压为0.25MPa，氮气与氩气比例为1:4，即氮分压为20％。当加热炉温度到达1050℃时，将炉胆送入管式加热炉内，待炉胆温度达到1050℃并稳定时计时，保温时间根据装炉量和管材壁厚而定，范围为5～60分钟。在每道次热处理后，对管材进行内外表面机械磨抛处理。
成品管材检验结果如下：外径1.8±0.02mm，壁厚0.09±0.01mm，氮含量1.15重量％，锰含量15.45重量％，屈服强度781MPa、抗拉强度1215MPa、轴向延伸率56％，点蚀电位1090mV。其中，屈服强度、抗拉强度以及延伸率的测定方法与实施例1中相同。管材轴向剖面金相组织如图5所示，为单一奥氏体组织，晶粒度≥7级。并且，按照实施例1中所述的粗糙度测定方法测得的管材的内表面粗糙度Ra 内＝0.07μm、外表面粗糙度Ra 外＝0.05μm。
实施例3 高氮无镍奥氏体不锈钢无缝薄壁管材3
取氮含量为0.62重量％、锰含量为15.4重量％的高氮无镍不锈钢锻造态棒材，经深孔钻机加工制得管坯，管坯尺寸为Φ30×6mm。设计成品管材尺寸为Φ4.5×0.19mm。冷变形道次为15，每道次变形量为40～50％。每道次分三次冷变形，每次变形量依次为该道次变形量的45～50％、30～35％和20～25％。每道次冷变形后对管材表面进行超声清洗，去除表面润滑剂。干燥后装入可抽真空和加压的热处理炉胆内，炉胆材料为2520高温合金，内有三个测温热偶实时监测温度。炉胆内抽真空至10 -1Pa后持续抽气10分钟以上，关闭抽真空系统阀门。向炉胆内充入氮气与氩气的混合气体，总气压为0.30MPa，氮气与氩气比例为1:3，即氮分压为25％。当加热炉温度到达1100℃时，将炉胆送入管式加热炉内，待炉胆温度达到1100℃并稳定时计时，保温时间根据装炉量和管材壁厚而定，范围为15～60分钟。在每道次热处理后，对管材进行内外表面磨抛处理。
成品管材检验结果如下：外径4.5±0.02mm，壁厚0.19±0.01mm，氮含量为1.08重量％，锰含量15.41重量％，屈服强度711MPa、抗拉强度1112MPa、轴向延伸率55％，点蚀电位1040mV。其中，屈服强度、抗拉强度以及延伸率的测定方法与实施例1中相同。管材轴向剖面金相组织如图6所示，为单一奥氏体组织，晶粒度≥7级。并且，按照实施例1中所述的粗糙度测定方法测得的管材的内表面粗糙度Ra 内＝0.058μm、外表面粗糙度Ra 外＝0.053μm。
实施例4 高氮无镍不锈钢血管支架的表面精整和精准成型
(1)高氮无镍不锈钢血管支架的抛光前表面预处理
用激光将实施例2的高氮无镍奥氏体不锈钢无缝薄壁管材切割成冠脉支架，支架结构如图7所示。支架在球囊上的压握直径为0.9mm，支架扩张直径为2.5mm。该支架抛光前需要通过酸洗预处理，去除支架表面因激光加工产生的氧化层。预处理目标是全部去除支架表面的氧化层，避免电化学抛光过程中氧化层对抛光液交换的阻隔。酸洗液为以硫酸和双氧水为主要组成成分的溶液。酸洗过程中控制酸洗液温度在10～50℃。酸洗后用大量流水冲洗支架，以除去支架表面残留的酸洗液。
(2)高氮无镍不锈钢血管支架的表面精整和精准成型
支架表面精整和精准成型是通过本发明的电化学抛光实现的，电化学抛光装置示意图见图8。如图所示，本发明的电化学抛光装置由图8A(抛光装置主视图)和图8B(抛光装置俯视图)来展现。该装置主要由五部分组成，(1)抛光槽，材质为聚丙烯材质或玻璃材质的抛光槽，尺寸可根据抛光件的大小适当调整；(2)阴极板，材质为不锈钢圆板位于抛光槽底部；(3)限位棉，材质为聚丙烯海绵或密胺海绵等，用于限制抛光件与阴极间的距离；(4)抛光挂件或称抛光夹具，材质为铂金细丝，尺寸在0.8～1.2mm，尺寸依抛光管件内径而定；(5)抛光液，抛光液浸没阴极板、限位棉和抛光挂件，抛光件滚动抛光过程保持抛光件完全浸没在抛光液中。
本发明的电化学抛光中，抛光液为高氯酸、冰乙酸和缓蚀剂的混合物。其中，高氯酸与冰乙酸的体积比为1：4，缓蚀液占总抛光液体积的2％～8％，抛光温度为15℃，阴极板材质为不锈钢金属，金属电极材料为铂金，抛光电压为15V，依支架尺寸大小而定。
