CN111840659A

CN111840659A - High-safety blood vessel support without nickel metal medicine elution and its making method

Info

Publication number: CN111840659A
Application number: CN202010364623.2A
Authority: CN
Inventors: 李文; 白树功
Original assignee: Zhongke Yi'an Medical Technology Beijing Co ltd
Current assignee: Zhongke Yi'an Medical Technology Beijing Co ltd
Priority date: 2020-04-30
Filing date: 2020-04-30
Publication date: 2020-10-30
Anticipated expiration: 2040-04-30
Also published as: CN111840659B

Abstract

The invention relates to a high-safety nickel-free metal drug eluting intravascular stent and a manufacturing method thereof. The nitrogen content of the material is further improved in the process of preparing the bracket pipe by a step-by-step nitriding mode, and the high-nitrogen nickel-free austenitic stainless steel with the nitrogen content of 0.8-1.2% is obtained and used as a bracket metal platform material. By adopting rolling line contact type electrochemical polishing, the surface of the stent forms a micron-sized convex-concave structure through grains with different orientations, and the binding force of the stent metal material and the drug coating is improved. The intravascular stent has the characteristics of long fatigue life, high biological safety and high binding force between a drug coating and a matrix.

Description

High-safety blood vessel support without nickel metal medicine elution and its making method

Technical Field

The invention relates to the field of medical appliances, in particular to a nickel-free metal drug eluting intravascular stent with long service life and high safety and a manufacturing method thereof.

Background

Stent implantation is currently the most effective and safe means of treating vascular stenosis, and over the course of over 30 years, stent implantation and stent fabrication techniques have matured substantially. Coronary stents generally adopt a method of preparing a drug coating on the surface of a metal stent, and the stent is fixed at a target lesion part of a blood vessel by balloon dilatation, plays a role of long-term physical support on the lesion blood vessel and participates in blood circulation of the blood vessel. However, some patients still have stent segment restenosis, thrombosis and late stent failure after stent implantation. The reason for this may be related to the following factors: (1) in the process of implanting the stent and in the initial stage of implanting, the drug coating on the surface of the stent falls off to generate thrombus; (2) stent fracture or collapse due to long term fatigue of the stent (current stent design life is 10 years); (3) the incidence of restenosis in stents is high in metal-allergic patients, and nickel allergy is the most frequent in metal-allergic patients.

In order to further improve the safety and service life of the implanted stent and avoid the restenosis of the stent section caused by nickel allergy, material researchers are constantly dedicated to developing a stent metal material with higher biosecurity and better mechanical property. The high-nitrogen nickel-free stainless steel (patent document 1) which is independently developed by the metal research institute of the Chinese academy of sciences and is not added with harmful nickel elements comprises the following components: cr: 17-22%, Mn: 12-20%, Mo: 1-3%, Cu: 0.5-1.5%, N: 0.4-0.7%, Ni: less than or equal to 0.02 percent, C: less than or equal to 0.03%, Si: less than or equal to 0.75 percent, S: less than or equal to 0.01 percent, P less than or equal to 0.025 percent, Fe: and (4) the balance. The material has the characteristics of high strength, high fatigue strength, high corrosion resistance, stable tissue and the like, and has obvious advantages when being used as an implant material.

In the aspects of structural design and manufacturing technology of the bracket, people also continuously pursue reasonable matching of mechanical properties such as supporting strength and the like of the bracket, so that the bracket has better clinical operability and clinical safety. In the aspect of improving the bonding strength between the drug coating and the matrix, stent manufacturers seek to make the drug coating on the surface of the stent firmer by methods such as surface modification, gradient coating preparation and the like. The technologies of the "method for roughening surface of metal material" (patent document 2) of the university of northeast China and the "titanium or titanium alloy material with surface of micro-nano coarse structure and preparation method" (patent document 3) of the university of Sichuan have certain effects on improving surface area and increasing the bonding firmness of the stent and the coating.

Documents of the prior art

Patent document

Patent document 1: CN1519387A

Patent document 2: CN101255593A

Patent document 3: CN103668390A

Disclosure of Invention

Problems to be solved by the invention

For chromium-manganese-nitrogen high-nitrogen nickel-free austenitic stainless steel, because the saturation vapor pressure of manganese is very high, manganese volatilizes from the free surface with low constraint force when the material is subjected to high-temperature heat treatment, and a manganese-poor layer is formed on the surface. In the preparation process of the thin-walled tube for the intravascular stent, the manganese poor layer on the surface of the tube becomes thick continuously along with the increase of the heat treatment times, and the tube cracks when the wall thickness and the manganese poor layer reach a certain proportion.

In addition, the preparation of the thin-wall pipe material necessarily goes through two processes of deformation and heat treatment. Due to the large deformation resistance of the material, the pipe prepared by the conventional process is difficult to realize high dimensional precision and is easy to generate cracks. Furthermore, the conventional heat treatment process may cause a manganese-poor layer to be formed on the surface of the pipe, change the surface material composition, fail to form stable austenite on the surface, and may cause cracking during deformation. Therefore, the product is difficult to meet the requirements of the field of vascular stents on high precision and high stability of stainless steel pipes. In view of the above, the high nitrogen nickel-free stainless steel of patent document 1 still has room for improvement.

In addition, the surface treatment processes described in patent documents 2 and 3 are difficult to obtain an ideal effect for a tubular mesh stent having a mesh of only 0.08 to 0.1 mm. Therefore, there is a strong need to find surface roughening techniques that are more suitable for stent fabrication techniques.

