An absorbable covered stent for treating perforation during coronary intervention

Abstract

The invention discloses an absorbable coated stent for treating perforation during coronary intervention, belonging to the field of medical equipment; the absorbable coated stent comprises: a tubular improved coating and an elastic metal stent wound around the outside of the improved coating; the improved coating is prepared by mixing PLA and polycaprolactone PCL in a mass ratio of 1:1, dissolving in an organic solvent, and then preparing a tubular coating, and then coating the surface of the coating with anti-proliferation drugs, anti-inflammatory drugs, antiplatelet drugs, endothelial repair promoting drugs, antioxidants, anti-fibrosis drugs and antibacterial drugs, and then drying; the elastic metal stent adopts magnesium-titanium alloy, forms a mesh structure stent by laser cutting, and then is polished and passivated before being wound and fixed on the coating surface; by selecting a degradable polylactic acid and polycaprolactone composite material with good biocompatibility as the coating material, it is ensured that the stent can be gradually absorbed after completing the therapeutic function, and does not cause long-term mechanical stimulation and inflammatory response.

Description

Technical Field

[0001] The present invention belongs to the field of medical equipment, and in particular relates to an absorbable covered stent for treating coronary intervention perforation. Background Art

[0002] The covered stent method mainly delivers the covered stent in a compressed state to the location of the vascular lesion, and releases it after accurate positioning. The expanded covered stent will cover the diseased blood vessel, rely on the covering film on it to isolate the vascular lesion and form a new blood flow channel, thereby achieving the purpose of treatment. Since the covered stent needs to be implanted inside the blood vessel to play the role of a vascular channel, the covering of the covered stent needs to meet good biocompatibility, certain expansion plasticity and mechanical durability;

[0003] Currently, the materials of covered stents are mostly polytetrafluoroethylene (PTFE) or polyethylene terephthalate (PET). Their non-absorbable properties will cause them to exist in blood vessels for a long time, causing intimal hyperplasia and thrombosis risks, affecting long-term patency. Therefore, an absorbable covered stent is proposed to treat coronary intervention perforation. Summary of the invention

[0004] In view of the deficiencies in the prior art, the purpose of the present invention is to provide an absorbable covered stent for treating coronary intervention perforation, thereby solving the problems in the prior art.

[0005] The purpose of the present invention can be achieved through the following technical solutions:

[0006] An absorbable covered stent for treating perforation during coronary intervention, comprising a tubular improved covered membrane and an elastic metal stent wound around the outside of the improved covered membrane;

[0007] The improved coating is prepared by mixing PLA and polycaprolactone PCL in a mass ratio of 1:1, dissolving the mixture in an organic solvent, and then preparing a tubular coating. Anti-proliferation drugs, anti-inflammatory drugs, anti-platelet drugs, endothelial repair promoting drugs, antioxidants, anti-fibrosis drugs and antibacterial drugs are then coated on the surface of the coating, and finally drying the coating to obtain the improved coating.

[0008] The elastic metal bracket adopts magnesium-titanium alloy, is cut into a mesh structure bracket by laser, and then is polished and passivated, and then wound and fixed on the improved coating surface.

[0009] Furthermore, the organic solvent is: dichloromethane, ethyl acetate, ethanol, tetrahydrofuran, acetone or dichloroethane.

[0010] Furthermore, the anti-proliferative drug is one or more of rapamycin and paclitaxel; the anti-inflammatory drug is dexamethasone; the anti-platelet drug is clopidogrel; the endothelial repair promoting drug is VEGF or FGF; the antioxidant is vitamin E; the anti-fibrosis drug is imatinib; and the antibacterial drug is vancomycin.

[0011] Furthermore, the mass percentage of magnesium in the magnesium-titanium alloy is 3%.

[0012] Furthermore, the mass ratio of the anti-proliferative drug, anti-inflammatory drug, antiplatelet drug, endothelial repair promoting drug, antioxidant, anti-fibrosis drug and antibacterial drug is 8:3:2:2:2:2:1.

[0013] The above-mentioned method for preparing an absorbable covered stent for treating coronary intervention perforation comprises the following steps:

[0014] S1, PLA and polycaprolactone PC are mixed and dissolved in an organic solvent, and the mixture is stirred to obtain a polymer solution; the polymer solution is coated on the surface of a cylindrical mold; anti-proliferative drugs, anti-inflammatory drugs, anti-platelet drugs, endothelial repair promoting drugs, antioxidants, anti-fibrosis drugs and antibacterial drugs are added to the organic solvent to dissolve to obtain a drug solution, which is then coated on the surface of the film, and then dried and vacuum dried before demolding;

[0015] S2, using laser to cut magnesium-titanium alloy to form a hexagonal grid stent, and then electrochemically polishing and passivating the stent surface;

[0016] S3, heating the film to soften the surface of the film, and automatically winding the device, the elastic metal bracket is evenly wound and fixed on the outside of the film, and finally the assembled stent is heat treated.

