IMPLANTABLE DEVICE

Abstract

An implantable apparatus, including at least one corrodible zinc-containing portion, where a content range of zinc in the at least one zinc-containing portion is [30, 50) wt. % and zinc in the zinc-containing portion is an amorphous structure, or a content range of zinc in the at least one zinc-containing portion is [50, 70] wt. %, and a microscopic structure of zinc in the zinc-containing portion is at least one of an amorphous structure, a non-equiaxed structure, an ultrafine-grained structure, or an equiaxed structure with a grain size number of 7 to 14, or a content range of zinc in the at least one zinc-containing portion is (70, 100] wt. % and a microscopic structure of zinc in the zinc-containing portion is at least one of a non-equiaxed structure, an ultrafine-grained structure, or an equiaxed structure with a grain size number of 7 to 14.

Claims

1-19. (canceled)

20. An implantable device comprising: at least one corrodible zinc-containing portion, wherein the zinc content in the at least one zinc-containing portion ranges from [30,50) wt. % and the microstructure of zinc in the zinc-containing portion is an amorphous structure.

21. An implantable device comprising: at least one corrodible zinc-containing portion, wherein the zinc content in the at least one zinc-containing portion ranges from [50,70] wt. %, and the microstructure of zinc in the zinc-containing portion is at least one of an amorphous structure, an non-equiaxed structure, an ultrafine-grained structure or an equiaxed structure having a micro-grain size number of 7-14.

22. An implantable device comprising: at least one corrodible zinc-containing portion, wherein the zinc content in the at least one zinc-containing portion ranges from (70,100] wt. %, and the microstructure of zinc in the zinc-containing portion is at least one of an non-equiaxed structure, an ultrafine-grained structure or an equiaxed structure having a micro-grain size number of 7-14.

23. The implantable device of claim 22, wherein the zinc-containing portion has a thickness greater than 100 nm.

24. The implantable device of claim 22, wherein zinc is present in the zinc-containing portion in the form of elemental zinc or a zinc alloy.

25. The implantable device of claim 24, wherein the zinc alloy is an alloy of zinc and at least one of iron, magnesium, manganese, copper or strontium, or an alloy of zinc doped with at least one of carbon, nitrogen, oxygen, boron or silicon.

26. The implantable device of claim 22, wherein the implantable device comprises a substrate, the substrate at least partially is comprised of, or is at least partially in contact with, the zinc-containing portion.

27. The implantable device of claim 26, wherein the substrate is in contact with the zinc-containing portion in a manner selected from at least one of the following: the zinc-containing portion at least partially covers the surface of the substrate; or the substrate being provided with a gap, a groove or a hole in which the zinc-containing portion is disposed; or the substrate being provided with an cavity in which the zinc-containing portion is filled.

28. The implantable device of claim 26, wherein the substrate is at least partially made of iron or an iron alloy.

29. The implantable device of claim 26, wherein the substrate is at least partially made of a polymer.

30. The implantable device of claim 29, wherein the polymer is selected from at least one of a degradable polymer, a non-degradable polymer, or a copolymer formed by copolymerizing at least one monomer forming the degradable polymer and at least one monomer forming the non-degradable polymer, the degradable polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polycarbonate, Polysuccinate or poly (-hydroxybutyrate), the non-degradable polymer is selected from the group consisting of polystyrene, polytetrafluoroethylene, polymethylmethacrylate or polyethylene terephthalate.

31. The implantable device of claim 26, wherein the implantable device further comprises an outer layer in contact with the substrate and/or the zinc-containing portion, the outer layer has a porous structure, or the outer layer comprises at least one of degradable resins, corrodible metals or alloys, or water-soluble polymers.

32. The implantable device of claim 31, wherein the outer layer comprises at least one polyester selected from at least one of degradable polyesters, non-degradable polyestera, or copolymers formed by copolymerizing at least one monomer forming the degradable polyester and at least one monomer forming the non-degradable polyester, the degradable polyester is selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polycarbonate, Polysuccinate or poly (-hydroxybutyrate), the non-degradable polyester is selected from the group consisting of polystyrene, polytetrafluoroethylene, polymethylmethacrylate or polyethylene terephthalate.

33. The implantable device of claim 32, wherein the polyester is in contact with the substrate in a manner selected from at least one of the following: the polyester at least partially covers the surface of the substrate; or the substrate being provided with a gap, a groove or a hole in which the polyester is disposed; the polyester is in contact with the zinc-containing portion in a manner selected from at least one of the following: the polyester at least partially covers the surface of the zinc-containing part; or the zinc-containing portion being provided with a gap, a groove or a hole in which the polyester is disposed.

