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 clinical arrhythmia, and thromboembolism is the leading cause of death in patients with AF. Clinical data show that over 90% of thrombosis in patients with AF is associated with the left atrial appendage (LAA). Currently, LAA occlusion surgery has become a proven method for preventing thromboembolism. After implantation of an LAA occluder, it takes at least 4-6 weeks for complete endothelialization to occur, necessitating continuous anticoagulant therapy during this process. Applying an anticoagulant coating to the surface of the LAA occluder can effectively reduce the risk of coagulation and the risk of some complications. Among the many complications of LAA occlusion surgery, device surface thrombosis is a very common long-term complication after surgery. Its causes are complex and diverse, related to factors such as the patient's own coagulation disorder, postoperative anticoagulant medication, the shape and occlusion of the LAA and occluder, and a very high risk of embolism after detachment. Therefore, thrombosis seriously affects the safety of device use, and anticoagulant treatment of medical device surfaces that come into contact with blood for extended periods is extremely necessary.

[0003] Currently, the main clinical strategy for addressing anticoagulation is to administer antibiotics and anticoagulants as adjuvant therapy through systemic administration. However, long-term use of antibiotics and anticoagulants inevitably leads to a series of side effects, such as antibiotic resistance and thrombocytopenia, and can even cause bleeding. However, most of the surface modification methods reported so far are complex, require repeated surface pretreatment, involve toxic chemicals, and pose safety concerns. Therefore, a safer and simpler way to achieve anticoagulant treatment on device surfaces is needed. Utility Model Content

[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 more common in the existing related technologies.

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

[0006] an expandable frame, the expandable frame being transitionable 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 connecting unit provided at a proximal end of the expandable frame and capable of connecting to and disconnecting from a delivery system; and

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

[0010] Optionally, the coating includes a fiber bundle including 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 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 covering film other than that covered by the anticoagulant coating is a non-anticoagulant area, the non-anticoagulant area includes the non-anticoagulant coating and / or the exposed portion of the covering film, and the hydrophobicity of the non-anticoagulant coating is inferior to that of the covering film.

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

[0015] The non-anticoagulant coating comprises 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 anti-coagulation coating has at least one of the following features:

[0019] The anti-coagulation coating is more hydrophobic than the covering film;

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

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

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

[0023] The anti-coagulation coating is composed of a fluorine-containing polymer.

[0024] Optionally, the anti-coagulation coating includes 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 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 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 this 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 anti-coagulant coating is provided on at least a portion of the outer surface of the membrane, 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 anti-coagulant coating can also effectively avoid tissue adhesion during the implantation process, improve operability, and reduce damage caused by operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Those skilled in the art will appreciate that the accompanying 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 1 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 structural diagram of a single-sided anticoagulant film according to an embodiment of the present application;

[0033] Figure 3 1 is a schematic cross-sectional view of a braided mesh membrane with an anti-coagulant 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 51 is a schematic structural diagram of the left atrial appendage occluder according to Example 1 of the present application;

[0036] Figure 6 Schematic diagram of the structure of the left atrial appendage occluder described in Example 2 of the present application;

[0037] Figure 7 It is a structural schematic diagram 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 embodiments 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 embodiments, 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, and the drawings only show the components related to the present application rather than the number, shape and size of the components during actual implementation. The type, quantity and proportion of each component during actual implementation can be changed at will, and the component layout type may also be more complicated.

[0041] In addition, each embodiment described below has one or more technical features. However, this does not mean that users of this application must implement all technical features in any embodiment at the same time, or that they can only implement some or all technical features in different embodiments separately. In other words, as long as implementation is possible, those skilled in the art can, based on the disclosure of this application and depending on design specifications or implementation requirements, selectively implement some or all technical features in any embodiment, or selectively implement a combination of some or all technical features in multiple embodiments, thereby increasing the flexibility of the implementation of this application.

[0042] As used in this specification, the singular forms "a", "an", and "the" include plural objects, the plural form "a number" includes more than two objects, and unless the content clearly indicates otherwise, "several" is used to indicate an indefinite quantity. As used in this specification, the term "or" is generally used in the sense of including "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 communication of two elements or the interaction relationship between two elements. Relational terms such as "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", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this 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 operate in a specific orientation, and therefore should not be understood as limiting this application. For those of ordinary skill in the art, the specific meanings of the above terms in this 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 "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 membrane 2 is shown. Figure 1 The connection unit 3 is also magnified and highlighted with 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] Connecting unit 3 is disposed at the proximal end of expandable frame 1 and is configured to releasably connect to the distal end of the delivery system. In some cases, connecting unit 3 may include a threaded member having internal threads that is threadedly connected to the distal end of the delivery system. However, this is not limiting. In practice, connecting unit 3 may be connected to the distal end of the delivery system using various methods, as long as the connection is releasable.

