Left auricle sealing device

Abstract

The present application relates to a left atrial appendage closure device comprising: a frame; a film disposed along at least a portion of an outer surface of the frame; the anti-coagulation composite coating is arranged on at least one part of the outer surface of the covering film; the anticoagulant composite coating comprises a first bonding layer and a second anticoagulant layer which are arranged from inside to outside in the thickness direction of the covering film. Through the configuration, the risk that thrombus is formed on the surface of the instrument can be reduced, the endothelialization process is accelerated, meanwhile, the firmness of the whole coating is improved, the risk that the coating falls off is reduced, and the long-term anticoagulation effect can be kept.

Description

Technical Field

[0001] The present application relates to the field of medical devices, and in particular to a left atrial appendage closure device with an anticoagulant composite coating. Background Art

[0002] Atrial fibrillation (AF) is a common cardiac 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 is a proven method for preventing thromboembolism.

[0003] After the left atrial appendage occluder is implanted, it takes at least 4-6 weeks for complete endothelialization to occur. Therefore, during this process, continuous anticoagulant treatment is required. Applying an anticoagulant coating on the surface of the left atrial appendage occluder can effectively reduce the risk of coagulation and the risk of some complications. Among the many complications of left atrial appendage occlusion surgery, thrombosis on the surface of the occluder is a very common complication in the long term after surgery. Its causes are complex and diverse, and are related to many factors such as the patient's own coagulation disease, postoperative anticoagulant medication, the shape and occlusion of the left atrial appendage and 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 device surface that is in contact with blood for a long time is very necessary.

[0004] However, the current main clinical strategy for dealing with the problem of anticoagulation is to use systemic administration of antibiotics and anticoagulants as auxiliary treatment. However, long-term use of antibiotics and anticoagulants will inevitably cause a series of side effects, such as antibiotic resistance and thrombocytopenia, and may even cause bleeding. Therefore, the best way is to directly set an anticoagulant coating on the surface of the device. However, most of the existing anticoagulation methods use heparin coatings, and the heparin coatings are chemically grafted to the surface of the device. This process involves surface modification, which is complex and requires repeated surface pretreatment. It also involves toxic chemical reagents and other issues, and its safety is worrying. In particular, the coating is easy to fall off and cannot maintain a long-term anticoagulant effect.

[0005] It should be noted that the information disclosed in the background technology section of this application is only intended to deepen the understanding of the general background technology of this application, and should not be regarded as an admission or any form of implication that the information constitutes prior art already known to those skilled in the art. Utility Model Content

[0006] In view of this, the purpose of the present application is to provide a left atrial appendage closure device that can effectively reduce the risk of thrombus formation on the device surface and accelerate the endothelialization process.

[0007] To achieve the above-mentioned objectives, the present application provides a left atrial appendage closure device, which includes: a frame; a coating, which is arranged along at least a portion of the outer surface of the frame; and an anticoagulant composite coating, which is arranged on at least a portion of the outer surface of the coating; the anticoagulant composite coating includes a first adhesive layer and a second anticoagulant layer arranged from the inside to the outside along the thickness direction of the coating.

[0008] Optionally, the coating includes a fiber bundle including a plurality of fiber filaments, and the anti-coagulation composite coating is provided on the exposed surfaces of the outer fiber filaments in the fiber bundle and in the gaps between the outer fiber filaments.

[0009] Optionally, the material of the coating is one of polyethylene, polypropylene, polyester, polyurethane, and polyethylene terephthalate.

[0010] Optionally, the pore size of the coating is 50 μm to 300 μm.

[0011] Optionally, the first adhesive layer includes one of polyamide, polycarbonate, polydimethylsiloxane, polycaprolactone, methyl cellulose, ethyl cellulose, and polybutylene adipate / terephthalate.

[0012] Optionally, the thickness of the first adhesive layer does not exceed 0.1 μm.

[0013] Optionally, the second anticoagulation layer has at least one of the following characteristics:

[0014] The thickness of the second anticoagulant layer does not exceed 1 μm;

[0015] The surface contact angle of the second anti-coagulation layer is 100° to 130°;

[0016] The second anti-coagulation layer is composed of a fluorine-containing polymer.

[0017] Optionally, the second anti-coagulation layer includes one of polytetrafluoroethylene, polyvinylidene fluoride, fluorinated ethylene propylene copolymer, and polyvinylidene fluoride-hexafluoropropylene copolymer.

