WO2021203762A1 - 含锌医疗器械 - Google Patents

含锌医疗器械 Download PDF

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Publication number
WO2021203762A1
WO2021203762A1 PCT/CN2021/000059 CN2021000059W WO2021203762A1 WO 2021203762 A1 WO2021203762 A1 WO 2021203762A1 CN 2021000059 W CN2021000059 W CN 2021000059W WO 2021203762 A1 WO2021203762 A1 WO 2021203762A1
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Prior art keywords
polylactic acid
zinc
coating
average thickness
acid coating
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PCT/CN2021/000059
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English (en)
French (fr)
Inventor
张德元
齐海萍
林文娇
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元心科技(深圳)有限公司
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Priority to EP21785225.0A priority Critical patent/EP4134109A4/en
Priority to US17/915,430 priority patent/US20230142931A1/en
Publication of WO2021203762A1 publication Critical patent/WO2021203762A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/047—Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • C08L67/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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    • A—HUMAN NECESSITIES
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    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices

Definitions

  • the invention relates to the field of interventional medical devices, in particular to a zinc-containing medical device.
  • the matrix materials of absorbable implantable medical devices are mainly selected from degradable polymers and corrosive metals.
  • degradable polymers polylactic acid has the most application. Its advantage is that it can be completely degraded. The degradation products are carbon dioxide and water. Its disadvantage is insufficient mechanical properties.
  • the advantages of corrodible metals are easy processing plasticity and high mechanical strength. Corrosive metals commonly used clinically mainly include magnesium and magnesium-based alloys, iron and iron-based alloys, zinc and zinc-based alloys.
  • the device needs to maintain structural integrity and have sufficient mechanical properties during the time period after implantation to the recovery of the diseased site and normal shape and function. This requires that the early corrosion rate or degradation rate of absorbable implantable medical devices is as slow as possible.
  • the corrosion of corrodible metal materials will generate corrosion products including metal ions. Higher metal ion concentrations may cause toxicity and lead to biological risks. For example, it has been reported that the cytotoxicity (50 ⁇ mol/L, 70 ⁇ mol/L, and 265 ⁇ mol/L) concentrations of zinc ions on fibroblasts, smooth muscle cells, and endothelial cells are respectively. Therefore, for zinc-containing medical devices, the corrosion rate of zinc must be controlled to maintain sufficient mechanical properties and reduce the zinc ion concentration during the repair period, thereby further reducing biological risks.
  • a zinc-containing medical device includes a zinc-containing substrate and a polylactic acid coating on the surface of the zinc-containing substrate, the thickness of the polylactic acid coating is x, and the x satisfies the formula:
  • the polylactic acid is polyracemic lactic acid
  • the a 0.0336ln(Mn)-0.1449
  • b -0.472ln(Mn)+2.152
  • c 1.1604ln(Mn)-5.7128;
  • the polylactic acid is poly-L-lactic acid
  • the a -0.006ln(Mn)+0.03441
  • b 0.0648ln(Mn)-0.3662
  • c -0.162ln(Mn)+0.7847;
  • the Mn is the weight average molecular weight of polylactic acid in kilodaltons, and the unit of x is micrometers.
  • the zinc-containing substrate has an outer surface, an inner surface and a side surface
  • the polylactic acid coating at least covers the outer surface or the inner surface or the side surface
  • the polylactic acid Is a polyracemic lactic acid
  • the weight average molecular weight of the polylactic acid is 100 to 300 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 5.2 to 11.5 microns
  • the polylactic acid coating The average thickness of the part of the layer located on the inner surface is 5.2 to 11.5 micrometers
  • the average thickness of the part of the polylactic acid coating layer located on the side surface is 5.2 to 11.5 micrometers.
  • the zinc-containing substrate has an outer surface, an inner surface and a side surface
  • the polylactic acid coating at least covers the outer surface or the inner surface or the side surface
  • the polylactic acid It is polyracemic lactic acid
  • the weight average molecular weight of the polylactic acid is 10-100 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 2-9 microns
  • the polylactic acid coating The average thickness of the part of the layer located on the inner surface is 2-9 micrometers
  • the average thickness of the part of the polylactic acid coating layer located on the side surface is 2-9 micrometers.
  • the zinc-containing substrate has an outer surface, an inner surface and a side surface
  • the polylactic acid coating at least covers the outer surface or the inner surface or the side surface
  • the polylactic acid Is polyracemic lactic acid
  • the weight average molecular weight of the polylactic acid is 2-10 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 1.5-5.5 microns
  • the polylactic acid coating The average thickness of the part of the layer located on the inner surface is 1.5-5.5 micrometers
  • the average thickness of the part of the polylactic acid coating layer located on the side surface is 1.5-5.5 micrometers.
  • the zinc-containing substrate has an outer surface, an inner surface and a side surface
  • the polylactic acid coating at least covers 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 to 300 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 9 to 22 microns
  • the average thickness of the part located on the inner surface is 9-22 micrometers
  • the average thickness of the part located on the side surface of the polylactic acid coating is 9-22 micrometers.
  • the zinc-containing substrate has an outer surface, an inner surface and a side surface
  • the polylactic acid coating at least covers 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 to 200 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 7 to 13 microns
  • the average thickness of the part located on the inner surface is 7-13 micrometers
  • the average thickness of the part located on the side surface of the polylactic acid coating is 7-13 micrometers.
  • the zinc-containing substrate has an outer surface, an inner surface and a side surface
  • the polylactic acid coating covers the outer surface, the inner surface and the side surface
  • the polylactic acid coating is located on the
  • the average thickness of the part of the outer surface is x
  • the average thickness of the part of the polylactic acid coating on the inner surface is x
  • the average thickness of the polylactic acid coating on the side surface is x an outer side, the inner ⁇ x x, x ⁇ x inner side and the outer x, x x, and the at least one side satisfies the following formula:
  • the polylactic acid is polyracemic lactic acid
  • the a 0.0336ln(Mn)-0.1449
  • b -0.472ln(Mn)+2.152
  • c 1.1604ln(Mn)-5.7128;
  • the polylactic acid is poly-L-lactic acid
  • the a -0.006ln(Mn)+0.03441
  • b 0.0648ln(Mn)-0.3662
  • c -0.162ln(Mn)+0.7847;
  • the Mn is the weight average molecular weight of polylactic acid in kilodaltons, and the unit of x is micrometers.
  • the material of the zinc-containing substrate is pure zinc or zinc alloy; or, the zinc-containing substrate includes a body and a zinc-containing layer attached to the body, and the zinc-containing layer The material is pure zinc or zinc alloy.
  • the mass percentage of zinc in the zinc alloy is 50%-99.99%
  • the mass percentage of zinc in the zinc alloy is 50% to 99.99%.
  • the zinc-containing layer covers the entire surface of the body.
  • the polylactic acid coating contains active drugs.
  • Figure 1 is a pathological section of the tissue around the zinc-based stent of Example 5 after implantation of the zinc-based stent in the rabbit iliac artery one month later.
  • a zinc-containing medical device includes a zinc-containing substrate and a polylactic acid coating disposed on the zinc-containing substrate.
  • the zinc-containing matrix is an absorbable matrix.
  • the polylactic acid coating covers at least part of the surface of the zinc-containing substrate.
  • the material of the zinc-containing matrix is pure zinc or zinc alloy, that is, the zinc-containing matrix is made of pure zinc or zinc alloy.
  • the zinc-containing matrix is a hollow lumen structure made of pure zinc or zinc alloy.
  • zinc alloy is an alloy that can be absorbed by organisms.
  • 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 kind. It should be noted that the alloying elements in the zinc alloy are non-toxic and harmless elements to living organisms. Or, the content of alloying elements is low, which is not enough to produce toxic effects on organisms.
  • the mass percentage of zinc in the zinc alloy is 50%-99.99%.
  • 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 pure zinc or zinc alloy.
  • the material of the body is absorbable metal or absorbable polymer.
  • the absorbable metal is pure iron or iron-based alloys.
  • 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.
  • the alloying elements in the zinc alloy are selected from C, N, O, S, P, Ce, Mn, Ca, Cu, Pd, Si, W, Ti, Co, Cr, Cu And at least one of Re. It should be noted that the alloying elements in the zinc alloy are non-toxic and harmless elements to living organisms. Or, the content of alloying elements is low, which is not enough to produce toxic effects on organisms. In one embodiment, the mass percentage of zinc in the zinc alloy is 50%-99.99%.
  • the zinc-containing substrate is a substrate formed of pure zinc or zinc alloy or a zinc-containing substrate includes a body and a zinc-containing layer attached to the body
  • the zinc-containing substrate has an outer surface, an inner surface and Side surface.
  • the polylactic acid coating covers at least the outer surface of the zinc-containing substrate.
  • the polylactic acid coating at least covers the inner surface of the zinc-containing substrate.
  • the polylactic acid coating at least covers the side surface of the zinc-containing substrate.
  • the inner surface is the surface that is in direct contact with body fluids (for example, blood)
  • the outer surface is the surface that is in direct contact with the tissue wall (for example, blood vessel wall)
  • the side surface is connected to the inner surface.
