Sustained-release drug-loaded degradable zinc-magnesium alloy stent material and preparation method therefor

Abstract

A sustained-release drug-loaded degradable zinc-magnesium alloy stent material and a preparation method therefor. Batching is performed on the basis of the elemental composition of an alloy material; under a protective atmosphere, a zinc ingot is heated and melted, heat preservation is carried out after a magnesium ingot is added, and refining and casting are performed to form a slab; heat preservation is performed on the slab, the slab is air-cooled to room temperature and then immediately rolled, the amount of rolling deformation per each pass is controlled within 1.0 mm, and the rolling directions of adjacent passes are at 90º to each other until a plate having a thickness of 1.0 ± 0.3 mm is formed by rolling; the plate is treated at 180-200ºC for 3.5-4.5 h and ultrasonically cleaned; and then, the plate is heated and rolled. The elemental composition of the prepared alloy material is: 97.0-97.5% of zinc and 2.5-3.0% of magnesium; the tensile strength is greater than 150.0 MPa, and the elongation is greater than 2.0%; and the surface pore size is 0.5-1.5 μm, so that uneven drug distribution is eliminated, the drug release time is prolonged, and an optimal degradation rate is achieved in the human body.

Description

A sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material and its preparation method Technical Field

[0001] This invention belongs to the field of medical bioalloy material processing technology, specifically relating to a sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material and its preparation method. Background Technology

[0002] With economic and social development and changes in people's dietary structure, the incidence of coronary heart disease in China is showing a trend of increasing among younger people, becoming a major disease threatening health and happiness. Interventional treatment, which involves placing vascular stents at the site of vascular blockage or stenosis to treat coronary heart disease, has advantages such as rapid postoperative recovery, fewer complications, and lower risks, making it significantly superior to other treatment methods. Currently, vascular stents have evolved over decades from the initial metallic stents to the current biodegradable stents. Biodegradable stents can be degraded and absorbed after a period of time in the body, showing broad application prospects. However, their reactive nature and rapid degradation in the human body lead to insufficient retention time in the blood vessels, often resulting in failure before vascular remodeling is completed (approximately 6 months to 1 year). Based on these shortcomings, this invention aims to provide a sustained-release drug-loaded biodegradable zinc-magnesium alloy stent material and its preparation method. While fully meeting stent strength requirements, it slows down the degradation cycle and improves drug adhesion and release time on the stent, thereby preparing a biodegradable vascular stent that better meets the requirements for human implantation. Technical solutions

[0003] The first objective of this invention is to provide a method for preparing a sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material; the second objective of this invention is to provide a sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material.

[0004] The first objective of this invention is achieved as follows: the preparation method of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material includes the steps of batching, casting, homogenization treatment, rolling, annealing, and high surface treatment, specifically including:

[0005] A. Ingredients: The ingredients are prepared according to the elemental composition of the zinc-magnesium alloy support material. The raw materials used are zinc ingots with a mass fraction of 99.99% and magnesium ingots with a mass fraction of 99.95%.

[0006] B. Casting: Under a protective atmosphere, heat the zinc ingot to 440~480℃ to melt it, then add magnesium ingot, hold for 5~10 minutes, then add NH4Cl to refine for 5~10 minutes, and cast into a 10mm thick slab.

[0007] C. Homogenization treatment: Keep the slab at 220~250℃ for 3~5 hours, and then air cool to room temperature.

[0008] D. Rolling: The slab cooled to room temperature is rolled immediately at a speed of 60~120mm / min. The rolling deformation in each pass is controlled within 1.0mm. The rolling directions of adjacent passes are 90° to each other until a plate with a thickness of 1.0±0.3mm is rolled.

[0009] E. Annealing: Treat the board at 180~200℃ for 3.5~4.5h, then ultrasonically clean it with acetone for 20~30min.

[0010] F. High surface treatment: Heat the cleaned board to 220~250℃, roll it back and forth 10~20 times, roll speed 5~10mm / s, and load pressure 50~100N.

[0011] The second objective of this invention is achieved as follows: the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material is prepared by the aforementioned method, and its elemental composition is: zinc 97.0~97.5%, magnesium 2.5~3.0%; tensile strength >150.0MPa, elongation >2.0%; surface pore size 0.5~1.5μm; and corrosion rate in Hank's simulated solution 0.10~0.15mm / year. Beneficial effects

[0012] Compared with the prior art, this invention has outstanding substantive features and significant progress:

[0013] 1. By controlling the alloy composition, the zinc-magnesium alloy scaffold material achieves the optimal degradation rate in the human body. The corrosion rate after 30 days of immersion in Hank's simulated solution is 0.10~0.15 mm / year, ensuring that the implant's function is not affected by excessively fast or slow degradation, thus guaranteeing the full completion of the vascular remodeling process. The degradation products are mainly zinc phosphate, zinc carbonate, and magnesium chloride, which have no toxic side effects on the human body.

