Zinc-containing medical device

Abstract

The application relates to a zinc-containing medical device, which comprises a zinc-containing base body and a polylactic acid coating arranged on the zinc-containing base body, wherein the thickness of the polylactic acid coating is x micrometers, and x and the weight average molecular weight Mn kilodaltons of the polylactic acid satisfy the formula: the corrosion rate of zinc in the base body is small, the mechanical properties can be maintained for a sufficient repair period, and the biological risk is low. When the polylactic acid is poly-racemic lactic acid, a=0.0336ln(Mn)-0.1449, b=-0.472ln(Mn)+2.1524, and c=1.1604ln(Mn)-5.7128; when the polylactic acid is poly-lactic acid, a=-0.006ln(Mn)+0.03441, b=0.0648ln(Mn)-0.3662, and c=-0.162ln(Mn)+0.7847.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of interventional medical devices, in particular to a zinc-containing medical device. BACKGROUND

[0002] This section provides background information only and can not necessarily be prior art.

[0003] At present, the base materials of absorbable implantable medical devices are mainly selected from degradable polymers and corroding metals. Among the degradable polymers, polylactic acid is most commonly used, which has the advantages of complete degradation and degradation products of carbon dioxide and water, but has the disadvantage of insufficient mechanical properties. The corroding metals have the advantages of easy processing plasticity and large mechanical strength. The commonly used corroding metals in clinical applications mainly include magnesium and magnesium-based alloys, iron and iron-based alloys, and zinc and zinc-based alloys.

[0004] From the perspective of clinical application, on the one hand, the device needs to maintain structural integrity and have sufficient mechanical properties during the period from implantation to recovery of the lesion site and restoration of normal morphology and function. This requires that the early corrosion rate or degradation rate of the absorbable implantable medical device be as slow as possible. On the other hand, the corrosion of the corroding metal material generates corrosion products including metal ions. Higher metal ion concentration can be toxic, leading to biological risks. For example, it has been reported that the cytotoxicity (median lethal dose) of zinc ions on fibroblasts, smooth muscle cells and endothelial cells is 50 μmol / L, 70 μmol / L and 265 μmol / L, respectively. Therefore, for zinc-containing medical devices, the corrosion rate of zinc must be controlled to maintain sufficient mechanical properties during the repair period and reduce the concentration of zinc ions, thereby further reducing the biological risk. SUMMARY

[0005] Therefore, it is necessary to provide a zinc-containing absorbable device that can maintain sufficient mechanical properties during the repair period and has a lower biological risk.

[0006] A zinc-containing medical device, comprising a zinc-containing base and a polylactic acid coating layer provided on the surface of the zinc-containing base, wherein the thickness of the polylactic acid coating layer is x , the thickness of the polylactic acid coating layer is x satisfies the formula: ;

[0007] wherein, when the polylactic acid is poly-racemic lactic acid, a = 0.0336ln(Mn)-0.1449, b =-0.472ln(Mn)+2.1524, c = 1.1604ln(Mn)-5.7128;

[0008] when the polylactic acid is poly-L-lactic acid, a = -0.006ln(Mn) + 0.03441, b = 0.0648ln(Mn) - 0.3662, c = -0.162ln(Mn) + 0.7847;

[0009] Mn is the weight average molecular weight of the polylactic acid, in kilodaltons, x in micrometers.

[0010] In one embodiment, the zinc-containing substrate has an outer surface, an inner surface, and a side surface, the polylactic acid coating covers at least the outer surface or the inner surface or the side surface, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 100-300 kDa, and the average thickness of the portion of the polylactic acid coating located on the outer surface is 5.2-11.5 micrometers; the average thickness of the portion of the polylactic acid coating located on the inner surface is 5.2-11.5 micrometers; the average thickness of the portion of the polylactic acid coating located on the side surface is 5.2-11.5 micrometers.

[0011] In one embodiment, the zinc-containing substrate has an outer surface, an inner surface, and a side surface, the polylactic acid coating covers at least the outer surface or the inner surface or the side surface, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 10-100 kDa, and the average thickness of the portion of the polylactic acid coating located on the outer surface is 2-9 micrometers; the average thickness of the portion of the polylactic acid coating located on the inner surface is 2-9 micrometers; the average thickness of the portion of the polylactic acid coating located on the side surface is 2-9 micrometers.

[0012] In one embodiment, the zinc-containing substrate has an outer surface, an inner surface, and a side surface, the polylactic acid coating covers at least the outer surface or the inner surface or the side surface, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 2-10 kDa, and the average thickness of the portion of the polylactic acid coating located on the outer surface is 1.5-5.5 micrometers; the average thickness of the portion of the polylactic acid coating located on the inner surface is 1.5-5.5 micrometers; the average thickness of the portion of the polylactic acid coating located on the side surface is 1.5-5.5 micrometers.

[0013] In one embodiment, the zinc-containing substrate has an outer surface, an inner surface, and a side surface, the polylactic acid coating covers at least the outer surface or the inner surface or the side surface, the polylactic acid is poly-L-lactic acid, the weight average molecular weight of the poly-L-lactic acid is 200-300 kDa, and the average thickness of the polylactic acid coating on the outer surface is 9-22 microns; the average thickness of the polylactic acid coating on the inner surface is 9-22 microns; and the average thickness of the polylactic acid coating on the side surface is 9-22 microns.

[0014] In one embodiment, the zinc-containing substrate has an outer surface, an inner surface, and a side surface, the polylactic acid coating covers at least the outer surface or the inner surface or the side surface, the polylactic acid is poly-L-lactic acid, the weight average molecular weight of the poly-L-lactic acid is 50-200 kDa, and the average thickness of the polylactic acid coating on the outer surface is 7-13 microns; the average thickness of the polylactic acid coating on the inner surface is 7-13 microns; and the average thickness of the polylactic acid coating on the side surface is 7-13 microns.

[0015] In one embodiment, the zinc-containing substrate has an outer surface, an inner surface, and a side surface, the polylactic acid coating covers at least the outer surface or the inner surface or the side surface, the polylactic acid is poly-L-lactic acid, the weight average molecular weight of the poly-L-lactic acid is 50-200 kDa, and the average thickness of the polylactic acid coating on the outer surface is 7-13 microns; the average thickness of the polylactic acid coating on the inner surface is 7-13 microns; and the average thickness of the polylactic acid coating on the side surface is 7-13 microns. x 外 , the average thickness of the polylactic acid coating on the inner surface is x 内 , the average thickness of the polylactic acid coating on the side surface is x 侧 , x 内 ≤ x 外 , x 内 ≤ x 侧 , and the x 外 , x 内 and x 侧 at least one satisfies the following formula:

[0016] , x = x 内 , x 侧 or x 外 ;

[0017] When the polylactic acid is poly-racemic lactic acid, a = 0.0336ln(Mn) - 0.1449, b = -0.472ln(Mn) + 2.1524, and c = 1.1604ln(Mn) - 5.7128;

[0018] When the polylactic acid is poly-lactic acid, a = -0.006ln(Mn) + 0.03441, b = 0.0648ln(Mn) - 0.3662, and c = -0.162ln(Mn) + 0.7847;

[0019] Mn is the weight average molecular weight of the polylactic acid, in kilodaltons, x in micrometers.