In view of the above problems of the prior art, an object of the present invention is to provide a vascular stent having a longer lifespan and higher safety and a method of manufacturing the same.

Means for solving the problems

In order to solve the above problems, the present inventors have conducted extensive studies on stent tubes and methods for surface treatment of tubes, and have obtained the following findings for the first time. By utilizing the characteristics of high fatigue strength, high corrosion resistance, high tissue stability and no harmful nickel element of the high-nitrogen nickel-free stainless steel material, and further by the structural design of the stent and the roughening treatment process of the surface of the metal platform of the stent, the intravascular stent with longer service life and higher safety can be obtained.

The present invention has been completed based on the above findings, and the gist of the present invention is as follows.

1. A nickel-free metal drug-eluting intravascular stent, which is characterized in that,

the metal platform material of the bracket is high-nitrogen nickel-free austenitic stainless steel, and the metal platform material comprises the following components in percentage by weight: cr: 17-20%, Mn: 14-18%, Mo: 1-3%, N: 0.8-1.2%, Si: less than or equal to 0.75 percent, Cu: less than or equal to 0.25 percent, C: less than or equal to 0.03%, Si: less than or equal to 0.01 percent, P: less than or equal to 0.025 percent, Ni: less than or equal to 0.05 percent, Fe: the balance of the weight percentage is as follows,

The metal platform material has a tensile strength of 1100MPa or more, a fatigue strength of 570MPa or more in a solid solution state, a fatigue strength of 750MPa or more in 20% cold deformation,

the pitting potential of the metal platform material in physiological saline and PBS buffer solution is more than 1000mV,

and when the cold deformation of the metal platform material reaches 50%, the metal platform material still has a single austenite structure, and the grain size is more than or equal to 7 grades.

2. The nickel-free metal drug-eluting stent according to the above 1, wherein the deformation amount of all deformation points of the stent during crimping and expansion deformation is 15-25%, and the fatigue strength of the deformed part of the stent is 750MPa or more.

3. The nickel-free metal drug-eluting intravascular stent according to 1 or 2, wherein the crystal grains with different orientations on the surface of the stent metal platform form a micron-sized convex-concave structure, and the height difference between the crystal grains is 0.1-0.5 μm.

4. The nickel-free metal drug-eluting vascular stent according to 1 or 2, which is used for cardiovascular and cerebrovascular vessels.

5. The nickel-free metal drug-eluting vascular stent according to the above 4, which is used for coronary arteries.

6. A manufacturing method of a nickel-free metal drug eluting intravascular stent is characterized in that when a stent tube is prepared, a high-nitrogen nickel-free austenitic stainless steel tube blank with the nitrogen content of less than 0.7 weight percent is subjected to cold deformation and heat treatment, the nitrogen content in the tube is improved to 0.8-1.2 percent while the tube is formed and the dimensional accuracy is controlled, manganese volatilization of a surface layer is realized,

In a single pass, carrying out gradient decreasing cold deformation for 2-3 times, wherein the cumulative deformation of the pass is less than or equal to 50 percent, the single cold deformation is less than or equal to 30 percent,

and performing heat treatment after performing the gradient decreasing cold deformation for 2-3 times in each pass, wherein the heat treatment temperature is 1000-1150 ℃, and the treatment time is 5-90 minutes.

7. The method for manufacturing the nickel-free metal drug-eluting intravascular stent according to the above 6, wherein the heat treatment temperature is 1045 to 1055 ℃, the partial pressure of nitrogen in the applied atmosphere is 5 to 30%, the rest is inert gas, and the pressure in the furnace is 1.5 to 3 atm.

8. The manufacturing method of the nickel-free metal drug-eluting intravascular stent according to the 6 or 7, wherein when the outer diameter of the tube is larger than or equal to 3.0mm, the cold deformation is performed for 3 times in each pass, and the deformation of each pass is 45-50%, 30-35% and 20-25% of the deformation of the pass in sequence; when the outer diameter of the pipe is less than 3.0mm, carrying out cold deformation for 2 times in each pass, wherein the deformation of each time is 55-60% and 40-45% of the deformation of the pass in sequence.

9. The method for manufacturing a nickel-free metal drug-eluting intravascular stent according to the above 6 or 7, wherein the tube is cut into the stent metal platform by laser, the stent metal platform is continuously in rolling linear contact with the metal electrode by adopting rolling linear contact type electrochemical polishing, the thinning and the membrane breaking speed of the polishing liquid membrane at the convex part of the surface of the stent metal platform are controlled by controlling the rolling speed, the rapid and uniform surface finishing is carried out on the stent metal platform,

Meanwhile, the metal electrode is made of different inert metal materials different from the support metal platform, so that the metal electrode is conducted with the support metal platform in a continuous rolling linear contact mode, the surface of the support metal platform forms a micron-sized convex-concave structure through grains with different orientations by utilizing the micro potential difference between the metal electrode and the support metal platform, and the height difference between the grains is 0.1-0.5 mu m.

10. The method for manufacturing a nickel-free metal drug-eluting vascular stent according to the above 9, wherein in the rolling wire contact type electrochemical polishing, the electrochemical polishing solution comprises perchloric acid, glacial acetic acid and a corrosion inhibitor, and the volume ratio of perchloric acid to glacial acetic acid, namely perchloric acid/glacial acetic acid, is 1: 4-1: 20, the volume ratio of the corrosion inhibitor in the polishing solution is 2-8%, the electrochemical treatment temperature is controlled at 10-40 ℃, and the current density is controlled at 0.8-1.0A/cm²And the polishing rolling speed is controlled to be 2-2.5 cm/s.