34. The implantable device of claim 31, wherein the outer layer comprises at least one corrodible metal or alloy, and the mass fraction of zinc in the metal or alloy is less than or equal to 0.1%.

35. The implantable device of claim 31, wherein the outer layer further comprises at least one active agent selected from at least one of cytostatic agents, corticosteroids, prostacyclins, antibiotics, cytostatic agents, immunosuppressive agents, anti-inflammatory agents, anti-angiogenic agents, anti-stenosis agents, anti-thrombotic agents, anti-sensitizing agents, or anti-tumor agents.

36. The implantable device of claim 22, wherein the implantable device is a degradable implantable device, a partially degradable implantable device, or a non-degradable implantable device.

37. The implantable device of claim 22, wherein the implantable device comprises a vascular stent, a biliary stent, an esophageal stent, a urethral stent, or a vena cava filter.

38. The implantable device of claim 37, wherein the vena cava filter is at least partially made of a shape memory material, the shape memory material comprising a nickel titanium alloy.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0051] FIG. 1 is a schematic view showing the structure of the vena cava filter of Embodiment 1;

[0052] FIG. 2 is a pathological section of the tissue surrounding the vascular stent of Embodiment 5 after the stent being implanted into a coronary artery vessel of a minipig for one month;

[0053] FIG. 3 is a pathological section of the tissue surrounding the vascular stent of Embodiment 6 after the sent being implanted into a coronary artery vessel of a minipig for three month;

[0054] FIG. 4 is a pathological section of the tissues surrounding the vascular stent of Embodiment 10 after the stent being implanted into a coronary artery vessel of a minipig for one month;

[0055] FIG. 5 is a pathological section of the tissues surrounding the vascular stent of Comparative Embodiment 1 after the stent being implanted into a coronary artery vessel of a minipig for one month;

[0056] FIG. 6 is a pathological section of the tissue surrounding the vascular stent of Comparative Example 3 after the stent being implanted into a coronary artery vessel of a minipig for one month.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0057] First, the measurement method related to embodiments of the present disclosure is described as follows:

Measurement of Zinc Content in Zinc-Containing Portion of Implantable Device

[0058] The zinc content in the zinc-containing portion is determined by a X-ray photoelectron spectroscopy (XPS) or a scanning electron microscopy (SEM) as follows: based on the actual position of the zinc-containing portion in the implantable device, a cross section of the zinc-containing portion of the implanted device is exposed by one or more methods selecting from the group consisting of resin embedding followed by grinding, direct grinding and ion sputtering. Then the cross-section was observed through XPS or SEM by randomly selecting a square region within the cross-section and the zinc content of the square region was measured by an energy dispersive spectrometeran accessory of XPS or SEM. The above steps are repeated and measured the zinc content of square regions with the same area in at least three sections of the zinc-containing portion. An average value is obtained by summarizing the zinc content of the square region of each section then averaging it as the zinc content of the zinc-containing portion.

XPS is ESCALAB 250Xi X-ray photoelectron spectrometer from Thermo Fisher, and SEM is JSM6510 Scanning Electron Microscope from Japan Electronics Co., Ltd., or the like.

Measurement of Microstructure and Grain Size of Zinc in Zinc-Containing Portion of Implantable Device

[0059] The grain size of zinc in the zinc-containing portion of the implantable device is measured according to GB/T 6394-2002 or ASTM E112-13 and will not be described further herein.

Thickness Measurement of Zinc-Containing Portion of Implantable Device

[0060] The thickness of the zinc-containing portion was measured by the following method: A part of the zinc-containing portion of the implantable device is embedded and secured by resin and ground and polished on a metallographic specimen pre-mill until a section of the zinc-containing portion of the implantable device was exposed. At least three sections perpendicular to the surface of the device were selected and then observed using SEM. And the position of the zinc-containing portion in the cross section was determined again by an energy dispersive spectrometeran accessory of the SEM, to measure the thickness of at least three positions in the zinc-containing portion along the normal direction of the surface of the implantable device. And an average value is obtained by summarizing the thicknesses at multiple positions of the zinc-containing portion in each section then averaging it as the thickness of the zinc-containing portion.

[0061] SEM is JSM6510 Scanning Electron Microscope from Japan Electronics Co., Ltd., or the like.

Measurement of Stenosis Rate in Tissues Surrounding the Zinc-Containing Portion

[0062] The stenosis rate in the tissues surrounding the zinc-containing portion was measured by animal implantation experiments. Taking a vascular stent as an example, the measurement includes the following steps. Several Vascular stents were implanted into blood vessels of several test animals respectively. The vascular stent and the vascular tissues surrounding the vascular stent were then removed at a predetermined observation time, such as 1 month, 3 months, and 6 months respectively. After a pathological section of the stent together with the vascular tissues, the section was observed using a DM2500 microscope from LEICA, Germany, and the lumen area of the section in which the zinc-containing portion of the device was located and the original lumen area were measured. Then, the luminal stenosis rate=(original lumen area-existing lumen area)/original lumen area100%.