  • the polylactic acid coating covers the outer surface, inner surface, and side surface of the zinc-containing substrate.
  • the zinc-containing medical device When the zinc-containing medical device is implanted in a living body, zinc corrosion can produce zinc phosphate, while polylactic acid degrades to produce carboxyl and hydroxyl groups. Zinc phosphate can react with carboxyl and hydroxyl groups to form complexes, thereby preventing further corrosion of zinc. Therefore, the zinc corrosion rate of the zinc-containing medical device containing the polylactic acid coating is lower than the zinc corrosion rate of the zinc-containing medical device not containing the polylactic acid coating. At the same time, the hydrogen ions produced by the degradation of polylactic acid will accelerate the corrosion of metals. 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 polylactic acid degradation products will affect the corrosion inhibition and corrosion promotion effects of the polylactic acid coating on zinc corrosion.
  • the nature of the polylactic acid in the polylactic acid coating is an important factor affecting the degradation rate of polylactic acid.
  • the thickness of the polylactic acid coating affects the total amount of polylactic acid degradation products.
  • the thickness of the polylactic acid coating is x in micrometers ( ⁇ m), and x satisfies the formula:
  • 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, and the unit is kilodaltons (kDa). That is, when calculating the sizes of a, b, and c, the value of Mn is calculated by bringing the value corresponding to kDa into the formula, and the calculated value is directly used in the above formula or relational expression.
  • the thickness x of the polylactic acid coating is taken into the above formula or relational formula
  • the corresponding value when the thickness of the polylactic acid coating is taken in micrometers is taken into the aforementioned relational formula for comparison.
  • the thickness x of the above-mentioned polylactic acid coating refers to the average thickness of the part of the polylactic acid coating on the outer surface x outside , the average thickness of the part of the polylactic acid coating on the inner surface x inner or the polylactic acid coating on the side surface
  • the average thickness of the portion on the x side that is, at least one of x outer , x inner, and x side satisfies the above formula.
  • x outer , x inner, and x side all satisfy the above formula.
  • the corrosion rate of zinc in the zinc-containing substrate is lower.
  • the corrosion rate of zinc is small, that is, the corrosion rate of the zinc-containing substrate itself is small, so as to avoid the zinc-containing substrate from corroding too fast and losing the mechanics too quickly Performance, which is conducive to maintaining sufficient mechanical properties during the repair period.
  • the zinc-containing matrix includes a body and a zinc-containing layer attached to the body, and the material of the zinc-containing layer is pure zinc or zinc alloy, the zinc-containing layer covers the surface of the body and can physically isolate the body and body fluids. The corrosion rate of the zinc-containing layer is small, which is beneficial to delay the protection period of the body, thereby helping to maintain sufficient mechanical properties during the repair period.
  • the concentration of zinc corrosion products accumulated in the tissue is small, which reduces the biological risk.
  • the corrosion rate of zinc in the zinc-containing substrate is lower.
  • the material of lactic acid is the same, and the distribution mode of the polylactic acid coating is the same.
  • the corrosion rate of zinc in the zinc-containing medical device containing the polylactic acid coating is lower than that of the device not containing the polylactic acid coating.
  • the polylactic acid is polyracemic lactic acid
  • the weight average molecular weight of the polyracemic lactic acid is 100 to 300 kDa
  • the average thickness of the portion of the polylactic acid coating on the outer surface is 5.2 to 11.5 microns.
  • the average thickness of the part of the polylactic acid coating on the inner surface is 5.2 to 11.5 microns.
  • the average thickness of the part of the polylactic acid coating on the side surface is 5.2 to 11.5 microns.
  • the average thickness of all surfaces of the polylactic acid coating is 5.2 to 11.5 microns.
  • the polylactic acid is polyracemic lactic acid
  • the weight average molecular weight of the polyracemic lactic acid is 10-100 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 2-9 microns.
  • the average thickness of the part of the polylactic acid coating on the inner surface is 2-9 microns.
  • the average thickness of the part of the polylactic acid coating on the side surface is 2-9 microns. In one embodiment, the average thickness of all surfaces of the polylactic acid coating is 2-9 microns.
  • the polylactic acid is polyracemic lactic acid
  • the weight average molecular weight of the polyracemic lactic acid is 2-10 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 1.5-5.5 microns.
  • the average thickness of the part located on the inner surface of the polylactic acid coating is 1.5-5.5 microns.
  • the average thickness of the part of the polylactic acid coating on the side surface is 1.5-5.5 microns. In one embodiment, the average thickness of all surfaces of the polylactic acid coating is 1.5-5.5 microns.
  • the polylactic acid is polyracemic lactic acid
  • the weight average molecular weight of the polyracemic lactic acid is 200 kDa
  • the average thickness of the portion of the polylactic acid coating on the outer surface is 9.1 micrometers.
  • the average thickness of the part of the polylactic acid coating on the inner surface is 9.1 micrometers.
  • the average thickness of the part of the polylactic acid coating on the side surface is 9.1 micrometers.
  • the average thickness of all surfaces of the polylactic acid coating is 9.1 microns.
  • the polylactic acid is polyracemic lactic acid
  • the weight average molecular weight of the polyracemic lactic acid is 50 kDa
  • the average thickness of the portion of the polylactic acid coating on the outer surface is 4.9 microns.
  • the average thickness of the part of the polylactic acid coating on the inner surface is 4.9 micrometers.
  • the average thickness of the part located on the side surface of the polylactic acid coating is 4.9 micrometers.
  • the average thickness of all surfaces of the polylactic acid coating is 4.9 microns.
  • the polylactic acid is polyracemic lactic acid
  • the weight average molecular weight of the polyracemic lactic acid is 5 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 3.6 micrometers.
  • the average thickness of the part of the polylactic acid coating on the inner surface is 3.6 micrometers.
  • the average thickness of the part of the polylactic acid coating on the side surface is 3.6 micrometers. In one embodiment, the average thickness of all surfaces of the polylactic acid coating is 3.6 microns.
  • the polylactic acid is poly-L-lactic acid
  • the weight-average molecular weight of the poly-racemic lactic acid is 200-300 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 9-22 microns or that of the polylactic acid coating.
  • the average thickness of the part located on the inner surface is 9-22 micrometers or the average thickness of the part of the side surface where the polylactic acid coating is located is 9-22 micrometers.
  • the average thickness of all surfaces of the polylactic acid coating is 9-22 microns.
  • the polylactic acid is poly-L-lactic acid
  • the weight-average molecular weight of the poly-L-lactic acid is 50-200kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 7-13 microns or the polylactic acid coating is located
  • the average thickness of the part of the inner surface is 7-13 micrometers or the average thickness of the part of the side surface at the position of the polylactic acid coating is 7-13 micrometers.
  • the average thickness of all surfaces of the polylactic acid coating is 7-13 microns.
  • the polylactic acid is poly-L-lactic acid
  • the weight-average molecular weight of the poly-L-lactic acid is 300 kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 19.7 microns or the part of the polylactic acid coating on the inner surface
  • the average thickness of the part of the side surface at the position of the polylactic acid coating is 19.7 micrometers or the average thickness of 19.7 micrometers.
  • the average thickness of all surfaces of the polylactic acid coating is 19.7 microns.
  • the polylactic acid is poly-L-lactic acid
  • the weight-average molecular weight of the poly-L-lactic acid is 100kDa
  • the average thickness of the part of the polylactic acid coating on the outer surface is 9.4 microns or the part of the polylactic acid coating on the inner surface
  • the average thickness of the polylactic acid coating is 9.4 microns or the average thickness of the part of the side surface at the position of the polylactic acid coating is 9.4 microns.
  • the average thickness of all surfaces of the polylactic acid coating is 9.4 microns.
  • the polylactic acid coating contains active drugs.
  • the active drug is selected from at least one drug selected from the group consisting of drugs that inhibit vascular proliferation, antiplatelet drugs, antithrombotic drugs, anti-inflammatory drugs, and anti-sensitizing drugs.
  • the drug for inhibiting vascular proliferation is selected from at least one of paclitaxel, rapamycin and derivatives thereof.
  • the antiplatelet drug may be cilostazol.
  • the antithrombotic drug may be heparin.
  • the anti-inflammatory drug may be dexamethasone.
  • the anti-allergenic drug is selected from at least one of calcium gluconate, chlorpheniramine and cortisone.
  • the active drug may be distributed in at least one of the outer surface, the inner surface and the side surface of the zinc-containing matrix.
  • the polylactic acid is polyracemic lactic acid
  • the weight average molecular weight of the polyracemic lactic acid is 5 kDa.
  • the average thickness of the part of the polylactic acid coating on the inner surface and the side surface is 0, that is, there is no polylactic acid coating on the inner surface and the side surface.
  • the part located on the outer surface contains sirolimus, the average thickness of the polylactic acid-sirolimus coating is 5.4 microns, and the average thickness of the part located on the outer surface of the polylactic acid coating is 3.6 microns.
  • the mass ratio of polylactic acid to sirolimus is 2:1.
  • the polylactic acid is polyracemic lactic acid, and the weight average molecular weight of the polyracemic lactic acid is 200 kDa.
