An alloy cardiovascular stent and its surface coating process

Abstract

The present invention relates to the technical field of cardiovascular stents, and particularly to an alloy cardiovascular stent and its surface coating process. After electrolytic polishing, washing, and drying of the magnesium alloy vascular stent, it is immersed in a sodium hydroxide solution for alkali heat treatment, and after washing and drying, a pretreated magnesium alloy vascular stent is obtained; the pretreated magnesium alloy vascular stent is immersed in a dopamine solution for reaction to obtain a polydopamine-modified magnesium alloy vascular stent; a polymer coating is prepared on the surface of the polydopamine-modified magnesium alloy vascular stent by physical spraying to obtain a polymer-modified magnesium alloy vascular stent; the polymer-modified magnesium alloy vascular stent is immersed in a nanoparticle solution, and after ultraviolet light irradiation, washing, and drying, it is obtained. The present invention not only improves the corrosion resistance of the magnesium alloy vascular stent, effectively reduces the degradation rate of the stent in the body, but also endows the surface of the stent with good biocompatibility.

Description

Technical Field

[0001] The present invention relates to the technical field of cardiovascular stents, and particularly to an alloy cardiovascular stent and its surface coating process. Background Art

[0002] An alloy cardiovascular stent is an important medical device for treating cardiovascular diseases, usually made of high-strength alloy materials to ensure effective support for blood vessels after implantation and prevent restenosis. With the change of people's lifestyle and the arrival of an aging society, the incidence of cardiovascular diseases has been increasing year by year. There is an urgent need to develop safer and more effective stent materials and surface coating technologies to improve the biocompatibility and anti-thrombosis ability of stents.

[0003] Alloys such as titanium alloys and magnesium alloys are increasingly used in the research and development of biomedical materials and devices due to their good mechanical properties and biocompatibility. And biomedical magnesium alloy materials can be degraded and absorbed in the human body, making magnesium alloys a research hotspot in the field of degradable cardiovascular stents in recent years.

[0004] However, the degradation rate of magnesium alloy vascular stents in the human body is too fast, resulting in the premature loss of mechanical support of the stent and limiting its clinical application. In addition, the rapid accumulation of corrosion products such as hydrogen and hydroxide ions generated by degradation will also cause adverse reactions to the surrounding tissues and affect the blood vessel remodeling process. Therefore, much work has been devoted to improving the corrosion resistance of magnesium alloys through surface coating modification, including metal oxide coatings, fluoride coatings, calcium phosphate coatings and polymer coatings. Since polymer coatings can serve as drug reservoirs and can be further functionalized with biomolecules, they have additional advantages compared to other stent coating materials. However, the wettability of polymer coatings on the magnesium alloy substrate is poor, and during the surface improvement process of the magnesium alloy substrate, the coating effect is poor and the adhesion is limited, ultimately resulting in poor and unstable anti-corrosion effect of the magnesium alloy substrate. In addition, the rapid precipitation of hydrogen caused by the degradation of the magnesium matrix may lead to the formation of cavities under the coating, and then cause the polymer fragments to peel off from the stent, resulting in adverse consequences for clinical use.

[0005] Therefore, we propose an alloy cardiovascular stent and its surface coating process. Summary of the Invention

[0006] The purpose of the present invention is to provide an alloy cardiovascular stent and its surface coating process to solve the problems raised in the prior art.

[0007] To achieve the above purpose, the present invention provides the following technical solutions:

[0008] A surface coating process for an alloy cardiovascular stent includes the following steps:

[0009] Step S1: After electrolytic polishing, washing, and drying the magnesium alloy vascular stent, immerse it in a sodium hydroxide solution and treat it at 50 - 60 °C for 22 - 24 h. After washing and drying, a pretreated magnesium alloy vascular stent is obtained;

[0010] Step S2: Adjust the pH of the Tris-HCl buffer solution to 8.5, add dopamine hydrochloride and mix evenly to obtain a dopamine solution; immerse the pretreated magnesium alloy vascular stent in the dopamine solution and react at 35 - 40 °C for 22 - 24 h to form a polydopamine coating. After washing and drying, a polydopamine-modified magnesium alloy vascular stent is obtained;

[0011] Step S3: Use physical spraying to prepare a polymer coating on the surface of the polydopamine-modified magnesium alloy vascular stent to obtain a polymer-modified magnesium alloy vascular stent;

[0012] Step S4: Immerse the polymer-modified magnesium alloy vascular stent in a nanoparticle solution for ultraviolet irradiation to form a nanoparticle coating. After washing and drying, it is obtained.

