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CN118750076B - An occluder - Google Patents

An occluder
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Publication number
CN118750076B
CN118750076BCN202410875615.2ACN202410875615ACN118750076BCN 118750076 BCN118750076 BCN 118750076BCN 202410875615 ACN202410875615 ACN 202410875615ACN 118750076 BCN118750076 BCN 118750076B
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China
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wall member
hollow channel
occluder
plugging
wire
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CN118750076A (en
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陈娟
苏岭
胡金鹏
张翔
王永丽
冯睿
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Shanghai Shape Memory Alloy Material Co Ltd
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Shanghai Shape Memory Alloy Material Co Ltd
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Abstract

The invention discloses an occluder, and relates to the technical field of medical appliances. The plugging device comprises a plugging support and two binding pieces, wherein the plugging support comprises an inner wall member, an outer wall member and flow blocking objects filled between the inner wall member and the outer wall member, the inner wall member is connected with two ends of the outer wall member, the inner wall member surrounds a hollow channel which allows the through blocking objects to pass through, the plugging support is in a lantern shape, a columnar shape or an irregular shape, and the two binding pieces are respectively coated at two ends of the plugging support along the length direction of the hollow channel and are used for binding the radial dimension of the hollow channel. The invention provides a structure of an occluder, which is used for filling and occluding a cavity with a penetrable barrier in the cavity, and can effectively reduce the occurrence rate of internal leakage.

Description

Plugging device
Technical Field
The invention relates to the technical field of medical instruments, in particular to an occluder.
Background
Endoluminal repair of abdominal aortic aneurysms (Endovascular Abdominal Aortic Repair, EVAR) is increasingly used clinically due to its minimally invasive, safe, etc. advantages. The main complication after EVAR surgery is endoleak. The highest proportion is that type II endoleak enters the tumor cavity through branch arteries (such as lumbar artery, inferior mesenteric artery, internal iliac artery, auxiliary renal artery and the like) to lead the tumor cavity to be continuously expanded, and the rupture causes serious consequences when serious.
Embolization of the responsible vessel (inferior mesenteric artery or lumbar artery) is the most common way to treat type II endoleaks, but due to the anatomical distortion of part of the side branch vessels, the time-consuming and low success rate of the superior selection is achieved, and the risk of distal vascular embolization caused by tumor luminal thrombus shedding exists during the treatment. In actual clinical practice, it was found that prophylactic filling of tumor cavities when EVAR was performed could also reduce the incidence of type II endoleaks.
The most common abdominal aortic aneurysm is a shuttle-shaped, and the cavity left after the implantation of the covered stent is in an irregular structure with small gaps between the proximal end and the wall of a blood vessel and large gaps between the middle part and the wall of the blood vessel. The plugging devices on the market at present are difficult to be filled effectively, and the incidence rate of II-type internal leakage is still high.
Disclosure of Invention
The invention mainly aims to provide an occluder which aims to improve the occlusion effect and reduce the incidence of II-type internal leakage.
To achieve the above object, the present invention provides an occluder comprising:
The plugging support comprises an inner wall member, an outer wall member and a flow blocking object filled between the inner wall member and the outer wall member, wherein the inner wall member is connected with two ends of the outer wall member, the inner wall member surrounds a hollow channel which allows the through blocking object to pass through, the plugging support is in a lantern shape, a columnar shape or an irregular shape, and
And the two binding pieces are respectively coated at two ends of the plugging support along the length direction of the hollow channel and are used for binding the radial dimension of the hollow channel.
Optionally, the inner wall member extends in a direction approaching the outer wall member at least at one portion along a length direction of the hollow passage to form a radially extending passage communicating with the hollow passage.
Optionally, the axial cross section of the radially extending channel is bar-shaped, circular arc-shaped or t-shaped.
Optionally, the flow-blocking object comprises at least one of a fibrous membrane, a water-swellable foam material, and a hydrogel material.
Optionally, the inner wall member and the outer wall member are each formed by a single-layer, double-layer or multi-layer woven mesh, and the woven mesh is made of at least one of PPDO degradable filaments, PLA degradable filaments and nickel-titanium alloy filaments.
