CN112022234B

CN112022234B - Implantable device and preparation method thereof

Info

Publication number: CN112022234B
Application number: CN201910413514.2A
Authority: CN
Inventors: 陈贤淼; 刘琮; 李博宁
Original assignee: Lifetech Scientific Shenzhen Co Ltd
Current assignee: Lifetech Scientific Shenzhen Co Ltd
Priority date: 2019-05-17
Filing date: 2019-05-17
Publication date: 2022-05-20
Anticipated expiration: 2039-05-17
Also published as: CN112022234A; WO2020233523A1

Abstract

The invention relates to an implantable device and a preparation method thereof. The implantable device comprises a frame, the frame comprises a plurality of silk threads, the silk threads are staggered to form a plurality of network nodes, the implantable device further comprises a plurality of markers, the markers are arranged on at least part of the network nodes, each marker corresponds to each network node, and each marker comprises a material which can be seen under the medical imaging device. The implantable device has better visibility under the medical imaging equipment.

Description

Implantable device and preparation method thereof

Technical Field

The invention relates to the field of medical instruments, in particular to an implantable instrument and a preparation method thereof.

Background

Minimally invasive treatment methods, in which an implantable device is implanted into the human body via a catheter, are currently becoming more and more important. For example, implantation of vascular stents for the treatment of vascular stenosis, aneurysms, etc.; implanting the occluder to treat Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD), Patent Ductus Arteriosus (PDA) and Patent Foramen Ovale (PFO) congenital heart disease, etc.

At present, implantable devices such as blood vessel stents, occluders and the like are mostly made of metal wires or polymer wires. During use, a doctor usually determines the shape and position of the implantable device by means of a medical imaging device such as Digital Subtraction Angiography (DSA). DSA makes use of the difference in radiopacity of the implantable device and tissue under X-rays to render the implantable device visible. The visibility under X-ray is related to the material composing the implanted device, and generally, the material with high atomic coefficient, large density and large size has better radiopacity under X-ray, for example, common nickel-titanium alloy, stainless steel and the like have good visibility because of better radiopacity under X-ray. However, the polymer material is generally composed of C, H, O, which has a low density, resulting in poor visibility of the device made of the polymer material under X-ray.

Disclosure of Invention

In view of the above, there is a need for an implantable device with better visibility under medical imaging equipment.

An implantable device comprising a frame comprising a plurality of wires that are interlaced to form a plurality of network nodes, a plurality of markers disposed on at least a portion of the plurality of network nodes, and a plurality of markers and at least a portion of the plurality of network nodes, each marker corresponding to each network node, each marker comprising a material that is visible under a medical imaging device.

At least part of the plurality of network nodes of the implantable device are provided with a plurality of markers, and each marker comprises a material visible under the medical imaging equipment, so that the implantable device has better visibility under the medical imaging equipment.

Drawings

FIG. 1 is a schematic structural view of an embodiment of an occluding device;

FIG. 2 is a schematic view of the braiding of the occluding device shown in FIG. 1;

figure 3 is a top view of the occluding device shown in figure 1;

FIG. 4 is a schematic structural diagram of a tag according to one embodiment;

FIG. 5 is a schematic structural view of another embodiment of a tag;

FIG. 6 is a schematic view of the distribution of the markers according to an embodiment;

FIG. 7 is a schematic view of the distribution of a marker according to another embodiment;

FIG. 8 is an enlarged view of a portion of FIG. 7;

FIG. 9 is a schematic view of a structure of one embodiment of a stent;

fig. 10 is an image of the occluder of embodiment 1 under a DSA device.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with 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.

To more clearly describe the structure of the present invention, the terms "distal" and "proximal" are used as terms of orientation that are conventional in the field of interventional medical devices, wherein "distal" refers to the end that is distal from the operator during the procedure and "proximal" refers to the end that is proximal to the operator during the procedure.

An implantable device with better visibility under medical imaging equipment is provided, so that an operator can judge the shape and the position of the implantable device in an interventional operation. The medical imaging device may be an X-ray imaging device, a fluorescence imaging device, or other medical imaging device that can be used to determine the location of the implantable device within the body and identify the morphology of the implantable device. The implantable device will be described below by taking the occluding device as an example.

Referring to fig. 1, one embodiment of an occluding device 100 includes a frame 20. The frame 20 has a mesh structure woven from a plurality of threads. The material of the wire may be a metal that is not corrodible in the living body, and the wire may be a nitinol wire, a cobalt-chromium alloy wire, a stainless steel wire, or the like, for example. Alternatively, the thread may be made of a biodegradable material. For example, the biodegradable material may be poly (racemic lactic acid) (PDLLA), poly (D-lactic acid) (PDLA), poly (L-lactic acid) (PLLA), poly (glycolic acid) (PGA), poly (lactic-co-glycolic acid) (PLGA), poly (hydroxy fatty acid ester) (PHA), Polydioxanone (PDO), or Polycaprolactone (PCL), etc. In the present embodiment, the frame 20 includes a first plugging unit 22, a second plugging unit 24, and a waist portion 26. The two ends of the waist 26 are respectively connected with the first plugging unit 22 and the second plugging unit 24 to form a two-disc and one-waist structure with two large ends and a small middle. The first plugging unit 22, the second plugging unit 24 and the waist portion 26 are of an integral structure.

It is understood that in other embodiments, the structure of the frame 20 is not limited to a two-pan, one-waist structure with large ends and small middle. For example, the number of the plugging units in the frame 20 is one, and in this case, the plugging units are connected to the waist to form a plugging frame having a substantially T-shaped cross section.

The frame 20 is woven from a plurality of wires. For example, the frame 20 is formed by knitting two or more sets of yarns with different directions and then shaping the yarns. Referring to fig. 2, taking two sets of filaments as an example, the frame 20 is formed by weaving a set of longitude filaments 210 and a set of latitude filaments 220 in an up-and-down staggered manner. The locations where longwire 210 and latitudinal wire 220 intersect form a plurality of network nodes 230.

Referring to fig. 2 and 3, the occluding device 100 further comprises a plurality of markers 40, the plurality of markers 40 are disposed on at least a portion of the plurality of network nodes 230 of the frame 20, and each marker 40 corresponds to each network node 230. I.e., all of the network nodes 230 of the frame 20, one marker 40 is disposed on each network node 230. Alternatively, one marker 40 may be provided on each network node 230 of a portion of the network nodes 230 of the frame 20.

Each marker 40 comprises a material that is visible under the medical imaging device so that the occluder 100 is better visible under the medical imaging device so that the operator can accurately determine the shape and position of the occluder 100 during an interventional procedure.

In one embodiment, the material visible under the medical imaging device is a radiopaque material, such that each marker 40 is visible under the X-ray medical imaging device.

In one embodiment, the radiopaque material of the markers 40 is a radiopaque material with adhesive properties such that each marker 40 can be reliably secured to the frame 20 by virtue of the radiopaque material. In one embodiment, the radiopaque material having adhesive properties is an iodine-containing polymeric material, for example, the radiopaque material is selected from at least one of iodinated polylactic acid, iodinated polycarbonate, iodinated cellulose, iodinated methacrylate, iodinated polyurethane, and iodinated poly-epsilon-caprolactone.

The radiopaque material with the adhesive property is selected, so that the marker 40 can be visible under the X-ray medical imaging equipment on one hand; on the other hand, the marker 40 can be reliably arranged on the frame 20; yet another aspect enables marker 40 to secure longitude and

latitude wires

210 and 220 at network node 230 to form a fixed network node, thereby improving the stability of frame 20.

