Coronary rapamycin targeted elution stent and preparation method thereof

Abstract

The invention discloses a coronary rapamycin targeted elution stent which is thin in wall, small in occupied space, good in blood vessel trafficability, small in interference on blood flow, beneficial to maintaining normal blood flow, high in supporting force and pushing force, more flexible in the conveying process and capable of passing through tortuous and narrow coronary artery diseased regions more easily. The stent body can be well attached to the blood vessel wall, the gap between the stent body and the blood vessel wall is reduced, growth and covering of vascular endothelial cells are facilitated, and the risk of thrombosis and restenosis is reduced; the connecting piece is omega-shaped, so that the bracket main body can form enough radial strength; the polymer coating coated on the surface of the stent main body not only can finish precise sustained release of a drug, but also can realize complete degradation, and the polymer coating can promote growth and repair of vascular endothelial cells, accelerate the vascular endothelialization process, and is beneficial to recovery of normal physiological functions of blood vessels, so that the stent has a good application prospect. And the risk of thrombosis and restenosis is reduced.

Description

Technical Field

[0001] The present invention relates to the field of medicine and medical equipment, and in particular to a coronary rapamycin targeted eluting stent and a preparation method thereof. Background Art

[0002] Drug-eluting stents use a bare metal stent platform to carry anti-intimal hyperplasia drugs, which are eluted and released locally in the blood vessels, effectively inhibiting intimal hyperplasia in the stent to prevent restenosis within the stent. The effective use of drug-eluting stents can greatly reduce the incidence of restenosis and re-interventional surgery. Since current drug-eluting stents generally have problems such as insufficient support, poor permeability within blood vessels, and low drug release rate, the surgical risk increases and complications are easily caused. Summary of the invention

[0003] In order to solve the above problems, one of the purposes of the present application is to provide a coronary rapamycin targeted eluting stent, comprising:

[0004] The stent body is composed of a plurality of annular components coaxially arranged to form a retractable and expandable tubular body, and adjacent annular components are connected by Ω-shaped connectors. The thickness of the annular components is 40-45 μm, the length of the tubular body in the retracted state is 6-8 mm, the length of the tubular body in the expanded state is 50-52 mm, the diameter of the tubular body in the retracted state is 2-3 mm, and the diameter of the tubular body in the expanded state is 5-6 mm; the annular components are composed of a plurality of V-shaped parts, the corners of the V-shaped parts are arc-shaped, and the thickness of the corners is 5-10 μm thicker than other parts of the V-shaped parts. When the tubular body is retracted, it is in a waiting state for implantation, and when it is expanded, it is in an implanted state;

[0005] The polymer coating comprises a first coating, a second coating and a third coating which are stacked in sequence, and the first coating is coated on the surface of the stent body.

[0006] The stent body has a thin wall and occupies a small space in the blood vessel, which has little interference with blood flow and is conducive to maintaining normal blood flow. It is more flexible during transportation and can more easily pass through tortuous and narrow coronary artery lesions. It can fit the blood vessel wall well, reduce the gap between the stent body and the blood vessel wall, and is also conducive to the growth and coverage of vascular endothelial cells, reducing the risk of thrombosis and restenosis; the Ω-shaped connector is conducive to the formation of sufficient radial strength of the stent body; the polymer coating coated on the surface of the stent body can not only achieve precise sustained release of drugs but also achieve complete degradation, and the polymer coating can also promote the growth and repair of vascular endothelial cells, accelerate the process of vascular endothelialization, help restore the normal physiological function of blood vessels, and reduce the risk of thrombosis and restenosis.

[0007] Preferably, the stent body is made of nickel-titanium alloy material, in which the nickel content is 51.5-54.5% and the titanium content is 45.5-48.5%. By fine-tuning the ratio of nickel and titanium elements, the nickel content is slightly increased to reduce the phase transition temperature of the stent body, so that the stent body can ensure sufficient radial strength at body temperature while ensuring good flexibility and the ability to adapt to the anatomical structure of the blood vessel. The elastic modulus of this nickel-titanium alloy in the low-temperature stable phase is between 22 and 32 GPa.