[0020] In one embodiment, the zinc-containing substrate is pure zinc or a zinc alloy; or, the zinc-containing substrate comprises a body and a zinc-containing layer attached to the body, and the material of the zinc-containing layer is pure zinc or a zinc alloy.

[0021] In one embodiment, when the material of the zinc-containing substrate is pure zinc or a zinc alloy, the mass percentage of zinc in the zinc alloy is 50% to 99.99%.

[0022] When the zinc-containing substrate comprises a body and a zinc-containing layer attached to the body, and the material of the zinc-containing layer is a zinc alloy, the mass percentage of zinc in the zinc alloy is 50% to 99.99%.

[0023] In one embodiment, the zinc-containing layer covers the entire surface of the body.

[0024] In one embodiment, the polylactic acid coating contains an active drug.

[0025] Experiments have shown that, when the weight average molecular weight Mn (kilodaltons) of the polylactic acid in the polylactic acid coating and the thickness of the polylactic acid coating x (micrometers) satisfy the formula: , When the polylactic acid is poly-racemic lactic acid, a = 0.0336ln(Mn)-0.1449, b = -0.472ln(Mn)+2.1524, c = 1.1604ln(Mn)-5.7128; when the polylactic acid is poly-lactic acid, a = -0.006ln(Mn)+0.03441, b = 0.0648ln(Mn)-0.3662, c = -0.162ln(Mn)+0.7847; the corrosion rate of zinc in the zinc-containing substrate is small, avoiding the zinc-containing substrate from corroding too fast, and enabling the zinc-containing substrate to maintain sufficient mechanical properties within the repair period. Moreover, the corrosion rate of zinc in the zinc-containing substrate is small, which can avoid the zinc ion concentration from accumulating too high, and is conducive to reducing the biological risk. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 Figure 4 is a pathological section of the tissue around the zinc-based stent of Example 5 one month after the zinc-based stent was implanted in the iliac artery of a rabbit. DETAILED DESCRIPTION

[0027] In order to make the above objectives, features and advantages of the present application more apparent, specific embodiments of the present application will be described in detail below with reference to the accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. However, the present application can be practiced in a number of different ways beyond the specific details described herein. It is, therefore, to be understood that the present application is not intended to be limited by the specific implementations disclosed below.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0029] A zinc-containing medical device according to an embodiment includes a zinc-containing substrate and a polylactic acid coating disposed on the zinc-containing substrate. The zinc-containing substrate is an absorbable substrate. The polylactic acid coating covers at least part of the surface of the zinc-containing substrate.

[0030] In an embodiment, the material of the zinc-containing substrate is pure zinc or a zinc alloy, i.e., the zinc-containing substrate is made of pure zinc or a zinc alloy. For example, the zinc-containing substrate is a hollow tube structure made of pure zinc or a zinc alloy. The zinc alloy is a biocompatible alloy.

[0031] In one embodiment, the alloying elements in the zinc alloy are selected from at least one of C, N, O, S, P, Ce, Mn, Ca, Cu, Pd, Si, W, Ti, Co, Cr, Cu and Re. It is noted that the alloying elements in the zinc alloy are elements that are non-toxic and harmless to living organisms. Alternatively, the alloying elements are present in a low amount that is insufficient to cause toxic effects to living organisms.

[0032] In one embodiment, the zinc alloy contains 50% to 99.99% zinc by mass.

[0033] In another embodiment, the zinc-containing substrate comprises a body and a zinc-containing layer attached to the body, and the material of the zinc-containing layer is pure zinc or a zinc alloy. The material of the body is a bioabsorbable metal or a bioabsorbable polymer. For example, the bioabsorbable metal is pure iron or an iron-based alloy. The zinc-containing layer covers at least part of the surface of the body. In one embodiment, the zinc-containing layer covers the entire surface of the body.

[0034] When the material of the zinc-containing layer is a zinc alloy, the alloying elements in the zinc alloy are selected from at least one of C, N, O, S, P, Ce, Mn, Ca, Cu, Pd, Si, W, Ti, Co, Cr, Cu and Re. It is noted that the alloying elements in the zinc alloy are elements that are non-toxic and harmless to living organisms. Alternatively, the alloying elements are present in a low amount that is insufficient to cause toxic effects to living organisms. In one embodiment, the zinc alloy contains 50% to 99.99% zinc by mass.

[0035] Whether the zinc-containing substrate is a substrate formed of pure zinc or a zinc alloy or the zinc-containing substrate comprises a body and a zinc-containing layer attached to the body, in one embodiment, the zinc-containing substrate has an outer surface, an inner surface and a side surface. The polylactic acid coating covers at least the outer surface of the zinc-containing substrate. Alternatively, the polylactic acid coating covers at least the inner surface of the zinc-containing substrate. Alternatively, the polylactic acid coating covers at least the side surface of the zinc-containing substrate. Here, the inner surface is a surface that is in direct contact with a body fluid (e.g. blood) when the zinc-containing medical device is implanted in a living body, the outer surface is a surface that is in direct contact with a tissue wall (e.g. a blood vessel wall), and the side surface connects the inner surface and the outer surface.

[0036] In one embodiment, the polylactic acid coating covers the outer surface, the inner surface and the side surface of the zinc-containing substrate.

[0037] When the zinc-containing medical device is implanted into a living body, zinc corrosion can generate zinc phosphate, and at the same time, polylactic acid degradation generates carboxyl and hydroxyl groups. Zinc phosphate can react with carboxyl and hydroxyl groups to generate a complex, thereby hindering further corrosion of zinc. Thus, the zinc corrosion rate of the zinc-containing medical device comprising a polylactic acid coating is less than the zinc corrosion rate of the zinc-containing medical device not comprising a polylactic acid coating. At the same time, hydrogen ions generated by the degradation of polylactic acid can accelerate the corrosion of the metal. That is, the polylactic acid coating has both corrosion inhibition and corrosion promotion effects on the corrosion rate of zinc in the zinc-containing substrate. The release rate and cumulative concentration of the degradation products of polylactic acid affect the corrosion inhibition and corrosion promotion effects of polylactic acid coating on zinc corrosion. The properties of polylactic acid in the polylactic acid coating are important factors affecting the degradation rate of polylactic acid. The thickness of the polylactic acid coating affects the total amount of polylactic acid degradation products.

[0038] The thickness of the polylactic acid coating is x , in units of microns (μm), x satisfying the formula: .