Optionally, the tie down is a film, cloth or wire.
Optionally, the film is at least one of PPDO film, PLA film, PCL film, PLCL film and PTFE film, and/or the cloth is elastic woven cloth woven by PA or PET elastic yarn.
Optionally, the filament is at least one of a PA or PET stretch filament, PPDO degradable filament, PLA degradable filament, PCL degradable filament, PLCL degradable filament.
Optionally, the flow inhibitor and the tie-down are both deposited to carry a material having antimicrobial efficacy in at least one of a dipping, a blended electrospinning or a hybrid synthesis.
Optionally, the material is at least one of triclosan, curcumin, chitosan and tetracycline hydrochloride.
The plugging device comprises a plugging support and two binding pieces, wherein the plugging support comprises an inner wall member, an outer wall member and a flow blocking object filled between the inner wall member and the outer wall member, the inner wall member is connected with two ends of the outer wall member, the inner wall member surrounds a hollow channel which allows the through blocking object to pass through, the plugging support is in a lantern shape, a columnar shape or an irregular shape, and the two binding pieces are respectively coated at two ends of the plugging support along the length direction of the hollow channel and are used for binding the radial dimension of the hollow channel. It can be understood that the structure of the plugging device provided by the invention is used for plugging and plugging a cavity with a penetrable barrier in the interior, and the plugging support is in a lantern shape, a column shape or an irregular shape, is suitable for the shape of a cavity or a sac, can effectively fill a gap, improves the plugging effect, and is beneficial to reducing the incidence rate of II-type internal leakage.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to the structures shown in these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic illustration of an embodiment of an occluder of the present invention;
FIG. 2 is a perspective view of one embodiment of an occluder of the present invention;
FIG. 3 is a cross-sectional view of one embodiment of an occluding device of the present invention;
FIG. 4 is a cross-sectional view of another embodiment of the occluding device of the present invention;
FIG. 5 is a cross-sectional view of yet another embodiment of an occluding device of the present invention;
FIG. 6 is a cross-sectional view of yet another embodiment of an occluding device of the present invention;
FIG. 7 is a diagram of an embodiment of an occluding device of the present invention showing the preparation of antimicrobial material in the form of a stopper and a tie down;
FIG. 8 is a block diagram of a constriction of one end of a wire bundle in an embodiment of the occluder of the present invention;
FIG. 9 is a schematic view of one end side of an occluder in accordance with one embodiment of the present invention;
fig. 10 is a cross-sectional view of one end side of an occluder in an embodiment of the present invention.
Reference numerals illustrate:
10. The device comprises a plugging bracket, a binding member, a 200-part covered stent, an 11-part inner wall member, a 12-part outer wall member, a 13-part choke, a 10 a-part hollow passage and a 10 b-part radial extending passage.
The achievement of the objects, functional features and advantages of the present invention will be further described with reference to the accompanying drawings, in conjunction with the embodiments.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without any inventive effort, are intended to be within the scope of the invention.
It should be noted that all directional indicators (such as up, down, left, right, front, and rear are used in the embodiments of the present invention) are merely for explaining the relative positional relationship, movement conditions, and the like between the components in a certain specific posture (as shown in the drawings), and if the specific posture is changed, the directional indicators are changed accordingly.
In the description of the present invention, unless explicitly stated or limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected, mechanically connected, electrically connected, directly connected, indirectly connected via an intervening medium, or in communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.
Furthermore, the description of "first," "second," etc. in this disclosure is for descriptive purposes only and is not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In addition, the meaning of "and/or" as it appears throughout is meant to include three side-by-side schemes, for example, "A and/or B", including the A scheme, or the B scheme, or the scheme where A and B meet at the same time. In addition, the technical solutions of the embodiments may be combined with each other, but it is necessary to base that the technical solutions can be realized by those skilled in the art, and when the technical solutions are contradictory or cannot be realized, the combination of the technical solutions should be considered to be absent and not within the scope of protection claimed in the present invention.
The invention proposes an occluder for the plugged closure of a cavity with a through barrier inside, without limitation.