11. The method for manufacturing a nickel-free metal drug-eluting stent according to the above 9 or 10, wherein the dissimilar inert metal material is platinum or tantalum.

12. The method for manufacturing a nickel-free metal drug-eluting stent according to the above 11, wherein the dissimilar inert metal material is platinum.

Effects of the invention

According to the invention, the high-nitrogen nickel-free stainless steel material which has high fatigue performance and high corrosion performance and is obtained by a step-by-step nitriding mode is adopted as the support metal platform material, so that the support metal platform has high mechanical property and fatigue strength, and the support has longer fatigue life.

Through the structural design of controlling the deformation of the support deformation point, the fatigue strength of the support is further improved, and the service cycle of the support is longer.

In addition, the surface of the metal platform of the stent is roughened by rolling line contact type electrochemical polishing, and a micron-sized convex-concave structure is formed by grains with different orientations, so that the binding force between the metal platform of the stent and a drug coating is increased, and the drug coating on the surface of the stent can better resist deformation and damage possibly caused by fatigue. Therefore, the coating of the stent is not easy to fall off in the deformation, conveying and service processes, and the risk of generating thrombus in the initial stage of stent implantation is reduced. Also, since the surface roughening method of the present invention does not require introduction of foreign substances, safety is higher compared to a chemical surface roughening method using corrosion. Further, the surface roughening method of the present invention does not have a problem of reduction in fatigue life caused by a physical surface roughening method such as roughening and sandblasting.

In addition, the stent material adopts high-nitrogen nickel-free austenitic stainless steel, harmful nickel elements with sensitization and carcinogenesis are not actively added in the material, and the material has excellent corrosion resistance, so that the risk of restenosis possibly caused by metal ion dissolution or nickel allergy after the drug coating on the surface of the stent is degraded is reduced.

The high-safety nickel-free metal drug-eluting intravascular stent has the characteristics of long service life and low risk, so that the high-safety nickel-free metal drug-eluting intravascular stent is expected to improve the life quality of implanted patients and benefits the society.

Drawings

FIG. 1 is a photograph showing the metallographic structure of an axial cross section of a pipe material of Φ 3.0X 0.11mm in example 1. The microstructure is a metallographic structure photo which is shot by a Zeiss Observer Z1M metallographic microscope and has the magnification of 100 times according to a GB/T6397-.

FIG. 2 is a photograph of the metallographic structure showing an axial section of a pipe of Φ 1.8X 0.09mm in example 2. The microstructure is a metallographic structure photo which is shot by a Zeiss Observer Z1M metallographic microscope and has the magnification of 100 times according to a GB/T6397-.

FIG. 3 is a photograph showing the metallographic structure of an axial section of a pipe material of Φ 4.5X 0.19mm in example 3. The microstructure is a metallographic structure photo which is shot by a Zeiss Observer Z1M metallographic microscope and has the magnification of 100 times according to a GB/T6397-.

FIG. 4 is a diagram showing the stent structure of example 4 with a nominal diameter of 2.5 mm.

FIG. 5 is a schematic diagram illustrating a roll-to-roll wire contact electrochemical polishing apparatus of the present invention. Fig. 5A is a front view of the polishing apparatus. Fig. 5B is a plan view of the polishing apparatus.

Fig. 6 is a graph showing the macro and micro topography 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. 6A and 6B are macro topography diagrams of the surface of the high nitrogen nickel-free stainless steel vascular stent, wherein fig. 6B is a partial enlarged view of fig. 6A. FIG. 6C is a microscopic topography of the surface of a high nitrogen nickel-free stainless steel stent.

Fig. 7 is a graph showing the post-surface-finishing, precision-shaping, and surface micropatterning topography of the 316L stainless steel vascular stent of example 5. FIG. 7A is a surface topography of a 316L stainless steel vascular stent under a metallographic microscope. FIG. 7B is a microscopic topography of the surface of a 316L stainless steel stent.

FIG. 8 is a diagram showing the structure of a stent of nominal diameter 2.5mm of example 6.

FIG. 9 is a diagram showing the structure of a stent of example 7 having a nominal diameter of 3.0 mm.

Fig. 10 is a scanning electron micrograph showing a roughened surface of a stent metal platform of example 7.

Fig. 11 is a diagram showing a confocal laser photograph of the roughened stent metal platform surface of example 7.

FIG. 12 is a photograph showing a scanning electron microscope photograph of the stent of example 7 after fatigue of the surface coating layer.

FIG. 13 is a graph showing coating firmness comparison results for stent metal platform surfaces after different surface treatments. Fig. 13A shows the surface topography of the sprayed drug coating after the stent metal platform surface is roughened and modified by the roughening of the invention after the stent is crimped and expanded. Fig. 13B shows the surface morphology of the drug coating directly sprayed on the surface of the metal platform of the stent after conventional electrochemical polishing without roughening modification after stent crimping expansion.

Detailed Description

The support metal platform material adopts high-nitrogen nickel-free austenitic stainless steel with high strength, high fatigue strength and high corrosion resistance, and comprises the following components in percentage by weight: cr: 17-20%, Mn: 14-18%, Mo: 1-3%, N: 0.8-1.2%, Si: less than or equal to 0.75 percent, Cu: less than or equal to 0.25 percent, C: less than or equal to 0.03%, Si: less than or equal to 0.01 percent, P: less than or equal to 0.025 percent, Ni: less than or equal to 0.05 percent and the balance of Fe.