[0047] The expandable frame 1 is preferably a self-expanding structure and can be made of various self-expanding materials. 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 converted between the compressed state and the expanded state. For example, in some cases, during the delivery of the left atrial appendage occluder via the delivery system, the expandable frame 1 is in a compressed state. Once the expandable frame 1 is pushed out of the delivery system and released, the expandable frame 1 expands to the expanded state (i.e., the use form) on its own.

[0048] The shape of the expandable frame 1 is not limited. As depicted in the figure, the expandable frame 1 is shaped like a cage with an open distal end and a closed proximal end. That is, the entire left atrial appendage occluder is similar in shape to a hemispherical plug. This structure is suitable for the shape of the left atrial appendage opening in most patients. Of course, the shape of the expandable frame 1 can be adjusted and varied depending on the usage scenario and is therefore not limited to the structural form depicted in the figure.

[0049] At least a portion 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 blood flow. In some embodiments, the coating 2 can prevent thrombi (i.e., blood clots, etc.) from passing through the coating 2 and exiting the left atrial appendage into the bloodstream. In some embodiments, the coating 2 can also promote endothelial cell growth, reducing the risk of restenosis.

[0050] Specifically, the coating 2 is provided 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 provided 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, forming 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 along the outer surface of the expandable frame 1 to any extent, for example, extending to cover almost the entire outer surface of the expandable frame 1.

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

[0052] The height of the covering 2 may not exceed two-thirds 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 covering 2 refers to the distance that the covering 2 extends from the proximal end to the distal end of the expandable frame 1.

[0053] It should also be understood that although the membrane 2 itself has good mechanical properties, biological stability and safety, its anticoagulant effect is generally poor. Therefore, it is necessary to select a more hydrophobic material for anticoagulant treatment. Therefore, the membrane 2 needs to be provided with an anticoagulant coating 4.

[0054] refer to Figures 1 to 4 , the anti-coagulation 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 anti-coagulation coating 4 are all non-anticoagulation areas 5. It is worth noting that the expandable frame 1 and the connecting unit 3 may basically be free of the anti-coagulation coating 4, or in other words, the surface of the metal part is not provided with the anti-coagulation coating 4. Specifically, the connecting unit 3 usually does not need to be provided with a coating 2, so the anti-coagulation coating 4 does not need to be provided at the connecting unit 3, otherwise the anti-coagulation 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-anticoagulation described in this application are with respect to the coating 2.

[0055] With such a configuration, on the one hand, the formation of thrombus can be effectively inhibited through the anti-coagulant 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 anti-coagulant 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 an anticoagulant coating 4 needs to be provided on at least 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 to be anticoagulated. This single-sided anticoagulation can not only reduce the material consumption and reduce the cost, 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 covering 2 using a suitable method, such as ultrasonic spraying, physical / chemical vapor deposition, plasma coating, or atomized spraying. Ultrasonic spraying is preferred for better coating results. The anticoagulant coating 4 can be applied before or after the covering 2 is placed on the expandable frame 1. In short, the anticoagulant coating 4 does not coat the entire covering 2, but it can effectively coat at least a portion of the outer surface 21 of the covering 2 and be substantially uniform along the entire covering 2, ultimately achieving better 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 extent to which the anticoagulant coating 4 covers the surfaces of the outer fiber filaments 202 of the fiber bundle 201. Here, the consideration is given to distinguishing, at a microscopic level, between fiber filaments 202 provided with the anticoagulant coating 4 and those not provided with the anticoagulant coating 4. In other words, 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 covering membrane 2 is a fiber mesh woven membrane, it includes one or more fiber bundles 201. Each fiber bundle 201 may include an appropriate number of fiber filaments 202. The fiber filaments 202 are individual filaments. After an appropriate number of fiber filaments 202 are twisted to form the fiber bundles 201, the one or more fiber bundles 201 are then braided, knitted, woven, electrospun, or otherwise formed into the fiber mesh structure of the covering membrane 2.