[0014] 2. The hemolysis rate caused by this alloy composition is far below 5%, meeting the requirements for hemolysis percentage in biomaterials according to standard ASTM F756-08. It does not cause significant damage to red blood cells upon contact with blood, thus meeting the requirements for blood compatibility in biomaterials. Platelet adhesion tests and dynamic coagulation time tests show that this alloy does not cause significant changes in blood composition, nor does it induce blood aggregation, thus preventing the formation of new thrombi and improving blood flow.

[0015] 3. By controlling the rolling and annealing processes, the residual stress inside the zinc-magnesium alloy support material is eliminated to the greatest extent, improving the material's strength, toughness, and isotropy. Its tensile strength is >150.0MPa and elongation is >2.0%.

[0016] 4. The zinc-magnesium alloy stent material prepared by the method described in this invention has uniformly distributed micropores of 0.5~1.5μm with consistent pore size and adjustable dimensions. This facilitates drug coating on the stent surface, eliminates uneven drug distribution, prolongs drug release time, and ensures the therapeutic effect of the stent. Attached Figure Description

[0017] Figure 1 shows the morphology of micropores on the surface of the alloy scaffold material prepared in Example 1;

[0018] Figure 2 is a SEM image of platelets adhering to the surface of the alloy scaffold material prepared in Example 1. Embodiments of the present invention

[0019] The present invention will be further described below, but this is not intended to limit the invention in any way. Any modifications or substitutions made based on the teachings of the present invention shall fall within the scope of protection of the present invention.

[0020] The preparation method of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material includes the following steps: batching, casting, homogenization treatment, rolling, annealing, and high surface treatment, specifically including:

[0021] A. Ingredients: The ingredients are prepared according to the elemental composition of the zinc-magnesium alloy support material. The raw materials used are zinc ingots with a mass fraction of 99.99% and magnesium ingots with a mass fraction of 99.95%.

[0022] B. Casting: Under a protective atmosphere, heat the zinc ingot to 440~480℃ to melt it, then add magnesium ingot, hold for 5~10 minutes, then add NH4Cl to refine for 5~10 minutes, and cast into a 10mm thick slab.

[0023] C. Homogenization treatment: Keep the slab at 220~250℃ for 3~5 hours, and then air cool to room temperature.

[0024] D. Rolling: The slab cooled to room temperature is rolled immediately at a speed of 60~120mm / min. The rolling deformation in each pass is controlled within 1.0mm. The rolling directions of adjacent passes are 90° to each other until a plate with a thickness of 1.0±0.3mm is rolled.

[0025] E. Annealing: Treat the board at 180~200℃ for 3.5~4.5h, then ultrasonically clean it with acetone for 20~30min.

[0026] F. High surface treatment: Heat the cleaned board to 220~250℃, roll it back and forth 10~20 times, roll speed 5~10mm / s, and load pressure 50~100N.

[0027] In the casting process, the protective atmosphere is argon. The preferred melting temperature is 450℃.

[0028] In the rolling process, the rolling direction of adjacent passes being 90° to each other means that after the previous rolling pass is completed, the rolling direction is rotated by 90° to proceed to the next rolling pass.

[0029] In the high surface treatment process, the rolling pressing refers to a working method that combines microwave induction heating and static load rolling. Rollers with uniformly distributed and adjustable-size protrusions are used. The heating refers to microwave induction heating, that is, heating the material using a microwave generator inside the roller. The microwave induction heat input density is 10~15 W / s, preferably 12 W / s.

[0030] The sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material was prepared using the aforementioned method. Its elemental composition is: zinc 97.0~97.5%, magnesium 2.5~3.0%; tensile strength >150.0 MPa, elongation >2.0%; surface pore size 0.5~1.5 μm; corrosion rate after immersion in Hank's simulated solution for 30 days is 0.10~0.15 mm / year. The alloy hemolysis rate is <5%, meeting the requirements of ASTM F756-08 standard; the dynamic coagulation time on the alloy surface is >60 min.