  • the average thickness of the part of the polylactic acid coating on the inner surface is 8 microns; the part of the polylactic acid coating on the side surface and the outer surface contains sirolimus, which is a polylactic acid-sirolimus coating.
  • the mass ratio of lactic acid to sirolimus is 6:1, the average thickness of the polylactic acid-sirolimus coating on the side surface and the outer surface part is 10.6 ⁇ m, and the average thickness of the polylactic acid coating is converted to 9.1 ⁇ m.
  • the above-mentioned zinc-containing medical devices can be vascular stents, non-vascular endoluminal stents, occluders, orthopedic implants, dental implants, respiratory implants, gynecological implants, andrology implants, sutures or Bolts and so on.
  • the non-vascular intraluminal stent may be a tracheal stent, an esophageal stent, a urethral stent, an intestinal stent, or a biliary stent.
  • Orthopedic implants can be fixation screws, fixation rivets or bone plates.
  • other medical devices that need to achieve degradable absorption can be used as the medical devices of this embodiment.
  • the test system includes the liquid phase pump and sampler from Agilent, the Agilent PL MIXED-C GPC column (size: 7.5 ⁇ 300mm, 5 microns) from Agilent, the multi-angle laser light scattering instrument from Wyatt, and Differential detector.
  • the detection conditions are:
  • Mobile phase tetrahydrofuran; pump flow rate: 1 mL/min; injection volume: 100 ⁇ L; laser wavelength: 663.9 nm; test temperature: 35°C.
  • Use scanning electron microscopy to measure first fix the sample to be tested for coating thickness on the sample stage, then put the sample stage in the JFC-1600 gold spraying equipment to spray platinum, after spraying once, rotate 180 degrees and spray again to ensure all positions Was sprayed. Place the sample with gold sprayed on the surface of the Buehler room temperature resin curing agent mixed reagent prepared in a ratio of 5:1, and let it stand for more than 8 hours before it can be released from the sample shell. Divide the sealed sample into 3 sections evenly, and polish each section with a semi-automatic polishing machine in accordance with the sample polishing procedure, and polish the cross section of the sample to be measured until there are no wear marks.
  • the polished sample is fixed on the stage of the scanning electron microscope, and the entire stage is placed in the JFC-1600 gold spraying equipment for gold spraying for 20 seconds. Put the gold-sprayed sample into the JSM-6510 scanning electron microscope for thickness measurement. Measure the thickness of the inner surface coating, the side surface coating thickness and the outer surface coating thickness for each section; if there are multiple rods in each section, at least 3 rods are randomly selected to measure the thickness of the inner surface coating and the side surface of the rod Coating thickness and outer surface coating thickness.
  • the calculated average thickness of all measured inner surface coatings is the average thickness of the inner surface coating of the device, and the calculated average thickness of all measured side surface coatings is the average thickness of the device side surface coating.
  • the average thickness of the surface coating is calculated as the average thickness of the outer surface coating of the device.
  • Detection by weightlessness method implant the zinc-containing medical device into the rabbit body, and at the scheduled observation time point, such as 1 month, 3 months..., the rabbit is put to death, and the zinc-containing medical device is taken out. Carefully remove the tissue on the zinc-containing medical device as much as possible, and then soak the zinc-containing medical device in a saturated glycine solution and ultrasonically clean it. After 1 minute, remove the zinc-containing medical device from the glycine solution and quickly wash it with water for 10 seconds , And then soak the cleaned zinc-containing medical equipment in 1mol/L sodium hydroxide solution for more than 24 hours to completely dissolve the zinc, and then detect the zinc concentration in the sodium hydroxide solution by atomic absorption spectroscopy (abbreviated as AAS).
  • AAS atomic absorption spectroscopy
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Polylactic acid has 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 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Polylactic acid has a molecular weight of 200kDa
  • 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 6 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Polyracemic lactic acid has 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 16 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • 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 measured zinc corrosion rates were 12%, 20%, and 18%, respectively.
  • the corrosion rate of zinc in the zinc-based stent of Example 1 is the smallest.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Polylactic acid has a molecular weight of 50 kDa
  • the average thickness of the polylactic acid coating on the outer surface is 6 ⁇ m
  • the average thickness of the polylactic acid coating on the side surface is 5.5 ⁇ m
  • the average thickness of the polylactic acid coating on the inner surface is 4.9 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Polylactic acid has a molecular weight of 50 kDa
  • the average thickness of the polylactic acid coating on the outer surface is 6 ⁇ m
  • the average thickness of the polylactic acid coating on the side surface is 5.5 ⁇ m
  • the average thickness of the polylactic acid coating on the inner surface is 2.5 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Polylactic acid has a molecular weight of 50 kDa
  • the average thickness of the polylactic acid coating on the outer surface is 6 ⁇ m
  • the average thickness of the polylactic acid coating on the side surface is 5.5 ⁇ m
  • the average thickness of the polylactic acid coating on the inner surface is 8 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • 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 measured zinc corrosion rate was 18%, 28% and 24%, respectively.
  • the corrosion rate of zinc in the zinc-based stent of Example 2 is the smallest.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the 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 5mg
  • the stent base is coated with polylactic acid.
  • the polylactic acid in the layer is polylactic acid with a molecular weight of 5kDa
  • the mass ratio of polylactic acid to sirolimus is 2:1
  • the average thickness of the polylactic acid-sirolimus coating is 5.4 ⁇ m.
  • the average thickness of the lactic acid coating is 3.6 ⁇ m.
  • the polylactic acid-sirolimus coating is prepared by 3D printing.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base, the material of the stent base is pure zinc, the mass of the stent base is 5mg, and there is no polylactic acid coating on the base. .
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the 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 5mg
  • the stent base is coated with polylactic acid.
  • the polylactic acid in the layer is polylactic acid with a molecular weight of 5kDa
  • the mass ratio of polylactic acid to sirolimus is 2:1
  • the average thickness of the polylactic acid-sirolimus coating is 12 ⁇ m, converted to polylactic acid
  • the average thickness of the coating is 8 ⁇ m.
  • the polylactic acid-sirolimus coating is prepared by spraying.
  • 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 measured zinc corrosion rates were 11%, 17%, and 13%, respectively.
  • the corrosion rate of zinc in the zinc-based stent of Example 3 is the smallest.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is zinc alloy
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Poly-L-lactic acid has 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 are all 19.6 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Poly-L-lactic acid has 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 are all 10 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • Zinc-based stent the specification is 3.0mm ⁇ 8mm, including the stent base and the polylactic acid coating that completely covers the surface of the stent base.
  • the material of the stent base is pure zinc
  • the mass of the stent base is 5mg
  • the polylactic acid in the polylactic acid coating is Poly-L-lactic acid has 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 are all 30 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • 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 measured zinc corrosion rates were 21%, 29%, and 27%, respectively.
  • the corrosion rate of zinc in the zinc-based stent of Example 4 is the smallest.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, and a polylactic acid-sirolimus coating that covers the surface of the pure zinc layer.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the mass ratio of the polylactide-sirolimus coating on the inner surface is 10:1, and the thickness of the polylactide-sirolimus coating on the inner surface is 5.5 ⁇ m.
  • the thickness of the polylactic acid coating is converted to 5 ⁇ m; the mass ratio of polylactic acid to sirolimus on the side surface and the outer surface is 6:1, and the thickness of the polylactide-sirolimus coating on the side surface and the outer surface is 10.6 ⁇ m, converted The thickness of the polylactic acid coating is 9.1 ⁇ m.
  • the polylactic acid coating and the polylactic acid-sirolimus coating are prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, and a polylactic acid-sirolimus coating that covers the surface of the pure zinc layer.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the mass ratio of the polylactide-sirolimus coating on the inner surface is 10:1, and the thickness of the polylactide-sirolimus coating on the inner surface is 5.5 ⁇ m.
  • the thickness of the polylactic acid coating is converted to 5 ⁇ m; the mass ratio of polyracemic lactic acid and sirolimus on the side surface and the outer surface is 6:1, and the thickness of the polyracemic lactic acid-sirolimus coating on the side surface and the outer surface is 7 ⁇ m.
  • the thickness of the lactic acid coating is 6 ⁇ m.
  • the polylactic acid coating and the polylactic acid coating-sirolimus are prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, and a polylactic acid-sirolimus coating that covers the surface of the pure zinc layer.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the mass ratio of the polylactide-sirolimus coating on the inner surface is 10:1, and the thickness of the polylactide-sirolimus coating on the inner surface is 5.5 ⁇ m.
  • the thickness of the polylactic acid coating is converted to 5 ⁇ m; the mass ratio of polyracemic lactic acid to sirolimus on the side surface and the outer surface is 6:1, and the thickness of the polylactic acid-sirolimus coating on the side surface and the outer surface is 17.5 ⁇ m.
  • the thickness of the lactic acid coating is 15 ⁇ m.
  • the polylactic acid coating and the polylactic acid-sirolimus coating are prepared by spraying.
  • the iron-based stents of Example 5, Comparative Example 5-1 and Comparative Example 5-2 were respectively implanted into the iliac arteries of three rabbits, and were taken out one month later.