[0060] Those skilled in the art will appreciate that the anticoagulant coating 4 does not encapsulate every fiber filament 202 in the fiber bundle 201. Furthermore, the anticoagulant coating 4 is only disposed on the outside of the fiber bundle 201 and does not penetrate the fiber bundle 201 to reach the interior of the fiber bundle 201. Therefore, the anticoagulant coating 4 is absent from the internal fiber filaments 202, thereby achieving single-sided anticoagulation. Furthermore, the anticoagulant coating 4 does not block the fiber bundles 201 on the coating 2 and the mesh formed by the interweaving of the fiber bundles 201, thereby not affecting the performance of the coating 2 itself and allowing the coating 2 to maintain its original pore structure (i.e., mesh).

[0061] Furthermore, the membrane 2, when constructed as a fiber mesh braided membrane, offers superior mechanical support. Furthermore, the pores of the fiber mesh braided membrane allow blood to flow through while preventing the passage of thrombi. Thus, the membrane 2 itself has a porous structure. Preferably, the pore size of the membrane 2 is between 50 μm and 300 μm; this pore size facilitates the passage of blood through the membrane 2 while effectively preventing the passage of thrombi.

[0062] Preferably, the anticoagulant coating 4 is applied to the outer surface 21 of the coating 2 by ultrasonic spraying. This 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 ultrasonic spraying process has good process stability and is easy to adjust and control process parameters, making the process more stable and reliable. The advantages of ultrasonic spraying are also that it uses less material and is low in cost.

[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 while not easily falling off, thus improving safety and effectiveness and not affecting the insertion of the occluder into the sheath.

[0064] Furthermore, the anticoagulant effect can be improved by controlling the surface contact angle of the anticoagulant coating 4. Studies have shown that the surface contact angle of the anticoagulant 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 mentioned above, the anticoagulant coating 4 needs to be provided at least on the portion of the outer surface 21 of the coating 2 that is in direct contact with the blood. 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 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 anti-coagulant 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) 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 other than the proximal portion 210 is the distal portion 220.

[0067] The distal portion 220 is the anchoring area and needs to conform to the LAA wall to ensure the stability of the occluder after implantation, allowing the occluder to stably and effectively occlude the LAA. The proximal portion 210 is essentially not used for anchoring support. It faces the atrial side and is positioned at the entrance of the LAA, in contact with blood, without the need for anchoring.

[0068] Preferably, the anticoagulant coating 4 extends from the proximal end of the expandable frame 1 to 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 dimensions. The area of ​​the membrane 2 other than that covered by the anticoagulant coating 4 is a non-anticoagulant area 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 anti-coagulant coating 4 is also beneficial for 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. In particular, when the anti-coagulant coating 4 is coated with a fluoropolymer, 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 sheathing performance and anchoring performance, achieving low sheathing force and high anchoring force without sacrificing other aspects of the device's performance, while also increasing the safety of the occluder. In this application, although the maximum outer diameter of the expandable frame 1 is covered by the anticoagulant coating 4, the fixation of the occluder is primarily ensured by the anchoring of the non-anticoagulant region 5, and therefore, the anticoagulant coating 4 does not affect the stability of the entire occluder.

[0071] Furthermore, the non-anticoagulant region 5 can be directly formed of 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. Furthermore, 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, under normal circumstances, the non-anticoagulant coating is less hydrophobic than the coating 2, which facilitates rapid coagulation within the occluder and fills the internal area of ​​the occluder. Alternatively, the non-anticoagulant coating may be made of a non-anticoagulant polymer material with hydrophilic groups.

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

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

[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 combination coating of at least two polymers.

[0077] In some embodiments, the anti-coagulation coating 4 includes a fluoropolymer, specifically a combination of one or more fluoropolymers. Preferably, the anti-coagulation coating 4 is composed of a fluoropolymer. When the anti-coagulation coating 4 includes a fluoropolymer, the surface of the anti-coagulation coating 4 exhibits a highly 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 does 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 fluoropolymer also has good film-forming properties, which can make the anticoagulant coating 4 evenly 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, with good biosafety and stability. Of course, the fluoropolymer also has good biocompatibility and stable properties, and can play a long-term and stable anticoagulant effect. Therefore, when performing anticoagulant treatment, there is no need to administer antibiotics and anticoagulants through systemic administration, which can avoid a series of side effects caused by long-term medication.

[0079] Optionally, the anti-coagulation coating 4 includes polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), fluorinated ethylene propylene copolymer (FEP), polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP), or other fluoropolymers with similar properties, and may include a combination of one or more of these fluoropolymers. Preferably, the anti-coagulation coating 4 is composed of polyvinylidene fluoride-hexafluoropropylene copolymer. This type of anti-coagulation coating 4 is relatively more effective and safe, is not easily detached, and has a good long-term anti-coagulation effect.