[0031] Example 1

[0032] Preparation of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material:

[0033] A. Ingredients: The ingredients are prepared according to the elemental composition of the zinc-magnesium alloy support material. The raw materials used are zinc ingots with a mass fraction of 99.99% and magnesium ingots with a mass fraction of 99.95%.

[0034] B. Casting: Under argon protection, the zinc ingot is heated to 440℃ and melted. Then, magnesium ingot is added, and the temperature is maintained for 10 minutes. NH4Cl is then added and refined for 5 minutes. The mixture is then cast into a 10mm thick slab.

[0035] C. Homogenization treatment: The slab is kept at 220℃ for 5 hours and then air-cooled to room temperature.

[0036] D. Rolling: The slab cooled to room temperature is rolled immediately at a speed of 120 mm / min. The rolling deformation in each pass is controlled within 1.0 mm. After the previous rolling pass is completed, the rolling direction is rotated 90° for the next rolling pass. After multiple rolling passes, a plate with a thickness of 1.0 ± 0.3 mm is finally obtained.

[0037] E. Annealing: Treat the board at 200℃ for 3.5 hours, then add acetone to an ultrasonic cleaner to clean the surface of the annealed board for 20 minutes.

[0038] F. High Surface Treatment: A combination of microwave induction heating and static roll pressing is used to achieve a high surface treatment of the sheet material. The rollers are made of hard alloy steel and contain an internal microwave generator for heating the sheet. The microwave induction heat input density is 12 W / s, heating the cleaned sheet to 240°C. The roller surface has evenly distributed protrusions, and the rolling is performed 20 times at a speed of 10 mm / s with a loading pressure of 50 N.

[0039] The composition and performance testing methods of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material prepared by the method described in this embodiment are as follows:

[0040] Composition was determined according to GB / T 12689-2010 "Chemical Analysis Methods for Zinc and Zinc Alloys". Mechanical properties were determined according to GB / T 228.1-2021 "Metallic Materials - Tensile Testing - Part 1: Test at Room Temperature". Hemolysis performance of medical devices was evaluated according to ASTM F756-08.

[0041] The results are as follows:

[0042] The elemental composition of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material prepared by the method described in this embodiment is: 97.5% zinc and 2.5% magnesium; tensile strength 156.0 MPa, elongation 3.4%; surface pore size 0.5~1.5 μm; corrosion rate of 0.15 mm / year after immersion in Hank's simulated solution for 30 days; alloy hemolysis rate of 2.1%, which meets the requirement of less than 5% in ASTM F756-08 standard; and dynamic coagulation time of alloy surface of 85 min.

[0043] Example 2

[0044] Preparation of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material:

[0045] A. Ingredients: Same as in Example 1.

[0046] B. Casting: Under argon protection, the zinc ingot is heated to 450℃ and melted, then magnesium ingot is added, the temperature is held for 7 minutes, then NH4Cl is added and refined for 8 minutes, and then cast into a 10mm thick slab.

[0047] C. Homogenization treatment: The slab is kept at 235℃ for 4 hours and then air-cooled to room temperature.

[0048] D. Rolling: The slab cooled to room temperature is rolled immediately at a speed of 90 mm / min. The rolling deformation in each pass is controlled within 1.0 mm. After the previous rolling pass is completed, the rolling direction is rotated 90° for the next rolling pass. After multiple rolling passes, a plate with a thickness of 1.0 ± 0.3 mm is finally obtained.

[0049] E. Annealing: Treat the board at 190℃ for 4.0h, then add acetone to the ultrasonic cleaner to clean the surface of the annealed board for 25min.

[0050] F. High Surface Treatment: The heating and rolling process is the same as in Example 1. Microwave-induced heat input density is 15 W / s, heating the cleaned board to 220°C. The pressure roller reciprocates 16 times at a speed of 8 mm / s, with a loading pressure of 75 N.

[0051] The composition and performance testing methods of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material prepared by the method described in this embodiment are the same as those in Example 1.

[0052] The results are as follows:

[0053] The elemental composition of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material prepared by the method described in this embodiment is: 97.2% zinc and 2.8% magnesium; tensile strength 153.5 MPa, elongation 2.8%; surface pore size 0.5~1.5 μm; corrosion rate of 0.14 mm / year after immersion in Hank's simulated solution for 30 days; alloy hemolysis rate 1.8%, which meets the requirement of less than 5% in ASTM F756-08 standard; dynamic coagulation time of alloy surface 78 min.

[0054] Example 3

[0055] Preparation of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material:

[0056] A. Ingredients: Same as in Example 1.