[0039] wherein, and when the polylactic acid is poly-racemic lactic acid, a = 0.0336ln(Mn)-0.1449, b =-0.472ln(Mn)+2.1524, c = 1.1604ln(Mn)-5.7128;

[0040] when the polylactic acid is poly-lactic acid, a =-0.006ln(Mn)+0.03441, b = 0.0648ln(Mn)-0.3662, c =-0.162ln(Mn)+0.7847.

[0041] wherein, Mn is the weight average molecular weight of the polylactic acid, in units of kilodaltons (kDa). That is, when calculating the sizes of a, b and c, the value of Mn is brought into the formula in the size of the value corresponding to kDa, and the calculated value is directly used in the above formula or relationship. When the thickness of the polylactic acid coating x is brought into the above formula or relationship, the value corresponding to the unit of microns of the thickness of the polylactic acid coating is brought into the above relationship for comparison.

[0042] The thickness of the above polylactic acid coating x refers to the average thickness of the portion of the polylactic acid coating located on the outer surface x 外 , the average thickness of the portion of the polylactic acid coating located on the inner surface x 内 or the average thickness of the portion of the polylactic acid coating located on the side surface x 侧 , that is x 外 ,x 内 and x 侧 At least one of them satisfies the above formula.

[0043] In one implementation, x 内 ≤ x 外 , x 内 ≤ x 侧 ,and x 外 , x 内 and x 侧 At least one of them satisfies the following formula: , x = x 内 , x 侧 or x 外 .

[0044] In one implementation, x 外 , x 内 and x 侧 All of them satisfy the above formula.

[0045] Experiments have shown that when the thickness of the polylactic acid coating, the type of polylactic acid, and the molecular weight of polylactic acid satisfy the above-mentioned relationship, the corrosion inhibition effect of the polylactic acid coating on the corrosion rate of zinc in the zinc-containing substrate is dominant, resulting in a lower corrosion rate of zinc.

[0046] By setting a thickness of [missing information] on a zinc-containing substrate x A micron-sized polylactic acid (PLA) coating, using a suitable PLA, results in a low corrosion rate of zinc in the zinc-containing substrate. When the zinc-containing substrate is made of pure zinc or a zinc alloy, the low corrosion rate of zinc, meaning the substrate itself has a low corrosion rate, prevents it from corroding too quickly and losing its mechanical properties prematurely, thus helping to maintain sufficient mechanical properties during the repair period. When the zinc-containing substrate includes the substrate itself and a zinc-containing layer attached to it, and the zinc-containing layer is made of pure zinc or a zinc alloy, the zinc-containing layer coats the surface of the substrate, physically isolating it from the body fluids. The low corrosion rate of the zinc-containing layer helps to prolong the protection period of the substrate, thereby helping to maintain sufficient mechanical properties during the repair period.

[0047] And, since the corrosion rate of zinc is small, the concentration of zinc corrosion products accumulated in the tissue is small, reducing the biological risk.

[0048] It should be noted that when the thickness of the polylactic acid coating is x When the above formula is satisfied, the corrosion rate of zinc in the zinc-containing substrate is small, which means that the comparison is made under the premise that other conditions are the same, such as the same zinc-containing substrate, the same polylactic acid material, and the same distribution of the polylactic acid coating. Or, under the premise that the zinc-containing substrate is the same, the corrosion rate of zinc of the zinc-containing medical device containing the above polylactic acid coating is smaller than that of the device without the polylactic acid coating.

[0049] In an embodiment, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 100-300 kDa, and the average thickness of the part of the polylactic acid coating located on the outer surface is 5.2-11.5 microns. And / or, the average thickness of the part of the polylactic acid coating located on the inner surface is 5.2-11.5 microns. And / or, the average thickness of the part of the polylactic acid coating located on the side surface is 5.2-11.5 microns. In an embodiment, the average thickness of all surfaces of the polylactic acid coating is 5.2-11.5 microns.

[0050] In an embodiment, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 10-100 kDa, and the average thickness of the part of the polylactic acid coating located on the outer surface is 2-9 microns. And / or, the average thickness of the part of the polylactic acid coating located on the inner surface is 2-9 microns. And / or, the average thickness of the part of the polylactic acid coating located on the side surface is 2-9 microns. In an embodiment, the average thickness of all surfaces of the polylactic acid coating is 2-9 microns.

[0051] In an embodiment, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 2-10 kDa, and the average thickness of the part of the polylactic acid coating located on the outer surface is 1.5-5.5 microns. And / or, the average thickness of the part of the polylactic acid coating located on the inner surface is 1.5-5.5 microns. And / or, the average thickness of the part of the polylactic acid coating located on the side surface is 1.5-5.5 microns. In an embodiment, the average thickness of all surfaces of the polylactic acid coating is 1.5-5.5 microns.

[0052] In an embodiment, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 200 kDa, and the average thickness of the part of the polylactic acid coating located on the outer surface is 9.1 microns. And / or, the average thickness of the part of the polylactic acid coating located on the inner surface is 9.1 microns. And / or, the average thickness of the part of the polylactic acid coating located on the side surface is 9.1 microns. In an embodiment, the average thickness of all surfaces of the polylactic acid coating is 9.1 microns.

[0053] In an embodiment, the polylactic acid is poly-DL-lactic acid, the poly-DL-lactic acid has a weight average molecular weight of 50 kDa, and the average thickness of the portion of the polylactic acid coating layer on the outer surface is 4.9 micrometers. And / or, the average thickness of the portion of the polylactic acid coating layer on the inner surface is 4.9 micrometers. And / or, the average thickness of the portion of the polylactic acid coating layer on the side surface is 4.9 micrometers. Or in an embodiment, the average thickness of all surfaces of the polylactic acid coating layer is 4.9 micrometers.

[0054] In an embodiment, the polylactic acid is poly-DL-lactic acid, the poly-DL-lactic acid has a weight average molecular weight of 5 kDa, and the average thickness of the portion of the polylactic acid coating layer on the outer surface is 3.6 micrometers. And / or, the average thickness of the portion of the polylactic acid coating layer on the inner surface is 3.6 micrometers. And / or, the average thickness of the portion of the polylactic acid coating layer on the side surface is 3.6 micrometers. Or in an embodiment, the average thickness of all surfaces of the polylactic acid coating layer is 3.6 micrometers.

[0055] In an embodiment, the polylactic acid is poly-L-lactic acid, the poly-L-lactic acid has a weight average molecular weight of 200-300 kDa, and the average thickness of the portion of the polylactic acid coating layer on the outer surface is 9-22 micrometers or the average thickness of the portion of the polylactic acid coating layer on the inner surface is 9-22 micrometers or the average thickness of the portion of the polylactic acid coating layer on the side surface is 9-22 micrometers. Or in an embodiment, the average thickness of all surfaces of the polylactic acid coating layer is 9-22 micrometers.