[0017] Furthermore, in S1, the concentration of the polymer solution is 20% w / v, and the viscosity is 400 mPa·s; when coating the polymer solution, the rotation speed of the cylindrical mold is 100 rpm, and the coating is performed 3 times; the concentration of the configured drug solution is 0.5 mg / mL; the drying temperature is 40°C, and the time is 25 min; the vacuum drying temperature is 30°C, the drying time is 5 h, and the vacuum degree is -0.08 MPa.

[0018] Furthermore, in S2, the opening rate of the stent is 70%, and the opening size is 150 microns; wherein, the laser cutting adopts a YAG laser with a power of 1.5w, a pulse frequency of 30kHz, and a cutting speed of 30mm / s.

[0019] Furthermore, in S3, the heating temperature of the coating is 55°C, the heating time is 4 minutes, the tension range of the automatic winding equipment is controlled to be 10-15N, the winding speed is 12cm / min, and the number of winding layers is 2.

[0020] Furthermore, in S3, the heat treatment temperature is 60° C. and the heat treatment time is 8 min.

[0021] Beneficial effects of the present invention:

[0022] 1. The present invention selects a degradable polymer material (polylactic acid and polycaprolactone composite material) with good biocompatibility as the coating material to ensure that the stent can be gradually absorbed after completing its therapeutic function without causing long-term mechanical stimulation and inflammatory response.

[0023] 2. The present invention achieves the following effects by coating anti-proliferative drugs, anti-inflammatory drugs, antiplatelet drugs, endothelial repair-promoting drugs, antioxidants, anti-fibrosis drugs and antibacterial drugs on the surface of the coating: inhibiting vascular intimal hyperplasia, reducing local inflammatory response, preventing the risk of thrombosis caused by excessive aggregation of platelets on the surface of the stent, promoting the rapid repair of damaged vascular endothelial cells, reducing the inflammatory response caused by oxidative stress, reducing the fibrosis that may occur after stent implantation, and preventing postoperative infection.

[0024] 3. When preparing the metal stent, the surface of the stent is electrochemically polished to remove burrs and improve the surface smoothness of the metal stent, thereby reducing stimulation to the blood vessel wall. The surface of the stent is passivated to slow down the degradation rate of the magnesium-titanium alloy and prevent the degradation process from being too fast.

[0025] 4. When preparing the coated stent, the present invention wraps the elastic metal stent around the coating and fixes it. Then, the heat treatment temperature and time of the metal stent are reasonably controlled to improve the bonding strength between the coating and the metal stent while avoiding failure of the drug layer due to excessive temperature. DETAILED DESCRIPTION

[0026] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solution of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] Example 1

[0028] An absorbable covered stent for treating perforation during coronary intervention, comprising a tubular improved covered membrane and an elastic metal stent wrapped around the outside of the covered membrane;

[0029] The improved coating is prepared by mixing polylactic acid (PLA) and polycaprolactone (PCL) in a mass ratio of 1:1, dissolving the mixture in an organic solvent, and then forming a film to obtain a tubular coating. Then, anti-proliferation drugs, anti-inflammatory drugs, anti-platelet drugs, endothelial repair promoting drugs, antioxidants, anti-fibrosis drugs and antibacterial drugs are coated on the surface of the coating, and then the drugs are solidified by drying to obtain the improved coating.

[0030] The mass ratio of anti-proliferative drugs, anti-inflammatory drugs, antiplatelet drugs, endothelial repair promoting drugs, antioxidants, anti-fibrotic drugs and antibacterial drugs is 8:3:2:2:2:2:1.

[0031] The elastic metal stent is made of magnesium-titanium alloy (Ti accounts for 3% wt), and is formed into a mesh structure stent by laser cutting, and then is polished and passivated, and then wound and fixed on the improved coating surface.

[0032] The organic solvent is: dichloromethane, ethyl acetate, ethanol, tetrahydrofuran, acetone or dichloroethane.

[0033] Wherein, the anti-proliferative drug is one or more of rapamycin and paclitaxel, which can inhibit the proliferation of vascular intimal membrane.

[0034] The anti-inflammatory drug is dexamethasone, which can effectively reduce local inflammatory response, reduce immune response and local inflammatory cell infiltration that may be caused after stent implantation, thereby further reducing the risk of vascular restenosis.

[0035] The antiplatelet drug is clopidogrel, which can prevent excessive aggregation of platelets on the surface of the stent and reduce the risk of thrombosis. Through the sustained-release system, this type of drug can be gradually released in the early stage after the implantation of the covered stent to help prevent acute stent thrombosis.