[0080] Preferably, the friction coefficient of the anticoagulant coating 4 is less than that of the non-anticoagulant region 5 on the coating 2 to reduce the insertion force of the occluder. More preferably, the friction coefficient of the anticoagulant coating 4 does not exceed 0.3, so as to achieve both anticoagulation and friction reduction. For example, when a fluoropolymer coating is used, the friction coefficient of the fluoropolymer should not exceed 0.1 for optimal results.

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

[0083] The present application will be 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] Example 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 areas 5 are directly PET knitted coating materials.

[0087] In a separate contact angle test, the contact angles of the anti-coagulation area and the non-anticoagulation area of ​​the PET knitted film 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 anticoagulant region 101.99 Uncoated non-anticoagulant area 78.24

[0090] As can be seen from Table 1, the contact angle of the PVDF-HFP anticoagulant area is greater than 90°, which indicates that the PVDF-HFP coating 41 has good hydrophobicity, while the contact angle of the uncoated non-anticoagulant area is less than 90°, which indicates that the hydrophobicity of the uncoated non-anticoagulant area is worse than that of the PVDF-HFP anticoagulant 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 soaking in whole blood 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 anticoagulant region 35min Uncoated non-anticoagulant area 10min

[0094] According to Table 2, the PVDF-HFP anticoagulation area and the uncoated non-anticoagulation area showed obvious differences in coagulation time, confirming 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] Example 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, so that 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 anti-coagulation 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 anticoagulant area 108.42 Uncoated non-anticoagulant area 78.24

[0101] As can be seen from Table 3, the contact angle of the PTFE anticoagulant area is greater than 90°, indicating that the PTFE coating 42 has good hydrophobicity, while the contact angle of the uncoated non-anticoagulant area is less than 90°, indicating that the hydrophobicity of the uncoated non-anticoagulant area is worse than that of the PTFE anticoagulant 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 soaking in whole blood 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 anticoagulant 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, confirming 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] Example 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 portion 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. 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 portion of 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-anticoagulant area 5.

[0110] In a separate contact angle test, the contact angles of the anti-coagulation 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] As can be seen from Table 5, 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 angles of the non-anticoagulation areas of Examples 1 and 2, indicating 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 soaking in whole blood 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 showed obvious differences in coagulation time, confirming 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 anti-coagulant coating 4 on at least part of the outer surface of its covering 2. The anti-coagulant coating 4 enhances the anti-coagulant performance of the occluder surface, thereby reducing the possibility of thrombus formation on the occluder surface. At the same time, the hydrophobicity of the anti-coagulant 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-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned 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-described embodiments merely represent several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present application. It should be noted that a person skilled in the art may make various modifications and improvements without departing from the scope of the present application, and all such modifications and improvements fall within the scope of protection of the present application.

Claims

1. A left atrial appendage occluder, characterized in that: include: an expandable frame, the expandable frame being transitionable 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 connecting unit, the connecting unit being disposed at a proximal end of the expandable frame and capable of connecting to and disconnecting from a delivery system; as well as An anti-coagulation coating covers only at least a portion of the outer surface of the covering membrane.

2. The left atrial appendage occluder according to claim 1, characterized in that: The coating includes a fiber bundle including a plurality of fiber filaments. 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.

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

4. The left atrial appendage occluder according to claim 2, 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, characterized in that: The areas of the covering 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 covering film. The hydrophobicity of the non-anticoagulant coating is inferior to that of the covering film.

6. The left atrial appendage occluder according to claim 5, characterized in that: The non-anticoagulant coating has at least one of the following characteristics: The non-anticoagulant coating comprises 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, characterized in that: The anti-coagulation coating has at least one of the following characteristics: The anti-coagulation coating is more hydrophobic than the covering film; The thickness of the anti-coagulation coating is less than or equal to 1 μm; The surface contact angle of the anti-coagulation coating is 100° to 130°; The friction coefficient of the anti-coagulation coating is smaller than the friction coefficient of the non-anticoagulation area on the coating; The anti-coagulation coating is composed of a fluorine-containing polymer.

8. The left atrial appendage occluder according to claim 7, characterized in that: The anti-coagulation coating comprises 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, characterized in that: 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.

10. The left atrial appendage occluder according to claim 1, 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 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 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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