[0018] Optionally, it further comprises a connecting structure, which is provided at the proximal end of the frame and is used for detachable connection with the delivery system; the surface of the connecting structure and the surface of the frame are not provided with the anti-coagulation composite coating;

[0019] And / or, the coating has a proximal portion and a distal portion axially arranged from the proximal end to the distal end of the frame, the proximal portion extends from the proximal end of the frame and covers the maximum outer diameter of the frame, and the anticoagulation composite coating is arranged on the entire outer surface of the proximal portion and extends beyond the maximum outer diameter of the frame.

[0020] Optionally, the covering film is configured to have the anticoagulant composite coating only on at least a portion of its outer surface, and the covering film is further configured so that except for the surface provided with the anticoagulant composite coating, all other surfaces are non-anticoagulant areas.

[0021] The left atrial appendage closure device provided above includes: a frame; a coating, which is arranged along at least a portion of the outer surface of the frame; and an anticoagulant composite coating, which is arranged on at least a portion of the outer surface of the coating; the anticoagulant composite coating includes a first adhesive layer and a second anticoagulant layer arranged from the inside to the outside along the thickness direction of the coating.

[0022] With such a configuration, on the one hand, since an anticoagulant composite coating including a second anticoagulant layer is provided on the outer surface of the membrane, the surface of the membrane can play an anticoagulant role through the second anticoagulant layer, thereby reducing the risk of thrombosis on the surface of the device and accelerating the endothelialization process. On the other hand, since the first adhesive layer has both hydrophilic and hydrophobic properties, it can be better combined with the membrane and the second anticoagulant layer, thereby increasing the firmness of the entire coating, reducing the risk of coating shedding, and maintaining a long-term anticoagulant effect. In addition, since the anticoagulant composite coating is bonded to the membrane surface by physical coating, the process is simple and the safety is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] 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.

[0024] Figure 1 1 is a schematic structural diagram of a left atrial appendage closure device according to an embodiment of the present application, with detail A highlighting the proximal connection structure;

[0025] Figure 2 This is a schematic structural diagram of an embodiment of the present application in which an anti-coagulation composite coating is provided on at least a portion of the outer surface of the coating;

[0026] Figure 3 1 is a schematic cross-sectional view of a braided mesh membrane with an anticoagulant composite coating and its fiber bundle according to an embodiment of the present application;

[0027] Figure 4 1 is a schematic structural diagram of the left atrial appendage closure device according to Example 1 of the present application;

[0028] Figure 5 2 is a schematic structural diagram of the left atrial appendage closure device according to Example 2 of the present application;

[0029] Figure 6 It is a structural schematic diagram of the left atrial appendage closure device described in Example 3 of the present application.

[0030] In the attached figure:

[0031] 1-frame; 11-distal tail; 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 structure; 4-anticoagulant composite coating; 41-first adhesive layer; 42-second anticoagulant layer. DETAILED DESCRIPTION

[0032] 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.

[0033] 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.

[0034] 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.

[0035] In this application document, the term "axial" used generally refers to the direction along the central axis of the left atrial appendage closure device, "circumferential" refers to the direction around the central axis of the left atrial appendage closure device, and "radial" generally refers to the diameter direction of the left atrial appendage closure device, 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 closure device, and "inner side" refers to the direction close to the central axis of the left atrial appendage closure device; 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 closure device. Although non-restrictive, the "distal end" generally refers to the end of the left atrial appendage closure device 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 closure device closer to the operator. In this article, "not more than" means less than or equal to, and "not less than" means greater than or equal to.

[0036] The core of this application is to provide a left atrial appendage closure device to solve the common problem of blood coagulation on the surface of medical devices in the existing related technologies.

[0037] Figure 1 The structural state of the left atrial appendage closure device in some embodiments is schematically described. Figure 1 As shown, the left atrial appendage closure device includes: an expandable frame 1; a covering 2 provided on the frame 1; and a connecting structure 3 that can be connected to and disconnected from a delivery system.

[0038] The frame 1 is preferably a self-expanding structure. The frame 1 can be made of any suitable material, and nickel-titanium alloy is currently the best. Optionally, the frame 1 is made by cutting a nickel-titanium tube. The frame 1 has a compressed state and an expanded state, and can be freely converted between the compressed state and the expanded state. Specifically, during the transportation of the left atrial appendage closure device via the conveying system, the frame 1 is in a compressed state, and once the frame 1 is pushed out of the conveying system and released, the frame 1 expands to the expanded state (i.e., the use form) on its own.

