Degradable plugging device with drug sustained release function and preparation method and application thereof

Abstract

The invention belongs to the field of medical apparatus and instruments, and provides a degradable plugging device with a drug sustained release function and a preparation method and application of the degradable plugging device. The preparation method of the plugging device comprises the steps that magnesium alloy wires coated with the degradable polymer coating are woven into the plugging device support body, after vacuum heat preservation and shaping are conducted, surface film covering is conducted through an electrostatic spinning solution, the electrostatic spinning solution is sprayed to the center film layer, the center film layer is placed in the center of the plugging device support body, and the center flow blocking film is obtained; and the central flow choking film layer and the plugging device bracket main body are connected and fixed through a local dissolution-re-solidification method. The electrostatic spinning solution is prepared by dissolving a degradable polymer in an organic solvent, adding silicon dioxide nanoparticles loaded with a sustained-release drug into the solution, magnetically stirring and fully dispersing. The plugging device can be used for repairing clinical congenital heart diseases, and local functional treatment is achieved while a secondary operation is avoided.

Description

Technical Field

[0001] The invention discloses a degradable occluder with a drug sustained-release function and a preparation method and application thereof, belonging to the technical field of medical devices. Background Art

[0002] An occluder is a repair device used to treat congenital heart disease. Currently, most occluders are made of bioinert metals, such as nickel-titanium alloy wires and titanium alloy wires. Although these wires have good mechanical properties, they cannot be degraded in the body and will remain in the human body permanently or require surgery to remove them, which has some adverse effects on the patient's postoperative life. In recent years, degradable magnesium metal has gradually shown good potential in the application field of medical devices, and several magnesium alloy medical devices have obtained clinical use permits. The development of magnesium alloy preparation technology has also made mass production of high-strength and toughness ultrafine magnesium alloys possible. Therefore, the use of magnesium alloys instead of bioinert metals to prepare occluders not only retains the performance advantages of metals, but also perfectly avoids the potential risks brought about by the permanent retention of devices.

[0003] For a long time, patent atrial septal defect, ventricular septal defect, ductus arteriosus, tetralogy of Fallot, transposition of the great arteries and other congenital heart diseases have caused many troubles for patients and clinicians. In the existing technology, non-degradable occluders do not have ideal therapeutic effects because they cannot achieve targeted treatment of local lesions. With the introduction of the concept of drug delivery and personalized customization of devices in the past decade, the use of degradable materials to achieve sustained release of drugs in the local environment while completing the function of assisting tissue repair has become an effective means to deal with difficult-to-heal tissues, which makes specific treatment of these diseases possible. Summary of the invention

[0004] The purpose of the present invention is to provide a degradable occluder with drug sustained release function and its preparation method and application, which aims to treat congenital heart disease while avoiding secondary surgery to remove the device or permanent retention, and can also achieve targeted treatment of local lesions by carrying different drugs. It has great application prospects in the treatment of congenital heart disease.

[0005] The technical solution provided by the present invention is as follows:

[0006] A method for preparing an electrospinning solution for a degradable occluder coating comprises the following steps: dissolving a degradable polymer in an organic solvent, adding silica nanospheres loaded with sustained-release drugs into the solution, and fully dispersing the solution after magnetic stirring to obtain a degradable occluder coating with a drug sustained-release function; the degradable polymer comprises one or more of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, polydioxane, and polydioxanone.

[0007] Furthermore, the sustained-release drug includes one or more of lidocaine, ibuprofen, diclofenac, dexamethasone, curcumin, resveratrol, and gentamicin; the sustained-release period of the sustained-release drug is 1 to 21 days; the organic solvent is dichloromethane.

[0008] Furthermore, the concentration of the silica nanospheres loaded with the sustained-release drug in the electrospinning solution is 0.1 to 30 mg / mL, and the average diameter of the silica nanospheres loaded with the sustained-release drug is 20 to 800 nm.

