Left auricle plugging device

Abstract

The application relates to a left atrial appendage occluder comprising: an expandable frame capable of switching between a compressed state and an expanded state; a film disposed along at least a portion of an outer surface of the expandable frame; the connecting unit is arranged at the near end of the expandable frame and can be connected with and disconnected from the conveying system; and an anticoagulant coating disposed only on at least a portion of the outer surface of the covering film. The risk that thrombus is formed on the surface of the left atrial appendage occluder can be reduced, and the endothelialization process is accelerated.

Description

Technical Field

[0001] The present application relates to the field of medical devices, and in particular to a left atrial appendage occluder for single-sided anticoagulation. Background Art

[0002] Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and thromboembolism is the main cause of death in patients with AF. Clinical data show that more than 90% of thrombosis in patients with AF is related to the left atrial appendage. At present, prevention of thromboembolism by left atrial appendage occlusion has become a mature method. After the implantation of the left atrial appendage occluder, it takes at least 4-6 weeks to achieve complete endothelialization. Therefore, continuous anticoagulant drug treatment is required during this process. Coating an anticoagulant coating on the surface of the left atrial appendage occluder can effectively reduce the risk of coagulation and reduce the risk of some complications. Among the many complications of left atrial appendage occlusion, thrombosis on the surface of the device is a very common complication in the long term after surgery. Its causes are complex and diverse, and are related to multiple factors such as the patient's own coagulation disease, postoperative anticoagulant drug conditions, the shape and occlusion of the left atrial appendage and the occluder, and there is a very high risk of embolism after detachment. Therefore, the formation of thrombus seriously affects the safety of device use, and anticoagulant treatment of the surface of medical devices that are in contact with blood for a long time is very necessary.

[0003] At present, the main strategy for dealing with the problem of anticoagulation in clinical practice is to use systemic administration of antibiotics and anticoagulants for auxiliary treatment. However, long-term use of antibiotics and anticoagulants will inevitably cause a series of side effects. For example, antibiotic resistance and thrombocytopenia, and even bleeding. However, most of the surface modification methods reported so far have complex processes, require repeated surface pretreatment, involve toxic chemical reagents, and other issues, and their safety is worrying. Therefore, it is necessary to achieve anticoagulation treatment on the surface of the device in a safer and simpler way. Summary of the invention

[0004] In view of this, the purpose of the present application is to provide a left atrial appendage occluder to solve the problem of blood coagulation on the surface of medical devices which is relatively common in the existing related technologies.

[0005] To achieve the above objectives, the present application provides a left atrial appendage occluder, which comprises:

[0006] an expandable frame, the expandable frame being capable of transitioning between a compressed state and an expanded state;

[0007] a coating disposed along at least a portion of an outer surface of the expandable frame;

[0008] a connection unit disposed at a proximal end of the expandable frame and capable of connecting to and disconnecting from a delivery system; and

[0009] The anti-coagulation coating only covers at least a portion of the outer surface of the coating.

[0010] Optionally, the coating includes a fiber bundle, the fiber bundle includes a plurality of fiber filaments, and the anti-coagulation coating covers the exposed surfaces of the outer fiber filaments in the fiber bundle and the gaps between the outer fiber filaments.

[0011] Optionally, the material of the coating is at least one of polyethylene, polypropylene, polyester, polyurethane, and polyethylene terephthalate.

[0012] Optionally, the pore size of the coating is 50 μm to 300 μm.

[0013] Optionally, the area of ​​the film other than that covered by the anticoagulant coating is a non-anticoagulant area, and the non-anticoagulant area includes the non-anticoagulant coating and / or the exposed portion of the film, and the hydrophobicity of the non-anticoagulant coating is inferior to that of the film.

[0014] Optionally, the non-anticoagulant coating has at least one of the following features:

[0015] The non-anticoagulant coating comprises at least one of polyacrylamide, polyvinyl alcohol, polyvinyl pyrrolidone, polyetherimide, polyester, and polyurethane;

[0016] The thickness of the non-anticoagulant coating is less than or equal to 0.1 μm;

[0017] The surface contact angle of the non-anticoagulant coating is 45° to 90°.

[0018] Optionally, the anticoagulant coating has at least one of the following features:

[0019] The anticoagulation coating has a better hydrophobicity than the covering film;

[0020] The thickness of the anticoagulant coating is less than or equal to 1 μm;

[0021] The surface contact angle of the anticoagulant coating is 100° to 130°;

[0022] The friction coefficient of the anticoagulant coating is smaller than the friction coefficient of the non-anticoagulant area on the coating;

[0023] The anticoagulant coating includes a fluoropolymer.

[0024] Optionally, the anticoagulation coating includes at least one of polytetrafluoroethylene, polyvinylidene fluoride, fluorinated ethylene propylene copolymer, and polyvinylidene fluoride and hexafluoropropylene copolymer.

[0025] Optionally, the fluorine content of the anticoagulant coating is 8 to 80 μg / cm 2 , and / or, the friction coefficient of the fluoropolymer does not exceed 0.1.

