A drug-loaded stainless steel stent and its preparation process

Abstract

The present invention relates to the technical field of stainless steel, and specifically to a stainless steel stent loaded with drugs and its preparation process. By adding benzophenone acetone solution, unsaturated monomers, and modified hydroxyapatite, a coating is prepared on the surface of the stainless steel stent to obtain a pretreated stainless steel stent. Then, a quaternization reaction is carried out on the surface of the pretreated stainless steel stent to obtain a quaternized coating. By adding chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and mercaptopropionic acid, mercaptochitosan is prepared; the stainless steel stent with a quaternized coating is immersed in a mixed solution of mercaptochitosan and a photoinitiator to prepare a composite coating. The stainless steel stent with a composite coating is immersed in a growth factor medicine solution to obtain the finished product. In summary, the coating prepared on the surface of the stainless steel stent in the present invention has good antibacterial properties and adhesion, so it has broad application prospects in the technical field of stainless steel.

Description

Technical Field

[0001] The present invention relates to the technical field of stainless steel, and specifically to a drug-loaded stainless steel stent and its preparation process. Background Art

[0002] Cardiovascular diseases are one of the main causes of death globally. Therefore, it is crucial to develop effective treatment means. In this regard, the application of stainless steel stents has provided patients with a better quality of life and survival rate. On the one hand, the application of stainless steel stents has significantly improved the prognosis of patients, enabling them to resume normal life and work. The timely implantation of the stent can effectively restore blood flow, relieve angina symptoms, and reduce the risk of myocardial infarction. In addition, the use of stainless steel stents has also promoted the implementation of secondary prevention measures, enabling patients to better manage their lifestyle and drug treatment after surgery, thereby reducing the incidence of cardiovascular events. On the other hand, the progress of stainless steel stent technology is also reflected in the combination with drug release systems. Many new drug-coated stents release drugs on the surface of the stent, further reducing the risk of restenosis. This drug coating not only improves the anti-thrombotic property of the stent but also enhances the treatment effect, effectively managing the cardiovascular health of patients.

[0003] However, after being implanted into the human body, due to the characteristics of its material, the stainless steel stent is prone to become a place for bacteria to attach and proliferate. The biofilm formed by these bacteria can cause difficult-to-treat infections, and in severe cases, it may trigger life-threatening complications such as sepsis. Therefore, there is an urgent need to improve the antibacterial performance of the stent, thereby effectively inhibiting the attachment of bacteria and reducing the probability of infection occurrence, and improving the postoperative survival rate of patients. In addition, the surface of the stent is usually coated with drugs or other functional materials to enhance its biocompatibility and treatment effect. If the adhesion performance of the coating is insufficient, the coating may fall off during or after the stent implantation. The detached coating particles may trigger an inflammatory reaction or thrombosis in the blood vessel, and in severe cases, it may lead to complications such as restenosis or embolism of the blood vessel. Therefore, improving the adhesion performance of the coating can effectively prevent these adverse events from occurring and ensure the safety of the stent.

[0004] To overcome the defects of the prior art, the present invention provides a drug-loaded stainless steel stent and its preparation process. Summary of the Invention

[0005] The purpose of the present invention is to provide a drug-loaded stainless steel stent and its preparation process to solve the problems in the prior art.

[0006] To solve the above technical problems, the present invention provides the following technical solutions:

[0007] A preparation process of a drug-loaded stainless steel stent, comprising the following steps:

[0008] Step 1: Wash the stainless-steel stent with water, alcohol, and acid, take it out and immerse it in unsaturated monomers, add modified hydroxyapatite, then add benzophenone acetone solution, and initiate polymerization with ultraviolet light at 360 - 365 nm for 30 - 40 min to obtain a pretreated stainless-steel stent; then immerse the pretreated stainless-steel stent in 1-bromooctane solution and carry out quaternization reaction at 70 - 75 °C for 20 - 24 h. After the reaction, wash and dry it to obtain a quaternized coating;

[0009] Step 2: Dissolve mercaptochitosan and photoinitiator 2,2-dimethoxy-2-phenylacetophenone in toluene to obtain a mixed solution; then immerse the stainless-steel stent prepared in Step 1 in the mixed solution and carry out ultraviolet light reaction at 360 - 365 nm for 15 - 20 h. After the reaction, wash it with alcohol and dry it under vacuum to obtain a composite coating;

[0010] Step 3: Dissolve the growth factor in deionized water to obtain a medicated solution; immerse the stainless-steel stent treated in Step 2 in the medicated solution for 15 - 25 h, and then rinse it with deionized water for 4 - 6 h to obtain the finished product.

