CN113116615B - Absorbable metal instrument - Google Patents

Absorbable metal instrument Download PDF

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Publication number
CN113116615B
CN113116615B CN201911412829.1A CN201911412829A CN113116615B CN 113116615 B CN113116615 B CN 113116615B CN 201911412829 A CN201911412829 A CN 201911412829A CN 113116615 B CN113116615 B CN 113116615B
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corrosion
holes
thickness
absorbable metal
hole
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CN113116615A (en
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林文娇
曹瀚文
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Biotyx Medical Shenzhen Co Ltd
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Biotyx Medical Shenzhen Co Ltd
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Priority to CN201911412829.1A priority Critical patent/CN113116615B/en
Priority to PCT/CN2020/092485 priority patent/WO2021135055A1/en
Publication of CN113116615A publication Critical patent/CN113116615A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/9155—Adjacent bands being connected to each other
    • A61F2002/91575—Adjacent bands being connected to each other connected peak to trough
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Optics & Photonics (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Physics & Mathematics (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Prostheses (AREA)

Abstract

The invention relates to an absorbable metal instrument, which comprises an absorbable metal base body, a corrosion inhibiting layer and a corrosion promoting layer, wherein the corrosion inhibiting layer is arranged on the absorbable metal base body, the corrosion promoting layer covers the corrosion inhibiting layer, a plurality of through holes are formed in a partial area of the absorbable metal base body, and the thickness of the part, located in the through holes, of the corrosion inhibiting layer is smaller than that of the other part of the corrosion inhibiting layer; and/or the thickness of the corrosion-promoting layer at the parts of the through holes is larger than that of other parts of the corrosion-promoting layer. The absorbable metal instrument can be deconstructed relatively quickly.

Description

Absorbable metal instrument
Technical Field
The invention relates to the field of implantable medical devices, in particular to an absorbable metal device.
Background
This section provides background information related to the present disclosure only and is not necessarily prior art.
Currently, in the field of absorbable implantable devices, the most widely used materials include degradable polymers, magnesium-based alloys and iron-based alloys. Among the degradable polymers, polylactic acid is most widely used, and has the advantages of complete degradation and absorption by organisms, and the degradation products are carbon dioxide and water, so that the degradable polymers are friendly to human bodies. The disadvantage is that the mechanical properties of the degradable polymer based device are insufficient compared to metal based devices, and if the same mechanical properties as metal based devices are achieved, the size of the degradable polymer based device needs to be larger than the metal based device, which limits the application of the degradable polymer based device. Magnesium-based alloy and iron-based alloy have the advantages of easy processing and shaping and high mechanical strength, but the magnesium-based alloy has too high corrosion rate in human body and can only meet the mechanical property of early implantation by increasing the size of the magnesium-based alloy instrument, which also limits the application of the magnesium-based alloy instrument. Iron-based materials are considered to be absorbable and safe metal materials, and iron-based devices have strong supporting force, so that attention is paid. However, iron-based absorbable devices suffer from slow corrosion.
From the clinical application perspective, after the absorbable implantable device has completed its intended use, and the diseased site has healed and recovered to normal form and function, the earlier the time point at which the device loses mechanical properties so as not to bind the implanted site due to corrosion or degradation is the better, without causing new biocompatibility problems, to avoid the device from limiting the normal development of the implanted site too long. For example, when a vascular stent is implanted into a blood vessel of a newborn or infant, if the time for the vascular stent to lose mechanical properties is later after the implantation site is repaired, the vascular stent may restrict the normal growth and development of the blood vessel of the newborn or infant. Further, when the stent remains in the blood vessel for a long period of time, the portion where the stent is located becomes a new stenosis, thereby causing adverse effects.
Disclosure of Invention
Based on this, there is a need for an absorbable metal instrument that can be circumferentially deconstructed relatively quickly.
An absorbable metal device comprises an absorbable metal substrate, a corrosion inhibiting layer and an erosion promoting layer, wherein the erosion inhibiting layer is arranged on the absorbable metal substrate, the erosion promoting layer covers the corrosion inhibiting layer, a plurality of through holes are formed in a partial area of the absorbable metal substrate, and the thickness of the part, located in the through holes, of the corrosion inhibiting layer is smaller than that of the other part of the corrosion inhibiting layer; and/or the thickness of the corrosion-promoting layer at the parts of the through holes is larger than that of other parts of the corrosion-promoting layer.
In one embodiment, the absorbable metal substrate comprises a plurality of wavy annular structures arranged along the axial direction, each wavy annular structure comprises a plurality of supporting rods and a plurality of connecting rods, two ends of each supporting rod are respectively connected with two adjacent connecting rods to form the wavy annular structure, and at least one supporting rod of each wavy annular structure is provided with the plurality of through holes.
In one embodiment, only one support rod on each wavy annular structure is provided with a plurality of through holes, so that when the plurality of wavy annular structures are deconstructed from the positions where the through holes are formed, the unfolding outline of the absorbable metal instrument is in a diamond shape or a rectangular shape;
or, a plurality of through holes are formed on a plurality of supporting rods on each wave-shaped annular structure, and the distribution rules of the through holes on each supporting rod are the same, so that when the wave-shaped annular structures are deconstructed from the positions provided with the through holes, the unfolding outline of the absorbable metal instrument is in a plurality of rhombuses or a plurality of rectangles.
In one embodiment, the hollow-out rate of each support rod provided with the through hole is 7% -35%.
In one embodiment, the distance between the edge of the through hole and the edge of the support rod where the through hole is located is 25-100 micrometers.
In one embodiment, when the distribution rules of the plurality of through holes on each support rod are the same, when the plurality of wavy annular structures are deconstructed from the positions provided with the through holes, the expansion profile of the absorbable metal instrument is in one or more rhombuses or in one or more rectangles, the distance between any two adjacent through holes is greater than or equal to 20 micrometers, and the percentage of the aperture of any one through hole in the width direction of the support rod to the width of the support rod is less than or equal to 57%;
or the through holes on each supporting rod are distributed in a plurality of rows along the length direction of the supporting rod, the distance between any two adjacent through holes is greater than or equal to 20 micrometers, and the percentage of the sum of the aperture diameters of the through holes along the width direction of the supporting rod and the width of the supporting rod is less than or equal to 57%.
In one embodiment, the volume of the absorbable metal matrix per unit area of luminal tissue is 6.4-36 μm and the coverage of the absorbable metal matrix is 8-12% in the nominal expanded state.
In one embodiment, the difference between the thickness of the part of the corrosion-promoting layer in the through hole and the thickness of the other part of the corrosion-promoting layer is 0.3-3 μm, and the difference between the thickness of the part of the corrosion-promoting layer in the through hole and the thickness of the other part of the corrosion-promoting layer is 3-47 μm.
In one embodiment, the thickness of the part of the etching buffer layer, which is positioned in the through hole, ranges from 0.2 to 2 μm, and the thickness of the other part of the etching buffer layer ranges from 0.5 to 5 μm; the thickness range of the corrosion-promoting layer positioned at the through hole part is 6-50 mu m, and the thickness range of other parts of the corrosion-promoting layer is 3-30 mu m.
In one embodiment, the material of the absorbable metal matrix is an iron-based material, the material of the corrosion-inhibiting layer is pure zinc or zinc alloy, and the material of the corrosion-promoting layer is polyester.