[0063] The implantable device provided by embodiments in the present disclosure is further described below with reference to the figures and embodiments. It can be understood that the following embodiments are only exemplary embodiments of the disclosure and are non-limiting. Any modification and equivalent replacement and improvement, and the like, of embodiments in this disclosure are within the spirit and principle of this disclosure and are intended to remain within the scope of the invention.

Embodiment 1

[0064] FIG. 1 showed a vena cava filter made of a nitinol material. The filter was mainly composed of a number of supporting rods 11, one end of each support rod 11 being provided with a fixing anchor 12. After being implanted, the anchors 12 penetrated the inner wall of the blood vessel to fix the vena cava filter. After the fixing anchors 12 of the vena cava filter and the supporting rods 11 connected with the fixing anchor 12 being subjected to surface treatment, a zinc layer was plated by an electroplating method, thus the vena cava filter of this embodiment was obtained, the electroplating process parameters were as follows: composition of electroplating solution: zinc chloride 50 g/L, potassium chloride 150 g/L, boric acid 20 g/L, pH of the electroplating solution: 5, plating temperature: 20 C., current density: 5 A/dm.sup.2. In the vena cava filter of the embodiment, the zinc-containing portion was a zinc plating on the fixing anchor and the filter rod connected to it.

[0065] In the vena cava filter provided in Embodiment 1, the zinc content in the zinc-containing portion (i.e., the zinc plating on the fixing anchor and the filter rod connected to it) was 99.6 wt % as measured by the above measurement method, and the microstructure of zinc was a nano-scale ultrafine-grained structure. The thickness of the zinc-containing portion was 0.5 microns.

[0066] The vena cava filter provided in Embodiment 1 was implanted into the inferior vena cava of a dog. One month after implantation, the filter and the vascular tissues surrounding the filter were removed, the vascular tissues surrounding the anchors of the vena cava filter were separated, and a pathological analysis was conducted on the vascular tissues surrounding the anchors. The results showed that after the vena cava filter provided by Embodiment 1 being implanted into the animal for one month, there was no obvious hyperplasia of smooth muscle cells in the vascular tissues surrounding the anchors, and there was also no significant neointima attached to the anchors and the filter rods connected to it.

Embodiment 2

[0067] The vascular stent of Embodiment 2 was made using a pure zinc material. In the vascular stent of the embodiment, the zinc-containing portion was the entire pure zinc stent.

[0068] The zinc content in the zinc-containing portion of the vascular stent provided in Embodiment 2 was 99.9 wt. % as measured by the above measurement method. The microstructure of zinc is an equiaxed structure with a micro-grain size number of 14. The thickness of the zinc-containing portion was 120 microns.

[0069] The vascular stent provided by Embodiment 2 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. It was followed up one month after implantation, during which the stent and the vascular tissues surrounding the stent were removed and a pathological analysis was conducted on the vascular tissues. The pathological analysis results showed that the vascular stent provided by Embodiment 2 can effectively inhibit hyperplasia of smooth muscle cells of the vascular tissues surrounding the stent after the stent being implanted into an animal for one month, and endothelial cells grew normally, no cell necrosis occurred, and the luminal stenosis rate was 36% as measured by the above method.

Embodiment 3

[0070] A zinc layer was uniformly plated on the surface of the 316 L stainless steel stent by an electroplating method. The electroplating process parameters were as follows to obtain the vascular stent of the embodiment: composition of electroplating solution: zinc chloride 50 g/L, potassium chloride 150 g/L, boric acid 20 g/L, pH of the electroplating solution: 5, electroplating temperature: 20 C., current density: 5 A/dm.sup.2. In the vascular stent of this embodiment, the zinc-containing portion was a zinc plating covering the entire surface of the 316 L stainless steel stent, and the thickness of the stainless steel stent was 120 mum.

[0071] The zinc content in the zinc-containing portion (i.e., the zinc plating) in the vascular stent provided in Embodiment 3 was 99 wt. % as measured by the above measurement method. The microstructure of zinc was an ultrafine-grained structure. The thickness of the zinc-containing portion was 1 micron.