[0056] In an embodiment, the polylactic acid is poly-L-lactic acid, the poly-L-lactic acid has a weight average molecular weight of 50-200 kDa, and the average thickness of the portion of the polylactic acid coating layer on the outer surface is 7-13 micrometers or the average thickness of the portion of the polylactic acid coating layer on the inner surface is 7-13 micrometers or the average thickness of the portion of the polylactic acid coating layer on the side surface is 7-13 micrometers. Or in an embodiment, the average thickness of all surfaces of the polylactic acid coating layer is 7-13 micrometers.

[0057] In an embodiment, the polylactic acid is poly-L-lactic acid, the poly-L-lactic acid has a weight average molecular weight of 300 kDa, and the average thickness of the portion of the polylactic acid coating layer on the outer surface is 19.7 micrometers or the average thickness of the portion of the polylactic acid coating layer on the inner surface is 19.7 micrometers or the average thickness of the portion of the polylactic acid coating layer on the side surface is 19.7 micrometers. Or in an embodiment, the average thickness of all surfaces of the polylactic acid coating layer is 19.7 micrometers.

[0058] In one embodiment, the polylactic acid is poly-L-lactic acid, the weight average molecular weight of the poly-L-lactic acid is 100 kDa, the average thickness of the portion of the polylactic acid coating layer located on the outer surface is 9.4 microns or the average thickness of the portion of the polylactic acid coating layer located on the inner surface is 9.4 microns or the average thickness of the portion of the polylactic acid coating layer located on the side surface is 9.4 microns. In one embodiment, the average thickness of the polylactic acid coating layer on all surfaces is 9.4 microns.

[0059] In one embodiment, the polylactic acid coating layer contains an active drug. In one embodiment, the active drug is selected from at least one of an anti-angiogenic drug, an anti-platelet drug, an anti-thrombus drug, an anti-inflammatory drug and an anti-allergic drug. The anti-angiogenic drug is selected from at least one of paclitaxel, rapamycin and derivatives thereof. The anti-platelet drug can be cilostazol. The anti-thrombus drug can be heparin. The anti-inflammatory drug can be dexamethasone. The anti-allergic drug is selected from at least one of calcium gluconate, chlorpheniramine and cortisone. When the polylactic acid coating layer contains an active drug, i.e. the polylactic acid is mixed with the active drug to form a mixed coating layer, the thickness of the polylactic acid coating layer can be converted from the thickness of the mixed coating layer according to the mass ratio of the polylactic acid to the drug, polylactic acid coating layer thickness (μm) = mixed coating layer thickness (μm) x mass percentage of polylactic acid. x In one embodiment, the active drug can be distributed in at least one of the outer surface, the inner surface and the side surface of the zinc-containing substrate.

[0060] In one embodiment, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 5 kDa. The average thickness of the portion of the polylactic acid coating layer located on the inner surface and the side surface is 0, i.e. there is no polylactic acid coating layer on the inner surface and the side surface. The portion located on the outer surface contains sirolimus, the average thickness of the polylactic acid-sirolimus coating layer is 5.4 microns, and the average thickness of the portion of the polylactic acid coating layer located on the outer surface is converted to 3.6 microns. The mass ratio of the polylactic acid to sirolimus is 2:1.

[0061] In one embodiment, the polylactic acid is poly-DL-lactic acid, the weight average molecular weight of the poly-DL-lactic acid is 200 kDa. The average thickness of the portion of the polylactic acid coating layer located on the inner surface is 8 microns. The portions of the polylactic acid coating layer located on the side surface and the outer surface both contain sirolimus, i.e. they are polylactic acid-sirolimus coating layers, the mass ratio of the polylactic acid to sirolimus is 6:1, the average thickness of the poly-DL-lactic acid-sirolimus coating layer located on the side surface and the outer surface is 10.6 microns, and the average thickness of the polylactic acid coating layer is converted to 9.1 microns.

[0062] The above-mentioned medical device containing zinc can be a vascular stent, a non-vascular endoluminal stent, an occluder, an orthopedic implant, a dental implant, a respiratory implant, a gynecological implant, an andrological implant, a suture or a bolt, etc. The non-vascular endoluminal stent can be a tracheal stent, an esophageal stent, a urethral stent, an intestinal stent or a biliary stent. The orthopedic implant can be a fixation screw, a fixation rivet or a bone plate. Of course, other medical devices that need to achieve degradable absorption can also be used as the medical device of the present embodiment.

[0063] The above-mentioned medical device containing zinc is further described below through specific examples.

[0064] The test method of the following examples is as follows:

[0065] 1. Determination of weight average molecular weight of polylactic acid

[0066] A GPC-multiple angle laser light scattering instrument combined molecular weight test system of Wyatt Company in the United States was used for detection. The test system includes a liquid phase pump and a sample injector of Agilent Company in the United States, a GPC column (size: 7.5*300mm, 5 microns) of Agilent PLMIXED-C type of Agilent Company in the United States, a multiple angle laser light scattering instrument and a differential detector of Wyatt Company in the United States. The detection conditions are as follows:

[0067] Mobile phase: tetrahydrofuran; pump flow rate: 1 mL / min; sample amount: 100 μL; laser wavelength: 663.9 nm; test temperature: 35°C.

[0068] 2. Determination of thickness of polylactic acid coating

[0069] The sample to be tested for coating thickness is first fixed to a sample stage, and then the sample stage is placed in a JFC-1600 gold spraying device for spraying. After one spraying, the sample stage is rotated by 180 degrees and sprayed again to ensure that all positions are sprayed. The sample with the surface sprayed with gold is placed in a Tagle room temperature resin curing agent mixed reagent prepared at a ratio of 5:1, and left to stand for more than 8 hours before being removed from the sample shell. The sealed sample is evenly divided into 3 sections, and each section is polished and ground according to the sample polishing and grinding program using a semi-automatic polishing and grinding machine. The sample cross section to be measured is polished to be free of grinding marks. The polished sample is fixed to the sample stage of a scanning electron microscope, and the entire sample stage is placed in a JFC-1600 gold spraying device for spraying for 20 seconds. The sample sprayed with gold is placed in a JSM-6510 scanning electron microscope for thickness measurement. The inner surface coating thickness, side surface coating thickness and outer surface coating thickness of each cross section are measured respectively; if there are multiple rods in each cross section, the inner surface coating thickness, side surface coating thickness and outer surface coating thickness of at least 3 rods are randomly measured. The average thickness of all measured inner surface coatings is the average thickness of the inner surface coating of the device, the average thickness of all measured side surface coatings is the average thickness of the side surface coating of the device, and the average thickness of all measured outer surface coatings is the average thickness of the outer surface coating of the device.