[0036] The endothelial repair-promoting drug uses vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF), which can promote the rapid repair of damaged vascular endothelial cells, thereby shortening the time for the endothelium to cover the stent, improving vascular function and reducing the risk of thrombosis.

[0037] The antioxidant is vitamin E, which can neutralize free radicals in blood vessels, reduce inflammatory reactions caused by oxidative stress, and protect the vascular endothelium, reducing inflammatory reactions and tissue damage after implantation.

[0038] The anti-fibrosis drug uses imatinib, which is used to inhibit the excessive proliferation and fibrosis reaction of vascular smooth muscle cells, and can reduce the fibrosis that may occur after stent implantation, and further reduce the restenosis rate.

[0039] The antibacterial drug is vancomycin, which can effectively prevent postoperative infection, especially in patients with a higher risk of infection.

[0040] Example 2

[0041] In this embodiment, a method for preparing an absorbable covered stent for treating coronary intervention perforation is provided, comprising the following steps:

[0042] S1, preparation of improved coating;

[0043] 1) PLA and polycaprolactone PCL were mixed in a mass ratio of 1:1, dissolved in an organic solvent (dichloromethane) using a magnetic stirrer, and stirred evenly to obtain a polymer solution with a concentration of 20% w / v and a viscosity of 400 mPa·s; wherein the speed of the magnetic stirrer was 500 rpm, the stirring time was 1 hour, and the dissolution temperature was 20°C.

[0044] 2) The polymer solution is uniformly coated on the surface of the cylindrical mold by spraying to form a uniform film; wherein, during spraying, the rotation speed of the cylindrical mold is 100 rpm, the coating is performed 3 times, and the film thickness reaches 80 microns.

[0045] 3) Rapamycin, dexamethasone, clopidogrel, VEGF, vitamin E, imatinib and vancomycin were added to an organic solvent (dichloromethane) in a mass ratio of 8:3:2:2:2:2:1 to obtain a drug solution with a concentration of 0.5 mg / mL, which was then evenly coated on the surface of the film by electrostatic spraying and dried at 40°C for 25 min to allow the drug layer to be evenly attached and the solvent to be completely volatilized; the electrostatic spraying method used an electrostatic sprayer with a spraying voltage of 8 KV and a spraying distance of 15 cm.

[0046] 4) Drying the film in a vacuum drying oven, and then demolding from the mold to obtain a tubular film with a drug coating; wherein the drying temperature is 30° C., the drying time is 5 hours, and the vacuum degree is -0.08 Mpa.

[0047] S2, preparation of elastic metal stent;

[0048] 1) Magnesium-titanium alloy (Ti accounts for 3% wt) is selected and laser cut to form a hexagonal grid stent to ensure the elasticity and expandability of the stent. The opening rate of the stent is 70%, and the opening size is 150 microns, which is consistent with the anatomical characteristics of the blood vessels. Among them, the laser cutting uses a high-precision fiber laser (YAG laser) with a power of 1.5w, a pulse frequency of 30kHz, and a cutting speed of 30mm / s. This ensures that the stent material will not be deformed by heat during the cutting process, ensuring accurate cutting.

[0049] 2) electrochemical polishing and passivation treatment of the stent surface;

[0050] The voltage of the electrochemical polishing treatment is 20V, the polishing time is 10min, and the electrolyte is a phosphate buffer solution with a concentration of 8%.

[0051] The treatment solution for the passivation treatment is: a passivation solution containing calcium phosphate with a concentration of 3%. The immersion time is 20 minutes. A passivation film is formed on the surface of the stent to slow down the degradation rate and prevent the rapid dissolution of magnesium ions.

[0052] S3, combination of coated and flexible metal stent

[0053] 1) Heating the film softens the surface of the film and enhances its adhesion to the elastic metal bracket;

[0054] In this embodiment, the heating temperature of the coating is 55°C and the heating time is 4 minutes, which can effectively soften the surface without excessively degrading the material; the heating method adopts a hot air circulation oven to ensure that the temperature is uniform and reaches the target value quickly and stably.

[0055] 2) Using automatic winding equipment, the elastic metal stent is evenly wound and fixed on the outside of the film;

[0056] In this embodiment, the tension range of the automatic winding equipment is controlled between 10-15N to avoid deformation of the stent due to excessive tension, and a tension sensor is used for real-time monitoring to ensure the consistency of each winding; the winding speed is 12cm / min to ensure uniform winding and avoid position errors caused by too fast a speed; the number of winding layers is 2 to ensure close adhesion of the film and structural stability of the stent. The winding direction is right-handed, starting from one end of the stent and gradually moving to the other end to ensure uniform force on the stent.

