TWI542336B - Method for manufacturing blood vessel stent of polylactide bioplastics - Google Patents

Description

Method for manufacturing vascular stent of polylactide bioplastic

The present invention relates to a method of manufacturing a blood vessel stent, and more particularly to a method of manufacturing a degradable blood vessel stent.

In modern life, cardiovascular disease is one of the most common problems, and arteriosclerosis and myocardial obstruction are the main reasons, which are related to diet, obesity and lack of exercise, and treatment of arteriosclerosis and myocardial occlusion. The first method is bypass surgery, and the other is implantation of a blood vessel stent. In the operation of implanting a vascular stent, the surgical procedure is roughly as follows: the vascular stent is inserted from the thigh blood vessel to the lesion point, and then the balloon enclosed in the blood vessel stent is inflated to expand and support the blood vessel stent. The blood vessel wall is then removed by deflation of the balloon, and the vascular stent continues to support the vessel wall at the original lesion site. In this way, the vascular stent is implanted at the location of the lesion to support the stenotic or obstructed blood vessels, keeping the blood flow in the blood vessels clear, providing sufficient oxygen between the heart and the organs to solve the stenosis or obstruction of the blood vessels. The vascular problem, and can greatly reduce the risk of occlusion after completion of vascular repair.

According to the traditional vascular stent manufacturing method, there are two methods, such as laser processing or lithography exposure processing. Among them, laser processing uses a laser processing machine to apply a three-dimensional cutting forming to a metal material, but the laser processing machine operates. It is not easy, and the high strength of the laser during the cutting process will reduce the strength of the material, and the metal material may leave a rough edge and a rough surface after cutting. The burrs and rough surfaces left by the edges may interfere with the flow of blood and may even damage the blood cells or other components of the blood. The lithography exposure processing is performed by lithographic etching of the metal material in a planar state, and then forming a blood vessel stent by a coiling process. However, the vascular stent processed by the lithography is characterized in that the etching portion is uneven and irregular, and the mesh structure of the stent is not easily formed according to a predetermined pattern.

However, regardless of the processing method of any of the above-mentioned vascular stents, most of them rely on the import of foreign-made vascular stents to supply the domestic medical market. Therefore, in order to solve the current technical deficiencies in production, it is necessary to use domestic manufacturers. Familiar processing techniques are used to create vascular stents to address the aforementioned problems.

In order to solve the deficiencies of the prior art, the object of the present invention is mainly to make a blood vessel stent with a plastic dropable material, in order to overcome the difficulties of the prior art in the process and technology.

According to the object of the present invention, the present invention provides a method for manufacturing a degradable blood vessel stent, which comprises forming a thin tube by plastic processing, using a heat treatment to weaken the internal stress of the thin tube to form a heat treatment thin tube, and cutting the heat treatment thin tube with an energy beam. Forming a thin tube of a pattern, and then heat-treating the thin tube of the pattern to weaken the internal stress in the cutting process, forming a secondary heat treatment thin tube, immersing the secondary heat treatment thin tube in the acid washing liquid, and applying ultrasonic waves to the acid washing liquid, The slag, the oil stain and the carbonized film layer on the surface of the secondary heat treatment thin tube are removed to form a desiccated thin tube, and the de-stained thin tube is pressed onto the balloon or the balloon to form a degradable blood vessel support.

Among them, the degradable material is polylactic acid, polylactic acid or polyglutamic acid.

Wherein, the plastic working process is performed by using a straw making machine and then extruding the mold to form a thin tube.

Wherein, the energy beam is provided by a laser cutting machine, the processing conditions of the laser cutting machine include pulse frequency: 80~120kHz, pulse width: 0.8-1.5ms, working energy: 4.5~6W, working auxiliary gas Pressure: 10~20Bar, defocusing amount: -0.2~0.3mm, cutting speed: 20mm/s, laser wavelength: 1055λ.