[0072] The vascular stent of Embodiment 3 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. It was then followed up 1 month after implantation. During the follow-up, the stent and the vascular tissues surrounding the stent were removed, and a pathological analysis of the tissues surrounding the stent showed that after the vascular stent provided by Embodiment 3 being implanted into the animal for one month, there was no obvious hyperplasia of smooth muscle cells in the tissues surrounding the vascular stent, and the endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 38% as measured by the above measurement method.

Embodiment 4

[0073] A number of grooves were carved on the surface of the 316 L stainless steel vascular stent to a depth of 20 microns, and elemental zinc with the zinc content of 99 wt. % was tightly embedded into the grooves to obtain the vascular stent of the embodiment. In the vascular stent of the embodiment, the zinc-containing portion was elemental zinc embedded in the grooves, and the thickness of the stainless steel stent was 120 micrometers.

[0074] The zinc content in the zinc-containing portion (i.e., the zinc alloy embedded in the grooves) in the vascular stent provided in Embodiment 4 was 99 wt. % as measured by the above measurement method, the microstructure of zinc was a non-equiaxed crystal structure, and the thickness of the zinc-containing portion was 20 micrometers.

[0075] The vascular stent provided in Embodiment 4 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. One month after implantation, the stent and the vascular tissue surrounding the stent were removed, and a pathological analysis was conducted on the vascular tissues. The results showed that after the vascular stent provided by the embodiment 4 being implanted into the animal for 1 month, there was no obvious hyperplasia of smooth muscle cells in the tissues surrounding the stent, and the endothelial cells of the vascular tissue grow normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 28% as measured by the above measurement method.

Embodiment 5

[0076] A zinc layer was uniformly plated on the surface of a pure iron stent by an electroplating method. The electroplating process parameters were as follows to obtain the vascular stent of the embodiment: composition of electroplating solution: zinc chloride 50 g/L, potassium chloride 150 g/L, boric acid 20 g/L, pH of the electroplating solution: 5, electroplating temperature: 20 C., current density: 5 A/dm.sup.2. In the vascular stent of the embodiment, the zinc-containing portion was the zinc plating covering the entire surface of the pure iron stent, and the thickness of the pure iron stent was 60 microns.

[0077] The zinc content in the zinc-containing portion (i.e., the zinc plating) in the vascular stent provided by Embodiment 5 was 99 wt. % as measured by the above measurement method. The microstructure of zinc was an ultrafine-grained structure. The thickness of the zinc-containing portion was 1 micron.

[0078] The vascular stent of Embodiment 5 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. It was then followed up 1 month after implantation. During the follow-up, the stent and the vascular tissues surrounding the stent were removed, a pathological analysis was conducted on the tissues surrounding the stent, and the pathological pictures were shown in FIG. 2. The pathological analysis results showed that after the vascular stent provided by Embodiment 5 being implanted into the animal for one month, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 30% as measured by the above measurement method.

Embodiment 6

[0079] A zinc layer was uniformly plated on the surface of the pure iron stent by an electroplating method. The electroplating process parameters were as follows to obtain the vascular stent of this embodiment: composition of electroplating solution: zinc oxide 15 g/L, ferrous sulfate.7H2O 5 g/L, sodium hydroxide 100 g/L, triethanolamine 25 ml/L, temperature: 25 C., current density: 1 A/dm.sup.2. In the vascular stent of the embodiment, the zinc-containing portion was a zinc plating covering the entire surface of the pure iron stent, the thickness of the stent being 60 microns.

[0080] The zinc content in the zinc-containing portion (i.e., the zinc plating) in the vascular stent provided by Embodiment 6 was 80 wt. % as measured by the above measurement method, and the microstructure of zinc was an ultrafine-grained structure. The thickness of the zinc-containing portion was 1 micron.

[0081] The vascular stent provided in Embodiment 6 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. After 3 months of implantation, the stent and the vascular tissues surrounding the stent were removed and a pathological analysis was conducted on the vascular tissues, the pathological picture was shown in FIG. 3. The pathological analysis results showed that after the vascular stent provided by the embodiment 6 being implanted into the animal for 3 months, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 30% as measured by the above measurement method.

Embodiment 7

[0082] A zinc layer was uniformly plated on the surface of the pure iron stent by an electroplating method. The electroplating process parameters are as follows to obtain the vascular stent of the embodiment: composition of electroplating solution: zinc oxide 15 g/L, ferrous sulfate.7H2O 5 g/L, sodium hydroxide 100 g/L, triethanolamine 25 mL/L, temperature: 25 C., current density: 1 A/dm.sup.2. In the vascular stent of the embodiment, the zinc-containing portion is a zinc plating covering the entire surface of the pure iron stent, the thickness of the pure iron stent being 60 microns.