[0039] The shape of the frame 1 is not limited. Common occluders include plug-type occluders and disc-type occluders. For the plug-type occluder described in the figure, the frame 1 is basically a mesh cage structure with an open distal end and a closed proximal end. The shape of the entire left atrial appendage closure device is similar to a hemispherical plug. This structure is suitable for the shape of the left atrial appendage opening of most patients. Of course, the shape of the frame 1 can be adjusted and changed according to the usage scenario and is therefore not limited to the structural shape described in the figure.

[0040] At least a portion of the outer surface of the frame 1 is covered by the membrane 2 to form a sealing disk surface, which can be used to isolate blood flow. In some embodiments, the membrane 2 can prevent thrombi (i.e., blood clots, etc.) from passing through the membrane 2 and exiting the left atrial appendage into the bloodstream. In some embodiments, the membrane 2 can also promote endothelial cell growth, reducing the risk of restenosis.

[0041] Specifically, the coating 2 is disposed along at least a portion of the outer surface of the frame 1, covering at least a portion of the outer surface of the frame 1. For example, in some cases, the coating 2 may be disposed along a portion of the outer surface of the frame 1, leaving the distal end 11 of the frame 1 exposed outside the coating 2, forming a skirt. The skirt generally curves inward to prevent damage to tissue structures caused by the skirt of the frame 1 during and after implantation. However, those skilled in the art will appreciate that the coating 2 may extend along the outer surface of the frame 1 to any extent, such as extending to cover substantially the entire outer surface of the frame 1.

[0042] The membrane 2 can be 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 (PE), polypropylene (PP), polyester, polyurethane (PU), polyethylene terephthalate (PET) or other materials, and the membrane 2 can include a single material or a combination of multiple materials.

[0043] The height of the coating 2 may not exceed two-thirds of the total height of the frame 1, but is not limited thereto. The total height of the frame 1 refers to the distance from the proximal end to the distal end of the frame 1. The height of the coating 2 refers to the distance that the coating 2 extends from the proximal end to the distal end of the frame 1.

[0044] Connecting structure 3 is disposed at the proximal end of frame 1 and can be releasably connected to the distal end of the delivery system using a suitable structure. For example, connecting structure 3 may include internal threads that are threadedly connected to the distal end of the delivery system. However, this threaded connection is not limiting; in practice, connecting structure 3 can be releasably connected to the distal end of the delivery system using various means.

[0045] It should also be understood that although the membrane 2 itself has good mechanical properties, biostability and safety, the anticoagulant effect of the membrane material is generally poor, so it is necessary to select a more hydrophobic material for anticoagulant treatment.

[0046] like Figures 1 to 3 As shown, in various embodiments of the present application, the left atrial appendage closure device further includes an anticoagulant composite coating 4, which is disposed on at least a portion of the outer surface 21 of the coating 2. The anticoagulant composite coating 4 has an anticoagulant effect, which can reduce the risk of thrombosis on the device surface and accelerate the endothelialization process. Preferably, the coating 2 is provided with the anticoagulant composite coating 4 only on its outer surface 21. Except for the surface provided with the anticoagulant composite coating 4, the other surfaces are non-anticoagulant areas. Specifically, the connection structure 3 generally does not require the coating 2, so the anticoagulant composite coating 4 is not required at the connection structure 3. If provided, the anticoagulant composite coating 4 is easily detached. The frame 1 is primarily responsible for providing support. If the anticoagulant composite coating 4 is provided on the frame 1, the anticoagulant composite coating 4 is easily detached during the device compression, gripping and release process. Therefore, the anticoagulant composite coating 4 is not required on the frame 1. Therefore, the anticoagulant and non-anticoagulant terms described in this application are specific to the coating 2.

[0047] In more detail, Figure 2 and Figure 3As shown, the anticoagulation composite coating 4 is a double-layer structure, which includes a first adhesive layer 41 and a second anticoagulation layer 42 arranged from the inside to the outside along the thickness direction of the coating 2. The first adhesive layer 41 contains an amphiphilic polymer. An amphiphilic polymer refers to a polymer that has both hydrophilic and hydrophobic properties, specifically a high molecular polymer that contains both hydrophilic groups and hydrophobic groups. In addition to the amphiphilic polymer, the first adhesive layer 41 may contain other components or no longer contain other components. Preferably, the first adhesive layer 41 is composed only of an amphiphilic polymer, for example, including one amphiphilic polymer or a combination of multiple amphiphilic polymers.