In one embodiment, the radiopaque material of the marker 40 is a radiopaque material that does not have adhesive properties. In this embodiment, the marker 40 further comprises an adhesive. In one embodiment, the radiopaque material without blocking properties is selected from at least one of a metal, an inorganic salt, and an organic material. Wherein the metal is at least one selected from gold, platinum, tungsten, iridium, osmium, rhenium, rhodium and tantalum. The inorganic salt is at least one selected from barium sulfate, sodium iodide and bismuth subcarbonate. The organic material is at least one selected from iopamidol, ioversol, diatrizoate and iopromide. The material of the adhesion agent is at least one selected from polyethylene terephthalate, polypropylene, polyethylene, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polyhydroxyalkanoate, polydioxanone and polycaprolactone. Wherein the polylactic acid is poly-L-lactic acid, poly-D-lactic acid or poly-D-lactic acid.

The adhesive facilitates, on the one hand, the reliable positioning of the tag 40 on the frame 20 and, on the other hand, enables the tag 40 to fix the latitudinal 210 and longitudinal 220 threads at the network node 230 to form a fixed network node, thereby improving the stability of the frame 20.

Referring to fig. 4, in one embodiment, the tag 40 is a single layer structure with the radiopaque material dispersed in the adhesive (the radiopaque material is represented by the small dots at 40 in fig. 4). In the marker 40, the higher the content of the radiopaque material, the better the visual effect of the marker 40 under the X-ray medical imaging apparatus. However, the higher the content of the radio-opaque material, the lower the content of the adhesive, so that the bonding force of the marker 40 to the longitude and

latitude wires

210 and 220 at the network node 230 is reduced and the detachment is liable to occur. Therefore, in one embodiment, the mass ratio of the adhesive to the radiopaque material is 0.1-2: 1 for each marker 40. The higher the mass of the radiopaque material, the better the visibility of the marker 40 under the radiographic imaging device, but too high a mass of the radiopaque material may result in an excessively large volume of the marker 40, which may affect the delivery performance of the occluding device 100. Thus, in one embodiment, the radiopaque material is present in an amount of 0.01 to 2 milligrams per marker 40 for both visibility and volume. In one embodiment, the mass ratio of the adhesive to the radiopaque material is 0.125-2: 1, and the mass of the radiopaque material is 0.1-2 mg.

Referring to FIG. 5, in another embodiment, the tag 40 is a multi-layer structure including an innermost layer 42, an outermost layer 44, and at least one intermediate layer 46 positioned between the innermost layer 42 and the outermost layer 44. Wherein the innermost layer 42 and the outermost layer 44 are both made of adhesive, and at least one intermediate layer 46 is made of radio-opaque material or a mixture of radio-opaque material and adhesive. When the material of at least one intermediate layer 46 is a radiopaque material, the material is a radiopaque material with adhesive properties or a radiopaque material without adhesive properties. The innermost layer 42 and the outermost layer 44 may be the same material or different materials. When the material of at least one intermediate layer 46 is a mixture of a radiopaque material and an adhesive, the adhesive in the intermediate layer 46 may be the same material as or different from the innermost layer 42 and the outermost layer 44. When the number of intermediate layers 46 is greater than 1, the materials of the different intermediate layers 46 may be the same or different.

In one embodiment, the intermediate layer 46 is a radiopaque material with adhesive properties or a mixture of any of the radiopaque materials (including radiopaque materials with adhesive properties and radiopaque materials without adhesive properties) and an adhesive, such that the adhesive properties between the intermediate layer 46 and the innermost and

outermost layers

42, 46 are better to avoid delamination of the marker 40 which can lead to agglomeration of the radiopaque material.

When the number of layers of the marker 40 is too large, the volume of the marker 40 is too large, and the compressed volume of the occluding device 100 is too large, so that it is difficult to load the occluding device 100 in a delivery sheath for delivery. To ensure visibility of the marker 40 and reliable connection of the marker 40 to the latitudinal 210 and longitudinal 220 wires at the network node 230 while integrating the compressed volume of the occluding device 100, in one embodiment, the marker 40 is a multi-layered structure comprising 3-7 layers. In one embodiment, the mass ratio of the adhesive to the radio-opaque material in each of the markers 40 of the multi-layered structure is 0.1-2: 1, and the mass of the radio-opaque material is 0.01-2 mg. In one embodiment, the mass ratio of the adhesive to the radiopaque material is 0.125-2: 1, and the mass of the radiopaque material is 0.1-2 mg.

Referring to fig. 1 again, the first plugging unit 22 is a mesh disk structure. The first plugging unit 22 comprises a first distal plugging disc 222, a first proximal plugging disc 224 and a first ridge 226 connecting the first distal plugging disc 222 and the first proximal plugging disc 224. The second plugging unit 24 is also of a mesh disk structure. The second plugging unit 24 comprises a second distal plugging disc 242, a second proximal plugging disc 244 and a second ridge 246 connecting the second distal plugging disc 242 and the second proximal plugging disc 244.

In one embodiment, all of the markers 40 of the occluding device 100 are disposed on the first occluding unit 22. In one embodiment, all of the markers 40 of the occluding device 100 are disposed on the first distal occluding disk 222 of the first occluding unit 22. Referring to fig. 6, in one embodiment, the number of markers 40 disposed on the first distal blocking disk 222 is 2, two markers 40 are disposed at two ends of the first distal blocking disk 222, and a connection line of the two markers 40 passes through a geometric center of the first distal blocking disk 222. And the distance from the edge of each marker 40 to the edge of the first distal containment disc 222 is 0 to 2 millimeters. That is, when the first distal occluding disk 222 has a width of D1 and the length of the line connecting the edges of the two markers 40 and passing through the geometric centers of the two markers 40 is D2, D1 is greater than or equal to D2 and the difference between D1 and D2 is 0 to 4 mm. Wherein the width D1 of the first distal occluding disk 222 is the length of a line passing through the geometric center of the first distal occluding disk 222 and extending from both ends to the edge of the first distal occluding disk 222, the line being parallel to a line connecting the edges of the two markers 40 and passing through the geometric centers of the two markers 40. For example, in one embodiment, when the first distal occluding disk 222 is circular, D1 refers to the diameter of the first distal occluding disk 222, and two markers 40 are disposed on either end of a diameter of the first distal occluding disk 222; when the first distal occluding disk 222 is an oval shape, D1 refers to the length of the major axis or the length of the minor axis of the oval shape, and the two markers 40 are disposed at both ends of the major axis or the minor axis of the first distal occluding disk 222.

In one embodiment, when the number of markers 40 provided on the first distal occluding disk 222 is 3, two of the markers 40 are provided in the above-described arrangement. Another marker 40 may be placed anywhere else on the first distal occluding disk 222.

In one embodiment, the number of markers 40 is 3, and 3 markers 40 are uniformly disposed on the first distal blocking disk 222, i.e., the included angle between any two adjacent markers 40 is 120 degrees. The angle is defined as the angle between the marker 30 and a line defined by the geometric center of the first distal occluding disk 222.

In one embodiment, the number of markers 40 is 3, 2 markers 40 are disposed on the first distal occluding disk 222 and another marker 30 is disposed on the first proximal occluding disk 224 in the manner described above and defines a plane perpendicular to the longitudinal central axis I-I of the occluding device 100, and the angle between any two adjacent markers 40 in the projection of the 3 markers 40 on the first distal occluding disk 222 and the first proximal occluding disk 224 onto the plane is 120 degrees. The angle is defined as the angle between the projection of the marker 30 and a line defined by the geometric center of the projection of the first distal occluding disk 222 or the first proximal occluding disk 224 (which are coincident).

In one embodiment, when the number of markers 40 disposed on the first distal occluding disk 222 is greater than or equal to 4, the circumscribed figure of the plurality of markers 40 on the first distal occluding disk 222 is the same as the shape of the first distal occluding disk 222, and the geometric center of the circumscribed figure of the plurality of markers 40 coincides with the geometric center of the first distal occluding disk 222.

In one embodiment, the circumscribed pattern of the plurality of markers 40 on the first distal containment disc 222 is spaced from 0 to 2mm from the edge of the first distal containment disc 222.