[0013] Further, in step S1, the process conditions for electrolytic polishing are: electrolytic polishing for 4 - 6 min under the conditions of a voltage of 10 - 12 V and a current of 0.2 - 0.5 A.

[0014] Further, in step S1, the concentration of the sodium hydroxide solution is 1 - 2 mol / L.

[0015] Further, in step S2, the concentration of the Tris-HCl buffer solution is 0.01 mol / L, and the concentration of the dopamine solution is 3 - 5 g / L.

[0016] Further, in step S3, the preparation method of the spraying solution for physical spraying is as follows:

[0017] Step (1): Mix 2-methylene-1,3-dioxepane, ethyl 3-aminocrotonate, diethylene glycol divinyl ether, 2-(2-carboxyethylthio)thiocarbonylsulfanylpropanoic acid, azobisisobutyronitrile, and 1,4-dioxane evenly. After three freeze-pump thaw cycles for degassing, fill with nitrogen and react at 70 - 80 °C for 22 - 24 h. After cooling to room temperature, precipitate and dry to obtain a hyperbranched polymer;

[0018] Step (2): Mix the hyperbranched polymer and dichloromethane evenly to obtain a spraying solution.

[0019] Further, in the step (1), the hyperbranched polymer comprises the following weight components: 3 - 5 parts of 2 - methylene - 1,3 - dioxepane, 2.5 - 3.0 parts of ethyl 3 - aminocrotonate, 8 - 10 parts of diethylene glycol divinyl ether, 1 - 2 parts of 2-(2 - carboxyethylsulfanylthiocarbonylsulfanyl)propanoic acid, 0.1 - 0.3 parts of azobisisobutyronitrile, and 100 - 110 parts of 1,4 - dioxane.

[0020] Further, in the step (2), the concentration of the spraying liquid is 5 - 15 wt%.

[0021] In the above - mentioned technical solution, using 2-(2 - carboxyethylsulfanylthiocarbonylsulfanyl)propanoic acid as the RAFT reagent and azobisisobutyronitrile as the initiator, a main - chain - degradable hyperbranched polymer was prepared by radical ring - opening copolymerization (rROP) of 2 - methylene - 1,3 - dioxepane, ethyl 3 - aminocrotonate and diethylene glycol divinyl ether, and amino groups and a small amount of unreacted vinyl ether double bonds were introduced into the side chains. Among them, the amino groups can undergo Schiff - base reaction with the polydopamine coating to enhance the anti - corrosion performance of the coating, and the double bonds can form a cross - linked network during the subsequent photocuring process to enhance the adhesion of the coating.

[0022] Further, the thickness of the polymer coating is 10 - 50 μm.

[0023] Further, in the step S4, the preparation method of the nanoparticle solution is as follows:

[0024] Step A: Mix malic acid and deionized water evenly, treat at 200 - 210 °C for 5 - 6 h, cool to room temperature, and obtain carbon dots after centrifugation and dialysis.

[0025] Step B: Disperse chitosan in deionized water, add hydrochloric acid to adjust the pH = 6 - 7, then add 1 - ethyl - (3 - dimethylaminopropyl)carbodiimide hydrochloride, N - hydroxysuccinimide and L - cysteine and mix evenly. React under dark conditions for 22 - 24 h, and obtain thiolated chitosan after dialysis and drying.

[0026] Mix hyaluronic acid, carbon dots and deionized water evenly, add 1 - ethyl - (3 - dimethylaminopropyl)carbodiimide hydrochloride and N - hydroxysuccinimide and mix evenly, then add thiolated chitosan, react for 8 - 10 h, and obtain nanoparticles after dialysis and drying.

[0027] Step C: Mix the nanoparticles, photoinitiator and dichloromethane evenly to obtain the nanoparticle solution.

