CN115069957A

CN115069957A - Processing method of novel medical titanium alloy coronary artery drug-coated stent

Info

Publication number: CN115069957A
Application number: CN202210717108.7A
Authority: CN
Inventors: 王效增; 周铁楠; 柏春光; 张志强; 李雕峰; 杨锐; 孙景阳
Original assignee: Zhongke Ruijin Shandong Titanium Technology Co ltd; Institute of Metal Research of CAS; General Hospital of Shenyang Military Region
Current assignee: Zhongke Ruijin Shandong Titanium Technology Co ltd; Institute of Metal Research of CAS; General Hospital of Shenyang Military Region
Priority date: 2022-06-23
Filing date: 2022-06-23
Publication date: 2022-09-20

Abstract

The invention belongs to the technical field of cardiovascular stent processing, and relates to a processing method of a novel medical titanium alloy coronary artery drug-coated stent. The titanium alloy comprises the following chemical components in percentage by mass: 5.0 to 14.0 percent of Mn, less than or equal to 0.30 percent of Fe, less than or equal to 0.16 percent of O, less than or equal to 0.01 percent of N, less than or equal to 0.001 percent of H, and the balance of Ti. The invention adopts a vacuum consumable electrode arc furnace to smelt alloy cast ingots, and processes of forging, hot rolling and the like are carried out to prepare titanium alloy bars, then a finished product of titanium alloy capillary is prepared by mechanical perforation, peeling, centerless grinding, cold rolling, cold drawing and straightening, and a metal bracket is prepared by processes of microsecond optical fiber laser engraving, vacuum heat treatment, electrochemical polishing and the like. And then, spraying the medicinal solution on the outer surface of the metal stent by using a spraying machine, and airing in a clean environment, thereby preparing the novel titanium alloy coronary artery medicinal coating stent.

Description

Processing method of novel medical titanium alloy coronary artery drug-coated stent

Technical Field

The invention belongs to the technical field of cardiovascular stent processing, and particularly relates to a processing method of a novel medical titanium alloy coronary artery drug-coated stent, which is particularly suitable for a TiMn alloy coronary artery drug-coated stent.

Background

At present, coronary stents are usually made of 316L stainless steel (nominal composition: 00Cr17Ni12Mo 2), NiTi alloy (nominal composition: Ni55.8Ti), L605 cobalt alloy (nominal composition: Co20Cr15W10 Ni) and MP35N cobalt alloy (nominal composition: Co35Ni20Cr10 Mo). However, these alloys all contain Cr and Ni elements, and although they exist as metal compounds and are protected by a passivation film, these metals still have the risk of ion precipitation of harmful elements after being implanted into the human body, and it is necessary to evaluate the corrosion resistance and biocompatibility of these materials in the human environment for a long time. A novel coronary artery stent metal material is searched, the problem of the risk of precipitation of harmful element ions in the existing metal material is solved, and the novel coronary artery stent metal material becomes the research front of material discipline and medicine.

Disclosure of Invention

The invention provides a processing method of a TiMn medical titanium alloy coronary artery drug-coated stent, which solves the problem that after the stent is implanted into a human body, harmful metal ions are separated out under the influence of a corrosive medium to damage the health of the patient.

In order to solve the above technical problems, the present invention specifically provides the following technical solutions.

A novel medical titanium alloy coronary artery drug-coated stent comprises the following chemical components in percentage by mass of a titanium alloy gold Kirschner wire material: 5.0 to 14.0 percent of Mn, less than or equal to 0.30 percent of Fe, less than or equal to 0.16 percent of O, less than or equal to 0.01 percent of N, less than or equal to 0.001 percent of H, and the balance of Ti.

The method comprises the steps of smelting an alloy ingot by using a vacuum consumable arc furnace, forging, hot rolling and the like to obtain a titanium alloy bar, then performing mechanical perforation, peeling, centerless grinding, cold rolling, cold drawing and straightening to obtain a final finished product of a titanium alloy capillary tube, and finally performing microsecond optical fiber laser engraving, vacuum heat treatment, electrochemical polishing and the like to prepare a finished product of a metal bracket. And then mixing polylactic-co-glycolic acid (PLGA) and rapamycin in proportion to form a solution, uniformly spraying the medicinal solution on the outer surface of the metal stent by using a spraying machine, airing in a clean environment, and finally conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment to prepare the novel titanium alloy coronary artery medicament coating stent.

