Degradable metal drug delivery stent for orbit reconstruction as well as preparation method and application of degradable metal drug delivery stent

Abstract

The invention discloses a degradable metal drug delivery stent for orbit reconstruction as well as a preparation method and application of the degradable metal drug delivery stent. The degradable metal drug delivery stent for orbital reconstruction prepared by the invention is processed by adopting zinc alloy powder in combination with a 3D printing technology, the degradable metal drug delivery stent comprises a base shell and a porous metal structure, the base shell and the porous metal structure are connected into a whole, and the whole structure is degradable, so that the preparation process is simple, and the cost is low. The solid shell guarantees the overall mechanical strength of the drug delivery structure; the porous structure increases the contact area between the implant and body fluid, overcomes the inherent defects of slow degradation process and uncontrollable degradation rate of a zinc alloy degradable material, and realizes the effect of light weight.

Description

Technical Field

[0001] The present invention belongs to the field of biotechnology, and in particular relates to a degradable metal drug delivery stent for orbital reconstruction, and a preparation method and application thereof. Background Art

[0002] The current application of 3D printing technology in ophthalmology is primarily focused on personalized implant construction and preoperative planning. Because orbital bone has lower stress requirements than limb bones, but higher requirements for material biocompatibility and other performance aspects, and is closer to the eyeball, implants must be fully aligned with the orbit and possess anti-inflammatory properties without affecting the normal physiological function of the eyeball. Currently, in clinical cases requiring orbital reconstruction for thyroid exophthalmos or orbital fractures, flat titanium mesh structures are often used. Orbital reconstruction is achieved through the use of flexible titanium mesh, leveraging the stability and bioinertness of titanium alloy to provide mechanical support during orbital bone reconstruction.

[0003] After orbital reconstruction surgery, some patients need to take multiple medications through injections and other means, which cannot achieve stable drug release. The current titanium mesh structure does not have the function of carrying drugs, so patients need to go to the hospital for injections many times, which increases the financial burden on patients, and the stability of drug treatment cannot be guaranteed, and the effect is often poor. In addition, the titanium mesh is a foreign body in the body. Long-term implantation may cause chronic inflammation due to friction with surrounding tissues, and may cause discomfort in the vicinity of the eyeball. When the orbit is subjected to external forces (such as strenuous exercise), the titanium alloy implant may also be displaced, broken or worn, and severe cases may require secondary surgery.

[0004] To solve the above situation, the present invention intends to construct a degradable metal drug delivery stent for orbital reconstruction to solve the implantation defects of the existing titanium mesh structure. Summary of the Invention

[0005] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, the present invention provides a degradable metal drug delivery stent for orbital reconstruction.

[0006] The present invention also provides a method for preparing a degradable metal drug delivery stent for orbital reconstruction.

[0007] The present invention also proposes the application of the above-mentioned degradable metal drug delivery stent for orbital reconstruction.

[0008] The present invention also provides a product.

[0009] According to one aspect of the present invention, a degradable metal drug delivery stent for orbital reconstruction is proposed. The degradable metal drug delivery stent comprises a base shell and a porous metal structure, wherein the base shell is connected to the porous metal structure.

[0010] In some embodiments of the present invention, the base shell is a solid structure.

[0011] In some embodiments of the present invention, the base shell is made of an inorganic ceramic material, a synthetic polymer material, a degradable metal material or a composite material, and all of them are degradable materials.

[0012] In some embodiments of the present invention, the degradable metal material comprises zinc alloy.

[0013] In some embodiments of the present invention, the zinc alloy comprises a zinc-magnesium-copper alloy.

[0014] In some embodiments of the present invention, the zinc content in the zinc-magnesium-copper alloy accounts for 98%-99%.

[0015] In some embodiments of the present invention, the base shell has a thickness of 3-7 mm, for example, 3 mm, 4 mm, 5 mm, 6 mm, or 7 mm. The base shells of the present invention may have varying thicknesses. By controlling the thickness of the base shells, cross-release of the drug packages can be achieved, thereby extending the drug release period.

[0016] In some embodiments of the present invention, the material of the porous metal structure is a degradable metal material.

[0017] In some embodiments of the present invention, the degradable metal material comprises zinc alloy.

[0018] In some embodiments of the present invention, the zinc alloy comprises a zinc-magnesium-copper alloy.

[0019] In some embodiments of the present invention, the surface and interior of the porous metal structure have different porosities and pore sizes.