Wherein, the heat treatment step of the thin tube or the pattern thin tube comprises annealing the furnace at a temperature of 3 to 5 degrees Celsius per minute, heating to an annealing temperature (for example, 50 to 60 degrees Celsius), and placing a thin tube or a pattern tube at the temperature of 0.5. ~1.5 hours, then cool the thin tube or pattern tube to room temperature at 1 to 3 degrees Celsius per minute; apply the thin tube or pattern to the distilled water and apply ultrasonic waves to vortex the tube or The thin tube of the pattern is 3 to 5 minutes; finally, the thin tube or the pattern tube is air-dried in the air.

Wherein, the force of the desiccant tube pressed against the balloon or the balloon is between the stress and the plastic interval.

By this design, the manufacturing method of the degradable blood vessel stent has the following advantages:

1. The material is easy to obtain and the price is low.

2. Processing is convenient and fast, and the cost is low.

3. Fine-cut by energy beam, the degradable vascular stent is made of high quality and low impurity.

4. Using the annealing heat treatment method, the internal stress of the degradable blood vessel stent is small.

5. A degradable vascular stent made by heat treatment with a smooth surface and no sharp passivated edges.

6. The selection of materials and the high-quality production method make the degradable vascular stents have corrosion resistance and low repellency.

S101~S106‧‧‧Step procedure

S201~S204‧‧‧Step process

S301~S303‧‧‧Step procedure

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic view showing the manufacturing process of an embodiment of the present invention.

Fig. 2 is a schematic view showing the annealing process of an embodiment of the present invention.

Figure 3 is a schematic diagram of the flow before step 105 to step 106 of Figure 2.

The invention will be described with reference to the accompanying drawings, and the embodiments of the present invention are described in detail below, and the drawings used in the text are used to describe the features, the contents and the advantages of the invention. The subject matter is only for the purpose of illustration and supplementary description, and is not necessarily the true proportion and precise formula dosage after the implementation of the present invention. Therefore, the relationship between the attached process and the dosage of the formula should not be limited, and the patent scope of the present invention in practical implementation is limited. And in the previous description.

Referring to FIG. 1 , an embodiment of a method for manufacturing a degradable blood vessel stent of the present invention includes at least the following steps: S101: plastically processing a degradable material to form a thin tube; for example, before and after high precision. The mold is made, and the processing method of the straw making machine is used to manufacture a thin tube which can degrade the blood vessel stent. The advantages of the straw making machine are simple processing, short forming time, smooth inner and outer surfaces, high parallel precision and dimensional accuracy, and low internal stress during processing; S102: heat treatment is used to weaken the internal stress of the thin tube to form a heat treatment once. S10: The primary heat treatment thin tube is cut into a pattern thin tube according to a predetermined pattern by using an energy beam; for example, the heat treatment thin tube is cut by the energy beam provided by the laser cutting machine, and the light energy is absorbed by the heat treatment tube to make the light It can be converted into heat energy, and the heat treatment thin tube is heated and melted to form a pattern thin tube; S104: using heat treatment to weaken the internal stress of the pattern thin tube to form a secondary heat treatment thin tube; S105: cleaning the secondary heat treatment thin tube to form the desiccated thin tube; for example, immersing the secondary heat treatment thin tube in the acid washing liquid, and applying the acid washing liquid to the acid washing liquid Acoustic wave, used to remove the slag, oil stain and carbonized film layer generated by the secondary heat treatment thin tube cutting process to form a desiccated thin tube; S106: press the desiccated thin tube onto the balloon or the balloon to form a degradable blood vessel stent The force of the press is controlled between the stress (Sy) and the plastic zone (Plastic Zone).

In the present invention, the selection of the degradable material needs to include a combination of mechanical mechanics and physical properties, in accordance with the American Society of Testing & Materials (ASTM) or the Food and Drug Administration. Abbreviation: FDA) standards, for example: need to have biocompatibility, X-ray (x-ray) and magnetic resonance imaging MRI (magnetic resonance imaging) visibility, radial rebound flexibility, transportability, grip The post-degradable material may be polylactic acid, polylactic acid or polyglutamic acid in a small change in the outer contour and the long-term integrity. However, the present invention is not limited thereto, and any of various degradable materials satisfying the foregoing characteristics are within the scope of the claimed invention.