The through holes are formed in partial areas of the absorbable metal instrument, the thickness of the corrosion-inhibiting layer in the area with the through holes is smaller than that of the area without the through holes, the thickness of the corrosion-promoting layer in the area with the through holes is larger than that of the area without the through holes, the corrosion rate of the area with the through holes is adjusted to be larger than that of the area without the through holes, the area with the through holes is preferentially broken, and accordingly rapid circumferential deconstruction is achieved.
Drawings
FIG. 1 is a schematic view of one embodiment of an absorbable metal instrument;
FIG. 2 is a schematic diagram of a corrugated loop structure according to an embodiment;
FIG. 3 is a cross-sectional view of a connection between a support rod and a connection rod of a corrugated loop structure according to an embodiment;
FIG. 4 is a schematic diagram of the connection between the support rod and the connection rod of the wavy annular structure according to one embodiment;
FIG. 5 isbase:Sub>A cross-sectional view taken along line A-A of FIG. 4;
FIG. 6 is a cross-sectional view taken along line B-B of FIG. 4;
FIG. 7 is a schematic view of an embodiment of the area of the corrosion-inhibiting layer or corrosion-promoting layer at the via;
FIG. 8 is a schematic view of another embodiment of a region of a corrosion-inhibiting layer or corrosion-promoting layer at a via;
FIG. 9 is a schematic structural view of another embodiment absorbable metal instrument;
FIG. 10 is a schematic view of a deployed configuration of an embodiment of a wavy annular structure of an absorbable metal instrument circumferentially deconstructed;
FIG. 11 is a schematic view of another embodiment of a deployed configuration of a wavy annular structure of an absorbable metal instrument circumferentially deconstructed;
fig. 12 is a partially enlarged view of fig. 11.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, embodiments accompanying figures are described in detail below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather should be construed as broadly as the present invention is capable of modification in various respects, all without departing from the spirit and scope of the present invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
In the field of interventional medical devices, the "distal end" is defined as the end that is distal from the operator during the procedure, and the "proximal end" is defined as the end that is proximal to the operator during the procedure. "axial" refers to a direction parallel to the line joining the centers of the distal and proximal ends of the medical device, and "radial" refers to a direction perpendicular to the axial direction. "circumferential" refers to the circumferential direction, i.e., the direction about the axis of the lumen device.
The present disclosure provides an absorbable metal instrument that can be deconstructed relatively quickly.
Referring to fig. 1, an absorbable metal device 100 according to one embodiment includes an absorbable metal matrix 10, where the absorbable metal matrix 10 includes a plurality of axially aligned wavy annular structures 110. Referring also to fig. 2, the wavy annular structure 110 is a closed annular structure having a peak and a valley structure. Any adjacent two of the wavy annular structures 110 are axially connected by a connecting member 120, so that a plurality of the wavy annular structures 11 arranged in the axial direction form a lumen structure.
As shown in fig. 2, each of the wavy annular structures 110 includes a plurality of support rods 111 and a plurality of connection rods 112. The support rods 111 are generally bar-shaped rods and the connecting rods 112 are generally arc-shaped or arched rods. Referring to fig. 3, two ends of each supporting rod 111 are respectively connected to two adjacent connecting rods 112, and each connecting rod 112 connects two adjacent supporting rods 111 to form a corrugated ring structure 110. Wherein one connecting rod 112 forms a wave crest and the other connecting rod 112 forms a wave trough.
Referring again to fig. 2, each support rod 111 has an outer surface 1111, an inner surface 1112 opposite to the outer surface 1111, and two opposite side surfaces 1114 connecting the outer surface 1111 and the inner surface 1112. When absorbable metal device 100 is a vascular stent, after absorbable metal device 100 is implanted in a blood vessel, outer surface 1111 is a surface that abuts the inner wall of the blood vessel, and inner surface 1112 is a surface that is in direct contact with blood. At least one support rod 111 of each wavy annular structure 110 is provided with a plurality of through holes 1113. The through hole 1113 extends through the outer surface 1111 and the inner surface 112 of the support rod 111. In other embodiments, the through hole 1113 penetrates through both side surfaces 1114 of the support rod 111.
In one embodiment, the connector 120 is substantially "omega" shaped. It should be noted that in other embodiments, the shape of the connecting element 120 is not limited to "Ω", and any shape of the connecting element 120 that can ensure the axial connection of the plurality of wavy annular structures 110 and does not affect the compression and expansion of the absorbable metal instrument 100 is suitable.
Referring to fig. 4, 5 and 6, resorbable metal device 100 further includes a corrosion-inhibiting layer 120 and an erosion-promoting layer 130 disposed on resorbable metal substrate 10. Wherein, the corrosion-inhibiting layer 120 covers the whole surface of the absorbable metal matrix 10, and the corrosion-promoting layer 130 completely covers the corrosion-inhibiting layer 120.
In one embodiment, the thickness of the portion of the etching stop layer 120 located in the through hole 1113 is less than the thickness of the other portion of the etching stop layer 120, and the thickness of the portion of the corrosion-promoting layer 130 located in the through hole 1113 is greater than the thickness of the other portion of the corrosion-promoting layer 130. As shown in fig. 7, the portion of the etching resist layer 120 located at the through hole 1113 refers to the portion of the etching resist layer 120 covering the region R of the support rod 111. The portion of the corrosion-promoting layer 130 located at the through hole 1113 also refers to the portion of the corrosion-promoting layer 130 that covers the region R of the corrosion-inhibiting layer 120.
The region R shown in fig. 7 extends from one end of the support rod 111 to the other end thereof in the width direction B of the support rod 111, and extends from the outermost through hole 1113 at one end to the outermost through hole 1113 at the other end thereof in the longitudinal direction L. When the through holes 1113 at both ends in the length direction L of the support rod 111 are located at the edges of both ends of the support rod 111, respectively, the entire support rod 111 is the region R, as shown in fig. 8.
When the absorbable metal device 100 is implanted in vivo, the corrosion-inhibiting layer 120 can isolate the absorbable metal matrix 10 from body fluids to a certain extent, so as to retard the corrosion of the absorbable metal matrix 10. As the corrosion-inhibiting layer 120 is consumed, the absorbable metal substrate 10 is exposed and corrodes more rapidly. Also, at a later stage of implantation, as corrosion-promoting layer 130 is consumed or degraded, corrosion-promoting layer 130 can release corrosion-promoting substances to accelerate corrosion of absorbable metal substrate 10. The corrosion rates of the absorbable metal matrix 10 at different stages of implantation are controlled by the erosion retarding layer 120 and the corrosion promoting layer 130 to avoid over-rapid corrosion of the absorbable metal matrix 10 or to completely prevent corrosion of the absorbable metal matrix 10 during the early stages of implantation. Also, the resorbable metal matrix 10 is able to corrode rapidly at the end of implantation.
