Preparation method of alloy stent with composite coating

Abstract

The invention discloses a preparation method of an alloy stent with a composite coating, and relates to the technical field of medical alloy stents. According to the technical scheme, hexadecyl trimethyl ammonium bromide is used as a template, mesoporous silica nanoparticles are prepared through hydrolytic condensation and hydrochloric acid-methanol template removal, after a drug is loaded, chitosan is used for coating, cysteamine is combined to introduce a disulfide bond, and pH / oxidation dual-response drug-loading particles are constructed; finally, the alloy stent serves as a working electrode, the calcium-phosphorus coating drug-loaded stent is prepared through electro-deposition, precise slow release of drugs is achieved, and treatment safety and effectiveness are improved.

Description

Technical Field

[0001] This invention relates to the field of medical alloy stent technology, specifically to a method for preparing an alloy stent with a composite coating. Background Technology

[0002] In the medical field, absorbable stents have been widely used due to their advantage of being able to gradually degrade in the body after treatment, thus avoiding long-term complications caused by permanent implants.

[0003] However, existing stents still have significant shortcomings in clinical applications, which limit the therapeutic effect and safety. On the one hand, some drug-eluting absorbable stents may trigger allergic reactions in a small number of patients due to the characteristics of the drugs they carry (such as certain antibiotics and antiproliferative drugs), leading to rashes, local inflammation, or even more serious immune reactions. On the other hand, the drug release process is difficult to control precisely, often resulting in problems such as excessive initial release (increasing the risk of toxic side effects) or insufficient release in the later stages (failing to maintain a sustained therapeutic effect). Especially in complex physiological environments such as natural cavities, the stability of drug release is even more difficult to guarantee. It is urgent to address these clinical pain points by optimizing the stent drug delivery system and drug release mechanism. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing an alloy scaffold with a composite coating, so as to solve the problems existing in the prior art.

[0005] To solve the above-mentioned technical problems, the present invention provides the following technical solution: A method for preparing an alloy scaffold with a composite coating is disclosed, applicable to an alloy scaffold with a composite coating. The alloy scaffold employs an electrodeposition method to deposit a calcium phosphate drug-loaded coating on its surface. The calcium phosphate drug-loaded coating comprises drug-loaded nanoparticles. The drug-loaded nanoparticles are constructed by adsorbing and loading drugs onto mesoporous silica nanoparticles, followed by chitosan encapsulation, then grafting double bonds with acryloyl chloride. Finally, the double bonds undergo a grafting reaction with cysteine, and the mixture is then deposited onto the alloy scaffold surface using an electrodeposition method. The alloy scaffold is made of any one of magnesium alloy, magnesium-zinc alloy, or zinc alloy. The method includes the following steps: S1. Mix 1 mg / mL of drug with 5 mg / mL of mesoporous silica nanoparticles at a volume ratio of 1:1. Stir at 25-35℃ for 24-28 hours, centrifuge, and wash with deionized water and ethanol alternately 3-5 times to obtain drug-loaded nanoparticles. S2. Add drug-loaded nanoparticles to 100-120 times their mass of ethanol and ultrasonically disperse for 10-15 min. Adjust the pH to 3.5-4.5 with acetic acid. Then add 1-1.5 times their mass of (3-glycidylpropoxy)trimethoxysilane and stir at 25-35℃ for 3-4 h. Then add 200-220 times their mass of chitosan solution and stir at 25-35℃ for 24-28 h. After the reaction is complete, centrifuge and wash with anhydrous ethanol and deionized water alternately 3-5 times. Finally, freeze-dry to obtain chitosan-coated drug-loaded nanoparticles. S3. Add chitosan-coated drug-loaded nanoparticles to 100-120 times their weight in dichloromethane, purge with argon gas to remove oxygen, then add 0.1-0.3 times the weight of the chitosan-coated drug-loaded nanoparticles in triethylamine and 0.5-0.8 times the weight of the chitosan-coated drug-loaded nanoparticles in acryloyl chloride. Stir and react at 25-35℃ for 4-6 hours. Then wash with water-ethanol and deionized water alternately 3-5 times, then soak in peptide solution and shake and react at 25-35℃ for 2-3 hours to obtain dual-response drug-loaded particles. S4. Using an alloy support as the working electrode, graphite as the counter electrode, and a calomel electrode as the reference electrode, place them in an electrodeposition solution with a current density of 0.5 mA•cm. -2 Drug-loaded alloy scaffolds were prepared by deposition at a temperature of 25-35℃ for 1-2 hours.