[0070] 3. Corrosion rate of zinc in zinc-containing medical devices

[0071] The weight loss method is used to detect: the zinc-containing medical device is implanted into a rabbit, and at a predetermined observation time point, such as 1 month, 3 months, …, the rabbit is sacrificed and the zinc-containing medical device is removed. After carefully removing the tissue on the zinc-containing medical device as much as possible, the zinc-containing medical device is then soaked in a saturated glycine solution and ultrasonically cleaned. After 1 minute, the zinc-containing medical device is removed from the glycine solution and quickly washed with clean water for 10 seconds. The washed zinc-containing medical device is then soaked in a 1 mol / L sodium hydroxide solution for 24 hours or more to completely dissolve the zinc. The zinc concentration in the sodium hydroxide solution is then detected by atomic absorption spectrometry (AAS). The corrosion rate of zinc in the zinc-containing medical device can be calculated.

[0072] Example 1

[0073] A zinc-based stent with a specification of 3.0 mm x 8 mm includes a stent base and a polylactic acid coating completely covering the surface of the stent base. The material of the stent base is pure zinc, and the mass of the stent base is 5 mg. The polylactic acid in the polylactic acid coating is poly-racemic lactic acid with a molecular weight of 200 kDa. The average thickness of the polylactic acid coating on the outer surface, the average thickness of the polylactic acid coating on the side surface, and the average thickness of the polylactic acid coating on the inner surface are all 9.1 μm. The polylactic acid coating is prepared by spraying.

[0074] Comparative Example 1-1

[0075] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating completely covering the surface of the stent base, the material of the stent base being pure zinc, the mass of the stent base being 5 mg, the polylactic acid in the polylactic acid coating being poly-racemic lactic acid with a molecular weight of 200 kDa, the average thickness of the polylactic acid coating on the outer surface, the average thickness of the polylactic acid coating on the side surface and the average thickness of the polylactic acid coating on the inner surface all being 6 μm. The polylactic acid coating is prepared by spraying.

[0076] Comparative Example 1-2

[0077] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating completely covering the surface of the stent base, the material of the stent base being pure zinc, the mass of the stent base being 5 mg, the polylactic acid in the polylactic acid coating being poly-racemic lactic acid with a molecular weight of 200 kDa, the average thickness of the polylactic acid coating on the outer surface, the average thickness of the polylactic acid coating on the side surface and the average thickness of the polylactic acid coating on the inner surface all being 16 μm. The polylactic acid coating is prepared by spraying.

[0078] The zinc-based stents of Example 1, Comparative Example 1-1 and Comparative Example 1-2 were respectively implanted into the iliac arteries of three rabbits, and were taken out after 6 months. The zinc corrosion rates were measured to be 12%, 20% and 18% respectively. The zinc corrosion rate of the zinc-based stent of Example 1 was the smallest.

[0079] Example 2

[0080] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating completely covering the surface of the stent base, the material of the stent base being pure zinc, the mass of the stent base being 5 mg, the polylactic acid in the polylactic acid coating being poly-racemic lactic acid with a molecular weight of 50 kDa, the average thickness of the polylactic acid coating on the outer surface being 6 μm, the average thickness of the polylactic acid coating on the side surface being 5.5 μm, and the average thickness of the polylactic acid coating on the inner surface being 4.9 μm. The polylactic acid coating is prepared by spraying.

[0081] Comparative Example 2-1

[0082] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating completely covering the surface of the stent base, the material of the stent base being pure zinc, the mass of the stent base being 5 mg, the polylactic acid in the polylactic acid coating being poly-racemic lactic acid with a molecular weight of 50 kDa, the average thickness of the polylactic acid coating on the outer surface being 6 μm, the average thickness of the polylactic acid coating on the side surface being 5.5 μm, and the average thickness of the polylactic acid coating on the inner surface being 2.5 μm. The polylactic acid coating is prepared by spraying.

[0083] Comparative Example 2-2

[0084] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating covering the surface of the stent base, the material of the stent base is pure zinc, the mass of the stent base is 5 mg, the polylactic acid in the polylactic acid coating is poly-DL-lactic acid with a molecular weight of 50 kDa, the average thickness of the polylactic acid coating on the outer surface is 6 μm, the average thickness of the polylactic acid coating on the side surface is 5.5 μm, and the average thickness of the polylactic acid coating on the inner surface is 8 μm. The polylactic acid coating is prepared by spraying.

[0085] The zinc-based stents of Example 2, Comparative Example 2-1 and Comparative Example 2-2 were respectively implanted into the iliac arteries of three rabbits, and were taken out after 6 months. The zinc corrosion rates were measured to be 18%, 28% and 24% respectively. The zinc corrosion rate of the zinc-based stent of Example 2 is the smallest.

[0086] Example 3

[0087] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid-sirolimus coating covering only the outer surface of the stent base, the material of the stent base is pure zinc, the mass of the stent base is 5 mg, the polylactic acid in the polylactic acid coating is poly-DL-lactic acid with a molecular weight of 5 kDa, the mass ratio of poly-DL-lactic acid to sirolimus is 2:1, the average thickness of the polylactic acid-sirolimus coating is 5.4 μm, and the average thickness of the equivalent polylactic acid coating is 3.6 μm. The polylactic acid-sirolimus coating is prepared by 3D printing.

[0088] Comparative Example 3-1

[0089] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base, the material of the stent base is pure zinc, the mass of the stent base is 5 mg, and there is no polylactic acid coating on the base.

[0090] Comparative Example 3-2

[0091] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid-sirolimus coating covering only the outer surface of the stent base, the material of the stent base is pure zinc, the mass of the stent base is 5 mg, the polylactic acid in the polylactic acid coating is poly-DL-lactic acid with a molecular weight of 5 kDa, the mass ratio of poly-DL-lactic acid to sirolimus is 2:1, the average thickness of the polylactic acid-sirolimus coating is 12 μm, and the average thickness of the equivalent polylactic acid coating is 8 μm. The polylactic acid-sirolimus coating is prepared by spraying.

[0092] The zinc-based stents of Example 3, Comparative Example 3-1 and Comparative Example 3-2 were respectively implanted into the iliac arteries of three rabbits, and were taken out after 3 months. The zinc corrosion rates were measured to be 11%, 17% and 13% respectively. The zinc corrosion rate of the zinc-based stent of Example 3 is the smallest.

[0093] Example 4

[0094] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating completely covering the surface of the stent base, the material of the stent base being a zinc alloy, the mass of the stent base being 5 mg, the polylactic acid in the polylactic acid coating being poly-L-lactic acid with a molecular weight of 300 kDa, the average thickness of the polylactic acid coating on the outer surface, the average thickness of the polylactic acid coating on the side surface and the average thickness of the polylactic acid coating on the inner surface all being 19.6 μm. The polylactic acid coating was prepared by spraying.