  • the measured zinc corrosion rates were 30%, 56% and 44%, respectively.
  • the corrosion rate of zinc in the zinc-based stent of Example 5 is the smallest.
  • the pathological section is shown in FIG.
  • the iron-based stent includes a stent body made of iron-based alloy, a pure zinc layer completely covering the surface of the stent body, a polylactic acid coating covering the inner surface of the pure zinc layer, covering the side surface of the pure zinc layer and Polylactic acid-sirolimus coating on the outer surface.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polyracemic lactic acid coating on the inner surface is 6 ⁇ m; the mass ratio of polyracemic lactic acid to sirolimus on the side surface and the outer surface is 3:1, and the polyracemic lactic acid-western The thickness of the rolimus coating is 14.7 ⁇ m, which is equivalent to 11 ⁇ m of the polylactic acid coating.
  • the iron-based stent includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, a polylactic acid coating that covers the inner surface of the pure zinc layer, and a side surface of the pure zinc layer. And the outer surface is polylactic acid-sirolimus coating.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polyracemic lactic acid coating on the inner surface is 6 ⁇ m; the mass ratio of polyracemic lactic acid to sirolimus on the side surface and the outer surface is 3:1, and the polyracemic lactic acid-western
  • the thickness of the Rolimus coating is 8 ⁇ m, and the thickness of the polylactic acid coating is 6 ⁇ m.
  • the polylactic acid coating-sirolimus is prepared by spraying.
  • the iron-based stent includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, a polylactic acid coating that covers the inner surface of the pure zinc layer, and a side surface of the pure zinc layer. And the outer surface is polylactic acid-sirolimus coating.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface is 6 ⁇ m; the mass ratio of polylactic acid to sirolimus on the side surface and the outer surface is 3:1, and the polylactic acid-sirolimus on the side surface and the outer surface
  • the thickness of the moss coating is 21 ⁇ m, and the thickness of the polylactic acid coating is 15.8 ⁇ m.
  • the polylactic acid coating and the polylactic acid-sirolimus coating are prepared by spraying.
  • 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 one month later.
  • the measured zinc corrosion rates were 33%, 54% and 49%, respectively.
  • the corrosion rate of zinc in the zinc-based stent of Example 6 is the smallest.
  • the iron-based stent includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, a polylactic acid coating that covers the inner and side surfaces of the pure zinc layer, and a pure zinc layer. Polylactic acid-sirolimus coating on the outer surface.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface and the side surface is 4.5 ⁇ m; the mass ratio of polylactic acid to sirolimus on the outer surface is 4:1, and the average thickness is both 8.8 ⁇ m, converted to polylactic acid
  • the coating thickness is 7.1 ⁇ m.
  • the polylactic acid coating and the polylactic acid-sirolimus coating are prepared by spraying.
  • the iron-based stent includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, a polylactic acid coating that covers the inner and side surfaces of the pure zinc layer, and a pure zinc layer. Polylactic acid-sirolimus coating on the outer surface.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface and the side surface is 4.5 ⁇ m; the mass ratio of polylactic acid to sirolimus on the outer surface is 4:1, and the average thickness is both 6 ⁇ m.
  • the layer thickness is 4.8 ⁇ m.
  • the polylactic acid coating and the polylactic acid-sirolimus coating are prepared by spraying.
  • the iron-based stent includes a stent body made of iron-based alloy, a pure zinc layer that completely covers the surface of the stent body, a polylactic acid coating that covers the inner and side surfaces of the pure zinc layer, and a pure zinc layer. Polylactic acid-sirolimus coating on the outer surface.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner and side surfaces is 4.5 ⁇ m; the mass ratio of polylactic acid to sirolimus on the outer surface is 4:1, and the average thickness is both 14.5 ⁇ m, converted to polylactic acid
  • the coating thickness is 11.6 ⁇ m.
  • the polylactic acid coating and the polylactic acid-sirolimus coating are prepared by spraying.
  • 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 were taken out one month later.
  • the measured zinc corrosion rates were 51%, 61%, and 63%, respectively.
  • the corrosion rate of zinc in the zinc-based stent of Example 7 is the smallest.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface is 5.1 ⁇ m
  • the average thickness of the polylactic acid coating on the outer and side surfaces is 7.1 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface was 5.1 ⁇ m
  • the average thickness of the polylactic acid coating on the outer and side surfaces was both 6.3 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface is 5.1 ⁇ m
  • the average thickness of the polylactic acid coating on the outer and side surfaces is 14.8 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stents of Example 8, Comparative Example 8-1, and Comparative Example 8-2 were respectively implanted into the iliac arteries of three rabbits, and taken out one month later.
  • the measured zinc corrosion rates were 48%, 54%, and 66%, respectively.
  • the corrosion rate of zinc in the iron-based stent of Example 8 is the smallest.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface was 7.1 ⁇ m
  • the average thickness of the polylactic acid coating on the outer and side surfaces was 11.1 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface is 7.1 ⁇ m
  • the average thickness of the polylactic acid coating on the outer and side surfaces is 6.7 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 200 kDa.
  • the average thickness of the polylactic acid coating on the inner surface was 7.1 ⁇ m
  • the average thickness of the polylactic acid coating on the outer and side surfaces was 16.6 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stents of Example 9, Comparative Example 9-1, and Comparative Example 9-2 were respectively implanted into the iliac arteries of three rabbits, and taken out one month later.
  • the measured zinc corrosion rates were 44%, 64%, and 62%, respectively.
  • the corrosion rate of zinc in the iron-based stent of Example 9 is the smallest.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 100 kDa.
  • the average thickness of the polylactic acid coating on the inner surface, outer surface and side surface is 7.3 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 100 kDa.
  • the average thickness of the polylactic acid coating on the inner surface, outer surface and side surface is 4 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stent has a specification of 3.0mm ⁇ 8mm and includes a stent body made of iron-based alloy and a polylactic acid coating that completely covers the surface of the stent base.
  • the iron mass of the stent body is 4 mg
  • the zinc layer mass is 250 ⁇ g
  • the polylactic acid in the coating is polylactic acid with a molecular weight of 100 kDa.
  • the average thickness of the polylactic acid coating on the inner surface, outer surface and side surface is 11 ⁇ m.
  • the polylactic acid coating is prepared by spraying.
  • the iron-based stents of Example 10, Comparative Example 10-1 and Comparative Example 10-2 were respectively implanted into the iliac arteries of three rabbits, and were taken out one month later.
  • the measured zinc corrosion rates were 48%, 69%, and 55%, respectively.
  • the corrosion rate of zinc in the iron-based stent of Example 10 is the smallest.