Referring to fig. 1 to 6, in some embodiments of the present invention, the plugging device comprises a plugging bracket 10 and two binding pieces 20, wherein the plugging bracket 10 comprises an inner wall member 11, an outer wall member 12 and a flow blocking object 13 filled between the inner wall member 11 and the outer wall member 12, the inner wall member 11 is connected with two ends of the outer wall member 12, the inner wall member 11 and the outer wall member 12 can be in an integrated structure or assembled by more than two parts, the inner wall member 11 surrounds a hollow channel 10a which allows the penetration blocking object to pass through, the plugging bracket 10 is in a lantern shape, a column shape or an irregular shape, and the two binding pieces 20 are respectively coated on two ends of the plugging bracket 10 along the length direction of the hollow channel 10a and are used for binding the radial dimension of the hollow channel 10 a. As shown in fig. 1, the penetrating barrier may be a stent graft 200, and the shape, size, etc. of the penetrating barrier are not limited, and the hollow channel 10a should be designed to fit the specific penetrating barrier.
In this embodiment, the outer wall of the occluder, viewed from the side, may be in the form of a lantern, column or other irregular pattern that conforms to the shape of the lumen or capsular bag. Seen from the side of the inner wall of the occluder, it may be cylindrical, diamond-shaped or other irregular pattern that conforms to the shape of the penetrable barrier.
In this embodiment, the inner wall member 11 and the outer wall member 12 may be woven from degradable wires or wires with shape memory function, so that the occluder is suitable for use in a lumen or a pouch with a penetrating barrier.
The binding 20 may be a film, cloth, wire, or the like, and is made of a medical material, which is not particularly limited herein.
It can be understood that the structure of the plugging device provided by the invention is used for plugging and plugging a cavity with a penetrable barrier in the interior, and the plugging support 10 is lantern-shaped, columnar or irregular and is adapted to the shape of a cavity or a sac, so that the gap can be effectively filled, the plugging effect is improved, and the occurrence rate of II-type internal leakage is reduced.
To enhance the support stability of the occluding device 10 and further to enhance the compliance of the occluding device to accommodate more application environments, referring to figures 3 to 6, in some embodiments, the inner wall member 11 extends at least one portion along the length of the hollow channel 10a to a position proximal to the outer wall member 12 to form a radially extending channel 10b in communication with the hollow channel 10 a. In the present embodiment, the axial cross section of the radially extending channel 10b is bar-shaped, circular arc-shaped, or "t" shaped, etc., which is not limited thereto.
It should be noted that the outer vertical surface of the outer wall member 12 of the plugging device should keep continuity, and at least one part of the inner wall member 11 is abutted against the outer wall member 12, so as to play a role of supporting the outer wall member 12, and help to promote the supporting stability of the plugging stent 10. In addition, the protruding part of the inner wall member 11 forming the radial extension channel 10b increases the length of the inner wall member 11 after being axially straightened, and the length is adjusted to be the same as the length of the outer wall member 12 after being axially straightened, so that the plugging device can be ensured to select a sheath tube with small caliber as much as possible during interventional delivery.
In one embodiment, as shown in FIG. 3, the flow resistor 13 comprises at least one of a fibrous membrane, a water-swellable foam material, a hydrogel material, and the like. Therefore, the plugging device has better adaptability and is beneficial to improving the plugging effect.
Referring mainly to fig. 2, in an embodiment, the inner wall member 11 and the outer wall member 12 are each formed by a single-layer, double-layer or multi-layer woven mesh, and the woven mesh is made of at least one of PPDO degradable filaments, PLA degradable filaments and nitinol filaments. The setting can make this plugging device and chamber way or bag shape adaptation on the one hand, on the other hand can also solve the spare part of postoperative plugging device and leave over in the human body and produce the problem of harm.
To ensure that the cinch port is flexible, referring to fig. 1-6, in one embodiment the tie down 20 may preferably be a film, cloth or wire. Specifically, the film may be at least one of PPDO film, PLA film, PCL film, PLCL film, PTFE film, etc., the cloth may be elastic woven cloth made of PA or PET elastic yarn, etc., and the yarn may be at least one of PA or PET elastic yarn, PPDO degradable yarn, PLA degradable yarn, PCL degradable yarn, PLCL degradable yarn, etc.