A processing method of a novel medical titanium alloy coronary artery drug-coated stent specifically comprises the following steps:

step one, preparing a titanium alloy ingot by adopting vacuum consumable melting;

secondly, forging by adopting a quick forging machine and a precision forging machine;

step three, hot rolling is carried out by adopting a horizontal rolling mill to prepare a rough bar blank with a proper size;

step four, obtaining a rough pipe blank after mechanical drilling processing is adopted; the surface roughness is improved by peeling and centerless grinding;

step five, cold rolling is carried out by adopting a cold rolling mill, and a thin tube blank is obtained after repeated annealing treatment in the middle;

sixthly, drawing deformation of the tube blank is carried out by adopting drawing equipment to obtain a capillary tube blank;

seventhly, straightening the wires by adopting a slide block straightening machine;

step eight, engraving a coronary artery stent blank by microsecond optical fiber laser;

step nine, carrying out vacuum heat treatment on the support blank;

step ten, carrying out electrochemical polishing on the support blank to prepare a finished metal support;

step eleven, preparing a drug solution of polylactic-co-glycolic acid (PLGA) and rapamycin;

step twelve, uniformly spraying the medicinal solution on the outer surface of the metal bracket by using a spraying machine, and airing in a clean environment; and (3) conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment to prepare the novel titanium alloy coronary artery drug-coated stent.

Further, in the first step, titanium sponge, metal Mn, metal Fe and compound TiO are required to be adopted ₂ Preparing materials according to the components of the titanium alloy, adopting vacuum self-consumption three-time smelting, filling argon in the smelting process, wherein the argon filling pressure is 5000-10000 Pa in the first smelting process, and the argon filling pressure is 20000-30000 Pa in the second and third smelting processes, and obtaining the TiMn titanium alloy cast ingot.

Further, in the second step, cogging forging is required to be carried out at 1000-1100 ℃, finish forging is carried out at 800-950 ℃, the heat preservation time is controlled to be 1-6 h, and the deformation amount of each firing is not less than 60%.

Further, in the third step, the rolling temperature is controlled to be 750-850 ℃, the heat preservation time is 1-2 hours, and the deformation of each pass is controlled to be within 15%.

Further, in the fourth step, firstly, the rolled bar blank is machined into a proper length, then the rolled blank is prepared into a TiMn alloy pipe blank by adopting a precise drilling process, and the roughness Ra of the inner surface is controlled within 1.6 mu m; the roughness Ra of the outer surface of the tube blank is controlled within 1.6 mu m through the peeling and centerless grinding processes.

Further, in the fifth step, the tube blank is subjected to multi-pass cold rolling deformation on a cold rolling tube mill, the single-pass deformation is controlled to be 10-25%, then intermediate vacuum annealing treatment is carried out, then cold rolling is carried out continuously, and finally the thin-gauge TiMn alloy tube blank is prepared.

Further, in the sixth step, multi-pass cold-drawing deformation of the thin tube blank is carried out on a drawing machine, the single-pass deformation amount is controlled to be 10-20%, then intermediate vacuum annealing treatment is carried out, and then cold drawing is continued, so that the TiMn alloy capillary tube blank is finally prepared.

Further, in the seventh step, straightening of the capillary is performed by using a straightener, and the bending degree needs to be ensured to be less than 0.3 mm/m.

Further, in the eighth step, firstly, the long capillary tube is processed into the length required by the coronary artery stent, and then microsecond fiber laser is adopted to carve a coronary artery stent blank, wherein the pulse width is 10-30 mus, the laser power is 100-300W, and the pulse frequency is 8000-15000 Hz.

Further, in the ninth step, the coronary artery blank is subjected to vacuum heat treatment, the heat treatment temperature is 600-700 ℃, the temperature is kept for 5-15 min, and the coronary artery blank is discharged from the furnace after being rapidly cooled by liquid nitrogen, so that the internal stress formed on the stent blank during laser engraving is eliminated, and the mechanical property of the stent is further adjusted.

Further, in the step ten, performing electrochemical polishing on the stent blank, wherein the polishing solution is 6 vol.% perchloric acid, 35 vol.% n-butanol and 59 vol.% methanol, the voltage is 10-20V, the temperature is-20 to-30 ℃, and the roughness Ra of the inner surface and the outer surface is less than 0.1 μm, so as to prepare the finished titanium alloy stent.