[0009] Furthermore, the preparation method of the silica nanospheres loaded with the sustained-release drug includes: slowly dropping tetraethyl orthosilicate into an ethanol / water mixed solvent, adding an alkali or acid catalyst, and then adding the sustained-release drug, and stirring at 25 - 40 °C for 2 - 4 h; the volume ratio of tetraethyl orthosilicate, ethanol, water, and the catalyst is 1:5 - 8:1 - 4:2 - 4; after hydrolysis, a sol is formed, and the silica nanospheres loaded with the sustained-release drug are obtained through aging and drying.

[0010] The present invention also provides an electrospinning solution for a degradable occluder coating, which is prepared by the above preparation method.

[0011] The present invention also provides a preparation method of a degradable occluder with a drug sustained-release function, including the following steps: weaving a pretreated magnesium alloy wire into the main body of the occluder stent, after vacuum heat preservation and shaping, using the above electrospinning solution for surface coating, spraying the electrospinning solution at the center of the occluder stent main body to obtain a central flow-blocking membrane, and connecting and fixing the central flow-blocking membrane and the occluder stent main body by a local dissolution-re-solidification method; the pretreatment step includes: uniformly coating a degradable polymer coating on the surface of the magnesium alloy wire.

[0012] Furthermore, the diameter of the magnesium alloy wire is 50 μm - 500 μm, the coating thickness of the degradable polymer is 1 - 50 μm, and the coating thickness of the electrospinning solution is 20 - 500 μm.

[0013] Furthermore, after connecting and fixing the central flow-blocking membrane and the occluder stent main body, it is dried at 40 - 50 °C for 6 - 48 h.

[0014] Furthermore, the dissolution-re-solidification method is to apply an organic solvent to the connection part, and after drying at room temperature, the two are connected as a whole.

[0015] The present invention also provides a degradable occluder with a drug sustained-release function, which is prepared by the above preparation method.

[0016] A degradable occluder with drug sustained-release function, comprising: an occluder stent and a flow-blocking membrane, wherein the occluder stent is a magnesium alloy braided stent, and the flow-blocking membrane is an electrostatic spinning membrane layer capable of sustained-release of drugs; a preparation method thereof comprises the following steps:

[0017] 1) Pre-treating the magnesium alloy wire, the pre-treating step comprising: uniformly coating the surface of the magnesium alloy wire with a degradable polymer coating, wherein the coated magnesium alloy wire has a diameter of 50 μm-500 μm and a thickness of 1 μm-50 μm. Subsequently, the coated magnesium alloy wire is woven into the main body of the occluder stent, and the occluder stent is formed at 40 o C-70 o C, vacuum heat preservation and shaping for 12h-48h; the preparation method of the degradable polymer coating comprises: dissolving the degradable polymer in an organic solvent, wherein the organic solvent is dichloromethane, and the mass volume ratio of the degradable polymer to the organic solvent is 0.1-0.2 g / mL, to obtain a degradable polymer solution;

[0018] 2) preparing an electrospinning solution, adding silica nanoparticles loaded with sustained-release drugs to the degradable polymer solution prepared in step 1), stirring the solution by magnetic force at 50 rpm to 1500 rpm for 6 h to 24 h, and then fully dispersing the solution for use;

[0019] The method for preparing silica nanoparticles loaded with sustained-release drugs comprises: slowly dropping tetraethyl silicate (TEOS) into an ethanol / water mixed solvent, adding an alkali or acid catalyst, wherein the alkali catalyst is 25% NH3·H2O and the acid catalyst is 0.1 M HCl; then adding the sustained-release drug, and stirring at 25-40°C for 2-4 hours. The volume ratio of TEOS, ethanol, water and catalyst is 1:5-8:1-4:2-4, wherein 1-5 mg / mL of sustained-release drugs such as lidocaine are added; after hydrolysis, a sol is formed, and silica nanoparticles loaded with sustained-release drugs are obtained by aging and drying; the hydrolysis is that TEOS reacts with water when stirred in an aqueous solution to form a sol; the aging step comprises: transferring the sol to a sealed glass bottle, aging at 25°C-40°C for 36-48 hours, and gently shaking the bottle every hour; after aging, washing with ethanol 3 times to remove free drugs; the drying is vacuum drying at 40°C for 12 hours.