[0020] In some embodiments of the present invention, the porosity of the surface of the porous metal structure is 40-50%; for example, it can be 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%.

[0021] In some embodiments of the present invention, the porosity of the interior of the porous metal structure is 60-80%; for example, it can be 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%.

[0022] In some embodiments of the present invention, the porosity of the interior of the porous metal structure is 65-75%.

[0023] In some embodiments of the present invention, the pore size of the surface of the porous metal structure is 200-300 μm.

[0024] In some embodiments of the present invention, the pore size of the surface of the porous metal structure is 220-280 μm.

[0025] In some embodiments of the present invention, the pore size of the surface of the porous metal structure is 240-260 μm.

[0026] In some embodiments of the present invention, the pore size of the surface of the porous metal structure is 245-255 μm.

[0027] In some embodiments of the present invention, the pore size inside the porous metal structure is 500-800 μm.

[0028] In some embodiments of the present invention, the pore size inside the porous metal structure is 500-700 μm.

[0029] In some embodiments of the present invention, the pore size of the porous metal structure is 550-650 μm.

[0030] In some embodiments of the present invention, the pore size inside the porous metal structure is 580-620 μm.

[0031] In some embodiments of the present invention, the pore size inside the porous metal structure is 590-710 μm.

[0032] In some embodiments of the present invention, the diameter of the pillars of the porous metal structure is 200-400 μm.

[0033] In some embodiments of the present invention, the diameter of the pillars of the porous metal structure is 250-350 μm.

[0034] In some embodiments of the present invention, the diameter of the pillars of the porous metal structure is 280-320 μm.

[0035] In some embodiments of the present invention, the diameter of the pillars of the porous metal structure is 290-310 μm.

[0036] In some embodiments of the present invention, the porous metal structure is constructed by interlacing continuous curved surfaces; the porous metal structure is internally connected horizontally and vertically to form horizontal and vertical intersecting channels. The porous metal structure of the present invention is not a traditional disordered porous structure. It is interconnected by curved surfaces rather than traditional metal ribs to form a drug package that is connected horizontally and vertically. The closer to the eyeball, the denser the longitudinal connection, and the farther away from the eyeball, the denser the transverse connection, which can ensure stable drug release. In the present invention, the combination of the porous structure and the shell structure can greatly improve the overall structural strength. At the same time, the solid shell structure can ensure stability in the initial implantation, prevent the release of drugs in the porous structure, and can gradually release drugs as the degradation process progresses.

[0037] In some embodiments of the present invention, drugs are carried in the channels.

[0038] In some embodiments of the present invention, the surface of the degradable metal drug delivery stent is slightly rough.

[0039] In some embodiments of the present invention, the surface roughness of the degradable metal drug delivery stent is 2-5 μm.

[0040] According to the second aspect of the present invention, a method for preparing the above-mentioned degradable metal drug delivery stent for orbital reconstruction is proposed, which includes the following steps: preparing zinc alloy into a light-cured ceramic slurry, and printing and preparing it according to the stent model through a 3D printing method.

[0041] In some embodiments of the present invention, the zinc alloy comprises a zinc-magnesium-copper alloy.

[0042] In some embodiments of the present invention, before the 3D printing, the step of vacuum drying the zinc alloy is also included.

[0043] In some embodiments of the present invention, the vacuum drying conditions are: 110-130°C for 3-5h, vacuum degree ≤ 1×10-2 m bar.

[0044] In some embodiments of the present invention, the photocurable ceramic slurry further includes a photosensitive resin system and a biocompatible additive.

[0045] In some embodiments of the present invention, the photosensitive resin system includes a base resin, a diluent monomer, and a cross-linking agent, and is used to provide a photocurable cross-linked network.

[0046] In some embodiments of the present invention, the mass proportion of the photosensitive resin system in the photocurable ceramic slurry is 28% to 45%.

[0047] In some embodiments of the present invention, the base resin comprises poly(lactic acid-glycolic acid) copolymer, and the double bond content is ≥80%.

[0048] In some embodiments of the present invention, the matrix resin system accounts for 20-30% by mass in the light-curing ceramic slurry.

[0049] In some embodiments of the present invention, the diluent monomer comprises hydroxyethyl methacrylate.

[0050] In some embodiments of the present invention, the mass proportion of the diluent monomer in the photocurable ceramic slurry is 5-10%.

[0051] In some embodiments of the present invention, the crosslinking agent comprises trimethylolpropane triacrylate.