For example, referring to fig. 7, when the first distal blocking disk 222 is a circle, the distribution locus of the plurality of markers 40 on the first distal blocking disk 222, i.e. the circumscribed figure of the plurality of markers 40, is a circle, and the center of the distribution locus of the plurality of markers 40 on the first distal blocking disk 22 coincides with the center of the first distal blocking disk 222. Referring to fig. 8, the distance between the circumscribed circle R of the plurality of markers 40 and the edge of the first distal blocking disk 222 is L, and the size of L is in the range of 0 to 2 mm.

It is understood that the shape of the first distal occluding disk 222 is not limited to circular and may be other shapes, such as oval, square, etc., and accordingly, the circumscribed figure of the plurality of markers 40 on the first distal occluding disk 222 is the same as the shape of the first distal occluding disk 222 and may be oval, square, etc.

In another embodiment, all of the markers 40 of the occluding device 100 are disposed on the first proximal occluding disk 224 of the first occluding unit 22. The plurality of markers 40 are disposed on the first proximal occluding disk 224 in the same manner as described above for the first distal occluding disk 222 and will not be described in detail herein.

In the implantation process, the first plugging unit 22 of the plugging device 100 is released first, and after it is confirmed that the first plugging unit 22 is accurately positioned, that is, after it is confirmed that the first plugging unit 22 adheres to the wall of the defect site, the second plugging unit 24 is released, so that the first plugging unit 22 and the second plugging unit 24 adhere to the wall of the defect site well, and a good plugging effect is obtained. The plurality of markers 40 are arranged in the above manner, and after implantation, the overall profile of the first plugging unit 22 can be judged by means of medical imaging equipment, and it is confirmed that the first plugging unit 22 has a good shape, and after the first plugging unit 22 adheres to the wall of the defect, the second plugging unit 24 is released, thereby facilitating accurate positioning of the plugging device 100.

Since the edges of the first distal occluding disk 222 and the first proximal occluding disk 224 of the first occluding unit 22 are overlapped after implantation, for example, as shown in fig. 6, the markers 40 at points a and d are overlapped to form a point indicating one extreme position of the first occluding unit 22, and the markers 40 at points b and c are overlapped to form a point indicating the other extreme position of the first occluding unit 22. Thus, the provision of a plurality of markers 40 on one of the first distal occluding disk 222 and the first proximal occluding disk 224 ensures the visibility of the first occluding unit 22 under the medical imaging device.

In a more specific embodiment, the circumscribed pattern of the plurality of markers 40 on the first distal occluding disk 222 is spaced 0 to 2mm from the edge of the first distal occluding disk 222. That is, the edges of the plurality of markers 40 located on the first distal occluding disk 222 that are distal from the geometric center of the first distal occluding disk 222 are all aligned with the edge of the first distal occluding disk 222. Alternatively, the plurality of markers 40 located on the first distal containment disc 222 are each closer to the geometric center of the first distal containment disc 222 than the edge of the first distal containment disc 222, and the edge of each marker 40 distal to the geometric center of the first distal containment disc 222 is less than or equal to 2 millimeters from the edge of the first distal containment disc 222. Or, the distance from the external connection pattern of the plurality of markers 40 on the second distal end plugging disc 242 to the edge of the second distal end plugging disc 242 is 0 to 2mm, and the meaning of 0 to 2mm is the same as that of the above, and is not described again.

During the implantation process, when the first plugging unit 22 is released and gradually approaches and adheres to the defect site, the edge of the first plugging unit 22 first contacts with the defect site. Therefore, identifying the extreme positions of the first occluding unit 22 facilitates accurate positioning of the occluding device 100. The distance from the circumscribed figure of the plurality of markers 40 on the first distal occluding disk 222 to the edge of the first distal occluding disk 222 is 0-2 mm or the distance from the circumscribed figure of the plurality of markers 40 on the second distal occluding disk 242 to the edge of the second distal occluding disk 242 is 0-2 mm, which is beneficial to identifying the limit position of the first occluding unit 22, thereby being beneficial to accurately positioning the occluding device 100.

In a more specific embodiment, whether the plurality of markers 40 are distributed on the first distal containment disc 222 or the plurality of markers 40 are distributed on the first proximal containment disc 224, or a portion of the markers 40 are disposed on the first distal containment disc 222 and another portion of the markers 40 are disposed on the first proximal containment disc 224, the plurality of markers 40 on each disc are evenly distributed, i.e., the distance between every two adjacent markers 40 is equal. It will be appreciated that in other embodiments, the plurality of markers 40 on each disc are not uniformly distributed. Alternatively, one of the first distal occluding disk 222 and the first proximal occluding disk 224 has a plurality of markers 40 uniformly distributed and the other of the plurality of markers 40 is non-uniformly distributed.

In a more specific embodiment, some of all of the markers 40 of the occluding device 100 are disposed on the first distal occluding disk 222 and another portion are disposed on the first proximal occluding disk 224. The plurality of markers 40 disposed on the first distal occluding disk 222 and the plurality of markers 40 disposed on the first proximal disk 224 are distributed in the same manner as described above.

Alternatively, in one embodiment, some of all of the markers 40 of the occluding device 100 are disposed on the first occluding unit 22 and another portion are disposed on the second occluding unit 24. The plurality of markers 40 disposed on the first plugging unit 22 may be disposed entirely on the first distal plugging disc 222, entirely on the first proximal plugging disc 224, or partially on the first distal plugging disc 222 and the other on the first proximal plugging disc 224 in the same manner as described above. The plurality of markers 40 disposed on the second occluding unit 24 may be disposed entirely on the second distal occluding disk 242, entirely on the second proximal occluding disk 244, or partially on the second distal occluding disk 242 and partially on the second proximal occluding disk 244 in the same manner as described above.

The markers 40 are simultaneously arranged on the first plugging unit 22 and the second plugging unit 24, which is beneficial to accurately positioning the plugging device 100 on one hand, and is beneficial to judging the overall shape of the plugging device 100 on the other hand, so as to confirm that the release shape of the plugging device 100 is good and meet the plugging requirement.

In one embodiment, whether the plurality of markers 40 are disposed only on the first plugging unit 22, only on the second plugging unit 24, or both the first plugging unit 22 and the second plugging unit 24 are disposed with the plurality of markers 40. The number of markers 40 on each occlusion disk is 2 to 36. Namely, the number of the plurality of markers 40 on the first plugging unit 22 is 2-36; and/or the number of the plurality of markers 40 on the second plugging unit 24 is 2-36. The number of markers on each occluding disk is 2-36, which takes into account the requirements of visibility and flexibility of delivery of the occluding device 100.

In one embodiment, at least a portion of the plurality of markers 40 is disposed on the waist 26 of the occluding device 100. After the occluder 100 is implanted into the defect part, the waist 26 is positioned at the opening of the defect part and blocks the opening, and the marker 40 is arranged on the waist 26, which is beneficial to identifying the position and the shape of the waist 26 and enables the interventional operation to be carried out smoothly.

In one embodiment, the number of markers 40 provided at the waist 26 is 2, and two markers 40 are respectively provided at opposite edges of the waist 26 to indicate the extreme positions of the waist 26. Referring again to fig. 1, the two opposite edges of the waist portion 26 refer to two opposite edges of a cross section perpendicular to the longitudinal central axis I-I of the waist portion 26 and parallel to the first plugging unit 22 or the second plugging unit 24. For example, when the above-described cross-sectional shape of the waist portion 26 is circular, the two markers 40 are located at both ends of a diameter of the cross-sectional shape of the waist portion, respectively.

In one embodiment, the number of the markers 40 disposed at the waist portion 26 is greater than 2, and a plurality of markers 40 with a number greater than 2 are distributed along the circumference of the waist portion 26, and the markers 40 are located on the same plane. Which plane is perpendicular to the longitudinal central axis I-I of the occluding device 100.

In another embodiment, when the axial length of the waist 26 is large, multiple turns of the marker 40 are arranged along the circumference of the waist 26, the multiple markers 40 of each turn are located on the same plane perpendicular to the longitudinal central axis I-I of the occluding device 100, and the plane where the multiple markers 40 of each turn are located is parallel to the plane where the multiple markers 40 of the other turns are located.