[0057] B. Casting: Under argon protection, the zinc ingot is heated to 480℃ and melted. Then, magnesium ingot is added and kept at that temperature for 5 minutes. Then, NH4Cl is added and refined for 10 minutes. The mixture is then cast into a 10mm thick slab.

[0058] C. Homogenization treatment: Hold the slab at 250℃ for 3 hours and then air cool it to room temperature.

[0059] D. Rolling: The slab cooled to room temperature is rolled immediately at a speed of 60 mm / min. The rolling deformation in each pass is controlled within 1.0 mm. After the previous rolling pass is completed, the rolling direction is rotated 90° for the next rolling pass. After multiple rolling passes, a plate with a thickness of 1.0 ± 0.3 mm is finally obtained.

[0060] E. Annealing: Treat the board at 180℃ for 4.5 hours, then add acetone to an ultrasonic cleaner to clean the surface of the annealed board for 30 minutes.

[0061] F. High Surface Treatment: The heating and rolling process is the same as in Example 1. Microwave-induced heat input density is 10 W / s, heating the cleaned board to 250°C. The pressure roller reciprocates 10 times at a speed of 5 mm / s, with a loading pressure of 100 N.

[0062] The composition and performance testing methods of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material prepared by the method described in this embodiment are the same as those in Example 1.

[0063] The results are as follows:

[0064] The elemental composition of the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material prepared by the method described in this embodiment is: 97.0% zinc and 3.0% magnesium; tensile strength 156.8 MPa, elongation 2.3%; surface pore size 0.5~1.5 μm; corrosion rate of 0.10 mm / year after immersion in Hank's simulated solution for 30 days; alloy hemolysis rate 1.8%, which meets the requirement of less than 5% in ASTM F756-08 standard; dynamic coagulation time of alloy surface 82 min.

Claims

1. A method for preparing a sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material, characterized in that... The processes include batching, casting, homogenization, rolling, annealing, and high surface treatment, specifically including: A. Ingredients: The ingredients are prepared according to the elemental composition of the zinc-magnesium alloy support material. The raw materials used are zinc ingots with a mass fraction of 99.99% and magnesium ingots with a mass fraction of 99.95%. B. Casting: Under a protective atmosphere, heat the zinc ingot to 440~480℃ to melt it, then add magnesium ingot, hold for 5~10 minutes, then add NH4Cl to refine for 5~10 minutes, and cast into a 10mm thick slab. C. Homogenization treatment: Keep the slab at 220~250℃ for 3~5 hours, and then air cool to room temperature; D. Rolling: The slab cooled to room temperature is rolled immediately at a speed of 60~120mm / min. The rolling deformation in each pass is controlled within 1.0mm. The rolling directions of adjacent passes are 90° to each other until a plate with a thickness of 1.0±0.3mm is rolled. E. Annealing: Treat the board at 180~200℃ for 3.5~4.5h, then ultrasonically clean it with acetone for 20~30min; F. High surface treatment: Heat the cleaned board to 220~250℃, roll it back and forth 10~20 times, roll speed 5~10mm / s, and load pressure 50~100N.

2. The method for preparing the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material according to claim 1, characterized in that, In the casting process, the protective atmosphere is argon.

3. The method for preparing the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material according to claim 1, characterized in that, In the casting process, the melting temperature is 450°C.

4. The method for preparing the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material according to claim 1, characterized in that, In the rolling process, the rolling direction of adjacent passes being 90° to each other means that after the previous rolling pass is completed, the rolling direction is rotated by 90° to proceed to the next rolling pass.

5. The method for preparing the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material according to claim 1, characterized in that, In the high surface treatment process, the roller pressing uses rollers with consistent convex head shape, uniform distribution, and adjustable size.

6. The method for preparing the sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material according to claim 1, characterized in that, In the high surface treatment process, the heating refers to microwave induction heating, and the microwave induction heat input density is 10~15w / s.

7. A sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material, characterized in that, It is prepared by the preparation method according to any one of claims 1 to 6.

8. The sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material according to claim 7, characterized in that, The elemental composition of the zinc-magnesium alloy support material is: zinc 97.0~97.5%, magnesium 2.5~3.0%; tensile strength >150.0MPa, elongation >2.0%; surface pore size 0.5~1.5μm; corrosion rate in Hank's simulated solution is 0.10~0.15mm / year.

9. The sustained-release drug-loaded biodegradable zinc-magnesium alloy scaffold material according to claim 7, characterized in that, The zinc-magnesium alloy stent material has an alloy hemolysis rate of <5% and a dynamic coagulation time on the alloy surface of >60 min.

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