In order to obtain the bracket metal platform material with high nitrogen content and simultaneously inhibiting the volatilization of manganese in the material, the nitrogen content in the pipe is increased by gradually pressurizing and nitriding while the cold deformation stress is eliminated by heat treatment to realize solid solution in the preparation process of the bracket pipe. Therefore, the tensile strength of the obtained stent metal platform material can reach more than 1100MPa, and the fatigue strength is more than 570MPa, which is far higher than the fatigue strength of the mainstream stent material clinically used at present.

Through the structural design of the bracket, the deformation of all the mesh wires of the bracket during pressure holding and expansion deformation is 15-25%, so that the fatigue strength of the deformed part (long-term fatigue) of the bracket is improved to more than 750 MPa. Therefore, the risk of late fracture and collapse of the bracket is reduced, the long-term safety and effectiveness of the bracket in the body are improved to the maximum extent, the bracket has longer fatigue life, and the safe service cycle of the bracket is prolonged.

In addition, the corrosion potential of the bracket metal platform material in physiological saline and PBS buffer solution can reach more than 1000mV, and the surface corrosion resistance of the bracket metal platform material is not required to be improved through passivation treatment. Because the metal platform material of the stent has excellent corrosion resistance and harmful nickel elements with sensitization and carcinogenesis are not added in the material, after the drug coating on the surface of the stent is degraded, the metal material has high biological safety, and the risk of late stage restenosis of a stent section is reduced.

The surface finishing and size control of the metal platform of the bracket are realized by adopting a rolling line contact type electrochemical polishing mode after the bracket pipe is cut and formed by laser. The electrolytic polishing solution used in the electrochemical polishing is a mixed solution of perchloric acid and glacial acetic acid, to which a small amount, for example, 5% of a corrosion inhibitor is added. The components of the polishing solution, the polishing current density and the reaction temperature are controlled to ensure that the surface of the bracket is smooth. Meanwhile, by controlling the electrode potential, the crystal grains with different orientations have different polishing amounts, the micro-roughening of the surface of the metal platform of the bracket is realized, and the height difference of 0.1-0.5 mu m is formed, so that the binding force between the metal platform of the bracket and the drug coating is increased.

The method is characterized in that a medicine coating for inhibiting smooth muscle cell proliferation is prepared on the surface of the stent in an ultrasonic atomization spraying mode, and the medicine coating on the surface of the stent is combined with a matrix in high strength by controlling a spraying process and roughening the surface of the metal platform of the stent. The drug is preferably rapamycin and its derivatives. Therefore, the coating of the stent cannot be damaged or fall off in the processes of assembly, transportation and expansion, and the coating cannot be seriously damaged due to fatigue of the stent and scouring of blood flow before the stent is coated on an endothelium, so that the risk of thrombus generation at the initial stage of stent implantation is reduced.

The high-safety nickel-free metal drug-eluting stent can be used for cardiovascular and cerebrovascular vessels, other arteries, venous vessels and the like, and is preferably used for coronary arteries.

The present invention will be described in detail below based on examples. However, the examples are merely illustrative of the present invention and do not limit the scope of the present invention.

Example 1 high nitrogen nickel-free austenitic stainless steel seamless thin-walled tube 1

A high-nitrogen nickel-free stainless steel forged bar with the nitrogen content of 0.62 wt% and the manganese content of 15.4 wt% is taken and processed by a deep hole drilling machine to obtain a tube blank, and the size of the tube blank is phi 30 x 6 mm. The size of the finished pipe is designed to be phi 3.0 multiplied by 0.11 mm. Cold deformation pass 17 And the deformation of each pass is 40-50%. And carrying out cold deformation for three times in each pass, wherein the single deformation is 45-50%, 30-35% and 20-25% of the deformation of the pass in sequence. And (4) carrying out ultrasonic cleaning on the surface of the pipe after each cold deformation, and removing the surface lubricant. After drying, the mixture is put into a heat treatment furnace pipe which can be vacuumized and pressurized, the material of the furnace pipe is 2520 high-temperature alloy, and three temperature measuring thermocouples are arranged in the furnace pipe to monitor the temperature in real time. The furnace pipe is vacuumized to 10 degrees^-1Continuously exhausting air for more than 10 minutes after Pa, and closing a valve of the vacuum-pumping system. The furnace pipe is filled with mixed gas of nitrogen and argon, the total pressure is 0.15MPa, the ratio of nitrogen to argon is 1:9, namely the nitrogen partial pressure is 10%. When the temperature of the heating furnace reaches 1100 ℃, the furnace pipe is conveyed into the tubular heating furnace, when the temperature of the furnace pipe reaches 1100 ℃ and is stable, the heat preservation time is determined according to the charging amount and the wall thickness of the pipe, and the range is 5-60 minutes. And after each heat treatment, mechanically grinding and polishing the inner surface and the outer surface of the pipe.