具体抛光操作为：阴极置于盛有电化学抛光液的容器底部，阴极 上放置多孔海绵状限位板，直径为0.9mm的铂丝穿过支架，通过移动铂丝，使支架以20mm/s的线速度在限位板上匀速滚动，到达预设抛光效果后停止，纯净水清洗支架后，再用NaOH溶液中和支架表面的残余酸性抛光液。抛光后的支架应表面光滑、支架网丝结构均匀、并满足支架标称重量要求，从而实现支架的表面精整和精准成型。
(3)高氮无镍不锈钢血管支架表面精整和精准成型后的形貌
本实施例的经表面精整和精准成型后的高氮无镍不锈钢血管支架表面形貌如图9所示。由该图可知，本发明的表面修饰方法可以使高氮无镍不锈钢血管支架表面被均匀抛光，因此适用于血管支架的表面精整和精密成型。
实施例5 316L不锈钢血管支架的表面精整、精准成型和表面微图案化
(1)316L不锈钢血管支架的抛光前表面预处理
316L不锈钢血管支架抛光前需要通过酸洗预处理，去除支架表面因激光加工产生的氧化层。预处理目标是全部去除支架表面的氧化层，避免电化学抛光过程中，氧化层对抛光液交换的阻隔。酸洗液为以硝酸和氢氟酸为主要组成成分的溶液。酸洗过程中控制酸洗液温度在10～50℃。酸洗后用大量流水冲洗支架，以除去支架表面残留的酸洗液。
(2)316L不锈钢血管支架的表面精整、精准成型和表面微图案化
支架表面精整和精准成型是通过电化学抛光实现的，具体电化学抛光方法与实施例4相同。抛光液成分组成、滚动速度、抛光时间等抛光条件与实施例4中相同。抛光温度为15℃，阴极板材质为不锈钢金属，金属电极材料为铂金，抛光电压为25V，依支架尺寸大小而定。抛光过程采用连续线接触滚动抛光的方式，抛光后的支架应满足支架标称重量要求，支架表面出现晶粒取向微图案，从而实现支架的表面 精整、精准成型和表面微图案化。
(3)316L不锈钢血管支架表面精整和精准成型后的形貌
本实施例的经表面精整和精准成型后的316L不锈钢血管支架表面形貌如图10所示。由该图可知，本发明的表面修饰方法可以使316L不锈钢血管支架表面在被均匀抛光的同时实现微图案化，因此适用于血管支架的表面精整、精密成型和微图案化。
实施例6
用表1所示成分的高氮钢棒材，采用实施例2所述的渗氮方法制备支架管材，管坯尺寸为Φ30×6mm。冷变形道次为21次，热处理时炉内压力0.25MPa，氮分压为20％，热处理温度1050℃，保温时间30～5分钟。在每道次热处理后，对管材进行内外表面机械磨抛。依据GB/T20124钢铁氮含量的测定惰性气体熔融热导法(常规方法)，用TCH600氮氢氧分析仪测定管材中的氮含量，测得成品管材氮含量为1.10重量％。依据GB/T 228.1-2010金属材料拉伸试验第1部分：室温试验方法，用Z150力学试验机对成品管材的拉伸性能进行了测定，测得成品管材的屈服强度为761MPa、抗拉强度为1215MPa、轴向延伸率为56％。依据YY/T 1074外科植入物不锈钢产品点蚀电位，用GAMRY Reference600电化学工作站进行了电化学腐蚀分析，测得管材点蚀电位1090mV。
表1.支架管材制备中使用的棒材的化学成分
Figure PCTCN2020125095-appb-000001
用激光将该管材切割成冠脉支架，其结构如图11所示。支架在球囊上的压握直径为0.9mm，支架扩张直径为2.5mm。支架在压握和扩张时的网丝变形量为15～25％。经有限元分析，支架的疲劳安全系数为3.77，依据《YY/T 0808-2010血管支架体外脉动耐久性标准测试方 法》，用RDTL-0200支架疲劳测试系统测试了支架的疲劳性能。将支架释放于与支架尺寸匹配的半顺应性硅胶管中，管内工作介质为37±2℃的PBS缓冲液，在顺应管内部脉动施加压力，最低压力为75-80mmHg，最高压力为160-165mmHg，脉动频率为45Hz。支架经5.7亿次疲劳(使用寿命15年)后，未发现支架断裂和塌陷。
实施例7
用表2所示成分的高氮钢棒材，采用如下条件的渗氮方法制备支架管材，管坯尺寸为Φ30×6mm。冷变形道次为21次，热处理时炉内压力0.25MPa，氮分压为20％，热处理温度1050℃，保温时间30～5分钟。在每道次热处理后，对管材进行内外表面机械磨抛处理。成品管材氮含量为1.12重量％，通过与实施例6同样的方法测得的屈服强度为782MPa、抗拉强度为1190MPa、轴向延伸率为54％、管材点蚀电位1060mV。