[0052] In some embodiments of the present invention, the cross-linking agent accounts for 3-5% by weight in the photocurable ceramic slurry.

[0053] In some embodiments of the present invention, the biocompatible additive includes at least one of a dispersant, a photoinitiator, a toughening agent, an antibacterial agent, and a defoaming agent.

[0054] In some embodiments of the present invention, the dispersant comprises gelatin hydrolysate with a molecular weight of 10-30 kDa.

[0055] In some embodiments of the present invention, the mass of the dispersant accounts for 0.5% to 1% of the mass of the zinc alloy.

[0056] In some embodiments of the present invention, the photoinitiator includes camphorquinone and ethyl 4-dimethylaminobenzoate.

[0057] In some embodiments of the present invention, the mass of the camphorquinone accounts for 0.5% to 1% of the mass of the zinc alloy.

[0058] In some embodiments of the present invention, the mass of the ethyl 4-dimethylaminobenzoate accounts for 0.2% to 0.5% of the mass of the zinc alloy.

[0059] In some embodiments of the present invention, the toughening agent comprises type I collagen.

[0060] In some embodiments of the present invention, the mass of the toughening agent accounts for 0.5% to 1% of the mass of the zinc alloy.

[0061] In some embodiments of the present invention, the antibacterial agent comprises nanosilver.

[0062] In some embodiments of the present invention, the mass of the antibacterial agent accounts for 0.1% to 0.3% of the mass of the zinc alloy.

[0063] In some embodiments of the present invention, the defoaming agent comprises Tween 80.

[0064] In some embodiments of the present invention, the mass of the defoaming agent accounts for 0.1% to 0.3% of the mass of the zinc alloy.

[0065] In some embodiments of the present invention, the stent model is established based on patient imaging data by inputting the patient imaging data into three-dimensional reconstruction software.

[0066] In some embodiments of the present invention, the patient imaging data is a CT image of the patient.

[0067] In some embodiments of the present invention, the CT image is obtained by CT scanning, and the CT scanning parameters are as follows: slice thickness ≤ 0.625 mm, voltage 115-125 kV, current 190-210 mA.

[0068] In some embodiments of the present invention, the CT scanning parameters are as follows: slice thickness ≤ 0.625 mm, voltage 120 kV, current 200 mA.

[0069] In some embodiments of the present invention, the three-dimensional reconstruction software includes Mimics.

[0070] In some embodiments of the present invention, the setting parameters of the 3D reconstruction software are as follows: threshold segmentation (HU value) is 200-3000, and grid accuracy is ≤0.1 mm.

[0071] In some embodiments of the present invention, the parameters of the 3D printing method include: laser power of 150-300W; scanning power of 800-1200mm / s; layer thickness of 30-50μm; scanning spacing of 80-120μm; and substrate preheating temperature of 200-400°C.

[0072] In some embodiments of the present invention, the parameters of the 3D printing method include: laser power of 220-280W; scanning power of 850-1000mm / s; layer thickness of 35-45μm; scanning spacing of 90-110μm; and substrate preheating temperature of 250-350°C.

[0073] In some embodiments of the present invention, the parameters of the 3D printing method include: laser power of 240-260W; scanning power of 850-950mm / s; layer thickness of 38-42μm; scanning spacing of 95-105μm; and substrate preheating temperature of 280-320°C.

[0074] In some embodiments of the present invention, the method further comprises the step of heat treating the degradable metal drug delivery stent, wherein the heat treatment conditions are: hot isostatic pressing (HIP) at 900-940°C for 1-3h in a 90-110MPa argon atmosphere to eliminate internal stress.

[0075] In some embodiments of the present invention, the heat treatment conditions are: hot isostatic pressing (HIP) at 920° C. for 2 h in a 100 MPa argon atmosphere to eliminate internal stress.

[0076] In some embodiments of the present invention, the method further comprises the step of surface modification of the degradable metal drug delivery stent, so that the surface roughness of the degradable metal drug delivery stent is 2-5 μm.

[0077] The surface modification method includes one or more of oxygen plasma treatment, coating modification, coupling modification, NaOH immersion, plasma treatment, and organic solvent corrosion to increase surface roughness.

[0078] In some embodiments of the present invention, the organic solvent etching includes acid etching.

[0079] In some embodiments of the present invention, the surface modification method is acid etching, and the acid treatment time is 10-30 min, for example, 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, 16 min, 17 min, 18 min, 19 min, 20 min, 21 min, 22 min, 23 min, 24 min, 25 min, 26 min, 27 min, 28 min, 29 min, or 30 min.