[0095] Comparative Example 4-1

[0096] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating completely covering the surface of the stent base, the material of the stent base being pure zinc, the mass of the stent base being 5 mg, the polylactic acid in the polylactic acid coating being poly-L-lactic acid with a molecular weight of 300 kDa, the average thickness of the polylactic acid coating on the outer surface, the average thickness of the polylactic acid coating on the side surface and the average thickness of the polylactic acid coating on the inner surface all being 10 μm. The polylactic acid coating was prepared by spraying.

[0097] Comparative Example 4-2

[0098] A zinc-based stent with a size of 3.0 mm x 8 mm, comprising a stent base and a polylactic acid coating completely covering the surface of the stent base, the material of the stent base being pure zinc, the mass of the stent base being 5 mg, the polylactic acid in the polylactic acid coating being poly-L-lactic acid with a molecular weight of 300 kDa, the average thickness of the polylactic acid coating on the outer surface, the average thickness of the polylactic acid coating on the side surface and the average thickness of the polylactic acid coating on the inner surface all being 30 μm. The polylactic acid coating was prepared by spraying.

[0099] The zinc-based stents of Example 4, Comparative Example 4-1 and Comparative Example 4-2 were respectively implanted into the iliac arteries of three rabbits, and were taken out after 6 months. The zinc corrosion rates were measured to be 21%, 29% and 27% respectively. The zinc corrosion rate of the zinc-based stent of Example 4 was the smallest.

[0100] Example 5

[0101] The iron-based stent has a specification of 3.0 mm x 8 mm, and comprises a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, and a polylactic acid-sirolimus coating layer covering the surface of the pure zinc layer. The mass of iron in the stent body is 4 mg, the mass of the zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The mass ratio of the poly-DL-lactic acid-sirolimus coating layer on the inner surface is 10:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the inner surface is all 5.5 μm, and the equivalent polylactic acid coating layer thickness is 5 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface is 6:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface is all 10.6 μm, and the equivalent polylactic acid coating layer thickness is 9.1 μm. The polylactic acid coating layer and the poly-DL-lactic acid-sirolimus coating layer are prepared by spraying.

[0102] Comparative Example 5-1

[0103] The iron-based stent has a specification of 3.0 mm x 8 mm, and comprises a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, and a polylactic acid-sirolimus coating layer covering the surface of the pure zinc layer. The mass of iron in the stent body is 4 mg, the mass of the zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The mass ratio of the poly-DL-lactic acid-sirolimus coating layer on the inner surface is 10:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the inner surface is all 5.5 μm, and the equivalent polylactic acid coating layer thickness is 5 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface is 6:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface is all 7 μm, and the equivalent polylactic acid coating layer thickness is 6 μm. The polylactic acid coating layer and the poly-DL-lactic acid-sirolimus coating layer are prepared by spraying.

[0104] Comparative Example 5-2

[0105] The iron-based stent has a specification of 3.0 mm x 8 mm, and comprises a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, and a polylactic acid-sirolimus coating layer covering the surface of the pure zinc layer. The mass of iron in the stent body is 4 mg, the mass of the zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The mass ratio of the poly-DL-lactic acid-sirolimus coating layer on the inner surface is 10:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the inner surface is all 5.5 μm, and the equivalent polylactic acid coating layer thickness is 5 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface is 6:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface is all 17.5 μm, and the equivalent polylactic acid coating layer thickness is 15 μm. The polylactic acid coating layer and the poly-DL-lactic acid-sirolimus coating layer are prepared by spraying.

[0106] The iron-based stents of Example 5, Comparative Example 5-1 and Comparative Example 5-2 were implanted into the iliac arteries of three rabbits respectively, and were removed after 1 month. The zinc corrosion rates were measured to be 30%, 56% and 44% respectively. The zinc-based stent of Example 5 had the smallest corrosion rate of zinc, and the pathological section thereof is shown in Figure 5, wherein there was a small amount of inflammatory cell infiltration around the stent, and no obvious abnormal changes such as tissue necrosis. Figure 1

[0107] Example 6

[0108] The iron-based stent had a specification of 3.0 mm x 8 mm, and comprised a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, a polylactic acid coating layer covering the inner surface of the pure zinc layer, and a polylactic acid-sirolimus coating layer covering the side surface and the outer surface of the pure zinc layer. The mass of iron in the stent body was 4 mg, the mass of the zinc layer was 250 μg, and the polylactic acid in the coating layer was all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface was 6 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface was 3:1, and the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface was both 14.7 μm, and the equivalent polylactic acid coating layer thickness was 11 μm.

[0109] Comparative Example 6-1

[0110] The iron-based stent had a specification of 3.0 mm x 8 mm, and comprised a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, a polylactic acid coating layer covering the inner surface of the pure zinc layer, and a polylactic acid-sirolimus coating layer covering the side surface and the outer surface of the pure zinc layer. The mass of iron in the stent body was 4 mg, the mass of the zinc layer was 250 μg, and the polylactic acid in the coating layer was all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface was 6 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface was 3:1, and the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface was both 14.7 μm, and the equivalent polylactic acid coating layer thickness was 11 μm.

[0111] Comparative Example 6-2

[0112] ​The iron-based stent has a specification of 3.0 mm x 8 mm, and comprises a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, a polylactic acid coating layer covering the inner surface of the pure zinc layer, and a polylactic acid-sirolimus coating layer covering the side surface and the outer surface of the pure zinc layer. The mass of iron in the stent body is 4 mg, the mass of the zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface is 6 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface is 3:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface is 21 μm, and the equivalent polylactic acid coating layer thickness is 15.8 μm. The polylactic acid coating layer and the polylactic acid-sirolimus coating layer are prepared by spraying.

[0113] The iron-based stents of Example 6, Comparative Example 6-1 and Comparative Example 6-2 were respectively implanted into the iliac arteries of three rabbits, and were taken out after one month. The zinc corrosion rates were measured to be 33%, 54% and 49% respectively. The zinc-based stent of Example 6 has the smallest corrosion rate of zinc.

[0114] Example 7

[0115] The iron-based stent has a specification of 3.0 mm x 8 mm, and comprises a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, a polylactic acid coating layer covering the inner surface of the pure zinc layer, and a polylactic acid-sirolimus coating layer covering the side surface and the outer surface of the pure zinc layer. The mass of iron in the stent body is 4 mg, the mass of the zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface is 6 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface is 3:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface is 21 μm, and the equivalent polylactic acid coating layer thickness is 15.8 μm. The polylactic acid coating layer and the polylactic acid-sirolimus coating layer are prepared by spraying.

[0116] Comparative Example 7-1

[0117] The iron-based stent has a specification of 3.0 mm x 8 mm, and comprises a stent body made of an iron-based alloy, a pure zinc layer completely covering the surface of the stent body, a polylactic acid coating layer covering the inner surface of the pure zinc layer, and a polylactic acid-sirolimus coating layer covering the side surface and the outer surface of the pure zinc layer. The mass of iron in the stent body is 4 mg, the mass of the zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface is 6 μm; the mass ratio of poly-DL-lactic acid to sirolimus on the side surface and the outer surface is 3:1, the thickness of the poly-DL-lactic acid-sirolimus coating layer on the side surface and the outer surface is 21 μm, and the equivalent polylactic acid coating layer thickness is 15.8 μm. The polylactic acid coating layer and the polylactic acid-sirolimus coating layer are prepared by spraying.