[0008] Preferably, the spray solution for the first coating layer is composed of 1 to 10 parts of L-polylactic acid and 90 to 99 parts of hexafluoroisopropanol by mass. L-polylactic acid is a degradable polymer, which can be used as a drug storage reservoir to control the release rate of rapamycin. As L-polylactic acid gradually degrades, rapamycin will continue to be released, ensuring that the drug plays a role throughout the entire process of vascular repair; hexafluoroisopropanol has good solubility, and by adjusting the ratio of L-polylactic acid and hexafluoroisopropanol, it can be ensured that L-polylactic acid is evenly dispersed in hexafluoroisopropanol. By adjusting the ratio of L-polylactic acid and hexafluoroisopropanol, the first coating layer can be ensured to be more stable and smooth, improve the biocompatibility of the eluting stent, reduce the risk of thrombosis, and the easy evaporation of hexafluoroisopropanol can promote the rapid solidification of L-polylactic acid and form a stable structure, and there is no need to worry that hexafluoroisopropanol will remain and affect the safety of the final product.

[0009] Preferably, the spray solution for the second coating layer is composed of 2 to 5 parts of L-polylactic acid, 0.5 to 1.5 parts of rapamycin and 93.5 to 97.5 parts of hexafluoroisopropanol in parts by mass. L-polylactic acid is a degradable material that can gradually degrade into harmless products in the body. Its degradation process is slow and will not cause obvious inflammatory reactions. It also provides a stable environment for the sustained release of drugs. L-polylactic acid also has high mechanical strength and flexibility, which can provide good support and compliance for the system stent, enable the eluting stent to adapt to the bending and deformation of the blood vessel, reduce the damage of the stent to the blood vessel wall, and improve the implantation success rate and long-term stability of the stent. Rapamycin has a strong immunosuppressive and anti-proliferative effect. After polyvinylpyrrolidone is dissolved, rapamycin begins to be released slowly and continuously to maintain the local drug concentration and inhibit the excessive proliferation of the vascular endothelium for a long time. By adjusting the ratio between L-polylactic acid, rapamycin and hexafluoroisopropanol, it can be ensured that L-polylactic acid and rapamycin are completely dissolved in hexafluoroisopropanol, which is convenient for later spraying without clogging the nozzle, and also ensures the uniformity and consistency of the coating.

[0010] Preferably, the spray solution for the third coating is composed of 5 to 15 parts of polyvinyl pyrrolidone and 85 to 95 parts of hexafluoroisopropanol in terms of mass fractions. Polyvinyl pyrrolidone has good hydrophilicity and can dissolve rapidly in the early stage of eluting stent implantation, so that a small amount of rapamycin is quickly released. The rapidly released rapamycin can inhibit the proliferation of smooth muscle cells in a short time, prevent the occurrence of acute thrombosis and vascular restenosis; polyvinyl pyrrolidone also has good biocompatibility, can reduce the inflammatory response and foreign body reaction caused by the implantation of eluting stent, it can form a protective film on the surface of the stent body, reduce the adhesion of proteins and cells in the blood to the stent, and reduce the risk of thrombosis; by adjusting the ratio of polyvinyl pyrrolidone and hexafluoroisopropanol, it is ensured that polyvinyl pyrrolidone is completely dissolved in hexafluoroisopropanol, which is convenient for later spraying without clogging the nozzle, and also ensures the uniformity and consistency of the coating.

[0011] Another object of the present application is to provide a method for preparing a coronary rapamycin targeted eluting stent, comprising the following steps:

[0012] Preparation of the stent body: A preform is obtained by accurately cutting a predetermined pattern from the tube using laser cutting technology, and the stent body is obtained by pickling and polishing the preform;

[0013] Spraying polymer coating: The first coating, the second coating and the third coating are sprayed on the surface of the stent body in sequence by using ultrasonic spraying technology, and then irradiated and sterilized to obtain the finished product.