[0020] 3) The outer side of the stent formed in step (1) is coated with the electrospinning solution in step (2), wherein the thickness of the outer electrospinning membrane layer is 20-500 μm.

[0021] 4) Spray the electrospinning solution onto a film with a thickness of 200 - 1000 μm, and cut the film into the shape of the central blocking film; connect and fix the outer film layer of the central blocking film and the electrospinning solution film layer on the surface of the magnesium alloy wire by the local dissolution - re - solidification method.

[0022] 5) Dry the plug in step (4) at 40 o °C - 50 o °C for 6 h - 48 h.

[0023] The magnesium alloy wire is finally obtained by melting and casting the magnesium alloy material into an ingot, followed by homogenization heat treatment, extrusion, cold drawing, and heat treatment.

[0024] The magnesium alloy is one of magnesium - aluminum alloy, magnesium - manganese alloy, magnesium - zinc alloy, magnesium - zirconium alloy, magnesium - rare earth alloy, magnesium - alkaline earth alloy, magnesium - lithium alloy, magnesium - calcium alloy, or magnesium - silver alloy, or a multi - component magnesium alloy composed of combinations of these systems.

[0025] The present invention also provides the application of the above - mentioned plug in the preparation of medical devices for congenital heart diseases.

[0026] Drug release is achieved through novel nano - silica microspheres, realizing specific treatment of local lesions. At the same time, customized requirements for different affected areas can be achieved by controlling the nano - microsphere size, drug type, and release time.

[0027] Changing the nano - microsphere size is based on the Einstein diffusion equation:

[0028]

[0029]

[0030] t diff refers to the diffusion time, x 2 refers to the mean square displacement of diffusion, D refers to the diffusion coefficient; T refers to the temperature, refers to the viscosity, K B refers to the Boltzmann constant, r refers to the particle radius;

[0031] The larger the microsphere, the longer the diffusion time; the higher the temperature or the lower the viscosity, the shorter the diffusion time.

[0032] Match the human tissue healing rate through different drug release times and degradation rates.

[0033] Beneficial effects

[0034] The present invention relates to a degradable plug with a drug - sustained release function, its preparation method and application. By combining the magnesium alloy wire braiding technology and the electrospinning technology, in - vivo degradation of the plug is achieved.

[0035] The occluder of the present invention uses a method of covering two layers of membranes inside and outside to perform polymer film coating on the surface pretreatment of the wire material, and then covering an electrospun membrane layer on the outside, which makes up for the toughness defect of the metal matrix itself. By combining the connection method of polymer dissolution-re-solidification, the outer membrane layer is connected and fixed to the wire pretreatment membrane layer, enhancing the tight combination of the flow-blocking layer and the stent body.

[0036] The degradable occluder with drug slow-release function of the present invention solves the problem that existing occluders need a second operation to be removed after completing the task during the implantation process. Traditional occluders (such as nickel-titanium alloys) need to be permanently implanted in the body, which may cause long-term inflammation, thrombosis or tissue irritation risks. However, the present invention uses a degradable material, magnesium alloy, which gradually degrades after completing the occlusion function and is finally metabolized and absorbed by the human body, reducing long-term complications. This further reduces the harm of the cardiac occluder to the human body. At the same time, a slow-release drug coating is evenly attached to the outside of the cardiac occluder, reducing vascular damage to patients and promoting rapid wound healing of patients, achieving the purpose of treating diseases.

