Absorbable implantable medical device

Abstract

The invention discloses an absorbable implantable medical device which comprises an iron-based base body and a degradable polymer layer arranged on at least part of the surface of the iron-based base body, the degradable polymer layer comprises a degradable polymer, and the medical device further comprises an inert protective layer arranged on the whole surface of the iron-based base body. The absorbable implantable medical device is basically not corroded or corroded at a relatively low speed within 1-6 months after being implanted into a body, and can meet the clinical mechanical property requirement on the early stage of implantation of the device within the period of time.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to an absorbable implantable medical device. Background Art

[0002] Implantable medical devices are implanted in patients to repair diseased areas. For example, vascular stents are implanted in diseased areas to support narrowed and occluded blood vessels, reducing elastic recoil and reshaping of the vessels and maintaining unobstructed blood flow. Implantable medical devices can be divided into absorbable and non-absorbable implantable medical devices. Since absorbable implantable medical devices gradually degrade and are absorbed by the body until they completely disappear after implantation, they are ideal for treating cardiovascular diseases and other diseases. Currently, the materials used for absorbable implantable medical devices mainly include polymers, magnesium-based alloys, and iron-based alloys. Compared to metal materials, polymer materials have weaker mechanical properties. To achieve the same mechanical properties as metal-based devices, polymer-based devices must be larger than metal-based devices, which limits their application. Magnesium-based alloy devices corrode too quickly in the human body, and the only way to meet the clinical mechanical properties requirements of the device in the early stages of implantation is to increase their size, which also limits their application.

[0003] From a clinical application perspective, once an absorbable implantable medical device has fulfilled its intended purpose, the lesion has healed and restored its normal morphology and function, the shorter the time it takes for the device to completely degrade and be absorbed by the body, the better, provided it does not cause new biocompatibility issues. Depending on the location of the device in clinical application, the healing period for the lesion is generally considered to be 1 to 6 months. During this period, the device must maintain structural integrity and sufficient mechanical properties. Iron-based alloys have good biocompatibility, but they corrode slowly in the body. Consequently, iron-based alloy devices still require a long time to fully degrade after the lesion has healed, failing to meet the clinical requirements for the degradation performance of degradable devices.

[0004] Existing research indicates that accelerating the corrosion rate of iron-based alloys by directly coating them with biodegradable polyester coatings is not ideal. Early in the implantation period, the iron-based alloy corrodes rapidly due to the rapid degradation of the biodegradable polyester, resulting in the device failing to maintain its structural integrity and adequate mechanical properties within 1 to 6 months after implantation. Summary of the Invention

[0005] Based on this, the present invention provides an absorbable implantable medical device, which basically does not corrode or corrodes at a slower rate within 1 to 6 months after implantation in the body, and can meet the clinical mechanical performance requirements for the early stage of device implantation during this period.

[0006] In a first aspect, the present invention provides an absorbable implantable medical device comprising an iron-based substrate and a degradable polymer layer disposed on at least a portion of the surface of the iron-based substrate, wherein the degradable polymer layer comprises a degradable polymer, and the medical device further comprises an inert protective layer disposed on the entire surface of the iron-based substrate.

[0007] The present invention provides an inert protective layer on the entire surface of the iron-based substrate, which can effectively reduce or avoid the contact of the iron-based substrate with the external environment (such as external physiological solutions or substances produced by degradation of the degradable polymer layer) within 1 to 6 months of the early implantation, thereby slowing down the early corrosion rate of the iron-based substrate and ensuring that the device has sufficient mechanical properties in the early stage.

[0008] Furthermore, the present invention controls the thickness of the inert protective layer on the surface of the iron-based substrate so that the inert protective layer gradually disintegrates after all the diseased areas have healed and gradually exposes the iron-based substrate to the external environment (such as the external physiological environment or the environment of substances produced by the degradation of degradable polymers), thereby accelerating the corrosion rate of the iron-based substrate.

[0009] In some embodiments, the thickness of the inert protective layer is 0.020 μm to 6 μm; in other embodiments, the thickness of the inert protective layer is [0.02, 0.1) μm, or (0.1, 1) μm, or (1, 6) μm.

[0010] In some embodiments, the inert protective layer comprises an inert compound; the inert compound has an in vitro immersion corrosion rate of ≤2.0 mm / y.

[0011] In some embodiments, the water permeability of the inert protective layer is 1*10 -13 g·mm / (m 2 h)~1*10 - 2 g·mm / (m 2 ·h).

[0012] In some embodiments, the inert compound includes at least one of magnesium stearate, parylene, polyethylene, polyvinyl chloride, polyacrylate, polyethyl acrylate, polymethyl acrylate, polymethacrylate, polyethyl acrylate, polymethyl methacrylate, polytetrafluoroethylene, polyamide, polyamideimide, polyetherimide, polyethersulfone, poly(iso)butylene, polyvinyl fluoride, polyvinyl alcohol, polyurethane, polybutylene terephthalate, silicone, polyphosphazene, styrene, and derivatives.

[0013] In some embodiments, the parylene comprises at least one of parylene N, parylene C, parylene D, parylene F, and parylene HT.

[0014] In some embodiments, the degradable polymer layer covers at least a portion of the surface of the inert protective layer.

[0015] In some embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer is 5 kDa to 1000 kDa; and the thickness of the degradable polymer layer is 0.5 μm to 100 μm.

[0016] In some embodiments, the degradable polymer layer includes at least one degradable polymer layer located outside the inert protective layer and at least one degradable polymer layer located inside the inert protective layer.

[0017] In some embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is greater than the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer.

[0018] In some embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is at least 5 times the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer.

[0019] In some embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is 5 to 20 times the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer.

[0020] In some embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is 25 kDa to 700 kDa, and the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer is 5 kDa to 100 kDa.

[0021] In some embodiments, the thickness of the degradable polymer layer located inside the inert protective layer is 0.5 μm to 20 μm, and the thickness of the degradable polymer layer located outside the inert protective layer is 1 μm to 10 μm.

[0022] In some embodiments, the medical device further comprises a complexing agent layer disposed on at least a portion of the surface of the iron-based substrate, and the complexing agent layer is located inside the inert protective layer, and the complexing agent layer comprises a complexing agent.

[0023] In some embodiments, the complexing agent layer further includes a polymer carrier, and the mass ratio of the complexing agent to the polymer carrier is (0.2-1.5):1; the polymer carrier includes a degradable polymer.

[0024] In some embodiments, the complexing agent layer has a thickness of 0.05 μm to 10 μm.

[0025] In some embodiments, the complexing agent contains at least one coordinating group, and the coordinating group includes at least one of a hydroxyl group, a thiol group, an amine group, an aromatic heterocyclic group, a nitroso group, a carbonyl group, a sulfo group, a phosphate group, a hydroxamic acid group or an organic phosphine group on a condensed aromatic hydrocarbon; the hydroxyl group on the condensed aromatic hydrocarbon includes a phenolic hydroxyl group; the aromatic heterocyclic group includes at least one of a furyl group, a pyrrolyl group, an imidazole group, a triazole group, a thienyl group, a thiazolyl group, a pyridyl group, a pyridone group, a pyranyl group, a pyrone group, a pyrimidine group, a pyridazinyl group, a pyrazinyl group, a quinolyl group, an isoquinolyl group, a phthalazinyl group, a pteridinyl group, an indolyl group, a purinyl group or a phenanthroline group.

[0026] The complexing agents containing hydroxyl groups on condensed ring aromatic hydrocarbons include 8-hydroxyquinoline, 8-hydroxyquinaldine, 4,5-dihydroxybenzene-1,3-disulfonic acid sodium, 4-[3,5-di-hydroxyphenyl-1H-1,2,4-triazole]-benzoic acid, 1-(2-pyridylazo)-2-naphthol; the complexing agents containing thiol groups include 8-mercaptoquinoline, thioglycolic acid, dimercaptopropanol, 5-methyl-2-mercaptobenzoic acid methyl ester; the complexing agents containing amine groups include ethylenediamine, triethylenetetramine, ethylenediaminetetraacetic acid, ethylenediaminetetraethyl The complexing agent containing an aromatic heterocyclic group includes o-phenanthroline, bipyridine, porphyrin, porphine, chlorophyll, hemoglobin or 1,2-dimethyl-3-hydroxy-4-pyridone; the complexing agent containing a nitroso group includes 1-nitroso- 2-naphthol or 1-nitroso-2-naphthol-6-sodium sulfonate; the complexing agent containing sulfonyl group includes sulfosalicylic acid or 8-hydroxyquinoline-5-sulfonic acid; the complexing agent containing phosphoric acid group includes pyrophosphoric acid, tripolyphosphoric acid, hexametapolyphosphoric acid, polyphosphoric acid, sodium pyrophosphate, sodium hexametapolyphosphate or ammonium polyphosphate; the complexing agent containing organic phosphine includes potassium diethylenetriamine penta (methylene phosphonate) or sodium ethylenediamine tetra (methylene phosphonate); the complexing agent containing carbonyl group includes carboxylic acid and its salt, anhydride, ester, amide, polycarboxylic acid or polyanhydride; the complexing agent containing carbonyl group includes The complexing agent includes gluconic acid, oxalic acid, tartaric acid, malic acid, oxaloacetic acid, fumaric acid, maleic acid, citric acid, nitrilotriacetic acid, diethylenetriamine pentacarboxylic acid, alginic acid, glutamic acid, aspartic acid, ornithine, lysine, 1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, potassium citrate, calcium citrate, glyceryl citrate, acetylsalicylic acid, sulfosalicylamide, polyaspartic acid, polyglutamic acid, polyornithine, polylysine or polymaleic anhydride; the complexing agent containing a hydroxamic acid group includes deferoxamine.

[0027] In some embodiments, the degradable polymer comprises at least one of a degradable polyester, a degradable polyanhydride, a degradable polyamino acid, and a binary or multinary degradable copolymer formed by copolymerization of monomers of degradable polyester, degradable polyamino acid and / or degradable polyanhydride, wherein:

[0028] The degradable polyester includes at least one of polylactic acid, polyglycolic acid, polylactic glycolic acid, polycaprolactone, polyhydroxyalkanoate, polyacrylate, polysuccinate, poly(β-hydroxybutyrate), polyethylene adipate, polysalicylic anhydride, polytrimethylene carbonate, polydioxane, poly(β-alkanoate), and polyhydroxybutyrate valerate copolymer.

[0029] The degradable polyanhydride includes at least one of poly 1,3-bis(p-carboxyphenoxy)propane-sebacic acid, poly erucic acid dimer-sebacic acid or poly fumaric acid-sebacic acid, polyoxalic anhydride, polysuccinic anhydride, polyadipic anhydride, polysebacic anhydride, polydodecanoic anhydride, polycitric anhydride, polymalic anhydride, polysuccinic anhydride, polytartaric anhydride, polyitaconic anhydride and polymaleic anhydride.

[0030] The degradable polyamino acid includes at least one of polyglycine, polyalanine, polyvaline, polyleucine, polyisoleucine, polymethionine, polyproline, polytryptophan, polyserine, polytyrosine, polycysteine, polyphenylalanine, polyasparagine, polyglutamine, polythreonine, polyarginine, polyhistidine, polyselenocysteine, polypyrroline, polyglutamic acid, polyaspartic acid, polyornithine, polylysine and derivatives thereof.

[0031] In some embodiments, the at least one degradable polymer layer is mixed with an active drug, and the active drug includes at least one of an anti-angiogenesis drug, an anti-platelet drug, an anti-thrombotic drug, an anti-inflammatory drug and an anti-allergic drug; the anti-angiogenesis drug includes at least one of paclitaxel, sirolimus, rapamycin and its derivatives; the anti-platelet drug includes cilostazol; the anti-thrombotic drug includes heparin; the anti-inflammatory drug includes dexamethasone; the anti-allergic drug includes at least one of diphenhydramine, chlorpheniramine, promethazine, hydrocortisone, triamcinolone acetonide, methylprednisolone, loratadine, fexofenadine, levocetirizine, mizolastine and ebastine.

[0032] In some embodiments, the corrosion expansion ratio of the iron-based substrate during the corrosion process is ≥1.5; the corrosion expansion ratio of the iron-based substrate during the corrosion process is ≥2.

[0033] In some embodiments, the iron-based matrix is ​​pure iron or an iron alloy, wherein the iron content of the iron alloy is ≥ 95%, and the iron alloy is nitrided iron.