[0014] Preferably, the specific steps of pickling and polishing the preform include:

[0015] Remove burrs from the preform surface by mechanical grinding;

[0016] Pickling: Prepare a mixed acid solution, mix 5-9wt% hydrofluoric acid, 8-12wt% nitric acid and 79-87wt% water; first treat the surface of the preform with 1-2mol / LNaOH solution at 80-90°C for 10-20min to remove existing impurities and oxide film, then ultrasonically clean the preform with acetone, anhydrous ethanol and deionized water in sequence, each time for 5-10min; then blow nitrogen gas on the surface of the preform; finally immerse the preform in the mixed acid solution, let it stand at 25-37°C for 6-12h, take it out, clean it with deionized water, and dry it;

[0017] Electropolishing: A mixture of 3-7wt% perchloric acid, 5-15wt% glacial acetic acid and 88-92wt% ethylene glycol is used as the electrolyte to electropolish the pickled preforms. The electrolyte temperature is controlled at 60-70°C and the current density is controlled at 10-25A / dm 2, the polishing time is controlled at 5 to 8 minutes, and the stent body with an outer surface roughness of 5 to 10 nanometers is obtained. This pickling and polishing process can ensure that the copper sulfide polymer coating is well attached to the outer surface of the stent body, and can ensure the comfort of the patient after the stent is implanted; the stent body with an outer surface roughness of 5 to 10 nanometers is conducive to the slow release of rapamycin, so that 70% of rapamycin is released to the blood vessel wall within 7 days, and the continuous release is greater than 90 days. On the 90th day, the rapamycin concentration acting on the blood vessel wall is still greater than 2.239ng / mg, and the appropriate electrolyte temperature, current density and polishing time will affect the final roughness of the outer surface of the stent body.

[0018] Preferably, the mixed acid solution is obtained by mixing 7 wt % of hydrofluoric acid, 10 wt % of nitric acid and 83 wt % of water.

[0019] Preferably, the electrolyte is obtained by mixing 5 wt % perchloric acid, 10 wt % glacial acetic acid and 90 wt % ethylene glycol.

[0020] Preferably, the spraying step specifically includes:

[0021] Turn on the power of the sprayer, ultrasonic power supply and constant current pump. After the nitrogen meter on the sprayer is stable, discharge the solvent pre-installed on the constant current pump, fill it with the spray solution for the first coating, click the fast forward button on the constant current pump, so that the spray solution for the first coating fills the entire channel and can drip from the nozzle; set the flow rate of the constant current pump to 0.06-0.1 ml / min, the nitrogen pressure of the sprayer to 1.7-2.1 Psi, the operating power of the sprayer to 3.0-5.0 W, and the moving speed of the spray head of the sprayer to 0.1-0.15 cm / s; aim the nozzle at the main body of the bracket to complete the first spraying; then fill it with the spray solution for the second coating and repeat the above operation to complete the second spraying of the main body of the bracket; finally fill it with the spray solution for the third coating and repeat the above operation to complete the third spraying of the main body of the bracket; nitrogen purge during the spraying process allows hexafluoroisopropanol to evaporate quickly. The thickness of the polymer coating must be strictly controlled within a specific range. If the polymer coating is too thick, it may affect the flexibility and expansion performance of the eluting stent, while if the polymer coating is too thin, it may not provide sufficient rapamycin release. The above-mentioned spraying process can ensure the consistency and accuracy of the coating thickness.

[0022] The beneficial effects are as follows: the eluting stent provided by the present application has a thin wall, occupies a small space, has good vascular permeability, has little interference with blood flow, is conducive to maintaining normal blood flow, has strong supporting force and driving force, is more flexible during transportation, can more easily pass through tortuous and narrow coronary artery lesions, and can fit the blood vessel wall well, reduce the gap between the stent body and the blood vessel wall, and is also conducive to the growth and coverage of vascular endothelial cells, reducing the risk of thrombosis and restenosis; the Ω-shaped connector is conducive to the formation of sufficient radial strength of the stent body; the polymer coating coated on the surface of the stent body can not only achieve precise sustained release of drugs but also achieve complete degradation, and the polymer coating can also promote the growth and repair of vascular endothelial cells, accelerate the process of vascular endothelialization, help restore the normal physiological function of blood vessels, and reduce the risk of thrombosis and restenosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0024] Figure 1 This is a schematic diagram of the structure of the coronary rapamycin targeted eluting stent of this application;

[0025] Figure 2 This is a comparison chart of the coronary arteries before and after the coronary rapamycin targeted eluting stent implantation for this application;

[0026] In the figure:

[0027] 1. Ring assembly; 11. V-shaped piece; 2. Ω-shaped connector. DETAILED DESCRIPTION

[0028] The present invention is further described in detail below in conjunction with specific embodiments so that those skilled in the art can understand the present invention more clearly.