[0011] Preferably, in Step 1, the unsaturated monomers include methacrylic acid, N,N-dimethylaminoethyl methacrylate, 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, 3-methacryloyldopamine, and the reaction molar ratio is 1:(3 - 4):2:(3 - 4); the dosage of the modified hydroxyapatite is 8 - 10 wt% of the total mass of the unsaturated monomers, and the benzophenone acetone solution is 20 - 25 wt%.

[0012] Preferably, the preparation process of the modified hydroxyapatite is as follows: Mix acrylic acid, p-toluenesulfonic acid, and hydroquinone, then add nano-hydroxyapatite and disperse it by ultrasonic for 15 - 20 min, and then carry out heating and reflux condensation reaction for 2 - 4 h. After the reaction, carry out suction filtration and drying to obtain the modified hydroxyapatite.

[0013] Preferably, the component contents of the modified hydroxyapatite are as follows: by mass fraction, 35 - 40% acrylic acid, 8 - 10% p-toluenesulfonic acid, 0.5 - 0.7% hydroquinone, and the balance is nano-hydroxyapatite.

[0014] Preferably, in Step 1, dissolve 1-bromooctane in N,N-dimethylformamide to obtain a 1-bromooctane solution with a concentration of 10 - 15 g / ml.

[0015] Preferably, in Step 2, the reaction mass ratio of mercaptochitosan and photoinitiator 2,2-dimethoxy-2-phenylacetophenone is (90 - 95):1.

[0016] Preferably, the preparation process of thiolated chitosan is as follows: adding chitosan powder into a mixed solvent, stirring for 30 - 40 min, then adding 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid, reacting for 12 - 15 h under dark conditions, and after the reaction, washing with water, washing with alcohol, and drying to obtain thiolated chitosan.

[0017] Preferably, the mixed solvent consists of acetonitrile and deionized water, and the mixing volume ratio is (1.5 - 2.0):1; the reaction mass ratio of chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid is 1:1:(0.7 - 0.8).

[0018] Preferably, in step three, the concentration of the liquid medicine is 20 - 30 wt%.

[0019] The beneficial effects of the present invention are as follows:

[0020] The characteristics of the present invention are that in step one, a coating is prepared on the surface of a stainless steel stent by adding benzophenone acetone solution, unsaturated monomers, and modified hydroxyapatite to obtain a pretreated stainless steel stent. The coating prepared on the surface of the stainless steel stent substrate can uniformly and stably cover the surface of the substrate, improving the wear resistance of the substrate. The unsaturated monomers include methacrylic acid, N,N-dimethylaminoethyl methacrylate, 2-(2-methoxyethoxy)ethyl methacrylate, 3-methacryloyldopamine; by adding 2-(2-methoxyethoxy)ethyl methacrylate, a flexible antifouling chain segment is introduced into the polymer, which can effectively improve the antifouling and antibacterial properties of the surface of the stainless steel stent; in this step, by adding 3-methacryloyldopamine monomer, a dopamine fragment is introduced into the polymer, which can effectively improve the adhesion and mechanical stability of the surface of the stainless steel stent; by adding modified hydroxyapatite, hydroxyapatite with good biocompatibility is introduced into the polymer, which can significantly enhance the adhesion strength of the coating, promote cell attachment and proliferation, and support bioremediation. Further, in this step, the pretreated stainless steel stent is immersed in 1-bromooctane solution for quaternization treatment to obtain a quaternary ammonium salt bactericidal chain segment, thereby effectively improving the antibacterial property of the surface of the stainless steel stent.

[0021] The characteristics of the present invention are as follows. In step two, thiolated chitosan is prepared by adding chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and mercaptopropionic acid. The stainless steel stent with a quaternized coating is immersed in a mixed solution of thiolated chitosan and a photoinitiator, and a composite coating is prepared through a thiol-ene click reaction. This step introduces chitosan with natural antibacterial properties into the surface coating, which can effectively inhibit the growth of bacteria and reduce the risk of infection on the surface of biomaterials. In addition, chitosan can also promote tissue repair and regeneration, and has a positive effect on the healing of damaged tissues.