The invention adopts the binding pieces 20 such as films, cloth or wires to bind the openings at the two ends of the plugging support 10, so that the radial dimension of the end part of the hollow channel 10a which is surrounded by the inner wall member 11 and is suitable for the penetrable barrier can be effectively limited, and the penetrable barrier with a certain proportion larger than the radial dimension of the hollow channel 10a in the unstressed natural state can be allowed to pass through.
In this embodiment, the length of the binding member 20 can be the same as the perimeter of the end face of the hollow channel 10a in the unstressed natural state, so that the binding member has a good binding effect and saves the material cost.
To further enhance the safety of the operation, referring to fig. 7, in an embodiment, the choke 13 and the binder 20 may carry the material with antibacterial effect by at least one deposition of soaking, blending electrostatic spinning or mixed synthesis.
In this embodiment, the material may be at least one of triclosan, curcumin, chitosan, tetracycline hydrochloride, and the like, which is not limited herein.
In one embodiment, the plugging stent 10 is a stent which is made by weaving 1 PPDO degradable filaments with the wire diameter of 3-0 in a cross direction one by one into a net shape with two through ends, and shaping the net shape at a high temperature of 70-110 ℃ through a loading die. As shown in fig. 2, the plugging stent 10 comprises an inner wall member 11 and an outer wall member 12, wherein the inner wall member 11 and the outer wall member 12 are formed by single-layer woven mesh. The plugging stent 10 is lantern-shaped as viewed from the side of the outer wall.
In this embodiment, the two axial ends of the plugging stent 10 should avoid retaining free degradable filaments, and after the degradable filaments are woven to the two axial ends, the degradable filaments are folded back towards the middle part far away from the two ends to be continuously woven in a one-to-one manner, and each folding back forms a closed loop at the two axial ends. As shown in fig. 8, after 1-5 degradable filaments of 3-0 wire diameter standard PPDO pass through the closed loop in bunching order, the two free filaments are tightened to enclose the hollow channel 10a adapting to the penetrable barrier on the inner wall of the bracket, and the radial dimension of the outlets at the two axial ends is between 90% -100% of the radial dimension of the penetrable barrier. The loose tows after tightening are knotted or continuously woven in a one-to-one manner towards the middle part far away from the two ends.
In this embodiment, the PLCL film is filled between the outer wall member 12 and the inner wall member 11 of the occlusion stent 10. The film is obtained by blending PLCL high molecular polymer and triclosan and then electrospinning by an electrospinning technology, and can provide antibacterial effect. Preferably, the thickness is in the range of 0.05mm to 0.15 mm. The film is stitched on the inner side of the outer wall by PPDO stitching lines with the diameter of 6-0 stitch lines, and the length of the stitched film in the axial direction of the plugging bracket 10 after being unfolded is 100% -150% of the length of the plugging bracket 10 after being pulled into a strip shape.
As shown in fig. 2, the inner wall member 11 of the stent 10 of the present embodiment protrudes toward the outer wall member 12 in the middle of the maximum radial length of the entire stent 10 to abut against the outer wall member 12. The protruding portion is circular arc-shaped when viewed from the side. The joint of the inner wall and the outer wall at the two end faces is taken as a clamping point, and the ratio of the length of the continuous outer wall member 12 after being straightened along the axial direction to the length of the inner wall member 11 with the convex part after being straightened along the axial direction is 100% -105%, and the length of the continuous outer wall member is not more than 5mm. The arrangement can maintain the shape of the outer wall of the plugging stent 10 to ensure the plugging effect, and can ensure that the plugging device can select a sheath tube with small caliber as much as possible during interventional delivery.
When in use, the occluder of the present embodiment requires interventional delivery into the affected area. The small-caliber metal tube penetrates through the hollow channel 10a of the plugging device, the plugging device is elongated in axial stretching, the closed rings at the two axial ends of the plugging device are hung on two padlock devices of the conveying device along the axial direction of the small-caliber metal tube, and the padlock devices, the elongated plugging device and the small-caliber metal tube in the elongated plugging device are accommodated in the large-caliber outer sheath tube. The guide wire penetrates into the small-caliber metal tube to guide and establish a conveying path. After reaching the target position, unlocking the distal padlock device of the delivery system, releasing the distal end of the occluder, gradually releasing the occluder proximally by withdrawing the sheath until the proximal padlock device of the delivery system is finally unlocked, withdrawing the delivery system, retaining the guide wire penetrating through the hollow channel 10a of the occluder, and guiding the implantation of the penetrating barrier such as the stent graft 200. The implemented state can be seen in fig. 1.