The thickness of the portion of the etching stop layer 120 located in the through hole 1113 is smaller than the thickness of the other portion of the etching stop layer 120, so that the portion of the etching stop layer 120 located in the through hole 1113 is preferentially consumed, and the area of the support rod 111 where the through hole 1113 is opened is preferentially exposed. Moreover, the thickness of the corrosion-promoting layer 130 at the through hole 1113 is greater than the thickness of the other parts of the corrosion-promoting layer 130, so that the concentration of the corrosion-promoting substances accumulated around the area of the support rod 111 provided with the through hole 1113 is higher, and the corrosion of the area of the support rod 111 provided with the through hole 1113 can be accelerated. Therefore, in the later stage of implantation, the region of the support rod 111 provided with the through hole 1113 can be corroded quickly, so that the support rod 111 can be broken from the through hole 1113 quickly, and the absorbable metal matrix 10 can be rapidly circumferentially destructed to lose mechanical properties, for example, the absorbable metal matrix 10 can be rapidly destructed to lose radial support properties, so that the constraint on the healed diseased region can be relieved as soon as possible, and the healed tissue can normally develop.
When resorbable metal instrument 100 is implanted into the luminal tissue, resorbable metal instrument 100 is able to radially support the luminal tissue. In each wavy annular structure 110, the supporting rod 111 mainly supports the supporting rod 111, the through hole 1113 is formed in the supporting rod 111, the corrosion-promoting layer 120 forms the thickness difference between the area with the through hole 1113 and the area without the through hole 1113, and the corrosion-promoting layer 130 forms the thickness difference between the area with the through hole 1113 and the area without the through hole 1113, so that the area with the through hole 1113 of the supporting rod 111 is preferentially broken, and as soon as the supporting rod 111 is broken, the radial supporting force of the absorbable metal device 100 on the tissue is weakened or eliminated, so that the tissue is released from being bound as soon as possible, and normal development starts as soon as possible.
The low oxygen environment may cause the corrosion rate of the absorbable metal substrate 10 to slow down, and the through hole 1113, the corrosion-slowing layer 120 and the corrosion-promoting layer 130 cooperate to regulate the corrosion rate, so that when the absorbable metal device 100 is applied to some diseased regions with low blood oxygen content, such as pulmonary artery, inferior knee vein, etc., the corrosion rate of the absorbable metal substrate 10 still meets the clinical requirement.
In another embodiment, the portion of the corrosion-inhibiting layer 120 located in the through-hole 1113 has a thickness less than the thickness of the other portion of the corrosion-inhibiting layer 120, and the corrosion-promoting layer 130 is a coating with a uniform thickness, i.e., the thickness of the portion of the corrosion-promoting layer 130 located in the through-hole 1113 is equal to the thickness of the other portion of the corrosion-promoting layer 130. By making the thickness of the portion of the resist layer 120 located in the through hole 1113 low, the region of the absorbable metal base 10 in which the through hole 1113 is opened is preferentially broken. And the corrosion-promoting layer 130 has a uniform thickness to control the absorbable cycle of the entire absorbable metal matrix 10.
In another embodiment, the etching stop layer 120 is a coating or plating layer with a uniform thickness, i.e., the etching stop layer 120 has a thickness in the region of the through hole 1113 equal to the thickness of the other regions. The thickness of the portion of the corrosion-promoting layer 130 located at the via 1113 is greater than the thickness of the other portion of the corrosion-promoting layer 130. The preferential fracture of the region of the absorbable metal substrate 10 in which the through hole 1113 is formed is achieved by making the thickness of the portion of the erosion promoting layer 130 located at the through hole 1113 large. Also, the thickness of the corrosion-inhibiting layer 120 is uniform to control the time to initiate corrosion throughout the entire resorbable substrate 10.
Referring to fig. 9, in one embodiment, in each of the corrugated annular structures 110 of the absorbable metal substrate 10, only the through holes 1113 are formed on the respective support rods 111, and the corrosion-inhibiting layer 120 and the corrosion-promoting layer 130 are disposed with the above-mentioned thickness difference. As long as the support rod 111 formed with the through hole 1113 is preferentially broken, the absorbable metal base 10 can be rapidly destructed from the circumferential direction.
In the embodiment shown in fig. 1, each support rod 111 of each corrugated annular structure 110 has a plurality of through holes 1113. Moreover, the erosion-retarding layer 120 and the erosion-promoting layer 130 are arranged according to the corresponding thickness difference, so that the corrugated annular structure 110 is more completely destructed in the circumferential direction, the time of completely losing the mechanical property is earlier, and the normal development of tissues is more facilitated.
In addition, the through holes 1113 can increase the creeping area and the creeping path of endothelial cells, which is beneficial to accelerating endothelialization and improving the firmness of intimal coating, thereby reducing the risk of thrombus and embolism. Meanwhile, under the conditions of equal wall thickness, the same specific structure and the same number of the wavy annular structures 110, compared with the design without through holes, the mode of providing the through holes 1113 can significantly reduce the surface coverage rate of the absorbable metal device 100, so that the volume of the absorbable metal substrate 10 per unit tissue area (for example, per unit blood vessel area) is significantly reduced, and the lower the volume of the absorbable metal substrate 10 per unit tissue area is, the faster the corrosion rate is and the shorter the absorption period is. Each support rod 111 of each wavy annular structure 110 is provided with a plurality of through holes 1113, so that the effects of reducing the risk of thrombus and embolism, improving the corrosion rate and reducing the absorption period are better.
Referring to fig. 3 again, in one embodiment, the plurality of through holes 1113 are arranged in a row and are spaced apart from each other along the length direction L of the supporting rod 111.
In one embodiment, when the plurality of through holes 1113 are aligned in a row and spaced apart from each other along the longitudinal direction L of the support rod 111, the distance between the edge of any one of the through holes 1113 and the edge of the support rod 111 in the width direction B is L. The edge of the support rod 111 refers to an edge of the support rod 111 extending in the longitudinal direction L, and the edge of the through hole 1113 refers to an edge closest to the edge of the support rod 111. When the value of L is less than 25 microns, it may cause fracture at the through-hole 1113 during expansion of the resorbable metal device 100. When the value of L is larger than 100 μm, the aperture of the through hole 1113 itself is required to be small, which causes the advantage of opening the through hole 1113 to be insignificant. Thus, L ranges from 25 microns to 100 microns.
In one embodiment, when the plurality of through holes 1113 are arranged in a row and spaced along the length direction L of the support rod 111, the distance between any two adjacent through holes 1113 is greater than or equal to 20 μm. And, the aperture size of each through hole 1113 in the width direction B of the support rod 111 accounts for less than or equal to 57% of the width of the support rod 111 to avoid the through hole 1113 from being broken during the expansion process.
In another embodiment, the plurality of through holes 1113 of each support rod 111 are not limited to be arranged in a row, but are arranged in a plurality of rows and at intervals along the length direction L of the support rod 111.
In one embodiment, when the plurality of through holes 1113 are arranged in a plurality of rows and spaced apart along the length direction L of the supporting rod 111, the distance between any two adjacent through holes 1113 is greater than or equal to 20 μm. And, the sum of the hole diameters of the plurality of through holes 1113 arranged in the width direction B of the support rod 111 accounts for 57% or less of the width of the support rod 111 to prevent the through holes 1113 from being broken during the expansion.
In other embodiments, the plurality of through holes 1113 are arranged on the support rod 111 randomly or irregularly.
In one embodiment, the hollow rate of each supporting rod 111 with the through holes 1113 is 7% to 35% no matter how the plurality of through holes 1113 are arranged on each supporting rod 111. The hollow rate is greater than 7% to ensure that the corrosion rate of the position provided with the through hole 1113 is greater than that of other parts, and the creeping area and the creeping path of endothelial cells can be increased, and simultaneously the surface coverage rate of the absorbable metal instrument 100 is effectively reduced. The hollow-out rate is less than 35% to guarantee that the supporting rod 111 has sufficient mechanical strength, avoid splitting in the expansion process.