Further, in the eleventh step, PLGA is dissolved in ethyl acetate or tetrahydrofuran and fully stirred, then a proper amount of rapamycin is added, and a uniform solution is formed after further fully stirring, so that the drug loading in the finished stent coating is ensured to be 2-3 mug/mm ² 。

Further, in the twelfth step, the metal support is placed into the sleeve and fixed on automatic ultrasonic spraying equipment, and then ultrasonic atomization spraying is carried out, wherein the spraying air pressure is 0.2-0.28 MPa, the atomization power is 1.2-2.0W, the liquid inlet speed is 0.1-0.2 mL/min, and the thickness of the coating is 5-6 microns; and after the spraying is finished, airing in a clean environment, and then carrying out vacuum drying for 24-48 h. And (3) conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment, thereby preparing the novel titanium alloy coronary artery drug-coated stent.

The design idea of the invention is as follows:

the alloy comprises the following components in percentage by mass: 5.8 to 6.2 percent of Al element, 3.8 to 4.2 percent of V element, 0.15 to 0.2 percent of Fe element, 0.08 to 0.13 percent of O element, less than or equal to 0.05 percent of C element, less than or equal to 0.005 percent of H element, less than or equal to 0.01 percent of N element, and the balance of Ti; the design idea of the components is as follows: the strength of titanium is improved by adding Mn element necessary for human body, a novel medical titanium alloy is formed, the risk of human body injury caused by precipitation of harmful elements is thoroughly eliminated, and the requirement of the coronary artery drug-coated stent on the performance of raw materials is met.

The invention adopts a special processing technology, adopts a vacuum consumable electrode arc furnace to smelt an alloy cast ingot, then adopts the working procedures of forging, hot rolling and the like, can effectively control the strength and the grain size of the alloy by controlling the heating temperature and the deformation amount in hot processing, realizes the reasonable matching of the strength and the plasticity, prepares a titanium alloy bar, then can effectively control the strength and the plasticity of the alloy by mechanical perforation, peeling, centerless grinding, cold rolling, cold drawing and straightening and by the deformation amount of cold rolling and drawing and the intermediate annealing temperature, thereby preparing the final finished product of the titanium alloy capillary; finally, the support structure is finely carved by microsecond fiber laser to realize the accurate forming of the support; effectively reducing the roughness of the inner surface and the outer surface of the stent by high-precision machining hole making and electrochemical polishing, thereby preparing the qualified coronary artery metal stent; the novel titanium alloy coronary artery drug-coated stent is prepared by mixing PLGA and rapamycin solution, spraying the solution on a metal stent by using an ultrasonic atomization spraying machine and drying.

Compared with the prior art, the invention has the following advantages and beneficial effects.

1. The invention provides a preparation method of a novel medical titanium alloy coronary artery drug coating stent, which can be used for producing titanium alloy bars, tubes and coronary artery stents with various specifications and providing alloy raw materials for medical instruments in cardiovascular medicine.

2. The strength of titanium is improved by adding Mn element necessary for human body, a novel medical titanium alloy is formed, the risk of human body injury caused by precipitation of harmful elements is thoroughly eliminated, and the requirement of coronary artery stent on the performance of raw materials is met.

3. According to the invention, the support structure is finely carved by microsecond optical fiber laser, so that the accurate forming of the support is realized; the roughness of the inner surface and the outer surface of the stent is effectively reduced through high-precision machining hole making and electrochemical polishing, so that the qualified coronary artery drug coating stent is prepared.

Drawings

FIG. 1 the microstructure of a phi 4.0mm gauge TiMn alloy tube prepared in example 1.

FIG. 2 the microstructure of a phi 3.0mm gauge TiMn alloy tube prepared in example 2.

FIG. 3 the microstructure of a 2.75mm diameter TiMn alloy tube made in example 3.

FIG. 4 the microstructure of a 2.25mm gauge TiMn alloy tube made in example 4.

Detailed Description

Some embodiments of the invention are disclosed below, and those skilled in the art can appropriately modify the process parameters to achieve the invention according to the disclosure herein. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.

A novel medical titanium alloy coronary artery drug coating stent comprises the following chemical components in percentage by mass of titanium alloy gold Kirschner wire materials: 5.0 to 14.0 percent of Mn, less than or equal to 0.30 percent of Fe, less than or equal to 0.16 percent of O, less than or equal to 0.01 percent of N, less than or equal to 0.001 percent of H, and the balance of Ti.

step nine, carrying out vacuum heat treatment on the support blank;

Further, in the eleventh step, PLGA is dissolved in ethyl acetate or tetrahydrofuran and fully stirred, then a proper amount of rapamycin is added, and a uniform solution is formed after further full stirring, so that the drug loading rate in the finished stent coating is ensured to be 2-3 mu g/mm ² 。

Example 1.