In another embodiment, the plugging stent 10 is a stent formed by braiding 144 nickel-titanium alloy wires with the diameter of 0.06mm on a netting device to form a net shape with two through ends, and shaping the net shape at a high temperature of 500-600 ℃ through a shaping die. The bracket comprises an inner wall member 11 and an outer wall member 12, wherein the inner wall member 11 and the outer wall member 12 are both formed by double-layer woven meshes. The side surface of the outer wall of the bracket is in a lantern shape.
As shown in fig. 6, in this embodiment, the inner wall of the plugging stent 10 protrudes in the middle section along the axial direction of the through passage toward the outer wall in a t shape, the width of the protruding mesh in the gap between the inner wall and the outer wall along the axial direction of the through passage is 2mm to 10mm, and the length of the mesh abutting against the outer wall along the axial direction of the through passage is 10mm to 40mm. This arrangement provides sufficient support to the outer wall of the stent to maintain the morphology so that the occluder can meet the occluding requirements of a fusiform abdominal aortic aneurysm endoluminal prosthesis.
As shown in fig. 9 and 10, the two ends of the plugging support 10 along the axial direction of the through passage in this embodiment are wrapped with elastic PLCL films, the lengths of the films on the outer wall and the inner wall from the end face are in the range of 2 mm-10 mm, so as to achieve a better binding effect, and two free edges of the films are continuously sewn on the inner wall and the outer wall at a position about 1mm from the edge by using non-degradable sutures with 6-0 wire diameter. The diameter of the expanded covered stent 200 implanted in the through channel is larger than that of the hollow channel 10a, so that the hollow channel 10a and the films coated at the two ends of the hollow channel are expanded and cannot be broken, and the reliability of the occluder is greatly improved.
In this embodiment, the pores between the inner and outer walls of the occluding stent 10 are filled with a water-swellable hydrogel material. The hydrogel material has two states of a dry state and a wet state which swells when meeting water, tetracycline hydrochloride is added into the solution for synthesizing the hydrogel, and the solution is volatilized and becomes powder to be granular, and the woven mesh is woven by filaments and a plurality of filaments, so that the density is high, the pores are small, and the dry state hydrogel fabric is arranged between the inner wall and the outer wall and cannot leak. After the occluder is implanted in a body, the dry hydrogel absorbs water to expand and fill the pores between the inner wall and the outer wall, so that the resistance of the occluder to blood is improved, and meanwhile, the antibacterial effect is provided.
The occluder of this embodiment requires interventional delivery into the site of the patient during use. The hollow channel 10a of the plugging device is penetrated by a small-caliber metal tube, the axial stretching plugging device is in a strip shape, the two axial ends of the plugging device are pressed by two pressing and locking devices of the conveying device along the axial direction of the small-caliber metal tube, and the pressing and locking devices, the strip-shaped plugging device and the small-caliber metal tube in the strip-shaped plugging device are accommodated in a large-caliber outer sheath tube. The guide wire penetrates into the small-caliber metal tube to guide and establish a conveying path. After reaching the target position, unlocking the distal end locking device of the delivery system, releasing the distal end of the occluder, gradually releasing the occluder towards the proximal end by withdrawing the outer sheath until the proximal end locking device of the delivery system is finally unlocked, withdrawing the delivery system, retaining the guide wire penetrating through the hollow channel 10a of the occluder, and guiding the implantation of the penetrating barrier such as the stent graft 200. The implemented state can be seen in fig. 1 and 6.
The foregoing description is only of the optional embodiments of the present invention, and is not intended to limit the scope of the invention, and all the equivalent structural changes made by the description of the present invention and the accompanying drawings or the direct/indirect application in other related technical fields are included in the scope of the invention.