In the present invention, in order to control the tube wall concentricity of the thin tube within a reasonable range (for example, ±0.005~±0.015mm), it is preferable to use a high-precision straw to make a machining machine, and perform step S101; The specification of the thin tube prepared by S101 can be: 1. The outer diameter of the tube is 1~5mm; 2. The wall thickness is 0.06~1mm; 3. The tube length is 8~36mm; 4. The surface roughness is lower than its absolute value. Arithmetic mean (Ra) 16~25nm; 5. The concentric difference is less than 0.001~0.025mm.

In the present invention, since the size of the degradable blood vessel stent is small, it is difficult for a general mechanical manufacturing method to process a complex degradable blood vessel stent mesh shape. Therefore, in step 103, the energy beam is cut once by the laser cutting machine. The reason for the thin tube is that the laser cutting machine can process a small and uniform slit width, and has less processing slag, good processing surface quality, small heat influence, and easy control.

Furthermore, in the step 103, the present invention further includes designing a preset pattern of a structural cell (Cell) of the degradable vascular stent by using a computer-aided drawing software, and further transferring to Computer Aided Engineering (CAE). ), the optimal data for force analysis, distribution and volume change; through the distribution of data and mechanical graphics, modify or change the shape, size, thickness, size, etc. of the design model to achieve enhanced mesh strength Purpose, then import the laser cutting machine to do the pre-processing path processing to simulate the cutting path of the vascular stent, modify the programming language, and finally input the program file of the cutting path after the simulation setting is input to the controller of the laser cutting machine for processing. , the degradable blood vessel stent having the same structure as the preset pattern can be cut. In order to automatically remove the portion of the heat treatment tube that is removed once, or to facilitate the ultrasonic vibration to fall off in step S105, the cutting path is designed to remove the larger area material by cutting the larger area material into segments. Small pieces.

In the present invention, in step 103, the laser cutting machine uses a working auxiliary gas that blows various suitable materials coaxially with the lens to prevent the lens that emits the laser beam from being contaminated and blown away in the cutting area of the laser cutting machine. The slag at the bottom, the working auxiliary gas is preferably compressed air or inert gas, so that the surface of the hot material of the thin tube is heat treated once, the oxidation and exothermic reaction are minimized, the cutting speed is increased, and the melting and evaporation materials are quickly removed. And can suppress It burns excessively. Furthermore, the working setting conditions of the laser cutting machine include: (1) pulse frequency: 80~120 kHz; (2) pulse width: 0.8-1.5 ms; (3) working energy: 4.5~6 W; (4) work assist Gas: compressed air or inert gas, the output pressure is 10~20 Bar; (5) defocusing amount: -0.2~0.3mm; (6) cutting speed: 15~25mm/s (7) working voltage: 200V~480V ; and (8) laser wavelength: 1055λ

The preferred working bar is: pulse frequency: 100 kHz, pulse width: 1 ms, working energy: 5 W, working auxiliary gas: 15 Bar, defocusing amount: 0.3 mm, cutting speed: 20 mm/s, and working voltage: 450V.

In the present invention, the operating condition of the ultrasonic wave in step S104 is: (1) ultrasonic frequency: 16 kHz to 24 kHz, preferably 20 kHz; (2) operation time: 3 to 5 minutes; (3) operating temperature : 20~45 °C.

Among them, ultrasonic waves are used to cause a liquid to generate a cavitation effect (CAVITATION) to clean the secondary heat treatment thin tube, thereby cutting the energy beam caused by the high-temperature cutting of the slit or the deep hole, and the generated slag, oil stain and carbonized film layer and the like Easy to peel off and clean.