[0037] The degradable occluder with drug slow-release function of the present invention solves the problem that the existing stent content is relatively single and often lacks the function of sterilization, and it is easy to occur intraoperative infection and postoperative infection during the operation, affecting the use. The electrospinning-microsphere preparation method adopted by the present invention loads drugs such as antibacterial and anti-inflammatory drugs into silica porous microspheres, and then dissolves the microspheres in the electrospinning solution. The synergistic effect can solve the infection problem during the operation and improve the effect of human tissue repair. Both the magnesium matrix and the drug slow-release coating can contact human tissues and cells, which helps magnesium metal and the coating to regulate cell behavior, promote human wound healing and tissue regeneration, making the electrospinning coating have a certain sterilization function.

[0038] The degradable occluder with drug slow-release function of the present invention realizes that the degradation process of the existing cardiac occluder can be synchronized with tissue regeneration, provides a scaffold for autologous tissue growth, and realizes "dynamic healing". By regulating the degradation time through material ratio, it matches the healing cycles of different individuals. The drug release scheme is flexible, and the drug type, dose and release curve can be designed according to clinical needs. Description of the Drawings

[0039] Figure 1 It is a side view of the occluder stent;

[0040] Figure 2 It is a front view of the occluder stent;

[0041] Figure 3 It is a cross-sectional view of the occluder stent;

[0042] Figure 4 It is a test chart of the antibacterial performance of Examples 1-5 and Comparative Examples 1 and 2.

[0043] Reference numerals: 1, occluder stent; 2, central flow-blocking membrane; 3, silicon dioxide nanospheres; 4, magnesium alloy wire; 5, degradable polymer. Detailed implementation mode

[0044] The present invention provides a degradable occluder with a drug sustained-release function, its preparation method and application, which can be applied to the treatment of congenital heart diseases in the human body. The present invention will be further described below.

[0045] Example 1

[0046] In this embodiment, the preparation method of the occluder: for the atrial septal defect in congenital heart diseases, a degradable occluder with a drug sustained-release function is prepared. A magnesium-zinc alloy wire with a diameter of 50 μm and a uniform polylactic acid coating of 1 μm is woven into the main body of the occluder stent 1, and vacuum heat-treated and shaped at 70 o °C for 12 h. The preparation method of the polylactic acid coating includes: dissolving polylactic acid in an organic solvent, the organic solvent is dichloromethane, and the mass-volume ratio of polylactic acid to the organic solvent is 0.1 g / mL to obtain a polylactic acid solution.

[0047] Prepare a polylactic acid electrospinning solution: add silicon dioxide nanospheres 3 loaded with ibuprofen sustained-release drugs at a concentration of 30 mg / mL to the polylactic acid solution prepared in the above step. The diameter of the silicon dioxide nanospheres 3 is 200 nm, and the drug release period is 21 days. After being sufficiently dispersed by magnetic stirring at 50 revolutions per minute for 6 h, it is reserved for use. The preparation method of the silicon dioxide nanospheres loaded with ibuprofen sustained-release drugs includes: slowly dripping tetraethyl orthosilicate (TEOS) into an ethanol / water mixed solvent, adding 25% NH3·H2O, and then adding the sustained-release drug, and stirring at 25 °C for 3 h. The volume ratio of TEOS, ethanol, water and the catalyst is 1:5:1:2, and 5 mg / mL ibuprofen sustained-release drug is added; after hydrolysis, a sol is formed, and the sol is aged and dried to obtain silicon dioxide nanospheres loaded with the sustained-release drug; the hydrolysis is that TEOS reacts with water when stirring in an aqueous solution to form a sol; the aging step includes: transferring the sol to a sealed glass bottle, standing and aging at 25 °C for 36 hours, and gently shaking the bottle body every hour; after aging, washing with ethanol 3 times to remove free drugs; the drying is vacuum drying at 40 °C for 12 h.

