CN101357089A - A kind of manufacturing method of biodegradable magnesium alloy intravascular stent - Google Patents

Abstract

The invention discloses a method for manufacturing a biodegradable magnesium alloy intravascular stent, which comprises the following steps: precision engraving and molding: designing and drawing the required intravascular stent pattern and introducing the pattern into a laser engraving machine; under the protection of an inert gas, Precisely engrave the magnesium alloy capillary with a laser engraving machine; surface brightening treatment: put the precisely engraved intravascular stent into a weakly acidic organic solvent for ultrasonic vibration washing for 1-5 minutes, and the organic solvent is composed of distilled water and absolute ethanol and 5.5<pH value<6.5 weak acid mixed with a volume ratio of 1-5:50-90:5-10; Cleaning: Put the brightened surface-treated intravascular stent into the non-reactive metal magnesium Wash in detergent and dry. The invention has simple process steps and simple operation, and the pattern of the intravascular stent to be processed and prepared is easy to change and precisely controlled, and the matrix of the intravascular stent can also be guaranteed not to be oxidized at the same time of processing and preparation.

Description

A kind of manufacturing method of biodegradable magnesium alloy intravascular stent

technical field

The invention relates to a preparation process of a metal internal stent used in the field of vascular interventional therapy in the Department of Cardiology, in particular to a production method of a biodegradable magnesium alloy intravascular stent.

Background technique

Intravascular stents were initially used in the treatment of unsatisfactory or damaged vessels after percutaneous angioplasty, and in repairing complex injuries caused by bypass grafts. Compared with simple PTCA, the incidence of acute occlusion and restenosis caused by vascular stent implantation in the human body is significantly reduced. Since the stent is in contact with blood for a long time, the hemocompatibility and biomechanical properties of the material will directly affect the clinical application effect.

At present, most of the stents that have been used clinically are made of metal, including 316L stainless steel, titanium alloy, cobalt-based alloy, tantalum-based alloy, magnesium alloy, etc. Most metal stent materials have good mechanical properties, but as time goes by, metal materials gradually age and corrode, releasing metal ions in body fluids, which may have adverse effects on the body. In addition, the stent is subjected to internal stress for a long time in the body, and fatigue fracture may occur after a long period of time. At present, the development trend in the field of metal stent research is to study materials with higher mechanical properties and better blood compatibility.

Magnesium alloys have low density, high specific strength and specific stiffness, especially have the characteristics of good biocompatibility, low elastic modulus, and can be gradually degraded in the body and effectively absorbed by the human body. In recent years, more and more magnesium alloys Materials are used in the development and application of surgical implantation devices such as bone plates and bone screws, and medical interventional devices such as intravascular stents. The magnesium alloy used as a vascular stent generally contains more than 90% magnesium, and its mechanical properties are equivalent to 316L stainless steel. It is the only metal stent material that can be used as a biodegradable absorber. Mg ions have no toxic side effects on the human body.

Since it can be dissolved and absorbed by blood, the magnesium alloy stent can be used for multiple interventional treatments in the same vascular lesion without the problem of stent overlap. Non-invasive examinations can be used for follow-up after admission. In 2004, the magnesium alloy coronary stent was first used in human clinical trials and achieved success. Recently, a new magnesium alloy degradable scaffold has been developed. Its composition is Mg-3Al-1Re, and studies have shown that it is safe and effective.

As the only absorbable metal stent, magnesium alloy stent has potential as a new type of stent, and its degradation products are non-toxic, which is an important direction for the development of metal stents. However, the plasticity of magnesium alloys at room temperature is very poor, and oxidation easily occurs during processing and preparation. Therefore, the deep and fine processing of high-end products of magnesium alloys has become a constraint for the application and development of magnesium alloys in high-tech fields such as biomedical engineering. bottleneck.

Early vascular stents were braided with alloy wires, especially the stents made of TiNi alloy wires were mostly braided. Later, it was found clinically that the precision and mechanical properties of the braided stent were poor, and the processing yield was low, so the laser engraving technology for the tube was developed. The structure of the laser engraved stent made of thin-diameter and thin-walled magnesium alloy tube is more stable, not easy to deform, and radially supported. The force is stronger, the processing efficiency is higher, and the gas can be used for protection during the processing, which can effectively control the oxidation of the workpiece surface, and the processed graphics are easy to change, which can reduce the production cost of the bracket. Magnesium alloy is very active, the surface is easily oxidized by the atmosphere, and most polar solvents such as water are prone to corrosion and dissolution, which brings great difficulties to the post-processing of magnesium alloy stents. Therefore, it is necessary to develop processing and post-processing technologies for biodegradable magnesium alloy stents.