[0028] In the above technical solution, malic acid is used as a raw material, and carboxyl-containing carbon dots are prepared by a hydrothermal carbonization method; through the condensation reaction of the amino group of chitosan and the carboxyl group of L-cysteine, a mercapto group is introduced to obtain mercapto chitosan, which also contains an amino group; through the further reaction of the carboxyl group of hyaluronic acid and carbon dots with the amino group of mercapto chitosan, nanoparticles are obtained. Under the action of a photoinitiator, it can further carry out a thiol-ene click reaction with the double bond in the polymer coating, making the loading of the nanoparticles more uniform and firm, thereby enhancing its stability in the coating.

[0029] Further, in step A, the mass ratio of malic acid to deionized water is 1:(20 - 22).

[0030] Further, in step B, the mass ratio of chitosan, deionized water, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide, and L-cysteine is 1:100:(7 - 8):(4.0 - 4.5):(2 - 4), and the concentration of hydrochloric acid is 1 mol / L.

[0031] Further, in step B, the mass ratio of hyaluronic acid, carbon dots, mercapto chitosan, and deionized water is 1:(0.3 - 0.5):(2 - 4):(500 - 1000).

[0032] Further, in step B, the mass ratio of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride to N-hydroxysuccinimide is 1:(0.3 - 0.4), and the mass of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride is 18 - 20 times the mass of hyaluronic acid.

[0033] Further, in step C, the mass ratio of the nanoparticles to the photoinitiator is 1:(0.1 - 0.3), and the concentration of the nanoparticle solution is 0.5 - 2.0 mg / mL.

[0034] Further, the photoinitiator is 2-hydroxy-2-methyl-1-phenyl-1-propanone.

[0035] Further, in step S4, the process conditions of ultraviolet light irradiation are: irradiated with ultraviolet light of 360 - 400 nm for 30 - 60 min, and the irradiation intensity is 20 - 35 mW / cm 2 。

[0036] Further, the thickness of the nanoparticle coating is 5 - 20 μm.

[0037] Compared with the prior art, the beneficial effects of the present invention are:

[0038] 1. An alloy cardiovascular stent and its surface coating process of the present invention. First, after electrolytic polishing, washing, and drying of the magnesium alloy stent, alkali heat treatment is carried out to initially improve the corrosion resistance of the material, and a pretreated magnesium alloy vascular stent is obtained; then, a polydopamine coating is deposited on the surface of the pretreated magnesium alloy vascular stent as a secondary modification platform, effectively solving the problem that the metal stent is too stable to be directly modified;

[0039] Subsequently, a polymer coating is prepared on the surface of the polydopamine-modified magnesium alloy vascular stent. The polymer is a hyperbranched polymer containing amino groups and double bonds, and its amino groups can undergo Schiff base reaction with the polydopamine coating, further improving the corrosion resistance of the material;

[0040] Chitosan (CS) is a product obtained by deacetylating part of natural polysaccharide chitin, and it has excellent biocompatibility, biodegradability, antibacterial property, non-toxicity, and osteoconductivity; hyaluronic acid (HA) is an important component of the extracellular matrix, and it has good anticoagulant, anti-proliferative, anti-inflammatory effects, and promotes the growth of endothelial cells; carbon dots (CDs) are a class of carbon-based nanomaterials with a size less than 10 nanometers and have excellent corrosion inhibition effects. Finally, through the further reaction of the carboxyl groups of hyaluronic acid and carbon dots with the amino groups of thiolated chitosan, nanoparticles are obtained; under the action of a photoinitiator, the thiol groups in the nanoparticles undergo thiol-ene click reaction with the double bonds in the polymer coating, so that the nanoparticles are loaded on the polymer coating to form a nanoparticle coating, which not only significantly improves the corrosion resistance of the magnesium alloy stent but also improves its biocompatibility. At the same time, the nanoparticles can act as drug carriers and enhance the therapeutic effect by covalently binding with drugs. Specific embodiments

[0041] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0042] In this embodiment, the magnesium alloy vascular stent: the grade is AZ31, the outer diameter is 3 mm, and the wall thickness is 0.2 mm.