[0048] Electrospin a 20-μm-thick film on the outer surface of the stent. Subsequently, continue to prepare a central flow-blocking membrane 2 with a thickness of 200 μm by electrospinning, place the central flow-blocking membrane 2 at the center of the stent, and connect and fix the outer membrane layer of the central flow-blocking membrane and the electrospinning solution film layer on the surface of the magnesium alloy wire 4 through a local dissolution-recoagulation method. Finally, dry the occluder at 50 o °C for 48 h.

[0049] Example 2

[0050] Preparation method of the occluder in this example: For ventricular septal defect in congenital heart disease, a degradable occluder with drug sustained-release function was prepared. A magnesium-calcium alloy wire with a diameter of 100 μm and a uniform poly(lactic-co-glycolic acid) copolymer coating of 20 μm was woven into the main body of the occluder stent 1, and vacuum heat-set at 40 o °C for 48 h. The preparation method of the poly(lactic-co-glycolic acid) copolymer coating includes: dissolving the poly(lactic-co-glycolic acid) copolymer in an organic solvent, the organic solvent is dichloromethane, and the mass-volume ratio of the poly(lactic-co-glycolic acid) copolymer to the organic solvent is 0.1 g / mL to obtain a poly(lactic-co-glycolic acid) copolymer solution.

[0051] Prepare the poly(lactic-co-glycolic acid) copolymer electrospinning solution: Add silica nanospheres 3 loaded with lidocaine sustained-release drug at a concentration of 20 mg / mL to the poly(lactic-co-glycolic acid) copolymer solution prepared in the above step. The diameter of the silica nanospheres 3 is 500 nm, and the drug release period is 15 days. After being fully dispersed by magnetic stirring at 400 revolutions per minute for 24 h, it is reserved for use. The preparation method of the silica nanospheres loaded with lidocaine sustained-release drug includes: slowly dripping tetraethyl orthosilicate (TEOS) into an ethanol / water mixed solvent, adding 0.1 M HCl, and then adding the sustained-release drug, and stirring at 25 °C for 3 h. The volume ratio of TEOS, ethanol, water and the catalyst is 1:5:1:2, and 5 mg / mL lidocaine sustained-release drug is added; after hydrolysis, a sol is formed, and the silica nanospheres loaded with the sustained-release drug are obtained through aging and drying; the hydrolysis is that TEOS reacts with water to form a sol when stirred in an aqueous solution; the aging step includes: transferring the sol to a sealed glass bottle, standing and aging at 25 °C for 36 hours, and gently shaking the bottle body every hour; after aging, washing with ethanol 3 times to remove free drugs; the drying is vacuum drying at 40 °C for 12 h.

[0052] Electrospin a 500-μm-thick film on the outer surface of the stent. Subsequently, continue to prepare the central blocking membrane 2 with a thickness of 800 μm by electrospinning, place the central blocking membrane 2 at the center of the stent, and connect and fix the outer membrane layer of the central blocking membrane and the electrospun liquid film layer on the surface of the magnesium alloy wire 4 through a local dissolution-re-solidification method. Finally, dry the occluder at 40 o °C for 6 h.

[0053] Example 3

[0054] Preparation method of the occluder in this embodiment: For ventricular septal defect and patent ductus arteriosus in congenital heart disease, a degradable occluder with drug sustained-release function is prepared. A magnesium-manganese alloy wire with a 30-μm uniform polycaprolactone coating and a diameter of 300 μm is braided into the main body of the occluder stent 1, and vacuum heat preservation and shaping are carried out at 60 o °C for 24 h. The preparation method of the polycaprolactone coating includes: dissolving polycaprolactone in an organic solvent, the organic solvent is dichloromethane, and the mass-volume ratio of polycaprolactone to the organic solvent is 0.1 g / mL to obtain a polycaprolactone solution.