In the above two embodiments, the plurality of markers 40 located on the same plane may be distributed at equal intervals or at unequal intervals.

Further, when the markers 40 are provided in a plurality of circles, the pitch between the markers 40 on the same plane (i.e., the pitch between any two adjacent markers on the same plane) may be equal to or different from the pitch between the markers 40 on the other plane (i.e., the pitch between any two adjacent markers on the same plane). The number of the plurality of markers 40 on the same plane may or may not be equal to the number of the plurality of markers 40 on another plane.

Referring again to fig. 1, in one embodiment, the occluding device 100 further comprises a distal head 60 and a proximal head 80. The distal closure 60 is connected to a first distal closure disc 222 for converging and securing one end of the wire, and the proximal plug 80 is connected to a second proximal closure disc 244 for converging and securing the other end of the wire. Also, the proximal plug 80 is detachably connected to the delivery system so that after the occluding device 100 is delivered to the lesion by the delivery system and released, the delivery system can be disconnected. An end marker 90 is provided on at least one of the distal head 60 and the proximal head 80 to indicate the two extreme positions of the longitudinal central axis I-I extension of the occluding device 100. The occluding device 100 shown in figure 1 is provided with two end markers 90 and the two end markers 90 are embedded in the distal head 60 and the proximal head 80, respectively. In other embodiments, the end marker 90 may be otherwise disposed on the distal head 60 and/or the proximal head 80, for example, the end marker 90 covers the surface of the distal head 60 and/or the proximal head 80.

It will be appreciated that the end marker structure 90 is a material underlying a medical imaging device. Such as the radiopaque or fluorescent materials described above. The end marker 90 may be in the form of a powder, for example, a solid powder of gold filled in the lumen of the distal seal 60 to form the end marker 90. Alternatively, the end marker structure 90 may be in the form of a band or membrane, for example, gold in the form of a band wrapped around the outer surface of the distal seal 60. The outer surface of the distal end socket is coated with membranous iodinated poly-epsilon-caprolactone.

At least a portion of the plurality of network nodes of the occluding device 100 are provided with a plurality of markers 40, and each marker 40 comprises a material visible under the medical imaging device, so that the occluding device 100 has better visibility under the light of the medical imaging device.

It is understood that in other embodiments, the material visible under the medical imaging device is a fluorescent material, such that the occluding device 100 is visible under a fluorescent medical imaging device.

Further, the implantable device is described by taking the stent as an example.

Referring to fig. 9, in one embodiment, the implantable device is a stent 200. The stent 200 is a luminal stent, and specifically may be an aortic stent, a coronary stent, a peripheral vascular stent, an airway stent, a urethral stent, an esophageal stent, an intestinal stent, a biliary stent, or the like. The stand 200 includes a frame 220. The frame is woven with a plurality of woven threads that are interlaced to form a plurality of network nodes 210, and then a plurality of markers 240 are formed on the frame 220 in the manner described above for forming the markers 40 on the frame 20 of the occluding device 100.

In one embodiment, a marker 240 is disposed on each network node 210 of the frame 220 to provide better visibility of the stent 200 under medical imaging equipment. Moreover, since the frame 220 is woven by weaving a plurality of silk threads into a grid-shaped woven mesh in a vertically staggered manner, the silk threads positioned at the upper layer and the lower layer in the woven mesh are only arranged in a staggered manner, and the silk threads are not fixedly connected with each other, which may result in poor stability of the woven mesh, and the marker 240 fixes the silk threads positioned at the upper layer and the lower layer at the network node 210 to form a fixed network node, so that the stent 200 has good stability, and is beneficial to resisting the impact of body fluid without deformation and displacement.

In another embodiment, a plurality of markers 240 are disposed on a portion of the network nodes 210 of the frame 220, and each network node 210 corresponds to each marker 240. No marker 240 is provided on another portion of network nodes 210 of frame 220. For example, in the embodiment shown in fig. 9, the markers 240 are disposed only on a portion of the network nodes 210 at both ends of the frame 220, which facilitates accurate determination of the position of the stent 200 in the vessel and facilitates maintaining the compliance of the stent 200.

The type of material and adhesive that is visible with the medical imaging device is the same as described above for the occluding device 100. The method of fixing the wires at the network nodes 210 by the adhesive to form fixed network nodes is also the same as the method of forming fixed network nodes by the adhesive in the occluder 100, for example, using leaching and/or spraying, and will not be described herein again.

It should be noted that the implantable device is described above by taking the occluding device 100 and the stent 200 as examples, and it should be understood that the implantable device is not limited to the occluding device 100 and the stent 200, and any device having a frame with a plurality of wires that are interlaced to form a plurality of network nodes is suitable.

It should be further noted that the placement of the markers (e.g., markers 40, markers 240) on the frame (e.g., frame 20, frame 220) of the implantable device in the above-mentioned manner is advantageous for improving the visibility of the implantable device under the medical imaging apparatus, especially for improving the visibility of the implantable device woven from polymer material wires, but the above-mentioned solution is not limited to the specific material of the wires, and the implantable device woven from pure metal wires or alloy wires is also applicable. For example, although the nitinol itself has a certain visibility under the medical imaging device, two markers are disposed at two ends of a diameter of the first distal occluding disk, and the two markers are used to further enhance the visibility of two extreme positions of the occluding device, thereby further facilitating the determination of the shape of the occluding device and the accurate positioning of the occluding device.

Further, a preparation method of the implantable device is provided, which comprises the following steps:

step 110: a frame is provided that includes a plurality of wires that are interlaced to form a plurality of network nodes.

The frame structure is different according to the type of the implanted device. For example, when the implantable device is an occluder, the frame is a frame for occlusion, and may be a two-disc one-waist structure including a first occluding unit, a second occluding unit and a waist, or a structure including one occluding disc and one waist, which is substantially T-shaped in cross section, and so on. When the implantable device is a vascular stent, the frame is a luminal structure.

Step 120: the plurality of markers are respectively arranged on at least part of the network nodes, each marker corresponds to each network node, and each marker comprises a material visible under the medical imaging equipment.

The material visible under the medical imaging device is a material such as a radiopaque material or a fluorescent material visible under the medical imaging device.

In one embodiment, the material visible under the medical imaging device is contacted with at least a portion of the network nodes of the frame, the material visible under the medical imaging device is attached to at least a portion of the network nodes of the frame, a plurality of markers are formed on at least a portion of the network nodes, and each marker corresponds to each network node in the plurality of markers and at least a portion of the plurality of network nodes.

In one embodiment, the step of contacting the material visible under the medical imaging device with at least a portion of the network nodes of the frame, attaching the material visible under the medical imaging device to at least a portion of the network nodes of the frame, forming the plurality of markers on at least a portion of the network nodes, and each marker corresponding to each network node in the plurality of markers and at least a portion of the plurality of network nodes comprises:

preparing a solution or suspension containing a material visible under a medical imaging device, contacting the solution or suspension containing the material visible under the medical imaging device with at least a portion of the network nodes of the frame, and after evaporation of a solvent of the solution or suspension containing the material visible under the medical imaging device, attaching the material visible under the medical imaging device to at least a portion of the network nodes of the frame, thereby forming a plurality of tags on at least a portion of the network nodes, and each tag corresponding to each network node in the plurality of tags and at least a portion of the plurality of network nodes.

When the material visible under the medical imaging device is a radiopaque material with adhesive properties, the radiopaque material with adhesive properties is dissolved in a solvent and formulated into a solution or suspension containing the material visible under the medical imaging device after sufficient dissolution.

When the material visible under the medical imaging device is a radiopaque material without adhesive properties and the formed marker further comprises an adhesive, the adhesive is dissolved in a solvent to prepare a solution, then the radiopaque material without adhesive properties is added into the solution, and after uniform mixing, the solution or suspension containing the material visible under the medical imaging device is prepared. When the radiopaque material having no blocking property is insoluble in the above solution, continuous stirring is required to prevent the radiopaque material having no blocking property from agglomerating to form a precipitate.