[0043] In the following examples and comparative examples, 1 part is equal to 10 g.

[0044] Example 1: A surface coating process of an alloy cardiovascular stent, including the following processes:

[0045] Step S1: The magnesium alloy vascular stent is subjected to electrolytic polishing (electrolytic polishing for 4 min under the conditions of a voltage of 10 V and a current of 0.2 A), washing, and drying, and then immersed in a 1 mol / L sodium hydroxide solution and treated at 50 °C for 22 h. After washing and drying, a pretreated magnesium alloy vascular stent is obtained;

[0046] Step S2: Adjust the pH of 0.01 mol / L Tris-HCl buffer to 8.5, add dopamine hydrochloride and mix evenly to obtain a 3 g / L dopamine solution; immerse the pretreated magnesium alloy vascular stent in the dopamine solution and react at 35 °C for 22 h to form a polydopamine coating. After washing and drying, a polydopamine-modified magnesium alloy vascular stent is obtained;

[0047] Step S3: A polymer coating is prepared on the surface of the polydopamine-modified magnesium alloy vascular stent by physical spraying to obtain a polymer-modified magnesium alloy vascular stent;

[0048] Step S4: Immerse the polymer-modified magnesium alloy vascular stent in the nanoparticle solution and irradiate it with 360 nm ultraviolet light for 30 min, with an irradiation intensity of 20 mW / cm 2 to form a nanoparticle coating. After washing and drying, it is obtained;

[0049] In Step S3, the preparation method of the spraying solution for the physical spraying method is as follows:

[0050] Step (1): Mix 3 parts of 2-methylene-1,3-dioxepane, 2.5 parts of ethyl 3-aminocrotonate, 8 parts of diethylene glycol divinyl ether, 1 part of 2-(2-carboxyethylthio)carbonothioylthiopropanoic acid, 0.1 part of azobisisobutyronitrile, and 100 parts of 1,4-dioxane evenly. After degassing through three freeze-pump-thaw cycles, fill with nitrogen and react at 70 °C for 22 h. After cooling to room temperature, precipitate and dry to obtain a hyperbranched polymer;

[0051] Step (2): Mix the hyperbranched polymer and dichloromethane evenly to obtain a 5 wt% spraying solution;

[0052] In Step S4, the preparation method of the nanoparticle solution is as follows:

[0053] Step A: Mix 0.3 part of malic acid and 6 parts of deionized water evenly, treat at 200 °C for 5 h, cool to room temperature, and after centrifugation and dialysis, obtain carbon dots;

[0054] Step B: Disperse 2 parts of chitosan in 200 parts of deionized water, adjust the pH to 6 by adding 1 mol / L hydrochloric acid, then add 14 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 8 parts of N-hydroxysuccinimide and 4 parts of L-cysteine and mix evenly. React for 22 h under dark conditions, and after dialysis and drying, thiolated chitosan is obtained;

[0055] Mix 1 part of hyaluronic acid, 0.3 part of carbon dots and 500 parts of deionized water evenly, add 18 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 5.4 parts of N-hydroxysuccinimide and mix evenly, then add 2 parts of thiolated chitosan and react for 8 h. After dialysis and drying, nanoparticles are obtained;

[0056] Step C: Mix 1 part of nanoparticles, 0.1 part of photoinitiator and dichloromethane evenly to obtain a 0.5 mg / mL nanoparticle solution.

[0057] Example 2: A surface coating process for an alloy cardiovascular stent, including the following processes:

[0058] Step S1: Electrolytically polish the magnesium alloy vascular stent (electrolytically polish for 5 min under the conditions of a voltage of 11 V and a current of 0.3 A), wash and dry it, then immerse it in a 1.5 mol / L sodium hydroxide solution and treat it at 55 °C for 23 h. After washing and drying, a pretreated magnesium alloy vascular stent is obtained;

[0059] Step S2: Adjust the pH of 0.01 mol / L Tris-HCl buffer to 8.5, add dopamine hydrochloride and mix evenly to obtain a 4 g / L dopamine solution; immerse the pretreated magnesium alloy vascular stent in the dopamine solution and react at 37 °C for 23 h to form a polydopamine coating. After washing and drying, a polydopamine-modified magnesium alloy vascular stent is obtained;