The inspection results of the finished pipe are as follows: 3.0 +/-0.02 mm of outer diameter, 0.11 +/-0.01 mm of wall thickness, 0.81 weight percent of nitrogen, 15.42 weight percent of manganese, 608MPa of yield strength, 1019MPa of tensile strength, 51 percent of axial elongation and 1000mV of pitting potential. The method for measuring the yield strength, the tensile strength and the elongation percentage is as follows: part 1 of the tensile test of metallic materials according to GB/T228.1-2010: room temperature test method, a Z150 mechanical testing machine is used for carrying out tensile test on the metal pipe. The metallographic structure of the axial section of the pipe is shown in figure 1 and is a single austenite structure, and the grain size is more than or equal to 7 grades. And measuring the roughness of the inner surface and the outer surface of the pipe by using an Alpha-Step IQ contact surface topography instrument according to the standards of GB/T3505-2009, GB/T1031-2009 and GB/T10610-2009, wherein the measurement results are respectively Ra _{Inner part}＝0.046μm、Ra_{Outer cover}＝0.039μm。

Example 2 high nitrogen nickel-free austenitic stainless steel seamless thin-walled tube 2

A high-nitrogen nickel-free stainless steel forged bar with the nitrogen content of 0.62 wt% and the manganese content of 15.4 wt% is taken and processed by a deep hole drilling machine to obtain a tube blank, and the size of the tube blank is phi 30 x 6 mm. The size of the finished pipe is designed to be phi 1.8 multiplied by 0.09 mm. The cold deformation pass is 21, and each passThe deformation amount is 40-50%. When the outer diameter of the pipe is larger than or equal to 3.0mm, carrying out cold deformation for three times in each pass, wherein the deformation of each pass is 45-50%, 30-35% and 20-25% of the deformation of the pass in sequence; when the outer diameter of the pipe is less than 3.0mm, cold deformation is carried out twice in each pass, and the deformation of each pass is 55-60% and 40-45% of the deformation of the pass in sequence. And (4) carrying out ultrasonic cleaning on the surface of the pipe after each cold deformation, and removing the surface lubricant. After drying, the mixture is put into a heat treatment furnace pipe which can be vacuumized and pressurized, the material of the furnace pipe is 2520 high-temperature alloy, and three temperature measuring thermocouples are arranged in the furnace pipe to monitor the temperature in real time. The furnace pipe is vacuumized to 10 degrees^-1Continuously exhausting air for more than 10 minutes after Pa, and closing a valve of the vacuum-pumping system. The furnace pipe is filled with mixed gas of nitrogen and argon, the total pressure is 0.25MPa, the ratio of nitrogen to argon is 1:4, namely the nitrogen partial pressure is 20%. When the temperature of the heating furnace reaches 1050 ℃, the furnace pipe is sent into the tubular heating furnace, when the temperature of the furnace pipe reaches 1050 ℃ and is stable, the heat preservation time is determined according to the charging amount and the wall thickness of the pipe, and the range is 5-60 minutes. And after each heat treatment, mechanically grinding and polishing the inner surface and the outer surface of the pipe.

The inspection results of the finished pipe are as follows: the external diameter is 1.8 +/-0.02 mm, the wall thickness is 0.09 +/-0.01 mm, the nitrogen content is 1.15 weight percent, the manganese content is 15.45 weight percent, the yield strength is 781MPa, the tensile strength is 1215MPa, the axial elongation is 56 percent, and the pitting potential is 1090 mV. The yield strength, tensile strength and elongation were measured in the same manner as in example 1. The metallographic structure of the axial section of the pipe is shown in figure 2 and is a single austenite structure, and the grain size is more than or equal to 7 grades. Further, the inner surface roughness Ra of the pipe material measured by the roughness measuring method described in example 1_{Inner part}0.07 μm, outer surface roughness Ra_{Outer cover}＝0.05μm。

Example 3 high nitrogen nickel-free austenitic stainless seamless thin-walled tube 3

A high-nitrogen nickel-free stainless steel forged bar with the nitrogen content of 0.62 wt% and the manganese content of 15.4 wt% is taken and processed by a deep hole drilling machine to obtain a tube blank, and the size of the tube blank is phi 30 x 6 mm. The size of the finished pipe is designed to be phi 4.5 multiplied by 0.19 mm. The cold deformation pass is 15, and the deformation of each pass is 40-50%. Cold deformation is divided into three times in each pass, and the deformation amount of each passThe deformation amount of the pass is 45-50%, 30-35% and 20-25% in sequence. And (4) carrying out ultrasonic cleaning on the surface of the pipe after each cold deformation, and removing the surface lubricant. After drying, the mixture is put into a heat treatment furnace pipe which can be vacuumized and pressurized, the material of the furnace pipe is 2520 high-temperature alloy, and three temperature measuring thermocouples are arranged in the furnace pipe to monitor the temperature in real time. The furnace pipe is vacuumized to 10 degrees ^-1Continuously exhausting air for more than 10 minutes after Pa, and closing a valve of the vacuum-pumping system. The furnace pipe is filled with mixed gas of nitrogen and argon, the total pressure is 0.30MPa, the ratio of nitrogen to argon is 1:3, namely the nitrogen partial pressure is 25%. When the temperature of the heating furnace reaches 1100 ℃, the furnace pipe is sent into the tubular heating furnace, when the temperature of the furnace pipe reaches 1100 ℃ and is stable, the heat preservation time is determined according to the charging amount and the wall thickness of the pipe, and the range is 15-60 minutes. And after each heat treatment, grinding and polishing the inner surface and the outer surface of the pipe.