表2.支架管材制备中使用的棒材的化学成分
Figure PCTCN2020125095-appb-000002
用激光将该管材切割成冠脉支架金属平台，其结构如图12所示。
对得到的冠脉支架金属平台进行如下电化学修饰：阴极置于盛有电化学抛光液的容器底部，阴极上放置多孔海绵状限位板，直径为0.9mm的铂丝穿过支架，通过移动铂丝，使支架以20mm/s的线速度在限位板上匀速滚动，到达预设抛光效果后停止，纯净水清洗支架后，再用NaOH溶液中和支架表面的残余酸性抛光液，使支架金属平台表面微粗糙化。电化学抛光液成分为高氯酸和冰乙酸，成分比例为1：10，电化学抛光液温度35±2℃，电化学电流密度2.3A/cm 2。图13和图14分别示出了粗糙化处理后支架金属平台表面的扫描电镜照片和激光共聚焦照片。经测量，粗糙化处理后的支架金属平台表面高度差约0.2μm。 然后，在支架表面通过超声雾化喷涂雷帕霉素药物涂层，依据《YY/T 0808-2010血管支架体外脉动耐久性标准测试方法》，用RDTL-0200支架疲劳测试系统测试了支架的疲劳性能。将支架释放于与支架尺寸匹配的半顺应性硅胶管中，管内工作介质为37±2℃的PBS缓冲液，在顺应管内部脉动施加压力，最低压力为75-80mmHg，最高压力为160-165mmHg，脉动频率为1.2Hz。将涂层支架在PBS缓冲液中模拟脉动与血流冲刷90天后的涂层形貌示于图15。由该结果可知，本发明的支架涂层未发生脱落和大面积损坏，涂层与基体具有高的结合强度。
实验例1 氮增加前后的力学性能变化
对于实施例1～3中使用的高氮无镍不锈钢锻造态棒材以及经高温渗氮进一步提高了材料内氮含量后得到的实施例1～3的成品管材进行了力学性能测定，屈服强度、抗拉强度以及延伸率的测定方法如下所述。依据GB/T 228.1-2010金属材料拉伸试验第1部分：室温试验方法，用Z150力学试验机对金属管材进行拉伸试验。
表3汇总示出了管材在不同氮含量下的力学性能，由该结果可知，随着氮含量的增加，材料的强度增加，塑性未见本质性变化。即，本发明实施例1～3得到了高尺寸精度、高表面质量的综合性能优良的高锰高氮无镍奥氏体不锈钢薄壁管材。
表3
Figure PCTCN2020125095-appb-000003
实验例2冷变形前后的组织结构变化
对于实施例3中第七道次冷变形及热处理后得到的Φ12×1.1mm高氮无镍不锈钢固溶态管材(N：0.92重量％)及其经21％、43％、66％冷变形后的高氮无镍不锈钢管材进行了X射线衍射谱测定，具体测定方法是依据JY/T 009-1996转靶多晶体X射线衍射方法通则，用Rigaku(理学)D/max 2500PC型X射线衍射仪对金属管材试样进行测定。
图16示出了管材在固溶状态和上述三种冷变形状态下高氮无镍不锈钢(N：0.92重量％)的X射线衍射谱，图中(111)晶面、(200)晶面、(220)晶面的X射线衍射谱是标准的奥氏体X射线衍射谱，所有衍射峰均未发生偏移，表明该材料在固溶状态和小于66％的冷变形状态下，均保持稳定的奥氏体组织。即，本发明得到的高氮无镍奥氏体不锈钢薄壁管材，在小于66％的冷变形状态下使用，不会影响奥氏体组织的稳定性。
实验例3经不同表面处理后的支架金属平台表面的涂层牢固度对比
支架表面的涂层牢固度指标是药物涂层的一个重要评价指标。本 发明采用的涂层牢固度评价方法如下：
(1)实验分组：I组为经常规电化学抛光后的支架(即，实施例4中的抛光前表面预处理后的高氮无镍不锈钢血管支架经常规电化学抛光后的支架)直接喷涂药物涂层，常规电化学抛光是指：用阳极夹持样件局部，通过往复运动实现样件的抛光；II组为经本发明的通过滚动线接触式电化学抛光进行表面粗糙化后的支架(即，实施例4中得到的经表面精整和精准成型后的高氮无镍不锈钢血管支架)直接喷涂药物涂层。支架干燥1天后，经环氧乙烷灭菌并解析7天。
(2)采用支架系统专用的装配设备—血管支架压握机对I组和II组的药物支架进行压握装配，组成支架系统。