[0060] Step S3: Prepare a polymer coating on the surface of the polydopamine-modified magnesium alloy vascular stent by physical spraying to obtain a polymer-modified magnesium alloy vascular stent;

[0061] Step S4: Immerse the polymer-modified magnesium alloy vascular stent in the nanoparticle solution and irradiate it with 380 nm ultraviolet light for 40 min, with an irradiation intensity of 30 mW / cm 2 , to form a nanoparticle coating. After washing and drying, it is obtained;

[0062] In Step S3, the preparation method of the spraying solution for the physical spraying method is as follows:

[0063] Step (1): Mix 4 parts of 2-methylene-1,3-dioxepane, 2.8 parts of ethyl 3-aminocrotonate, 9 parts of diethylene glycol divinyl ether, 1.5 parts of 2-(2-carboxyethylsulfanylthiocarbonylsulfanyl)propanoic acid, 0.2 part of azobisisobutyronitrile, and 105 parts of 1,4-dioxane uniformly. After degassing through three freeze-pump-thaw cycles, fill with nitrogen and react at 75 °C for 23 h. After cooling to room temperature, precipitate and dry to obtain a hyperbranched polymer;

[0064] Step (2): Mix the hyperbranched polymer and dichloromethane uniformly to obtain a 10 wt% spraying solution;

[0065] In step S4, the preparation method of the nanoparticle solution is as follows:

[0066] Step A: Mix 1 part of malic acid and 21 parts of deionized water uniformly, treat at 205 °C for 5.5 h, cool to room temperature, and after centrifugation and dialysis, obtain carbon dots;

[0067] Step B: Disperse 3 parts of chitosan in 300 parts of deionized water, add 1 mol / L hydrochloric acid to adjust the pH to 6.5, then add 22 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 13 parts of N-hydroxysuccinimide, and 9 parts of L-cysteine and mix uniformly. React in the dark for 23 h, and after dialysis and drying, obtain thiolated chitosan;

[0068] Mix 1 part of hyaluronic acid, 0.4 part of carbon dots, and 800 parts of deionized water uniformly, add 19 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 6.6 parts of N-hydroxysuccinimide and mix uniformly, then add 3 parts of thiolated chitosan and react for 9 h. After dialysis and drying, obtain nanoparticles;

[0069] Step C: Mix 1 part of nanoparticles, 0.2 part of photoinitiator, and dichloromethane uniformly to obtain a 1 mg / mL nanoparticle solution.

[0070] Example 3: A surface coating process for an alloy cardiovascular stent, including the following processes:

[0071] Step S1: Electropolish the magnesium alloy vascular stent (electropolish at a voltage of 12 V and a current of 0.5 A for 6 min), wash and dry, then immerse it in a 2 mol / L sodium hydroxide solution and treat at 60 °C for 24 h. After washing and drying, obtain a pretreated magnesium alloy vascular stent;

[0072] Step S2: Adjust the pH of 0.01 mol / L Tris-HCl buffer to 8.5, add dopamine hydrochloride and mix evenly to obtain a 5 g / L dopamine solution; Immerse the pretreated magnesium alloy vascular stent in the dopamine solution and react at 40 °C for 24 h to form a polydopamine coating. After washing and drying, a polydopamine-modified magnesium alloy vascular stent is obtained;

[0073] Step S3: Prepare a polymer coating on the surface of the polydopamine-modified magnesium alloy vascular stent by physical spraying to obtain a polymer-modified magnesium alloy vascular stent;

[0074] Step S4: Immerse the polymer-modified magnesium alloy vascular stent in the nanoparticle solution and irradiate it with 400 nm ultraviolet light for 60 min, with an irradiation intensity of 35 mW / cm 2 , to form a nanoparticle coating. After washing and drying, it is obtained;

[0075] In Step S3, the preparation method of the spraying solution for the physical spraying method is as follows:

[0076] Step (1): Mix 5 parts of 2-methyl-1,3-dioxepane, 3.0 parts of ethyl 3-aminocrotonate, 10 parts of diethylene glycol divinyl ether, 1-2 parts of 2-(2-carboxyethylthio)thiocarbonylsulfanylpropionic acid, 0.1-0.3 parts of azobisisobutyronitrile and 100-110 parts of 1,4-dioxane evenly. After degassing through three freeze-pump-thaw cycles, fill with nitrogen and react at 70-80 °C for 22-24 h. After cooling to room temperature, precipitate and dry to obtain a hyperbranched polymer;

[0077] Step (2): Mix the hyperbranched polymer and dichloromethane evenly to obtain a 15 wt% spraying solution;

[0078] In Step S4, the preparation method of the nanoparticle solution is as follows:

[0079] Step A: Mix 0.5 part of malic acid and deionized water evenly, treat at 210 °C for 6 h, cool to room temperature, and after centrifugation and dialysis, obtain carbon dots;

[0080] Step B: Disperse 4 parts of chitosan in 400 parts of deionized water, add 1 mol / L hydrochloric acid to adjust the pH to 7, then add 32 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 18 parts of N-hydroxysuccinimide and 16 parts of L-cysteine and mix evenly. React in the dark for 24 h, and after dialysis and drying, obtain thiolated chitosan;

[0081] Mix 1 part of hyaluronic acid, 0.5 part of carbon dots and 1000 parts of deionized water evenly, add 20 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 8 parts of N-hydroxysuccinimide and mix evenly, then add 4 parts of thiolated chitosan, react for 10 h, and obtain nanoparticles after dialysis and drying;

[0082] Step C: Mix the nanoparticles, photoinitiator and dichloromethane evenly to obtain a 2 mg / mL nanoparticle solution.

[0083] Comparative Example 1: A surface coating process for an alloy cardiovascular stent, including the following process:

[0084] Compared with Example 2, Comparative Example 1 does not include Step S2, and other steps are the same as those in Example 2.

[0085] Comparative Example 2: A surface coating process for an alloy cardiovascular stent, including the following process:

[0086] Compared with Example 2, Comparative Example 2 does not include Step S3, and other steps are the same as those in Example 2.

[0087] Comparative Example 3: A surface coating process for an alloy cardiovascular stent, including the following process:

[0088] Compared with Example 2, Comparative Example 3 does not include Step S4, and other steps are the same as those in Example 2.

[0089] Comparative Example 4: A surface coating process for an alloy cardiovascular stent, including the following process:

[0090] In Step S4, the preparation method of the nanoparticle solution is as follows:

[0091] Step A: Mix 1 part of malic acid and 21 parts of deionized water evenly, treat at 205 °C for 5.5 h, cool to room temperature, and obtain carbon dots after centrifugation and dialysis;

[0092] Step B: Disperse 3 parts of chitosan in 300 parts of deionized water, add 1 mol / L hydrochloric acid to adjust the pH to 6.5, then add 22 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 13 parts of N-hydroxysuccinimide and 9 parts of L-cysteine and mix evenly, react in the dark for 23 h, and obtain thiolated chitosan after dialysis and drying;

[0093] Mix 1 part of hyaluronic acid, 0.4 part of carbon dots and 800 parts of deionized water evenly, add 19 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 6.6 parts of N-hydroxysuccinimide and mix evenly, then add 0.5 part of thiolated chitosan, react for 9 h, and obtain nanoparticles after dialysis and drying;

[0094] Step C: Mix 1 part of nanoparticles, 0.2 photoinitiator and dichloromethane evenly to obtain a 1 mg / mL nanoparticle solution;

[0095] Compared with Example 2, in Step B of Comparative Example 4, the mass ratio of hyaluronic acid, carbon dots, and thiolated chitosan is 1:0.4:0.5, and other steps are the same as those in Example 2.

[0096] Experiment: Take the magnesium alloy cardiovascular stents prepared in Examples 1-3 and Comparative Examples 1-4, prepare specimens, and detect their performance and record the test results respectively:

[0097] Water contact angle test: Measure the water contact angle on the surface of the specimen with a Powereach JC2000C type contact angle goniometer, and the volume of a single water droplet is 5 μL.