[0034] In some embodiments, the absorbable implantable medical device includes a luminal stent, an occluder, a gasket, an artificial blood vessel, a dental implant, a vascular clip, a dental implant, a suture, a gynecological implant, a men's implant, a respiratory implant, or an orthopedic implant.

[0035] In some embodiments, the luminal stent comprises a vascular stent, a biliary stent, an esophageal stent, a urethral stent, an intestinal stent, or an airway stent.

[0036] The absorbable implantable medical device of the present invention basically does not corrode or corrodes at a relatively slow rate within 1 to 6 months after being implanted in the body, thereby ensuring that the device can maintain sufficient mechanical properties during the healing process of the lesion site; and after the lesion site is healed, the device can be rapidly degraded and absorbed, meeting the clinical requirements for the degradation performance of degradable devices. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 is a schematic cross-sectional view of an absorbable implantable medical device according to one embodiment;

[0038] Figure 2 Schematic diagram of the outer surface of an absorbable implantable medical device according to one embodiment, wherein a degradable polymer layer covers a portion of the surface of an inert protective layer;

[0039] Figure 3 is a schematic cross-sectional view of an absorbable implantable medical device according to another embodiment;

[0040] Figure 4 is a schematic cross-sectional view of another embodiment of an absorbable implantable medical device;

[0041] Figure 5 Schematic diagram of a degradable polymer layer partially covering the surface of an iron-based substrate in an absorbable implantable medical device according to one embodiment. DETAILED DESCRIPTION

[0042] The following are only preferred embodiments of the present invention. The protection of the present invention is not limited to the following preferred embodiments. For example, the embodiments are all described with vascular stents as examples, but this does not mean that the technical solution of the present invention is only applicable to vascular stents. It can also be applied to other implantable medical devices. It should be pointed out that for those skilled in the art, several variations and improvements made on the basis of this invention concept are within the scope of protection of the present invention. The reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0043] like Figures 1 to 5As shown, the present invention provides an absorbable implantable medical device 100, comprising an iron-based substrate 110 and a degradable polymer layer provided on the surface of the iron-based substrate 110, wherein the degradable polymer layer comprises a degradable polymer, and the medical device further comprises an inert protective layer 120 provided on the entire surface of the iron-based substrate 110.

[0044] The present invention provides an inert protective layer 120 on the entire surface of the iron-based matrix 110. During the 1 to 6 months after the iron-based matrix 110 is implanted in the body, the film formed by the inert protective layer can reduce or avoid the contact between the iron-based matrix and the external environment (such as the external physiological environment or the environment in which the substances produced by the degradation of the degradable polymer are located), thereby slowing down the early corrosion rate of the iron-based matrix, thereby ensuring that the absorbable implantable medical device has sufficient mechanical properties within 1 to 6 months of implantation. Furthermore, the present invention controls the thickness of the inert protective layer on the surface of the iron-based matrix so that the inert protective layer gradually disintegrates after the lesion site heals, exposing the iron-based matrix to the external environment (such as the physiological environment in the body or the environment in which the substances produced by the degradation of the degradable polymer are located), thereby accelerating the corrosion rate of the iron-based matrix. Therefore, the absorbable implantable medical device of the present invention can meet the clinical requirements for the early mechanical properties of the device and the corrosion / degradation performance after implantation.

[0045] It should be noted that the “disintegration” mentioned in the present invention refers to the complete disintegration of the film layer formed by the inert protective layer. At this time, the inert protective layer is no longer attached to the surface of the iron-based substrate.

[0046] It is understandable that the inert protective layer 120 can directly or indirectly cover the entire surface of the iron-based substrate 110. When the inert protective layer 120 indirectly covers the entire surface of the iron-based substrate 110, other coatings, such as a degradable polymer layer, are provided between the inert protective layer 120 and the iron-based substrate 110. In the present invention, the iron-based substrate is entirely wrapped by the inert protective layer. If a portion of the iron-based substrate 110 is not directly or indirectly covered by the inert protective layer, that is, if the iron-based substrate 110 is not entirely wrapped by the inert protective layer 120, the iron-based substrate 110 will first corrode and break from the unwrapped area, thereby easily causing adverse reactions such as thrombosis.

[0047] In some embodiments, the inert protective layer includes an inert compound. In the present invention, the inert compound in the inert protective layer is basically non-corrosive or its corrosion rate is much lower than the corrosion rate of the iron-based matrix. Therefore, the present invention adds an inert protective layer on the iron-based matrix. The inert protective layer not only has a lower corrosion rate, but also can form a film and directly or indirectly cover the entire surface of the iron-based matrix, thereby reducing or avoiding the contact between the iron-based matrix and the external environment (such as the external physiological environment or the environment where the substances produced by the degradation of degradable polymers are located), thereby slowing down the early corrosion rate of the iron-based matrix, and then ensuring that the absorbable iron-based implantable medical device has sufficient mechanical properties within the early 1 to 6 months.

[0048] Furthermore, the in vitro immersion corrosion rate of the inert protective layer of the present invention is ≤2.0 mm / y; further, the in vitro immersion corrosion rate of the inert protective layer of the present invention is ≤1.0 mm / y; further; the in vitro immersion corrosion rate of the inert protective layer of the present invention is ≤0.8 mm / y; further, the in vitro immersion corrosion rate of the inert protective layer of the present invention is ≤0.5 mm / y. In the present invention, if the corrosion rate of the inert protective layer is too fast, after the device is implanted in the body, as the inert protective layer gradually degrades, the thickness of the coating gradually becomes thinner or some pores / holes that do not cover the iron-based matrix gradually appear in the coating, that is, the iron-based matrix is ​​gradually exposed. In this case, the inert protective layer cannot effectively regulate the early corrosion rate of the iron-based matrix, and thus cannot ensure that the absorbable iron-based implantable device has sufficient mechanical properties in the early 1 to 6 months.

[0049] In some embodiments of the present invention, the water permeability of the inert protective layer is 1*10 -13 ~1*10 -2 g·mm / (m 2 h). Furthermore, the water permeability of the inert protective layer is 1*10 -10 ~1*10 -2 g·mm / (m 2 ·h); In other embodiments, the water permeability of the inert protective layer is 1*10 -13 g·mm / (m 2 h)~1*10 -3 g·mm / (m 2 ·h); further, the water permeability of the inert protective layer is 1*10 -8 ~1*10 -2 g·mm / (m 2 ·h); Furthermore, the water permeability of the inert protective layer is 1*10 -6 ~1*10 -2 g·mm / (m 2h). The water permeability of the inert protective layer directly affects the contact between the iron-based substrate and physiological fluids in the external environment, and therefore directly affects the corrosion rate of the iron-based substrate. If the water permeability of the inert protective layer is too low, the degradation rate of the iron-based substrate is very slow. The iron-based substrate expands slightly during the corrosion process, making it difficult for the inert polymer coating to disintegrate, which in turn affects the rapid degradation of the iron-based substrate later. If the water permeability of the inert protective layer is too high, the iron-based substrate degrades too quickly, and the absorbable iron-based implantable device cannot maintain adequate mechanical properties in the first 1 to 6 months.

[0050] In some embodiments, the thickness of the inert protective layer 120 is 0.02 μm to 6 μm. The thickness of the inert protective layer not only directly affects its own mechanical properties and water permeability, but also directly affects the mechanical properties of the device in the early stage of implantation and the corrosion / degradation performance in the later stage. If the thickness of the inert protective layer 120 is too thin and the inert protective layer has a large porosity, it cannot effectively reduce or avoid the contact between the iron-based matrix and the external environment (such as the external physiological environment or the environment of substances produced by the degradation of degradable polymers). At this time, the iron-based matrix 120 will corrode too quickly, resulting in insufficient mechanical properties in the early stage of device implantation. If the thickness of the inert protective layer 120 is too thick, on the one hand, the absorbable implantable medical device (such as a stent) may easily cause the inert protective layer to rupture during the expansion or compression process and expose the iron-based matrix to the external environment, causing the part of the device implanted in the body that is not covered by the inert protective layer to degrade first, thereby causing local fracture of the device. In this case, the part of the device that is broken may easily puncture the blood vessel wall and cause thrombosis; on the other hand, because the inert protective layer is too thick, after the lesion heals, the corrosion expansion of the iron-based matrix cannot effectively disintegrate the inert protective layer 120, resulting in the iron-based matrix being unable to fully contact the external environment (such as external physiological solutions or acidic substances produced by the degradation of degradable polymers), and thus unable to achieve faster corrosion in the later stage.

[0051] In some embodiments, the thickness of the inert protective layer 120 is [0.02, 0.1) μm, (0.1, 1) μm, or (1, 6] μm. In other embodiments, the thickness of the inert protective layer 120 is 0.02 μm to 0.098 μm, 0.12 μm to 0.98 μm, or 1.1 μm to 6 μm; in still other embodiments, the thickness of the inert protective layer 120 is 0.025 μm to 0.08 μm, 0.15 μm to 0.9 μm, or 1.1 μm to 6 μm. In a specific example, the thickness of the inert protective layer 120 can be 20 nm, 30nm, 40nm, 50nm, 65nm, 70nm, 85nm, 95nm, 150nm, 200nm, 225nm, 275nm, 300nm, 350nm, 400nm, 450nm, 500nm, 550nm, 6 00nm, 800nm, 1.2μm, 1.5μm, 2μm, 2.4μm, 2.8μm, 3μm, 3.2μm, 3.6μm, 3.8μm, 4μm, 4.2μm, 4.5μm, 4.8μm, 5.1μm, 5.5μm or 6μm.

[0052] It should be noted that the thickness of the inert protective layer in this application refers to the average thickness. The thickness of the inert protective layer over the entire surface of the iron-based substrate can be uniform or uneven. If the thickness is uneven, that is, the thickness of the inert protective layer in some areas is slightly thicker than that in other areas, the thickness of the inert protective layer in this application refers to the average thickness.

[0053] In some embodiments, the inert compound includes at least one of magnesium stearate, parylene, polyethylene, polyvinyl chloride, polyacrylate, polyethyl acrylate, polymethacrylate, polyethyl acrylate, polymethyl methacrylate, polymethyl acrylate, polytetrafluoroethylene, polyamide, polyamideimide, polyetherimide, polyethersulfone, poly(iso)butylene, polyvinyl fluoride, polyvinyl alcohol, polyurethane, polybutylene terephthalate, silicone, polyphosphazene, styrene, and derivatives thereof. The derivative refers to a derivative formed from any of the above polymers, including copolymers formed from monomers corresponding to any one or more of the above polymers and other monomers, and also includes copolymers or mixtures of copolymers formed from monomers corresponding to any of the above polymers. For example, in some embodiments of the present invention, the inert compound includes at least one of magnesium stearate, parylene, polyethylene, polyvinyl chloride, polyacrylate, polyethyl acrylate, polymethacrylate, polyethyl acrylate, polymethyl methacrylate, polymethyl acrylate, polytetrafluoroethylene, polyamide, polyamideimide, polyetherimide, polyethersulfone, poly(iso)butylene, polyvinyl fluoride, polyvinyl alcohol, polyurethane, polybutylene terephthalate, silicone, polyphosphazene, and styrene; in other embodiments of the present invention, the inert compound includes hard Copolymers formed by monomers corresponding to any one or more of the following polymers: magnesium stearate, parylene, polyethylene, polyvinyl chloride, polyacrylate, polyethyl acrylate, polymethacrylate, polyethyl acrylate, polymethyl methacrylate, polymethyl acrylate, polytetrafluoroethylene, polyamide, polyamideimide, polyetherimide, polyethersulfone, poly(iso)butylene, polyvinyl fluoride, polyvinyl alcohol, polyurethane, polybutylene terephthalate, silicone, polyphosphazene, styrene, and any other monomers; In some other embodiments of the present invention, the inert compound comprises The present invention also includes a copolymer or a mixture of copolymers formed by monomers corresponding to any one or more of magnesium stearate, parylene, polyethylene, polyvinyl chloride, polyacrylate, polyethyl acrylate, polymethacrylate, polyethyl acrylate, polymethyl methacrylate, polymethyl acrylate, polytetrafluoroethylene, polyamide, polyamideimide, polyetherimide, polyethersulfone, poly(iso)butylene, polyvinyl fluoride, polyvinyl alcohol, polyurethane, polybutylene terephthalate, silicone, polyphosphazene, and styrene; in some embodiments of the present invention, the inert compound The polymer includes a copolymer or copolymer mixture formed by at least one of magnesium stearate, parylene, polyethylene, polyvinyl chloride, polyacrylate, polyethyl acrylate, polymethacrylate, polyethyl acrylate, polymethyl methacrylate, polymethyl acrylate, polytetrafluoroethylene, polyamide, polyamideimide, polyetherimide, polyethersulfone, poly(iso)butylene, polyvinyl fluoride, polyvinyl alcohol, polyurethane, polybutylene terephthalate, silicone, polyphosphazene, and styrene and a monomer corresponding to any one or more of the above polymers and any other monomer.