[0055] Prepare a polycaprolactone electrospinning solution: Add silicon dioxide nanoparticles 3 loaded with curcumin sustained-release drug at a concentration of 10 mg / mL to the polycaprolactone solution prepared in the above step. The diameter of the silicon dioxide nanoparticles 3 is 300 nm, and the drug release period is 1 day. After magnetic stirring at 1000 revolutions per minute for 6 h for sufficient dispersion, it is reserved for use. The preparation method of the silicon dioxide nanoparticles loaded with curcumin sustained-release drug includes: slowly dripping tetraethyl orthosilicate (TEOS) into an ethanol / water mixed solvent, adding 0.1 M HCl, and then adding the sustained-release drug, and stirring at 25°C for 3 h. The volume ratio of TEOS, ethanol, water and the catalyst is 1:5:1:2, and 5 mg / mL curcumin sustained-release drug is added therein; after hydrolysis, a sol is formed, and the silicon dioxide nanoparticles loaded with the sustained-release drug are obtained through aging and drying; the hydrolysis is that TEOS reacts with water when stirred in an aqueous solution to form a sol; the aging step includes: transferring the sol to a sealed glass bottle, standing and aging at 25°C for 36 hours, and gently shaking the bottle body every hour; after aging, washing with ethanol 3 times to remove free drugs; the drying is vacuum drying at 40°C for 12 h.

[0056] Electrospin a 400-μm-thick film on the outer surface of the stent. Subsequently, continue to prepare a central blocking membrane 2 with a thickness of 600 μm by electrospinning, place the central blocking membrane 2 at the center of the stent, and connect and fix the outer membrane layer of the central blocking membrane and the electrospun liquid film layer on the surface of the magnesium alloy wire 4 through a local dissolution-recoagulation method. Finally, dry the occluder at 46 o °C for 48 h.

[0057] Example 4

[0058] Preparation method of the occluder in this embodiment: For tetralogy of Fallot in congenital heart disease, a degradable occluder with drug sustained-release function is prepared. A magnesium-zirconium alloy wire with a 14-μm uniform polydioxanone coating and a diameter of 220 μm is braided into the main body of the occluder stent 1, and at 65 oVacuum heat preservation and shaping at 36 h under C. The preparation method of the polydioxanone coating includes: dissolving polydioxanone in an organic solvent, the organic solvent being dichloromethane, and the mass-volume ratio of polydioxanone to the organic solvent being 0.1 g / mL to obtain a polydioxanone solution.

[0059] Prepare a polydioxanone electrospinning solution: add silica nanospheres 3 loaded with gentamicin sustained-release drug at a concentration of 20 mg / mL to the polydioxanone solution prepared in the above step. The diameter of the silica nanospheres 3 is 70 nm, and the drug release period is 14 days. After being sufficiently dispersed by magnetic stirring at 1500 revolutions per minute for 16 h, it is reserved for use. The preparation method of the silica nanospheres loaded with gentamicin sustained-release drug includes: slowly dripping tetraethyl orthosilicate (TEOS) into an ethanol / water mixed solvent, adding 0.1 M HCl, and then adding the sustained-release drug, and stirring at 25 °C for 3 h. The volume ratio of TEOS, ethanol, water, and the catalyst is 1:5:1:2, and 5 mg / mL of gentamicin sustained-release drug is added therein; after hydrolysis, a sol is formed, and the silica nanospheres loaded with the sustained-release drug are obtained through aging and drying; the hydrolysis is that TEOS reacts with water when stirred in an aqueous solution to form a sol; the aging step includes: transferring the sol to a sealed glass bottle, standing and aging at 25 °C for 36 hours, and gently shaking the bottle body every hour; after aging, washing with ethanol 3 times to remove free drugs; the drying is vacuum drying at 40 °C for 12 h.