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Abstract

本发明涉及一种含锌医疗器械，包括含锌的基体及设于含锌的基体上的聚乳酸涂层，聚乳酸涂层的厚度为x微米，当x与聚乳酸的重均分子量Mn千道尔顿满足公式(I)；基体中的锌的腐蚀速率较小，能在修复期内保持足够的力学性能，且生物学风险较低。其中，当聚乳酸为聚消旋乳酸时，a＝0.0336ln(Mn)-0.1449，b＝-0.472ln(Mn)+2.1524，c＝1.1604ln(Mn)-5.7128；聚乳酸为聚左旋乳酸，a＝-0.006ln(Mn)+0.03441，b＝0.0648ln(Mn)-0.3662，c＝-0.162ln(Mn)+0.7847。

Description

含锌医疗器械 技术领域
本发明涉及介入式医疗器械领域，特别是涉及一种含锌医疗器械。
背景技术
本部分提供的仅仅是与本公开相关的背景信息，其并不必然是现有技术。
目前可吸收植入医疗器械的基体材料主要选自可降解聚合物及可腐蚀金属。可降解聚合物中以聚乳酸应用最多，其优点是可完全降解，降解产物为二氧化碳及水，其缺点是机械性能不足。可腐蚀金属的优点是易加工塑性，机械强度大。临床上常用的可腐蚀金属主要包括镁及镁基合金、铁及铁基合金、锌及锌基合金。
从临床应用角度来说，一方面，从植入后至病变部位痊愈并恢复正常形态和功能的时间段内，器械需保持结构完整性和具有足够的力学性能。这就要求可吸收植入医疗器械早期腐蚀的速率或降解速率越慢越好。另一方面，可腐蚀金属材料的腐蚀，会生成包括金属离子在内的腐蚀产物。较高的金属离子浓度可能会产生毒性，导致生物学风险。例如，有报道称，锌离子对纤维细胞、平滑肌细胞和内皮细胞的细胞毒性(半数致死量)的浓度分别为50μmol/L、70μmol/L和265μmol/L。所以，对含锌医疗器械来说，必须控制锌的腐蚀速度，以在修复期内保持足够的力学性能并降低锌离子浓度，从而进一步降低生物学风险。
发明内容
基于此，有必要提供一种能够在修复期内保持足够的力学性能，且生物学风险较低的含锌可吸收器械。
一种含锌医疗器械，包括含锌的基体及设于所述含锌的基体表面上的聚乳酸涂层，所述聚乳酸涂层的厚度为x，所述x满足公式：
Figure PCTCN2021000059-appb-000001
Figure PCTCN2021000059-appb-000002
其中，当所述聚乳酸为聚消旋乳酸时，所述a＝0.0336ln(Mn)-0.1449， b＝-0.472ln(Mn)+2.1524，c＝1.1604ln(Mn)-5.7128；
当所述聚乳酸为聚左旋乳酸时，所述a＝-0.006ln(Mn)+0.03441，b＝0.0648ln(Mn)-0.3662，c＝-0.162ln(Mn)+0.7847；
所述Mn为聚乳酸的重均分子量，单位为千道尔顿，x的单位为微米。
在其中一个实施方式中，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚消旋乳酸，所述聚消旋乳酸的重均分子量为100～300kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为5.2～11.5微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为5.2～11.5微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为5.2～11.5微米。
在其中一个实施方式中，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚消旋乳酸，所述聚消旋乳酸的重均分子量为10～100kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为2～9微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为2～9微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为2～9微米。
在其中一个实施方式中，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚消旋乳酸，所述聚消旋乳酸的重均分子量为2～10kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为1.5～5.5微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为1.5～5.5微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为1.5～5.5微米。
在其中一个实施方式中，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚左旋乳酸，所述聚左旋乳酸的重均分子量为200～300kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为9～22微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为9～22微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为9～22微米。
在其中一个实施方式中，所述含锌的基体具有外表面、内表面和侧表面， 所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚左旋乳酸，所述聚左旋乳酸的重均分子量为50～200kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为7～13微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为7～13微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为7～13微米。
在其中一个实施方式中，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层覆盖所述外表面、内表面和侧表面，所述聚乳酸涂层的位于所述外表面的部分的平均厚度为x 外，所述聚乳酸涂层的位于所述内表面的部分的平均厚度为x 内，所述聚乳酸涂层的位于所述侧表面的平均厚度为x 侧，x 内≤x 外，x 内≤x 侧，且所述x 外、x 内和x 侧至少一个满足如下公式：
Figure PCTCN2021000059-appb-000003
x 侧或x 外；
其中，当所述聚乳酸为聚消旋乳酸时，所述a＝0.0336ln(Mn)-0.1449，b＝-0.472ln(Mn)+2.1524，c＝1.1604ln(Mn)-5.7128；
当所述聚乳酸为聚左旋乳酸时，所述a＝-0.006ln(Mn)+0.03441，b＝0.0648ln(Mn)-0.3662，c＝-0.162ln(Mn)+0.7847；
所述Mn为聚乳酸的重均分子量，单位为千道尔顿，x的单位为微米。
在其中一个实施方式中，所述含锌的基体的材料为纯锌或锌合金；或者，所述含锌的基体包括本体及附着于所述本体上的含锌层，且所述含锌层的材料为纯锌或锌合金。
在其中一个实施方式中，当所述含锌的基体的材料为纯锌或锌合金，所述锌合金中的锌的质量百分含量为50％～99.99％；
当所述含锌的基体包括本体及附着于所述本体上的含锌层，且所述含锌层的材料为锌合金时，所述锌合金中的锌的质量百分含量为50％～99.99％。
在其中一个实施方式中，所述含锌层覆盖所述本体的全部表面。
在其中一个实施方式中，所述聚乳酸涂层中含有活性药物。
经实验证明，当聚乳酸涂层中的聚乳酸的重均分子量Mn(千道尔顿)和聚乳酸涂层的厚度x(微米)满足公式：
Figure PCTCN2021000059-appb-000004
Figure PCTCN2021000059-appb-000005
且当聚乳酸为聚消旋乳酸时，a＝0.0336ln(Mn)-0.1449，b＝-0.472ln(Mn)+2.1524，c＝1.1604ln(Mn)-5.7128；当聚乳酸为聚左旋乳酸时，a＝-0.006ln(Mn)+0.03441，b＝0.0648ln(Mn)-0.3662，c＝-0.162ln(Mn)+0.7847；含锌的基体中的锌的腐蚀速率较小，避免该含锌的基体腐蚀过快，能够在修复期内保持足够的力学性能。并且，含锌的基体中的锌的腐蚀速率较小能够避免锌离子浓度累积过高，有利于降低生物学风险。
附图说明
图1为实施例5的锌基支架植入兔子髂动脉1个月后，锌基支架周围组织的病理切片图。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图对本发明的具体实施方式做详细的说明。在下面的描述中阐述了很多具体细节以便于充分理解本发明。但是本发明能够以很多不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似改进，因此本发明不受下面公开的具体实施的限制。
除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。
一实施方式的含锌医疗器械，包括含锌的基体和设置于含锌的基体上的聚乳酸涂层。其中，含锌的基体为可吸收基体。聚乳酸涂层至少覆盖含锌的基体的部分表面。
在一实施方式中，含锌的基体的材料为纯锌或锌合金，即含锌的基体由纯锌或锌合金制成。例如，含锌的基体为由纯锌或锌合金制成的镂空管腔结构。其中，锌合金为生物体可吸收的合金。
在一实施方式中，锌合金中的合金元素选自C、N、O、S、P、Ce、Mn、Ca、Cu、Pd、Si、W、Ti、Co、Cr、Cu及Re中至少一种。需要说明的是，锌合金中的合金元素为对生物体无毒无害的元素。或者，合金元素的含量较低， 不足以对生物体产生毒性作用。
在一实施方式中，锌合金中的锌的质量百分含量为50％～99.99％。
在另一实施方式中，含锌的基体包括本体及附着于本体上的含锌层，且含锌层的材料为纯锌或锌合金。本体的材料为可吸收金属或可吸收聚合物。例如，可吸收金属为纯铁或铁基合金。含锌层至少覆盖本体的部分表面。在一实施方式中，含锌层覆盖本体的全部表面。
当含锌层的材料为锌合金时，锌合金中的合金元素选自C、N、O、S、P、Ce、Mn、Ca、Cu、Pd、Si、W、Ti、Co、Cr、Cu及Re中至少一种。需要说明的是，锌合金中的合金元素为对生物体无毒无害的元素。或者，合金元素的含量较低，不足以对生物体产生毒性作用。在一实施方式中，锌合金中的锌的质量百分含量为50％～99.99％。