[0054] Selecting the right material allows the inert protective layer to more effectively regulate the mechanical properties of iron-based devices in the early stages of implantation and their corrosion / degradation properties later in life. By selecting the aforementioned materials and adopting an appropriate thickness, the inert protective layer of the present invention not only slows the corrosion rate of the iron-based substrate in the early stages but also, in conjunction with the degradable polymer layer, regulates the corrosion of the iron-based substrate later in life, thereby enabling the iron-based substrate to corrode and degrade rapidly.

[0055] In some embodiments, the parylene may include at least one of parylene N, parylene C, parylene D, parylene F, and parylene HT.

[0056] See also Figure 1 In certain embodiments of the present invention, the degradable polymer layer includes at least one degradable polymer layer 130, and the degradable polymer layer 130 covers at least a portion of the surface of the inert protective layer 120. The degradable polymer layer 130 of the present invention can control the release of the drug. Furthermore, after the lesion has healed, the acidic substances produced by the degradation of the degradable polymer layer 130 can accelerate the corrosion of the iron-based substrate, thereby shortening the corrosion cycle of the iron-based substrate. This allows the absorbable implantable medical device of the present invention to meet clinical requirements for the late-stage degradation performance of absorbable devices.

[0057] It is understood that the degradable polymer layer 130 covers the entire surface or a portion of the surface of the inert protective layer 120. Figure 2 This is an embodiment in which the degradable polymer layer 130 covers a portion of the surface of the inert protective layer 120 .

[0058] It should be noted that the surface of the present invention includes the outer surface, inner surface and side surface. The inert protective layer 120 covering the entire surface of the iron-based substrate 110 means that the inert protective layer 120 completely covers the inner surface, outer surface and side surface of the iron-based substrate.

[0059] In some embodiments, the weight-average molecular weight of the degradable polymer in the degradable polymer layer 130 is between 5 kDa and 1000 kDa. The molecular weight affects the degradation rate of the degradable polymer and the drug release rate. By controlling the weight-average molecular weight of the degradable polymer in the degradable polymer layer 130 within this range, the degradable polymer layer 130 can effectively control drug release and, at a later stage, control corrosion of the iron-based substrate, thereby allowing the iron-based substrate to rapidly corrode and degrade after the lesion has healed.

[0060] In some embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer 130 is 20 kDa to 800 kDa; in other embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer 130 is 50 kDa to 800 kDa; in still other embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer 130 is 100 kDa to 600 kDa; in still other embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer 130 is 200 kDa to 500 kDa.

[0061] In some embodiments of the present invention, the number of layers of the degradable polymer layer 130 is one or more. When the number of layers of the degradable polymer layer 130 is one, the polymer in the degradable polymer layer 130 is a mixture of polymers with different molecular weights, or a polymer with a specific molecular weight.

[0062] See also Figure 3 In some embodiments of the present invention, the degradable polymer layer 130 comprises multiple layers, including both a macromolecular degradable polymer layer 131 and a drug-loaded small molecule degradable polymer layer 132. The multi-layered structure of the degradable polymer layer 130 effectively controls drug release while also controlling corrosion of the iron-based substrate in the later stages, thereby enabling the iron-based substrate to corrode and degrade rapidly.

[0063] In some embodiments, the thickness of the degradable polymer layer 130 is 0.5 μm to 100 μm. In other embodiments, the thickness of the degradable polymer layer 130 is 1 μm to 90 μm; in yet other embodiments, the thickness of the degradable polymer layer 130 is 5 μm to 70 μm; and in yet other embodiments, the thickness of the degradable polymer layer 130 is 15 μm to 60 μm. The thickness of the degradable polymer layer 130 will affect the drug release and the corrosion of the iron-based matrix in the later stage. The thickness of the degradable polymer layer 130 of the present invention is controlled within this range, which can more effectively control the drug release, so that the drug in the coating can meet the requirements of both the release cycle and the release rate. At the same time, it can also effectively regulate the corrosion of the iron-based matrix in the later stage, thereby allowing the iron-based matrix to corrode and degrade rapidly after the lesion site heals. The present application can more effectively regulate the corrosion rate of absorbable implantable medical devices by simultaneously regulating the thickness of the inert protective layer, the thickness of the degradable polymer layer, and the molecular weight parameters, thereby meeting the clinical requirements for the early mechanical properties of the device and the corrosion / degradation performance after implantation.

[0064] See also Figure 4In certain embodiments of the present invention, the degradable polymer layer includes at least one degradable polymer layer 140 located outside the inert protective layer 120 and at least one degradable polymer layer 150 located inside. The outer degradable polymer layer 140 can be loaded with drugs and control drug release. During the 1-6 months after the device is implanted, the inert protective layer 120 can reduce or prevent the inner degradable polymer layer 150 and the iron-based matrix 110 from contacting the external environment (such as the external physiological environment or an environment containing acidic substances produced by degradation of the degradable polymer), thereby simultaneously delaying the early degradation of the inner degradable polymer layer 150 and the iron-based matrix 110. At a later stage, as the internal iron-based matrix and degradable polymer layer 150 degrade and expand in volume, the inert protective layer 120 disintegrates. At this time, the degradation of a large amount of degradable polymer in the inner degradable polymer layer 150 and the production of its degradation products can effectively accelerate the corrosion of the iron-based matrix.

[0065] It can be understood that the degradable polymer layer 150 located on the inner side covers at least part of the surface of the iron-based substrate 110; the inert protective layer 120 completely wraps the degradable polymer layer 150 and the iron-based substrate 110, and the degradable polymer layer 140 located on the outer side covers at least part of the surface of the inert protective layer 120.

[0066] It is understood that the degradable polymer layer 150 located on the inner side can cover the entire surface or part of the surface of the iron-based substrate 110. The degradable polymer layer 140 located on the outer side can cover the entire surface or part of the surface of the inert protective layer 120. Those skilled in the art can adopt appropriate covering methods as needed. Figure 5 This is an embodiment in which the degradable polymer layer 150 covers a portion of the surface of the iron-based substrate 110 .

[0067] In some embodiments, the weight-average molecular weight of the degradable polymer in the inner degradable polymer layer 150 is greater than the weight-average molecular weight of the degradable polymer in the outer degradable polymer layer 140, and the weight-average molecular weight of the degradable polymer in the inner degradable polymer layer 150 is at least five times the weight-average molecular weight of the degradable polymer in the outer degradable polymer layer 140. By controlling the multiple difference in the weight-average molecular weight of the degradable polymers in the inner and outer degradable polymer layers of the inert protective layer 120 within this range, the present invention can not only enable the smaller molecular weight degradable polymer layer 140 to effectively control drug release, but also ensure that the larger molecular weight degradable polymer layer 150 can effectively control the corrosion of the iron-based substrate after the lesion has healed, thereby allowing the iron-based substrate to corrode and degrade rapidly.

[0068] In some embodiments, the weight average molecular weight of the degradable polymer in the inner degradable polymer layer 150 is 5 to 20 times the weight average molecular weight of the degradable polymer in the outer degradable polymer layer 140. In other embodiments, the weight average molecular weight of the degradable polymer in the inner degradable polymer layer 150 is 8 to 16 times the weight average molecular weight of the degradable polymer in the outer degradable polymer layer 140.

[0069] In some embodiments, the weight-average molecular weight of the degradable polymer in the degradable polymer layer 150 is between 25 kDa and 700 kDa. Molecular weight affects the rate of polymer degradation. By controlling the weight-average molecular weight of the degradable polymer in the degradable polymer layer 150 within the aforementioned range, the present invention can coordinate with the iron-based matrix to disintegrate the inert protective layer 120 within a suitable timeframe, ensuring that the degradable polymer layer 150 effectively regulates corrosion of the iron-based matrix after the lesion has healed.

[0070] In some embodiments, the weight average molecular weight of the degradable polymer in the degradable polymer layer 140 is 5 kDa to 100 kDa. A suitable molecular weight can enable the degradable polymer layer 140 to more effectively control the release of drugs.

[0071] In some embodiments, the thickness of the degradable polymer layer 150 is between 0.5 μm and 20 μm. In other embodiments, the thickness of the degradable polymer layer 150 is between 4 μm and 18 μm. In yet other embodiments, the thickness of the degradable polymer layer 150 is between 5 μm and 18 μm. The present invention controls the thickness of the degradable polymer layer 150 within this range. This, in conjunction with the inert protective layer 120, ensures that the degradable polymer layer 150 effectively regulates corrosion of the iron-based substrate after the lesion has healed. If the degradable polymer layer 150 is too thin, its degradation cycle is too short. This can, on the one hand, lead to corrosion of the iron-based substrate, thereby affecting the early mechanical properties of the device. On the other hand, its premature degradation prevents the iron-based substrate from rapidly corroding due to a failure to provide an effective acidic environment after the lesion has healed. If the degradable polymer layer 150 is too thick, its degradation cycle is too long, making it difficult for the iron-based substrate to corrode and degrade rapidly even after the lesion has healed.

[0072] In some embodiments, the thickness of the degradable polymer layer 140 is 1 μm to 10 μm. In other embodiments, the thickness of the degradable polymer layer 140 is 2 μm to 7 μm. In still other embodiments, the thickness of the degradable polymer layer 140 is 3 μm to 6 μm. The thickness of the degradable polymer layer 140 of the present invention within this range can effectively control drug release.

[0073] It is understood that the number of layers of the degradable polymer layer 150 and the degradable polymer layer 140 can be one or more. When the number of layers of the degradable polymer layer 140 is multiple, it can contain a drug-loaded layer and a pure degradable polymer layer.

[0074] In some embodiments, the medical device further comprises a complexing agent layer (not shown) disposed on at least a portion of the surface of the iron-based substrate, and the complexing agent layer is located inside the inert protective layer, and the complexing agent layer comprises a complexing agent.

[0075] When medical devices are implanted in the body, the iron-based matrix corrodes and generates Fe 3+ and / or Fe 2+ As well as solid corrosion products (Fe(OH)2, Fe(OH)3, etc.), the complexing agent reacts with metal ions or solid corrosion products under physiological conditions to form water-soluble coordination compounds. This reduces the concentration of free metal ions and the insoluble solid corrosion products generated by metal matrix corrosion, allowing the corrosion products to be rapidly absorbed and metabolized by tissues. This not only facilitates the recovery of the lesion site but also reduces the possibility of adverse reactions caused by the long-term retention of corrosion products in the human body. Furthermore, the inert protective layer located outside the complexing agent layer can slow the early release rate of the complexing agent, making it more compatible with the release rate of metal ions, thereby enhancing the complexing effect.

[0076] In some embodiments, the complexing agent layer further comprises a polymer carrier, which comprises a degradable polymer. The degradation of the polymer is utilized to adjust the pH value, enhance the complexing ability of the complexing agent, and regulate the degradation rate of the corrosive substrate. The degradable polymer can be made of the same material as described above for the degradable polymer layer, and further details are omitted here.

[0077] In some embodiments, when the degradable polymer layer includes at least one degradable polymer layer 150 located inside the inert protective layer 120, the complexing agent layer and the degradable polymer layer 150 may be the same layer, i.e., the polymer layer 150 contains a complexing agent. In other embodiments, the degradable polymer layer 150 and the complexing agent layer may be different layers. In this case, the positions of the degradable polymer layer 150 and the complexing agent layer are not limited. The degradable polymer layer 150 may be located between the iron-based substrate 110 and the complexing agent layer, or between the complexing agent layer and the inert protective layer 120, or the degradable polymer layer 150 and the complexing agent layer may be alternately distributed between the iron-based substrate 110 and the inert protective layer 120.