In one embodiment, the material visible under the medical imaging device is attached to at least a portion of the network nodes of the frame by contacting the material visible under the medical imaging device with at least a portion of the network nodes of the frame using an immersion method. At least a portion of the frame is immersed in a solution or suspension containing a material that is visible under the medical imaging device, and the frame is then lifted from the solution or suspension containing the material that is visible under the medical imaging device. During the process of slowly lifting the frame from the solution or suspension containing the material visible under the medical imaging device, the residual solution or suspension forms a liquid film on the frame, the concentration of the solution is higher and higher due to the rapid volatilization of the solvent, the liquid film is broken under the action of the surface tension, the residual solute and/or particulate matters are enriched at least part of the network nodes of the frame, and finally the material visible under the medical imaging device and the adhesive (if any) are separated at the network nodes, namely the markers attached to the network nodes.

In one embodiment, the method further comprises the step of performing a gas injection treatment after the step of contacting the solution or suspension containing the material visible under the medical imaging device with at least a portion of the network nodes of the frame, after the step of evaporating the solvent of the solution or suspension containing the material visible under the medical imaging device, and before the step of attaching the material visible under the medical imaging device to at least a portion of the network nodes of the frame. The air-jet process is performed to forcibly blow the liquid film to deposit a material visible under the medical imaging device only on the network nodes to form markers attached to the network nodes.

In one embodiment, at least a portion of the frame is immersed in the solution or suspension containing the material visible under the medical imaging device for a period of time greater than or equal to 5 seconds, such that the solution or suspension containing the material visible under the medical imaging device sufficiently wets the frame to increase the amount of material visible under the medical imaging device that adheres to the frame.

In one embodiment, the frame is lifted from a solution or suspension containing material visible under the medical imaging device at a speed of 0.01 to 0.5 meters per second.

In one embodiment, if the amount of material visible under the medical imaging device that is deposited after a single leach is insufficient, multiple operations may be performed, i.e., the process of leaching may be repeated to immerse at least a portion of the frame in a solution or suspension containing material visible under the medical imaging device, and then the frame may be lifted from the solution or suspension containing material visible under the medical imaging device. The immersion time is shorter, preferably not more than 5 seconds, after the first leaching operation, and the second or subsequent repeated leaching operations. This is due to the fact that the solvent in the solution or suspension will re-dissolve at least part of the solute that was first precipitated upon repeated operation. The lifting speed is also required to be fast during the repeated operation, and in one embodiment, the lifting speed during the repeated operation is 0.05-1 meter per second (m/s).

In one embodiment, a solution or suspension containing material visible on the medical imaging device is applied by spraying or dropping onto at least a portion of the network nodes of the frame, the solvent is evaporated, and the material visible on the medical imaging device is deposited and attached to at least a portion of the network nodes of the frame. For example, when the marker has a multi-layer structure, the innermost layer, the intermediate layer, and the outermost layer of the marker are formed in this order by spraying or dropping. Instillation can be performed using instillation devices, such as infusion sets, syringes, and the like.

In one embodiment, the tag is formed by leaching and at least one of spraying and dripping. For example, the innermost layer of the marker is formed by leaching, and then the intermediate layer covering the innermost layer and the outermost layer covering the intermediate layer are formed in this order by spraying or dropping.

It will be appreciated that depending on the location to which the marker is actually attached, the particular portion of the frame may be immersed in a solution or suspension containing material visible under the medical imaging device, left for a certain period of time, and then slowly raised to the frame away from the solution or suspension containing material visible under the medical imaging device. For example, after the area where the marker is not desired to be attached is isolated, the frame is immersed in a solution or suspension containing a material that is visible under a medical imaging device to form the marker at the desired area. Alternatively, after a portion of the frame is immersed in a solution or suspension containing a material visible under the medical imaging device to form a marker on the frame, a solvent is sprayed onto the marker at certain locations to remove the marker, thereby leaving the marker at the particular locations. Alternatively, after the site where the marker is not required to be attached is isolated, a solution or suspension containing a material visible under a medical imaging device is sprayed only on the site where the marker is required to be attached to form the marker on the desired site. Alternatively, after the marker is formed on the frame by the spray method, a solvent is sprayed to the marker at a certain portion to remove the marker, thereby leaving the marker at the certain portion.

When the implantable device is an occluder, and the occluder further comprises a distal end seal and a proximal plug, a leaching or spraying method can be used to form a membranous end marker structure on at least one of the distal end seal and the proximal plug.

In one embodiment, after disposing the plurality of markers on at least a portion of the network nodes, respectively, a heat treatment step is further included. And carrying out heat treatment to improve the connection strength of the marker and the frame, so as to be beneficial to avoiding the falling of the marker from the frame.

In one embodiment, the step of heat treating comprises: and (3) placing the frame attached with the plurality of markers at the temperature of 45-110 ℃ for heat preservation for 5-60 min.

For most absorbable high molecular polymers, the temperature range of 45-110 ℃ is 10-60 ℃ higher than the glass transition temperature of the absorbable high molecular polymers, so that the temperature is kept at 45-110 ℃ for 5-60 min, which is favorable for improving the connection strength of the marker and the frame on one hand, and ensures that the temperature of heat treatment does not exceed the melting point or softening point temperature of the high molecular polymers on the other hand, thereby ensuring the stability of the integral structure and performance of the frame.

It should be noted that the concentration of the material visible on the medical imaging device and the adhesive in the solution or suspension containing the material visible on the medical imaging device is not required. The concentration of the materials and the adhesive agent which can be seen under the medical imaging equipment can be lower or higher or saturated, and the quality of the materials which can be seen under the medical imaging equipment can meet the requirement. It should be noted that when the concentration of solute or particulate matter is low, the quality of the material visible under the medical imaging device is limited in a single precipitation, and multiple operations are required to achieve the desired effect, so that the quality of the material visible under the medical imaging device attached to the network node meets the visual requirement.

In particular embodiments, the concentration of the adhesion agent solution may be 30mg/mL, 15mg/mL, 50mg/mL, 20mg/mL, 10mg/mL, or the like. Alternatively, the adhesive solution is a saturated solution. The solubility properties of the concentrations of materials visible under medical imaging equipment vary widely, and the concentrations may vary. Such as insoluble materials, e.g., gold, platinum, barium sulfate, etc., in amounts of 1%, 5%, 10%, etc. Inorganic iodides, such as sodium iodide, have a solubility of 158.7g in 100g of water at 0 ℃ due to their good solubility, and can be formulated at 20%, 40%, 50% or saturated solutions. Organic iodides, such as iopamidol, have a solubility in water greater than 8.2mg/mL and may be formulated to have a solubility of 2mg/mL, 4mg/mL, 6mg/mL, or saturated solutions.

When the diameter of the silk thread is larger, the concentration of the materials and the adhesive agents which are visible under the medical imaging equipment can be increased in the leaching process, so that more materials and adhesive agents which are visible under the medical imaging equipment are deposited at the network nodes to improve the visibility and the adhesion. Alternatively, the leaching step may be repeated multiple times to deposit more material and adhesive at the network nodes visible in the medical imaging device, improving visibility and adhesion.

The preparation method of the implantable device is simple in process, and firm and reliable markers can be formed on the frame, so that the visibility of the occluder under medical imaging equipment is improved.

The implantable device and the method for making the same are further described below by way of specific examples.