[0022] The characteristics of the present invention are as follows. In step three, the growth factor is dissolved in deionized water to obtain a medicated solution. The stainless steel stent with a composite coating is immersed in the medicated solution to obtain the finished product. In summary, the coating prepared on the surface of the stainless steel stent in the present invention has good antibacterial properties and adhesion, so it has broad application prospects in the field of stainless steel technology. Specific embodiments

[0023] The technical solutions in the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of 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 shall fall within the protection scope of the present invention.

[0024] Source of raw materials:

[0025] The stainless steel stent is specifically 316L stainless steel; the growth factor is epidermal growth factor; the particle size of nano-hydroxyapatite is 200 nm; the specification of chitosan powder is 100 mesh.

[0026] Example 1: Step one: Mix 40% acrylic acid, 10% p-toluenesulfonic acid, and 0.7% hydroquinone by mass fraction, then add 49.3% nano-hydroxyapatite and ultrasonically disperse for 20 min, and then heat and reflux for 4 h. After the reaction is completed, filter by suction and dry to obtain modified hydroxyapatite.

[0027] The stainless-steel stent is washed with water, alcohol, and acid, taken out, impregnated in an unsaturated monomer, modified hydroxyapatite is added, and then a 25 wt% benzophenone acetone solution is added. Polymerization is initiated by ultraviolet light at 365 nm for 40 min to obtain a pretreated stainless-steel stent; the unsaturated monomer includes 1 mol of methacrylic acid, 3.5 mol of N,N-dimethylaminoethyl methacrylate, 2 mol of 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, 3.5 mol of 3-methacryloyldopamine, and 120 ml of deionized water is used as a solvent; the dosage of the modified hydroxyapatite is 10 wt% of the total mass of the unsaturated monomer;

[0028] Then the pretreated stainless-steel stent is impregnated in a 1-bromooctane solution at 15 g / ml, and quaternization reaction is carried out at 75 °C for 24 h. After the reaction is completed, it is washed and dried to obtain a quaternized coating;

[0029] Step 2: Chitosan powder is added to a mixed solvent, stirred for 40 min, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid are added, and the reaction is carried out under dark conditions for 15 h. After the reaction is completed, it is washed with water, alcohol, and dried to obtain mercaptochitosan; the mixed solvent is composed of acetonitrile and deionized water, and the mixing volume ratio is 2:1; the reaction mass ratio of chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and mercaptopropionic acid is 1:1:0.8;

[0030] Mercaptochitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone are dissolved in toluene to obtain a mixed solution; then the stainless-steel stent prepared in Step 1 is impregnated in the mixed solution, and ultraviolet light reaction is carried out at 365 nm for 20 h. After the reaction is completed, it is washed with alcohol and vacuum dried to obtain a composite coating; the reaction mass ratio of mercaptochitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone is 95:1;

[0031] Step 3: The growth factor is dissolved in deionized water to obtain a medicinal solution; the stainless-steel stent treated in Step 2 is impregnated in the medicinal solution for 25 h, and then rinsed with deionized water for 6 h to obtain the finished product; the concentration of the medicinal solution is 30 wt%.

[0032] Example 2: Step 1: By mass fraction, 40% acrylic acid, 10% p-toluenesulfonic acid, and 0.7% hydroquinone are mixed, then 49.3% nano-hydroxyapatite is added and ultrasonically dispersed for 17 min, and then heated under reflux for 3 h. After the reaction is completed, it is filtered by suction and dried to obtain modified hydroxyapatite;

[0033] The stainless-steel stent is washed with water, alcohol, and acid, taken out and immersed in an unsaturated monomer. Modified hydroxyapatite is added, and then a 25 wt% benzophenone acetone solution is added. Polymerization is initiated by ultraviolet light at 365 nm for 35 min to obtain a pretreated stainless-steel stent; the unsaturated monomer includes 1 mol of methacrylic acid, 3.5 mol of N,N-dimethylaminoethyl methacrylate, 2 mol of 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, 3.5 mol of 3-methacryloyldopamine, and 120 ml of deionized water is used as a solvent; the dosage of the modified hydroxyapatite is 10 wt% of the total mass of the unsaturated monomer;

[0034] Then the pretreated stainless-steel stent is immersed in a 1-bromooctane solution at 15 g / ml, and quaternization reaction is carried out at 73 °C for 22 h. After the reaction is completed, it is washed and dried to obtain a quaternized coating;