[0029] The following embodiments are only used to illustrate the present invention, but are not limited to the scope of the present invention. Based on the specific embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without creative work belong to the protection scope of the present invention.

[0030] In the examples of the present invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art; in the examples of the present invention, unless otherwise specified, the technical means used are conventional means well known to those skilled in the art.

[0031] Source of raw materials:

[0032] Nickel-titanium alloy was purchased from Suzhou Haichuan Rare Metal Products Co., Ltd.;

[0033] Poly(L-lactic acid), PLLA-05, with an intrinsic viscosity range of 0.30-0.50 dL / g; PLLA-07, with an intrinsic viscosity range of 0.50-0.70 dL / g; both purchased from Shenzhen Boli Biomaterials Co., Ltd.; B6002-1, with an intrinsic viscosity range of 0.15-0.35 dL / g, purchased from EVONIK, USA;

[0034] Hexafluoroisopropanol was purchased from Zhongshan Dixin Chemical Co., Ltd.

[0035] Rapamycin was purchased from Hubei APT Bioengineering Co., Ltd.;

[0036] Polyvinyl pyrrolidone, K30, was purchased from Jinan Zhengkang Chemical Co., Ltd.;

[0037] Hydrofluoric acid was purchased from Dongguan Xunye Chemical Reagent Co., Ltd.;

[0038] Nitric acid was purchased from Guangdong Wengjiang Chemical Reagent Co., Ltd.;

[0039] NaOH, purchased from Wuhan Yixingda Chemical Co., Ltd.;

[0040] Acetone was purchased from Chengdu Xinghaitian Chemical Co., Ltd.

[0041] Anhydrous ethanol was purchased from Jinzhou Gucheng Chemical Reagent Co., Ltd.;

[0042] Perchloric acid was purchased from Guangdong Fangxin Biotechnology Co., Ltd.;

[0043] Glacial acetic acid was purchased from Jinan Chenxing Chemical Co., Ltd.

[0044] Ethylene glycol was purchased from Guangzhou Xiangqian Chemical Co., Ltd.;

[0045] The remaining reagents are commercially available.

[0046] Equipment source:

[0047] Sprayer, Chifei ultrasonic sprayer YAM3000, purchased from Wuhan Rongruijia Coating Electromechanical Equipment Co., Ltd.

[0048] Example 1

[0049] This embodiment provides a coronary rapamycin targeted eluting stent, comprising:

[0050] The stent body is made of nickel-titanium alloy material, wherein the nickel content of the nickel-titanium alloy is 51.5% and the titanium content is 48.5%. The stent body is composed of a plurality of annular components coaxially arranged to form a retractable and expandable tubular body, and adjacent annular components are connected by Ω-shaped connectors. The thickness of the annular components is 40 μm, and the length of the tubular body in the retracted state is 6 mm, and the length of the tubular body in the expanded state is 50 mm. The diameter of the tubular body in the retracted state is 2 mm, and the diameter of the tubular body in the expanded state is 5 mm; the annular components are composed of a plurality of V-shaped parts, and the corners of the V-shaped parts are arc-shaped, and the thickness of the corners is 5 μm thicker than that of other parts of the V-shaped parts;

[0051] A polymer coating, comprising a first coating, a second coating and a third coating which are sequentially stacked, wherein the first coating is coated on the surface of the stent body; wherein the spray solution for the first coating consists of 1 part of L-polylactic acid and 90 parts of hexafluoroisopropanol in terms of weight; the spray solution for the second coating consists of 2 parts of L-polylactic acid, 0.5 parts of rapamycin and 97.5 parts of hexafluoroisopropanol in terms of weight; and the spray solution for the third coating consists of 5 parts of polyvinyl pyrrolidone and 95 parts of hexafluoroisopropanol in terms of weight;

[0052] A method for preparing a coronary rapamycin targeted eluting stent comprises the following steps:

[0053] Preparation of the stent body: A preform is obtained by accurately cutting a predetermined pattern from the tube using laser cutting technology, and the stent body is obtained by pickling and polishing the preform;