Contents of the invention

The technical problem to be solved by the present invention is to provide a method for manufacturing a biodegradable magnesium alloy intravascular stent in view of the deficiencies in the above-mentioned prior art. Change and precise control, while processing and preparing, the matrix of the intravascular stent can also be guaranteed not to be oxidized.

In order to solve the above-mentioned technical problems, the technical solution adopted in the present invention is: a method for manufacturing a biodegradable magnesium alloy intravascular stent, characterized in that the method comprises the following steps:

(a) Precise engraving: design and draw the required engraved intravascular stent pattern and import the pattern into a laser engraving machine; under the protection of an inert gas, the magnesium alloy capillary with a diameter of Φ of 1-10mm is processed by the laser engraving machine Carrying out precision engraving and making a precisely engraved intravascular stent, the wall thickness of the magnesium alloy capillary is 0.1-0.5mm and it is a biodegradable medical magnesium alloy seamless tube;

The laser output power of the laser engraving machine is 20-50W, the laser output frequency is 1500-9000Hz, and the pulse width of the output laser is 0.1-0.5ms; The distance between the etched surfaces is 2-3mm, and the cutting speed is 70-150mm/min;

(b) Surface brightening treatment: put the precisely carved intravascular stent into a weakly acidic organic solvent and wash it with ultrasonic vibration for 1-5 minutes; the weakly acidic organic solvent is composed of distilled water, absolute ethanol and The weak acid with 5.5<PH value<6.5 is prepared by mixing the volume ratio of 1-5:50-90:5-10;

(c) Cleaning: the intravascular stent treated with surface brightening is put into a cleaning agent that does not react with metal magnesium for cleaning and then dried.

The weak acid with 5.5<pH value<6.5 described in step (b) is oxalic acid or citric acid.

The pattern on the precision-carved intravascular stent is a pipe network structure composed of multiple mirror-symmetrical figures in pairs, and the single mesh on the pipe network structure is circular, oval, rhombus or dovetail shape.

The cleaning agent described in step (c) is absolute ethanol.

The inert gas described in step (a) is argon.

Compared with the prior art, the present invention has the following advantages: 1. The process steps are simple, easy to operate, and easy to realize; 2. The pattern of the required processing and preparation of the intravascular stent is convenient for overall design, and the designed pattern is easy to change and controlled during the preparation process. Accurate and high precision, the selected raw materials are biocompatible and biodegradable thin-diameter thin-walled magnesium alloy seamless metal pipes, the outer diameter of the selected magnesium alloy capillary is Φ1-10mm, and the wall thickness is 0.1-0.5mm mm; 3. At the same time of processing and preparation, the matrix of the intravascular stent can also be guaranteed not to be oxidized, so that the surface post-treatment process of the stent matrix is simple and easy; 4. In practice, according to the different thin-diameter and thin-walled magnesium alloy tubes used Specifications, reasonable selection of processing parameters of the laser engraving machine, so that the surface quality of the cut vascular stent is better, the dimensional accuracy is higher, and the mechanical properties are better; 5. Because the magnesium alloy is very active, its surface is easily oxidized by the atmosphere, and Most polar solvents such as water and water are prone to corrosion and dissolution. Therefore, the surface treatment of the stent should be carried out in a weak acid organic solvent. Good treatment effect; 6. Wide range of applications. The laser engraving precision molding of the magnesium alloy capillary and the subsequent treatment process on the surface of the vascular stent after engraving and molding can not only be used for clinical treatment of vascular stenosis and biodegradable magnesium alloy blood vessels. The preparation of internal stents can also be used for the preparation of various blood vessels and non-vascular interventional stents in the human body such as coronary arteries and intracranial blood vessels. In summary, the magnesium alloy intravascular stent prepared by the present invention has excellent performance in all aspects. According to the demand for magnesium alloy stents in the medical field such as intravascular stents, and in view of the gaps in the current preparation process of magnesium alloy capillary laser engraving, Combined with the material properties of magnesium alloy materials, under the protection of inert gas (argon), select laser engraving equipment and control its processing parameters, so that the magnesium alloy intravascular stent can be precisely cut and shaped according to the pre-designed pattern requirements and can effectively avoid The surface of the material is oxidized, and then a high-quality biodegradable magnesium alloy intravascular stent with excellent comprehensive mechanical properties, good surface quality, and high geometric dimension accuracy that meets clinical applications can be obtained.