The titanium alloy Kirschner wire material of the embodiment comprises the following components in percentage by mass: 6.04% of Mn element, 0.18% of Fe element, 0.10% of O element, 0.0007% of H element, 0.005% of N element and the balance of Ti.

The processing method of the titanium alloy coronary artery drug coating stent comprises the following steps:

step one, adopting titanium sponge, metal Mn, metal Fe and compound TiO ₂ And preparing materials according to the components of the titanium alloy, and carrying out vacuum consumable three times of smelting, wherein the argon filling pressure during the first time of smelting is 7600MPa, the argon filling pressure during the second time of smelting is 25300Pa, and the argon filling pressure during the third time of smelting is 28700Pa, so that a phi 365mm titanium alloy ingot with stable and uniform components is obtained.

And step two, cogging and forging at 1070 ℃, finish forging at 850 ℃, keeping the temperature for 5 hours, and controlling the deformation amount at 72% each time.

And step three, rolling the forged rough bar blank by adopting a transverse rolling mill at the rolling temperature of 800 ℃ for 1.5h, controlling the deformation of each pass to be 15%, and preparing the titanium bar blank with the diameter of 20 mm.

And step four, processing the rolled bar billet into a proper length, then preparing a TiMn alloy pipe blank by adopting a drilling process, controlling the roughness Ra of the inner surface of the pipe blank to be 1.6 mu m, and controlling the roughness Ra of the outer surface of the pipe blank to be within 1.6 mu m by peeling and centerless grinding processes.

Step five, performing cold rolling deformation on the thick pipe blank on a cold rolling pipe mill, controlling the single-pass deformation to be 21%, and lubricating the core rod by using high-speed steel materials and lubricating oil; after oil removal, vacuum annealing is carried out at 700 ℃, the heat preservation time is 1h, then cold rolling deformation is carried out, and the process is circulated for a plurality of times, so that the titanium alloy tube blank with the diameter of 8mm is finally prepared.

Step six, performing cold drawing deformation on the titanium alloy tube blank on drawing equipment, wherein the single-pass deformation amount is controlled to be 10-18%, the core rod is made of high-speed steel materials, and lubricating oil is selected for lubrication; after oil removal, vacuum annealing is carried out at 650 ℃, the heat preservation time is 1h, then cold drawing deformation is carried out, and the steps are circulated for multiple times, so that the titanium alloy capillary tube with the diameter of 4.0mm is finally prepared.

And seventhly, straightening the capillary tube by using a straightening machine, wherein the straightness is less than 0.3mm/m after straightening. The room temperature tensile properties of the capillaries are shown in Table 1.

Table 1 mechanical properties test results of the TiMn alloy tube with a phi of 4.0mm prepared in example 1.

And step eight, firstly processing the long capillary tube into the length required by the coronary artery stent, and then engraving a coronary artery stent blank by microsecond fiber laser, wherein the pulse width is 18 microseconds, the laser power is 193W, and the pulse frequency is 13200 Hz.

And step nine, carrying out vacuum heat treatment on the coronary artery stent blank, wherein the heat treatment temperature is 680 ℃, preserving the heat for 11min, and discharging the coronary artery stent blank after the coronary artery stent blank is rapidly cooled by liquid nitrogen.

And step ten, carrying out electrochemical polishing on the bracket blank, wherein the polishing solution is 6 vol.% perchloric acid, 35 vol.% n-butanol and 59 vol.% methanol, the voltage is 17V, the temperature is-22 ℃, and the roughness Ra value of the inner surface and the outer surface is smaller than 0.1 mu m, so that the finished titanium alloy bracket is prepared.

Eleven, dissolving PLGA in ethyl acetate, fully stirring, then adding a proper amount of rapamycin, further fully stirring to form a uniform solution, and ensuring that the drug loading in the finished stent coating is 2.8 mu g/mm ² 。

Step twelve, placing the metal support into the sleeve, fixing the metal support on automatic ultrasonic spraying equipment, and then carrying out ultrasonic atomization spraying, wherein the spraying air pressure is 0.21MPa, the atomization power is 2.0W, the liquid inlet speed is 0.17 mL/min, and the thickness of the coating is 5.9 microns; after spraying, the paint was dried in a clean environment and then dried in vacuum for 46 h. And (3) conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment, thereby preparing the novel titanium alloy coronary artery drug-coated stent.

Example 2.