[0080] In some embodiments of the invention, the acid comprises hydrofluoric acid and nitric acid.

[0081] In some embodiments of the present invention, the ratio of the hydrofluoric acid to the nitric acid is 1:(2-4).

[0082] According to the third aspect of the present invention, the use of a degradable metal drug delivery stent in any of the following is proposed:

[0083] (1) Preparation of products for orbital reconstruction;

[0084] (2) Preparation of products for bone defect repair and regeneration;

[0085] (3) Bone cell culture;

[0086] (4) Prepare drug delivery products.

[0087] In some embodiments of the present invention, the method of using the product for orbital reconstruction includes: covering one side of the porous metal structure of the degradable metal drug delivery stent on the residual bone end of the orbit to be repaired, with the base shell portion facing outward.

[0088] In some embodiments of the present invention, the drugs contained in the drug delivery product include drugs for reducing inflammation and guiding bone regeneration.

[0089] According to some embodiments of the present invention, at least the following beneficial effects are achieved: the present invention provides a degradable metal drug delivery stent for orbital reconstruction, which is processed using zinc alloy powder combined with 3D printing technology. The degradable metal drug delivery stent includes a base shell and a porous metal structure. The base shell and the porous metal structure are connected into a whole. The structure as a whole is degradable, and the solid shell ensures the overall mechanical strength of the drug delivery structure; the porous structure increases the contact area between the implant and the body fluid, overcoming the inherent defects of the zinc alloy degradable material, which has a slow degradation process and uncontrollable degradation rate, while achieving a lightweight effect.

[0090] At the same time, the biodegradable metal drug delivery stent is matched with the shape of the patient's orbital defect to achieve complete fit between the implant and the orbit, adjacent to the eyeball tissue, reducing local tissue friction and lowering inflammation; when loaded with drugs, the drugs can be released from the position closest to the affected area, which is less painful and more effective than injections. BRIEF DESCRIPTION OF THE DRAWINGS

[0091] The present invention will be further described below with reference to the accompanying drawings and embodiments, in which:

[0092] Figure 1 is a schematic diagram of a degradable metal drug delivery stent for orbital reconstruction in an embodiment of the present invention;

[0093] Figure 2 is a schematic diagram of a degradable metal drug delivery stent for orbital reconstruction in an embodiment of the present invention;

[0094] Figure 3 is a schematic diagram of a degradable metal drug delivery stent for orbital reconstruction in an embodiment of the present invention;

[0095] Figure 4 This is a processing flow chart of a degradable metal drug delivery stent for orbital reconstruction according to an embodiment of the present invention;

[0096] Figure 5 This is a diagram showing the usage status of the degradable metal drug delivery stent for orbital reconstruction in an embodiment of the present invention. DETAILED DESCRIPTION

[0097] The following will clearly and completely describe the concept and technical effects of the present invention in conjunction with the embodiments to fully understand the purpose, features and effects of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0098] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or those recommended by the manufacturer. All reagents or instruments used, if the manufacturer is not specified, are commercially available conventional products.

[0099] Example 1

[0100] This embodiment provides a degradable metal drug delivery stent for orbital reconstruction, which is prepared by a degradable metal alloy (Zn-Mg-Cu alloy) using a 3D printing method. Figure 1-3 As shown in the figure, it can be seen that the degradable metal drug delivery stent includes: a base shell and a porous metal structure; the base shell is a solid structure with a thickness of 5 mm, and the base shell is connected to the porous metal structure; the porous metal structure is constructed by interlacing continuous curved surfaces, and the porous metal structure is connected horizontally and vertically to form a horizontal and vertical cross channel, which can carry drugs. At the same time, there will be several dead corners after the continuous curved surfaces are connected to each other, which can accommodate more drugs.

[0101] When the degradable metal drug delivery stent for orbital reconstruction is in use, one side of the porous metal structure covers the residual bone end, with the base shell part facing outward. The closer to the eyeball, the denser the longitudinal connection, and the farther away from the eyeball, the denser the lateral connection, which can ensure uniform drug release.