In the present invention, the pickling liquid is composed of a cleaning mixture added to a hydrogenation nano solution having a concentration of 10-20 g/L, and the cleaning mixture accounts for 99% by weight of the acid washing liquid and the hydrogenated sodium solution. 1% by weight of the pickling solution, wherein the cleaning mixture is made of 95% pure ethanol or The ethyl acetate having a purity of 75% is mixed with deionized water or pure water, wherein ethanol or ethyl acetate accounts for 1% by weight of the cleaning mixture, and deionized water or pure water accounts for 99% by weight of the cleaning mixture; The control conditions and steps of immersing in the pickling solution are: temperature control at 20-25 degrees, continuous soaking for 3-5 minutes; then heating to 35-45 degrees, continuous soaking for 3-5 minutes, and applying ultrasonic waves during the process .

In the present invention, the heat treatment process of steps 102 and 104 is to heat the thin tube or the pattern thin tube to the annealing temperature and keep it for a sufficient time to cool slowly; thereby improving the structure of the degradable material, and making the crystalline molecules and boundaries of the degradable material The structure is meticulous, and the internal stress generated after processing is removed and the toughness is enhanced and the boundary layer of the reduced structure, molecules and molecules is reduced to homogenize the tissue components. The foregoing heat treatment is an annealing treatment, and the annealing process comprises: S201: heating at an annealing temperature (for example, 55 ° C to 65 ° C) at a temperature of 3 to 5 ° C per minute using an annealing furnace, and thinning the thin tube or the pattern The annealing temperature is 0.5 to 1.5 hours, wherein the heating rate is preferably 3 degrees Celsius per minute, preferably 1 hour; S202: then the thin tube or the pattern tube is cooled to the chamber at a rate of 1 to 3 degrees per minute Celsius. Temperature, wherein the speed cooling is preferably reduced by 1 degree Celsius per minute; S203: the thin tube or the pattern thin tube is applied to the distilled water and subjected to ultrasonic waves to oscillate the thin tube or the pattern thin tube for 3 to 5 minutes; and S204: Finally, the thin tube or the pattern tube is air-dried in the air.

In the present invention, before completing steps 105 to 106, the following steps are performed on the desiccated straw: S301: neutralization cleaning of the desiccated straw; S302: decontaminating thin tube after drying or air-drying cleaning; S303: Check whether the surface of the desiccated straw after drying is defective, and discard if any, otherwise proceed to step 106.

Among them, the method of checking whether the surface of the desiccated thin tube after drying is defective is suitable for the non-destructive flaw detection method, and the non-destructive detection method generally adopts radiographic inspection, stress wave inspection, visual inspection and fluorescent penetrant inspection.

In the present invention, after the completion of step 106, the package sterilization can be further carried out to sterilize the microorganisms by radiation, and at the same time kill the reproducible bacteria, tuberculosis, mold and virus, etc., sterilization time is at least 5-30 minutes, sterilization The time is best for at least 5-15 minutes; while the radiation sterilization method uses γ-ray or β-ray radiation to pass through the ionization process, the atom impacts its kinetic energy into thermal energy and chemical energy, destroys the microbial genetic factor DNA, and achieves The effect of killing microorganisms is high in radiation penetration and the effect is also good.

In view of the above, the present invention overcomes the current international processing methods for degradable vascular stents compared with the prior art, and the present invention integrates and enhances domestic experience and related processing of drawing, extruding and annealing treatment of degradable materials. Machinery, using readily available materials and processing machinery, through a series of processing, to produce a degradable vascular stent suitable for the human body, and to achieve stable quality, smooth surface, high cleanliness, good corrosion resistance and low rejection.

The embodiments described above are merely illustrative of the technical spirit and the features of the present invention, and the purpose of the present invention is to enable those skilled in the art to understand the contents of the present invention and to implement the present invention. That is, the equivalent variations or modifications made by the spirit of the present invention should still be included in the scope of the present invention.