The titanium alloy Kirschner wire material of the embodiment comprises the following components in percentage by mass: the titanium alloy Kirschner wire material of the embodiment comprises the following components in percentage by mass: 13.4% of Mn element, 0.15% of Fe element, 0.12% of O element, 0.0004% of H element, 0.003% of N element and the balance of Ti.

step one, adopting titanium sponge, metal Mn, metal Fe and compound TiO ₂ And preparing materials according to the components of the titanium alloy, and carrying out vacuum consumable three times of smelting, wherein the argon filling pressure during the first time of smelting is 9700MPa, the argon filling pressure during the second time of smelting is 27000Pa, and the argon filling pressure during the third time of smelting is 29400Pa, so that a phi 365mm titanium alloy ingot with stable and uniform components is obtained.

And step two, cogging and forging at 1050 ℃, finish forging at 930 ℃, keeping the temperature for 4 hours, and controlling the deformation amount at 75% each time.

And step three, rolling the forged rough bar blank by adopting a transverse rolling mill, wherein the rolling temperature is 830 ℃, the heat preservation time is 2 hours, the deformation of each pass is controlled to be 12 percent, and the titanium bar blank with the diameter of 16mm is prepared.

Step five, performing cold rolling deformation on the thick pipe blank on a cold rolling pipe mill, wherein the single-pass deformation amount is controlled to be 23%, and the core rod is made of high-speed steel materials and lubricated by lubricating oil; after oil removal, vacuum annealing is carried out at 720 ℃, the heat preservation time is 1.5h, then cold rolling deformation is carried out, and the process is circulated for a plurality of passes, so that the titanium alloy tube blank with the diameter of 6mm is finally prepared.

Step six, performing cold drawing deformation on the titanium alloy tube blank on drawing equipment, wherein the single-pass deformation amount is controlled to be 15-20%, and the core rod is made of high-speed steel materials and lubricated by lubricating oil; after oil removal, vacuum annealing is carried out at 660 ℃, the heat preservation time is 0.5h, then cold drawing deformation is carried out, and the steps are circulated for multiple times, so that the titanium alloy capillary tube with the diameter of 3.0mm is finally prepared.

And seventhly, straightening the capillary tube by using a straightening machine, wherein the straightness is less than 0.3mm/m after straightening. The room temperature tensile properties of the capillaries are shown in Table 2.

Table 2 mechanical property test results of the TiMn alloy tube with a phi 3.0mm specification prepared in example 2.

And step eight, firstly processing the long capillary tube into the length required by the coronary artery stent, and then engraving a coronary artery stent blank by microsecond fiber laser, wherein the pulse width is 26 mu s, the laser power is 276W, and the pulse frequency is 11500 Hz.

And step nine, carrying out vacuum heat treatment on the coronary artery stent blank, wherein the heat treatment temperature is 650 ℃, keeping the temperature for 8min, and discharging the coronary artery stent blank after the coronary artery stent blank is rapidly cooled by liquid nitrogen.

Step ten, carrying out electrochemical polishing on the support blank, wherein the polishing solution is 6 vol.% perchloric acid, 35 vol.% n-butanol and 59 vol.% methanol, the voltage is 15V, the temperature is-28 ℃, and the roughness Ra of the inner surface and the outer surface is smaller than 0.1 mu m, so that the finished titanium alloy support is prepared.

Eleven, dissolving PLGA in tetrahydrofuran, fully stirring, then adding a proper amount of rapamycin, further fully stirring to form a uniform solution, and ensuring that the drug loading in the finished stent coating is 2.6 mu g/mm ² 。

Step twelve, placing the metal support into the sleeve, fixing the metal support on automatic ultrasonic spraying equipment, and then carrying out ultrasonic atomization spraying, wherein the spraying air pressure is 0.25MPa, the atomization power is 1.8W, the liquid inlet speed is 0.16 mL/min, and the thickness of the coating is 5.5 microns; after spraying, the paint is dried in a clean environment and then dried in vacuum for 36 hours. And (3) conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment, thereby preparing the novel titanium alloy coronary artery drug-coated stent.

Example 3.

The titanium alloy Kirschner wire material of the embodiment comprises the following components in percentage by mass: 8.7% of Mn element, 0.11% of Fe element, 0.15% of O element, 0.0005% of H element, 0.006% of N element and the balance of Ti.

step one, adopting titanium sponge, metal Mn, metal Fe and compound TiO ₂ And preparing materials according to the components of the titanium alloy, and adopting vacuum consumable three times of smelting, wherein the argon filling pressure during the first smelting is 5800MPa, the argon filling pressure during the second smelting is 22000Pa, and the argon filling pressure during the third smelting is 24900Pa, so that a phi 365mm titanium alloy ingot with stable and uniform components is obtained.