Claims (8)

Translated fromChinese
1.一种封堵器,其特征在于,包括:1. An occluder, comprising:封堵支架,包括内壁构件、外壁构件及填充于所述内壁构件与所述外壁构件之间的阻流物,所述内壁构件与所述外壁构件的两端相连接,所述内壁构件围绕形成允许贯通性阻隔物通过的中空通道,所述封堵支架呈灯笼状、柱状或不规则形状;所述内壁构件在沿所述中空通道的长度方向上至少一个部位向靠近所述外壁构件的方向延伸形成与所述中空通道连通的径向延伸通道;以及A blocking bracket, comprising an inner wall member, an outer wall member and a flow blocker filled between the inner wall member and the outer wall member, wherein the inner wall member is connected to both ends of the outer wall member, the inner wall member surrounds and forms a hollow channel allowing a through-blocker to pass through, and the blocking bracket is in a lantern shape, a columnar shape or an irregular shape; the inner wall member extends at least one portion along the length direction of the hollow channel toward the direction close to the outer wall member to form a radially extending channel communicating with the hollow channel; and两束缚件,分别包覆于所述封堵支架沿所述中空通道长度方向的两端,用于束缚所述中空通道的径向尺寸;所述束缚件为膜、布或丝。Two restraining members are respectively covered on the two ends of the blocking stent along the length direction of the hollow channel, and are used to restrain the radial dimension of the hollow channel; the restraining members are films, cloths or silks.2.如权利要求1所述的封堵器,其特征在于,所述径向延伸通道的轴向截面呈条形、圆弧形或“丁”字形。2. The occluder according to claim 1, characterized in that the axial cross-section of the radially extending channel is strip-shaped, arc-shaped or T-shaped.3.如权利要求1所述的封堵器,其特征在于,所述阻流物包括纤维膜、吸水可膨胀泡沫材料和水凝胶材料中的至少一种。3. The occluder according to claim 1, characterized in that the flow barrier comprises at least one of a fiber membrane, a water-absorbing expandable foam material and a hydrogel material.4.如权利要求1所述的封堵器,其特征在于,所述内壁构件和所述外壁构件均由单层、双层或多层编织网构成,所述编织网的材质为PPDO可降解丝、PLA可降解丝和镍钛合金丝中的至少一种。4. The occluder according to claim 1, characterized in that the inner wall component and the outer wall component are both composed of a single-layer, double-layer or multi-layer woven mesh, and the material of the woven mesh is at least one of PPDO degradable wire, PLA degradable wire and nickel-titanium alloy wire.5.如权利要求1所述的封堵器,其特征在于,所述膜为PPDO薄膜、PLA薄膜、PCL薄膜、PLCL薄膜和PTFE薄膜中的至少一种;和/或所述布为PA或PET弹丝织造而成的具有弹性的织造布。5. The occluder according to claim 1, characterized in that the membrane is at least one of a PPDO film, a PLA film, a PCL film, a PLCL film and a PTFE film; and/or the cloth is an elastic woven cloth woven from PA or PET elastic yarn.6.如权利要求1所述的封堵器,其特征在于,所述丝为PA或PET弹丝、PPDO可降解丝、PLA可降解丝、PCL可降解丝、PLCL可降解丝中的至少一种。6. The occluder according to claim 1, characterized in that the wire is at least one of PA or PET elastic wire, PPDO degradable wire, PLA degradable wire, PCL degradable wire, and PLCL degradable wire.7.如权利要求1所述的封堵器,其特征在于,所述阻流物和所述束缚件均以浸泡、共混静电纺或混合合成中至少一种沉积的方式携带具有抗菌功效的物料。7. The occluder according to claim 1, characterized in that the flow blocker and the restraining member both carry the material with antibacterial efficacy by at least one deposition method selected from the group consisting of immersion, co-blending electrospinning, or mixed synthesis.8.如权利要求7所述的封堵器,其特征在于,所述物料为三氯生、姜黄色素、壳聚糖及盐酸四环素中的至少一种。8. The occluder according to claim 7, characterized in that the material is at least one of triclosan, curcumin, chitosan and tetracycline hydrochloride.
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