[0054] Spraying polymer coating: using ultrasonic spraying technology to spray the first coating, the second coating and the third coating on the surface of the stent body in sequence, and then irradiating and sterilizing to obtain the finished product;

[0055] The specific steps of pickling and polishing the preforms include:

[0056] Remove burrs from the preform surface by mechanical grinding;

[0057] Pickling: Prepare a mixed acid solution, mix 5wt% hydrofluoric acid, 8wt% nitric acid and 87wt% water; first treat the surface of the preform with 1mol / LNaOH solution at 80°C for 10min, then ultrasonically clean the preform with acetone, anhydrous ethanol and deionized water in turn, each time for 5min; then blow nitrogen gas on the surface of the preform; finally immerse the preform in the mixed acid solution, stand at 25°C for 6h, take it out, clean it with deionized water, and dry it;

[0058] Electropolishing: A mixture of 3wt% perchloric acid, 5wt% glacial acetic acid and 92wt% ethylene glycol was used as the electrolyte to electropolish the pickled preforms. The electrolyte temperature was controlled at 60°C and the current density was controlled at 10A / dm 2, the polishing time is controlled at 5 min, and the stent body with an outer surface roughness of 5 nanometers is obtained;

[0059] The spraying steps specifically include:

[0060] Turn on the power of the sprayer, ultrasonic power supply and constant current pump. After the nitrogen meter on the sprayer is stable, discharge the solvent pre-installed on the constant current pump and fill it with the spray solution for the first coating. Click the fast forward button on the constant current pump to fill the entire channel with the spray solution for the first coating and allow it to drip from the nozzle. Set the flow rate of the constant current pump to 0.06ml / min, the nitrogen pressure of the sprayer to 1.7Psi, the operating power of the sprayer to 3.0W, and the moving speed of the spray nozzle to 0.1cm / s. Aim the nozzle at the main body of the stent to complete the first spraying. Then fill it with the spray solution for the second coating and repeat the above operation to complete the second spraying of the main body of the stent. Finally, fill it with the spray solution for the third coating and repeat the above operation to complete the third spraying of the main body of the stent.

[0061] Example 2

[0062] This embodiment provides a coronary rapamycin targeted eluting stent, comprising:

[0063] The stent body is made of nickel-titanium alloy material, wherein the nickel content of the nickel-titanium alloy is 54.5% and the titanium content is 45.5%. The stent body is composed of a plurality of annular components coaxially arranged to form a retractable and expandable tubular body, and adjacent annular components are connected by Ω-shaped connectors. The thickness of the annular components is 45 μm, and the length of the tubular body in the retracted state is 8 mm, and the length of the tubular body in the expanded state is 52 mm. The diameter of the tubular body in the retracted state is 3 mm, and the diameter of the tubular body in the expanded state is 6 mm. The annular components are composed of a plurality of V-shaped parts, and the corners of the V-shaped parts are arc-shaped, and the thickness of the corners is 10 μm thicker than that of other parts of the V-shaped parts.

[0064] A polymer coating, comprising a first coating, a second coating and a third coating which are sequentially stacked, wherein the first coating is coated on the surface of the stent body; wherein the spray solution for the first coating consists of 10 parts of L-polylactic acid and 90 parts of hexafluoroisopropanol in terms of weight; the spray solution for the second coating consists of 5 parts of L-polylactic acid, 1.5 parts of rapamycin and 93.5 parts of hexafluoroisopropanol in terms of weight; and the spray solution for the third coating consists of 15 parts of polyvinyl pyrrolidone and 85 parts of hexafluoroisopropanol in terms of weight;

[0065] A method for preparing a coronary rapamycin targeted eluting stent comprises the following steps:

[0066] Preparation of the stent body: A preform is obtained by accurately cutting a predetermined pattern from the tube using laser cutting technology, and the stent body is obtained by pickling and polishing the preform;

[0067] Spraying polymer coating: using ultrasonic spraying technology to spray the first coating, the second coating and the third coating on the surface of the stent body in sequence, and then irradiating and sterilizing to obtain the finished product;

[0068] The specific steps of pickling and polishing the preforms include:

[0069] Remove burrs from the preform surface by mechanical grinding;