And step two, cogging and forging at 1050 ℃, finish forging at 820 ℃, keeping the temperature for 3 hours, and controlling the deformation amount at 78% in each firing.

And step three, rolling the forged rough bar blank by adopting a transverse rolling mill, wherein the rolling temperature is 780 ℃, the heat preservation time is 1h, the deformation of each pass is controlled to be 15%, and the titanium bar blank with the diameter of 18mm is prepared.

Step five, performing cold rolling deformation on the thick pipe blank on a cold rolling pipe mill, wherein the single-pass deformation amount is controlled to be 18%, and the core rod is made of high-speed steel materials and lubricated by lubricating oil; after oil removal, vacuum annealing is carried out at 680 ℃ for 0.6h, then cold rolling deformation is carried out, and the process is circulated for multiple passes, so that the titanium alloy tube blank with the diameter of 5.5mm is finally prepared.

Step six, performing cold drawing deformation on the titanium alloy tube blank on drawing equipment, wherein the single-pass deformation amount is controlled to be 10-17%, the core rod is made of high-speed steel materials, and lubricating oil is selected for lubrication; after oil removal, vacuum annealing is carried out at 640 ℃ for 0.5h, then cold drawing deformation is carried out, and the steps are repeated for a plurality of times, so that the titanium alloy capillary tube with the diameter of 2.75mm is finally prepared.

And seventhly, straightening the capillary tube by using a straightening machine, wherein the straightness is less than 0.3mm/m after straightening. The room temperature tensile properties of the capillaries are shown in Table 3.

Table 3 mechanical properties test results of the TiMn alloy tube with a diameter of 2.75mm prepared in example 3.

And step eight, firstly processing the long capillary tube into the length required by the coronary artery stent, and then engraving a coronary artery stent blank by microsecond fiber laser, wherein the pulse width is 12 mu s, the laser power is 137W, and the pulse frequency is 9600 Hz.

And step nine, carrying out vacuum heat treatment on the coronary artery stent blank, wherein the heat treatment temperature is 650 ℃, keeping the temperature for 6min, and discharging the coronary artery stent blank after the coronary artery stent blank is rapidly cooled by liquid nitrogen.

Step ten, carrying out electrochemical polishing on the support blank, wherein the polishing solution is 6 vol.% perchloric acid, 35 vol.% n-butanol and 59 vol.% methanol, the voltage is 12V, the temperature is-27 ℃, and the roughness Ra of the inner surface and the outer surface is smaller than 0.1 mu m, so that the finished titanium alloy support is prepared.

Step eleven, dissolving PLGA in ethyl acetate, fully stirring, and then addingRapamycin in an amount to form a homogeneous solution after further thorough mixing to ensure a drug loading of 2.5 μ g/mm in the finished stent coating ² 。

Step twelve, placing the metal support into the sleeve, fixing the metal support on automatic ultrasonic spraying equipment, and then carrying out ultrasonic atomization spraying, wherein the spraying air pressure is 0.29MPa, the atomization power is 1.4W, the liquid inlet speed is 0.14 mL/min, and the thickness of the coating is 5.4 microns; after spraying, the paint was dried in a clean environment and then vacuum dried for 32 h. And (3) conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment, thereby preparing the novel titanium alloy coronary artery drug-coated stent.

Example 4.

The titanium alloy Kirschner wire material of the embodiment comprises the following components in percentage by mass: 11.3% of Mn element, 0.16% of Fe element, 0.095% of O element, 0.0004% of H element, 0.008% of N element, and the balance of Ti.

step one, adopting titanium sponge, metal Mn, metal Fe and compound TiO ₂ The components of the titanium alloy are proportioned, and the titanium alloy is smelted for three times by adopting vacuum consumable melting, wherein the argon filling pressure during the first smelting is 8300MPa, the argon filling pressure during the second smelting is 26800Pa, and the argon filling pressure during the third smelting is 29200Pa, so that a phi 365mm titanium alloy cast ingot with stable and uniform components is obtained.

And step two, cogging and forging at 1020 ℃, finish forging at 820 ℃, keeping the heat preservation time for 2 hours, and controlling the deformation amount at 65% in each firing.

And step three, rolling the forged rough bar blank by adopting a transverse rolling mill, wherein the rolling temperature is 760 ℃, the heat preservation time is 2 hours, the deformation of each pass is controlled to be 15%, and the titanium bar blank with the diameter of 14mm is prepared.