无论含锌的基体为由纯锌或锌合金形成的基体还是含锌的基体包括本体及附着于本体上的含锌层，在一实施方式中，含锌的基体均具有外表面、内表面和侧表面。聚乳酸涂层至少覆盖含锌的基体的外表面。或者，聚乳酸涂层至少覆盖含锌的基体的内表面。或者，聚乳酸涂层至少覆盖含锌的基体的侧表面。其中，当将含锌医疗器械植入体内中时，内表面为为与体液(例如血液)直接接触的表面，外表面为与组织壁(例如血管壁)直接接触的表面，侧表面连接内表面和外表面。
在一实施方式中，聚乳酸涂层覆盖含锌的基体的外表面、内表面和侧表面。
当将该含锌医疗器械植入生物体内时，锌腐蚀可以生成磷酸锌，同时聚乳酸降解产生羧基和羟基。磷酸锌可与羧基和羟基发生反应，生成络合物，从而阻碍锌的进一步腐蚀。因而，包含聚乳酸涂层的含锌医疗器械的锌腐蚀速率小于不包含聚乳酸涂层的含锌医疗器械的锌腐蚀速率。同时，聚乳酸降解产生的氢离子会加速金属的腐蚀。即聚乳酸涂层对含锌的基体中锌的腐蚀速率同时存在缓蚀作用和促腐蚀的作用。聚乳酸的降解产物的释放速率和累积浓度会影响聚乳酸涂层对锌腐蚀产生的缓蚀作用和促腐蚀作用。聚乳酸涂层中的聚乳酸自身的性质是影响聚乳酸的降解速率的重要因素。聚乳酸涂层的厚度影响聚乳酸降解产物的总量。
聚乳酸涂层的厚度为x，单位为微米(μm)，x满足公式：
Figure PCTCN2021000059-appb-000006
其中，且当聚乳酸为聚消旋乳酸时，a＝0.0336ln(Mn)-0.1449，b＝-0.472ln(Mn)+2.1524，c＝1.1604ln(Mn)-5.7128；
当聚乳酸为聚左旋乳酸时，a＝-0.006ln(Mn)+0.03441，b＝0.0648ln(Mn)-0.3662，c＝-0.162ln(Mn)+0.7847。
其中，Mn为聚乳酸的重均分子量，单位为千道尔顿(kDa)。即在计算a、b和c的大小时，Mn的数值按以kDa对应的数值的大小带入公式中计算，所计算得到的数值大小直接用于上述公式或关系式中。在将聚乳酸涂层的厚度x带入上述公式或关系式中时，将聚乳酸涂层的厚度取单位为微米时对应的数值带入上述关系式中进行比较。
上述聚乳酸涂层的厚度x是指聚乳酸涂层的位于外表面的部分的平均厚度x 外、聚乳酸涂层的位于内表面的部分的平均厚度x 内或聚乳酸涂层的位于侧表面的部分的平均厚度x 侧，即x 外、x 内和x 侧中的至少一个满足上述公式。
在一实施方式中，x 内≤x 外，x 内≤x 侧，并且x 外、x 内和x 侧中的至少一个满足如下公式：
Figure PCTCN2021000059-appb-000007
x＝x内，x 侧或x 外。
在一实施方式中，x 外、x 内和x 侧均满足上述公式。
经实验证明，当聚乳酸涂层的厚度、聚乳酸的种类和聚乳酸的分子量满足上述关系时，聚乳酸涂层对含锌的基体中锌的腐蚀速率的影响中，缓蚀作用为主导作用，使得锌的腐蚀速率较小。
通过在含锌的基体上设置厚度为x微米的聚乳酸涂层，并且选用合适的聚乳酸，使得含锌的基体中锌的腐蚀速率较小。当含锌的基体为由纯锌或锌合金形成的基体时，锌的腐蚀速率较小，即含锌的基体自身的腐蚀速率较小，避免含锌的基体腐蚀过快而过快地失去力学性能，因而有利于在修复期内保持足够的力学性能。当含锌的基体包括本体及附着于本体上的含锌层，且含锌层的材料为纯锌或锌合金时，含锌层包覆在本体的表面，能够物理隔离本体和体液。含锌层的腐蚀速率较小，有利于延缓对本体的保护期，从而有利于在修复期内保持足够的力学性能。
并且，由于锌的腐蚀速率较小，使得组织中积累的锌腐蚀产物的浓度较小，降低生物学风险。
需要说明的是，当聚乳酸涂层的厚度x满足上述公式时使含锌的基体中锌的腐蚀速率较小，是指在其他条件相同的前提下进行比较，如含锌的基体相同、聚乳酸的材料相同、聚乳酸涂层的分布方式相同。或者，在含锌的基体相同的前提下，含有上述聚乳酸涂层的含锌医疗器械的锌的腐蚀速率小于不含有该聚乳酸涂层的器械的腐蚀速率。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为100～300kDa，聚乳酸涂层的位于外表面的部分的平均厚度为5.2～11.5微米。和/或，聚乳酸涂层的位于内表面的部分的平均厚度为5.2～11.5微米。和/或，聚乳酸涂层的位于侧表面的部分的平均厚度为5.2～11.5微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为5.2～11.5微米。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为10～100kDa，聚乳酸涂层的位于外表面的部分的平均厚度为2～9微米。和/或，聚乳酸涂层的位于内表面的部分的平均厚度为2～9微米。和/或，聚乳酸涂层的位于侧表面的部分的平均厚度为2～9微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为2～9微米。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为2～10kDa，聚乳酸涂层的位于外表面的部分的平均厚度为1.5～5.5微米。和/或，聚乳酸涂层的位于内表面的部分的平均厚度为1.5～5.5微米。和/或，聚乳酸涂层的位于侧表面的部分的平均厚度为1.5～5.5微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为1.5～5.5微米。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为200kDa，聚乳酸涂层的位于外表面的部分的平均厚度为9.1微米。和/或，聚乳酸涂层的位于内表面的部分的平均厚度为9.1微米。和/或，聚乳酸涂层的位于侧表面的部分的平均厚度为9.1微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为9.1微米。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为50kDa，聚乳酸涂层的位于外表面的部分的平均厚度为4.9微米。和/或，聚乳酸涂层的 位于内表面的部分的平均厚度为4.9微米。和/或，聚乳酸涂层的位于侧表面的部分的平均厚度为4.9微米。或在一实施方式中，聚乳酸涂层所有表面的平均厚度均为4.9微米。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为5kDa，聚乳酸涂层的位于外表面的部分的平均厚度为3.6微米。和/或，聚乳酸涂层的位于内表面的部分的平均厚度为3.6微米。和/或，聚乳酸涂层的位于侧表面的部分的平均厚度为3.6微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为3.6微米。
在一实施方式中，聚乳酸为聚左旋乳酸，聚消旋乳酸的重均分子量为200～300kDa，聚乳酸涂层的位于外表面的部分的平均厚度为9～22微米或聚乳酸涂层的位于内表面的部分的平均厚度为9～22微米或聚乳酸涂层位置所述侧表面的部分的平均厚度为9～22微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为9～22微米。
在一实施方式中，聚乳酸为聚左旋乳酸，聚左旋乳酸的重均分子量为50～200kDa，聚乳酸涂层的位于外表面的部分的平均厚度为7～13微米或聚乳酸涂层的位于内表面的部分的平均厚度为7～13微米或聚乳酸涂层位置所述侧表面的部分的平均厚度为7～13微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为7～13微米。
在一实施方式中，聚乳酸为聚左旋乳酸，聚左旋乳酸的重均分子量为300kDa，聚乳酸涂层的位于外表面的部分的平均厚度为19.7微米或聚乳酸涂层的位于内表面的部分的平均厚度为19.7微米或聚乳酸涂层位置所述侧表面的部分的平均厚度为19.7微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为19.7微米。
在一实施方式中，聚乳酸为聚左旋乳酸，聚左旋乳酸的重均分子量为100kDa，聚乳酸涂层的位于外表面的部分的平均厚度为9.4微米或聚乳酸涂层的位于内表面的部分的平均厚度为9.4微米或聚乳酸涂层位置所述侧表面的部分的平均厚度为9.4微米。在一实施方式中，聚乳酸涂层所有表面的平均厚度均为9.4微米。
在一实施方式中，聚乳酸涂层中含有活性药物。在其中一个实施例中，活 性药物选自抑制血管增生的药物、抗血小板类药物、抗血栓类药物、抗炎症反应药物及抗致敏药物中的至少一种。抑制血管增生的药物选自紫杉醇、雷帕霉素及其衍生物中的至少一种。抗血小板类药物可以为西洛他唑。抗血栓类药物可以为肝素。抗炎症反应药物可以为地塞米松。抗致敏药物选自葡萄糖酸钙、扑尔敏及可的松的至少一种。当聚乳酸涂层中含有活性药物时，即聚乳酸与活性药物混合形成混合涂层时，聚乳酸涂层的厚度可由混合涂层的厚度按照聚乳酸与药物的质量比折算，聚乳酸涂层厚度(x)＝混合涂层厚度×聚乳酸的质量百分比。在其中一个实施例中，活性药物可以分布在含锌的基体的外表面、内表面和侧表面中的至少一个中。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为5kDa。聚乳酸涂层的位于内表面和侧表面的部分的平均厚度均为0，即内表面和侧表面无聚乳酸涂层。位于外表面的部分含有西罗莫司，聚乳酸-西罗莫司涂层的平均厚度为5.4微米，折算聚乳酸涂层的位于外表面的部分的平均厚度为3.6微米。其中聚乳酸与西罗莫司的质量比为2∶1。
在一实施方式中，聚乳酸为聚消旋乳酸，聚消旋乳酸的重均分子量为200kDa。聚乳酸涂层的位于内表面的部分的平均厚度为8微米；聚乳酸涂层的位于侧表面和外表面的部分均含有西罗莫司，即为聚乳酸-西罗莫司涂层，聚乳酸与西罗莫司的质量比为6∶1，位于侧表面和外表面部分的聚消旋乳酸-西罗莫司涂层的平均厚度均为10.6μm，折算聚乳酸涂层的平均厚度为9.1μm。
上述含锌医疗器械可以为血管支架、非血管腔内支架、封堵器、骨科植入物、齿科植入物、呼吸科植入物、妇科植入物、男科植入物、缝合线或者螺栓等等。非血管腔内支架可以为气管支架、食道支架、尿道支架、肠道支架或者胆道支架。骨科植入物可以为固定螺钉、固定铆钉或者骨板。当然，其他需要实现可降解吸收的医疗器械均可以作为本实施例的医疗器械。
以下通过具体实施例对上述含锌医疗器械进一步阐述。
以下实施例的测试方式如下：
1、聚乳酸的重均分子量测定
使用美国Wyatt公司的GPC-多角度激光光散射仪联用分子量测试系统进行检测。该测试系统包括美国安捷伦公司的液相泵和进样器、美国安捷伦公司的 Agilent PL MIXED-C型GPC柱(尺寸：7.5×300mm，5微米)、美国Wyatt公司的多角度激光光散射仪及示差检测器。检测条件为：
流动相：四氢呋喃；泵流速：1mL/min；进样量：100μL；激光波长：663.9nm；测试温度：35℃。
2、聚乳酸涂层的厚度测定