In view of preferential etching, the arrangement rules of the through holes 1113 on the support rods 111 of different wavy annular structures 110 may be the same or different. The number of the support rods 111 with the through holes 1113 on different wavy annular structures 110 may be the same or different. However, the through holes 1113 on the support rods 111 of different wavy annular structures 110 have the same arrangement rule, which is beneficial to reducing the stress concentration area.
In one embodiment, only one of the support rods 111 of each of the plurality of corrugated annular structures 110 has a plurality of through holes 1113 formed therein, such that when the plurality of corrugated annular structures 1110 are disassembled from the position where the through holes 1113 are formed therein, the absorbable metal device 100 has a diamond-shaped (as shown in fig. 10) or rectangular expanded contour.
According to the structure of the wavy annular structure 110 and the connection relationship of the wavy annular structures 110, a plurality of through holes 1113 are formed in one support rod 111 at a specific position of each wavy annular structure 110, and the arrangement rule of the through holes 1113 in each support rod 111 is the same (i.e., the relative position relationship and the size relationship between the through holes 1113 of each wavy annular structure 110 and the support rod 111 where the through holes are located are the same), so that when each wavy annular structure 110 is broken or deconstructed from the through holes 1113, the expanded contour of the absorbable metal device 100 is diamond-shaped or rectangular.
In another embodiment, a plurality of through holes 1113 are formed on the plurality of supporting rods 111 of each wavy annular structure 110, so that when the plurality of wavy annular structures 110 are disassembled from the position where the through holes 1113 are formed, the expanded profile of the absorbable metal device 100 has a plurality of diamonds or rectangles. The arrangement rule of the through holes 1113 on each support rod 111 is the same.
For example, in one embodiment, any one of the through holes 1113 of each support rod 111 of each wavy annular structure 110 is aligned with the corresponding through hole 1113 of the corresponding support rod 111 of the other wavy annular structure 110. For example, referring to fig. 11 (the line I-I in fig. 11 is the axial central axis of the absorbable metal substrate 10) and fig. 12, each of the support rods 111 of each of the corrugated ring structures 110 has four through holes 1113, and the four through holes 1113 are arranged in a row at intervals along the length direction L of the support rod 111. The four through holes 1113 are respectively connected with the four through holes 1113 on the corresponding support rods 111 of the other wavy annular structure 110 to form 4 straight lines a, b, c and d. Here, the corresponding support rods 111 refer to the support rods 1111 that are opposite in the axial direction, for example, five support rods 111 connected by straight lines a, b, c, and d shown in fig. 12. When each undulating annular structure 110 breaks away from the through hole 1113, the deployed profile of the absorbable metal device 100 is a plurality of rectangles.
The through holes 1113 are formed according to the above rules, so that each wavy annular structure 110 is broken regularly due to corrosion, and each wavy annular structure 110 can lose mechanical properties once broken, thereby eliminating the constraint on the healed tissue as early as possible.
In other embodiments, any one of the through holes 1113 of each support rod 111 of each wavy annular structure 110 and the corresponding through hole 1113 of the corresponding support rod 111 of the other wavy annular structure 110 are not necessarily strictly connected to form a straight line, and may be, for example, a wavy line in the axial direction or a zigzag line. Any opening rule of the through holes 1113 that can satisfy the requirement that the expanded contour of the absorbable metal device 100 has a plurality of rhombuses or a plurality of rectangles when all the wavy annular structures 110 are broken or deconstructed from the circumferential direction is applicable.
It should be noted that, no matter how the plurality of through holes 1113 are arranged on the same support rod 111, the number of the support rods 111 provided with the through holes 1113 on each wavy annular structure 110 is, whether the distribution and arrangement rules of the through holes 1113 on different wavy annular structures 110 are the same, and the shape of the through holes 1113 is not limited, and may be regular or irregular. For example, the through hole 1113 may be a circular hole, a polygonal hole, or the like.
In one embodiment, the edges of the through hole 1113 are rounded, which is advantageous for further reducing the mass of the absorbable metal substrate 10 and reducing the stress concentration area.
In one embodiment, the volume of the resorbable metal matrix 10 per unit area of luminal tissue is between 6.4 and 36 μm in the nominal expanded state. The coverage of the absorbable metal matrix 10 in the nominal expanded state is 8-12%. The lumen tissue is other lumen tissue such as blood vessel. Wherein, the nominal state refers to the state of the absorbable metal instrument 100 expanded under a nominal pressure. Nominal pressure refers to the design pressure at which expansion is performed.
The volume V of the absorbable metal matrix 10 per unit area of luminal tissue is calculated as follows:
V＝(π*D*L'*A)*T/(π*D*L')＝AT。
wherein D is the inner diameter of the blood vessel and the outer diameter of the metal substrate 10 after expansion, L' is the length of the metal substrate 10 after expansion to the state that the outer diameter is D, a is the coverage rate, i.e. the percentage of the outer surface area of the substrate directly contacting the inner wall of the blood vessel to the cylindrical surface area of the outer surface of the substrate after the metal substrate 10 is expanded to the outer diameter is D, and T is the wall thickness of the metal substrate 10 after expansion to the state that the outer diameter is D.
According to the above calculation formula, the volume of the absorbable metal substrate 10 per unit area of the lumen tissue can be regarded as the volume of the hollowed rectangular sheet material corresponding to the unit area of the lumen tissue. The smaller the volume of the hollowed rectangular sheet material per unit area of the lumen tissue means the shorter the period of corrosion and absorption of the material. When the volume of the absorbable metal matrix 10 per unit lumen tissue area is 6.4 to 36 μm and the coverage rate is 8 to 12%, the absorption cycle, the radial support performance and the expansion performance of the absorbable metal device 100 can be simultaneously considered.
In one embodiment, the thickness of the absorbable metal matrix 10 is greater than 80 μm, i.e., the thickness of the support rods 111 and the tie rods 112 is greater than 80 μm. The absorbable metal matrix 10 has a wall thickness greater than 80 μm and cooperates with the through-hole 1113, the erosion-retarding layer 120 and the corrosion-promoting layer 130 to provide the absorbable metal matrix 10 with sufficient mechanical properties during the repair period and to be able to deconstruct as early as possible after the repair period is completed.
In one embodiment, the material of absorbable metallic matrix 10 is an iron-based material, a magnesium-based material, or a zinc-based material. The iron-based material is pure iron or iron-based alloy, the magnesium-based material is pure magnesium or magnesium-based alloy, and the zinc-based material is pure zinc or zinc-based alloy. In one embodiment, the material of absorbable metal matrix 10 is an iron-based alloy containing no more than 2.11wt.% carbon.
In one embodiment, the material of the corrosion-inhibiting layer 120 is a metal material, and the electronegativity of the metal material is less than that of the material of the absorbable metal substrate 10, so that the corrosion of the corrosion-inhibiting layer 120 is earlier than that of the absorbable metal substrate 10.
In one embodiment, when the material of the absorbable metal matrix 10 is an iron-based material, the material of the erosion layer 120 is pure zinc, zinc alloy, pure magnesium or magnesium-based alloy.