Step five, performing cold rolling deformation on the thick pipe blank on a cold rolling pipe mill, wherein the single-pass deformation amount is controlled to be 13%, and the core rod is made of high-speed steel materials and lubricated by lubricating oil; after oil removal, vacuum annealing is carried out at 640 ℃, the heat preservation time is 0.8h, then cold rolling deformation is carried out, and the process is circulated for a plurality of passes, so that the titanium alloy tube blank with the diameter of 6mm is finally prepared.

Step six, performing cold drawing deformation on the titanium alloy tube blank on drawing equipment, wherein the single-pass deformation amount is controlled to be 12-20%, and the core rod is made of high-speed steel materials and lubricated by lubricating oil; after oil removal, vacuum annealing is carried out at 600 ℃ for 0.6h, then cold drawing deformation is carried out, and the steps are repeated for a plurality of times, so that the titanium alloy capillary tube with the diameter of 2.25mm is finally prepared.

And seventhly, straightening the capillary tube by using a straightening machine, wherein the straightness is less than 0.3mm/m after straightening. The room temperature tensile properties of the capillaries are shown in Table 4.

Table 4 mechanical properties test results of the TiMn alloy tube with a diameter of 2.25mm prepared in example 4.

And step eight, firstly processing the long capillary tube into the length required by the coronary artery stent, and then engraving a coronary artery stent blank by microsecond fiber laser, wherein the pulse width is 12 mu s, the laser power is 129W, and the pulse frequency is 11500 Hz.

And step nine, carrying out vacuum heat treatment on the coronary artery stent blank, wherein the heat treatment temperature is 620 ℃, keeping the temperature for 15min, and discharging the coronary artery stent blank after the coronary artery stent blank is rapidly cooled by liquid nitrogen.

Step ten, carrying out electrochemical polishing on the support blank, wherein the polishing solution is 6 vol.% perchloric acid, 35 vol.% n-butanol and 59 vol.% methanol, the voltage is 15V, the temperature is-25 ℃, and the roughness Ra of the inner surface and the outer surface is smaller than 0.1 mu m, so that the finished titanium alloy support is prepared.

Eleven, dissolving PLGA in tetrahydrofuran, fully stirring, then adding a proper amount of rapamycin, further fully stirring to form a uniform solution, and ensuring that the drug loading in the finished stent coating is 2.2 mu g/mm ² 。

Step twelve, placing the metal support into the sleeve, fixing the metal support on automatic ultrasonic spraying equipment, and then carrying out ultrasonic atomization spraying, wherein the spraying air pressure is 0.23 MPa, the atomization power is 1.6W, the liquid inlet speed is 0.11 mL/min, and the thickness of the coating is 5.2 microns; after spraying, the paint is dried in a clean environment and then dried in vacuum for 25 h. And (3) conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment, thereby preparing the novel titanium alloy coronary artery drug-coated stent.

The embodiment result shows that the invention provides a novel medical titanium alloy coronary artery drug coating stent processing method, which comprises the steps of smelting an alloy cast ingot by adopting a vacuum consumable arc furnace, then forging, hot rolling and the like, effectively controlling the strength and the grain size of the alloy by controlling the heating temperature and the deformation amount during hot processing, realizing reasonable matching of the strength and the plasticity, preparing a titanium alloy bar, and then effectively controlling the strength and the plasticity of the alloy by mechanical perforation, peeling, centerless grinding, rolling, drawing and straightening through cold rolling and drawing deformation amount and intermediate annealing temperature, thereby preparing a final finished product of a titanium alloy capillary tube with excellent mechanical property; the support structure is finely carved by microsecond optical fiber laser to realize the accurate forming of the support; effectively reducing the roughness of the inner surface and the outer surface of the stent by high-precision machining hole making and electrochemical polishing, thereby preparing the qualified coronary artery metal stent; the novel titanium alloy coronary artery drug-coated stent is prepared by mixing PLGA and rapamycin solution, spraying the solution on a metal stent by using an ultrasonic atomization spraying machine and drying.