[0070] Pickling: Prepare a mixed acid solution, mix 9wt% hydrofluoric acid, 12wt% nitric acid and 79wt% water; first treat the surface of the preform with a 2mol / LNaOH solution at 90°C for 20min, then ultrasonically clean the preform with acetone, anhydrous ethanol and deionized water in turn, each for 10min; then blow nitrogen gas on the surface of the preform; finally immerse the preform in the mixed acid solution, let it stand at 37°C for 12h, take it out, clean it with deionized water, and dry it;

[0071] Electropolishing: A mixture of 7wt% perchloric acid, 15wt% glacial acetic acid and 88wt% ethylene glycol was used as the electrolyte to electropolish the pickled preforms. The electrolyte temperature was controlled at 70°C and the current density was controlled at 25A / dm 2 , the polishing time is controlled at 8 min, and the stent body with an outer surface roughness of 10 nm is obtained;

[0072] The spraying steps specifically include:

[0073] Turn on the power of the sprayer, ultrasonic power supply and constant current pump. After the nitrogen meter on the sprayer is stable, discharge the solvent pre-installed on the constant current pump and fill it with the spray solution for the first coating. Click the fast forward button on the constant current pump to fill the entire channel with the spray solution for the first coating and allow it to drip from the nozzle. Set the flow rate of the constant current pump to 0.1 ml / min, the nitrogen pressure of the sprayer to 2.1 Psi, the operating power of the sprayer to 5.0 W, and the moving speed of the spray nozzle to 0.15 cm / s. Aim the nozzle at the main body of the stent to complete the first spraying. Then fill it with the spray solution for the second coating and repeat the above operation to complete the second spraying of the main body of the stent. Finally, fill it with the spray solution for the third coating and repeat the above operation to complete the third spraying of the main body of the stent.

[0074] Example 3

[0075] This embodiment provides a coronary rapamycin targeted eluting stent, comprising:

[0076] The stent body is made of nickel-titanium alloy material, wherein the nickel content of the nickel-titanium alloy is 53% and the titanium content is 47%. The stent body is composed of a plurality of annular components coaxially arranged to form a retractable and expandable tubular body, and adjacent annular components are connected by Ω-shaped connectors. The thickness of the annular components is 43 μm, and the length of the tubular body in the retracted state is 7 mm, and the length of the tubular body in the expanded state is 51 mm. The diameter of the tubular body in the retracted state is 2.5 mm, and the diameter of the tubular body in the expanded state is 5.5 mm. The annular components are composed of a plurality of V-shaped parts, and the corners of the V-shaped parts are arc-shaped, and the thickness of the corners is 7 μm thicker than that of other parts of the V-shaped parts.

[0077] A polymer coating, comprising a first coating, a second coating and a third coating which are sequentially stacked, wherein the first coating is coated on the surface of the stent body; wherein the spray solution for the first coating consists of 5 parts of L-polylactic acid and 95 parts of hexafluoroisopropanol in terms of weight; the spray solution for the second coating consists of 3.5 parts of L-polylactic acid, 1 part of rapamycin and 95.5 parts of hexafluoroisopropanol in terms of weight; and the spray solution for the third coating consists of 10 parts of polyvinyl pyrrolidone and 90 parts of hexafluoroisopropanol in terms of weight;

[0078] A method for preparing a coronary rapamycin targeted eluting stent comprises the following steps:

[0079] Preparation of the stent body: A preform is obtained by accurately cutting a predetermined pattern from the tube using laser cutting technology, and the stent body is obtained by pickling and polishing the preform;

[0080] Spraying polymer coating: using ultrasonic spraying technology to spray the first coating, the second coating and the third coating on the surface of the stent body in sequence, and then irradiating and sterilizing to obtain the finished product;

[0081] The specific steps of pickling and polishing the preforms include:

[0082] Remove burrs from the preform surface by mechanical grinding;

[0083] Pickling: Prepare a mixed acid solution, mix 7wt% hydrofluoric acid, 10wt% nitric acid and 83wt% water; first treat the surface of the preform with 1.5mol / LNaOH solution at 85°C for 15min, then ultrasonically clean the preform with acetone, anhydrous ethanol and deionized water in turn, each for 7min; then blow nitrogen gas on the surface of the preform; finally immerse the preform in the mixed acid solution, stand at 30°C for 9h, take it out, clean it with deionized water, and dry it;