In one embodiment, when the material of the absorbable metal matrix 10 is a zinc-based material, the material of the corrosion-inhibiting layer 120 is pure magnesium or a magnesium-based alloy.
In one embodiment, the corrosion-promoting layer 130 is a polyester. Degradation of the polyester can produce acidic species that accumulate around the absorbable metal substrate 10, creating an acidic environment. The corrosion rate of the absorbable metal matrix 10 in an acidic environment is relatively fast, so that the corrosion-promoting layer 130 is continuously degraded and continuously releases acidic substances to promote corrosion of the absorbable metal matrix 10 at the later stage of implantation.
In one embodiment, the material of corrosion-promoting layer 130 is a degradable polyester, a physical blend of a degradable polyester and a non-degradable polyester, or a copolymer of at least one degradable polyester-forming monomer and at least one non-degradable polyester-forming monomer.
In one embodiment, the degradable polyester is selected from any one or a physical blend of at least two of polylactic acid, polyglycolic acid, polybutylene succinate, poly (beta-hydroxybutyrate), polycaprolactone, polyethylene adipate, polypentanoate, polyhydroxyalkyl alcohol esters, and poly (malate). Alternatively, the degradable polyester is a copolymer of at least two monomers among the monomers forming the aforementioned degradable polyester.
In one embodiment, the non-degradable polyester is selected from any one or a physical blend of at least two of starch, chitosan, cellulose, polysaccharides and derivatives thereof, polyurethane (PU), polycarbonate, polymethylmethacrylate (PMMA), polystyrene (PS), polybutylene, polybutylmethacrylate (PBMA), and polyacrylamide. Alternatively, the non-degradable polyester is a copolymer of at least two monomers among the monomers forming the aforementioned non-degradable polyester.
In one embodiment, the absorbable metal matrix 10 is made of an iron-based material, the corrosion-inhibiting layer 120 is made of pure zinc or zinc alloy, and the corrosion-promoting layer 130 is made of degradable polyester. The difference between the thickness of the portion of the corrosion-inhibiting layer 120 located in the through hole 1113 and the thickness of the other portion of the corrosion-inhibiting layer 120 is in the range of 0.3 to 3 micrometers, and the difference between the thickness of the portion of the corrosion-promoting layer 130 located in the through hole 1113 and the thickness of the other portion of the corrosion-promoting layer 130 is in the range of 3 to 47 micrometers, so that the portion of the absorbable metal substrate 10 provided with the through hole 1113 can be preferentially broken, and the absorbable metal substrate 10 can be rapidly disassembled from the circumferential direction.
Under the premise that other conditions are the same, the through holes 1113 are formed, and the thickness of the part, located in the through holes 1113, of the corrosion-retarding layer 120 is smaller, so that the use amounts of metallic iron and zinc materials are reduced, the burden of tissue absorption and metabolism is reduced, and the biological risk is reduced.
In one embodiment, the thickness of the supporting rod 111 is 80 to 300 micrometers, the thickness of the portion of the etching stop layer 120 located in the through hole 1113 ranges from 0.2 to 2 micrometers, and the thickness of the other portion of the etching stop layer 120 ranges from 0.5 to 5 micrometers. The portion of the corrosion-promoting layer 130 located in the through hole 1113 has a thickness ranging from 6 to 50 microns, and the other portion of the corrosion-promoting layer 130 has a thickness ranging from 3 to 30 microns. Moreover, the hollow-out rate of each support rod 111 provided with the through hole 1113 is 7% -35%. The thickness of the support rod 111, the thickness of the corrosion-retarding layer 120 and the corrosion-promoting layer 130 are matched with the hollow-out rate of the support rod 111, so that the corrosion behavior of the absorbable metal instrument 100 meets the clinical use requirement, namely, enough mechanical support performance can be kept in the lesion repairing period, and after the repairing of the lesion part is completed, the absorbable metal instrument can be destructed in the circumferential direction as soon as possible, so that the mechanical performance is lost as soon as possible, the constraint on the healed lesion part is relieved as soon as possible, and the healed lesion part is normally developed as soon as possible.
In one embodiment, in the expanded state, the absorbable metal device 100 has an outer diameter of 5 to 18 mm and a wall thickness of 80 to 300 μm, and the corrosion-inhibiting layer 120 and the corrosion-promoting layer 130 are disposed as described above, so that the absorbable metal device 100 with an insufficient corrosion rate can be applied to patients in a growth period, such as infants and children, and after the repair is completed, the absorbable metal device 100 can be circumferentially deconstructed in the through hole 1113 area as soon as possible to release the constraint on the tissue as soon as possible, thereby avoiding affecting the growth and development of the tissue.
It should be noted that the thickness range of the portion of the etching stop layer 120 located in the through hole 1113 is 0.2 to 2 micrometers, and the thickness range of the other portion of the etching stop layer 120 is 0.5 to 5 micrometers, which means that the thickness of the portion located in the through hole 1113 may be any value within the range of 0.2 to 2 micrometers, for example, V1, and the thickness of the other portion may be any value within the range of 0.5 to 5 micrometers, for example, V2, but it is still required to ensure that V1 is smaller than V2. The thickness of the portion of the corrosion-promoting layer 130 located in the through hole 1113 ranges from 6 to 50 micrometers, and the thickness of the other portion of the corrosion-promoting layer 130 ranges from 3 to 30 micrometers.
It should be noted that, when the thickness of the etching stop layer 120 is not uniform and the thickness of the corrosion-promoting layer 130 is uniform, the difference between the thickness of the portion of the etching stop layer 120 located in the through hole 1113 and the thickness of the other portion of the etching stop layer 120 is in the range of 0.3 to 3 μm. The corrosion-promoting layer 130 has a thickness of 3 to 50 microns. When the thicknesses of the corrosion-promoting layers 130 are not uniform and the thicknesses of the corrosion-retarding layers 120 are uniform, the difference between the thickness of the part of the corrosion-promoting layer 130 located in the through hole 1113 and the thickness of the other part of the corrosion-promoting layer 130 is 3 to 47 micrometers, and the thickness of the corrosion-retarding layer 120 is 0.2 to 5 micrometers. The support rod 111 of the absorbable metal device 100 is provided with a through hole 1113, and the thickness of the corrosion-inhibiting layer 120 in the area provided with the through hole 1113 is smaller than that in the area without the through hole 1113, and the thickness of the corrosion-promoting layer 130 in the area provided with the through hole 1113 is larger than that in the area without the through hole 1113, so as to adjust the corrosion rate of the area provided with the through hole 1113 to be larger than that of the area without the through hole 1113, so that the area provided with the through hole 1113 is preferentially broken, and the device can be rapidly disassembled from the circumferential direction.
The position where the through hole 1113 is formed is not limited to the support rod 111, and in other embodiments, the through hole 1113 may be formed at a position where the fracture is required to be preferentially performed, and the corrosion-inhibiting layer 120 and the corrosion-promoting layer 130 having a thickness difference may be appropriately provided.
The absorbable metal device 100 may be a coronary stent, a peripheral stent, or a cerebrovascular stent.