[0057] performing heat treatment on the assembled stent graft;

[0058] During heat treatment, short-term heat treatment is required at an appropriate temperature to improve the bonding strength between the coating and the metal stent, but excessively high temperature should be avoided to cause the drug layer to fail. In this embodiment, the heat treatment temperature is 60°C. After experimental verification, this temperature can not only make the coating material better bond with the metal stent, but also will not be too high to cause dissolution and failure of the drug layer. The heat treatment time is 8 minutes. The heating method is to use a constant temperature oven for heating. Finally, it is naturally cooled to room temperature to ensure a firm bond between the coating and the metal stent.

[0059] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0060] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of the present invention to be protected.

Claims

1. An absorbable covered stent for treating perforation during coronary intervention, characterized in that: The invention comprises a tubular improved covering and an elastic metal bracket wrapped around the outer side of the improved covering; The improved coating is prepared by mixing PLA and polycaprolactone PCL in a mass ratio of 1:1, dissolving the mixture in an organic solvent, and then preparing a tubular coating. Anti-proliferation drugs, anti-inflammatory drugs, anti-platelet drugs, endothelial repair promoting drugs, antioxidants, anti-fibrosis drugs and antibacterial drugs are then coated on the surface of the coating, and finally drying the coating to obtain the improved coating. The elastic metal bracket adopts magnesium-titanium alloy, is cut into a mesh structure bracket by laser, and then is polished and passivated, and then wound and fixed on the improved coating surface.

2. The absorbable covered stent for treating perforation during coronary intervention according to claim 1, characterized in that: The organic solvent is: dichloromethane, ethyl acetate, ethanol, tetrahydrofuran, acetone or dichloroethane.

3. The absorbable covered stent for treating perforation during coronary intervention according to claim 1, characterized in that: The anti-proliferative drug is one or more of rapamycin and paclitaxel; the anti-inflammatory drug is dexamethasone; the anti-platelet drug is clopidogrel; the endothelial repair promoting drug is VEGF or FGF; the antioxidant is vitamin E; the anti-fibrosis drug is imatinib; and the antibacterial drug is vancomycin.

4. The absorbable covered stent for treating perforation during coronary intervention according to claim 1, characterized in that: The mass percentage of magnesium in the magnesium-titanium alloy is 3%.

5. The absorbable covered stent for treating perforation during coronary intervention according to claim 1 or 3, characterized in that: The mass ratio of the anti-proliferative drug, anti-inflammatory drug, anti-platelet drug, endothelial repair promoting drug, antioxidant, anti-fibrosis drug and antibacterial drug is 8:3:2:2:2:2:

1.

6. A method for preparing an absorbable covered stent for treating coronary intervention perforation according to any one of claims 1 to 5, characterized in that: The following steps are involved: S1, PLA and polycaprolactone PC are mixed and dissolved in an organic solvent, and the mixture is stirred to obtain a polymer solution; the polymer solution is coated on the surface of a cylindrical mold; anti-proliferative drugs, anti-inflammatory drugs, anti-platelet drugs, endothelial repair promoting drugs, antioxidants, anti-fibrosis drugs and antibacterial drugs are added to the organic solvent to dissolve to obtain a drug solution, which is then coated on the surface of the film, and then dried and vacuum dried before demolding; S2, using laser to cut magnesium-titanium alloy to form a hexagonal grid stent, and then electrochemically polishing and passivating the stent surface; S3, heating the film to soften the surface of the film, and automatically winding the device, the elastic metal bracket is evenly wound and fixed on the outside of the film, and finally the assembled stent is heat treated.

7. The method for preparing an absorbable covered stent for treating perforation during coronary intervention according to claim 6, characterized in that: In S1, the concentration of the polymer solution is 20% w / v and the viscosity is 400 mPa·s; when coating the polymer solution, the rotation speed of the cylindrical mold is 100 rpm and the coating is performed 3 times; the concentration of the configured drug solution is 0.5 mg / mL; the drying temperature is 40°C and the time is 25 min; the vacuum drying temperature is 30°C, the drying time is 5 h, and the vacuum degree is -0.08 MPa.

8. The method for preparing an absorbable covered stent for treating perforation during coronary intervention according to claim 6, characterized in that: In S2, the opening rate of the bracket is 70%, and the opening size is 150 microns; the laser used for laser cutting is YAG laser, the power is 1.5w, the pulse frequency is 30kHz, and the cutting speed is 30mm / s.

9. The method for preparing an absorbable covered stent for treating perforation during coronary intervention according to claim 6, characterized in that: In S3, the heating temperature of the coating is 55°C, the heating time is 4 minutes, the tension range of the automatic winding equipment is controlled to be 10-15N, the winding speed is 12cm / min, and the number of winding layers is 2.

10. The method for preparing an absorbable covered stent for treating perforation during coronary intervention according to claim 6, characterized in that: In S3, the heat treatment temperature is 60°C and the heat treatment time is 8 minutes.