The technical solution of the present invention will be described in further detail below with reference to the drawings and embodiments.

Description of drawings

Fig. 1 is a schematic diagram of a pattern structure of a stent in a blood vessel according to a first preferred embodiment of the present invention.

Fig. 2 is a schematic diagram of the pattern structure of the intravascular stent according to the second preferred embodiment of the present invention.

Fig. 3 is a schematic diagram of the pattern structure of the intravascular stent according to the third preferred embodiment of the present invention.

Explanation of reference signs:

1 - mesh;

Detailed ways

Example 1

A method for manufacturing a biodegradable magnesium alloy intravascular stent of the present invention comprises the following steps:

The first step, precision engraving and forming: design and draw the required engraved intravascular stent pattern and import the pattern into the laser engraving machine, specifically: first use the graphic design software, combined with the actual clinical use requirements, design and program a stent that conforms to the human body Various intravascular stent patterns required for various vascular and non-vascular interventional treatments, and then import the designed intravascular stent patterns into the laser engraving machine through the external port. The pattern on the precisely carved intravascular stent is a pipe network structure composed of multiple mirror-symmetrical figures in pairs, and the single mesh 1 on the pipe network structure is circular, oval, rhombus or Swallowtail.

Afterwards, under the protection of inert gas, the magnesium alloy capillary with a diameter of Φ1-10mm is precisely engraved by a laser engraving machine to obtain a precisely engraved intravascular stent. It should be noted that: before engraving, put the magnesium alloy capillary tube into the working platform of the laser engraving machine and accurately calibrate and position it before starting the laser engraving machine. The entire engraving and cutting process is carried out under the condition of inert gas protection. The magnesium alloy capillary has a wall thickness of 0.1-0.5mm and is a biodegradable medical magnesium alloy seamless pipe. The laser output power of the laser engraving machine is 20-50W, the laser output frequency is 1500-9000Hz, and the pulse width of the output laser is 0.1-0.5ms; The distance between the etched surfaces is 2-3mm, and the cutting speed is 70-150mm/min.

The second step, surface brightening treatment: put the precisely carved intravascular stent into a weakly acidic organic solvent and ultrasonically wash it for 1-5 minutes; the weakly acidic organic solvent is made of distilled water, absolute ethanol It is prepared by mixing with weak acid of 5.5<PH value<6.5 in the volume ratio of 1-5:50-90:5-10.

The third step, cleaning: put the intravascular stent treated with surface brightening into a cleaning agent that does not react with metal magnesium to clean and dry.

In this embodiment, the magnesium alloy capillary has a diameter Φ of 2 mm and a wall thickness of 0.2 mm. As shown in FIG. 1 , the designed and drawn pattern of the intravascular stent to be engraved is a pipe network structure composed of multiple mirror-symmetrical figures in pairs, and a single mesh 1 on the pipe network structure is elliptical. After importing the designed intravascular stent pattern into the laser engraving machine, adjust the working parameters of the laser engraving machine. The laser output power is 24-26W, the laser output frequency is 2500-3000Hz, and the pulse width is 0.3ms. The speed is 110-120mm/min. After fixing the magnesium alloy capillary with a specification of Φ2×0.2mm on the working platform of the laser engraving machine and performing precise positioning, the magnesium alloy capillary is positioned and cut under the protection of argon to obtain the intravascular stent with the desired pattern . Then, put the laser-engraved endovascular stent into a mixed solution prepared by mixing distilled water, absolute ethanol and citric acid in a ratio of 2:89:9 by volume and wash it with ultrasonic vibration for 1 minute. Finally, put the surface-brightened endovascular stent into absolute ethanol, rinse it and dry it.

Example 2

In this embodiment, the magnesium alloy capillary has a diameter Φ of 5 mm and a wall thickness of 0.4 mm. As shown in FIG. 2 , the designed and drawn pattern of the intravascular stent to be carved is a pipe network structure composed of multiple mirror-symmetrical figures in pairs, and the single mesh 1 on the pipe network structure is rhombus. After importing the designed intravascular stent pattern into the laser engraving machine, adjust the working parameters of the laser engraving machine. The laser output power is 42-44W, the laser output frequency is 7000-7500Hz, and the pulse width is 0.1ms. The speed is 80-90mm/min. After fixing the magnesium alloy capillary tube with a specification of Φ5×0.4mm on the working platform of the laser engraving machine and performing precise positioning, the magnesium alloy capillary tube is positioned and cut under the protection of argon to obtain the intravascular stent with the required pattern . Then, the laser-engraved endovascular stent was put into a mixed solution prepared by mixing distilled water, absolute ethanol and oxalic acid in a ratio of 5:85:10 by volume, and washed with ultrasonic vibration for 2 minutes. Finally, put the surface-brightened intravascular stent into absolute ethanol, rinse it and dry it.