Example 1

The method comprises the steps of taking a group of 18 parallel poly-L-lactic acid (PLLA) silk yarns with the silk diameter of 0.40mm as longitude silk yarns and a group of 18 parallel poly-L-lactic acid (PLLA) silk yarns with the silk diameter of 0.40mm as latitude silk yarns, interweaving the longitude silk yarns and the latitude silk yarns to form a woven mesh, and carrying out heat setting on the woven mesh to form a frame, wherein the frame comprises a first blocking unit, a second blocking unit and waists respectively connected with the first blocking unit and the second blocking unit, the frame comprises a plurality of network nodes, and the structures of the first blocking unit and the second blocking unit are the same as the structures of the first blocking unit and the second blocking unit, and are not repeated here. In this embodiment, the first blocking unit and the second blocking unit are both circular.

Dissolving poly-dl-lactic acid (PDLLA) in acetonitrile to prepare a poly-dl-lactic acid solution with the concentration of 30mg/mL, adding barium sulfate solid powder (the particle size is less than 0.1mm) into the poly-dl-lactic acid solution, and uniformly stirring to obtain a suspension containing the poly-dl-lactic acid and the barium sulfate, wherein the mass ratio of the poly-dl-lactic acid to the barium sulfate is 2: 1. After the whole frame (comprising the first plugging unit, the second plugging unit and the waist) is soaked in a suspension containing poly-dl-lactic acid and barium sulfate for 5s (the suspension is continuously stirred during the soaking process, barium sulfate particles are prevented from agglomerating and precipitating), the frame is lifted out of the suspension at the speed of 0.5m/s, the poly-dl-lactic acid and the barium sulfate are deposited on all network nodes of the frame, and after drying, markers attached to all network nodes of the frame are formed, wherein each marker corresponds to each network node, and the silk threads at the network nodes are fixed by the markers to form fixed network nodes. The mass of barium sulfate in each marker was 0.1 mg.

And (3) carrying out heat treatment on the frame with the formed marker at 70 ℃ for 5min to obtain the stopper.

The plugging device is implanted into the interatrial of the Bama pigs, and the implantation process is smooth. An image of the implanted occluder in a DSA device is shown in fig. 10, and a plurality of small black dots are a plurality of markers, so that the occluder can be better seen in the DSA device.

Example 2

The method comprises the steps of taking a group of 30 poly-L-lactic acid (PLLA) silk threads with the silk diameter of 0.10mm and arranged in parallel as longitude silk threads and a group of 30 poly-L-lactic acid (PLLA) silk threads with the silk diameter of 0.10mm and arranged in parallel as latitude silk threads to be woven in a vertically staggered mode to form a woven mesh, carrying out heat setting on the woven mesh to form a frame, wherein the frame comprises a first plugging unit, a second plugging unit and a waist part respectively connected with the first plugging unit and the second plugging unit, the frame comprises a plurality of network nodes, and the structures of the first plugging unit and the second plugging unit are the same as the structures of the first plugging unit and the second plugging unit, and are not repeated here. In this embodiment, the first blocking unit and the second blocking unit are both circular.

Dissolving poly-dl-lactic acid (PDLLA) in acetone to prepare a saturated poly-dl-lactic acid solution, adding sodium iodide solid powder (the particle size is less than 0.1mm) into the poly-dl-lactic acid solution, and uniformly stirring to obtain a solution containing poly-dl-lactic acid and sodium iodide, wherein the mass ratio of poly-dl-lactic acid to sodium iodide is 1: 1. After the first distal end plugging disc of the first plugging unit is immersed in a solution containing poly-dl-lactic acid and sodium iodide for 1min, the first distal end plugging disc is extracted from the solution at a speed of 0.1m/s, poly-dl-lactic acid and sodium iodide are deposited on all network nodes of the first distal end plugging disc, and after drying, markers which are 18 in number and are attached to all network nodes of the first distal end plugging disc are formed, wherein each marker corresponds to each network node, and the silk threads at the network nodes are fixed by the markers to form fixed network nodes. The mass of sodium iodide in each marker was 0.5 mg.

And immersing the second proximal plugging disc of the second plugging unit in a solution containing poly-dl-lactic acid and sodium iodide for 1min, extracting the second proximal plugging disc from the solution at a speed of 0.1m/s, depositing poly-dl-lactic acid and sodium iodide on all network nodes of the second proximal plugging disc, and drying to form markers which are attached to all network nodes of the second proximal plugging disc, wherein the number of the markers is 18, each marker corresponds to each network node, and the markers fix silk threads at the network nodes to form fixed network nodes. The mass of sodium iodide in each marker was 0.5 mg.

And (3) carrying out heat treatment on the frame with the formed marker at 60 ℃ for 30min to obtain the stopper.

The occluder is implanted into the interatrial space of the Bama pig, so that the occluder has better visibility under DSA equipment and smooth implantation process.

Example 3

Taking a group of 50 polyethylene terephthalate (PET) silk threads with the silk diameter of 0.10mm and arranged in parallel as longitude silk threads and a group of 50 polyethylene terephthalate silk threads with the silk diameter of 0.10mm and arranged in parallel as latitude silk threads to be woven in a vertically staggered mode to form a woven mesh, carrying out heat setting on the woven mesh to form a frame, wherein the frame comprises a first plugging unit, a second plugging unit and a waist part respectively connected with the first plugging unit and the second plugging unit, the frame comprises a plurality of network nodes, and the structures of the first plugging unit and the second plugging unit are the same as the structures of the first plugging unit and the second plugging unit, and are not repeated here. The occluder further comprises a distal end sealing head connected with the first distal end occluding disk and a proximal end plug connected with the second proximal end occluding disk, wherein in the embodiment, the first occluding unit and the second occluding unit are both circular. An end marking structure is embedded in the far-end bolt head, and the end marking structure is made of gold.

Dissolving poly-dl-lactic acid (PDLLA) in acetone to prepare a poly-dl-lactic acid solution with the concentration of 30mg/mL, adding gold solid powder (the particle size is less than 0.1mm) into the poly-dl-lactic acid solution, and uniformly stirring to obtain a suspension containing poly-dl-lactic acid and gold powder, wherein the mass ratio of the poly-dl-lactic acid to the gold powder is 1: 8. After a first far-end plugging disc of the first plugging unit is immersed in a suspension containing poly-dl-lactic acid and gold powder for 1min, the first far-end plugging disc is lifted out of the solution at a speed of 0.01m/s, poly-dl-lactic acid and gold powder are deposited on all network nodes of the first far-end plugging disc, after drying, markers attached to all network nodes of the first far-end plugging disc are formed, a solvent capable of dissolving poly-dl-lactic acid is sprayed on part of the markers, so that part of the markers fall off, and 20 markers distributed in a circle are formed on the first far-end plugging disc only, and the distance from a circumscribed circle of the 20 markers to the edge of the first far-end plugging disc is 2 mm. Each of the 20 markers corresponds to each network node, and the markers fix wires at the network nodes to form fixed network nodes. The mass of gold in each marker was 2 mg.

And (3) carrying out heat treatment on the frame with the formed marker at 70 ℃ for 20min to obtain the stopper.

Example 4

A group of 30 polyethylene terephthalate (PET) silk threads with the silk diameter of 0.30mm and arranged in parallel are used as longitude silk threads, a group of 30 polyethylene terephthalate (PET) silk threads with the silk diameter of 0.30mm and arranged in parallel are used as latitude silk threads and woven in a vertically staggered mode to form a woven mesh, the woven mesh is subjected to heat setting to form a frame, the frame comprises a first blocking unit, a second blocking unit and a waist portion respectively connected with the first blocking unit and the second blocking unit, the frame comprises a plurality of network nodes, and the structures of the first blocking unit and the second blocking unit are the same as those of the above structure, and are not repeated here. In this embodiment, the first blocking unit and the second blocking unit are both circular.