[0083] The zinc content in the zinc-containing portion (i.e., the zinc plating) in the vascular stent provided in Embodiment 7 was 80 wt. % as measured by the above measurement method, and the microstructure of zinc was an ultrafine-grained structure. The thickness of the zinc-containing portion was 0.5 microns.

[0084] The vascular stent provided by Embodiment 7 was implanted into a coronary artery vessel of a minipig to maintain an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. After 3 months of implantation, the stent and the vascular tissues surrounding the stent were removed and a pathological analysis was conducted on the vascular tissues. The pathological analysis results showed that after the vascular stent provided by Embodiment 7 being implanted into the animal for three months, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 38% as measured by the above measurement method.

Embodiment 8

[0085] A number of grooves were carved on the surface of the pure iron vascular stent to a depth of 20 microns, and zinc alloy with zinc content of 70 wt. % was tightly embedded into the grooves to obtain the vascular stent of the embodiment. In the vascular stent of the embodiment, the zinc-containing portion was zinc alloy embedded in the grooves, and the thickness of the stainless steel stent was 120 microns.

[0086] The zinc content in the zinc-containing portion (i.e., the zinc alloy embedded in the groove) in the vascular stent provided by Embodiment 8 was 70 wt. % as measured by the above measurement method, the microstructure of the zinc was an equiaxed crystal structure having a micro-grain size number of 10, and the thickness of the zinc-containing portion was 20 micrometers.

[0087] The vascular stent provided in Embodiment 8 was implanted into a coronary artery vascular of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. One month after implantation, the stent and the vascular tissue surrounding the stent were removed, and a pathological analysis was conducted on the vascular tissues. The results showed that after the stent provided by Embodiment 8 being implanted into the animal for one month, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 19% as measured by the above measurement method.

Embodiment 9

[0088] The vascular stent of Embodiment 9 was made of a zinc alloy material. In the vascular stent of the embodiment, the zinc-containing portion was the entire zinc alloy stent.

[0089] The zinc content in the zinc-containing portion of the vascular stent provided by Embodiment 9 was 60 wt. % as measured by the above measurement method. The microstructure of zinc was an equiaxed structure with a micro-grain size number of 7. The thickness of the zinc-containing portion was 120 microns.

[0090] The vascular stent provided by Embodiment 9 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. It was followed up one month after implantation, during which the stent and the vascular tissues surrounding the stent were removed, and a pathological analysis of the vascular tissues showed that after the stent provided by Embodiment 9 being implanted into the animal for one month, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 35% as measured by the above measurement method.

Embodiment 10

[0091] The vascular stent of Embodiment 10 was made of a zinc alloy material. In the vascular stent of the embodiment, the zinc-containing portion was the entire zinc alloy stent.

[0092] The zinc content in the zinc-containing portion of the vascular stent provided by Embodiment 10 was 60 wt. % as measured by the above measurement method. The microstructure of zinc was an amorphous structure. The thickness of the zinc-containing portion was 120 microns.

[0093] The vascular stent provided by Embodiment 10 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. It was followed up one month after implantation, during which the stent and the vascular tissue surrounding the stent were removed, and a pathological analysis was conducted on the vascular tissues, the results were shown in FIG. 4. The pathological analysis results showed that after the stent provided by Embodiment 10 being implanted into the animal for one month, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the vascular stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 35% as measured by the above measurement method.

Embodiment 11

[0094] The vascular stent of Embodiment 11 was made of a zinc alloy material. In the vascular stent of the embodiment, the zinc-containing portion was the entire zinc alloy stent.

[0095] The zinc content in the zinc-containing portion of the vascular stent provided in Embodiment 11 was 50 wt. % as measured by the above test method. The microstructure of zinc was an amorphous structure. The thickness of the zinc-containing portion was 120 microns.

[0096] The vascular stent provided by Embodiment 11 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. It was followed up one month of implantation, during which the stent and the vascular tissues surrounding the stent were removed, and a pathological analysis was conducted on the vascular tissues. The results showed that after the stent provided by Embodiment 11 being implanted into the animal for one month, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the vascular stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 30% as measured by the above test method.

Embodiment 12

[0097] The vascular stent of Embodiment 12 was made of a zinc alloy material. In the vascular stent of the embodiment, the zinc-containing portion was the entire zinc alloy stent.

[0098] The zinc content in the zinc-containing portion of the vascular stent provided by Embodiment 12 was 30 wt. % as measured by the above test method. The microstructure of zinc is an amorphous structure. The thickness of the zinc-containing portion was 120 microns.