[0102] Preparation process as Figure 4 As shown, use the following figure Figure 5 As shown, the specific preparation method is as follows:

[0103] 1. Obtaining a 3D skull reconstruction model from medical imaging

[0104] (1) CT scan: Obtain a CT image of the patient's skull model. The CT scanning parameters are as follows: slice thickness ≤ 0.625 mm, voltage 120 kV, current 200 mA (to ensure clear trabecular structure);

[0105] (2) The patient's CT image was imported into the three-dimensional reconstruction software Mimics 20.0 to generate a visual skull model. The parameters of the three-dimensional reconstruction software were set as follows: Mimics (Materialise) threshold segmentation (HU value 200-3000), grid accuracy ≤ 0.1 mm.

[0106] 2. Porous structure design and optimization

[0107] Core parameters:

[0108] Porosity: 70% in the main area (60%-80% is acceptable), 50% in the edge transition area (40%-50% is acceptable) (to prevent stress shielding);

[0109] Pore ​​size gradient design: surface pore size 250 μm (200-300 μm is acceptable) (promotes cell adhesion), internal pore size 600 μm (500-800 μm is acceptable) (promotes vascularization);

[0110] Pillar diameter: 300 μm (200-400 μm is acceptable) (the elastic modulus of the titanium alloy must match that of cancellous bone ≈ 1-5 GPa).

[0111] 3. Preparation of biodegradable metal drug delivery stents for orbital reconstruction

[0112] Experimental materials: zinc alloy (Zn-Mg-Cu alloy: zinc content 98.5%, magnesium content 0.5%, copper content 1.0%) powder (particle size 20-50 μm).

[0113] (1) Experimental material pretreatment: The zinc alloy powder was vacuum dried (vacuum drying conditions: 120℃×4h, vacuum degree ≤1×10-2 m bar).

[0114] (2) Preparation of photocurable ceramic slurry

[0115] Photocurable ceramics include ceramic powder, photosensitive resin system, and biocompatible additives. The ceramic powder uses degradable ceramic powder, and the photosensitive resin system includes a base resin, a diluent monomer, and a crosslinking agent to provide a photocurable crosslinking network. The biocompatible additives include: a dispersant: gelatin hydrolyzate (molecular weight 10-30kDa) accounting for 2.5% (2% to 3%) of the ceramic powder mass;

[0116] Photoinitiator: camphorquinone (CQ) accounts for 0.5% (0.5% to 1%) of the mass of the ceramic powder, and ethyl 4-dimethylaminobenzoate (EDMAB) accounts for 0.3% (0.2% to 0.5%) of the mass of the ceramic powder;

[0117] Toughening agent: Type I collagen accounts for 0.5% (0.5% to 1%) of the ceramic powder mass;

[0118] Antibacterial agent (optional): nano silver particles (particle size ≤ 50 nm) accounting for 0.1% (0.1% to 0.3%) of the ceramic powder mass;

[0119] Defoaming agent: Polysorbate 80 (Tween 80), accounting for 0.1% (0.1% to 0.3%) of the mass of the ceramic powder, medical grade HLB value 15-18.

[0120] The degradable ceramic powder used in this embodiment is a spherical zinc alloy powder (D50 = 10-50 μm, (Zn-Mg-Cu alloy: zinc content is 98.5%, magnesium content is 0.5%, copper content is 1.0%) powder (particle size 20-50 μm)), whose main phase is Zn.

[0121] In the photosensitive resin system used in this embodiment, the base resin is polylactic acid-glycolic acid copolymer (PLGA) with a double bond content of ≥80%; the diluent monomer is hydroxyethyl methacrylate (HEMA); and the crosslinking agent is trimethylolpropane triacrylate (TMPTA), which can improve the mechanical strength after curing.

[0122] The preparation process includes:

[0123] a) Raw material preparation: weigh the photosensitive resin system (the mass proportion of the photosensitive resin system in the photocurable ceramic slurry can be 28% to 45%, specifically 35% in this embodiment), wherein: (polylactic acid-co-glycolic acid (PLGA) modified acrylate (double bond content ≥80%, acid value ≤5mgKOH / g) mass proportion is 25% (20-30% is acceptable), hydroxyethyl methacrylate (HEMA) medical grade, purity 99% mass proportion is 7% (5-10% is acceptable), this diluent monomer can adjust the viscosity of the rubber compound to the target range of 3000-6000 MPa·s at 25°C, trimethylolpropane triacrylate (TMPTA) functionality ≥3, low toxicity, mass proportion is 3% (3-5% is acceptable), cross-linking agent improves the mechanical strength after curing (tensile strength ≥15 MPa), and preheat and dissolve them. After dissolution, add the dispersant, and stir magnetically for 40 minutes (30 minutes to 1 hour is acceptable) to ensure that all components are fully mixed;

[0124] b) Mixing and stirring: Add ceramic powder (ceramic powder accounts for 55%-72% by weight of the light-curing ceramic slurry) and disperse using a planetary ball mill (zirconia balls, ball-to-material ratio of 5:1, speed of 400 rpm) for 6 hours (5-9 hours is acceptable);

[0125] It should be noted that: zinc alloy powder is used in this application, and argon is introduced as a protective gas throughout the entire process.