[0026] Optionally, the anti-coagulation coating is not provided on the surface of the connecting unit and the surface of the expandable frame, and / or the coating has a proximal portion and a distal portion which are axially arranged from the proximal end to the distal end of the expandable frame, the proximal portion extends from the proximal end of the expandable frame and covers to the maximum outer diameter position of the expandable frame, and the anti-coagulation coating covers the entire outer surface of the proximal portion and extends beyond the maximum outer diameter of the expandable frame.

[0027] The left atrial appendage occluder provided in the present application has at least the following beneficial effects:

[0028] The left atrial appendage occluder provided above includes: an expandable frame, which can be converted between a compressed state and an expanded state; a coating, which is arranged along at least a portion of the outer surface of the expandable frame; a connecting unit, which is arranged at the proximal end of the expandable frame and can be connected to and disconnected from the delivery system; and an anti-coagulation coating, which only covers at least a portion of the outer surface of the coating.

[0029] With such a configuration, on the one hand, an anticoagulant coating is provided on at least a portion of the outer surface of the coating, which can effectively inhibit the formation of thrombus and thus accelerate the process of endothelialization. On the other hand, the hydrophobic surface provided by the anticoagulant coating can also effectively avoid tissue adhesion during implantation, improve operability, and reduce damage caused by operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Those skilled in the art will appreciate that the drawings are provided for a better understanding of the present application and do not constitute any limitation on the scope of the present application.

[0031] Figure 1 It is a schematic structural diagram of a left atrial appendage occluder according to an embodiment of the present application;

[0032] Figure 2 This is a schematic diagram of the structure of the single-sided anticoagulation film according to an embodiment of the present application;

[0033] Figure 3 This is a schematic cross-sectional view of a braided mesh coating with an anti-coagulation coating and its fiber bundle according to an embodiment of the present application;

[0034] Figure 4 is a cross-sectional view of a fiber bundle according to an embodiment of the present application;

[0035] Figure 5It is a schematic structural diagram of the left atrial appendage occluder described in Example 1 of the present application;

[0036] Figure 6 is a schematic structural diagram of the left atrial appendage occluder described in Example 2 of the present application;

[0037] Figure 7 It is a schematic diagram of the structure of the left atrial appendage occluder described in Example 3 of the present application.

[0038] In the attached figure:

[0039] 1-expandable frame; 11-distal part; 2-membrane; 201-fiber bundle; 202-fiber filament; 21-outer surface of the membrane; 22-inner surface of the membrane; 210-proximal part; 220-distal part; 3-connecting unit; 4-anticoagulant coating; 41-PVDF-HFP coating; 42-PTFE coating; 43-FEP hydrophobic coating; 5-non-anticoagulant area; 51-PAM amphiphilic coating. DETAILED DESCRIPTION

[0040] The following describes the implementation of the present application through specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the content disclosed in this specification. The present application can also be implemented or applied through other different specific implementations, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present application. It should be noted that the illustrations provided in the present embodiment only illustrate the basic concept of the present application in a schematic manner, so the diagram only shows the components related to the present application rather than drawing according to the number, shape and size of the components during actual implementation. The type, quantity and proportion of each component during actual implementation can be a random change, and its component layout type may also be more complicated.

[0041] In addition, each embodiment of the following description has one or more technical features, but this does not mean that the user of the present invention must implement all the technical features in any embodiment at the same time, or can only implement part or all of the technical features in different embodiments separately. In other words, under the premise that implementation is possible, those skilled in the art can selectively implement part or all of the technical features in any embodiment according to the disclosure of the present application and according to the design specifications or implementation requirements, or selectively implement a combination of part or all of the technical features in multiple embodiments, thereby increasing the flexibility of the implementation of the present application.

[0042] As used in this specification, the singular forms "one", "an", and "the" include plural objects, the plural form "a plurality" includes more than two objects, unless the content clearly indicates otherwise, and "several" is used to indicate an indefinite quantity. As used in this specification, the term "or" is usually used to include the meaning of "and / or", unless the content clearly indicates otherwise, and the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection. It can be a mechanical connection, a direct connection, or an indirect connection through an intermediate medium, and it can be the internal connection of two elements or the interaction relationship between two elements. Relational terms such as the terms "first", "second", etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations, nor do they indicate or imply relative importance or implicitly indicate the number of technical features indicated. It should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "axial", "radial", "circumferential" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present application. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to specific circumstances.

[0043] In this application document, the term "axial" used generally refers to the direction along the central axis of the left atrial appendage occluder, "circumferential" refers to the direction around the central axis of the left atrial appendage occluder, and "radial" generally refers to the diameter direction of the left atrial appendage occluder, that is, the direction perpendicular to the axial direction; the term "outer side" generally refers to the direction away from the central axis of the left atrial appendage occluder, and the "inner side" refers to the direction close to the central axis of the left atrial appendage occluder; the terms "distal end" and "proximal end" are described based on the relative orientation and relative position of the various components and elements of the left atrial appendage occluder. Although non-restrictive, the "distal end" generally refers to the end of the left atrial appendage occluder that first enters the patient's body during normal use, and the "proximal end" is the end opposite to the "distal end", that is, the end of the left atrial appendage occluder closer to the operator; the term "not more than" means less than or equal to.