[0099] The vascular stent provided by Embodiment 12 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. It was followed up one month after implantation, during which the stent and the vascular tissues surrounding the stent were removed, and a pathological analysis was conducted on the vascular tissues. The results showed that after the stent provided by Embodiment 12 being implanted into the animal for one month, there was no significant hyperplasia of smooth muscle cells in the tissues surrounding the vascular stent, and endothelial cells of the vascular tissues grew normally, and also no tissue cell necrosis occurred around the stent struts. The vascular stenosis rate was 35% as measured by the above measurement method.

Comparative Example 1

[0100] A number of grooves were carved on the surface of the 316 L stainless steel stent to a depth of 20 microns, and an elemental zinc with the zinc content of 99 wt. % was tightly embedded into the grooves to obtain the vascular stent of the comparative example, the thickness of the stainless steel stent was 120 microns. In the vascular stent of this comparative example, the zinc-containing portion was elemental zinc embedded into the grooves.

[0101] The zinc content in the zinc-containing portion (i.e., the zinc alloy embedded to in the grooves) in the vascular stent provided by Comparative Example 1 was 99 wt. % as measured by the above measurement method, the microstructure of zinc was amorphous and the thickness of the zinc-containing portion was 20 microns.

[0102] The vascular stent of Comparative Example 1 was implanted into a coronary artery vessel of a minipig. One month after implantation, the stent and the vascular tissue surrounding the stent were removed, and a pathological analysis was conducted on the vascular tissues, and the pathological pictures were shown in FIG. 5. As can be seen from FIG. 5, after the stent of Comparative Example 1 being implanted into the animal for one month, there was significant cell necrosis in the vascular tissues surrounding the vascular stent.

[0103] By comparing the two pathological analysis results of the vascular tissues surrounding the vascular stent respectively provided by Embodiment 4 and Comparative Example 1 one month after the stents being respectively implanted into an animal, it was found that in the vascular stent of Comparative Example 1, since the zinc content in the zinc-containing portion was not matched with the microstructure of zinc, the peak concentration of zinc corrosion products accumulated in the surrounding tissues exceeded the concentration that is toxic to normal tissue cells, and a significant cell necrosis occurred in the surrounding tissues. While in the vascular stent provided by Embodiment 4, by matching the zinc content in the zinc-containing portion on the surface of the stent with the microstructure of zinc, the mass of zinc corrosion products generated per unit time can be adjusted, such that the generated zinc corrosion products can inhibit hyperplasia of smooth muscle cells of vascular tissues surrounding the stent without causing cell necrosis.

Comparative Example 2

[0104] Zinc was uniformly plated on the surface of the 316 L stainless steel stent by an electroplating process to obtain the vascular stent of Comparative Example 2, the electroplating process parameters were as follows: composition of electroplating solution: zinc chloride 50 g/L, potassium chloride 150 g/L, boric acid 20 g/L, pH of the electroplating solution: 5, electroplating temperature: 20 C., current density: 5 A/dm.sup.2. In the vascular stent of Comparative Example 2, the zinc-containing portion was a zinc plating covering the entire surface of the pure iron stent, the stainless steel stent having a thickness of 120 m.

[0105] The content of zinc in the zinc-containing portion (i.e., the zinc plating) in the vascular stent of Comparative Example 2 was 99 wt. % as measured by the above measurement method, and the microstructure of the zinc was an ultrafine-grained structure. The thickness of the zinc-containing portion was 80 nm.

[0106] The vascular stents of Comparative Example 2 were implanted into a coronary artery vascular of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. The stents and the vascular tissues surrounding the stent were removed at 14 days and 1 month after implantation, respectively, and the vascular tissues were analyzed pathologically. The results of the pathological analysis showed that the smooth muscle cells of the tissues surrounding the stent were effectively inhibited at 14 days after implantation without cell necrosis, but hyperplasia of smooth muscle cells of the tissue surrounding the stent occurred obviously at 1 month after implantation, and the vascular stenosis rate was 44% as measured by the above method. Endothelial cells grew normally without cell necrosis.

[0107] The pathological analysis results of Comparative Example 2 showed that, in the vascular stent of Comparative Example 2, hyperplasia of smooth muscle cells in the tissues surrounding the zinc-containing portion can be inhibited by matching the zinc content in the zinc-containing portion with the microstructure of zinc, but the effect of inhibiting hyperplasia cannot be continuously maintained within one month due to the small thickness of the zinc-containing portion.

Comparative Example 3

[0108] The vascular stent of Comparative Example 3 was made of a zinc alloy material. In the vascular stent of this comparative example, the zinc-containing portion was the entire zinc alloy stent.

[0109] The zinc content in the zinc-containing portion of the vascular stent provided by Comparative Example 3 was 30 wt. % as measured by the above measurement method. The microstructure of zinc is an equiaxed structure with a micro-grain size number of 10. The thickness of the zinc-containing portion was 120 microns.