(3)用压力泵分别将上述装配的支架系统进行扩张处理，标称压力均为12atm。支架卸载后，进行扫描电镜观察，着重观察支架网丝变形量最大部位的涂层形貌。
图17示出了对经不同表面处理后的支架金属平台表面喷涂药物涂层后、支架压握扩张后的表面形貌。如图17B所示，经常规电化学抛光后直接喷涂药物涂层时，支架在扩张后局部会出现脱落现象。而如图17A所示，经过本发明的表面修饰后涂层有非常好的结合性能，即使经过较大的往复变形，涂层仍保持良好的形状特征。

Claims (25)

  1. 一种高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，
    N含量为0.7～1.3重量％，在固溶状态和66％以下冷变形状态下为单一奥氏体组织，晶粒度≥7级，
    所述管材的壁厚60～200μm，外径尺寸偏差±0.03mm，壁厚尺寸偏差±0.02mm，屈服强度≥600MPa，抗拉强度≥1000MPa，轴向延伸率≥50％，点蚀电位≥1000mV。
  2. 根据权利要求1所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，以重量％计，具有如下成分组成：Cr：17～20％、Mn：14～18％、Mo：1～4％、N：0.7～1.3％、Si：≤0.75％、Cu：≤0.25％、C：≤0.03％、Si：≤0.01％、P：≤0.025％、Ni：≤0.05％，余量为Fe。
  3. 根据权利要求1或2所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，该管材用于医疗器械、食品药品器械、首饰、仪器仪表领域。
  4. 根据权利要求1～3中任一项所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，该管材用于外科植入物。
  5. 根据权利要求4所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，所述外科植入物为人体管腔支架。
  6. 根据权利要求5所述的高氮无镍奥氏体不锈钢无缝薄壁管材，其特征在于，所述人体管腔支架为血管支架。
  7. 权利要求1～6中任一项所述的高氮无镍奥氏体不锈钢无缝薄壁管材的制备方法，其特征在于，将氮含量＜0.7重量％的高氮无镍奥氏体不锈钢管坯，通过冷变形和热处理相结合的方式，在管材成型和控 制尺寸精度的同时实现表面层无锰挥发，并提高管材中的氮含量，
    在单道次内，实施梯度递减的2～3次冷变形，道次累计变形量≤50％，单次冷变形量≤30％，
    在每道次实施所述梯度递减的2～3次冷变形后实施热处理，所述热处理温度为1000～1150℃，处理时间为5～90分钟。
  8. 根据权利要求7所述的制备方法，其特征在于，在所述热处理过程中施加氩气和氮气混合气体的正压气氛，冷态总气压为0.12～0.30MPa，氮气分压为5％～30％。
  9. 根据权利要求7或8所述的制备方法，其特征在于，管材外径≥3.0mm时，每道次实施3次冷变形，每次变形量依次为该道次变形量的45～50％、30～35％和20～25％；管材外径＜3.0mm时，每道次实施2次冷变形，每次变形量依次为该道次变形量的55～60％和40～45％。
  10. 根据权利要求7～9中任一项所述的制备方法，其特征在于，管材在热处理后机械清除内外表面富氮硬质层后再进行下一道次冷变形。
  11. 一种无镍金属药物洗脱血管支架，其特征在于，
    所述支架的金属平台材料为高氮无镍奥氏体不锈钢，该金属平台材料的成分组成以重量％计为：Cr：17～20％，Mn：14～18％，Mo：1～3％，N：0.8～1.2％，Si：≤0.75％，Cu：≤0.25％，C：≤0.03％，Si：≤0.01％，P：≤0.025％，Ni：≤0.05％，Fe：余量，
    所述金属平台材料的抗拉强度为1100MPa以上，固溶态时的疲劳强度为570MPa以上，20％冷变形时的疲劳强度为750MPa以上，
    所述金属平台材料在生理盐水和PBS缓冲液中的点蚀电位为1000mV以上，