[0118] Comparative Example 7-2

[0119] Iron-based stent, specification 3.0 mm x 8 mm, including a stent body made of iron-based alloy, a pure zinc layer completely covering the surface of the stent body, and a polylactic acid coating covering the inner surface and the side surface of the pure zinc layer, a polylactic acid-sirolimus coating covering the outer surface of the pure zinc layer. The mass of iron in the stent body is 4 mg, the mass of zinc layer is 250 μg, and the polylactic acid in the coating is all poly-racemic lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-racemic lactic acid coating on the inner surface and the side surface is both 4.5 μm; the mass ratio of poly-racemic lactic acid to sirolimus on the outer surface is 4:1, and the average thickness is both 14.5 μm, and the equivalent polylactic acid coating thickness is 11.6 μm. The polylactic acid coating and the polylactic acid-sirolimus coating are prepared by spraying.

[0120] The iron-based stents of Example 7, Comparative Example 7-1 and Comparative Example 7-2 were respectively implanted into the iliac arteries of three rabbits, and taken out after 1 month. The zinc corrosion rates were measured to be 51%, 61% and 63% respectively. The zinc corrosion rate of the zinc-based stent of Example 7 is the smallest.

[0121] Example 8

[0122] Iron-based stent, specification 3.0 mm x 8 mm, including a stent body made of iron-based alloy, and a polylactic acid coating completely covering the surface of the stent body. The mass of iron in the stent body is 4 mg, the mass of zinc layer is 250 μg, and the polylactic acid in the coating is all poly-racemic lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-racemic lactic acid coating on the inner surface is 5.1 μm, and the average thickness of the polylactic acid coating on the outer surface and the side surface is both 7.1 μm. The polylactic acid coating is prepared by spraying.

[0123] Comparative Example 8-1

[0124] Iron-based stent, specification 3.0 mm x 8 mm, including a stent body made of iron-based alloy, and a polylactic acid coating completely covering the surface of the stent body. The mass of iron in the stent body is 4 mg, the mass of zinc layer is 250 μg, and the polylactic acid in the coating is all poly-racemic lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-racemic lactic acid coating on the inner surface is 5.1 μm, and the average thickness of the polylactic acid coating on the outer surface and the side surface is both 7.1 μm. The polylactic acid coating is prepared by spraying.

[0125] Comparative Example 8-2

[0126] An iron-based stent with a size of 3.0 mm x 8 mm includes a stent body made of an iron-based alloy and a polylactic acid coating layer completely covering the surface of the stent body. The mass of iron in the stent body is 4 mg, the mass of zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface is 5.1 μm, and the average thickness of the polylactic acid coating layer on the outer surface and the side surface is 14.8 μm. The polylactic acid coating layer is prepared by spraying.

[0127] The iron-based stents of Example 8, Comparative Example 8-1 and Comparative Example 8-2 were implanted into the iliac arteries of three rabbits, respectively, and were taken out after 1 month. The zinc corrosion rates were measured to be 48%, 54% and 66%, respectively. The zinc corrosion rate of the iron-based stent of Example 8 is the smallest.

[0128] Example 9

[0129] An iron-based stent with a size of 3.0 mm x 8 mm includes a stent body made of an iron-based alloy and a polylactic acid coating layer completely covering the surface of the stent body. The mass of iron in the stent body is 4 mg, the mass of zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface is 7.1 μm, and the average thickness of the polylactic acid coating layer on the outer surface and the side surface is 11.1 μm. The polylactic acid coating layer is prepared by spraying.

[0130] Comparative Example 9-1

[0131] An iron-based stent with a size of 3.0 mm x 8 mm includes a stent body made of an iron-based alloy and a polylactic acid coating layer completely covering the surface of the stent body. The mass of iron in the stent body is 4 mg, the mass of zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface is 7.1 μm, and the average thickness of the polylactic acid coating layer on the outer surface and the side surface is 6.7 μm. The polylactic acid coating layer is prepared by spraying.

[0132] Comparative Example 9-2

[0133] An iron-based stent with a size of 3.0 mm x 8 mm includes a stent body made of an iron-based alloy and a polylactic acid coating layer completely covering the surface of the stent body. The mass of iron in the stent body is 4 mg, the mass of zinc layer is 250 μg, and the polylactic acid in the coating layer is all poly-DL-lactic acid with a molecular weight of 200 kDa. The average thickness of the poly-DL-lactic acid coating layer on the inner surface is 7.1 μm, and the average thickness of the polylactic acid coating layer on the outer surface and the side surface is 16.6 μm. The polylactic acid coating layer is prepared by spraying.

[0134] The iron-based stents of Example 9, Comparative Example 9-1 and Comparative Example 9-2 were implanted into the iliac arteries of three rabbits, respectively, and removed after 1 month. The zinc corrosion rates were measured to be 44%, 64% and 62%, respectively. The zinc corrosion rate of the iron-based stent of Example 9 was the smallest.

[0135] The iron-based stent of Example 10 had a size of 3.0 mm x 8 mm, and included a stent body made of an iron-based alloy, and a polylactic acid coating layer completely covering the surface of the stent body. The mass of iron in the stent body was 4 mg, the mass of zinc layer was 250 μg, and the polylactic acid in the coating layer was all poly-DL-lactic acid with a molecular weight of 100 kDa. The average thickness of the polylactic acid coating layer on the inner surface, the outer surface and the side surface was 7.3 μm. The polylactic acid coating layer was prepared by spraying. The iron-based stent of Comparative Example 10-1 had a size of 3.0 mm x 8 mm, and included a stent body made of an iron-based alloy, and a polylactic acid coating layer completely covering the surface of the stent body. The mass of iron in the stent body was 4 mg, the mass of zinc layer was 250 μg, and the polylactic acid in the coating layer was all poly-DL-lactic acid with a molecular weight of 100 kDa. The average thickness of the polylactic acid coating layer on the inner surface, the outer surface and the side surface was 4 μm. The polylactic acid coating layer was prepared by spraying. The iron-based stent of Comparative Example 10-2 had a size of 3.0 mm x 8 mm, and included a stent body made of an iron-based alloy, and a polylactic acid coating layer completely covering the surface of the stent body. The mass of iron in the stent body was 4 mg, the mass of zinc layer was 250 μg, and the polylactic acid in the coating layer was all poly-DL-lactic acid with a molecular weight of 100 kDa. The average thickness of the polylactic acid coating layer on the inner surface, the outer surface and the side surface was 11 μm. The polylactic acid coating layer was prepared by spraying. The iron-based stents of Example 10, Comparative Example 10-1 and Comparative Example 10-2 were implanted into the iliac arteries of three rabbits, respectively, and removed after 1 month. The zinc corrosion rates were measured to be 48%, 69% and 55%, respectively. The zinc corrosion rate of the iron-based stent of Example 10 was the smallest.