[0110] The vascular stent of Comparative Example 3 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion ratio in the range of 1.1:1 to 1.2:1 during implantation. One month after implantation, the stent and its vascular tissue surrounding the stent were removed and a pathological analysis was conducted on the vascular tissues, and the results were shown in FIG. 6. As can be seen from FIG. 6, when the vascular stent of Comparative Example 3 was implanted into an animal for 1 month, smooth muscle cells of vascular tissues surrounding the stent were proliferated seriously, and the stenosis rate of blood vessels was 43% as measured by the above method. Endothelial cells grew normally without cell necrosis.

[0111] By comparing the two pathological analysis results of the vascular tissues around the vascular stent respectively provided by Embodiment 12 and Comparative Example 3 one month after the stent being respectively implanted into an animal, it was found that in the vascular stent of Comparative Example 3, since the zinc content in the zinc-containing portion was not matched with the microstructure of zinc, the zinc corrosion product concentration in the surrounding tissues was too low to inhibit hyperplasia of smooth muscle cells in the tissues surrounding the zinc-containing portion. While in the vascular stent provided by Embodiment 12, by matching the zinc content in the zinc-containing portion on the surface of the stent with the microstructure of zinc, the mass of zinc corrosion products generated per unit time can be adjusted, such that the generated zinc corrosion product can inhibit hyperplasia of smooth muscle cells of vascular tissues surrounding the stent without causing cell necrosis.

Comparative Example 4

[0112] The stent used in this comparative example was a 316 L stainless steel stent having a thickness of 120 microns.

[0113] The vascular stent of Comparative Example 4 was implanted into a coronary artery vessel of a minipig, maintaining an over-expansion in the range of 1.1:1 to 1.2:1 during implantation. One month after implantation, the stent and the vascular tissue surrounding the stent were removed, and a pathological analysis of the vascular tissue showed that after the vascular stent of Comparative Example 4 being implanted for one month, the smooth muscle cells in the vascular tissues surrounding the stent proliferated severely, and the vascular stenosis rate was 45% as measured by the above method. Endothelial cells grew normally without cell necrosis.

[0114] As can be seen from Comparative Example 4, when there is no zinc corrosion product to inhibit hyperplasia of smooth muscle cells surrounding the stent struts, hyperplasia of smooth muscle cells occurred seriously, resulting in a high rate of vascular stenosis.

[0115] In summary, by matching the zinc content in the zinc-containing portion of the implanted device with the microstructure of zinc, the mass of the zinc corrosion product generated per unit time can be controlled, such that after the implantable device of the disclosure being implanted into an animal body, the concentration of the zinc corrosion product in the tissues surrounding the zinc-containing portion can inhibit hyperplasia of smooth muscle cells without causing death of smooth muscle cells, endothelial cells or normal tissue cells, so as to prevent tissue necrosis. However, it should be noted that if the local environment where the zinc-containing portion of the implantable device exists is a low pH environment, the low pH environment results from factors other than the mass and the microstructure of the zinc-containing portion of the apparatus, i.e., in addition to the zinc-containing portion of the device, results from degradation, dissolution of the device itself and/or other substances carried by the device, or chemical reaction thereof with other substance in vivo, for example, a low pH environment was caused by degradation of a degradable polylactic acid coating carried by a vascular stent. In this environment, the corrosion rate of the zinc-containing portion of the implantable device will be faster. Although the low pH value environment can accelerate the corrosion of the zinc-containing portion, if the corrosion rate of the zinc-containing portion is still controlled by the own features (ingredients and microstructure) of the zinc-containing portion, the own features of the zinc-containing portion of the corresponding implantable device should be adjusted towards the lower limit of the corrosion rate; if the corrosion rate of the zinc-containing portion has been controlled by a low pH environment, this disclosure is no longer applicable to this situation.

[0116] In addition, when the zinc content in the zinc-containing portion of the implantable device is in the range of [80,100] wt. %, and the microstructure of zinc in the zinc-containing portion is ultrafine-grained, the luminal stenosis rate after implantation of the device can be further reduced.

[0117] In addition, in embodiments in the disclosure, the time for maintaining the effective concentration of zinc corrosion products in the surrounding tissues is controlled by controlling the thickness of the zinc-containing portion (a thickness of greater than 100 nm), so that hyperplasia of smooth muscle cells in the tissues surrounding the zinc-containing portion can be effectively inhibited within one month after the implantable device being implanted into an animal.