[0035] Step 2: Chitosan powder is added to the mixed solvent, stirred for 35 min, and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid are added. The reaction is carried out under dark conditions for 13 h. After the reaction is completed, it is washed with water, alcohol, and dried to obtain thiolated chitosan; the mixed solvent is composed of acetonitrile and deionized water, and the mixing volume ratio is 2:1; the reaction mass ratio of chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and mercaptopropionic acid is 1:1:0.8;

[0036] Thiolated chitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone are dissolved in toluene to obtain a mixed solution; then the stainless-steel stent prepared in Step 1 is immersed in the mixed solution, and the reaction is carried out under ultraviolet light at 365 nm for 17 h. After the reaction is completed, it is washed with alcohol and vacuum dried to obtain a composite coating; the reaction mass ratio of thiolated chitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone is 95:1;

[0037] Step 3: The growth factor is dissolved in deionized water to obtain a medicated solution; the stainless-steel stent treated in Step 2 is immersed in the medicated solution for 20 h, and then rinsed with deionized water for 5 h to obtain the finished product; the concentration of the medicated solution is 30 wt%.

[0038] Example 3: Step 1: In terms of mass fraction, 40% acrylic acid, 10% p-toluenesulfonic acid, and 0.7% hydroquinone are mixed, and then 49.3% nano-hydroxyapatite is added and ultrasonically dispersed for 15 min, and then heated under reflux for 2 h. After the reaction is completed, it is filtered and dried to obtain modified hydroxyapatite;

[0039] The stainless steel stent is washed with water, alcohol, and pickled, taken out and immersed in an unsaturated monomer, modified hydroxyapatite is added, and then 25 wt% of benzophenone acetone solution is added. Polymerization is initiated by ultraviolet light at 365 nm for 30 min to obtain a pretreated stainless steel stent; the unsaturated monomer includes 1 mol of methacrylic acid, 3.5 mol of N,N-dimethylaminoethyl methacrylate, 2 mol of 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, 3.5 mol of 3-methacryloyldopamine, and 120 ml of deionized water is used as a solvent; the dosage of the modified hydroxyapatite is 10 wt% of the total mass of the unsaturated monomer;

[0040] Then the pretreated stainless steel stent is immersed in a 1-bromooctane solution of 15 g / ml, and quaternization reaction is carried out at 70 °C for 20 h. After the reaction is completed, it is washed and dried to obtain a quaternized coating;

[0041] Step 2: Chitosan powder is added to a mixed solvent, stirred for 30 min, and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid are added. The reaction is carried out under dark conditions for 12 h. After the reaction is completed, it is washed with water, alcohol, and dried to obtain mercaptochitosan; the mixed solvent is composed of acetonitrile and deionized water, and the mixing volume ratio is 2:1; the reaction mass ratio of chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid is 1:1:0.8;

[0042] Mercaptochitosan and photoinitiator 2,2-dimethoxy-2-phenylacetophenone are dissolved in toluene to obtain a mixed solution; then the stainless steel stent prepared in Step 1 is immersed in the mixed solution, and ultraviolet light reaction is carried out at 365 nm for 15 h. After the reaction is completed, it is washed with alcohol and vacuum dried to obtain a composite coating; the reaction mass ratio of mercaptochitosan and photoinitiator 2,2-dimethoxy-2-phenylacetophenone is 95:1;

[0043] Step 3: The growth factor is dissolved in deionized water to obtain a medicinal solution; the stainless steel stent treated in Step 2 is immersed in the medicinal solution for 15 h, and then rinsed with deionized water for 4 h to obtain the finished product; the concentration of the medicinal solution is 30 wt%.

[0044] Comparative Example 1: The reaction molar ratio of methacrylic acid, N,N-dimethylaminoethyl methacrylate, 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, and 3-methacryloyldopamine was changed to 1:1:2:1, and the rest was the same as in Example 1. The specific steps are as follows: Step 1: Mix 40% acrylic acid, 10% p-toluenesulfonic acid, and 0.7% hydroquinone by mass fraction, then add 49.3% nano-hydroxyapatite and ultrasonically disperse for 20 min, and then heat and reflux for 4 h. After the reaction, filter by suction and dry to obtain modified hydroxyapatite;