Example 3

In this embodiment, the magnesium alloy capillary has a diameter Φ of 6 mm and a wall thickness of 0.3 mm. As shown in FIG. 3 , the designed and drawn pattern of the intravascular stent to be carved is a pipe network structure composed of multiple mirror-symmetrical figures in pairs, and a single mesh 1 on the pipe network structure is dovetail-shaped. After importing the designed intravascular stent pattern into the laser engraving machine, adjust the working parameters of the laser engraving machine. The laser output power is 30-32W, the laser output frequency is 2500-3000Hz, and the pulse width is 0.3ms. The speed is 100-110mm/min. After fixing the magnesium alloy capillary tube with a specification of Φ6×0.3mm on the working platform of the laser engraving machine and performing precise positioning, the magnesium alloy capillary tube is positioned and cut under the protection of argon to obtain the intravascular stent with the required pattern . Then, put the laser-engraved endovascular stent into a mixed solution prepared by mixing distilled water, absolute ethanol and citric acid in a ratio of 3:88:9 by volume and wash it with ultrasonic vibration for 2 minutes. Finally, put the surface-brightened endovascular stent into absolute ethanol, rinse it and dry it.

To sum up, the process steps of the present invention are as follows: firstly, design and draw the desired intravascular stent pattern and import it into the laser engraving machine, after adjusting the working parameters of the laser engraving machine, accurately position the magnesium alloy capillary tube on the laser engraving machine, and then Under the protection of argon, the magnesium alloy tube is positioned and cut to obtain the desired pattern of intravascular stents, and finally the burrs and radial rough surfaces of the intravascular stents are removed by combined treatment of ultrasonic vibration and chemical washing.

The above are only preferred embodiments of the present invention, and do not limit the present invention in any way. All simple modifications, changes and equivalent structural changes made to the above embodiments according to the technical essence of the present invention still belong to the technical aspects of the present invention. within the scope of protection of the scheme.

Claims (5)

1. the manufacture method of a biodegradable magnesium alloy intravascular stent is characterized in that this method may further comprise the steps:

(a) accurate engraving molding: design and draw the endovascular stent pattern of required engraving molding and described pattern is imported laser engraving machine; Under inert gas shielding, is that the magnesium alloy capillary tube of 1-10mm carries out accurate engraving and makes endovascular stent through the molding of precision engraving by laser engraving machine to diameter of phi, and described magnesium alloy wall thickness capillaceous is 0.1-0.5mm and its for can biodegradable medical magnesium alloy seamless tubular goods;

The laser output power of described laser engraving machine is 20-50W, and laser output frequency is 1500-9000Hz, and the pulsewidth of the laser of exporting is 0.1-0.5ms; During laser engraving, the Laser emission mouth of described laser engraving machine and the distance that is etched between the surface are 2-3mm, and cutting speed is 70-150mm/min;

(b) surface-brightening is handled: described endovascular stent through the molding of precision engraving is put into be weakly acidic organic solvent for ultrasonic concussion washing 1-5 minute; It is described that to be weakly acidic organic solvent formulated for the mixed of 1-5: 50-90: 5-10 by volume by the weak acid of distilled water, dehydrated alcohol and 5.5＜pH value＜6.5;

(c) clean: will put into through the endovascular stent that surface-brightening is handled and clean with the nonreactive abluent of magnesium metal and dry.

2. according to the manufacture method of the described a kind of biodegradable magnesium alloy intravascular stent of claim 1, it is characterized in that: the weak acid of 5.5＜pH value＜6.5 is oxalic acid or citric acid described in the step (b).

3. according to the manufacture method of claim 1 or 2 described a kind of biodegradable magnesium alloy intravascular stents, it is characterized in that: described pattern on the endovascular stent of precision engraving molding is for being the pipe network structure that mirror symmetry figure is formed in twos by a plurality of, and the single mesh (1) on the described pipe network structure be circle, ellipse, rhombus or swallow-tail form.

4. according to the manufacture method of claim 1 or 2 described a kind of biodegradable magnesium alloy intravascular stents, it is characterized in that: the abluent described in the step (c) is a dehydrated alcohol.

5. according to the manufacture method of claim 1 or 2 described a kind of biodegradable magnesium alloy intravascular stents, it is characterized in that: the noble gas described in the step (a) is an argon.

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