[0006] As an optimization, the mesoporous silica nanoparticles include the following preparation steps: hexadecyltrimethylammonium bromide, 2 mol / L sodium hydroxide solution and deionized water are mixed at a mass ratio of 1:3~4:450~500, stirred for 30~40 min at a temperature of 75~85℃, and then tetraethyl orthosilicate with a mass of 5~6 times that of hexadecyltrimethylammonium bromide is added dropwise. After the addition is completed, the reaction continues for 3~4 h. After the reaction is completed, the mixture is cooled to room temperature, centrifuged, and washed 3~5 times alternately with anhydrous ethanol and deionized water. The mixture is then vacuum dried for 12~16 h, and the template agent is removed by acid extraction to obtain mesoporous silica nanoparticles.

[0007] As an optimization, the acid extraction method for removing the template agent includes the following steps: placing the mesoporous silica nanoparticles without template agent removal into a hydrochloric acid-methanol solution mixture prepared at a volume ratio of 1:100, refluxing at a temperature of 55~65℃ for 12~14h, then centrifuging, washing and drying to obtain the mesoporous silica nanoparticles.

[0008] As an optimization, the drug is either a glycopeptide antibiotic or a lipoglycopeptide antibiotic.

[0009] As an optimization, the chitosan solution includes the following preparation steps: adding chitosan to a 5% acetic acid solution with a mass fraction of 100-120 times the mass of chitosan, and stirring for 24-28 hours at a temperature of 25-35℃ to obtain the solution for later use.

[0010] As an optimization, the polypeptide solution includes the following preparation steps: ethanol and deionized water are mixed at a volume ratio of 1:9 to obtain an ethanol solution, then cysteamine is added to 200-250 times the volume of the ethanol solution, and then 1-2 times the mass of diisopropylamine is added, and the mixture is stirred evenly to obtain the polypeptide solution.

[0011] As an optimization, the electrodeposition solution consists of 0.04~0.05 mol / L calcium nitrate tetrahydrate, 0.02~0.03 mol / L ammonium dihydrogen phosphate, 0.1~0.2 mol / L sodium nitrate, 10~15 mL / L hydrogen peroxide, and 1~2 g / L dual-response drug-loaded particles, and the pH is adjusted to 4~5 with nitric acid and ammonia.

[0012] Compared with the prior art, the beneficial effects achieved by the present invention are: This application utilizes mesoporous silica as a base carrier, whose regular pores can efficiently load drugs. Subsequent chitosan encapsulation and dual-response modification form a multi-layered protective structure, ensuring continuous and stable drug release during the 120-hour sustained-release process. Simultaneously, a dual precise response mechanism is constructed. The first mechanism leverages the pH sensitivity of chitosan (swelling and dissociation in acidic environments) to achieve pH-responsive antibacterial action. The second mechanism introduces disulfide bonds through cysteine ​​(Cys), utilizing the oxidative bond-breaking property of disulfide bonds in oxidative environments to achieve oxidation-responsive drug release. These two mechanisms can precisely match the lesion site (such as the acidic microenvironment and oxidative stress at the site of infection), reducing drug waste in normal tissues and improving antibacterial specificity. In addition, the calcium-phosphorus coating is similar to the composition of human bone and has good biocompatibility. The alloy scaffold is a commonly used implant material in clinical practice, and vancomycin can target drug-resistant Gram-positive bacteria (suitable for implant infection prevention). The overall solution meets the clinical application needs of implants such as orthopedics, achieving sustained drug release and antibacterial effects while taking into account the compatibility of the scaffold with human tissues. Detailed Implementation