[0045] Wash the stainless steel stent with water, alcohol, and acid, take it out and immerse it in the unsaturated monomer, add the modified hydroxyapatite, and then add 25 wt% benzophenone acetone solution, and initiate polymerization with 365 nm ultraviolet light for 40 min to obtain a pretreated stainless steel stent; The unsaturated monomer includes 1 mol of methacrylic acid, 1 mol of N,N-dimethylaminoethyl methacrylate, 2 mol of 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, and 1 mol of 3-methacryloyldopamine, and 120 ml of deionized water is used as the solvent; The dosage of the modified hydroxyapatite is 10 wt% of the total mass of the unsaturated monomer;

[0046] Then immerse the pretreated stainless steel stent in a 1-bromooctane solution of 15 g / ml and carry out quaternization reaction at 75 °C for 24 h. After the reaction, wash and dry to obtain a quaternized coating;

[0047] Step 2: Add chitosan powder to the mixed solvent, stir for 40 min, then add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid, and react for 15 h under dark conditions. After the reaction, wash with water, alcohol, and dry to obtain mercaptochitosan; The mixed solvent is composed of acetonitrile and deionized water, and the mixing volume ratio is 2:1; The reaction mass ratio of chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and mercaptopropionic acid is 1:1:0.8;

[0048] Dissolve mercaptochitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone in toluene to obtain a mixed solution; Then immerse the stainless steel stent prepared in Step 1 in the mixed solution and carry out ultraviolet light reaction at 365 nm for 20 h. After the reaction, wash with alcohol and vacuum dry to obtain a composite coating; The reaction mass ratio of mercaptochitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone is 95:1;

[0049] Step 3: Dissolve the growth factor in deionized water to obtain a drug solution; Immerse the stainless steel stent treated in Step 2 in the drug solution for 25 h, and then rinse with deionized water for 6 h to obtain the finished product; The concentration of the drug solution is 30 wt%.

[0050] Comparative Example 2: Remove the modified hydroxyapatite, and the rest is the same as in Example 1. The specific steps are as follows: Step 1: Wash the stainless steel stent with water, alcohol, and acid, take it out and immerse it in the unsaturated monomer, then add 25 wt% of benzophenone acetone solution, and carry out ultraviolet-induced polymerization at 365 nm for 40 min to obtain a pretreated stainless steel stent; the unsaturated monomer includes 1 mol of methacrylic acid, 1 mol of N,N-dimethylaminoethyl methacrylate, 2 mol of 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, 1 mol of 3-methacryloyldopamine, and 120 ml of deionized water is used as the solvent;

[0051] Then immerse the pretreated stainless steel stent in a 1-bromooctane solution of 15 g / ml, carry out quaternization reaction at 75 °C for 24 h, and after the reaction is completed, wash and dry to obtain a quaternized coating;

[0052] Step 2: Add chitosan powder to the mixed solvent, stir for 40 min, then add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid, and react for 15 h under dark conditions. After the reaction is completed, wash with water, wash with alcohol, and dry to obtain mercaptochitosan; the mixed solvent is composed of acetonitrile and deionized water, and the mixing volume ratio is 2:1; the reaction mass ratio of chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and mercaptopropionic acid is 1:1:0.8;

[0053] Dissolve mercaptochitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone in toluene to obtain a mixed solution; then immerse the stainless steel stent prepared in Step 1 in the mixed solution, and carry out ultraviolet light reaction at 365 nm for 20 h. After the reaction is completed, wash with alcohol and vacuum dry to obtain a composite coating; the reaction mass ratio of mercaptochitosan and the photoinitiator 2,2-dimethoxy-2-phenylacetophenone is 95:1;

[0054] Step 3: Dissolve the growth factor in deionized water to obtain a medicinal solution; immerse the stainless steel stent treated in Step 2 in the medicinal solution for 25 h, and then rinse with deionized water for 6 h to obtain the finished product; the concentration of the medicinal solution is 30 wt%.