[0044] The core of this application is to provide a left atrial appendage occluder to solve the common problem of blood coagulation on the surface of medical devices in the existing related technologies.

[0045] Figure 1 A schematic structural diagram of a left atrial appendage occluder with a coating 2 is shown. Figure 1 The connection unit 3 is also magnified and highlighted by the detail A. Specifically, the left atrial appendage occluder may include: an expandable frame 1; a coating 2 covering the expandable frame 1; and a connection unit 3 that can be connected to and disconnected from a delivery system.

[0046] The connection unit 3 is disposed at the proximal end of the expandable frame 1 and is configured to be releasably connected to the distal end of the delivery system. In some cases, the connection unit 3 may include a threaded structure that is threadedly connected to the distal end of the delivery system, and the threaded structure has an internal thread. However, this is not restrictive. In practice, the connection unit 3 can be connected to the distal end of the delivery system by various means, as long as the connection can be released after the connection.

[0047] The expandable frame 1 is preferably a self-expanding structure and can be made of various materials that can achieve self-expansion. Preferably, the expandable frame 1 is made of nickel-titanium alloy. Optionally, the expandable frame 1 is formed by cutting a nickel-titanium tube. The expandable frame 1 has a compressed state and an expanded state, and can be freely switched between the compressed state and the expanded state. For example, in some cases, during the delivery of the left atrial appendage occluder via a delivery system, the expandable frame 1 is in a compressed state, and once the expandable frame 1 is pushed out of the delivery system and released, the expandable frame 1 expands autonomously to the expanded state (i.e., the use form).

[0048] The shape of the expandable frame 1 is not limited. Here, according to the description in the figure, the expandable frame 1 is in the shape of a mesh cage with an open distal end and a closed proximal end, that is, the shape of the entire left atrial appendage occluder is similar to a hemispherical plug, and this structure is suitable for the shape of the left atrial appendage opening of most patients. Of course, the shape of the expandable frame 1 can be adjusted and changed according to the usage scenario, and therefore, is not limited to the structural form described in the figure.

[0049] At least part of the outer surface of the expandable frame 1 is covered by the coating 2 to form a blocking disk surface, which can be used to isolate the blood flow. In some embodiments, the coating 2 can prevent thrombus (i.e., blood clots, etc.) from passing through the coating 2 and leaving the left atrial appendage to enter the blood flow. In some embodiments, the coating 2 can also promote endothelial cell growth, reduce the risk of restenosis, etc.

[0050] Specifically, the coating 2 is disposed along at least a portion of the outer surface of the expandable frame 1 to cover at least a portion of the outer surface of the expandable frame 1. For example, in some embodiments, the coating 2 is disposed along a portion of the outer surface of the expandable frame 1, so that the distal portion 11 of the expandable frame 1 is exposed to the outside of the coating 2 to form a skirt. The skirt is generally bent inward to prevent the skirt of the expandable frame 1 from causing damage to the tissue structure during and after implantation. However, it should be understood that in other application scenarios, the coating 2 can extend and cover along the outer surface of the expandable frame 1 to any extent, such as extending to cover almost the entire outer surface of the expandable frame 1.

[0051] The coating 2 is, for example, a knitted material, fiber, fabric, nonwoven, braided or other suitable structure, preferably a fiber mesh braided film. The coating 2 can be made of a suitable material, such as polyethylene, polypropylene, polyester, polyurethane, polyethylene terephthalate or other materials, and the coating 2 can include a material or a combination of multiple materials.

[0052] The height of the coating 2 may not exceed 2 / 3 of the total height of the expandable frame 1, but is not limited thereto. The total height of the expandable frame 1 refers to the distance from the proximal end to the distal end of the expandable frame 1. The height of the coating 2 refers to the distance covered by the coating 2 extending from the proximal end to the distal end of the expandable frame 1.

[0053] It should also be understood that although the film 2 itself has good mechanical properties, biological stability and safety, its anticoagulant effect is generally poor, so it is necessary to select a material with better hydrophobicity for anticoagulant treatment.

[0054] refer to Figures 1 to 4 , the anticoagulant coating 4 only covers at least a portion of the outer surface 21 of the coating 2, and the areas of the coating 2 other than those covered with the anticoagulant coating 4 are all non-anticoagulant areas 5. It is worth noting that the expandable frame 1 and the connecting unit 3 may basically be free of the anticoagulant coating 4, or in other words, the anticoagulant coating 4 is not provided on the surface of the metal part. Specifically, the connecting unit 3 usually does not need to be provided with the coating 2, so the anticoagulant coating 4 does not need to be provided at the connecting unit 3, otherwise the anticoagulant coating 4 is prone to the risk of falling off. The expandable frame 1 is mainly responsible for providing support. If a polymer coating is provided on the expandable frame 1, the polymer coating is more likely to fall off during the process of pressing and releasing the instrument. Therefore, the anticoagulation and non-anticoagulant described in this application are with respect to the coating 2.