[0078] In some embodiments, the mass ratio of the complexing agent to the polymer carrier is (0.2-1.5):1; by adjusting the mass ratio of the complexing agent to the polymer carrier within an appropriate range, the complexing ability of the complexing agent can be effectively enhanced and the degradation rate of the corrodible substrate can be adjusted.

[0079] In some embodiments, the thickness of the complexing agent layer is 0.05 μm to 10 μm; further, the thickness of the complexing agent layer is 0.5 μm to 10 μm; further, the thickness of the complexing agent layer is 0.5 μm to 8 μm; further, the thickness of the complexing agent layer is 0.5 μm to 6 μm; further, the thickness of the complexing agent layer is 2 μm to 8 μm; further, the thickness of the complexing agent layer is 3 μm to 6 μm. It is understood that the number of complexing agent layers can be one or more.

[0080] In some embodiments, the complexing agent contains at least one ligand, that is, the complexing agent can be a monodentate ligand and / or a polydentate ligand, wherein the monodentate ligand contains a single ligand and the polydentate ligand contains at least two ligands.

[0081] In some embodiments, the coordinating group includes at least one of a hydroxyl group, a thiol group, an amine group, an aromatic heterocyclic group, a nitroso group, a carbonyl group, a sulfonate group, a phosphate group, a hydroxamic acid group or an organic phosphine group and a hydroxamic acid-containing group on a condensed aromatic hydrocarbon.

[0082] In some embodiments, the hydroxyl group on the condensed aromatic hydrocarbon includes a phenolic hydroxyl group; the aromatic heterocyclic group includes at least one of a furyl group, a pyrrolyl group, an imidazolyl group, a triazolyl group, a thienyl group, a thiazolyl group, a pyridyl group, a pyridonyl group, a pyranyl group, a pyrone group, a pyrimidinyl group, a pyridazinyl group, a pyrazinyl group, a quinolyl group, an isoquinolyl group, a phthalazinyl group, a pteridinyl group, an indolyl group, a purinyl group, or a phenanthroline group.

[0083] In some embodiments, the monodentate ligand includes gluconic acid, glucoheptonic acid, glycolic acid, and derivatives or salts thereof. The multidentate ligand containing a hydroxyl group on a condensed aromatic hydrocarbon includes 8-hydroxyquinoline, 8-hydroxyquinaldine, 4,5-dihydroxybenzene-1,3-disulfonic acid sodium, 4-[3,5-di-hydroxyphenyl-1H-1,2,4-triazole]-benzoic acid, 1-(2-pyridylazo)-2-naphthol; the multidentate ligand containing a thiol group includes 8-mercaptoquinoline, thioglycolic acid, dimercaptopropanol, 5-methyl-2-mercaptobenzoic acid methyl ester; the multidentate ligand containing an amine group includes ethylenediamine, triethylenetetramine, ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid tetrasodium, triethylenetetramine, N-(2-hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid or N'-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]hydroxylamine]pentyl]-N-(5-aminopentyl)-N-hydroxysuccinamide; polydentate ligands containing aromatic heterocyclic groups include o-phenanthroline, bipyridine, porphyrin, porphine, chlorophyll, hemoglobin or 1,2-dimethyl-3-hydroxy-4-pyridone; polydentate ligands containing nitroso groups include 1-nitroso-2 -naphthol or sodium 1-nitroso-2-naphthol-6-sulfonate; multidentate ligands containing sulfonyl groups include sulfosalicylic acid or 8-hydroxyquinoline-5-sulfonic acid; multidentate ligands containing phosphoric acid groups include pyrophosphate, tripolyphosphate, hexametapolyphosphate, polyphosphoric acid, sodium pyrophosphate, sodium hexametapolyphosphate or ammonium polyphosphate; multidentate ligands containing organic phosphine groups include potassium diethylenetriamine penta (methylene phosphonate) or sodium ethylenediamine tetra (methylene phosphonate); multidentate ligands containing carbonyl groups include carboxylic acids and their salts, anhydrides, esters, amides, polycarboxylic acids or polyanhydrides; multidentate ligands containing carbonyl groups include carboxylic acids and their salts, anhydrides, esters, amides, polycarboxylic acids or polyanhydrides; The ligands include gluconic acid, oxalic acid, tartaric acid, malic acid, oxaloacetic acid, fumaric acid, maleic acid, citric acid, nitrilotriacetic acid, diethylenetriamine pentacarboxylic acid, alginic acid, glutamic acid, aspartic acid, ornithine, lysine, 1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, potassium citrate, calcium citrate, glyceryl citrate, acetylsalicylic acid, sulfosalicylamide, polyaspartic acid, polyglutamic acid, polyornithine, polylysine or polymaleic anhydride; the multidentate ligand containing a hydroxamic acid group includes deferoxamine.

[0084] In some embodiments, the above-mentioned degradable polymer includes at least one of degradable polyester, degradable polyanhydride, degradable polyamino acid, and binary or multi-component degradable copolymers formed by copolymerization of monomers of degradable polyester, degradable polyamino acid and / or degradable polyanhydride.

[0085] Among them, the degradable polyester includes at least one of polylactic acid, polyglycolic acid, polylactic glycolic acid, polycaprolactone, polyhydroxyalkanoate, polyacrylate, polysuccinate, poly(β-hydroxybutyrate), polyethylene adipate, polysalicylic anhydride, polytrimethylene carbonate, polydioxane, poly(β-alkanoate), and polyhydroxybutyrate valerate copolymer. In some embodiments, the degradable polyester can also be a physical mixture of at least two of polylactic acid, polyglycolic acid, polylactic glycolic acid, polycaprolactone, polyhydroxyalkanoate, polyacrylate, polysuccinate, poly(β-hydroxybutyrate), polyethylene adipate, polysalicylic anhydride, polytrimethylene carbonate, polydioxanone, poly(β-alkanoate), and polyhydroxybutyrate valerate copolymers; the degradable polyester can also be a copolymer formed by copolymerizing at least two of the monomers that form polylactic acid, polyglycolic acid, polysuccinate, poly(β-hydroxybutyrate), polycaprolactone, polyethylene adipate, polysalicylic anhydride, polytrimethylene carbonate, polydioxanone, poly(β-alkanoate), polylactic acid-glycolic acid copolymer and polyhydroxybutyrate valerate copolymer.

[0086] The degradable polyanhydride includes at least one of poly 1,3-bis(p-carboxyphenoxy)propane-sebacic acid, poly erucic acid dimer-sebacic acid or poly fumaric acid-sebacic acid, polyoxalic anhydride, polysuccinic anhydride, polyadipic anhydride, polysebacic anhydride, polydodecanoic anhydride, polycitric anhydride, polymalic anhydride, polysuccinic anhydride, polytartaric anhydride, polyitaconic anhydride and polymaleic anhydride;

[0087] The degradable polyamino acid includes at least one of polyglycine, polyalanine, polyvaline, polyleucine, polyisoleucine, polymethionine, polyproline, polytryptophan, polyserine, polytyrosine, polycysteine, polyphenylalanine, polyasparagine, polyglutamine, polythreonine, polyarginine, polyhistidine, polyselenocysteine, polypyrroline, polyglutamic acid, polyaspartic acid, polyornithine, polylysine and derivatives thereof.

[0088] In some embodiments, at least one degradable polymer layer is mixed with an active drug.

[0089] In some embodiments, at least one degradable polymer layer 130 is mixed with an active drug.

[0090] In some embodiments, at least one degradable polymer layer 140 is mixed with an active drug.

[0091] In some embodiments, the active drug includes at least one of angiogenesis inhibitors, antiplatelet drugs, antithrombotic drugs, anti-inflammatory drugs and anti-allergic drugs; the angiogenesis inhibitors include at least one of paclitaxel, sirolimus, rapamycin and their derivatives; the antiplatelet drugs include cilostazol; the antithrombotic drugs include heparin; the anti-inflammatory drugs include dexamethasone; the anti-allergic drugs include at least one of diphenhydramine, chlorpheniramine, promethazine, hydrocortisone, triamcinolone acetonide, methylprednisolone, loratadine, fexofenadine, levocetirizine, mizolastine and ebastine.

[0092] In some embodiments, the inert protective layer 120 is not mixed with an active pharmaceutical ingredient.

[0093] In some embodiments, the corrosion expansion rate of the iron-based substrate 110 during corrosion is ≥ 1.5; in other embodiments, the corrosion expansion rate of the iron-based substrate during corrosion is ≥ 2; in still other embodiments, the corrosion expansion rate of the iron-based substrate during corrosion is 2-8; and in still other embodiments, the corrosion expansion rate of the iron-based substrate during corrosion is 3-6. The volume expansion of the iron-based substrate during corrosion exerts an outward expansion force on the inert protective layer. When the corrosion expansion rate of the iron-based substrate reaches a certain value, the entire inert protective layer may be ruptured, causing it to completely disintegrate, thereby exposing the entire structure enclosed by the inert protective layer to the external environment. However, if the corrosion expansion rate of the iron-based matrix during the corrosion process is too low, it will not be enough to break through the entire inert protective layer; if the corrosion expansion rate of the iron-based matrix during the corrosion process is too high, it will cause other problems. For example, when the iron-based device is a vascular stent, if the expanded stent rod accounts for a large proportion in the radial direction of the entire blood vessel, it will significantly affect the dynamics of local blood flow through the stent rod, causing blood to more easily adhere to and deposit on the stent rod, thereby increasing the risk of thrombosis in the stent.

[0094] In some embodiments, the iron-based substrate 110 is a degradable iron-based substrate, such as degradable pure iron or an iron alloy, wherein the carbon content of the iron alloy is not greater than 2.11 wt.%, wherein the purity of the pure iron is not less than 99.5 wt.%. The alloying elements in the iron alloy are selected from at least one of carbon, nitrogen, phosphorus, silicon, sulfur, boron, cobalt, tungsten, manganese, tin, magnesium, zinc, zirconium, calcium, titanium, copper, gold, silver, platinum, and palladium. In some embodiments of the present invention, the iron content of the iron alloy is ≥ 95%; further, the iron content of the iron alloy is ≥ 97%.

[0095] In one embodiment, the iron alloys of the present invention include but are not limited to nitrided iron, iron-manganese alloys, iron-zinc alloys, iron-magnesium alloys, iron-calcium alloys, iron-zirconium alloys, iron-manganese-carbon alloys, iron-molybdenum alloys, iron-manganese-copper alloys, iron-manganese-silicon-carbon alloys, iron-silicon-manganese alloys, iron-copper alloys, iron-copper-manganese-carbon alloys, iron-gold alloys, iron-silver alloys, iron-manganese-silver alloys, iron-hydrogen alloys, iron-phosphorus alloys, iron-sulfur alloys, iron-boron alloys, iron-titanium alloys, and iron-titanium-carbon alloys.

[0096] In one embodiment, the nitrogen content in the nitrided iron is 0.01 to 0.25 wt.%.

[0097] In some embodiments, the absorbable implantable medical device 100 can be a luminal stent, an occluder, a gasket, an artificial blood vessel, a dental implant, a vascular clip, a dental implant, a suture, a gynecological implant, a men's implant, a respiratory implant, or an orthopedic implant.

[0098] In some embodiments, the luminal stent can be a vascular stent, a biliary stent, an esophageal stent, a urethral stent, an intestinal stent, or an airway stent. In some embodiments, the vascular stent includes stents used in all blood vessels, including but not limited to heart valve stents, coronary stents, pulmonary artery stents, covered stents, peripheral stents, vertebral artery stents, and renal artery stents. In some embodiments, the orthopedic implant includes at least one of a bone screw, a bone plate, a joint, an intramedullary nail, an anchor, a bolt, and an intervertebral fusion cage.

[0099] Test Method

[0100] 1. Inert protective layer thickness test

[0101] The thickness of the inert protective layer is tested using atomic force microscopy technology, and the test method is carried out in accordance with the standard "GB / T36969-2018 Nanotechnology-Method for Determination of Nanofilm Thickness by Atomic Force Microscopy".

[0102] 2. Real-time online film thickness monitoring of inert protective layer

[0103] When spraying an inert protective layer, a real-time online film thickness monitor is used for real-time monitoring. The specific operation method is to install a crystal control probe close to the support to be coated. During film deposition or spraying, the surface of the crystal oscillator is simultaneously coated with a film of the same thickness as the support to be coated. The deposition of the film changes the mass of the crystal oscillator, and thus its resonant frequency. By monitoring the change in resonant frequency in real time, the mass of the deposited film can be calculated. By combining this with the density of the coating film material or converting it with the film thickness parameters measured by atomic force microscopy, the thickness of the deposited film can be calculated in real time.