使用扫描电镜法测量：首先将需要测试涂层厚度的样品固定到样品台上，然后将样品台放到JFC-1600喷金设备中喷鉑金，喷完一次后旋转180度再喷一次保证所有位置被喷到。将表面喷好金的样品放置到按5∶1的比例调配好的标乐常温树脂固化剂混合试剂中，静置8个小时以上才可以脱离封样壳。将封好的样品平均分为3段，每段用半自动磨抛机按照样品抛磨的程序进行抛磨，要将需要测量的样品截面抛光到无磨痕。将抛磨好的样品固定到扫描电镜的载物台上，将整个载物台放置到JFC-1600喷金设备中进行喷金20s。将喷好金的样品放到JSM-6510扫描电镜中进行厚度测量。每个截面分别测量内表面涂层厚度、侧表面涂层厚度和外表面涂层厚度；如每个截面有多个杆，则随机取至少3个杆测量杆的内表面涂层厚度、侧表面涂层厚度和外表面涂层厚度。所有测量的内表面涂层的厚度计算平均值则为器械内表面涂层的平均厚度，所有测量的侧表面涂层的厚度计算平均值则为器械侧表面涂层的平均厚度，所有测量的外表面涂层的厚度计算平均值则为器械外表面涂层的平均厚度。
3、含锌医疗器械中锌的腐蚀速率测定
采用失重法检测：将含锌医疗器械植入兔子体内，在预定观察时间点，诸如1个月、3个月......，将兔子处死，并取出含锌医疗器械。小心将含锌医疗器械上的组织尽可能的去除后，随后将含锌医疗器械浸泡于饱和甘氨酸溶液中并超声清洗，1分钟后将含锌医疗器械从甘氨酸溶液中取出并迅速用清水清洗10s，再将清洗后的含锌医疗器械浸泡于1mol/L的氢氧化钠溶液24小时以上，以将锌完全溶解，然后通过原子吸收光谱法(简称AAS)检测氢氧化钠溶液中的锌浓度。通过计算可获得含锌医疗器械中锌的腐蚀速率。
实施例1
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中 的聚乳酸为聚消旋乳酸，分子量为200kDa，外表面的聚乳酸涂层的平均厚度、侧表面的聚乳酸涂层的平均厚度和内表面的聚乳酸涂层的平均厚度均为9.1μm。聚乳酸涂层采用喷涂法制备。
对比例1-1
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚消旋乳酸，分子量为200kDa，外表面的聚乳酸涂层的平均厚度、侧表面的聚乳酸涂层的平均厚度和内表面的聚乳酸涂层的平均厚度均为6μm。聚乳酸涂层采用喷涂法制备。
对比例1-2
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚消旋乳酸，分子量为200kDa，外表面的聚乳酸涂层的平均厚度、侧表面的聚乳酸涂层的平均厚度和内表面的聚乳酸涂层的平均厚度均为16μm。聚乳酸涂层采用喷涂法制备。
将实施例1、对比例1-1和对比例1-2的锌基支架分别植入三只兔子髂动脉中，6个月后取出。测得锌腐蚀速率分别12％、20％和18％。实施例1的锌基支架中锌的腐蚀速率最小。
实施例2
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚消旋乳酸，分子量为50kDa，外表面的聚乳酸涂层的平均厚度为6μm、侧表面的聚乳酸涂层的平均厚度为5.5μm，内表面的聚乳酸涂层的平均厚度为4.9μm。聚乳酸涂层采用喷涂法制备。
对比例2-1
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚消旋乳酸，分子量为50kDa，外表面的聚乳酸涂层的平均厚度为6μm、侧表面的聚乳酸涂层的平均厚度为5.5μm，内表面的聚乳酸涂层的平均厚 度为2.5μm。聚乳酸涂层采用喷涂法制备。
对比例2-2
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚消旋乳酸，分子量为50kDa，外表面的聚乳酸涂层的平均厚度为6μm、侧表面的聚乳酸涂层的平均厚度为5.5μm，内表面的聚乳酸涂层的平均厚度为8μm。聚乳酸涂层采用喷涂法制备。
将实施例2、对比例2-1和对比例2-2的锌基支架分别植入三只兔子髂动脉中，6个月后取出。测得锌腐蚀速率分别18％、28％和24％。实施例2的锌基支架中锌的腐蚀速率最小。
实施例3
锌基支架，规格为3.0mm×8mm，包括支架基体及仅覆盖支架基体外表面的聚乳酸-西罗莫司涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚消旋乳酸，分子量为5kDa，聚消旋乳酸与西罗莫司的质量比为2∶1，聚乳酸-西罗莫司涂层的平均厚度为5.4μm，折算聚乳酸涂层的平均厚度为3.6μm。聚乳酸-西罗莫司涂层采用3D打印法制备。
对比例3-1
锌基支架，规格为3.0mm×8mm，包括支架基体，支架基体的材料为纯锌，支架基体的质量为5mg，基体上无聚乳酸涂层。.
对比例3-2
锌基支架，规格为3.0mm×8mm，包括支架基体及仅覆盖支架基体外表面的聚乳酸-西罗莫司涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚消旋乳酸，分子量为5kDa，聚消旋乳酸与西罗莫司的质量比为2∶1，聚乳酸-西罗莫司涂层的平均厚度为12μm，折算聚乳酸涂层的平均厚度为8μm。聚乳酸-西罗莫司涂层采用喷涂法制备。
将实施例3、对比例3-1和对比例3-2的锌基支架分别植入三只兔子髂动脉中，3个月后取出。测得锌腐蚀速率分别11％、17％和13％。实施例3的锌基支架中锌的腐蚀速率最小。
实施例4
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为锌合金，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚左旋乳酸，分子量为300kDa，外表面的聚乳酸涂层的平均厚度、侧表面的聚乳酸涂层的平均厚度和内表面的聚乳酸涂层的平均厚度均为19.6μm。聚乳酸涂层采用喷涂法制备。
对比例4-1
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚左旋乳酸，分子量为300kDa，外表面的聚乳酸涂层的平均厚度、侧表面的聚乳酸涂层的平均厚度和内表面的聚乳酸涂层的平均厚度均为10μm。聚乳酸涂层采用喷涂法制备。
对比例4-2
锌基支架，规格为3.0mm×8mm，包括支架基体及完全覆盖支架基体表面的聚乳酸涂层，支架基体的材料为纯锌，支架基体的质量为5mg，聚乳酸涂层中的聚乳酸为聚左旋乳酸，分子量为300kDa，外表面的聚乳酸涂层的平均厚度、侧表面的聚乳酸涂层的平均厚度和内表面的聚乳酸涂层的平均厚度均为30μm。聚乳酸涂层采用喷涂法制备。
将实施例4、对比例4-1和对比例4-2的锌基支架分别植入三只兔子髂动脉中，6个月后取出。测得锌腐蚀速率分别21％、29％和27％。实施例4的锌基支架中锌的腐蚀速率最小。
实施例5
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层表面的聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸-西罗莫司涂层的质量比为10∶1，内表面的聚消旋乳酸-西罗莫司涂层的厚度均为5.5μm，折算聚乳酸涂层厚度为5μm；侧表面和外表面的聚消旋乳酸与西罗莫司的质量比为6∶1，侧表面和外表面的聚消旋乳酸-西罗莫司涂层的厚度均为10.6μm，折算聚乳酸涂层厚度为9.1μm。聚乳酸 涂层和聚乳酸-西罗莫司涂层采用喷涂法制备。
对比例5-1
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层的表面的聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸-西罗莫司涂层的质量比为10∶1，内表面的聚消旋乳酸-西罗莫司涂层的厚度均为5.5μm，折算聚乳酸涂层厚度为5μm；侧表面和外表面的聚消旋乳酸与西罗莫司的质量比为6∶1，侧表面和外表面的聚消旋乳酸-西罗莫司涂层的厚度均为7μm，折算聚乳酸涂层厚度为6μm。聚乳酸涂层和聚乳酸涂层-西罗莫司采用喷涂法制备。
对比例5-2
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层的表面的聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸-西罗莫司涂层的质量比为10∶1，内表面的聚消旋乳酸-西罗莫司涂层的厚度均为5.5μm，折算聚乳酸涂层厚度为5μm；侧表面和外表面聚消旋乳酸与西罗莫司的质量比为6∶1，侧表面和外表面的聚消旋乳酸-西罗莫司涂层的厚度均为17.5μm，折算聚乳酸涂层厚度为15μm。聚乳酸涂层和聚乳酸-西罗莫司涂层采用喷涂法制备。
将实施例5、对比例5-1和对比例5-2的铁基支架分别植入三只兔子髂动脉中，1个月后取出。测得锌腐蚀速率分别30％、56％和44％。实施例5的锌基支架中锌的腐蚀速率最小，其病理切片如图1所示，支架周围组织有少量炎症细胞浸润，无组织坏死等明显异常变化。
实施例6
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层内表面的聚乳酸涂层、覆盖纯锌层侧表面和外表面的聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为6μm；侧表面和外表面的聚消旋乳酸与西罗莫司的质量比为3∶1， 侧表面和外表面的聚消旋乳酸-西罗莫司涂层的厚度均为14.7μm，折算聚乳酸涂层厚度为11μm。
对比例6-1
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层的内表面的聚乳酸涂层、覆盖纯锌层侧表面和外表面聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为6μm；侧表面和外表面的聚消旋乳酸与西罗莫司的质量比为3∶1，侧表面和外表面的聚消旋乳酸-西罗莫司涂层的厚度均为8μm，折算聚乳酸涂层厚度为6μm。聚乳酸涂层-西罗莫司采用喷涂法制备。
对比例6-2
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层的内表面的聚乳酸涂层、覆盖纯锌层侧表面和外表面聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为6μm；侧表面和外表面聚消旋乳酸与西罗莫司的质量比为3∶1，侧表面和外表面的聚消旋乳酸-西罗莫司涂层的厚度均为21μm，折算聚乳酸涂层厚度为15.8μm。聚乳酸涂层和聚乳酸-西罗莫司涂层采用喷涂法制备。
将实施例6、对比例6-1和对比例6-2的铁基支架分别植入三只兔子髂动脉中，1个月后取出。测得锌腐蚀速率分别33％、54％和49％。实施例6的锌基支架中锌的腐蚀速率最小。
实施例7