[0126] c) Post-treatment: ultrasonic degassing is performed at 25° C., and then filtering is performed through a 0.22 μm sterile filter membrane before packaging for use.

[0127] (3) Preparation of degradable metal drug delivery stent

[0128] The photocurable ceramic slurry obtained after pretreatment was used to prepare a degradable metal drug delivery stent using a 3D printing method. The parameters finally optimized by 3D printing are shown in Table 1.

[0129] Table 1

[0130]

[0131]

[0132] (3) Post-treatment and surface modification

[0133] The degradable metal drug delivery stent obtained by 3D printing was successively subjected to heat treatment (treatment conditions: hot isostatic pressing (HIP) 920℃×2h / 100MPa argon to eliminate internal stress (residual stress <50MPa)) and surface modification (treatment conditions: acid etching (HNO3:HF=3:1, time 10-30min (specifically 20min)) to form micro-nanoscale roughness (Sa=2-5μm)) to prepare a degradable metal drug delivery stent for orbital reconstruction.

[0134] Test example

[0135] This test example tested the performance of the degradable metal drug delivery stent for orbital reconstruction prepared in Example 1.

[0136] 1. Mechanical properties test

[0137] (1) Tensile properties test

[0138] According to GB / T 228.1-2010 "Tensile tests on metallic materials - Part 1: Room temperature test methods", the following tensile properties test plan is designed:

[0139] S1. Sample preparation: The degradable metal drug delivery stent for orbital reconstruction prepared in Example 1 is prepared into a spline, and the spline is processed (removing supports, polishing, etc.) to ensure that the surface of the spline is uniform and smooth without gaps.

[0140] S2. Tensile Properties Test: A microcomputer-controlled electronic universal testing machine was used with a 100,000 N force transducer. The machine employed crosshead displacement control and a crosshead speed setting of 0.45 mm / min. Three specimens were tested.

[0141] S3. Print the test report and record the test results.

[0142] Table 2

[0143] Sample Code Tensile strength (MPa) Elongation Spline 1 431.25 55.10％ Spline 2 428.22 53.25％ Spline 3 433.21 56.21％ Reference value 430.89 54.85％

[0144] The results are shown in Table 2. It can be seen from the table that the degradable metal drug delivery stent prepared in Example 1 has a tensile strength of 430.89 MPa and an elongation of 54.85%.

[0145] (2) Compression performance test

[0146] According to GB / T 7314-2017 “Metallic Materials Room Temperature Compression Test Method”, the following compression performance test scheme is designed:

[0147] S1. Sample preparation: Remove the sample from the substrate and process the sample (remove support, polish, etc.) to ensure that the surface of the sample is uniform and smooth without gaps.

[0148] S2. Compression performance test

[0149] Place the specimen at the center of the lower platen of the testing machine and set the speed to 1 mm / min. Continue testing until the load drops or a collision occurs between the upper and lower blocks. Record the failure mode and measure the yield strength of each specimen.

[0150] Table 3

[0151] Sample Code Yield strength (MPa) Sample 1 354.21 Sample 2 359.25 Sample 3 356.21 Sample value 356.56

[0152] The results are shown in Table 3. It can be seen from the table that the degradable metal drug delivery stent prepared in Example 1 of the present invention meets the mechanical performance requirements of the implant in this part, and the structure effectively maintains the required mechanical strength.

[0153] 2. Degradation rate

[0154] (1) Experimental preparation

[0155] 1) Prepare the biodegradable metal drug delivery stent sample prepared in Example 1: prepare three samples, and prepare three parallel samples for each pore size at each time point to ensure the consistency and quality of the samples.

[0156] 2) Laboratory Equipment Preparation: Prepare several plastic test tubes, ensuring they are clean and free of impurities. Prepare sufficient deionized water for rinsing the samples. Prepare drying equipment and adjust it to the appropriate temperature (generally around 60°C to ensure rapid drying without affecting sample performance). Prepare plastic wrap to seal the test tubes.