[0104] 3. Thickness test of degradable polymer layer

[0105] The prepared coated stent was gold-sprayed, resin-embedded, and ground. Three cross-sections were selected, ground, and polished as evenly as possible along the length of the stent. On the premise of ensuring that the degradable polymer layer on the stent surface was not damaged, four stent rods with uniform circumferential distribution were randomly selected from each cross-section. The thickness of the degradable polymer layer on the inner and outer surfaces of the stent rods was measured, and the average value of the 12 measurement data was taken as the average thickness of the degradable polymer layer.

[0106] 4. Degradable polymer weight average molecular weight test

[0107] The weight-average molecular weight of the polymer was determined using a Wyatt GPC-multi-angle laser light scattering system. This system consisted of an Agilent liquid phase pump and injector, an Agilent PL MIXED-C GPC column (7.5 × 300 mm, 5 μm), a Wyatt multi-angle laser light scattering instrument, and a differential detector. The following testing conditions were used: mobile phase: tetrahydrofuran; pump flow rate: 1 mL / min; injection volume: 100 μL; laser wavelength: 663.9 nm; and testing temperature: 35°C.

[0108] 5. Corrosion rate test

[0109] The stents removed from the animal were treated with 1% sodium hydroxide to dissolve the tissue on the stents, and 5% tartaric acid cleaning solution was used to wash away the corrosion products on the stent rods. After dehydration and drying with 100% ethanol, the mass of the corrosion residue was weighed.

[0110] Corrosion rate = (stent mass at implantation - corrosion residue mass) / stent mass at implantation × 100%.

[0111] 6. Radial support force test

[0112] Clinically, the range between diastolic and systolic coronary blood pressure in normal individuals is 60 mmHg to 120 mmHg. Systolic blood pressure in patients with hypertension can reach 175 mmHg, or 23.3 kPa. During coronary artery spasm, systolic blood pressure reaches 400 mmHg, or 55 kPa. Therefore, clinically, effective coronary artery support by a vascular stent requires that the stent be able to withstand a systolic pressure of at least 23.3 kPa during coronary artery pulsation, and ideally, a systolic pressure of 55 kPa during vasospasm.

[0113] Animal implantation studies investigate whether the radial support strength of absorbable iron-based devices within one to six months of implantation meets clinical mechanical performance requirements for vascular stents. Specifically, the following steps are performed: The absorbable iron-based device is implanted into the blood vessels of the test animals. The absorbable iron-based device and surrounding tissue are then removed at predetermined observation time points, such as one, three, and six months. After absorbing any surface moisture, radial support strength testing is performed directly on the device using a radial support force tester manufactured by MSI.

[0114] 7. Corrosion expansion rate test of iron-based substrate

[0115] The iron-based stent implanted in animals that has been corroded in vivo or in vitro is dehydrated with gradient ethanol and then embedded and fixed with resin. A cross-section is then cut along the axis of the stent. The cross-sectional area of ​​the stent rod after corrosion is observed using a scanning electron microscope and compared with the cross-sectional area of ​​the stent rod before corrosion to calculate the corrosion expansion rate.

[0116] Corrosion expansion rate = cross-sectional area of ​​the stent after corrosion / cross-sectional area of ​​the stent before corrosion × 100%.

[0117] 8. In vitro immersion corrosion rate test of inert compounds

[0118] After drying, 100 mg of the coating formed by the inert compound is immersed in 50 mL of 0.9 wt.% NaCl salt solution and placed in a 37°C water bath shaker for 48 hours. After immersion, it is taken out, cleaned, dried at 60°C and weighed, recorded as M1, accurate to 0.001 mg, and the weight loss △M is recorded. Assuming that the corrosion rate is uniform over time, the in vitro immersion corrosion weight loss result is expressed as mm / y, and the calculation formula is (10 -2 ·△M) / (ρ·S·t), △M is in mg and substituted into the numerical calculation, t is converted into years and y and substituted into the numerical calculation, S is in cm 2 Substitute the numerical unit into the calculation, ρ is g / cm 2 Substitute the unit into the numerical calculation. If the material is pure iron, then ρ=7.8g / cm 2 .

[0119] 9. Water permeability test of inert protective layer

[0120] The water vapor transmission rate method is used and the test is carried out in accordance with the ASTM F1249 standard.

[0121] 10. Mass percentage of soluble iron corrosion products in corrosion products of iron-based medical devices

[0122] At 80°C, iron-based medical devices were immersed in 100 ml of PBS solution and corroded for 1.5 months. The soluble corrosion products generated by the corrosion of the iron-based medical devices were fully dissolved in the PBS solution. The soaking solution was filtered with an aqueous membrane with a pore size of 0.22 μm, and then the concentration of dissolved iron in the filtrate was tested by atomic absorption spectrometry (AAS). The mass of soluble iron dissolved in the PBS solution was m1 = cV, where V is the volume of the solution. The medical device was taken out, the rust was removed, and it was washed and weighed. The weight loss of the iron-based medical device was calculated to be △m, which is the mass of iron in the corrosion products of the iron-based medical device. The mass percentage W of soluble iron in the corrosion products of the iron-based medical device is shown in formula (1):

[0123] W=m1 / △m×100%(1)

[0124] W—mass percentage of soluble iron corrosion products in iron-based medical device corrosion products

[0125] m1—mass of soluble iron in PBS solution

[0126] △m—The mass of iron in the corrosion products of iron-based medical devices.

[0127] Example 1

[0128] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate, an N-type parylene layer covering the entire surface of the nitrided iron-based substrate, and a degradable polylactic acid drug-loaded coating covering the entire surface of the N-type parylene layer, wherein the thickness of the N-type parylene layer is 20 nm, the in vitro immersion corrosion rate of the N-type parylene layer is approximately 1.8 mm / y, and the water permeability is approximately 1*10 -2 g·mm / (m 2 ·h); the weight average molecular weight of the degradable polylactic acid is 1000 kDa, the thickness of the degradable polylactic acid drug-loaded coating is 10 μm, and the drug contained in the degradable polylactic acid drug-loaded coating is sirolimus, which is an anti-smooth muscle cell proliferation drug.

[0129] The preparation method of the absorbable implantable stent comprises the following steps:

[0130] A nitrided iron tube with a carbon content of 1.0 wt.% and a nitrogen content of 0.05 wt.% was selected as the iron-based substrate, and a 20 nm thick N-type parylene layer was deposited on the entire surface of the nitrided iron-based substrate by chemical vapor deposition.

[0131] A degradable polylactic acid layer loaded with sirolimus having a thickness of 10 μm and a weight average molecular weight of 1000 kDa was sprayed on the outside of the N-type parylene layer to obtain the absorbable implantable stent of this embodiment.

[0132] The stent of this example was implanted into the coronary artery of minipigs via minimally invasive intervention, and follow-up sampling was performed at various time points. The stent corrosion rate was measured to be 15% at 3 months, with a radial support force of 95 kPa. At 6 months, the corrosion rate was 30%, and the stent was completely degraded at 14 months. The corrosion expansion ratio of the iron-based matrix was approximately 3.5. The stent was completely immersed in PBS with a pH range of 7.4 ± 0.05. Disintegration of the parylene layer was observed after the stent was completely immersed in PBS for a period of time.

[0133] Example 2

[0134] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a pure iron substrate and a C-type parylene layer covering the entire surface of the pure iron substrate, and a degradable polylactic acid drug-loaded coating covering a portion of the surface of the C-type parylene layer, wherein the thickness of the C-type parylene layer is 120 nm, the in vitro immersion corrosion rate of the C-type parylene layer is about 1.4 mm / y, and the water permeability is about 5*10 -3 g·mm / (m 2 ·h); the weight average molecular weight of the degradable polylactic acid is 10 kDa, the thickness of the degradable polylactic acid drug-loaded coating is 100 μm, and the drug contained in the degradable polylactic acid drug-loaded coating is sirolimus, which is an anti-smooth muscle cell proliferation drug.

[0135] The preparation method of the absorbable implantable stent comprises the following steps:

[0136] A pure iron tube was selected as the iron-based substrate, and a C-type parylene layer with a thickness of 120 nm was deposited on the entire surface of the iron-based substrate using a chemical vapor deposition method.

[0137] A degradable polylactic acid layer with a thickness of 100 μm and a weight-average molecular weight of 10 kDa and loaded with sirolimus was sprayed on the outside of the C-type parylene layer to obtain the absorbable implantable stent of this embodiment.

[0138] The stent of this example was minimally invasively implanted into the coronary arteries of miniature pigs. Follow-up sampling at various time points revealed a 6% corrosion rate and a radial support force of 115 kPa at three months, an 18% corrosion rate at six months, and complete degradation at 16 months. The corrosion expansion coefficient of the iron-based matrix was 2.5. The stent was completely immersed in PBS with a pH range of 7.4 ± 0.05. Disintegration of the parylene layer was observed over time after soaking the stent.

[0139] Example 3

[0140] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate with a nitrogen content of 0.05 wt.%, a C-type parylene layer covering the entire surface of the nitrided iron-based substrate, and a degradable polylactic acid drug-loaded coating covering the entire surface of the C-type parylene layer, wherein the C-type parylene layer has a thickness of 580 nm, an in vitro immersion corrosion rate of the C-type parylene layer of approximately 1.1 mm / y, and a water permeability of approximately 5*10 -4 g·mm / (m 2 ·h);; The weight average molecular weight of the degradable polylactic acid is 200 kDa, the thickness of the degradable polylactic acid drug-loaded coating is 50 μm, and the drug contained in the degradable polylactic acid drug-loaded coating is sirolimus, which is an anti-smooth muscle cell proliferation drug.

[0141] The preparation method of the absorbable implantable stent comprises the following steps:

[0142] A nitrided iron tube with a nitrogen content of 0.05 wt.% was selected as the iron-based substrate, and a C-type parylene layer with a thickness of 580 nm was deposited on the entire surface of the iron-based substrate using a chemical vapor deposition method.

[0143] A degradable polylactic acid layer loaded with sirolimus having a thickness of 50 μm and a weight-average molecular weight of 200 kDa was sprayed on the outside of the C-type parylene layer to obtain the absorbable implantable stent of this embodiment.

[0144] The stent of this example was minimally invasively implanted into the coronary arteries of minipigs. Follow-up sampling at various time points revealed a 5% corrosion rate and a radial support force of 130 kPa at three months, a 15% corrosion rate at six months, and complete degradation at 18 months. The corrosion expansion coefficient of the iron-based matrix was 3.2. The stent was completely immersed in PBS (pH 7.4 ± 0.05) for a period of time, revealing disintegration of the parylene layer.

[0145] Example 4

[0146] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate and a L-polylactic acid layer covering the entire surface of the nitrided iron-based substrate, a C-type parylene layer covering the entire surface of the L-polylactic acid layer, and the C-type parylene layer covering the entire surface of the nitrided iron-based substrate, and a degradable polylactic acid drug-loaded coating covering a portion of the surface of the C-type parylene layer, wherein the L-polylactic acid has a molecular weight of 25 kDa and a thickness of 20 μm, the C-type parylene layer has a thickness of 20 nm, the C-type parylene layer has an in vitro immersion corrosion rate of approximately 1.8 mm / y, and a water permeability of approximately 0.8*10 -2 g·mm / (m 2·h); the thickness of the degradable polylactic acid drug-loaded coating is 8 μm, the weight-average molecular weight of the degradable polylactic acid is 5 kDa, and the drug contained in the degradable polylactic acid drug-loaded coating is paclitaxel, which is an anti-smooth muscle cell proliferation drug.

[0147] The preparation method of the absorbable implantable stent comprises the following steps:

[0148] A nitrided iron tube with a carbon content of 0.8 wt.% and a nitrogen content of 0.05 wt.% was selected as the iron-based substrate. A 20 μm thick layer of left-handed polylactic acid (PLA) with a molecular weight of 25 kDa was sprayed on the entire surface of the nitrided iron-based substrate. A 20 nm thick C-type parylene layer was then deposited on the entire surface of the L-type polylactic acid layer using chemical vapor deposition, and the C-type parylene layer covered the entire surface of the iron-based substrate.