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层内表面和侧表面的聚乳酸涂层、覆盖纯锌层外表面的聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面和侧表面的聚消旋乳酸涂层的平均厚度均为4.5μm；外表面的聚消旋乳酸与西罗莫司的质量比为4∶1，平均厚度均为8.8μm，折算聚乳酸涂层厚度为7.1μm。聚乳酸涂层和聚乳酸-西罗莫司涂层采用喷涂法制备。
对比例7-1
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层内表面和侧表面的聚乳酸涂层、覆盖纯锌层外表面的聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面和侧表面的聚消旋乳酸涂层的平均厚度均为4.5μm；外表面的聚消旋乳酸与西罗莫司的质量比为4∶1，平均厚度均为6μm，折算聚乳酸涂层厚度为4.8μm。聚乳酸涂层和聚乳酸-西罗莫司涂层采用喷涂法制备。
对比例7-2
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、完全覆盖支架本体表面的纯锌层及覆盖纯锌层内表面和侧表面的聚乳酸涂层、覆盖纯锌层外表面的聚乳酸-西罗莫司涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面和侧表面的聚消旋乳酸涂层的平均厚度均为4.5μm；外表面的聚消旋乳酸与西罗莫司的质量比为4∶1，平均厚度均为14.5μm，折算聚乳酸涂层厚度为11.6μm。聚乳酸涂层和聚乳酸-西罗莫司涂层采用喷涂法制备。
将实施例7、对比例7-1和对比例7-2的铁基支架分别植入三只兔子髂动脉中，1个月后取出。测得锌腐蚀速率分别51％、61％和63％。实施例7的锌基支架中锌的腐蚀速率最小。
实施例8
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为5.1μm，外表面和侧表面的聚乳酸涂层的平均厚度均为7.1μm。聚乳酸涂层采用喷涂法制备。
对比例8-1
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层 的平均厚度为5.1μm，外表面和侧表面的聚乳酸涂层的平均厚度均为6.3μm。聚乳酸涂层采用喷涂法制备。
对比例8-2
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为5.1μm，外表面和侧表面的聚乳酸涂层的平均厚度均为14.8μm。聚乳酸涂层采用喷涂法制备。
将实施例8、对比例8-1和对比例8-2的铁基支架分别植入三只兔子髂动脉中，1个月后取出。测得锌腐蚀速率分别48％、54％和66％。实施例8的铁基支架中锌的腐蚀速率最小。
实施例9
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为7.1μm，外表面和侧表面的聚乳酸涂层的平均厚度均为11.1μm。聚乳酸涂层采用喷涂法制备。
对比例9-1
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为7.1μm，外表面和侧表面的聚乳酸涂层的平均厚度均为6.7μm。聚乳酸涂层采用喷涂法制备。
对比例9-2
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为200kDa。内表面的聚消旋乳酸涂层的平均厚度为7.1μm，外表面和侧表面的聚乳酸涂层的平均厚度均为16.6μm。聚乳酸涂层采用喷涂法制备。
将实施例9、对比例9-1和对比例9-2的铁基支架分别植入三只兔子髂动脉中，1个月后取出。测得锌腐蚀速率分别44％、64％和62％。实施例9的铁基支架中锌的腐蚀速率最小。
实施例10
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为100kDa。内表面、外表面和侧表面的聚乳酸涂层的平均厚度均为7.3μm。聚乳酸涂层采用喷涂法制备。
对比例10-1
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为100kDa。内表面、外表面和侧表面的聚乳酸涂层的平均厚度均为4μm。聚乳酸涂层采用喷涂法制备。
对比例10-2
铁基支架，规格为3.0mm×8mm，包括铁基合金制成的支架本体、及完全覆盖支架基体表面的聚乳酸涂层。支架本体的铁质量为4mg，锌层质量为250μg，涂层中的聚乳酸均为聚消旋乳酸，分子量为100kDa。内表面、外表面和侧表面的聚乳酸涂层的平均厚度均为11μm。聚乳酸涂层采用喷涂法制备。
将实施例10、对比例10-1和对比例10-2的铁基支架分别植入三只兔子髂动脉中，1个月后取出。测得锌腐蚀速率分别48％、69％和55％。实施例10的铁基支架中锌的腐蚀速率最小。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权 利要求为准。

Claims (11)

  1. 一种含锌医疗器械，其特征在于，包括含锌的基体及设于所述含锌的基体表面上的聚乳酸涂层，所述聚乳酸涂层的厚度为x，所述x满足公式：
    Figure PCTCN2021000059-appb-100001
    其中，当所述聚乳酸为聚消旋乳酸时，所述a＝0.0336ln(Mn)-0.1449，b＝-0.472ln(Mn)+2.1524，c＝1.1604ln(Mn)-5.7128；
    当所述聚乳酸为聚左旋乳酸时，所述a＝-0.006ln(Mn)+0.03441，b＝0.0648ln(Mn)-0.3662，c＝-0.162ln(Mn)+0.7847；
    所述Mn为聚乳酸的重均分子量，单位为千道尔顿，x的单位为微米。
  2. 根据权利要求1所述的含锌医疗器械，其特征在于，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚消旋乳酸，所述聚消旋乳酸的重均分子量为100～300kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为5.2～11.5微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为5.2～11.5微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为5.2～11.5微米。
  3. 根据权利要求1所述的含锌医疗器械，其特征在于，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚消旋乳酸，所述聚消旋乳酸的重均分子量为10～100kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为2～9微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为2～9微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为2～9微米。
  4. 根据权利要求1所述的含锌医疗器械，其特征在于，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚消旋乳酸，所述聚消旋乳酸的重均分子量为2～10kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为1.5～5.5微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为1.5～5.5微米；所述 聚乳酸涂层的位于所述侧表面的部分的平均厚度为1.5～5.5微米。
  5. 根据权利要求1所述的含锌医疗器械，其特征在于，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚左旋乳酸，所述聚左旋乳酸的重均分子量为200～300kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为9～22微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为9～22微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为9～22微米。
  6. 根据权利要求1所述的含锌医疗器械，其特征在于，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层至少覆盖所述外表面或所述内表面或所述侧表面，所述聚乳酸为聚左旋乳酸，所述聚左旋乳酸的重均分子量为50～200kDa，且所述聚乳酸涂层的位于所述外表面的部分的平均厚度为7～13微米；所述聚乳酸涂层的位于所述内表面的部分的平均厚度为7～13微米；所述聚乳酸涂层的位于所述侧表面的部分的平均厚度为7～13微米。
  7. 根据权利要求1所述的含锌医疗器械，其特征在于，所述含锌的基体具有外表面、内表面和侧表面，所述聚乳酸涂层覆盖所述外表面、内表面和侧表面，所述聚乳酸涂层的位于所述外表面的部分的平均厚度为x 外，所述聚乳酸涂层的位于所述内表面的部分的平均厚度为x 内，所述聚乳酸涂层的位于所述侧表面的平均厚度为x 侧，x 内≤x 外，x 内≤x 侧，且所述x 外、x 内和x 侧至少一个满足如下公式：
    Figure PCTCN2021000059-appb-100002
    x＝x 内，x 侧或x 外；
    其中，当所述聚乳酸为聚消旋乳酸时，所述a＝0.0336ln(Mn)-0.1449，b＝-0.472ln(Mn)+2.1524，c＝1.1604ln(Mn)-5.7128；
    当所述聚乳酸为聚左旋乳酸时，所述a＝-0.006ln(Mn)+0.03441， b＝0.0648ln(Mn)-0.3662，c＝-0.162ln(Mn)+0.7847；
    所述Mn为聚乳酸的重均分子量，单位为千道尔顿，x的单位为微米。
  8. 根据权利要求1所述的含锌医疗器械，其特征在于，所述含锌的基体的材料为纯锌或锌合金；或者，所述含锌的基体包括本体及附着于所述本体上的含锌层，且所述含锌层的材料为纯锌或锌合金。
  9. 根据权利要求8所述的含锌医疗器械，其特征在于，
    当所述含锌的基体的材料为纯锌或锌合金，所述锌合金中的锌的质量百分含量为50％～99.99％；
    当所述含锌的基体包括本体及附着于所述本体上的含锌层，且所述含锌层的材料为锌合金时，所述锌合金中的锌的质量百分含量为50％～99.99％。
  10. 根据权利要求8所述的含锌医疗器械，其特征在于，所述含锌层覆盖所述本体的全部表面。
  11. 根据权利要求1所述的含锌医疗器械，其特征在于，所述聚乳酸涂层中含有活性药物。
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