S101~S106‧‧‧Step procedure

Claims (9)

A method for manufacturing a vascular stent of a polylactide bioplastic comprises the steps of: plastically processing a degradable material to form a thin tube; using a heat treatment to weaken a processing internal stress of the thin tube to form a heat treatment thin tube; using the energy beam for the first time The heat treatment thin tube is cut into a pattern thin tube according to a predetermined pattern; the heat treatment is used to weaken the processing internal stress or stress concentration of the pattern thin tube to form a secondary heat treatment thin tube; the secondary heat treatment thin tube is immersed in the acid washing liquid, and Ultrasonic wave is applied to the pickling liquid to remove the slag, oil stain and carbonized film layer generated by the secondary heat treatment thin tube cutting process to form a desiccated thin tube; the desiccated thin tube is pressed onto the balloon or the air bag to form Degrading the blood vessel stent; wherein the heat treatment is to add the thin tube or the pattern tube to 55-65 ° C; wherein the energy beam is provided by a laser cutting machine, and the processing condition of the laser cutting machine is pulse frequency: 80 ~120kHz, pulse width: 0.8-1.5ms, working energy: 4.5~6W, working auxiliary gas: 10~20Bar, defocusing amount: -0.2~0.3mm, Cutting speed: 15 ~ 25mm / s and Operating Voltage: 400V ~ 550V, laser wavelength: 1055λ. The method for producing a vascular stent of a polylactide-based bioplastic according to the above aspect of the invention, wherein the degradable material is polylactic acid, polylactic acid or polyglutamic acid. The method for producing a vascular stent of a polylactide-based bioplastic according to the above aspect of the invention, wherein the degradable vascular stent is formed, and then subjected to packaging sterilization treatment. A method for producing a vascular stent of a polylactide-based bioplastic according to claim 1, wherein The processing conditions of the laser cutting machine are further pulse frequency: 100 kHz, pulse width: 1 ms, working energy: 5 W, working auxiliary gas: 10-20 Bar, defocusing amount: 0.3 mm, cutting speed: 20 mm/s and Working voltage: 450V. The method for manufacturing a vascular stent for a polylactide-based bioplastic according to claim 1, wherein the control condition and the step of immersing the desiccant tube in the pickling solution are temperature control at 20-25 degrees Celsius, and 3- 5 minutes, then heated to 35-45 degrees for 3-5 minutes. The method for manufacturing a vascular stent of a polylactide-based bioplastic according to the invention of claim 6, wherein the pickling liquid is a cleaning mixture and a hydrogenation nano-solution having a concentration of 10-20 g/L, and The cleaning mixture accounts for 99% by weight of the acid washing liquid and the hydrogenated sodium solution accounts for 1% by weight of the acid washing liquid, wherein the cleaning mixture is made of ethanol having a purity of 95% or ethyl acetate having a purity of 75%. The ester is composed of deionized water or pure water, wherein the ethanol or the ethyl acetate accounts for 1% by weight of the cleaning mixture, and the deionized water or the pure water accounts for 99% by weight of the cleaning mixture. The method for manufacturing a vascular stent for a polylactide-based bioplastic according to claim 1, wherein the heat treatment comprises the steps of: annealing the furnace at a temperature of 3 to 5 degrees Celsius per minute, heating the annealing temperature, and The thin tube or the pattern tube is placed at this temperature for 0.5 to 1.5 hours; then the thin tube or pattern tube is cooled to room temperature at a rate of 1 to 3 degrees Celsius per minute; the thin tube or pattern tube is placed in distilled water and subjected to ultrasonic waves To make the tube or pattern tube clean for 3 to 5 minutes by oscillating it; and finally, place the tube or pattern tube in the air and air dry. The method for manufacturing a vascular stent of a polylactide-based bioplastic according to claim 1, wherein the force of the desiccant tube pressed against the balloon or the balloon is between the stress and the plastic interval. The method for manufacturing a vascular stent of a polylactide-based bioplastic according to claim 1, wherein when the ultrasonic wave is applied to the pickling solution, the ultrasonic wave operates at a frequency of 16 kHz to 24 kHz, an operating time of 3 to 5 minutes, and an operating temperature. 20~45°C.