[0149] A degradable polylactic acid layer with a thickness of 8 μm and a weight average molecular weight of 5 kDa and loaded with paclitaxel was sprayed on the outer surface of the C-type parylene layer to obtain the absorbable implantable stent of this embodiment.

[0150] The stent of this example was implanted into the coronary artery of minipigs via minimally invasive intervention, and follow-up sampling was performed at various time points. The corrosion rate of the stent was measured to be 12% at 3 months, with a radial support force of 110 kPa. At 6 months, the corrosion rate was 28%, and the stent was completely degraded at 14 months. The corrosion expansion ratio of the iron-based matrix was 3.1. The stent was completely immersed in PBS with a pH range of 7.4 ± 0.05. Disintegration of the parylene layer was observed after the stent was completely immersed in PBS at a pH of 7.4 ± 0.05 for a period of time.

[0151] Example 5

[0152] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate and a L-polylactic acid layer covering the entire surface of the nitrided iron-based substrate, an F-type parylene layer covering the entire surface of the L-polylactic acid layer, wherein the F-type parylene layer covers the entire surface of the nitrided iron-based substrate, and a degradable polylactic acid drug-loaded coating covering the entire surface of the F-type parylene layer, wherein the L-polylactic acid has a molecular weight of 700 kDa and a thickness of 5 μm, the F-type parylene layer has a thickness of 650 nm, the F-type parylene layer has an in vitro immersion corrosion rate of approximately 1.1 mm / y, and a water permeability of approximately 5*10 -4 g·mm / (m 2 ·h); the thickness of the degradable polylactic acid drug-loaded coating is 2 μm, the weight-average molecular weight of the degradable polylactic acid is 50 kDa, and the drug contained in the degradable polylactic acid drug-loaded coating is paclitaxel, which is an anti-smooth muscle cell proliferation drug.

[0153] The preparation method of the absorbable implantable stent comprises the following steps:

[0154] An iron tube with a nitrogen content of 0.15 wt.% was selected as the iron-based substrate. A 5 μm thick layer of left-handed polylactic acid (PLA) with a molecular weight of 700 kDa was sprayed on the entire surface of the nitrided iron-based substrate. A 650 nm thick layer of F-type parylene was then deposited on the entire surface of the L-handed polylactic acid layer using chemical vapor deposition, ensuring that the F-type parylene layer covered the entire surface of the iron-based substrate.

[0155] A degradable polylactic acid layer with a thickness of 2 μm and a weight average molecular weight of 50 kDa and loaded with paclitaxel was sprayed on the entire outer surface of the F-type parylene layer to obtain the absorbable implantable stent of this embodiment.

[0156] The stent of this example was implanted into the coronary artery of a miniature pig via minimally invasive intervention. Follow-up sampling at various time points revealed a 6% corrosion rate and a radial support force of 130 kPa at three months, a 16% corrosion rate at six months, and complete degradation at 18 months. The iron-based matrix exhibited a corrosion expansion rate of 3.8. The parylene layer disintegrated after the stent was completely immersed in PBS at a pH of 7.4 ± 0.05. After 1.5 months of accelerated in vitro corrosion, the mass percentage of soluble iron in the corrosion products was 12 wt.%.

[0157] Example 6

[0158] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate and a L-polylactic acid layer covering a portion of the surface of the nitrided iron-based substrate, a D-type parylene layer covering the entire surface of the L-polylactic acid layer, wherein the D-type parylene layer covers the entire surface of the nitrided iron-based substrate, and a degradable polylactic acid drug-loaded coating covering the entire surface of the D-type parylene layer, wherein the molecular weight of the L-polylactic acid is 200 kDa, the thickness of the L-polylactic acid layer is 10 μm, the thickness of the D-type parylene layer is 95 nm, the in vitro immersion corrosion rate of the D-type parylene layer is approximately 1.5 mm / y, and the water permeability is approximately 4*10 -3 g·mm / (m 2 ·h); the thickness of the degradable polylactic acid drug-loaded coating is 5 μm, the weight-average molecular weight of the degradable polylactic acid is 25 kDa, and the drug contained in the degradable polylactic acid drug-loaded coating is paclitaxel, which is an anti-smooth muscle cell proliferation drug.

[0159] The preparation method of the absorbable implantable stent comprises the following steps:

[0160] A nitrided iron tube with a carbon content of 1.2 wt.% and a nitrogen content of 0.05 wt.% was selected as the iron-based substrate. A 10 μm-thick layer of left-handed polylactic acid (PLA) with a molecular weight of 200 kDa was sprayed on a portion of the surface of the iron-based substrate. A 95 nm-thick layer of D-type parylene was then deposited on the entire surface of the L-type polylactic acid layer using chemical vapor deposition, ensuring that the D-type parylene layer covered the entire surface of the iron-based substrate.

[0161] A degradable polylactic acid layer with a thickness of 5 μm and a weight average molecular weight of 25 kDa and loaded with paclitaxel was sprayed on the entire outer surface of the D-type parylene layer to obtain the absorbable implantable stent of this embodiment.

[0162] The stent of this example was minimally invasively implanted into the coronary arteries of minipigs. Follow-up sampling at various time points revealed an 8% corrosion rate and a radial support force of 120 kPa at three months, a 20% corrosion rate at six months, and complete degradation at 12 months. The corrosion expansion rate of the iron-based matrix was 3.7. The stent was completely immersed in PBS (pH 7.4 ± 0.05) for a period of time, revealing disintegration of the parylene layer.

[0163] Example 7

[0164] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate and a polytetrafluoroethylene layer covering the entire surface of the nitrided iron-based substrate, and a degradable polyglycolic acid drug-carrying layer covering the entire surface of the polytetrafluoroethylene layer. The thickness of the polytetrafluoroethylene layer is 50 nm, the in vitro immersion corrosion rate of the polytetrafluoroethylene layer is about 1.6 mm / y, and the water permeability is about 1*10 -3 g·mm / (m 2 · h); the thickness of the degradable polyglycolic acid drug-loaded layer is 20 μm, the weight-average molecular weight of the degradable polyglycolic acid is 200 kDa, and the drug contained in the degradable polylactic acid drug-loaded coating is rapamycin that inhibits angiogenesis.

[0165] The preparation method of the absorbable implantable stent comprises the following steps:

[0166] A nitrided iron tube with a carbon content of 1 wt.% and a nitrogen content of 0.05 wt.% is selected as the iron-based substrate, and a polytetrafluoroethylene layer with a thickness of 50 nm is sprayed on the entire surface of the iron-based substrate so that the polytetrafluoroethylene layer covers the entire surface of the nitrided iron-based substrate.

[0167] A degradable polyglycolic acid layer with a thickness of 20 μm and a weight average molecular weight of 200 kDa and loaded with rapamycin is sprayed on the entire outer surface of the polytetrafluoroethylene layer to obtain the absorbable implantable stent of this embodiment.

[0168] The stent of this embodiment was implanted into the coronary artery of a miniature pig through a minimally invasive interventional approach, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 11% at 3 months, and the radial support force was 110 kPa. The corrosion rate was 25% at 6 months, and it was completely degraded at 14 months. The corrosion expansion rate of the iron-based matrix was 3.6. The stent was completely immersed in PBS with a pH range of 7.4±0.05. After soaking for a period of time, it was observed that the polytetrafluoroethylene layer disintegrated.

[0169] Example 8

[0170] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate, a C-type parylene layer covering the entire surface of the nitrided iron-based substrate, and a polylactic glycolic acid layer covering the entire surface of the C-type parylene layer, wherein the molecular weight of the polylactic glycolic acid is 300 kDa, the thickness of the polylactic glycolic acid layer is 60 μm, the thickness of the C-type parylene layer is 1.2 μm, the in vitro immersion corrosion rate of the C-type parylene layer is approximately 1 mm / y, and the water permeability is approximately 1*10 -5 g·mm / (m 2 h); the drug contained in the polylactic-co-glycolic acid coating is sirolimus, which inhibits smooth muscle cell proliferation.

[0171] The preparation method of the absorbable implantable stent comprises the following steps:

[0172] An iron tube with a nitrogen content of 0.1 wt.% was selected as the iron-based substrate, and a C-type parylene layer with a thickness of 1.2 μm was deposited on the entire surface of the iron-based substrate using a chemical vapor deposition method.

[0173] Sirolimus-loaded poly(lactic-co-glycolic acid) with a thickness of 60 μm and a weight-average molecular weight of 300 kDa was sprayed on the entire surface of the C-type parylene layer to obtain the absorbable implantable stent of this embodiment.

[0174] The stent of this example was implanted into the coronary artery of a miniature pig via minimally invasive intervention. Follow-up sampling was performed at various time points. The corrosion rate of the stent was 3% at three months, with a radial support force of 135 kPa. The corrosion rate was 13% at six months, and it was completely degraded at 20 months. The corrosion expansion ratio of the iron matrix was 3.5. The stent was completely immersed in PBS with a pH range of 7.4 ± 0.05. Disintegration of the parylene layer was observed during immersion. After 1.5 months of accelerated in vitro corrosion, the mass percentage of soluble iron in the corrosion products of the stent was 10 wt.%.

[0175] Example 9

[0176] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate and a polyvinyl chloride layer covering the entire surface of the nitrided iron-based substrate, and a polyoxalic anhydride layer covering the entire surface of the polyvinyl chloride layer, wherein the molecular weight of the polyoxalic anhydride is 500 kDa, the thickness of the polyoxalic anhydride layer is 40 μm, the thickness of the polyvinyl chloride layer is 3 μm, the in vitro immersion corrosion rate of the polyvinyl chloride layer is about 1.8 mm / y, and the water permeability is about 5*10 -3 g·mm / (m 2 h); the drug contained in the polyoxalic anhydride layer is sirolimus, which is an anti-smooth muscle cell proliferation drug.

[0177] The preparation method of the absorbable implantable stent comprises the following steps:

[0178] An iron pipe with a nitrogen content of 0.2% is selected as the iron-based substrate, and a polyvinyl chloride layer with a thickness of 3 μm is coated on the entire surface of the iron-based substrate.

[0179] Polyoxalic anhydride loaded with sirolimus having a weight average molecular weight of 500 kDa and a thickness of 40 μm was sprayed on the entire surface of the polyvinyl chloride layer to obtain the absorbable implantable stent of this embodiment.

[0180] The stent of this embodiment was implanted into the coronary artery of a miniature pig through a minimally invasive interventional approach, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 10% and the radial support force was 115 kPa at 3 months after implantation. The corrosion rate was 25% at 6 months, and it was completely degraded at 14 months. The corrosion expansion rate of the iron-based matrix was 5. The stent was completely immersed in PBS with a pH range of 7.4±0.05. After soaking for a period of time, it was observed that the polyvinyl chloride layer disintegrated.

[0181] Example 10

[0182] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate and a macromolecular L-polylactic acid layer covering the entire surface of the nitrided iron-based substrate, a polyurethane layer covering the entire surface of the macromolecular L-polylactic acid layer, and the polyurethane layer covering the entire surface of the nitrided iron-based substrate and a small molecule L-polylactic acid layer covering the entire surface of the polyurethane layer, wherein the molecular weight of the macromolecular L-polylactic acid is 500 kDa, the thickness of the macromolecular L-polylactic acid layer is 10 μm, the thickness of the polyurethane layer is 4.5 μm, the in vitro immersion corrosion rate of the polyurethane layer is about 1.8 mm / y, and the water permeability is about 8*10 -3 g·mm / (m 2 ·h); the thickness of the small molecule poly (L-lactic acid) layer is 5 μm, the weight average molecular weight of the small molecule poly (L-lactic acid) is 40 kDa, and the drug contained in the small molecule poly (L-lactic acid) layer is sirolimus, which is an anti-smooth muscle cell proliferation drug.

[0183] The preparation method of the absorbable implantable stent comprises the following steps:

[0184] An iron pipe with a nitrogen content of 0.18% is selected as the iron-based substrate, and a left-handed polylactic acid layer with a thickness of 10 μm and a weight-average molecular weight of 500 kDa is sprayed on the entire surface of the iron-based substrate. Then, a polyurethane layer with a thickness of 4.5 μm is sprayed on the entire surface of the left-handed polylactic acid layer, and the polyurethane layer covers the entire surface of the iron-based substrate.