The inspection results of the finished pipe are as follows: the external diameter is 4.5 +/-0.02 mm, the wall thickness is 0.19 +/-0.01 mm, the nitrogen content is 1.08 weight percent, the manganese content is 15.41 weight percent, the yield strength is 711MPa, the tensile strength is 1112MPa, the axial elongation is 55 percent, and the pitting potential is 1040 mV. The yield strength, tensile strength and elongation were measured in the same manner as in example 1. The metallographic structure of the axial section of the pipe is shown in figure 3 and is a single austenite structure, and the grain size is more than or equal to 7 grades. Further, the inner surface roughness Ra of the pipe material measured by the roughness measuring method described in example 1_{Inner part}0.058 μm, external surface roughness Ra_{Outer cover}＝0.053μm。

EXAMPLE 4 surface finishing and precision Molding of high Nitrogen Nickel-free stainless Steel vascular Stent

(1) Surface pretreatment before polishing of high-nitrogen nickel-free stainless steel intravascular stent

The high nitrogen nickel-free austenitic stainless steel seamless thin-walled tube material of example 2 was cut into coronary stents by laser, and the stent structure is shown in fig. 4. The pressing and holding diameter of the stent on the saccule is 0.9mm, and the expansion diameter of the stent is 2.5 mm. Before the support is polished, an oxidation layer generated on the surface of the support due to laser processing needs to be removed through acid washing pretreatment. The pretreatment aims at completely removing the oxide layer on the surface of the bracket and avoiding the obstruction of the oxide layer to the exchange of the polishing solution in the electrochemical polishing process. The pickling solution is a solution with sulfuric acid and hydrogen peroxide as main components. And controlling the temperature of the pickling solution to be 10-50 ℃ in the pickling process. After the acid washing, the stent is washed by a large amount of running water to remove the residual acid washing solution on the surface of the stent.

(2) Surface finishing and accurate molding of high-nitrogen nickel-free stainless steel intravascular stent

The surface finishing and precision shaping of the carrier are achieved by the electrochemical polishing of the present invention, the electrochemical polishing apparatus is schematically shown in FIG. 5. As shown in the drawings, the electrochemical polishing apparatus of the present invention is represented by fig. 5A (front view of the polishing apparatus) and fig. 5B (top view of the polishing apparatus). The device mainly comprises five parts, namely (1) a polishing groove made of polypropylene or glass, and the size of the polishing groove can be properly adjusted according to the size of a polishing piece; (2) the negative plate is made of a stainless steel circular plate and is positioned at the bottom of the polishing tank; (3) the limiting cotton is made of polypropylene sponge or melamine sponge and the like and is used for limiting the distance between the polishing piece and the cathode; (4) the polishing hanger or polishing clamp is made of platinum filaments, the size of the platinum filaments is 0.8-1.2 mm, and the size of the platinum filaments is determined according to the inner diameter of the polishing pipe; (5) the polishing liquid submerges the negative plate, the limiting cotton and the polishing hanging piece, and the polishing piece is kept to be completely immersed in the polishing liquid in the rolling polishing process of the polishing piece.

In the electrochemical polishing of the invention, the polishing solution is a mixture of perchloric acid, glacial acetic acid and a corrosion inhibitor. Wherein the volume ratio of perchloric acid to glacial acetic acid is 1: 4, the corrosion inhibition solution accounts for 2-8% of the volume of the total polishing solution, the polishing temperature is 15 ℃, the cathode plate is made of stainless steel metal, the metal electrode material is platinum, and the polishing voltage is 15V, which is determined according to the size of the bracket.

The specific polishing operation is as follows: the cathode is arranged at the bottom of a container filled with electrochemical polishing solution, a porous spongy limiting plate is arranged on the cathode, a platinum wire with the diameter of 0.9mm penetrates through the support, the support rolls on the limiting plate at a constant speed of 20mm/s by moving the platinum wire, the support stops after reaching a preset polishing effect, and after the support is cleaned by purified water, residual acidic polishing solution on the surface of the support is neutralized by NaOH solution. The polished bracket has smooth surface and uniform bracket mesh structure, and meets the nominal weight requirement of the bracket, thereby realizing the surface finishing and accurate molding of the bracket.

(3) Surface finishing and precisely-formed appearance of high-nitrogen nickel-free stainless steel intravascular stent

The surface appearance of the high-nitrogen nickel-free stainless steel intravascular stent subjected to surface finishing and precise molding is shown in fig. 6. As can be seen from the figure, the surface modification method of the invention can uniformly polish the surface of the high-nitrogen nickel-free stainless steel intravascular stent, thus being suitable for surface finishing and precise molding of the intravascular stent.

Example 5316L surface finishing, precision shaping and surface micropatterning of a stainless Steel vascular Stent

(1) Surface pretreatment before polishing of 316L stainless steel intravascular stent

Before polishing, the 316L stainless steel intravascular stent needs to be pretreated by acid cleaning to remove an oxide layer on the surface of the stent, which is generated by laser processing. The pretreatment aims at completely removing the oxide layer on the surface of the bracket and avoiding the obstruction of the oxide layer to the exchange of the polishing solution in the electrochemical polishing process. The pickling solution is a solution containing nitric acid and hydrofluoric acid as main components. And controlling the temperature of the pickling solution to be 10-50 ℃ in the pickling process. After the acid washing, the stent is washed by a large amount of running water to remove the residual acid washing solution on the surface of the stent.