[0055] With such a configuration, on the one hand, the formation of blood clots can be effectively inhibited through the anticoagulant coating 4, thereby accelerating the process of endothelialization, accelerating the blocking process, and reducing self-reaction. On the other hand, the hydrophobic outer surface provided by the anticoagulant coating 4 can also effectively avoid tissue adhesion during the implantation process, improve operability, and reduce damage caused by operation.

[0056] It should be understood that at least the anticoagulant coating 4 needs to be provided on the portion of the outer surface 21 of the coating 2 that is in direct contact with the blood; and the interior of most medical devices has little to do with thrombus and surface endothelialization, so the inner surface 22 of the coating 2 does not need anticoagulation treatment. This single-sided anticoagulation can not only reduce materials and costs, but also help to fix the entire left atrial appendage occluder. Here, when the inner surface 22 of the coating 2 is not anticoagulated, after the left atrial appendage occluder is implanted in the body, a blood clot filling the interior of the left atrial appendage occluder can be formed in a short time, which can help the device to be quickly fixed in the target position, making the entire left atrial appendage occluder more secure.

[0057] The anticoagulant coating 4 can be applied to the outer surface 21 of the coating 2 using a suitable method, such as ultrasonic spraying, physical / chemical vapor deposition, plasma coating, atomization spraying, etc. Ultrasonic spraying is preferred, and the coating effect is better. The anticoagulant coating 4 can be applied before the coating 2 is set on the expandable frame 1, or after the coating 2 is set on the expandable frame 1. In short, the anticoagulant coating 4 does not coat the entire coating 2, but can effectively coat at least part of the outer surface 21 of the coating 2, and is basically uniform along the coating 2, and finally can better achieve single-sided anticoagulation.

[0058] Specifically in this embodiment, the coating 2 is a fiber mesh woven membrane, wherein the anti-coagulation coating 4 only covers the exposed surface of the outer fiber filaments 202 in the fiber bundle 201, and the gaps between the outer fiber filaments 202 and the fiber filaments 202. Figure 4 shown. Figure 4 The dotted line in the figure emphasizes the range of the anticoagulant coating 4 covering the surface of the outer fiber filaments 202 of the fiber bundle 201. Here, the fiber filaments 202 provided with the anticoagulant coating 4 and those not provided with the anticoagulant coating 4 are distinguished under the microscopic morphology, that is, it is clarified that after the fiber mesh braided membrane covers the outer surface of the expandable frame 1, the inner fiber filaments 202 and the fiber filaments 202 whose surfaces are not exposed are not coated with the anticoagulant coating 4.

[0059] Combined with Figure 3When the coating 2 is a fiber mesh braided membrane, it includes one or more fiber bundles 201. Each fiber bundle 201 may include a suitable number of fiber filaments 202. The fiber filaments 202 are separate filaments. After a suitable number of fiber filaments 202 are wound to form a fiber bundle 201, one or more fiber bundles 201 are formed into a fiber mesh structure of the coating 2, for example, by braiding, knitting, weaving, electrospinning or other methods.

[0060] Those skilled in the art should know that the anticoagulant coating 4 does not encapsulate every fiber filament 202 in the fiber bundle 201. In addition, the anticoagulant coating 4 is only arranged on the outside of the fiber bundle 201, and does not pass through the fiber bundle 201 to reach the inner area of ​​the fiber bundle 201, so the inner fiber filament 202 does not have the anticoagulant coating 4, thereby achieving single-sided anticoagulation. At the same time, the anticoagulant coating 4 will not block the fiber bundle 201 on the coating 2 and the mesh formed by the interweaving of the fiber bundle 201, and will not affect the performance of the coating 2 itself, so that the coating 2 can maintain the original hole structure (i.e., mesh).

[0061] In addition, the mechanical support of the membrane 2 is good when it is a fiber mesh braided membrane, and the mesh of the fiber mesh braided membrane allows blood to flow through, but can prevent thrombus from passing through. Therefore, the membrane 2 itself is a porous structure. Preferably, the pore size of the membrane 2 is 50μm to 300μm; this pore size is conducive to blood passing through the membrane 2, but can effectively prevent thrombus from passing through.

[0062] Preferably, the anticoagulant coating 4 is applied to the outer surface 21 of the coating 2 by ultrasonic spraying. It may include dissolving the anticoagulant polymer material used for the anticoagulant coating 4 in a suitable solvent to form an anticoagulant solution, and then ultrasonically spraying the anticoagulant solution to the outer surface 21 of the coating 2. The ultrasonic spraying may be performed before or after the coating 2 is arranged on the expandable frame 1. Preferably, the ultrasonic spraying is performed after the coating 2 is arranged on the expandable frame 1, so that the spraying process is more controllable and the spraying effect is better. In addition, the process stability of ultrasonic spraying is good, and it is easy to adjust and control the process parameters, so that the process is more stable and reliable. The advantages of ultrasonic spraying are also that less materials are used and the cost is low.