[0185] A sirolimus-loaded poly (L-lactic acid) layer with a thickness of 5 μm and a weight-average molecular weight of 40 kDa was sprayed on the entire outer surface of the polyurethane layer to obtain the absorbable implantable stent of this embodiment.

[0186] The stent of this embodiment was implanted into the coronary artery of a miniature pig through a minimally invasive interventional approach, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 9% at 3 months after implantation, and the radial support force was 118 kPa. The corrosion rate was 23% at 6 months, and it was completely degraded at 14 months. The corrosion expansion rate of the iron-based matrix was 4.2. The stent was completely immersed in PBS with a pH range of 7.4±0.05. After soaking for a period of time, it was found that the polyurethane layer disintegrated.

[0187] Example 11

[0188] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, comprising a nitrided iron-based substrate and a macromolecular polyglycolic acid layer covering the entire surface of the nitrided iron-based substrate, a polytetrafluoroethylene layer covering the entire surface of the macromolecular polyglycolic acid layer, the polytetrafluoroethylene layer covering the entire surface of the nitrided iron-based substrate, and a small molecular weight L-polylactic acid layer covering the entire surface of the polytetrafluoroethylene layer, wherein the molecular weight of the polyglycolic acid is 350 kDa, the thickness of the polyglycolic acid layer is 15 μm, the thickness of the polytetrafluoroethylene layer is 6 μm, the in vitro immersion corrosion rate of the polytetrafluoroethylene layer is about 0.6 mm / y, and the water permeability is about 8*10 - 5 g·mm / (m 2 ·h); the thickness of the small molecule poly (L-lactic acid) layer is 6 μm, the weight average molecular weight of the small molecule poly (L-lactic acid) is 25 kDa, and the drug contained in the small molecule poly (L-lactic acid) layer is sirolimus, which is an anti-smooth muscle cell proliferation drug.

[0189] The preparation method of the absorbable implantable stent comprises the following steps:

[0190] An iron pipe with a nitrogen content of 0.25% is selected as the iron-based substrate, and a polyglycolic acid layer with a thickness of 15 μm and a weight-average molecular weight of 350 kDa is sprayed on the surface of the iron-based substrate. Then, a polytetrafluoroethylene layer with a thickness of 6 μm is coated on the entire surface of the polyglycolic acid layer, and the polytetrafluoroethylene layer covers the entire surface of the iron-based substrate.

[0191] A 6 μm thick poly(L-lactic acid) layer loaded with sirolimus having a weight average molecular weight of 25 kDa was sprayed on the entire outer surface of the polytetrafluoroethylene layer to obtain the absorbable implantable stent of this embodiment.

[0192] The stent of this embodiment was implanted into the coronary artery of a miniature pig via minimally invasive intervention. Follow-up sampling at various time points revealed a 0% corrosion rate and a radial support force of 145 kPa at three months, a 7% corrosion rate at six months, and complete degradation at 24 months. The corrosion expansion rate of the iron-based matrix was 6%. The stent of this embodiment was completely immersed in PBS with a pH range of 7.4±0.05. Disintegration of the tetrafluoroethylene layer was observed over a period of time. After 1.5 months of accelerated in vitro corrosion, the mass percentage of soluble iron in the corrosion products of the stent was 8 wt.%.

[0193] Example 12

[0194] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, which is basically the same as Example 8, except that it also includes a chelating agent layer, which is located between the nitrided iron-based matrix and the C-type parylene layer and completely covers the surface of the nitrided iron-based matrix.

[0195] The complexing agent layer includes tetrasodium ethylenediaminetetraacetic acid and polyglycolic acid in a mass ratio of 1:1, the thickness of the complexing agent layer is 6 μm, and the weight average molecular weight of the polyglycolic acid is 50 kDa.

[0196] The stent of this example was implanted into the coronary artery of a miniature pig via minimally invasive intervention. Follow-up sampling was performed at various time points. The corrosion rate of the stent was 4% at three months, with a radial support force of 132 kPa. The corrosion rate was 18% at six months, and complete degradation was observed at 14 months. The stent was completely immersed in PBS with a pH range of 7.4±0.05 for a period of time, revealing disintegration of the parylene layer. After 1.5 months of accelerated in vitro corrosion, the mass percentage of soluble iron in the corrosion products of the stent was 45 wt.%.

[0197] Example 13

[0198] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, which differs from Example 5 in that it further includes a chelating agent layer, which is located between the nitrided iron-based matrix and the F-type parylene layer and completely covers the surface of the nitrided iron-based matrix.

[0199] The complexing agent layer includes sodium gluconate and poly(lactic acid) in a mass ratio of 0.6:1, the thickness of the complexing agent layer is 3 μm, and the weight-average molecular weight of the poly(lactic acid) is 70 kDa.

[0200] The stent of this example was implanted into the coronary artery of a miniature pig via minimally invasive intervention. Follow-up sampling at various time points revealed a 5% corrosion rate and a radial support force of 130 kPa at three months, a 20% corrosion rate at six months, and complete degradation at 12 months. The stent was completely immersed in PBS at a pH of 7.4 ± 0.05 for a period of time, revealing disintegration of the parylene layer. After 1.5 months of accelerated in vitro corrosion, the mass percentage of soluble iron in the corrosion products of the stent was 38 wt.%.

[0201] Example 14

[0202] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, which differs from Example 5 in that it further includes a chelating agent layer, which is located between the nitrided iron-based matrix and the F-type parylene layer and completely covers the surface of the nitrided iron-based matrix.

[0203] The complexing agent layer includes triammonium citrate and polylactic glycolic acid in a mass ratio of 0.2:1, the thickness of the complexing agent layer is 0.1 μm, and the weight average molecular weight of the polylactic glycolic acid is 100 kDa.

[0204] The stent of this example was minimally invasively implanted into the coronary arteries of minipigs. Follow-up sampling at various time points revealed a 6% corrosion rate and a radial support force of 130 kPa at three months, an 18% corrosion rate at six months, and complete degradation at 16 months. The stent was completely immersed in PBS at a pH of 7.4 ± 0.05 for a period of time, revealing disintegration of the parylene layer. After 1.5 months of accelerated in vitro corrosion, the mass percentage of soluble iron in the corrosion products was 25 wt.%.

[0205] Example 15

[0206] The absorbable implantable medical device of this embodiment is an absorbable implantable stent. Unlike Example 8, this embodiment further includes a chelating agent layer, which is located between the nitrided iron-based substrate and the C-type parylene layer and completely covers the surface of the nitrided iron-based substrate. The chelating agent layer comprises sodium hexametapolyphosphate and has a thickness of 8 μm.

[0207] The stent of this example was minimally invasively implanted into the coronary arteries of minipigs. Follow-up sampling at various time points revealed a 3% corrosion rate and a radial support force of 135 kPa at three months, a 15% corrosion rate at six months, and complete degradation at 18 months. The stent was completely immersed in PBS at a pH of 7.4 ± 0.05 for a period of time, revealing disintegration of the parylene layer. After 1.5 months of accelerated in vitro corrosion, the mass percentage of soluble iron in the corrosion products was 35 wt.%.

[0208] Example 16

[0209] The absorbable implantable medical device of this embodiment is an absorbable implantable stent, which differs from Example 11 in that it further includes a chelating agent layer, which is located between the nitrided iron-based matrix and the polytetrafluoroethylene layer and completely covers the surface of the nitrided iron-based matrix.

[0210] The complexing agent layer includes sodium gluconate and poly(lactic acid) in a mass ratio of 1.5:1, the thickness of the complexing agent layer is 10 μm, and the weight average molecular weight of poly(lactic acid glycolic acid) is 10 kDa.

[0211] The stent of this embodiment was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. It was measured that the corrosion rate of the stent was 1% at 3 months after implantation, the radial support force was 142kPa, the corrosion rate was 18% at 6 months, and it was completely degraded at 16 months. The stent was completely immersed in PBS with a pH range of 7.4±0.05. After soaking for a period of time, it was found that the polytetrafluoroethylene layer disintegrated. After 1.5 months of accelerated corrosion in vitro, the mass percentage of soluble iron in the corrosion products of the stent was 40wt.%.

[0212] Comparative Example 1

[0213] The absorbable implantable medical device of this comparative example is an absorbable implantable stent, and the stent matrix is ​​a nitrided iron-based matrix with a nitrogen content of 0.05 wt.%.

[0214] A drug-loaded degradable polylactic acid with a weight-average molecular weight of 200 kDa is sprayed on the surface of the nitrided iron-based substrate to obtain a 50 μm thick degradable polylactic acid drug-loaded coating to obtain the absorbable implantable stent of this comparative example; wherein the anti-smooth muscle cell proliferation drug loaded in the degradable polylactic acid drug-loaded coating is sirolimus.

[0215] The stent of this comparative example was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 32% and the radial support force was 58 kPa at 3 months, and the corrosion rate of the stent was 45% at 6 months.

[0216] The stent of this comparative example differs from that of Example 3 in that the iron-based matrix is ​​not covered with a parylene layer. Experimental results show that within 3 months of stent implantation, the radial support force is insufficient and cannot meet the clinical mechanical performance requirements for early vascular stents.

[0217] Comparative Example 2

[0218] The absorbable implantable medical device of this comparative example is an absorbable implantable stent, and the stent matrix is ​​a nitrided iron-based matrix with a carbon content of 0.8 wt.% and a nitrogen content of 0.05 wt.%.

[0219] A 20 μm thick layer of L-lactic acid is sprayed on the surface of the iron-based substrate, and the molecular weight of the L-lactic acid is 25 kDa. Then, a drug-loaded degradable polylactic acid with a weight average molecular weight of 5 kDa is sprayed on the outside of the L-lactic acid layer to obtain an 8 μm thick degradable polylactic acid drug-loaded layer, thereby obtaining the absorbable implantable stent of this comparative example, wherein the drug loaded in the degradable polylactic acid drug-loaded coating is paclitaxel, which is an anti-smooth muscle cell proliferation drug.

[0220] The stent of this comparative example was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 35% at 3 months, the radial support force was 50 kPa, and the corrosion rate of the stent was 50% at 6 months.

[0221] The stent of this comparative example is not covered with a parylene layer compared to the iron-based matrix of Example 4. From the experimental results, it can be seen that within 3 months of stent implantation, the radial support force is insufficient and cannot meet the clinical mechanical performance requirements for early vascular stents.

[0222] Comparative Example 3

[0223] The absorbable implantable medical device in this comparative example is an absorbable implantable stent, and the stent substrate is a pure iron-based substrate; a C-type parylene coating with a thickness of 120 nm is deposited on a partial surface of the pure iron-based substrate (covering 70% of the pure iron-based substrate surface) by chemical vapor deposition.

[0224] The outer layer of the C-type parylene coating was sprayed with degradable polylactic acid loaded with sirolimus having a weight average molecular weight of 10 kDa to obtain a 100 μm thick degradable polylactic acid drug-loaded coating, thereby obtaining the absorbable implantable stent of this comparative example.

[0225] The stent of this comparative example was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. The stent broke one month after implantation, and the corrosion rate of the stent was measured to be 23% after three months, and the radial support force was 45 kPa.

[0226] The stent in this comparative example differs from that in Example 2 mainly in that the parylene layer covers part of the surface of the iron-based substrate. Experimental results show that the stent broke one month after implantation and had insufficient radial support force at three months, failing to meet the clinical mechanical performance requirements for early-stage vascular stents.

[0227] Comparative Example 4

[0228] The absorbable implantable medical device of this comparative example is an absorbable implantable stent, and the stent matrix is ​​a nitrided iron-based matrix.

[0229] A 10 μm thick layer of left-handed polylactic acid (PLA) with a molecular weight of 200 kDa was sprayed on the surface of a nitrided iron-based substrate having a carbon content of 1.2 wt.% and a nitrogen content of 0.05 wt.%. A 95 nm thick F-type parylene layer was then deposited on the surface of the polylactic acid layer using chemical vapor deposition, and the parylene layer covered the surface of the iron-based substrate (covering 60% of the surface of the iron-based substrate).

[0230] A degradable polylactic acid with a weight average molecular weight of 25 kDa and loaded with drugs was sprayed on the outside of the parylene layer to obtain a 5 μm thick degradable polylactic acid drug-loaded layer, thereby obtaining the absorbable implantable stent of this comparative example.

[0231] The stent of this comparative example was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. The stent broke 1.5 months after implantation, and the corrosion rate of the stent was 28% at 3 months, with a radial support force of 40 kPa.