[0084] Electropolishing: A mixture of 5wt% perchloric acid, 10wt% glacial acetic acid and 90wt% ethylene glycol was used as the electrolyte to electropolish the pickled preforms. The electrolyte temperature was controlled at 65°C and the current density was controlled at 17A / dm 2, the polishing time is controlled at 7 minutes, and the stent body with an outer surface roughness of 8 nanometers is obtained;

[0085] The spraying steps specifically include:

[0086] Turn on the power of the sprayer, ultrasonic power supply and constant current pump. After the nitrogen meter on the sprayer is stable, discharge the solvent pre-installed on the constant current pump and fill it with the spray solution for the first coating. Click the fast forward button on the constant current pump to fill the entire channel with the spray solution for the first coating and allow it to drip from the nozzle. Set the flow rate of the constant current pump to 0.08ml / min, the nitrogen pressure of the sprayer to 1.9Psi, the operating power of the sprayer to 4.0W and the moving speed of the spray nozzle to 0.12cm / s. Aim the nozzle at the main body of the stent to complete the first spraying. Then fill it with the spray solution for the second coating and repeat the above operation to complete the second spraying of the main body of the stent. Finally, fill it with the spray solution for the third coating and repeat the above operation to complete the third spraying of the main body of the stent.

[0087] Comparative Example 1

[0088] The comparative example is Abbott's coronary drug-eluting stent Xience-Sierra.

[0089] The coronary rapamycin targeted eluting stents prepared in Examples 1 to 3 and Comparative Example 1 were tested respectively.

[0090] Test method:

[0091] The coating thickness is tested according to the method of GB / T 33787-2017 "Surface treatment technology of medical devices Part 2: Determination of physical and chemical properties of polymer coatings on metal materials";

[0092] Passability, support force and pushing force are all tested in accordance with GB / T 25304-2010 "Special Requirements for Non-vascular Self-expanding Metal Stents" standard; passability (φ3.0) means that the eluting stent can smoothly pass through a blood vessel with a diameter of 3.0 mm or wider; support force refers to the support force that the eluting stent can provide to the blood vessel wall after it is implanted and deployed in the blood vessel; pushing force refers to the force required when the eluting stent is pushed to the target vascular lesion through the catheter;

[0093] The test results are shown in Table 1.

[0094]

[0095] From the experimental data in Table 1, it can be seen that in Examples 1 to 3, all indicators meet the national standards; comparing Example 1 with Comparative Example 1, the sum of the wall thickness and the coating thickness of the eluting stent of Example 1 is smaller than that of Comparative Example 1. In theory, the passability of Example 1 will be better, the supporting force of Example 1 is greater than that of Comparative Example 1, and the pushing force of Example 1 is equivalent to that of Comparative Example 1.

[0096] Figure 2 It is based on animal research on pigs, in which the coronary rapamycin targeted eluting stent prepared by this application was implanted in the left and right iliac arteries of the pigs, respectively. The specific testing method was carried out in accordance with YY / T 0675-2019 "Cardiovascular Implant Coronary Drug Eluting Stent", and images of the left and right iliac arteries were taken before, during and after the operation. By comparison, it was found that the coronary rapamycin targeted eluting stent prepared by this application did not show edge peeling or acute thrombosis during and after the operation, nor did it show intimal proliferation. The stent was immediately well attached, and the vascular wall and the eluting stent structure were intact.

[0097] The above is only an embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the scope of the claims of the present invention.

Claims

1. A coronary rapamycin targeted eluting stent, characterized in that: include: The stent body is composed of a plurality of annular components coaxially arranged to form a retractable and expandable tubular body, wherein adjacent annular components are connected by Ω-shaped connectors, wherein the thickness of the annular components is 40 to 45 μm, the length of the tubular body in the retracted state is 6 to 8 mm, the length of the tubular body in the expanded state is 50 to 52 mm, the diameter of the tubular body in the retracted state is 2 to 3 mm, and the diameter of the tubular body in the expanded state is 5 to 6 mm; the annular component is composed of a plurality of V-shaped parts, the corners of the V-shaped parts are arc-shaped, and the thickness of the corners is 5 to 10 μm thicker than that of other parts of the V-shaped parts; The polymer coating comprises a first coating, a second coating and a third coating which are stacked in sequence, wherein the first coating is coated on the surface of the stent body.