[0063] The thickness of the anticoagulant coating 4 should not be too large or too small. Preferably, the thickness of the anticoagulant coating 4 is less than or equal to 1 μm; this thickness can ensure the anticoagulant effect of the anticoagulant coating 4, and is not easy to fall off, with better safety and effectiveness, and does not affect the sheathing of the occluder.

[0064] Furthermore, the anticoagulation effect can be improved by controlling the surface contact angle of the anticoagulation coating 4. According to research, the surface contact angle of the anticoagulation coating 4 is preferably 100° to 130°, such as 100°, 110°, 120°, 130°, etc. This surface contact angle is beneficial for both efficient anticoagulation and better promotion of endothelialization.

[0065] As described above, at least the portion of the outer surface 21 of the coating 2 that is in direct contact with the blood needs to be provided with an anticoagulant coating 4. Therefore, the anticoagulant coating 4 needs to be provided at least on the occluding disk surface (i.e. Figure 1 The position of the middle section line) can cover the outer surface of the entire coating 2 at most.

[0066] Please refer to Figure 1 In this embodiment, the coating 2 has a proximal portion 210 and a distal portion 220 which are arranged axially from the proximal end to the distal end of the expandable frame 1; the proximal portion 210 and the distal portion 220 do not overlap, and both surround and cover the expandable frame 1, so that the coating 2 covers the expandable frame 1 on the circumferential side of the expandable frame 1. The entire outer surface of the proximal portion 210 is covered with an anticoagulant coating 4, while the entire outer surface of the distal portion 220 is a non-anticoagulant area 5. The proximal portion 210 needs to extend from the proximal end of the expandable frame 1 and cover the maximum outer diameter (Dmax) position of the expandable frame 1. The distal portion 220 extends from the junction with the proximal portion 210 to cover the distal end of the coating 2, that is, the area of ​​the coating 2 except the proximal portion 210 is the distal portion 220.

[0067] The distal part 220 is an anchoring area, which needs to fit with the wall of the left atrial appendage to ensure the stability of the occluder after implantation in the left atrial appendage, so that the occluder can stably and effectively block the left atrial appendage. The proximal part 210 is basically not used for anchoring support. It faces the atrial side, is positioned at the entrance of the left atrial appendage, contacts the blood, and does not need to be anchored.

[0068] Preferably, the anticoagulant coating 4 extends from the proximal end of the expandable frame 1 and covers the maximum outer diameter (Dmax) of the expandable frame 1. For example, the anticoagulant coating 4 extends beyond the maximum outer diameter (Dmax) of the expandable frame 1, so that the anticoagulant coating 4 can fully cover the maximum outer diameter of the expandable frame 1. The distance exceeding the maximum outer diameter can be 3 mm, 5 mm or other sizes. The areas of the coating 2 other than those covered with the anticoagulant coating 4 are all non-anticoagulant areas 5.

[0069] It should also be understood that the left atrial appendage occluder often needs to be collected or withdrawn from the delivery sheath during the delivery process or the withdrawal process. When entering and exiting the sheath, the presence of the anticoagulant coating 4 is also conducive to reducing the friction between the coating 2 and the sheath, so that the coating 2 at the maximum outer diameter (Dmax) position on the expandable frame 1 has a smaller sheathing force, especially when the anticoagulant coating 4 adopts a fluorine-containing polymer coating, a lower surface friction coefficient can be obtained, and the sheathing force is smaller. In addition, after the left atrial appendage occluder is implanted in the body, the friction between the coating 2 and the left atrial appendage wall can be increased by the non-anticoagulant area 5 on the coating 2, thereby enhancing the stability of the occluder after implantation.

[0070] Therefore, the anticoagulant region and the non-anticoagulant region 5 of the coating 2 can be used to balance the sheathing performance and the anchoring performance, and to achieve low sheathing force and high anchoring force without sacrificing other aspects of the device performance, and to increase the safety of the occluder. In the present application, although the maximum outer diameter position of the expandable frame 1 is covered by the anticoagulant coating 4, the fixation of the occluder is mainly guaranteed by the anchoring of the non-anticoagulant region 5, so the anticoagulant coating 4 will not affect the stability of the entire occluder.

[0071] Furthermore, the non-anticoagulant region 5 can be directly a coating material without any coating, that is, the portion of the coating 2 not provided with the anticoagulant coating 4 is exposed to directly form the non-anticoagulant region 5. In addition, the exposed portion of the coating 2 can be further provided with a non-anticoagulant coating, and the non-anticoagulant coating forms the non-anticoagulant region 5. Therefore, the non-anticoagulant region 5 can include both the non-anticoagulant coating and the exposed portion of the coating 2.

[0072] It should be understood that the non-anticoagulant coating is composed of a non-anticoagulant polymer material, which has fewer hydrophobic groups and poor hydrophobicity. Therefore, in general, the hydrophobicity of the non-anticoagulant coating is inferior to that of the coating 2, which is conducive to rapid coagulation inside the occluder and filling the internal area of ​​the occluder. In addition, the non-anticoagulant coating can also be made of a non-anticoagulant polymer material with a hydrophilic group.