[0232] The stent of this comparative example differs from that of Example 6 mainly in that the parylene layer does not completely cover the iron-based matrix and the L-polylactic acid layer. As shown in the experimental results, the stent broke 1.5 months after implantation, which cannot meet the clinical mechanical performance requirements for early vascular stents.

[0233] Comparative Example 5

[0234] The difference between this comparative example and Example 4 is that the thickness of the parylene layer is 10 nm and the water permeability is about 10 -1 g·mm / (m 2 ·h), and the in vitro immersion corrosion rate is 2.7mm / y.

[0235] The stent of this comparative example was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 22% and the radial support force was 65 kPa at 3 months after implantation, and the corrosion rate of the stent was 38% at 6 months.

[0236] The thickness of the parylene layer in this comparative example is too thin. Six months after the stent is implanted, the stent corrosion rate is high, resulting in insufficient radial support force, which cannot meet the clinical mechanical performance requirements for early vascular stents.

[0237] Comparative Example 6

[0238] This comparative example is basically the same as Example 1, except that the iron-based substrate is pure iron, the corrosion expansion rate is about 2, the thickness of the parylene layer is 6.5 μm, and the water permeability is about 10 -6 g / (m 2 ·24h), the in vitro immersion corrosion rate is 0.6mm / y.

[0239] The stent of this comparative example was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 0% at 3 months after implantation, the radial support force was 145 kPa, the corrosion rate of the stent was 8% at 6 months, and it was completely degraded in 3.5 years.

[0240] The thickness of the parylene layer and the molecular weight of the polylactic acid in this comparative example are too large, the thickness is too thick, and the degradation period is too long.

[0241] Comparative Example 7

[0242] The difference between this comparative example and Example 8 is that the metal substrate is different. This comparative example adopts a pure magnesium substrate, and its corrosion expansion rate is 1.

[0243] The stent of this comparative example was implanted into the coronary artery of a miniature pig through minimally invasive intervention, and follow-up sampling was performed at different time points. The corrosion rate of the stent was measured to be 3% at 3 months after implantation, the radial support force was 95 kPa, the corrosion rate of the stent was 8% at 6 months, and it was completely degraded in 4 years.

[0244] The present invention may have many other embodiments. Without departing from the spirit and essence of the present invention, those skilled in the art may make various corresponding changes and modifications based on the present invention, but these corresponding changes and modifications should all fall within the scope of protection of the claims attached to the present invention.

Claims

1. An absorbable implantable medical device comprising an iron-based substrate and a degradable polymer layer disposed on at least a portion of the surface of the iron-based substrate, wherein the degradable polymer layer comprises a degradable polymer, characterized in that: The medical device further comprises an inert protective layer provided on the entire surface of the iron-based substrate.

2. The absorbable implantable medical device according to claim 1, characterized in that: The thickness of the inert protective layer is 0.02 μm to 6 μm; the thickness of the inert protective layer is [0.02, 0.1) μm, or (0.1, 1) μm, or (1, 6) μm.

3. The absorbable implantable medical device according to claim 1, characterized in that: The inert protective layer comprises an inert compound; and the in vitro immersion corrosion rate of the inert protective layer is ≤2.0 mm / y.

4. The absorbable implantable medical device according to claim 1, characterized in that: The water permeability of the inert protective layer is 1*10 -13 g·mm / (m 2 h)~1*10 -2 g·mm / (m 2 ·h).

5. The absorbable implantable medical device according to claim 3, characterized in that: The inert compound includes at least one of magnesium stearate, parylene, polyethylene, polyvinyl chloride, polyacrylate, polyethyl acrylate, polymethacrylate, polyethyl acrylate, polymethyl methacrylate, polymethyl acrylate, polytetrafluoroethylene, polyamide, polyamideimide, polyetherimide, polyethersulfone, poly(iso)butylene, polyvinyl fluoride, polyvinyl alcohol, polyurethane, polybutylene terephthalate, silicone, polyphosphazene, styrene and derivatives thereof.

6. The absorbable implantable medical device according to claim 5, characterized in that: The parylene includes at least one of parylene C, parylene D, parylene F, parylene N, parylene M and parylene HT.

7. The absorbable implantable medical device according to claim 1, characterized in that: The degradable polymer layer covers at least a portion of the surface of the inert protective layer.

8. The absorbable implantable medical device according to claim 7, characterized in that: The weight average molecular weight of the degradable polymer in the degradable polymer layer is 5 kDa to 1000 kDa; and the thickness of the degradable polymer layer is 0.5 μm to 100 μm.

9. The absorbable implantable medical device according to claim 1, characterized in that: The degradable polymer layer includes at least one degradable polymer layer located outside the inert protective layer and at least one degradable polymer layer located inside the inert protective layer.

10. The absorbable implantable medical device according to claim 9, characterized in that: The weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is greater than the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer; The weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is at least 5 times the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer; The weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is 5 to 20 times the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer; The weight average molecular weight of the degradable polymer in the degradable polymer layer located inside the inert protective layer is 25 kDa to 700 kDa, and the weight average molecular weight of the degradable polymer in the degradable polymer layer located outside the inert protective layer is 5 kDa to 100 kDa; The thickness of the degradable polymer layer located inside the inert protective layer is 0.5 μm to 20 μm, and the thickness of the degradable polymer layer located outside the inert protective layer is 1 μm to 10 μm.

11. The absorbable implantable medical device according to claim 1, characterized in that: The medical device further comprises a complexing agent layer provided on at least a portion of the surface of the iron-based substrate, and the complexing agent layer is located inside the inert protective layer, and the complexing agent layer comprises a complexing agent.

12. The absorbable implantable medical device according to claim 11, characterized in that: The complexing agent layer further comprises a polymer carrier, wherein the mass ratio of the complexing agent to the polymer carrier is (0.2-1.5):1; the polymer carrier comprises a degradable polymer; The thickness of the complexing agent layer is 0.05 μm to 10 μm; The complexing agent contains at least one ligand, and the ligand includes at least one of a hydroxyl group, a sulfhydryl group, an amine group, an aromatic heterocyclic group, a nitroso group, a carbonyl group, a sulfo group, a phosphate group, a hydroxamic acid group or an organic phosphine group on a condensed ring aromatic hydrocarbon; the hydroxyl group on the condensed ring aromatic hydrocarbon includes a phenolic hydroxyl group; the aromatic heterocyclic group includes at least one of a furyl group, a pyrrolyl group, an imidazole group, a triazole group, a thienyl group, a thiazolyl group, a pyridyl group, a pyridone group, a pyranyl group, a pyrone group, a pyrimidinyl group, a pyridazinyl group, a pyrazinyl group, a quinolyl group, an isoquinolyl group, a phthalazinyl group, a pteridinyl group, an indolyl group, a purinyl group or a phenanthroline group; The complexing agents containing hydroxyl groups on condensed ring aromatic hydrocarbons include 8-hydroxyquinoline, 8-hydroxyquinaldine, 4,5-dihydroxybenzene-1,3-disulfonic acid sodium, 4-[3,5-di-hydroxyphenyl-1H-1,2,4-triazole]-benzoic acid, 1-(2-pyridylazo)-2-naphthol; the complexing agents containing thiol groups include 8-mercaptoquinoline, thioglycolic acid, dimercaptopropanol, 5-methyl-2-mercaptobenzoic acid methyl ester; the complexing agents containing amine groups include ethylenediamine, triethylenetetramine, ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid, tetrasodium, triethylenetetramine, N-(2-hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid or N'-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxybutyl]hydroxylamine]pentyl]-N-(5-aminopentyl)-N-hydroxysuccinamide; the complexing agent containing aromatic heterocyclic groups includes o-phenanthroline, bipyridine, porphyrin, porphine, chlorophyll, hemoglobin or 1,2-dimethyl-3-hydroxy-4-pyridone; the complexing agent containing nitroso groups includes 1-nitroso-2- naphthol or sodium 1-nitroso-2-naphthol-6-sulfonate; the complexing agent containing sulfonyl group includes sulfosalicylic acid or 8-hydroxyquinoline-5-sulfonic acid; the complexing agent containing phosphoric acid group includes pyrophosphoric acid, tripolyphosphoric acid, hexametapolyphosphoric acid, polyphosphoric acid, sodium pyrophosphate, sodium hexametapolyphosphate or ammonium polyphosphate; the complexing agent containing organic phosphine group includes potassium diethylenetriamine penta (methylene phosphonate) or sodium ethylenediamine tetra (methylene phosphonate); the complexing agent containing carbonyl group includes carboxylic acid and its salt, anhydride, ester, amide, polycarboxylic acid or polyanhydride; the complexing agent containing carbonyl group includes The complexing agent includes gluconic acid, oxalic acid, tartaric acid, malic acid, oxaloacetic acid, fumaric acid, maleic acid, citric acid, nitrilotriacetic acid, diethylenetriamine pentacarboxylic acid, alginic acid, glutamic acid, aspartic acid, ornithine, lysine, 1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, potassium citrate, calcium citrate, glyceryl citrate, acetylsalicylic acid, sulfosalicylamide, polyaspartic acid, polyglutamic acid, polyornithine, polylysine or polymaleic anhydride; the complexing agent containing a hydroxamic acid group includes deferoxamine.

13. The absorbable implantable medical device according to claim 1, 7, 9 or 12, characterized in that: The degradable polymer includes at least one of a degradable polyester, a degradable polyanhydride, a degradable polyamino acid, and a binary or multinary degradable copolymer formed by copolymerizing monomers corresponding to the degradable polyester, the degradable polyanhydride and / or the degradable polyamino acid, wherein: The degradable polyester comprises at least one of polylactic acid, polyglycolic acid, polylactic glycolic acid, polycaprolactone, polyhydroxyalkanoate, polyacrylate, polysuccinate, poly(β-hydroxybutyrate), polyethylene adipate, polysalicylic anhydride, polytrimethylene carbonate, polydioxanone, poly(β-alkanoate), and polyhydroxybutyrate valerate copolymer; The degradable polyanhydride includes at least one of poly 1,3-bis(p-carboxyphenoxy)propane-sebacic acid, poly erucic acid dimer-sebacic acid and poly fumaric acid-sebacic acid, polyoxalic anhydride, polysuccinic anhydride, polyadipic anhydride, polysebacic anhydride, polydodecanoic anhydride, polycitric anhydride, polymalic anhydride, polysuccinic anhydride, polytartaric anhydride, polyitaconic anhydride and polymaleic anhydride; The degradable polyamino acid includes at least one of polyglycine, polyalanine, polyvaline, polyleucine, polyisoleucine, polymethionine, polyproline, polytryptophan, polyserine, polytyrosine, polycysteine, polyphenylalanine, polyasparagine, polyglutamine, polythreonine, polyarginine, polyhistidine, polyselenocysteine, polypyrroline, polyglutamic acid, polyaspartic acid, polyornithine, polylysine and derivatives thereof.

14. The absorbable implantable medical device according to claim 1, 7 or 9, characterized in that: At least one of the degradable polymer layers is mixed with an active drug, and the active drug includes at least one of an anti-angiogenesis drug, an anti-platelet drug, an anti-thrombotic drug, an anti-inflammatory drug and an anti-allergic drug; the anti-angiogenesis drug includes at least one of paclitaxel, sirolimus, rapamycin and its derivatives; the anti-platelet drug includes cilostazol; the anti-thrombotic drug includes heparin; the anti-inflammatory drug includes dexamethasone; the anti-allergic drug includes at least one of diphenhydramine, chlorpheniramine, promethazine, hydrocortisone, triamcinolone acetonide, methylprednisolone, loratadine, fexofenadine, levocetirizine, mizolastine and ebastine.

15. The absorbable implantable medical device according to claim 1, characterized in that: The corrosion expansion rate of the iron-based substrate during the corrosion process is ≥1.5; the corrosion expansion rate of the iron-based substrate during the corrosion process is ≥2.

16. The absorbable implantable medical device according to claim 1, characterized in that: The iron-based matrix is ​​pure iron or an iron alloy; the iron content in the iron alloy is ≥95%; and the iron alloy is nitrided iron.

17. The absorbable implantable medical device according to claim 1, characterized in that: The absorbable implantable medical device includes a luminal stent, an occluder, a gasket, an artificial blood vessel, a dental implant, a vascular clip, a dental implant, a suture, a gynecological implant, a men's implant, a respiratory implant or an orthopedic implant.

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