[0013] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0014] Example 1 S1. Mix hexadecyltrimethylammonium bromide, 2 mol / L sodium hydroxide solution and deionized water at a mass ratio of 1:3:450. Stir for 30 min at 75℃. Then add 5 times the mass of tetraethyl orthosilicate of hexadecyltrimethylammonium bromide dropwise. Continue the reaction for 3 h after the addition is complete. After the reaction is complete, cool to room temperature, centrifuge, and wash three times alternately with anhydrous ethanol and deionized water. Vacuum dry for 12 h. Then place in a hydrochloric acid-methanol solution mixture prepared at a volume ratio of 1:100 and reflux at 55℃ for 12 h. After centrifugation, wash and dry to obtain mesoporous silica nanoparticles. S2. Mix 1 mg / mL vancomycin and 5 mg / mL mesoporous silica nanoparticles at a volume ratio of 1:1, stir for 24 h at 25 °C, centrifuge, and wash three times alternately with deionized water and ethanol to obtain drug-loaded nanoparticles. S3. Add drug-loaded nanoparticles to 100 times their mass of ethanol, ultrasonically disperse for 10 min, and adjust the pH to 3.5 with acetic acid. Then add (3-glycidylpropoxy)trimethoxysilane, which is 1 times the mass of the drug-loaded nanoparticles, and stir at 25°C for 3 h. Then add chitosan solution, which is 200 times the mass of the drug-loaded nanoparticles, and stir at 25°C for 24 h. After the reaction is complete, centrifuge and wash three times alternately with anhydrous ethanol and deionized water, and freeze-dry to obtain chitosan-coated drug-loaded nanoparticles. Add chitosan to 100 times its mass of 5% acetic acid solution and stir at 25°C for 24 h to obtain the final product. S4. Chitosan-coated drug-loaded nanoparticles were added to 100 times their volume of dichloromethane, and argon gas was passed through to remove oxygen. Then, 0.1 times the mass of the chitosan-coated drug-loaded nanoparticles of triethylamine and 0.5 times the mass of the chitosan-coated drug-loaded nanoparticles of acryloyl chloride were added. The mixture was stirred at 25°C for 4 hours. After that, the nanoparticles were washed three times alternately with ethanol and deionized water, and then immersed in a peptide solution. The mixture was shaken at 25°C for 2 hours to obtain dual-response drug-loaded particles. Ethanol and deionized water were mixed at a volume ratio of 1:9 to obtain an ethanol solution. Cysteine ​​was added to 200 times the volume of the ethanol solution, and then 1 times the mass of the cysteine ​​of diisopropylamine was added. The mixture was stirred evenly to obtain a peptide solution. S5. Using an alloy support as the working electrode, graphite as the counter electrode, and a calomel electrode as the reference electrode, place them in an electrodeposition solution with a current density of 0.5 mA•cm. -2Drug-loaded alloy scaffolds were prepared by deposition at 25℃ for 1 h. The electrodeposition solution consisted of 0.04 mol / L calcium nitrate tetrahydrate, 0.02 mol / L ammonium dihydrogen phosphate, 0.1 mol / L sodium nitrate, 10 mL / L hydrogen peroxide and 1 g / L dual-response drug-loaded particles, and the pH was adjusted to 4 with nitric acid and ammonia.

[0015] Example 2 S1. Hexadecyltrimethylammonium bromide, 2 mol / L sodium hydroxide solution, and deionized water were mixed at a mass ratio of 1:3.5:475 and stirred for 35 min at 80 °C. Then, tetraethyl orthosilicate (5.5 times the mass of hexadecyltrimethylammonium bromide) was added dropwise. After the addition was completed, the reaction was continued for 3.5 h. After the reaction was completed, the mixture was cooled to room temperature, centrifuged, and washed four times alternately with anhydrous ethanol and deionized water. The mixture was then vacuum dried for 14 h. After that, the mixture was placed in a hydrochloric acid-methanol solution mixture prepared at a volume ratio of 1:100 and refluxed at 60 °C for 13 h. After centrifugation, washing, and drying, mesoporous silica nanoparticles were obtained. S2. Mix 1 mg / mL vancomycin and 5 mg / mL mesoporous silica nanoparticles at a volume ratio of 1:1, stir for 26 h at 30 °C, centrifuge, and wash with deionized water and ethanol alternately 4 times to obtain drug-loaded nanoparticles. S3. Add drug-loaded nanoparticles to 110 times their mass of ethanol and ultrasonically disperse for 12.5 min. Adjust the pH to 4.0 with acetic acid. Then add 1.25 times their mass of (3-glycidylpropoxy)trimethoxysilane and stir at 30°C for 3.5 h. Then add 210 times their mass of chitosan solution and stir at 30°C for 26 h. After the reaction is complete, centrifuge and wash with anhydrous ethanol and deionized water alternately four times. Freeze-dry to obtain chitosan-coated drug-loaded nanoparticles. Add chitosan to 110 times their mass of 5% acetic acid solution and stir at 30°C for 26 h to obtain the final product. S4. Chitosan-coated drug-loaded nanoparticles were added to 110 times their volume of dichloromethane, and argon gas was passed through to remove oxygen. Then, 0.2 times the mass of the chitosan-coated drug-loaded nanoparticles of triethylamine and 0.65 times the mass of the chitosan-coated drug-loaded nanoparticles of acryloyl chloride were added. The mixture was stirred at 30°C for 5 hours. After that, the nanoparticles were washed four times alternately with ethanol and deionized water, and then immersed in a peptide solution. The mixture was shaken at 30°C for 2.5 hours to obtain dual-response drug-loaded particles. Ethanol and deionized water were mixed at a volume ratio of 1:9 to obtain an ethanol solution. Cysteine ​​was then added to 225 times the volume of the ethanol solution, followed by 1.5 times the mass of the cysteine ​​of diisopropylamine. The mixture was stirred until homogeneous to obtain a peptide solution. S5. Using an alloy support as the working electrode, graphite as the counter electrode, and a calomel electrode as the reference electrode, place them in an electrodeposition solution with a current density of 0.5 mA•cm. -2 Drug-loaded alloy scaffolds were prepared by deposition at 30℃ for 1.5 h. The electrodeposition solution consisted of 0.045 mol / L calcium nitrate tetrahydrate, 0.025 mol / L ammonium dihydrogen phosphate, 0.15 mol / L sodium nitrate, 12.5 mL / L hydrogen peroxide and 1.5 g / L dual-response drug-loaded particles, and the pH was adjusted to 4.5 with nitric acid and ammonia.