[0073] The non-anticoagulant coating may be covered on the inner surface 22 of the coating 2, or on the outer surface 21 of the coating 2. When the non-anticoagulant coating is covered on the outer surface 21 of the coating 2, the friction coefficient of the non-coagulant region 5 on the outer surface of the coating 2 may be increased, thereby increasing the friction between the coating 2 and the left atrial appendage wall, thereby enhancing the stability of the occluder after implantation.

[0074] Optionally, the non-anticoagulant coating comprises polyacrylamide (PAM), polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polyetherimide (PEI), polyester, polyurethane (PU) or other materials, and the non-anticoagulant coating may comprise one material or a combination of multiple materials thereof.

[0075] Optionally, the thickness of the non-anticoagulant coating is less than or equal to 0.1 μm. Optionally, the surface contact angle of the non-anticoagulant coating is 45° to 90°, such as 45°, 50°, 55°, 60°, 65°, 70°, 75°, 80°, 85° or 90°.

[0076] In addition, the anti-coagulation coating 4 can be a single polymer coating or a combined coating of at least two polymers.

[0077] In some embodiments, the anticoagulation coating 4 includes a fluorine-containing polymer, specifically a combination of one or more fluorine-containing polymers. When the anticoagulation coating 4 includes a fluorine-containing polymer, the surface of the anticoagulation coating 4 generally exhibits a high hydrophobic property due to the presence of fluorine groups.

[0078] Specifically, the hydrophobic surface of the anticoagulant coating 4 makes it difficult for fibrinogen and platelets that induce thrombosis to adhere to the surface of the coating 2, and thus will not cause a coagulation reaction, thereby achieving the anticoagulant effect; at the same time, the hydrophobic properties of the fluorine group allow albumin to be firmly adsorbed on the surface of the anticoagulant coating 4, promoting the migration and crawling of endothelial cells, thereby accelerating the endothelialization of the material surface to effectively reduce complications; the fluorine-containing polymer also has good film-forming properties, which can make the anticoagulant coating 4 uniformly coated on the outer surface 21 of the coating 2 and quickly solidify into a film, and firmly bonded to the coating 2, not easy to fall off, and will not form particles falling, and has good biological safety and stability. Of course, the fluorine-containing polymer also has good biocompatibility and stable properties, and can play a long-term and stable anticoagulant effect. Therefore, when conducting anticoagulant treatment, there is no need to perform antibiotic and anticoagulant drug auxiliary instructions through systemic administration, which can avoid a series of side effects caused by long-term medication.

[0079] Optionally, the anticoagulant coating 4 includes polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), fluorinated ethylene propylene copolymer (FEP), polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP), etc., or other fluorinated polymers with similar properties, and may include a combination of one or more of these fluorinated polymers. Preferably, the anticoagulant coating 4 is composed of polyvinylidene fluoride-hexafluoropropylene copolymer, and the effectiveness and safety of such anticoagulant coating 4 are relatively better, not easy to fall off, and have a good long-term anticoagulant effect.

[0080] Preferably, the friction coefficient of the anticoagulant coating 4 is less than the friction coefficient of the non-anticoagulant area 5 on the coating 2 to reduce the sheathing force of the occluder. More preferably, the friction coefficient of the anticoagulant coating 4 does not exceed 0.3, so that it can reduce friction while playing an anticoagulant role. For example, when a fluoropolymer coating is used, the friction coefficient of the fluoropolymer does not exceed 0.1 to achieve the best effect.

[0081] Preferably, the fluorine content of the anticoagulant coating 4 is 8 to 80 μg / cm 2 Preferably, the fluorine content is 16.4 μg / cm 2 .

[0082] The anticoagulation coating 4 may also be made of a polymer having a higher hydrophobicity than the coating 2. For example, the polymer used as the anticoagulation coating 4 may be polystyrene, polydimethylsiloxane or other materials. In practice, the anticoagulation coating 4 may include one polymer or a combination of multiple polymers.

[0083] The present application is further described below through the following specific examples. Of course, the following specific examples are only used for illustration and are not used to limit the present application in any way.

[0084] Embodiment 1

[0085] Please refer to Figure 5 In the first embodiment of the present application, an expandable frame 1 formed by cutting a nickel-titanium tube is provided, and a portion of the outer surface of the expandable frame 1 is covered with a layer of PET knitted film 2.

[0086] The proximal portion 210 of the coating 2 is a sealing disk surface. At this time, the outer surface of the proximal portion 210 is covered with a PVDF-HFP coating 41, for example by ultrasonic spraying, to form an anti-coagulation area; and except for the surface of the coating 2 provided with the PVDF-HFP coating 41, the other surfaces are non-anticoagulation areas 5, and the non-anticoagulation area 5 is directly a PET knitted coating material.

[0087] In a separate contact angle test, the contact angles of the anticoagulation area and the non-anticoagulation area of ​​the PET knitted coating relative to pure water were tested. The test results are shown in Table 1 below.