Dissolving Polyhydroxybutyrate (PHB) in chloroform to prepare a polyhydroxybutyrate solution with the concentration of 50mg/mL, adding solid powder of iopamidol (the particle size is less than 0.1mm) into the polyhydroxybutyrate solution, and uniformly stirring to obtain a suspension containing polyhydroxybutyrate and iopamidol, wherein the mass ratio of polyhydroxybutyrate to iopamidol is 0.5: 1. After dipping the first distal end blocking disk of the first blocking unit in a suspension containing polyhydroxybutyrate and iopamidol for 30s, the first distal end blocking disk is lifted out of the solution at a speed of 0.1m/s, polyhydroxybutyrate and iopamidol are deposited on all network nodes of the first distal end blocking disk, after drying, markers attached to all network nodes of the first distal end blocking disk are formed, chloroform is sprayed on part of the markers, so that part of the markers are peeled off, and 15 markers distributed in a circle are formed on the first distal end blocking disk only, wherein the distance from a circumscribed circle of the 15 markers to the edge of the first distal end blocking disk is 1 mm. Each marker corresponds to each network node in the 15 markers, and the markers fix wires at the network nodes to form fixed network nodes. The mass of iopamidol in each marker was 1 mg.

After dipping the second proximal blocking disk of the second blocking unit in a suspension containing polyhydroxybutyrate and iopamidol for 30s, the second proximal blocking disk was extracted from the suspension at a speed of 0.1m/s, polyhydroxybutyrate and iopamidol were deposited on all network nodes of the second proximal blocking disk, after drying, markers attached to all network nodes of the second proximal blocking disk were formed, chloroform was sprayed on a part of the markers to cause a part of the markers to fall off, thereby forming 15 markers circumferentially distributed only on the second proximal blocking disk, and the distance from the circumscribed circle of the 15 markers to the edge of the second proximal blocking disk was 1 mm. Each marker corresponds to each network node in the 15 markers, and the markers fix wires at the network nodes to form fixed network nodes. The mass of iopamidol in each marker was 1 mg.

And (3) carrying out heat treatment on the frame with the formed marker at 45 ℃ for 15min to obtain the stopper.

Example 5

The method comprises the steps of taking a group of 20 poly-L-lactic acid (PLLA) silk threads with the silk diameter of 0.40mm and arranged in parallel as longitude silk threads and a group of 20 poly-L-lactic acid (PLLA) silk threads with the silk diameter of 0.40mm and arranged in parallel as latitude silk threads to be woven in a vertically staggered mode to form a woven mesh, carrying out heat setting on the woven mesh to form a frame, wherein the frame comprises a first plugging unit, a second plugging unit and a waist part respectively connected with the first plugging unit and the second plugging unit, the frame comprises a plurality of network nodes, and the structures of the first plugging unit and the second plugging unit are the same as the structures of the first plugging unit and the second plugging unit, and are not repeated here. In this embodiment, the first blocking unit and the second blocking unit are both circular.

Dissolving poly-racemic lactic acid (PDLLA) in ethyl acetate to prepare a poly-racemic lactic acid solution with the concentration of 20 mg/mL; dissolving iopamidol in ethanol to prepare an iopamidol solution with the concentration of 50 mg/mL; polylactic-co-glycolic acid (PLGA) was dissolved in dichloroethane to prepare a polylactic-co-glycolic acid solution having a concentration of 20 mg/mL. Spraying a poly-dl-lactic acid solution on two network nodes of the first far-end plugging disc, fully drying, and repeating the spraying and drying operations for 5 times to form a PDLLA layer; spraying iopamidol solution on the outer surface of the PDLLA layer, fully drying, and repeating the spraying and drying operations for 5 times to form an iopamidol layer coating the PDLLA layer; and finally spraying a polylactic acid-glycolic acid copolymer solution on the outer surface of the iopamidol layer, fully drying, repeating the spraying and drying operations for 5 times to form a PLGA layer coating the iopamidol layer, and forming two markers on the first far-end plugging disc. The two markers are located at two ends of a diameter of the first far-end plugging disc, and the distance from the edges of the two markers to the edge of the first far-end plugging disc is 0 mm. The mass of iopamidol in each marker is 2mg, and the mass ratio of the poly-racemic lactic acid, the iopamidol and the poly-lactic acid-glycolic acid copolymer is 2:5: 2.

And (3) carrying out heat treatment on the frame with the formed marker at 55 ℃ for 15min to obtain the stopper.

Example 6

A group of 14 polyethylene terephthalate (PET) silk threads with the silk diameter of 0.30mm and arranged in parallel are taken as longitude silk threads, a group of 14 polyethylene terephthalate silk threads with the silk diameter of 0.30mm and arranged in parallel are taken as latitude silk threads and woven in a vertically staggered mode to form a woven mesh, the woven mesh is subjected to heat setting to form a frame, the frame comprises a first plugging unit, a second plugging unit and a waist part respectively connected with the first plugging unit and the second plugging unit, the frame comprises a plurality of network nodes, and the structures of the first plugging unit and the second plugging unit are the same as those of the above structure, and the description is omitted here. In this embodiment, the first blocking unit and the second blocking unit are both circular.

Dissolving Polydioxanone (PDO) in tetrachloroethane to prepare Polydioxanone (PDO) solution with the concentration of 10mg/mL, adding bismuth subcarbonate into the polydioxanone solution, and uniformly stirring to obtain suspension containing polydioxanone and bismuth subcarbonate, wherein the mass ratio of polydioxanone to bismuth subcarbonate is 1.5: 1. After the first distal plugging disc of the first plugging unit was immersed in the suspension containing polydioxanone and bismuth subcarbonate for 5 seconds (the suspension was continuously stirred during the immersion process to prevent the bismuth subcarbonate particles from agglomerating and precipitating), the first distal plugging disc was lifted out of the suspension at a speed of 0.5m/s, and the poly (racemic lactic acid) and bismuth subcarbonate were deposited on all network nodes of the first distal plugging disc, and the leaching operation was repeated 2 times due to the low concentration. And secondly and thirdly, respectively soaking the first far-end plugging disc in a suspension containing polydioxanone and bismuth subcarbonate for 3s and 2s, quickly lifting at the speed of 0.2m/s and 1.0m/s, and drying to form markers attached to all network nodes of the first far-end plugging disc, wherein the number of the markers is 25, each marker corresponds to each network node, and the markers fix silk threads at the network nodes to form fixed network nodes. The mass of basic bismuth carbonate in each marker was about 0.2 mg.

The occluder is implanted in the interatrial septum of a Bama pig, so that the occluder has better visibility under a DSA device.

Example 7

A group of 30 polyethylene terephthalate (PET) silk threads which are arranged in parallel and have the silk diameter of 0.30mm are used as longitude silk threads, a group of 30 polyethylene terephthalate (PET) silk threads which are arranged in parallel and have the silk diameter of 0.30mm are used as latitude silk threads, the PET silk threads are woven in a vertically staggered mode to form a woven mesh, the woven mesh is subjected to heat setting to form a frame, the frame comprises a first blocking unit, a second blocking unit and waists which are respectively connected with the first blocking unit and the second blocking unit, the frame comprises a plurality of network nodes, the structures of the first blocking unit and the second blocking unit are the same as those of the above structure, and the description is omitted here. In this embodiment, the first blocking unit and the second blocking unit are both circular.

Dissolving iodinated poly-epsilon-caprolactone (I-PCL, the content of I is 11 wt.%) in chloroform to prepare an iodinated poly-epsilon-caprolactone solution with the concentration of 10mg/mL, dropwise adding the iodinated poly-epsilon-caprolactone solution on all network nodes of the first far-end plugging disc by using an injector, drying to form markers attached to all network nodes of the first far-end plugging disc, wherein the number of the markers is 36, each marker corresponds to each network node, and the markers fix silk threads at the network nodes to form fixed network nodes, so that the plugging device is obtained. The mass of each marker was 0.2 mg.

Example 8

A group of 20 Polydioxanone (PDO) wires with the wire diameter of 0.40mm are taken as longitude wires, a group of 20 polydioxanone wires with the wire diameter of 0.40mm, which are arranged in parallel, are taken as latitude wires, and are woven up and down in a staggered mode to form a tubular framework, and the tubular framework comprises a plurality of network nodes.