[0016] Example 3 S1. Hexadecyltrimethylammonium bromide, 2 mol / L sodium hydroxide solution, and deionized water were mixed at a mass ratio of 1:4:500 and stirred at 85℃ for 40 min. Then, tetraethyl orthosilicate with a mass of 6 times that of hexadecyltrimethylammonium bromide was added dropwise. After the addition was completed, the reaction was continued for 4 h. After the reaction was completed, the mixture was cooled to room temperature, centrifuged, and washed 5 times alternately with anhydrous ethanol and deionized water. The mixture was then vacuum dried for 16 h. After that, the mixture was placed in a hydrochloric acid-methanol solution mixture prepared at a volume ratio of 1:100 and refluxed at 65℃ for 14 h. After centrifugation, washing, and drying, mesoporous silica nanoparticles were obtained. S2. Mix 1 mg / mL vancomycin and 5 mg / mL mesoporous silica nanoparticles at a volume ratio of 1:1, stir for 28 h at 35 °C, centrifuge, and wash with deionized water and ethanol alternately 5 times to obtain drug-loaded nanoparticles. S3. Add drug-loaded nanoparticles to 120 times their mass of ethanol and ultrasonically disperse for 15 min. Adjust the pH to 4.5 with acetic acid. Then add 1.5 times their mass of (3-glycidylpropoxy)trimethoxysilane and stir at 35°C for 4 h. Then add 220 times their mass of chitosan solution and stir at 35°C for 28 h. After the reaction is complete, centrifuge and wash with anhydrous ethanol and deionized water alternately 5 times. Freeze-dry to obtain chitosan-coated drug-loaded nanoparticles. Add chitosan to 120 times their mass of 5% acetic acid solution and stir at 35°C for 28 h to obtain the final product. S4. Chitosan-coated drug-loaded nanoparticles were added to 120 times their volume of dichloromethane, and argon gas was passed through to remove oxygen. Then, 0.3 times the mass of the chitosan-coated drug-loaded nanoparticles of triethylamine and 0.8 times the mass of the chitosan-coated drug-loaded nanoparticles of acryloyl chloride were added. The mixture was stirred at 35°C for 6 hours. Afterward, the nanoparticles were washed 5 times alternately with ethanol and deionized water, and then immersed in a peptide solution. The mixture was shaken at 35°C for 3 hours to obtain dual-response drug-loaded particles. Ethanol and deionized water were mixed at a volume ratio of 1:9 to obtain an ethanol solution. Cysteine ​​was added to 250 times the volume of the ethanol solution, and then 2 times the mass of the cysteine ​​of diisopropylamine was added. The mixture was stirred evenly to obtain a peptide solution. S5. Using an alloy support as the working electrode, graphite as the counter electrode, and a calomel electrode as the reference electrode, place them in an electrodeposition solution with a current density of 0.5 mA•cm. -2 Drug-loaded alloy scaffolds were prepared by deposition at 35℃ for 2 hours. The electrodeposition solution consisted of 0.05 mol / L calcium nitrate tetrahydrate, 0.03 mol / L ammonium dihydrogen phosphate, 0.2 mol / L sodium nitrate, 15 mL / L hydrogen peroxide and 2 g / L dual-response drug-loaded particles, and the pH was adjusted to 5 with nitric acid and ammonia.