[0098] Immersion weight loss experiment: Immerse the specimens in Hank's dynamic simulated body fluid for 288 h respectively, then clean them with 180 g / L chromic acid solution to remove corrosion products, and then reweigh them. Evaluate the corrosion resistance of different specimens by calculating the corrosion rate.

[0099] Antibacterial experiment: After putting the specimens into labeled centrifuge tubes and sterilizing them, add activated bacteria and LB broth, and place the centrifuge tubes in a constant temperature shaker (37 °C) for 24 h. Then use a pipette to aspirate an appropriate amount of the liquid in the centrifuge tube, dilute it by 10 5 times, aspirate 5 μL with a pipette, drop it on the agar-containing medium, and spread the diluted liquid evenly with a glass rod sterilized by baking with an alcohol lamp. Then seal the medium and place it in a constant temperature incubator for 24 h. Then count the number of colonies and calculate the antibacterial rate. The bacterial strain tested in the experiment is Staphylococcus aureus.

[0100] In vitro biocompatibility experiment: Mouse calvarial pre-osteoblasts (MC3T3-E1) cultivated in a cell incubator at 37 °C and CO 2 concentration of 5% were selected. The complete medium (DMEM) replaced every 48 h contains 1% penicillin, streptomycin and 10% fetal bovine serum (FBS). Passage is required when the cells grow to 80-90% confluence. Cells of the third to sixth generations were used for the experiment. After immersing the sterilized specimens in DMEM at 37 °C at a ratio of 1.25 cm 2 / mL for 24 h, obtain the extract, and store it at 4 °C for later use. To make the cells adhere, inoculate MC3T3-E1 cells into a 96-well plate (2×10 4Cells / mL) were placed in an incubator for 24 h, and then the DMEM was replaced with the extract and the culture was continued. After 3 days, the extract was removed, and DMEM containing 10% CCK-8 was added to the well plate. After incubation for 2 h, the absorbance was measured at 450 nm using a microplate spectrophotometer (Biotek, USA), and the cell viability was calculated. Cell viability (100%) = (A - B) / (C - B)×100%, where A corresponds to the absorbance of each sample group; B corresponds to the blank group, i.e., the absorbance of the complete medium; C corresponds to the negative control group, i.e., the absorbance of the complete medium containing cells.

[0101] The test results are as follows:

[0102] Water contact angle (°) Corrosion rate (mm / y) Antibacterial rate / % Cell survival rate / % Example 1 60 0.12 98.8 93 Example 2 56 0.08 99.5 95 Example 3 58 0.10 99.2 94 Comparative Example 1 75 0.15 96.7 90 Comparative Example 2 78 0.22 94.5 85 Comparative Example 3 67 0.18 85.6 88 Comparative Example 4 64 0.13 97.3 92

[0103] From the data in the above table, the following conclusions can be clearly obtained:

[0104] 1. Compared with Examples 1-3, the water contact angles and corrosion rates of the products obtained in Comparative Examples 1, 2, and 3 increased, while the antibacterial rates and cell viabilities decreased. This shows that under the synergistic effect of the multi-layer coatings of the polydopamine coating, polymer coating, and nanoparticle coating in the present invention, the stent exhibits stronger hydrophilicity and corrosion resistance, and significantly improves its antibacterial property and biocompatibility.

[0105] 2. Compared with Examples 1-3, the water contact angles and corrosion rates of the products obtained in Comparative Example 4 increased, while the antibacterial rates and cell viabilities decreased. It can be seen that when the addition amount of mercaptochitosan is reduced, the hydrophilicity, corrosion resistance, antibacterial property, and biocompatibility of the material will decrease. Therefore, the performance of the nanoparticles prepared in the present invention is affected by the ratio of each reagent in its preparation process, and the mass ratio within the above range is selected to achieve better performance effects.

[0106] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention. Therefore, in any aspect, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present invention.