[0055] Comparative Example 3: Remove Step 2, and the rest is the same as in Example 1. The specific steps are as follows: Step 1: Mix 40% acrylic acid, 10% p-toluenesulfonic acid, and 0.7% hydroquinone by mass fraction, then add 49.3% nano-hydroxyapatite and ultrasonically disperse for 20 min, and then heat and reflux for 4 h. After the reaction is completed, carry out suction filtration and drying to obtain modified hydroxyapatite;

[0056] The stainless steel bracket is washed with water, alcohol and acid, taken out and immersed in an unsaturated monomer, modified hydroxyapatite is added, and then 25wt% of benzophenone acetone solution is added, and polymerization is initiated by 365nm ultraviolet for 40min to obtain a pretreated stainless steel bracket; the unsaturated monomer includes 1mol of methacrylic acid, 1mol of methacrylic acid-N,N-dimethylaminoethyl ester, 2mol of 2-methyl-2-acrylic acid-2-(2-methoxyethoxy)ethyl ester, and 1mol of 3-methacryloyl dopamine, and 120ml of deionized water is used as a solvent; the amount of the modified hydroxyapatite is 10wt% of the total mass of the unsaturated monomer;

[0057] Then, the pretreated stainless steel stent was immersed in a 15 g / ml 1-bromooctane solution and subjected to a quaternization reaction at 75° C. for 24 h. After the reaction was completed, the quaternized coating was obtained by washing and drying.

[0058] Step 2: dissolving the growth factor in deionized water to obtain a drug solution; immersing the stainless steel stent with the quaternized ammonium coating in the drug solution for 25 hours, and then rinsing with deionized water for 6 hours to obtain a finished product; the concentration of the drug solution is 30wt%.

[0059] Detection test:

[0060] Antibacterial performance test: The coating on the surface of the finished stainless steel stent prepared by the present invention was evenly scraped, and the scraped product was added with phosphate buffer to prepare a 3 μg / mL solution, and then 10 mL of the inoculated Staphylococcus aureus solution was added, and the mixture was cultured at 28°C for 3 h. The solution was diluted and inoculated into the culture medium, and cultured at 28°C for 20 h. The number of colony growth was observed and recorded, and the antibacterial rate was calculated.

[0061] Cell activity test: The coating on the surface of the finished stainless steel stent prepared by the present invention was evenly scraped, and the scraped product was added to DMED culture medium and soaked for 48 hours to obtain a standby sample solution. L-929 fibroblasts were cultured in 5% CO 2 The cells were cultured at a constant temperature of 37°C. The cells were added to the sample solution and cultured for 4 days. MTT detection reagent was added and cultured for 4 hours at 37°C in the dark. Sodium dodecyl sulfate was added and mixed evenly. Finally, the cell activity was calculated by testing the absorbance of the sample solution.

[0062] Adhesion performance test: In the preparation process of the present invention, 1wt% of aniline blue dye is added to the unsaturated monomer to prepare a pretreated stainless steel bracket, which is then quaternized to obtain a stainless steel bracket with a quaternized coating as a sample. The tape is fully adhered to the surface of the sample, and the degree of coating peeling on the surface of the sample is recorded by taking pictures. The results are as follows:

[0063]

[0064] Conclusion: The dosages in Examples 1 to 3 remain unchanged, and only some reaction parameters are modified. It can be seen from the experimental data that there are no obvious fluctuations in the various properties of the specimens.

[0065] Comparative Example 1: The reaction molar ratio of methacrylic acid, N,N-dimethylaminoethyl methacrylate, 2-(2-methoxyethoxy)ethyl 2-methyl-2-propenoate, and 3-methacryloyldopamine was changed to 1:1:2:1, and the rest was the same as in Example 1. It can be seen from the experimental data that compared with Example 1, the antibacterial rate became 94.6%, the cell viability became 83%, and the degree of coating peeling was that there were small fragments or particles peeling on the surface. The reason for the analysis is that when preparing the quaternized coating, the present invention prepares a coating with good antibacterial and adhesion properties by setting the preferred reaction molar ratio. Therefore, after changing the reaction molar ratio to 1:1:2:1, both the antibacterial chain segment and the adhesion chain segment are reduced, so the antibacterial rate decreases, the cell viability decreases, and the degree of coating peeling becomes larger.

[0066] Comparative Example 2: The modified hydroxyapatite was removed, and the rest was the same as in Example 1. It can be seen from the experimental data that compared with Example 1, the cell viability became 85%, and the degree of coating peeling was that there was obvious peeling in some areas. The reason for the analysis is that hydroxyapatite can significantly enhance the adhesion strength of the coating, promote cell adhesion and proliferation. Therefore, after removing the modified hydroxyapatite, the cell viability decreases and the degree of coating peeling becomes larger.