[0088] Table 1 Contact angles of anticoagulated blood area and non-anticoagulated blood (°)

[0089] area Contact angle (°) PVDF-HFP anticoagulation area 101.99 Uncoated non-anticoagulant area 78.24

[0090] It can be seen from Table 1 that the contact angle of the PVDF-HFP anticoagulation area is greater than 90°, which indicates that the PVDF-HFP coating 41 has good hydrophobicity, while the contact angle of the uncoated non-anticoagulation area is less than 90°, indicating that the hydrophobicity of the uncoated non-anticoagulation area is worse than that of the PVDF-HFP anticoagulation area.

[0091] In another separate anticoagulation test, the coagulation performance of the anticoagulation area and the non-anticoagulation area of ​​the PET knitted film was characterized by whole blood immersion using adult pig arterial blood (without heparin). The results are shown in Table 2 below.

[0092] Table 2 Coagulation time of anticoagulated blood and non-anticoagulated blood (min)

[0093] area Coagulation time (min) PVDF-HFP anticoagulation area 35min Uncoated non-anticoagulant area 10min

[0094] According to Table 2, the PVDF-HFP anticoagulation area and the uncoated non-anticoagulation area show obvious differences in coagulation time, which confirms that the PVDF-HFP anticoagulation coating can effectively achieve a single-sided anticoagulation effect, and the anticoagulation effect is equivalent to the double-sided anticoagulation effect of the coating.

[0095] Embodiment 2

[0096] Please refer to Figure 6 In the second embodiment, an expandable frame 1 formed by cutting a nickel-titanium tube is provided, and a portion of the outer surface of the expandable frame 1 is covered with a layer of PET knitted film 2.

[0097] The proximal portion 210 of the coating 2 is still a sealing disk surface, and thus, the outer surface of the proximal portion 210 is covered with a PTFE coating 42, for example by ultrasonic spraying, to form an anti-coagulation area; and except for the surface with the PTFE coating 42, the other surfaces of the coating 2 are non-anticoagulation areas 5.

[0098] In a separate contact angle test, the contact angles of the anticoagulation area and the non-anticoagulation area of ​​the PET knitted film relative to pure water were tested. The test results are shown in Table 3 below.

[0099] Table 3 Contact angles of anticoagulated blood area and non-anticoagulated blood (°)

[0100] area Contact angle (°) PTFE anticoagulation area 108.42 Uncoated non-anticoagulant area 78.24

[0101] It can be seen from Table 3 that the contact angle of the PTFE anticoagulation area is greater than 90°, indicating that the PTFE coating 42 has good hydrophobicity, while the contact angle of the uncoated non-anticoagulation area is less than 90°, indicating that the hydrophobicity of the uncoated non-anticoagulation area is worse than that of the PTFE anticoagulation area.

[0102] In another separate anticoagulation test, the coagulation performance of the anticoagulation area and the non-anticoagulation area of ​​the PET knitted film was characterized by whole blood immersion using adult pig arterial blood (without heparin). The results are shown in Table 4 below.

[0103] Table 4 Coagulation time of anticoagulated blood and non-anticoagulated blood (min)

[0104] area Coagulation time (min) PTFE anticoagulation area 40min Uncoated non-anticoagulant area 10min

[0105] According to Table 4, the PTFE anticoagulation area and the uncoated non-anticoagulation area also showed obvious differences in coagulation time, which confirmed that the PTFE anticoagulation coating can effectively achieve a single-sided anticoagulation effect, and the anticoagulation effect is equivalent to the double-sided anticoagulation effect of the coating.

[0106] Embodiment 3

[0107] Please refer to Figure 7 In the third embodiment, an expandable frame 1 formed by cutting a nickel-titanium tube is provided, and a part of the outer surface of the expandable frame 1 is covered with a layer of PET knitted film 2.

[0108] The proximal portion 210 of the coating 2 is the sealing disk surface, and therefore, the outer surface of the proximal portion 210 is covered with a FEP hydrophobic coating 43, for example, by ultrasonic spraying, to form an anti-coagulation area.

[0109] The difference from Example 1 and Example 2 is that the inner surface 22 of the coating 2 of this embodiment is covered with a PAM (polyacrylamide) amphiphilic coating 51, and the outer surface 21 of the PET knitted film that is not provided with the FEP hydrophobic coating 43 is directly a PET knitted coating material, all of which form a non-anticoagulation area 5.

[0110] In a separate contact angle test, the contact angles of the anticoagulation area and the non-anticoagulation area of ​​the PET knitted film relative to pure water were tested. The test results are shown in Table 5 below.

[0111] Table 5 Contact angles of anticoagulated blood area and non-anticoagulated blood (°)

[0112] area Contact angle (°) FEP Anticoagulation Area 112.95 PAM non-anticoagulant area 47.4

[0113] It can be seen from Table 5 that the contact angle of the FEP anti-coagulation area is also greater than 90°, indicating that the hydrophobicity of the FEP hydrophobic coating 43 is also good, while the contact angle of the PAM non-anticoagulation area is smaller than the contact angle of the non-anticoagulation area of ​​Example 1 and Example 2, which indicates that the hydrophobicity of the PAM non-anticoagulation area is worse.