[0118] It can be understood that, embodiments in the present disclosure are schematically illustrated by the implantable devices provided by Embodiments 1 to 12 respectively, each zinc-containing portion of which is formed of elemental zinc or zinc alloy with the same composition and same ingredient (the zinc alloy is an alloy formed by zinc and at least one of iron, magnesium, manganese, copper or strontium, or an alloy formed by zinc doped with at least one of carbon, nitrogen, oxygen, boron or silicon), In embodiments provided by the disclosure, the implantable device can also have a number of zinc-containing portions, each zinc-containing portion having a different composition. For example, in a number of zinc-containing portions of an implantable device, part of zinc-containing portions may be formed of elemental zinc, and the remaining of zinc-containing portions may be comprised of a zinc alloy. As another example, in the number of zinc-containing portions of the implantable device, the zinc content and the microstructure of zinc in each zinc-containing portion may also be different from each other. As another example, by controlling the plating process conditions, the zinc microstructure may have a variety of different structural morphology in a certain zinc-containing portion of the implantable device. As long as the zinc content in each zinc-containing portion is matched with the microstructure of zinc, the zinc concentration in the tissue surrounding the zinc-containing portion can be controlled, so that the purpose of inhibiting hyperplasia of smooth muscle cells in the surrounding tissues can be achieved.

[0119] It can also be understood that the embodiments of the present disclosure are only schematically illustrated by the implantable devices provided by Embodiment 1 to 12 respectively, in which elemental zinc or zinc alloy was used as a plating, or the entire device substrate was formed of elemental zinc or zinc alloy. The implanted device includes a substrate, and the substrate at least partially includes the zinc-containing portion or at least partially in contact with the zinc-containing portion, and in the technical solution provided by the disclosure, the zinc-containing portion (i.e. the zinc plating) can only partially cover the surface of the substrate; or the substrate is provided with a gap, a groove or a hole in which the zinc-containing portion (for example, elemental zinc) is disposed; or the substrate is provided with an cavity in which the zinc-containing portion is filled. In the above embodiment, as long as the zinc content in the zinc-containing portion is matched with the microstructure of zinc, hyperplasia of smooth muscle cells of the tissues surrounding the zinc-containing portion can be inhibited without causing necrosis of normal tissue cells.

[0120] It can also be understood that the substrate is at least partially made of iron or an iron alloy, the substrate is at least partially made of a polymer selected from at least one of degradable polymers, non-degradable polymers or copolymers formed by copolymerizing of at least one monomer forming the degradable polymer and at least one monomer forming the non-degradable polymer, the degradable polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polysuccinate or poly (-hydroxybutyrate), the non-degradable polymer is selected from the group consisting of polystyrene, polytetrafluoroethylene, polymethylmethacrylate, polycarbonate or polyethylene terephthalate. It should also be understood that the implantable device of one embodiment of the present disclosure further includes an outer layer in contact with the substrate and/or the zinc-containing portion, the outer layer has a porous structure, or the outer layer includes at least one of degradable resins, corrodible metals or alloys, or water-soluble polymers. For example, the outer layer includes at least one polyester selected from the group consisting of a degradable polyester, a non-degradable polyester or a copolymer formed by copolymerizing at least one monomer forming the degradable polyester and at least one monomer forming the non-degradable polyester, the degradable polyester is selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polysuccinate or poly (-hydroxybutyrate), the non-degradable polyester being selected from the group consisting of polystyrene, polytetrafluoroethylene, polymethylmethacrylate, polycarbonate or polyethylene terephthalate. In another example, the outer layer may further includes at least one corrodible metal or alloy, and the mass fraction of zinc thereof is less than or equal to 0.1%. In another example, the outer layer may include at least partially water-soluble polymers, or the outer layer may have a porous structure so long as the outer layer can ensure that the zinc-containing portion can be in direct or indirect contact with body fluid.

[0121] It can also be understood that in embodiments provided by the disclosure, the polyester can also only partially cover the surface of the substrate; or the substrate is provided with gaps, grooves or holes in which the polyester may be disposed.

[0122] It can also be understood that in embodiments provided by the disclosure, the polyester can also only partially cover the surface of the zinc-containing portion; or the zinc-containing portion may be provided with gaps, grooves or holes in which the polyester is disposed.

[0123] It can also be understood that the embodiments provided by the present disclosure may also be applicable to other implantable devices such as tracheal stents, biliary stents, esophageal stents, urethral stents or vena cava filters.

[0124] The embodiments of the present disclosure have been described above with reference to the accompanying drawings, but the present disclosure is not limited to the specific embodiments described above, which are merely illustrative and not restrictive, and those skilled in the art can make many forms of the disclosure without departing from the spirit and scope of the disclosure as claimed, which are all within the scope of the present disclosure.