(2) Surface finishing, precise molding and surface micropatterning of 316L stainless steel intravascular stent

The surface finishing and the precise molding of the stent are realized by electrochemical polishing, and the specific electrochemical polishing method is the same as that of the embodiment 4. The polishing conditions such as the composition of the polishing liquid, the rolling speed, and the polishing time were the same as those in example 4. The polishing temperature is 15 ℃, the cathode plate is made of stainless steel metal, the metal electrode is made of platinum, and the polishing voltage is 25V and is determined according to the size of the bracket. The polishing process adopts a continuous line contact rolling polishing mode, the polished bracket meets the nominal weight requirement of the bracket, and the surface of the bracket has grain orientation micro-patterns, thereby realizing the surface finishing, the accurate molding and the surface micro-patterning of the bracket.

(3) Surface finishing and precisely molded appearance of 316L stainless steel intravascular stent

The surface topography of the 316L stainless steel vascular stent of this example after surface finishing and precision molding is shown in FIG. 7. It can be seen from the figure that the surface modification method of the present invention can achieve micropatterning while the surface of the 316L stainless steel vascular stent is uniformly polished, and thus is suitable for surface finishing, precision molding and micropatterning of the vascular stent.

Example 6

A stent tube was produced by nitriding as described in example 2 using a high nitrogen steel bar having the composition shown in Table 1, and the tube blank had a size of phi 30X 6 mm. The cold deformation pass is 21 times, the pressure in the furnace is 0.25MPa during heat treatment, the nitrogen partial pressure is 20%, the heat treatment temperature is 1050 ℃, and the heat preservation time is 30-5 minutes. And mechanically grinding and polishing the inner surface and the outer surface of the pipe after each heat treatment. According to the method for determining the content of iron and nitrogen in GB/T20124 steel by using the melting thermal conductivity of inert gas (conventional method), the nitrogen content in the pipe is determined by using a TCH600 nitrogen-hydrogen-oxygen analyzer, and the nitrogen content of the finished pipe is 1.10 weight percent. Part 1 of the tensile test of metallic materials according to GB/T228.1-2010: the room temperature test method is characterized in that the tensile property of the finished pipe is measured by using a Z150 mechanical testing machine, and the yield strength of the finished pipe is 761MPa, the tensile strength of the finished pipe is 1215MPa, and the axial elongation of the finished pipe is 56 percent. And (3) carrying out electrochemical corrosion analysis by using a GARY Reference600 electrochemical workstation according to the pitting potential of the YY/T1074 surgical implant stainless steel product, and measuring the pitting potential 1090mV of the pipe.

TABLE 1 chemical composition of bars used in Stent tube preparation

The tube was cut into coronary stents with a laser, the structure of which is shown in fig. 8. The pressing and holding diameter of the stent on the saccule is 0.9mm, and the expansion diameter of the stent is 2.5 mm. The deformation amount of the mesh when the stent is pressed, held and expanded is 15-25%. Through finite element analysis, the fatigue safety coefficient of the stent is 3.77, and the fatigue performance of the stent is tested by using an RDTL-0200 stent fatigue test system according to the YY/T0808 and 2010 intravascular stent in-vitro pulsation durability standard test method. The stent is released in a semi-compliant silicone tube matched with the size of the stent, the working medium in the tube is PBS buffer solution at 37 +/-2 ℃, the pressure is exerted in a pulsating mode in the compliant tube, the lowest pressure is 75-80mmHg, the highest pressure is 160-165mmHg, and the pulsating frequency is 45 Hz. After 5.7 million fatigue (15 years of service life) the stent did not crack and collapse.

Example 7

A bracket pipe is prepared by a nitriding method under the following conditions by using a high-nitrogen steel bar material with the components shown in Table 2, and the size of a pipe blank is phi 30 multiplied by 6 mm. The cold deformation pass is 21 times, the pressure in the furnace is 0.25MPa during heat treatment, the nitrogen partial pressure is 20%, the heat treatment temperature is 1050 ℃, and the heat preservation time is 30-5 minutes. And after each heat treatment, mechanically grinding and polishing the inner surface and the outer surface of the pipe. The finished pipe had a nitrogen content of 1.12 wt%, a yield strength of 782MPa, a tensile strength of 1190MPa, an axial elongation of 54%, and a pipe pitting potential of 1060mV, measured in the same manner as in example 6.

TABLE 2 chemical composition of bars used in Stent tube preparation

The tube was cut into coronary stent metal platforms with laser, the structure of which is shown in fig. 9.

And performing the following electrochemical modification on the obtained coronary stent metal platform: the cathode is arranged at the bottom of a container filled with electrochemical polishing solution, a porous spongy limiting plate is arranged on the cathode, a platinum wire with the diameter of 0.9mm penetrates through the support, the support rolls on the limiting plate at a constant speed of 20mm/s by moving the platinum wire, the support stops after reaching a preset polishing effect, and after the support is cleaned by purified water, residual acidic polishing solution on the surface of the support is neutralized by NaOH solution, so that the surface of a metal platform of the support is roughened slightly. The electrochemical polishing solution comprises perchloric acid and glacial acetic acid in a ratio of 1: 10, the temperature of the electrochemical polishing solution is 35 +/-2 ℃, and the electrochemical current density is 2.3A/cm². Fig. 10 and 11 show a scanning electron micrograph and a confocal laser micrograph of the metal platform surface of the stent after the roughening treatment, respectively. Measured and roughened bracket metal platformThe difference in surface height is about 0.2 μm. And then, spraying a rapamycin drug coating on the surface of the stent by ultrasonic atomization, and testing the fatigue performance of the stent by using an RDTL-0200 stent fatigue test system according to YY/T0808-2010 intravascular stent in-vitro pulsation durability standard test method. The stent is released in a semi-compliant silicone tube matched with the size of the stent, the working medium in the tube is PBS buffer solution at 37 +/-2 ℃, the pressure is exerted in a pulsating mode in the compliant tube, the lowest pressure is 75-80mmHg, the highest pressure is 160-165mmHg, and the pulsating frequency is 1.2 Hz. The morphology of the coating after 90 days of simulated pulsatile and blood flow washout of the coated stent in PBS buffer is shown in FIG. 12. From the results, it was found that the stent coating of the present invention did not suffer from exfoliation and extensive damage, and the coating had high bonding strength with the substrate.