Claims

1. A surface coating process for an alloy cardiovascular stent, characterized in that: The steps include: Step S1: electropolishing, washing, and drying the magnesium alloy vascular stent, immersing it in a sodium hydroxide solution, and treating it at 50-60° C. for 22-24 hours, and obtaining a pretreated magnesium alloy vascular stent after washing and drying; Step S2: adjusting the pH of the Tris-HCl buffer to 8.5, adding dopamine hydrochloride and mixing evenly to obtain a dopamine solution; The pretreated magnesium alloy vascular stent is immersed in a dopamine solution, reacted at 35-40° C. for 22-24 hours to form a polydopamine coating, and after washing and drying, a polydopamine-modified magnesium alloy vascular stent is obtained; Step S3: preparing a polymer coating on the surface of the polydopamine-modified magnesium alloy vascular stent by a physical spraying method to obtain a polymer-modified magnesium alloy vascular stent; The preparation method of the spray liquid of the physical spraying method is as follows: Step (1): 2-methylene-1,3-dioxepane, ethyl 3-aminocrotonate, diethylene glycol divinyl ether, 2-(2-carboxyethylsulfanylthiocarbonylsulfanyl)propionic acid, azobisisobutyronitrile and 1,4-dioxane are mixed uniformly, degassed through three freeze-vacuum-thaw cycles, filled with nitrogen, reacted at 70-80° C. for 22-24 hours, cooled to room temperature, precipitated and dried to obtain a hyperbranched polymer; Step (2): uniformly mixing the hyperbranched polymer and dichloromethane to obtain a spraying liquid; Step S4: immersing the polymer-modified magnesium alloy vascular stent in a nanoparticle solution and irradiating it with ultraviolet light to form a nanoparticle coating, which is then washed and dried to obtain a nanoparticle coating; The preparation method of nanoparticle solution is as follows: Step A: Malic acid and deionized water are mixed evenly, treated at 200-210° C. for 5-6 hours, cooled to room temperature, and centrifuged and dialyzed to obtain carbon dots; Step B: Disperse chitosan in deionized water, add hydrochloric acid to adjust the pH to 6-7, then add 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, N-hydroxysuccinimide and L-cysteine ​​and mix well, react in the dark for 22-24 hours, dialyze and dry to obtain thiolated chitosan; The hyaluronic acid, carbon dots and deionized water were mixed evenly, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide were added and mixed evenly, and then thiolated chitosan was added, and the mixture was reacted for 8-10 hours, and nanoparticles were obtained after dialysis and drying; Step C: Evenly mix the nanoparticles, the photoinitiator and dichloromethane to obtain a nanoparticle solution.

2. The surface coating process of an alloy cardiovascular stent according to claim 1, characterized in that: In step S1, the concentration of the sodium hydroxide solution is 1-2 mol / L.

3. The surface coating process of an alloy cardiovascular stent according to claim 1, characterized in that: In step S2, the concentration of the Tris-HCl buffer is 0.01 mol / L, and the concentration of the dopamine solution is 3-5 g / L.

4. The surface coating process of an alloy cardiovascular stent according to claim 1, characterized in that: In the step (1), the hyperbranched polymer comprises the following components by weight: 3-5 parts of 2-methylene-1,3-dioxepane, 2.5-3.0 parts of ethyl 3-aminocrotonate, 8-10 parts of diethylene glycol divinyl ether, 1-2 parts of 2-(2-carboxyethylsulfanylthiocarbonylsulfanyl)propionic acid, 0.1-0.3 parts of azobisisobutyronitrile, and 100-110 parts of 1,4-dioxane.

5. The surface coating process of an alloy cardiovascular stent according to claim 1, characterized in that: In the step (2), the concentration of the spraying liquid is 5-15wt%.

6. The surface coating process of an alloy cardiovascular stent according to claim 1, characterized in that: In the step B, the mass ratio of hyaluronic acid, carbon dots, thiolated chitosan and deionized water is 1:(0.3-0.5):(2-4):(500-1000).

7. The surface coating process of an alloy cardiovascular stent according to claim 1, characterized in that: In the step C, the mass ratio of the nanoparticles to the photoinitiator is 1:(0.1-0.3), and the concentration of the nanoparticle solution is 0.5-2.0 mg / mL.

8. The surface coating process of an alloy cardiovascular stent according to claim 1, characterized in that: In step S4, the ultraviolet irradiation process conditions are: irradiation with 360-400nm ultraviolet rays for 30-60min, and irradiation intensity of 20-35mW / cm 2 .