[0157] 3) Solution Preparation: Prepare the immersion solution (Hank's balanced salt solution). The solution composition should be precisely tailored to the physiological environment simulated in the experiment. Ensure that a sufficient amount of solution is prepared to meet the weekly solution changes throughout the experiment.

[0158] (2) Experimental steps

[0159] 1) Sample placement: Fix each parallel porous zinc sample with a thin wire or a suitable hanging device to ensure that the sample can be suspended inside the plastic test tube and does not contact the test tube wall.

[0160] 2) Tube Sealing: Add an appropriate amount of the prepared solution to the plastic tube containing the sample, ensuring that the solution completely submerges the sample. Seal the tube tightly with plastic wrap to ensure a tight seal, preventing the solution from evaporating and foreign matter from entering.

[0161] 3) Place in water bath: Carefully place the sealed test tube in a 37°C constant temperature water bath, ensuring that the test tube is stable and will not tip over.

[0162] 4) Solution Replacement: Open the water bath regularly each week and remove the test tubes. Carefully remove the plastic wrap and slowly pour out the solution from the test tubes, taking care not to splash the solution onto the samples. Then, rinse the inside of the test tubes with fresh solution, add fresh solution until the samples are completely submerged, reseal with plastic wrap, and return to the water bath.

[0163] 5) Sample removal and processing: At the preset immersion time points (three days, one week, two weeks, four weeks, six weeks, eight weeks, 12 weeks), remove the test tubes at the corresponding time points from the water bath.

[0164] Carefully open the plastic wrap, take out the sample with tweezers, place the sample in a container filled with deionized water, and gently shake the container to allow the deionized water to rinse the sample surface for about 30 seconds to remove the residual immersion solution on the surface.

[0165] Place the rinsed sample on a clean filter paper to absorb excess surface moisture, then place it in a drying device, set the temperature to 60°C, and dry it for about 1-2 hours until the sample is completely dry.

[0166] 6) pH Test (First Week): During the first week of immersion, remove the test tube from the water bath regularly each day. Carefully insert clean pH test paper or a pH meter into the solution in the test tube to measure the pH of the solution. Record the pH value and the corresponding measurement time for each measurement. After the measurement is completed, reseal the test tube and return it to the water bath.

[0167] 7) Weight loss measurement: After removing the sample from the immersion solution at a predetermined time point, clean it with chromic acid solution, remove any residual chromic acid with deionized water in an ultrasonic cleaner, dry it, and weigh it. The following formula is used to calculate the weight loss:

[0168]

[0169] Where m1 is the weight of the porous zinc samples of two sizes before immersion; m2 is the weight of the porous zinc samples of two sizes after removing corrosion products, and t is the immersion time.

[0170] Table 4

[0171]

[0172] The results are shown in Table 4. It can be seen from the table that the degradable metal drug delivery stent prepared in Example 1 of the present invention has excellent degradability.

[0173] 3. In vitro release experiment

[0174] Experimental Materials:

[0175] Simulated body fluid: Hank's solution, Ringer's solution or PBS solution (pH 7.4±0.1) compatible with zinc alloy degradation was selected.

[0176] Zinc alloy samples: porous zinc alloy specimens loaded with levofloxacin drug, with uniform dimensions.

[0177] (1) Experimental steps

[0178] 1) Solution preparation:

[0179] Prepare Hank's solution or PBS solution (pH 7.4 ± 0.1) according to the standard recipe and calibrate using a pH meter.

[0180] Preheat the constant temperature water bath to 37±0.5℃ (consistent with the electrochemical corrosion test conditions).

[0181] 2) Sample pretreatment:

[0182] The sample surface was cleaned of impurities by ultrasonic cleaning with deionized water, dried with nitrogen, and then weighed (accurate to 0.1 mg).

[0183] Hang the sample vertically in a glass test tube, ensuring that it does not touch the tube wall (e.g., fix it with a polytetrafluoroethylene stand).

[0184] 3) In vitro release experiment:

[0185] Add 10 mL of simulated body fluid to the test tube to completely submerge the sample.

[0186] Seal the test tube and place it in a 37±0.5℃ water bath and keep it still.

[0187] 4) Sampling and testing:

[0188] Time point setting: sampling at 3 days, 7 days, 14 days, 28 days, 42 days, 56 days and 84 days respectively.

[0189] Parallel sample setting: Take 3 sets of parallel samples at each time point and record the sampling time.

[0190] 5) Sample processing:

[0191] Remove the sample, quickly rinse the residual solution on the surface with deionized water, and absorb it dry with filter paper.