[0060] Electrospin a 150-μm-thick film on the outer surface of the stent. Subsequently, continue to prepare a central blocking membrane 2 with a thickness of 650 μm by electrospinning, place the central blocking membrane 2 at the center of the stent, and connect and fix the outer membrane layer of the central blocking membrane and the electrospun liquid film layer on the surface of the magnesium alloy wire 4 through a local dissolution-recoagulation method. Finally, dry the occluder at 42 o C for 40 h.

[0061] Example 5

[0062] The preparation method of the occluder in this example: For transposition of the great arteries in congenital heart disease, prepare a degradable occluder with a drug sustained-release function. Weave a magnesium-zinc alloy wire with a diameter of 500 μm and a uniform 50-μm polylactic acid coating into the main body of the occluder stent 1, and carry out vacuum heat preservation and shaping at 55 o C for 48 h. The preparation method of the polylactic acid coating includes: dissolving polylactic acid in an organic solvent, the organic solvent being dichloromethane, and the mass-volume ratio of polylactic acid to the organic solvent being 0.1 g / mL to obtain a polylactic acid solution.

[0063] Preparation of poly(lactic acid) electrospinning solution: Add silicon dioxide nanospheres 3 loaded with dexamethasone sustained-release drug into the poly(lactic acid) solution prepared in the above step at a concentration of 20 mg / mL. The diameter of the silicon dioxide nanospheres 3 is 800 nm, and the drug release period is 18 days. After being sufficiently dispersed by magnetic stirring at 500 revolutions per minute for 12 h, it is reserved for use. The preparation method of the silicon dioxide nanospheres loaded with dexamethasone sustained-release drug includes: slowly dripping tetraethyl orthosilicate (TEOS) into an ethanol / water mixed solvent, adding 25% NH3·H2O, and then adding the sustained-release drug, and stirring at 25 °C for 3 h. The volume ratio of TEOS, ethanol, water, and the catalyst is 1:5:1:2, and 5 mg / mL dexamethasone sustained-release drug is added therein; after hydrolysis, a sol is formed, and the silicon dioxide nanospheres loaded with the sustained-release drug are obtained through aging and drying; the hydrolysis is that TEOS reacts with water when stirred in an aqueous solution to form a sol; the aging step includes: transferring the sol to a sealed glass bottle, standing and aging at 25 °C for 36 hours, and gently shaking the bottle body every hour; after aging, it is washed 3 times with ethanol to remove free drugs; the drying is vacuum drying at 40 °C for 12 h.

[0064] Electrospin a 500-μm-thick film on the outer surface of the stent. Subsequently, continue to prepare a central blocking membrane 2 with a thickness of 1000 μm by electrospinning, place the central blocking membrane 2 at the center of the stent, and connect and fix the outer membrane layer of the central blocking membrane and the electrospun liquid film layer on the surface of the magnesium alloy wire 4 through a local dissolution-recoagulation method. Finally, dry the occluder at 40 o °C for 48 h.

[0065] Comparative Example 1

[0066] Compared with Examples 1-5, the occluder is a magnesium-zinc alloy wire with a 1-μm uniform poly(lactic acid) coating and a diameter of 500 μm. Since in Examples 1-5 and Comparative Example 1, the coating in the examples is a polymer coating loaded with a sustained-release drug, and the comparative example does not adopt the combination of electrospinning and silicon dioxide nanospheres loaded with a sustained-release drug, the antibacterial effect of Examples 1-5 is better than that of Example 1. The reason is that the release of the sustained-release drug improves the antibacterial effect, indicating that better technical effects can be obtained by adding drug-loaded microspheres in electrospinning.

[0067] Comparative Example 2

[0068] Compared with Examples 1-5, the occluder material is a poly(lactic acid) wire with a diameter of 500 μm.

[0069] Since in Examples 1-5 and Comparative Example 2, the comparative example does not use a magnesium-zinc alloy and only a polymer wire exists, and the examples use a magnesium wire as the matrix, the antibacterial effect of Examples 1-5 is better than that of Example 2. The reason is that Mg 2+The release increases the antibacterial effect, indicating that better technical effects can be obtained by using a magnesium alloy wire as the substrate.