2. The coronary rapamycin targeted eluting stent according to claim 1, characterized in that: The support body is made of nickel-titanium alloy material, wherein the nickel content of the nickel-titanium alloy is 51.5-54.5%, and the titanium content is 45.5-48.5%.

3. The coronary rapamycin targeted eluting stent according to claim 1, characterized in that: The spraying solution for the first coating layer consists of 1 to 10 parts of L-polylactic acid and 90 to 99 parts of hexafluoroisopropanol in terms of mass fractions.

4. The coronary rapamycin targeted eluting stent according to claim 1, characterized in that: The spray solution for the second coating layer consists of 2 to 5 parts of L-polylactic acid, 0.5 to 1.5 parts of rapamycin and 93.5 to 97.5 parts of hexafluoroisopropanol in parts by mass.

5. The coronary rapamycin targeted eluting stent according to claim 1, characterized in that: The spray solution for the third coating layer is composed of 5 to 15 parts of polyvinyl pyrrolidone and 85 to 95 parts of hexafluoroisopropanol in terms of mass fractions.

6. A method for preparing a coronary rapamycin targeted eluting stent according to any one of claims 1 to 5, characterized in that: The following steps are involved: Preparation of the stent body: using laser cutting technology to accurately cut out a predetermined pattern from a tube to obtain a preformed part, and pickling and polishing the preformed part to obtain the stent body; Spraying the polymer coating: using ultrasonic spraying technology to spray the first coating, the second coating and the third coating on the surface of the stent body in sequence, and then irradiating and sterilizing to obtain a finished product.

7. The method for preparing the coronary rapamycin targeted eluting stent according to claim 6, characterized in that: The specific steps of pickling and polishing the preform include: Removing burrs from the surface of the preform by mechanical grinding; Pickling: preparing a mixed acid solution, mixing 5-9wt% hydrofluoric acid, 8-12wt% nitric acid and 79-87wt% water; first treating the surface of the preform with a 1-2mol / LNaOH solution at 80-90°C for 10-20min, then ultrasonically cleaning the preform with acetone, anhydrous ethanol and deionized water in sequence, each time for 5-10min; then drying the surface of the preform with nitrogen; finally immersing the preform in the mixed acid solution, standing at 25-37°C for 6-12h, taking it out and cleaning it with deionized water, and drying it; Electropolishing: A mixture of 3-7wt% perchloric acid, 5-15wt% glacial acetic acid and 88-92wt% ethylene glycol is used as an electrolyte to electropolish the preform after pickling. The electrolyte temperature is controlled at 60-70°C and the current density is controlled at 10-25A / dm 2 , the polishing time is controlled at 5 to 8 minutes to obtain the stent body with an outer surface roughness of 5 to 10 nanometers.

8. The method for preparing the coronary rapamycin targeted eluting stent according to claim 7, characterized in that: The mixed acid solution is obtained by mixing 7 wt % of hydrofluoric acid, 10 wt % of nitric acid and 83 wt % of water.

9. The method for preparing the coronary rapamycin targeted eluting stent according to claim 7, characterized in that: The electrolyte is obtained by mixing 5wt% perchloric acid, 10wt% glacial acetic acid and 90wt% ethylene glycol.

10. The method for preparing the coronary rapamycin targeted eluting stent according to claim 7, characterized in that: The spraying step specifically includes: Turn on the power of the sprayer, the ultrasonic power supply and the constant current pump. After the nitrogen meter on the sprayer is stable, discharge the solvent pre-installed on the constant current pump, fill it with the spray solution for the first coating, click the fast forward button on the constant current pump, so that the spray solution for the first coating fills the entire channel and can drip from the nozzle; set the flow rate of the constant current pump to 0.06-0.1 ml / min, the nitrogen pressure of the sprayer to 1.7-2.1 Psi, the operating power of the sprayer to 3.0-5.0 W, and the moving speed of the spray head of the sprayer to 0.1-0.15 cm / s; aim the nozzle at the bracket body to complete the first spraying; then fill it with the spray solution for the second coating and repeat the above operation to complete the second spraying of the bracket body; finally fill it with the spray solution for the third coating and repeat the above operation to complete the third spraying of the bracket body.

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