[0192] The sample was placed in 5 mL of methanol and ultrasonically extracted for 30 minutes to extract the drug.

[0193] 6) Data processing:

[0194] The cumulative drug release was calculated based on the drug concentration of the extract and the sample mass:

[0195]

[0196] Where: C is the drug concentration (μg / mL), V is the volume of the extract (mL), and m is the sample mass (mg). The drug release curve was plotted and the average release rate (μg / day) was calculated, resulting in the following table.

[0197] Table 5

[0198]

[0199] The results are shown in Table 5. It can be seen from the table that the degradable metal drug delivery stent prepared in Example 1 of the present invention has excellent sustained-release performance.

[0200] While the embodiments of the present invention have been described in detail above with reference to the accompanying drawings, the present invention is not limited to the embodiments described above. Various modifications may be made within the scope of knowledge possessed by a person skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof may be combined with one another unless there is a conflict.

Claims

1. A degradable metal drug delivery stent for orbital reconstruction, characterized in that: The degradable metal drug delivery stent comprises a base shell and a porous metal structure; the base shell is connected to the porous metal structure.

2. The degradable metal drug delivery stent according to claim 1, characterized in that: The base shell is a solid structure; And / or, the base shell is made of an inorganic ceramic material, a synthetic polymer material, a degradable metal material or a composite material, and all of them are degradable materials; And / or, the base shell has a thickness of 3-7 mm.

3. The degradable metal drug delivery stent according to claim 1, characterized in that: The material of the porous metal structure is a degradable metal material; Preferably, the degradable metal material comprises zinc alloy; More preferably, the zinc alloy comprises a zinc-magnesium-copper alloy.

4. The degradable metal drug delivery stent according to claim 1, characterized in that: The surface and interior of the porous metal structure have different porosities and pore sizes; Preferably, the porosity of the surface of the porous metal structure is 40-50%; Preferably, the porosity of the interior of the porous metal structure is 60-80%; Preferably, the pore size of the surface of the porous metal structure is 200-300 μm; Preferably, the pore size inside the porous metal structure is 500-800 μm; Preferably, the diameter of the pillars of the porous metal structure is 200-400 μm; And / or, the porous metal structure is constructed by interlacing continuous curved surfaces; the porous metal structure is interconnected in the horizontal and vertical directions to form channels that intersect horizontally and vertically; Preferably, the drug to be administered in the degradable metal drug delivery stent is carried in the channel.

5. The degradable metal drug delivery stent according to claim 1, characterized in that: The surface of the degradable metal drug delivery stent is slightly rough; Preferably, the surface roughness of the degradable metal drug delivery stent is 2-5 μm.

6. A method for preparing the degradable metal drug delivery stent according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: preparing a zinc alloy into a light-cured ceramic slurry, and printing and preparing the slurry according to a bracket model using a 3D printing method.

7. The preparation method according to claim 6, characterized in that Before the 3D printing, the method further comprises the step of vacuum drying the zinc alloy; Preferably, the vacuum drying process is carried out under the following conditions: 110-130°C for 3-5 hours, with a vacuum degree of ≤1×10-2 m bar; And / or, the stent model is established based on patient imaging data by inputting the patient imaging data into three-dimensional reconstruction software; Preferably, the patient imaging data is a CT image of the patient; And / or, the parameters of the 3D printing method include: laser power of 150-300W; scanning power of 800-1200mm / s; layer thickness of 30-50μm; scanning spacing of 80-120μm; and substrate preheating temperature of 200-400°C.

8. The preparation method according to claim 6, characterized in that The method further comprises the step of performing surface modification on the degradable metal drug delivery stent, so that the surface roughness of the degradable metal drug delivery stent is 2-5 μm; Preferably, the surface modification method includes one or more of oxygen plasma treatment, coating modification, coupling modification, NaOH immersion, plasma treatment, and organic solvent corrosion to increase surface roughness.

9. Use of the degradable metal drug delivery stent according to any one of claims 1 to 5 in any of the following: (1) Preparation of products for orbital reconstruction; (2) Preparation of products for bone defect repair and regeneration; (3) Bone cell culture; (4) Prepare drug delivery products.

10. The use according to claim 9, characterized in that The method for using the product for orbital reconstruction comprises: covering one side of the porous metal structure of the degradable metal drug delivery stent on the residual bone end of the orbit to be repaired, with the base shell portion facing outward.

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