[0070] The antibacterial properties of Examples 1-5 and Comparative Examples 1 and 2 were tested, and the results are as Figure 4 shown. Compared with Comparative Example 1, Examples 1-5 have stronger antibacterial properties. The antibacterial property of Comparative Example 1 is better than that of Comparative Example 2, but it is still inferior to that of the examples.

[0071] The porous silica microspheres containing the sustained-release drug prepared by the present invention are combined with the degradable polymer to keep their due activity in the polymer, and are coated on the occluder stent by electrospinning, having the ability to match the healing speed of human tissues and good antibacterial functions.

Claims

1. A preparation method of an electrospinning solution for a degradable occluder coating, characterized in that, The following steps are involved: The degradable polymer is dissolved in an organic solvent, and silica nanoparticles loaded with sustained-release drugs are added to the solution, and the solution is fully dispersed after magnetic stirring to obtain a degradable occluder coating with drug sustained-release function; the degradable polymer includes one or more of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, polydioxane, and polydioxanone.

2. The preparation method of the electrospinning solution for the degradable occluder coating according to claim 1, wherein The sustained-release drug comprises one or more of lidocaine, ibuprofen, diclofenac, dexamethasone, curcumin, resveratrol, and gentamicin; the sustained-release period of the sustained-release drug is 1 to 21 days; and the organic solvent is dichloromethane.

3. The preparation method of the electrospinning solution for the degradable occluder coating according to claim 1, wherein, The concentration of the silicon dioxide nano-microspheres loaded with sustained-release drugs in the electrospinning solution is 0.1-30 mg / mL, and the average diameter of the silicon dioxide nano-microspheres loaded with sustained-release drugs is 20-800 nm.

4. The preparation method of the electrospinning solution for the degradable occluder coating according to claim 1, wherein The preparation method of the silica nanoparticles loaded with sustained-release drugs comprises: slowly dropping ethyl silicate into an ethanol / water mixed solvent, adding an alkali or acid catalyst, then adding the sustained-release drug, and stirring at 25-40° C. for 2-4 hours; the volume ratio of ethyl silicate, ethanol, water and catalyst is 1:5-8:1-4:2-4; hydrolysis forms a sol, and aging and drying are performed to obtain the silica nanoparticles loaded with sustained-release drugs.

5. An electrospinning solution for a degradable occluder coating, characterized in that, Prepared by the preparation method according to any one of claims 1 to 4.

6. A preparation method of a degradable occluder with drug sustained-release function, characterized in that, The following steps are involved: The pretreated magnesium alloy wire is woven into the occluder stent body, and after vacuum insulation and shaping, the surface is coated with the electrospinning solution described in claim 5, and the central film layer sprayed with the electrospinning solution is placed at the center of the occluder stent body to obtain a central flow-blocking film, and the central flow-blocking film and the occluder stent body are connected and fixed by a local dissolution-resolidification method; The pretreatment step includes: uniformly coating a degradable polymer coating on the surface of the magnesium alloy wire.

7. The preparation method of the degradable occluder with drug sustained release function according to claim 6, characterized in that, The diameter of the magnesium alloy wire is 50 μm-500 μm, the coating thickness of the degradable polymer is 1-50 μm, and the coating thickness of the electrostatic spinning solution is 20-500 μm.

8. The preparation method of the degradable occluder with drug sustained release function according to claim 6, characterized in that, After the central flow-blocking membrane and the occluder stent body are connected and fixed, they are dried at 40-50°C for 6-48 hours.

9. A degradable occluder with a drug sustained-release function, characterized in that, The method is prepared by any one of claims 6 to 8.

10. Use of the degradable occluder with drug sustained-release function as claimed in claim 9 in the preparation of medical devices for congenital heart disease.

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