Absorbable metal instrument 100 may be prepared using methods known to those skilled in the art. For example, a hollow absorbable metal tube is cut to form a substrate, and then through holes 1113 are formed in the substrate to form an absorbable metal substrate 10, and then the substrate is plated by an electrochemical method to form the corrosion-inhibiting layer 120. In the process of preparing the etching stop layer 120, the through hole 1113 may be physically blocked or other methods may be used, so that the thickness of the etching stop layer 120 at the through hole 1113 is smaller than that at other positions. Further, the corrosion-promoting layer 130 is formed by spraying or other methods. In preparing the corrosion-promoting layer 130, the thickness of the corrosion-promoting layer 130 at the through hole 1113 may be made larger than that at a position without the through hole 1113 by increasing the spraying time at the through hole 1113, or the like.
It should be noted that the absorbable metal instrument 100 described above is a lumen instrument. The absorbable metal devices of the present disclosure are not limited to luminal devices, however, and any device requiring localized preferential rupture may be suitable.
The absorbable metal device of the present disclosure is further illustrated by the following specific embodiments by taking the blood vessel stent as an example.
1. The stents of the following specific examples and comparative examples were prepared as follows:
and (3) coating by adopting an electrochemical method to form a corrosion-slowing layer on the support substrate with the through hole, wherein the through hole is physically shielded in the coating process. An ultrasonic spraying method is adopted to form an erosion promoting layer on the erosion retarding layer, and the spraying time is increased at the through hole. The stent of the comparative example was prepared without physical shielding and increased spray time.
2. The test method of the following specific examples is as follows:
1. determination of mass loss rate: before implantation, the mass of the stent is M 0 Taking out the implanted stent from the blood vessel at a preset observation time point, soaking the stent in 1mol/L sodium hydroxide solution to digest tissues and a corrosion-resistant layer, then taking out the stent and fragments thereof from the sodium hydroxide solution, putting the stent and fragments thereof into 3 percent tartaric acid with mass percent concentration for ultrasonic treatment to ensure that corrosion products and polymer layers on the surface of the stent are completely peeled off or dissolved in the 3 percent tartaric acid with mass percent concentration, taking out the rest un-corroded stent matrix or fragments thereof, drying and weighing the stent matrix or fragments with mass M t . The mass loss rate is calculated according to the following formula:
W＝(|M t -M 0 |)*100％/M 0 。
wherein, W is the mass loss rate;
M t -the mass of the remaining stent matrix after corrosion;
M 0 the initial mass of the stent.
2. Method for testing coating thickness:
2.1 fixing the bracket needing to test the thickness of the coating on a sample table, then placing the sample table in JFC-1600 gold spraying equipment to spray gold, rotating 180 degrees after spraying, spraying again, and spraying 80s on each surface to ensure that all positions are sprayed.
2.2 vertically placing the bracket with the gold sprayed on the surface into a position as shown in the specification of 5:1, keeping the bracket in a vertical state in the normal-temperature resin curing agent mixed reagent prepared according to the proportion of 1, and then standing for more than 8 hours to separate from the sample sealing shell.
2.3 polishing the sealed sample by using a semi-automatic polishing machine according to the polishing procedure of the sample, wherein the cross section of the sample to be measured needs to be polished to be free of grinding marks. Fixing the polished sample on an objective table of a scanning electron microscope, and pasting a conductive adhesive near the cross section of the bracket to extend to the edge metal area of the objective table; and placing the whole object stage into JFC-1600 gold spraying equipment for spraying for 20s.
2.4, putting the sample sprayed with gold into a JSM-6510 scanning electron microscope, amplifying the sample to the largest multiple as possible by using 2 grades, and adjusting the sample to the clearest degree to measure the thickness, wherein the section of the whole support rod is ensured to be in the visual field range; any 1 typical support bar per section was taken and each support bar was measured at 1 coating thickness point per side. The number of cross sections to be tested can be determined according to the situation, and 6 cross sections (typical 6 cross sections: 6 cross sections of through holes and non-through holes at the far end, the near end and the middle section of the stent) are recommended to be selected and tested for each stent.
3. Endothelialization rate test:
implanting the stent into the left pulmonary artery branch, taking out the blood vessel where the stent is located after a certain time, soaking the blood vessel with glutaraldehyde (such as 6 h), drying, then cutting the blood vessel along the axial direction, spraying gold, and observing the endothelial coverage rate of the stent by SEM measurement, wherein the condition that the endothelial coverage rate reaches 98% or more is regarded as complete endothelialization.
4. The method for testing the hollow-out rate and the through hole parameters of the support rod comprises the following steps:
the distance between the edge of the through hole and the edge of the supporting rod is obtained by measuring under a three-dimensional measuring microscope with the precision reaching 0.001 mm;
the hollow-out rate of the supporting rod is as follows: (S1/S2) × 100%
S1: the total surface area of the through holes is measured by CAD software;
s2: the surface area of the support rod is measured by CAD software.
Example 1
A support is characterized in that a base material is an iron-based alloy with carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are axially arranged, and each support rod of the waveform annular structures is provided with a plurality of through holes. The through holes are distributed in a row at intervals along the length direction of the supporting rod. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The distance between two adjacent through holes on each support rod is 20 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 57%. The shape of the through hole is triangle-like. The shortest distance between the edge of the through-hole and the edge of the support bar was 25 μm. The hollow-out rate of each supporting rod is 20%. In the nominal expanded state, the surface coverage of the stent was 9%, the wall thickness of the matrix was 110 μm, the volume of the stent per unit vessel area was 9.9 μm, and the material of the erosion reduction layer was pure zinc. The thickness of the portion of the resist layer covering the through-hole was 1 μm, and the thickness of the other portion of the resist layer was 2.5 μm. The material of the corrosion-promoting layer is polylactic acid, the thickness of the part of the corrosion-promoting layer covering the through hole is 25 μm, and the thickness of the other part of the corrosion-promoting layer is 20 μm.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, completely endothelializing the samples of 1 month, and basically realizing circumferential deconstruction when most of the stents are corroded and broken at through holes of supporting rods at 9 months, wherein the weight loss reaches 48.36%.
Example 2
A support is characterized in that a base material is an iron-based alloy with the carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are arranged along the axial direction, and each support rod of the waveform annular structures is provided with a plurality of through holes. The through holes are distributed in a row at intervals along the length direction of the supporting rod. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The shortest distance between two adjacent through holes on each support rod is 25 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 47%. The shape of the through hole is circular. The distance between the edge of the through-hole and the edge of the support bar was 35 μm. The hollow-out rate of each supporting rod is 20%. In the nominal expanded state, the surface coverage of the stent was 9%, the wall thickness of the base was 110 μm, the volume of the stent per unit area of the vessel was 9.9 μm, and the material of the erosion resistant layer was pure zinc. The thickness of the portion of the resist layer covering the through-hole was 1 μm, and the thickness of the other portion of the resist layer was 2.5 μm. The material of the corrosion-promoting layer is polylactic acid, the thickness of the part of the corrosion-promoting layer covering the through hole is 25 μm, and the thickness of the other part of the corrosion-promoting layer is 20 μm.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, completely endothelializing the samples of 1 month, and basically realizing circumferential deconstruction when most of the stents are corroded and broken at through holes of supporting rods at 9 months, wherein the weight loss reaches 49.56%.