[0017] Example 4 The only difference from Example 2 is step S5: the alloy support is used as the working electrode, graphite as the counter electrode, and calomel electrode as the reference electrode, and the electrodes are placed in the electrodeposition solution with a current density of 0.5 mA•cm. -2 Drug-loaded alloy scaffolds were prepared by deposition at 30℃ for 1.5 h. The electrodeposition solution consisted of 0.045 mol / L calcium nitrate tetrahydrate, 0.025 mol / L ammonium dihydrogen phosphate, 0.15 mol / L sodium nitrate, 12.5 mL / L hydrogen peroxide, and 1.5 g / L chitosan-coated drug-loaded nanoparticles, and the pH was adjusted to 4.5 with nitric acid and ammonia. Example 5 The only difference from Example 2 is step S5: the alloy support is used as the working electrode, graphite as the counter electrode, and calomel electrode as the reference electrode, and the electrodes are placed in the electrodeposition solution with a current density of 0.5 mA•cm. -2 Drug-loaded alloy scaffolds were prepared by deposition at 30℃ for 1.5 h. The electrodeposition solution consisted of 0.045 mol / L calcium nitrate tetrahydrate, 0.025 mol / L ammonium dihydrogen phosphate, 0.15 mol / L sodium nitrate, 12.5 mL / L hydrogen peroxide and 1.5 g / L drug-loaded nanoparticles, and the pH was adjusted to 4.5 with nitric acid and ammonia. Performance testing: The alloy scaffolds prepared in Examples 1-5 were placed in (A) pH 7.4 10 μg / mL enzyme PBS solution, (B) pH 5.0 10 μg / mL enzyme PBS solution, (C) pH 7.4 PBS solution, and (D) pH 5.0 PBS solution, and the cumulative release of vancomycin was measured after immersion for 120 h; the experimental results are shown in Table 1 below; Table 1 Sample A / (μg / mL) B / (μg / mL) C / (μg / mL) D / (μg / mL) Example 1 138.9±9.8 192.6±4.4 101.6±8.8 173.1±9.9 Example 2 143.1±14.3 196.2±9.6 105.3±12.4 175.8±6.7 Example 3 147.0±11.2 195.8±7.2 109.3±7.3 172.6±9.6 Example 4 135.1±12.1 188.5±7.9 97.3±11.6 169.5±4.4 Example 5 131.5±8.2 185.3±5.1 93.4±7.5 166.0±6.2 The data in Table 1 show that Examples 1-3 had the highest drug release under dual stimulation (acid + enzyme) conditions, verifying the effectiveness of the dual-response design. However, Examples 4 (only chitosan-coated drug particles) and 5 (no drug particles coated) did not undergo complete dual-response modification, lacked enzyme-sensitive bonds, and had weak pH responsiveness. They could only release drugs through passive diffusion or chitosan swelling, and the interface between the carrier and the scaffold was weak and prone to detachment. As a result, the cumulative release over 120 hours was lower than that of Examples 1-3.

[0018] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No markings in the claims should be construed as limiting the scope of the claims.