    并且，所述金属平台材料在冷变形量达50％时，仍具有单一奥氏体组织，晶粒度≥7级。
  12. 根据权利要求11所述的无镍金属药物洗脱血管支架，其中，所述支架的所有变形点在压握和扩张变形时的变形量为15～25％，所述支架变形部位的疲劳强度为750MPa以上。
  13. 根据权利要求11或12所述的无镍金属药物洗脱血管支架，其中，在所述支架金属平台的表面，不同取向的晶粒形成微米级凸凹结构，晶粒间的高度差为0.1～0.5μm。
  14. 根据权利要求11～13中任一项所述的无镍金属药物洗脱血管支架，其用于心脑血管。
  15. 根据权利要求14所述的无镍金属药物洗脱血管支架，其用于冠状动脉。
  16. 一种无镍金属药物洗脱血管支架的制造方法，其特征在于，在支架管材制备时，将氮含量＜0.7重量％的高氮无镍奥氏体不锈钢管坯，通过冷变形和热处理相结合的方式，在管材成型和控制尺寸精度的同时，提高管材中的氮含量至0.8～1.2％并实现表面层无锰挥发，在单道次内，实施梯度递减的2～3次冷变形，道次累计变形量≤50％，单次冷变形量≤30％，
    在每道次实施所述梯度递减的2～3次冷变形后实施热处理，所述热处理温度为1000～1150℃，处理时间为5～90分钟。
  17. 根据权利要求16所述的无镍金属药物洗脱血管支架的制造方法，其中，所述热处理温度为1045～1055℃，施加的气氛中的氮分压为5～30％，其余为惰性气体，炉内压力为1.5～3atm。
  18. 根据权利要求16或17所述的无镍金属药物洗脱血管支架的制造方法，其中，管材外径≥3.0mm时，每道次实施3次冷变形，每 次变形量依次为该道次变形量的45～50％、30～35％和20～25％；管材外径＜3.0mm时，每道次实施2次冷变形，每次变形量依次为该道次变形量的55～60％和40～45％。
  19. 根据权利要求16～18中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，用激光将所述管材切割成支架金属平台，采用滚动线接触式电化学抛光，将所述支架金属平台与金属电极连续滚动线性接触，通过控制滚动速度，控制支架金属平台表面凸起处的抛光液膜的减薄和破膜速度，对该支架金属平台进行表面精整，
    同时，所述金属电极选择不同于所述支架金属平台的异种惰性金属材料，使所述金属电极与所述支架金属平台以连续滚动线性接触的方式导通，利用所述金属电极与该支架金属平台之间的微电位差，使该支架金属平台的表面通过不同取向的晶粒形成微米级凸凹结构，晶粒间的高度差为0.1～0.5μm。
  20. 根据权利要求19所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，电流密度控制在0.8～1.0A/cm 2。
  21. 根据权利要求19或20所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，电化学处理温度控制在10～40℃。
  22. 根据权利要求19～21中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，电化学抛光液的成分包括高氯酸、冰乙酸以及缓蚀剂，高氯酸与冰乙酸的体积比、即高氯酸/冰乙酸为1：4～1：20，缓蚀剂在抛光液中的体积比例为2～8％。
  23. 根据权利要求19～22中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，滚动线接触式电化学抛光中，抛光滚动速度 控制在2～2.5cm/s。
  24. 根据权利要求19～23中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，所述异种惰性金属材料为铂金或钽。
  25. 根据权利要求19～24中任一项所述的无镍金属药物洗脱血管支架的制造方法，其中，所述异种惰性金属材料为铂金。
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