Example 3
A support is characterized in that a base material is an iron-based alloy with carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are axially arranged, and a plurality of through holes are respectively formed in half of support rods of the waveform annular structures. The through holes are distributed in a row at intervals along the length direction of the supporting rod. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The shortest distance between two adjacent through holes on each support rod is 30 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 52%. The shape of the through hole is circular. The distance between the edge of the through-hole and the edge of the support bar was 100 μm. The hollow-out rate of each supporting rod is 10%. In the nominal expanded state, the surface coverage of the stent was 10.5%, the wall thickness of the matrix was 110 μm, the volume of the stent per unit area of the vessel was 11.55 μm, and the material of the erosion resistant layer was pure zinc. The thickness of the portion of the resist layer covering the through-hole was 1 μm, and the thickness of the other portion of the resist layer was 2.5 μm. The material of the corrosion-promoting layer is polylactic acid, the thickness of the part of the corrosion-promoting layer covering the through hole is 25 mu m, and the thickness of the other part of the corrosion-promoting layer is 20 mu m.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, completely endothelializing the samples of 1 month, and basically realizing circumferential deconstruction when most of the stents are corroded and broken at through holes and connecting pieces of the supporting rods at 9 months, wherein the weight loss reaches 35.27%.
Example 4
A support is characterized in that a base material is an iron-based alloy with carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are axially arranged, and a support rod of each waveform annular structure is respectively provided with a plurality of through holes. The through holes are distributed in a row at intervals along the length direction of the supporting rod. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The distance between two adjacent through holes on each support rod is 30 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 52%. The shape of the through hole is circular. The shortest distance between the edge of the through-hole and the edge of the support bar was 25 μm. The hollow-out rate of each supporting rod is 20%. In the nominal expanded state, the surface coverage of the stent is 12%, the wall thickness of the matrix is 300 μm, the volume of the stent per unit area of the vessel is 36 μm, and the material of the erosion reduction layer is pure zinc. The thickness of the portion of the resist layer covering the through-hole was 2 μm, and the thickness of the other portion of the resist layer was 5 μm. The material of the corrosion-promoting layer is polylactic acid, the thickness of the part of the corrosion-promoting layer covering the through hole is 6 μm, and the thickness of the other part of the corrosion-promoting layer is 3 μm.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, wherein complete endothelialization does not exist in 1 month, most of corrosion fractures of the stents occur at through holes and connecting pieces of the supporting rods in 9 months, circumferential deconstruction is basically realized, and weight loss reaches 18.95%.
Example 5
A support is characterized in that a base material is an iron-based alloy with carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are axially arranged, and each support rod of the waveform annular structures is provided with a plurality of through holes. The through holes are distributed in a row at intervals along the length direction of the supporting rod. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The shortest distance between two adjacent through holes on each support rod is 20 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 57%. The shape of the through hole is triangle-like. The distance between the edge of the through-hole and the edge of the support bar was 25 μm. The hollow-out rate of each supporting rod is 7%. In the nominal expanded state, the surface coverage of the stent was 11%, the wall thickness of the matrix was 91 μm, the volume of the stent per unit area of the vessel was 10 μm, and the material of the erosion control layer was pure zinc. The thickness of the portion of the resist layer covering the through-hole was 1 μm, and the thickness of the other portion of the resist layer was 2.5 μm. The material of the corrosion-promoting layer is polylactic acid, the thickness of the part of the corrosion-promoting layer covering the through hole is 25 μm, and the thickness of the other part of the corrosion-promoting layer is 20 μm.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, completely endothelializing the samples of 1 month, and basically realizing circumferential deconstruction when most of the stents are corroded and broken at through holes of supporting rods at 9 months, wherein the weight loss reaches 47.28%.
Example 6
A support is characterized in that a base material is an iron-based alloy with carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are axially arranged, and each support rod of the waveform annular structures is provided with a plurality of through holes. The through holes are distributed in a row at intervals along the length direction of the supporting rod. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The shortest distance between two adjacent through holes on each support rod is 20 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 57%. The shape of the through hole is triangle-like. The distance between the edge of the through-hole and the edge of the support bar was 25 μm. The hollow-out rate of each supporting rod is 35%. In the nominal expanded state, the surface coverage of the stent was 8%, the wall thickness of the matrix was 80 μm, the volume of the stent per unit vessel area was 6.4 μm, and the material of the erosion reduction layer was pure zinc. The thickness of the portion of the resist layer covering the through-hole was 0.2 μm, and the thickness of the other portion of the resist layer was 0.5 μm. The material of the corrosion-promoting layer is polylactic acid, the thickness of the part of the corrosion-promoting layer covering the through hole is 50 mu m, and the thickness of the other part of the corrosion-promoting layer is 3 mu m.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, completely endothelializing the samples of 1 month, and basically realizing circumferential deconstruction when most of the stents are corroded and broken at through holes of supporting rods at 9 months, wherein the weight loss reaches 64.75%.
Example 7
A support is characterized in that a base material is an iron-based alloy with carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are axially arranged, and each support rod of the waveform annular structures is provided with a plurality of through holes. A plurality of through-holes are just in a row distribution along the length direction interval of bracing piece. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The shortest distance between two adjacent through holes on each support rod is 20 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 57%. The shape of the through hole is triangle-like. The distance between the edge of the through-hole and the edge of the support bar was 25 μm. The hollow-out rate of each supporting rod is 7%. In the nominal expanded state, the surface coverage of the stent was 11%, the wall thickness of the matrix was 91 μm, the volume of the stent per unit area of the vessel was 10 μm, and the material of the erosion reduction layer was pure zinc. The thickness of the portion of the resist layer covering the through-hole was 1 μm, and the thickness of the other portion of the resist layer was 2.5 μm. The corrosion-promoting layer is made of polylactic acid and has a thickness of 20 μm.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, completely endothelializing the samples of 1 month, and basically realizing circumferential deconstruction when most of the stents are corroded and broken at through holes of supporting rods at 9 months, wherein the weight loss reaches 45.36%.
Example 8
A support is characterized in that a base material is an iron-based alloy with carbon content not higher than 2.11wt.%, the base comprises a plurality of waveform annular structures which are axially arranged, and each support rod of the waveform annular structures is provided with a plurality of through holes. The through holes are distributed in a row at intervals along the length direction of the supporting rod. And the through holes on the support rods which are opposite in the axial direction and have different wavy annular structures are respectively connected into a plurality of straight lines in the axial direction. The shortest distance between two adjacent through holes on each support rod is 20 micrometers. The percentage of the aperture of any one through hole in the width direction of the support bar to the width of the support bar was 57%. The shape of the through hole is triangle-like. The distance between the edge of the through-hole and the edge of the support bar was 25 μm. The hollow-out rate of each supporting rod is 7%. In the nominal expanded state, the surface coverage of the stent was 11%, the wall thickness of the matrix was 91 μm, the volume of the stent per unit area of the vessel was 10 μm, and the material of the erosion control layer was pure zinc. The material of the corrosion-resistant layer is pure zinc, and the thickness of the corrosion-resistant layer is 2.5 mu m. The material of the corrosion-promoting layer is polylactic acid, the thickness of the part of the corrosion-promoting layer covering the through hole is 25 μm, and the thickness of the other part of the corrosion-promoting layer is 20 μm.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, completely endothelializing the samples of 1 month, and basically realizing circumferential deconstruction when most of the stents are corroded and broken at through holes of supporting rods at 9 months, wherein the weight loss reaches 45.63%.