[0067] Comparative Example 3: Step 2 was removed, and the rest was the same as in Example 1. It can be seen from the experimental data that compared with Example 1, the antibacterial rate became 90.8%, and the cell viability became 81%. The reason for the analysis is that the present invention introduces chitosan with natural antibacterial properties on the surface of the stainless steel stent with a hydrogel carrier coating, which can effectively inhibit the growth of bacteria, reduce the risk of infection on the surface of the biomaterial, and improve the cell viability. Therefore, after removing Step 2, the antibacterial rate decreases and the cell viability decreases.

[0068] It should be noted that in this article, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprising", "including" or any other variant thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device comprising a series of elements not only includes those elements, but also includes other elements not expressly listed, or also includes elements inherent to such process, method, article or device.

[0069] Finally, it should be noted that the above are only preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or perform equivalent replacements for some of the technical features. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A process for preparing a drug-loaded stainless steel stent, characterized in that: The following steps are involved: Step 1: Mix acrylic acid, p-toluenesulfonic acid and hydroquinone, add nano-hydroxyapatite and disperse by ultrasonic for 15-20 minutes, heat and condense under reflux for 2-4 hours, and after the reaction is completed, filter and dry to obtain modified hydroxyapatite; The stainless steel bracket is washed with water, alcohol and acid, taken out and immersed in unsaturated monomers, modified hydroxyapatite is added, and benzophenone acetone solution is added, and polymerization is initiated by 360-365nm ultraviolet for 30-40min to obtain a pretreated stainless steel bracket; the pretreated stainless steel bracket is then immersed in 1-bromooctane solution, and quaternization reaction is carried out at 70-75°C for 20-24h, and after the reaction is completed, it is washed and dried to obtain a quaternized coating; the unsaturated monomers include methacrylic acid, methacrylic acid-N,N-dimethylaminoethyl ester, 2-methyl-2-acrylic acid-2-(2-methoxyethoxy)ethyl ester, and 3-methacryloyl dopamine, and the reaction molar ratio is 1: (3-4): 2: (3-4); the amount of the modified hydroxyapatite is 8-10wt% of the total mass of the unsaturated monomers, and the amount of the benzophenone acetone solution is 20-25wt%; Step 2: dissolving thiolated chitosan and photoinitiator 2,2-dimethoxy-2-phenylacetophenone in toluene to obtain a mixed solution; then immersing the stainless steel stent prepared in step 1 in the mixed solution, reacting under 360-365nm ultraviolet light for 15-20h, and washing with alcohol and vacuum drying after the reaction to obtain a composite coating; Step 3: dissolving the growth factor in deionized water to obtain a drug solution; immersing the stainless steel stent obtained in step 2 in the drug solution for 15-25 hours, and then rinsing with deionized water for 4-6 hours to obtain a finished product.

2. The process for preparing a drug-loaded stainless steel stent according to claim 1, characterized in that: In step 1, the contents of the components of the modified hydroxyapatite are: by mass fraction, 35-40% acrylic acid, 8-10% p-toluenesulfonic acid, 0.5-0.7% hydroquinone, and the remainder is nano-hydroxyapatite.

3. The process for preparing a drug-loaded stainless steel stent according to claim 1, characterized in that: In step 1, 1-bromooctane is dissolved in N,N-dimethylformamide to obtain a 1-bromooctane solution with a concentration of 10-15 g / mL.

4. The process for preparing a drug-loaded stainless steel stent according to claim 1, characterized in that: In step 2, the reaction mass ratio of thiolated chitosan and photoinitiator 2,2-dimethoxy-2-phenylacetophenone is (90-95):

1.

5. The process for preparing a drug-loaded stainless steel stent according to claim 4, characterized in that: The preparation process of thiolated chitosan is as follows: chitosan powder is added to a mixed solvent, stirred for 30-40 minutes, and then 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and mercaptopropionic acid are added, reacted in the dark for 12-15 hours, and after the reaction is completed, the thiolated chitosan is obtained by washing with water, washing with alcohol, and drying.

6. The process for preparing a drug-loaded stainless steel stent according to claim 5, characterized in that: The mixed solvent consists of acetonitrile and deionized water, and the mixing volume ratio is (1.5-2.0):1; the reaction mass ratio of chitosan powder, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and mercaptopropionic acid is 1:1:(0.7-0.8).

7. The process for preparing a drug-loaded stainless steel stent according to claim 1, characterized in that: In step three, the concentration of the drug solution is 20-30wt%.

8. A drug-loaded stainless steel stent, characterized in that: Prepared according to the preparation process according to any one of claims 1 to 7.

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