Experimental example 1 contrast of coating firmness on the surface of a metallic platform of a stent after different surface treatments

The coating firmness index of the surface of the stent is an important evaluation index of the drug coating. The method for evaluating the coating firmness is as follows:

(1) grouping experiments: group I is the stent after conventional electrochemical polishing (i.e., the stent after conventional electrochemical polishing of the high-nitrogen nickel-free stainless steel intravascular stent pre-surface treated before polishing in example 4) by directly spraying a drug coating, the conventional electrochemical polishing refers to: clamping the local part of the sample by using an anode, and polishing the sample by reciprocating motion; group II is a stent having a roughened surface by rolling wire contact electrochemical polishing according to the present invention (i.e., the high-nitrogen nickel-free stainless steel vascular stent obtained in example 4 after surface finishing and precision molding) directly sprayed with a drug coating. After drying the scaffolds for 1 day, they were sterilized with ethylene oxide and resolved for 7 days.

(2) And (3) adopting a special assembling device for the stent system, namely a vascular stent crimping machine to perform crimping assembly on the drug stents of the group I and the group II to form the stent system.

(3) The above assembled stent systems were individually expanded using a pressure pump, and the nominal pressure was 12 atm. And after the support is unloaded, carrying out scanning electron microscope observation, and emphasizing the observation of the coating morphology of the position with the maximum deformation of the mesh wire of the support.

FIG. 13 shows the surface topography of the stent after crimping and expansion after spraying drug coatings on the surface of the metal platform of the stent after different surface treatments. As shown in fig. 13B, when the drug coating is directly sprayed after conventional electrochemical polishing, the stent may partially fall off after expansion. As shown in fig. 13A, the coating layer after the surface modification of the present invention has very good bonding properties, and the coating layer maintains good shape characteristics even after a large reciprocating deformation.

Claims

2. The nickel-free metal-drug-eluting vascular stent according to claim 1, wherein the amount of deformation of all deformation points of the stent during crimping and expansion deformation is 15 to 25%, and the fatigue strength of the deformed portion of the stent is 750MPa or more.

3. The nickel-free metal drug-eluting vascular stent as defined in claim 1 or 2, wherein on the surface of the stent metal platform, the differently oriented grains form a micron-sized convex-concave structure, and the height difference between the grains is 0.1-0.5 μm.

4. The nickel-free metal drug-eluting vascular stent according to claim 1 or 2, which is used for cardiovascular and cerebrovascular applications.

5. The nickel-free metal drug-eluting vascular stent of claim 4, for use in a coronary artery.

7. The method for manufacturing a nickel-free metal drug-eluting stent according to claim 6, wherein the heat treatment temperature is 1045 to 1055 ℃, the partial pressure of nitrogen in the applied atmosphere is 5 to 30%, the rest is inert gas, and the pressure in the furnace is 1.5 to 3 atm.

8. The method for manufacturing the nickel-free metal drug-eluting vascular stent as claimed in claim 6 or 7, wherein when the outer diameter of the tube is larger than or equal to 3.0mm, each pass is subjected to cold deformation for 3 times, and the deformation of each pass is 45-50%, 30-35% and 20-25% of the deformation of the pass in sequence; when the outer diameter of the pipe is less than 3.0mm, carrying out cold deformation for 2 times in each pass, wherein the deformation of each time is 55-60% and 40-45% of the deformation of the pass in sequence.

9. The method for manufacturing a nickel-free metal drug-eluting vascular stent as defined in claim 6 or 7, wherein the tube is cut into stent metal platforms by laser, the stent metal platforms are continuously rolled and linearly contacted with the metal electrode by rolling linear contact electrochemical polishing, the stent metal platforms are surface-finished by controlling the rolling speed, the reduction of the polishing liquid film at the protrusions of the stent metal platforms and the speed of film breaking,

10. The method for manufacturing a nickel-free metal drug-eluting vascular stent as defined in claim 9, wherein the electrochemical polishing solution comprises perchloric acid, glacial acetic acid and a corrosion inhibitor in rolling wire contact electrochemical polishing, and the volume ratio of perchloric acid to glacial acetic acid, i.e. perchloric acid/glacial acetic acid, is 1: 4-1: 20, the volume ratio of the corrosion inhibitor in the polishing solution is 2-8%, the electrochemical treatment temperature is controlled at 10-40 ℃, and the current density is controlled at 0.8-1.0A/cm²And the polishing rolling speed is controlled to be 2-2.5 cm/s.

11. The method of manufacturing a nickel-free metal drug-eluting vascular stent as defined in claim 9 or 10, wherein the dissimilar inert metal material is platinum or tantalum.

12. The method of manufacturing a nickel-free metal drug-eluting vascular stent as defined in claim 11, wherein the dissimilar inert metal material is platinum.