Comparative example 1
A stent is characterized in that a matrix material is an iron-based alloy with carbon content not higher than 2.11wt.%, the matrix comprises a plurality of wave-shaped annular structures which are arranged along the axial direction, and all supporting rods of the wave-shaped annular structures are not provided with through holes. In the nominal expanded state, the surface coverage of the stent was 15%, the wall thickness of the matrix was 85 μm, and the volume of the stent per blood vessel area was 12.75 μm. The material of the corrosion-resistant layer is pure zinc, and the thickness of the corrosion-resistant layer is 2.5 mu m. The corrosion-promoting layer is made of polylactic acid, and the thickness of the corrosion-promoting layer is 25 mu m.
Respectively implanting a plurality of the batches of the stents into left pulmonary artery branches of a plurality of pigs, respectively sampling and analyzing 1 month and 9 months after implantation, taking SEM pictures of samples of 1 month, taking CT pictures of samples of 9 months, wherein complete endothelialization does not occur in 1 month, most corrosion fractures of the stents occur at the connecting pieces in 9 months, circumferential deconstruction is not realized, and the weight loss reaches 28.18%.
All possible combinations of the technical features of the above embodiments may not be described for the sake of brevity, but should be considered as within the scope of the present disclosure as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is specific and detailed, but not to be understood as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (9)

1. An absorbable metal device comprises an absorbable metal substrate and is characterized by further comprising a corrosion inhibiting layer arranged on the absorbable metal substrate and an erosion promoting layer covering the corrosion inhibiting layer, wherein a plurality of through holes are formed in a partial area of the absorbable metal substrate, and the thickness of the part, located in the through holes, of the corrosion inhibiting layer is smaller than that of the other part of the corrosion inhibiting layer; and/or the thickness of the corrosion-promoting layer at the parts of the through holes is larger than that of other parts of the corrosion-promoting layer;
the absorbable metal substrate comprises a plurality of wave-shaped annular structures which are arranged along the axial direction, each wave-shaped annular structure comprises a plurality of supporting rods and a plurality of connecting rods, two ends of each supporting rod are respectively connected with two adjacent connecting rods to form the wave-shaped annular structure, and at least one of the supporting rods of the wave-shaped annular structure is provided with a plurality of through holes.
2. The absorbable metal device of claim 1, wherein a plurality of the through holes are formed in only one support rod of each wavy annular structure, such that when the plurality of wavy annular structures are disassembled from the positions where the through holes are formed, the absorbable metal device has a diamond or rectangular unfolding outline;
or, a plurality of through holes are formed on a plurality of supporting rods on each wave-shaped annular structure, and the distribution rules of the through holes on each supporting rod are the same, so that when the wave-shaped annular structures are deconstructed from the positions provided with the through holes, the unfolding outline of the absorbable metal instrument is in a plurality of rhombuses or a plurality of rectangles.
3. The absorbable metal device of claim 1, wherein the openness of each of the support rods having the through holes defined therein is in the range of 7% to 35%.
4. The absorbable metal device of claim 1, wherein the distance between the edge of the through-hole and the edge of the strut at which the through-hole is located is between 25 microns and 100 microns.
5. The absorbable metal device of claim 1, wherein when the distribution of the plurality of through holes on each support rod is the same, such that when the plurality of wavy annular structures are deconstructed from the positions where the through holes are opened, the unfolding profile of the absorbable metal device is in one or more rhombuses or in one or more rectangles, the distance between any two adjacent through holes is greater than or equal to 20 microns, and the percentage of the aperture of any one through hole in the width direction of the support rod to the width of the support rod is less than or equal to 57%;
or the through holes on each supporting rod are distributed in multiple rows along the length direction of the supporting rod, the distance between any two adjacent through holes is greater than or equal to 20 micrometers, and the percentage of the sum of the apertures of the through holes along the width direction of the supporting rod and the width of the supporting rod is less than or equal to 57%.
6. The absorbable metal of claim 1, wherein the absorbable metal matrix has a volume per luminal tissue area of 6.4 to 36 μm and a coverage of 8 to 12% in the nominal expanded state.
7. The absorbable metal device of claim 1, wherein the thickness of the portion of the corrosion-inhibiting layer through the through-hole differs from the thickness of the other portions of the corrosion-inhibiting layer by a value in the range of 0.3 to 3 μm, and the thickness of the portion of the corrosion-promoting layer through the through-hole differs from the thickness of the other portions of the corrosion-promoting layer by a value in the range of 3 to 47 μm.
8. The absorbable metal device of claim 1, wherein the thickness of the through-hole portion of the corrosion-inhibiting layer is in the range of 0.2-2 μm, and the thickness of the other portion of the corrosion-inhibiting layer is in the range of 0.5-5 μm; the thickness range of the corrosion-promoting layer positioned at the through hole part is 6-50 mu m, and the thickness range of other parts of the corrosion-promoting layer is 3-30 mu m.
9. The absorbable metal device of claim 1, wherein the absorbable metal matrix material is an iron-based material, the corrosion-inhibiting layer material is pure zinc or a zinc alloy, and the corrosion-promoting layer material is polyester.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1857742A (en) * 2005-04-30 2006-11-08 中国科学院金属研究所 Biomedicine implant material with controllable degrading rate and its application
CN104415403A (en) * 2013-08-20 2015-03-18 苏州纳晶医药技术有限公司 Controllably-degradable magnesium-based metal material
CN108525022A (en) * 2018-04-15 2018-09-14 烟台浩忆生物科技有限公司 A kind of slewing biodegradation hemostatic clamp and preparation method thereof
CN109966562A (en) * 2017-12-27 2019-07-05 先健科技(深圳)有限公司 Absorbable metal bracket

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040249443A1 (en) * 2001-08-20 2004-12-09 Shanley John F. Expandable medical device for treating cardiac arrhythmias
EP1834606B1 (en) * 2006-03-16 2013-04-24 CID S.p.A. Stents
US20100292776A1 (en) * 2009-05-14 2010-11-18 Boston Scientific Scimed, Inc. Bioerodible Endoprosthesis
CN102525701B (en) * 2010-12-21 2015-06-17 先健科技(深圳)有限公司 Absorbable blood vessel stent
DE102013004625A1 (en) * 2013-03-16 2014-09-18 Universitätsklinikum Freiburg Bioresorbable stent
CN106581778B (en) * 2015-10-14 2020-07-21 先健科技(深圳)有限公司 Absorbable iron-based alloy implanted medical instrument and preparation method thereof
CN106924822B (en) * 2015-12-31 2020-02-28 先健科技(深圳)有限公司 Absorbable iron-based alloy internal fixation implantation medical instrument
CN109954171A (en) * 2017-12-26 2019-07-02 先健科技(深圳)有限公司 Absorbable implantable device
CN110075369B (en) * 2019-04-11 2020-11-06 复旦大学 Metal-polymer composite stent capable of regulating degradation rate by multilayer design and preparation method and application thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1857742A (en) * 2005-04-30 2006-11-08 中国科学院金属研究所 Biomedicine implant material with controllable degrading rate and its application
CN104415403A (en) * 2013-08-20 2015-03-18 苏州纳晶医药技术有限公司 Controllably-degradable magnesium-based metal material
CN109966562A (en) * 2017-12-27 2019-07-05 先健科技(深圳)有限公司 Absorbable metal bracket
CN108525022A (en) * 2018-04-15 2018-09-14 烟台浩忆生物科技有限公司 A kind of slewing biodegradation hemostatic clamp and preparation method thereof

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