[0136] Any combination of the technical features in the above-described embodiments can be made, and to make the description concise, all possible combinations of the technical features in the above-described embodiments are not described, however, as long as the combinations of the technical features do not exist, they should be considered as the scope of the description.

[0137] The above-described embodiments only express several implementation manners of the present application, and the description is relatively specific and detailed, however, it should not be understood as a limitation on the scope of the patent right of the present application. It should be pointed out that, for ordinary skilled in the art, several modifications and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent right of the present application should be subject to the appended claims.

Claims

1. A zinc-containing medical device, characterized in that, The invention includes a zinc-containing substrate and a polylactic acid (PLA) coating disposed on the surface of the zinc-containing substrate. The zinc-containing substrate has an outer surface, an inner surface, and a side surface. The PLA coating covers the outer surface, the inner surface, and the side surface. The average thickness of the portion of the PLA coating located on the outer surface is [missing information]. x 外 The average thickness of the polylactic acid coating located on the inner surface is x 内 The average thickness of the polylactic acid coating on the side surface is x 侧 The average thickness of the polylactic acid coating on at least two of the inner, side, and outer surfaces is not the same, and the x 外 , x 内 and x 侧 At least one satisfies the following formula: , x = x 内 , x 侧 or x 外 ; Wherein, when the polylactic acid is polyracemic lactic acid, a = 0.0336ln(Mn) - 0.1449, b = -0.472ln(Mn) + 2.1524, c = 1.1604ln(Mn) - 5.7128; When the polylactic acid is poly-L-lactic acid, a = -0.006ln(Mn) + 0.03441, b = 0.0648ln(Mn) - 0.3662, c = -0.162ln(Mn) + 0.7847; Mn is the weight-average molecular weight of polylactic acid, measured in kilodaltons. x The unit is micrometer; The polylactic acid is polyracemic lactic acid, the weight-average molecular weight of which is 100-300 kDa, and the average thickness of the polylactic acid coating on the outer surface is 5.2-11.5 micrometers; the average thickness of the polylactic acid coating on the inner surface is 5.2-11.5 micrometers; the average thickness of the polylactic acid coating on the side surface is 5.2-11.5 micrometers; or The polylactic acid is polyracemic lactic acid, the weight-average molecular weight of which is 10-100 kDa, and the average thickness of the polylactic acid coating on the outer surface is 2-9 micrometers; the average thickness of the polylactic acid coating on the inner surface is 2-9 micrometers; the average thickness of the polylactic acid coating on the side surface is 2-9 micrometers; or The polylactic acid is polyracemic lactic acid, the weight-average molecular weight of which is 2-10 kDa, and the average thickness of the polylactic acid coating on the outer surface is 1.5-5.5 micrometers; the average thickness of the polylactic acid coating on the inner surface is 1.5-5.5 micrometers; the average thickness of the polylactic acid coating on the side surface is 1.5-5.5 micrometers; or The polylactic acid is poly-L-lactic acid, the weight-average molecular weight of which is 200-300 kDa, and the average thickness of the polylactic acid coating on the outer surface is 9-22 micrometers; the average thickness of the polylactic acid coating on the inner surface is 9-22 micrometers; the average thickness of the polylactic acid coating on the side surface is 9-22 micrometers; or The polylactic acid is poly-L-lactic acid, the weight-average molecular weight of the poly-L-lactic acid is 50~200kDa, and the average thickness of the portion of the polylactic acid coating located on the outer surface is 7~13 micrometers; the average thickness of the portion of the polylactic acid coating located on the inner surface is 7~13 micrometers; and the average thickness of the portion of the polylactic acid coating located on the side surface is 7~13 micrometers.

2. A zinc-containing medical device, characterized in that, The invention includes a zinc-containing substrate and a polylactic acid (PLA) coating disposed on the surface of the zinc-containing substrate. The zinc-containing substrate has an outer surface, an inner surface, and a side surface. The PLA coating covers the outer surface, the inner surface, and the side surface. The average thickness of the portion of the PLA coating located on the outer surface is [missing information]. x 外 The average thickness of the polylactic acid coating located on the inner surface is x 内 The average thickness of the polylactic acid coating on the side surface is x 侧 , x 内 ≤ x 外 , x 内 ≤ x 侧 And the x 外 , x 内 and x 侧 At least one satisfies the following formula: , x = x 内 , x 侧 or x 外 Wherein, when the polylactic acid is polyracemic lactic acid, a = 0.0336ln(Mn) - 0.1449, b = -0.472ln(Mn) + 2.1524, c = 1.1604ln(Mn) - 5.7128; When the polylactic acid is poly-L-lactic acid, a = -0.006ln(Mn) + 0.03441, b = 0.0648ln(Mn) - 0.3662, c = -0.162ln(Mn) + 0.7847; Mn is the weight-average molecular weight of polylactic acid, measured in kilodaltons. x The unit is micrometer; The polylactic acid coating covers only a portion of the zinc surface of the zinc-containing substrate; The polylactic acid is polyracemic lactic acid, the weight-average molecular weight of which is 100-300 kDa, and the average thickness of the portion of the polylactic acid coating located on the outer surface is 5.2-11.5 micrometers; the average thickness of the portion of the polylactic acid coating located on the inner surface is 5.2-11.5 micrometers; and the average thickness of the portion of the polylactic acid coating located on the side surface is 5.2-11.5 micrometers.

3. The zinc-containing medical device according to any one of claims 1-2, characterized in that, The zinc-containing substrate is made of pure zinc or a zinc alloy; or, the zinc-containing substrate includes a body and a zinc-containing layer attached to the body, and the zinc-containing layer is made of pure zinc or a zinc alloy.

4. The zinc-containing medical device according to claim 3, characterized in that, When the zinc-containing matrix material is pure zinc or a zinc alloy, the zinc content in the zinc alloy is 50% to 99.99% by mass; When the zinc-containing substrate includes a body and a zinc-containing layer attached to the body, and the material of the zinc-containing layer is a zinc alloy, the zinc content in the zinc alloy is 50% to 99.99% by mass.

5. The zinc-containing medical device according to claim 3, characterized in that, The zinc-containing layer covers the entire surface of the body.

6. The zinc-containing medical device according to any one of claims 1-2, characterized in that, The polylactic acid coating contains an active pharmaceutical ingredient.

7. The zinc-containing medical device according to claim 1, characterized in that, The polylactic acid coating covers only a portion of the zinc surface of the zinc-containing substrate.

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