Claims

1. A method for preparing an alloy stent with a composite coating, applied to an alloy stent with a composite coating, wherein a calcium-phosphorus drug-loaded coating is deposited on the surface of the alloy stent by electrodeposition, and the calcium-phosphorus drug-loaded coating comprises drug-loaded nanoparticles; the drug-loaded nanoparticles are coated with chitosan after being adsorbed with drug-loaded mesoporous silica nanoparticles, then acryloyl chloride is grafted to introduce double bonds, and finally a grafting reaction is carried out with cysteamine through the double bonds, and then mixed with a calcium-phosphorus coating and deposited on the surface of the alloy stent by electrodeposition; the alloy stent is any one of magnesium alloy, magnesium-zinc alloy or zinc alloy, characterized in that, The method comprises the following steps: S1, mixing 1 mg / mL drug with 5 mg / mL mesoporous silica nanoparticles at a volume ratio of 1:1, stirring for 24-28 h at a temperature of 25-35 DEG C, centrifugal separation, washing with deionized water and ethanol alternately for 3-5 times, and preparing drug-loaded nanoparticles; S2, adding the drug-loaded nanoparticles into ethanol with a mass of 100-120 times of the drug-loaded nanoparticles, ultrasonic dispersion for 10-15 min, adjusting the pH to 3.5-4.5 by using acetic acid, then adding (3-glycidylpropoxy) trimethoxysilane with a mass of 1-1.5 times of the drug-loaded nanoparticles, stirring for 3-4 h at a temperature of 25-35 DEG C, then adding a chitosan solution with a mass of 200-220 times of the drug-loaded nanoparticles, stirring for 24-28 h at a temperature of 25-35 DEG C, centrifugal separation after the reaction is completed, washing with anhydrous ethanol and deionized water alternately for 3-5 times, and freeze-drying to prepare chitosan-coated drug-loaded nanoparticles; S3, adding the chitosan-coated drug-loaded nanoparticles into dichloromethane with a mass of 100-120 times, removing oxygen by argon, then adding triethylamine with a mass of 0.1-0.3 times of the chitosan-coated drug-loaded nanoparticles and acryloyl chloride with a mass of 0.5-0.8 times of the chitosan-coated drug-loaded nanoparticles, stirring for 4-6 h at a temperature of 25-35 DEG C, washing with ethanol and deionized water alternately for 3-5 times, and then soaking in a polypeptide solution, oscillating for 2-3 h at a temperature of 25-35 DEG C, to prepare double-responsive drug-loaded particles. S4, the alloy stent is taken as a working electrode, graphite is taken as a counter electrode, and a mercury-mercury electrode is taken as a reference electrode, which are placed in the electrodeposition solution, and the current density is 0.5 mA•cm -2 The drug-loaded alloy stent is prepared by depositing for 1-2 h at a temperature of 25-35 ℃.

2. The method of claim 1, wherein the alloy stent having a composite coating is prepared by the steps of: The mesoporous silica nanoparticles comprise the following preparation steps: mixing cetyltrimethylammonium bromide, 2 mol / L sodium hydroxide solution and deionized water at a mass ratio of 1:3-4:450-500, stirring for 30-40 min at a temperature of 75-85 DEG C, then adding tetraethyl orthosilicate with a mass of 5-6 times of the cetyltrimethylammonium bromide, continuing to react for 3-4 h after the addition is completed, cooling to room temperature after the reaction is completed, centrifugal separation, washing with anhydrous ethanol and deionized water alternately for 3-5 times, vacuum drying for 12-16 h, and removing the template by an acid extraction method to prepare mesoporous silica nanoparticles.

3. The method of claim 1, wherein the alloy stent having a composite coating is prepared by the steps of: The acid extraction method for removing the template comprises the following steps: placing the mesoporous silica nanoparticles without removing the template in a hydrochloric acid-methanol solution mixture prepared at a volume ratio of 1:100, refluxing for 12-14 h at a temperature of 55-65 DEG C, then centrifugal separation, and cleaning and drying to prepare mesoporous silica nanoparticles.

4. The method of claim 1, wherein the alloy stent having a composite coating is prepared by the steps of: The drug is any one of glycopeptide antibiotics or lipoglycopeptide antibiotics.

5. The method of claim 1, wherein the alloy stent having a composite coating is prepared by the steps of: The chitosan solution comprises the following preparation steps: adding chitosan into an acetic acid solution with a mass fraction of 5% and a mass of 100-120 times of the chitosan, stirring for 24-28 h at a temperature of 25-35 DEG C, and preparing for standby.

6. The method of claim 1, wherein the alloy stent having a composite coating is prepared by the steps of: The polypeptide solution comprises the following preparation steps: mixing ethanol and deionized water according to a volume ratio of 1:9 to prepare an ethanol solution, adding cysteamine into the 200-250 times ethanol solution, then adding 1-2 times cysteamine by mass of diisopropylamine, and stirring uniformly to prepare the polypeptide solution.

7. The method of claim 1, wherein the method further comprises: The electro-deposition solution is composed of 0.04-0.05 mol / L calcium nitrate tetrahydrate, 0.02-0.03 mol / L ammonium dihydrogen phosphate, 0.1-0.2 mol / L sodium nitrate, 10-15 mL / L hydrogen peroxide and 1-2 g / L double-response drug-loaded particles, and the pH is adjusted to 4-5 by nitric acid and ammonia water.