Dissolving poly-L-lactic acid (PLLA) in chloroform to prepare a saturated poly-L-lactic acid solution, adding platinum powder into the poly-L-lactic acid solution, and uniformly stirring to obtain a suspension containing poly-L-lactic acid and platinum powder, wherein the mass ratio of poly-L-lactic acid to platinum powder is 1: 2. The whole frame was immersed in a suspension containing poly (L-lactic acid) and platinum-gold powder for 30 seconds, then lifted off the suspension at a speed of 0.3m/s, subjected to air-jet treatment, and dried to form markers attached to all network nodes of the frame, the mass of platinum-gold powder in each marker being 1.5 mg.

And (3) carrying out heat treatment on the frame forming the marker at 110 ℃ for 5min to obtain the lumen implantation instrument.

The lumen implanting instrument is implanted into peripheral blood vessels of Bama pigs, the visibility of the lumen implanting instrument under DSA equipment is good, and the implantation process is smooth.

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

1. An implantable device comprising a frame comprising a plurality of wires that are interlaced to form a plurality of network nodes, wherein the implantable device further comprises a plurality of markers disposed on at least a portion of the plurality of network nodes, each marker corresponding to each network node, each marker comprising a material visible under a medical imaging device and an adhesive;

wherein the material visible under the medical imaging equipment is a radio-opaque material, and the mass ratio of the adhesive to the radio-opaque material is 0.1-2: 1.

2. The implantable device of claim 1, wherein each marker bonds each corresponding network node to form a fixed network node.

3. The implantable device of claim 1, wherein the marker is a single layer structure, the radiopaque material being dispersed in the adhesive; or,

the marker is of a multilayer structure, the multilayer structure comprises an innermost layer, an outermost layer and at least one intermediate layer positioned between the innermost layer and the outermost layer, the innermost layer and the outermost layer are both made of adhesive, and the at least one intermediate layer is made of a radio-opaque material or a mixed material of the radio-opaque material and the adhesive.

4. The implantable device of claim 1, wherein the mass of the radiopaque material in each marker is 0.01-2 mg.

5. The implantable device of claim 1, wherein the material of the adhesion agent is selected from at least one of polyethylene terephthalate, polypropylene, polyethylene, polylactic acid, polyglycolic acid, polylactic-co-glycolic acid, polyhydroxyalkanoate, polydioxanone, and polycaprolactone.

6. The implantable device of claim 1, wherein the radiopaque material is selected from at least one of a metal, an inorganic salt, and an organic material; the metal is selected from at least one of gold, platinum, tungsten, iridium, osmium, rhenium, rhodium and tantalum, the inorganic salt is selected from at least one of barium sulfate, sodium iodide and bismuth subcarbonate, and the organic material is selected from at least one of iopamidol, ioversol, diatrizoate, iopromide and iodine-containing high polymer materials.

7. The implantable device of claim 1, wherein the implantable device is an occluder, the occluder comprises the frame, and the frame comprises a first occluding unit, a second occluding unit, and a waist, both ends of the waist are connected to the first occluding unit and the second occluding unit, respectively, the first occluding unit comprises a first distal occluding disc, a first proximal occluding disc, and a first ridge connecting the first distal occluding disc and the first proximal occluding disc, the second occluding unit comprises a second distal occluding disc, a second proximal occluding disc, and a second ridge connecting the second distal occluding disc and the second proximal occluding disc, at least some of the plurality of markers are disposed on the first distal occluding disc and/or the first proximal occluding disc.

8. The implantable device of claim 7, wherein one of said plurality of markers is disposed partially on said first distal occluding disk and/or said first proximal occluding disk and another portion is disposed on said second distal occluding disk and/or said second proximal occluding disk.

9. The implantable device of claim 7, wherein at least two of the plurality of markers are disposed on the first distal occluding disk or the first proximal occluding disk;

in the at least two markers located on the first distal blocking disk, a connecting line of the two markers passes through the geometric center of the first distal blocking disk, and the distance from the edge of each marker to the edge of the first distal blocking disk in the two markers is 0-2 mm; or,

and in the at least two markers positioned on the first proximal blocking disk, a connecting line of the two markers penetrates through the geometric center of the first proximal blocking disk, and the distance from the edge of each marker to the edge of the first proximal blocking disk is 0-2 mm.

10. The implantable device of claim 7 or 8, wherein a circumscribed figure of the plurality of markers on the first distal occluding disk has the same shape as the first distal occluding disk, and a geometric center of the circumscribed figure of the plurality of markers coincides with the geometric center of the first distal occluding disk; or the circumscribed figure of the plurality of markers on the first proximal occluding disk is the same as the shape of the first proximal occluding disk, and the geometric center of the circumscribed figure of the plurality of markers coincides with the geometric center of the first proximal occluding disk.

11. The implantable device of claim 10, wherein the distance from the outer graph of the plurality of markers on the first distal occluding disk to the edge of the first distal occluding disk is 0-2 mm; or the distance from the edge of the external graph of the plurality of markers on the first near-end plugging disc to the edge of the first near-end plugging disc is 0-2 mm.

12. The implantable device of claim 7, wherein at least a portion of the plurality of markers are disposed on the waist.

13. The implantable device of claim 10, wherein the occluder further comprises a distal end cap coupled to the first distal end occluding disk and a proximal end plug coupled to the second proximal end occluding disk, at least one of the distal end cap and the proximal end plug having an end marker disposed thereon.

14. A method of making an implantable device, comprising the steps of:

providing a frame comprising a plurality of wires that are interlaced to form a plurality of network nodes;

disposing a plurality of markers on at least some of the network nodes, respectively, and each marker and at least some of the plurality of network nodes corresponds to each network node, and each marker includes a material visible under a medical imaging device and an adhesive;

15. The method of claim 14, wherein the step of separately disposing a plurality of markers on at least some of the network nodes, each marker corresponding to each network node, and at least some of the plurality of network nodes, each marker comprising a material visible under a medical imaging device comprises:

preparing a solution or suspension containing a material visible under a medical imaging device, contacting the solution or suspension containing the material visible under the medical imaging device with at least part of the network nodes of the frame, wherein the material visible under the medical imaging device is attached to at least part of the network nodes of the frame after a solvent of the solution or suspension containing the material visible under the medical imaging device is volatilized, the plurality of markers are formed on the at least part of the network nodes, and each marker corresponds to each network node in the plurality of markers and at least part of the plurality of network nodes;

wherein the step of contacting the solution or suspension containing the material visible under the medical imaging device with at least a portion of the network nodes of the frame comprises:

immersing at least a portion of the frame in the solution or suspension containing the material visible under the medical imaging device and then lifting the frame from the solution or suspension containing the material visible under the medical imaging device; or,

using a spraying or dripping method to contact the solution or suspension containing the material visible under the medical imaging equipment with at least part of the network nodes of the frame; or,

immersing at least a portion of the frame in the solution or suspension containing the material visible under the medical imaging device, then lifting the frame from the solution or suspension containing the material visible under the medical imaging device, and contacting the solution or suspension containing the material visible under the medical imaging device with at least one of spraying and dropping the solution or suspension containing the material visible under the medical imaging device to at least a portion of the network nodes of the frame.

16. The method of claim 15, wherein the immersing the at least a portion of the frame in the solution or suspension containing the material visible on the imaging device is performed for a period of time greater than or equal to 5 seconds, and the lifting the frame from the solution or suspension containing the material visible on the imaging device is performed at a speed of 0.01 to 0.5 meters per second.

17. The method of claim 15 or 16, wherein the step of contacting the solution or suspension containing the material visible under the medical imaging device with at least a portion of the network nodes of the frame, and attaching the material visible under the medical imaging device to at least a portion of the network nodes of the frame after the step of evaporating the solvent of the solution or suspension containing the material visible under the medical imaging device, further comprises a step of heat treating the solution or suspension containing the material visible under the medical imaging device, the step of heat treating comprising:

and (3) keeping the temperature of the frame attached with the markers at 45-110 ℃ for 5-60 min.