[0114] In another separate anticoagulation test, the coagulation performance of the anticoagulation area and the non-anticoagulation area of ​​the PET knitted film was characterized by whole blood immersion using adult pig arterial blood (without heparin). The results are shown in Table 6 below.

[0115] Table 6 Coagulation time of anticoagulated blood and non-anticoagulated blood (min)

[0116] area Coagulation time (min) FEP Anticoagulation Area 40min PAM non-anticoagulant area 5min

[0117] According to Table 6, the FEP anticoagulation area and the PAM non-anticoagulation area show obvious differences in coagulation time, which confirms that the FEP anticoagulation coating can effectively achieve a single-sided anticoagulation effect, and the anticoagulation effect is equivalent to the double-sided anticoagulation effect of the coating.

[0118] In summary, the present application provides a left atrial appendage occluder, which is provided with an anticoagulant coating 4 on at least part of the outer surface of its covering 2, and the anticoagulant coating 4 enhances the anticoagulant performance of the occluder surface, thereby reducing the possibility of thrombus formation on the occluder surface, and at the same time, the hydrophobicity of the anticoagulant coating 4 is also conducive to cell adhesion and migration, thereby accelerating the endothelialization process of the occluder surface, thereby accelerating the occlusion process and reducing self-reaction; and the hydrophobic surface can also effectively avoid tissue adhesion during the implantation of the occluder, thereby improving the operability of the device, reducing tissue structure damage caused by operation, and increasing the safety of the operation.

[0119] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0120] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the present application. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application.

Claims

1. A left atrial appendage occluder, It is characterized in that include: an expandable frame, the expandable frame being capable of transitioning between a compressed state and an expanded state; a coating disposed along at least a portion of an outer surface of the expandable frame; a connection unit, the connection unit being disposed at the proximal end of the expandable frame and being capable of connecting and disconnecting with the delivery system; as well as The anti-coagulation coating only covers at least a portion of the outer surface of the coating.

2. The left atrial appendage occluder according to claim 1, It is characterized in that The coating includes a fiber bundle, which includes a plurality of fiber filaments. The anti-blood coagulation coating covers the exposed surfaces of the outer fiber filaments in the fiber bundle and the gaps between the outer fiber filaments.

3. The left atrial appendage occluder according to claim 1, It is characterized in that The material of the coating is at least one of polyethylene, polypropylene, polyester, polyurethane and polyethylene terephthalate.

4. The left atrial appendage occluder according to claim 2, It is characterized in that The pore size of the coating is 50 μm to 300 μm.

5. The left atrial appendage occluder according to claim 1, It is characterized in that The areas of the film other than those covered by the anticoagulant coating are all non-anticoagulant areas, and the non-anticoagulant areas include the non-anticoagulant coating and / or the exposed portion of the film, and the hydrophobicity of the non-anticoagulant coating is inferior to that of the film.

6. The left atrial appendage occluder according to claim 5, It is characterized in that The non-anticoagulant coating has at least one of the following characteristics: The non-anticoagulant coating comprises at least one of polyacrylamide, polyvinyl alcohol, polyvinyl pyrrolidone, polyetherimide, polyester, and polyurethane; The thickness of the non-anticoagulant coating is less than or equal to 0.1 μm; The surface contact angle of the non-anticoagulant coating is 45° to 90°.

7. The left atrial appendage occluder according to claim 1, It is characterized in that The anticoagulant coating has at least one of the following characteristics: The anticoagulation coating has better hydrophobicity than the covering film. The thickness of the anticoagulant coating is less than or equal to 1 μm; The surface contact angle of the anticoagulant coating is 100° to 130°; The friction coefficient of the anticoagulant coating is smaller than the friction coefficient of the non-anticoagulant area on the coating; The anticoagulant coating includes a fluoropolymer.

8. The left atrial appendage occluder according to claim 7, It is characterized in that The anticoagulation coating includes at least one of polytetrafluoroethylene, polyvinylidene fluoride, fluorinated ethylene propylene copolymer, and polyvinylidene fluoride and hexafluoropropylene copolymer.

9. The left atrial appendage occluder according to claim 7, It is characterized in that The fluorine content of the anticoagulant coating is 8-80 μg / cm 2 , and / or, the friction coefficient of the fluoropolymer does not exceed 0.

1.

10. The left atrial appendage occluder according to claim 1, It is characterized in that The anti-coagulation coating is not provided on the surface of the connecting unit and the surface of the expandable frame, and / or the coating has a proximal portion and a distal portion which are axially arranged from the proximal end to the distal end of the expandable frame, the proximal portion extends from the proximal end of the expandable frame and covers to the maximum outer diameter position of the expandable frame, and the anti-coagulation coating covers the entire outer surface of the proximal portion and extends beyond the maximum outer diameter of the expandable frame.

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