Claims

1. A processing method of a novel medical titanium alloy coronary artery drug-coated stent is characterized in that a titanium alloy Kirschner wire comprises the following chemical components in percentage by mass: 5.0 to 14.0 percent of Mn, less than or equal to 0.30 percent of Fe, less than or equal to 0.16 percent of O, less than or equal to 0.01 percent of N, less than or equal to 0.001 percent of H, and the balance of Ti;

the method comprises the following steps:

step one, adopting titanium sponge, metal Mn, metal Fe and compound TiO ₂ According to the composition of titanium alloyThe method comprises the following steps of smelting for three times by vacuum self-consumption, filling argon in the smelting process, filling argon at the pressure of 5000-10000 Pa in the first smelting process, and filling argon at the pressure of 20000-30000 Pa in the second and third smelting processes to obtain a TiMn titanium alloy cast ingot;

step three, carrying out hot rolling by adopting a transverse rolling mill, controlling the rolling temperature to be 750-850 ℃, keeping the temperature for 1-2 h, and controlling the deformation of each pass to be within 15%, so as to prepare a coarse bar blank with a proper size;

seventhly, straightening the wires by adopting a slide block straightening machine, wherein the bending degree is less than 0.3 mm/m;

step nine, carrying out vacuum heat treatment on the support blank;

2. The processing method of the novel medical titanium alloy coronary artery drug-coated stent as claimed in claim 1, wherein in the second step, cogging forging is required to be carried out at 1000-1100 ℃, finish forging is carried out at 800-950 ℃, the heat preservation time is controlled to be 1-6 h, and the deformation amount per firing is not less than 60%.

3. The processing method of the novel medical titanium alloy coronary artery drug-coated stent according to claim 1, characterized in that in the fourth step, firstly, the rolled bar stock is machined to a proper length, and then the rolled stock is prepared into a TiMn alloy tube blank by adopting a precise drilling process, wherein the roughness Ra of the inner surface is controlled within 1.6 μm; the roughness Ra of the outer surface of the tube blank is controlled within 1.6 mu m through the peeling and centerless grinding processes.

4. The processing method of the novel medical titanium alloy coronary artery drug-coated stent according to claim 1, characterized in that in the fifth step, a cold rolling mill is adopted to perform multi-pass cold rolling deformation of a tube blank, the single-pass deformation is controlled to be 10-25%, then intermediate vacuum annealing treatment is performed, then cold rolling is continued, and finally a thin-gauge TiMn alloy tube blank is prepared.

5. The processing method of the novel medical titanium alloy coronary artery drug-coated stent according to claim 1, characterized in that in the sixth step, the thin tube blank is subjected to multi-pass cold-drawing deformation on a drawing machine, the single-pass deformation is controlled to be 10-20%, then intermediate vacuum annealing treatment is performed, and then cold-drawing is continued, so that the TiMn alloy capillary tube blank is finally prepared.

6. The processing method of the novel medical titanium alloy coronary artery drug-coated stent according to claim 1, characterized in that in step eight, the long capillary is firstly processed into the length required by the coronary artery stent, and then the coronary artery stent blank is carved by microsecond fiber laser, the pulse width is 10-30 μ s, the laser power is 100-300W, and the pulse frequency is 8000-15000 Hz.

7. The processing method of the novel medical titanium alloy coronary artery drug-coated stent according to claim 1, wherein in the ninth step, the coronary artery blank is subjected to vacuum heat treatment at 600-700 ℃, is kept for 5-15 min, is rapidly cooled by liquid nitrogen, and is discharged.

8. The processing method of the novel medical titanium alloy coronary artery drug-coated stent as claimed in claim 1, wherein in the step ten, the stent blank is subjected to electrochemical polishing, the polishing solution is 6 vol.% perchloric acid, 35 vol.% n-butanol and 59 vol.% methanol, the voltage is 10-20V, the temperature is-20 to-30 ℃, and the roughness Ra value of the inner surface and the outer surface is less than 0.1 μm, so as to prepare the finished titanium alloy stent.

9. The processing method of the novel medical titanium alloy coronary artery drug-coated stent according to claim 1, characterized in that in the eleventh step, PLGA is dissolved in ethyl acetate or tetrahydrofuran and fully stirred, then a proper amount of rapamycin is added, and after further fully stirring, a uniform solution is formed, so that the drug-loading rate in the finished stent coating is ensured to be 2-3 μ g/mm ² 。

10. The processing method of the novel medical titanium alloy coronary artery drug-coated stent according to claim 1, characterized in that in the twelfth step, the metal stent is placed in a sleeve, fixed on an automatic ultrasonic spraying device, and then ultrasonic atomization spraying is carried out, wherein the spraying air pressure is 0.2-0.28 MPa, the atomization power is 1.2-2.0W, the liquid inlet rate is 0.1-0.2 mL/min, and the thickness of the coating is 5-6 μm; after spraying, airing in a clean environment, and then carrying out vacuum drying for 24-48 h; and (3) conveying the saccule to a proper position of the stent by using special pressing and holding machine equipment, thereby preparing the novel titanium alloy coronary artery drug-coated stent.