[0048] This configuration allows the outermost second anticoagulant layer 42 of the membrane 2 to form an anticoagulant outer surface. This anticoagulant outer surface effectively inhibits thrombus formation, thereby accelerating endothelialization and thus the occlusion process, reducing autoreactivity. Furthermore, the hydrophobic nature of the second anticoagulant layer 42 effectively prevents tissue adhesion during implantation, improving device operability, reducing tissue damage caused by device manipulation, and increasing surgical safety.

[0049] Specifically, when the anticoagulant outer surface of the coating 2 comes into contact with blood, the second anticoagulant layer 42 of the anticoagulant composite coating 4 effectively prevents blood from adhering to and clotting the device surface. In particular, when the second anticoagulant layer 42 is an inert hydrophobic polymer coating, the anticoagulant effect is even better. Inert hydrophobic polymer coatings primarily include fluoropolymer coatings. These inert hydrophobic polymer coatings utilize hydrophobicity to prevent the adhesion of plasma components, thereby achieving an anticoagulant effect.

[0050] At the same time, a first adhesive layer 41 (i.e., a coating interlayer) is present between the second anticoagulant layer 42 and the outer surface 21 of the covering 2. The first adhesive layer 41 is substantially completely covered by the second anticoagulant layer 42. Because the first adhesive layer 41 has both hydrophilic and hydrophobic properties, the first adhesive layer 41 can be well bonded to the covering 2 and the second anticoagulant layer 42, thereby increasing the firmness of the entire coating and reducing the risk of the coating falling off, especially when repeatedly pushed in the sheath, thereby enabling the coating to maintain a long-term anticoagulant effect.

[0051] The anticoagulation composite coating 4 can be applied to the outer surface 21 of the film 2 by a suitable method, such as physical coating, for example, ultrasonic spraying, dip coating, physical / chemical deposition, plasma coating, atomized spraying, etc., with ultrasonic spraying being a more suitable method. Here, since the anticoagulation composite coating 4 is bonded to the outer surface 21 of the film 2 by physical coating, the process is simple and safe.

[0052] In addition, compared with other methods, ultrasonic spraying is more stable and the preparation process is more controllable. Moreover, ultrasonic spraying is suitable for single-sided anticoagulation treatment 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 materials and is low in cost. Ultrasonic spraying can be performed before or after the coating 2 is set on the frame 1. Preferably, ultrasonic spraying is performed after the coating 2 is set on the frame 1, so that the spraying process is more controllable and the spraying effect is better.

[0053] Practical, at least need to be provided with anticoagulant composite coating 4 on the part that the outer surface 21 of coating 2 is in direct contact with blood, and the inside of most medical devices has little to do with thrombus and surface endothelialization, so the inner surface 22 of coating 2 does not need anticoagulant treatment. This single-sided anticoagulant treatment can reduce material consumption, reduce costs, and also help to fix the whole left atrial appendage closure device. Here, when the inner surface 22 of coating 2 is not anticoagulant, after the left atrial appendage closure device is implanted in the body, a blood clot filling the inside of frame 1 can be formed in a short time, which can help the left atrial appendage closure device to be fixed on the left atrial appendage place quickly, making the robustness of the whole left atrial appendage closure device better and not easy to shift.

[0054] In this embodiment, the anticoagulation composite coating 4 does not coat the entire membrane 2 , but only coats at least a portion of the outer surface 21 of the membrane 2 and is evenly arranged along the outer surface 21 of the membrane 2 , thereby achieving single-sided anticoagulation.

[0055] refer to Figure 3 As shown, in a preferred embodiment, the covering membrane 2 is a fiber mesh braided membrane, wherein the anticoagulation composite coating 4 only covers the exposed surfaces of the outer fiber filaments 202 in the fiber bundle 201, as well as the gaps between the outer fiber filaments 202 and the fiber filaments 202. Here, the consideration is to distinguish between the fiber filaments 202 provided with the anticoagulation composite coating 4 and those not provided with the anticoagulation composite coating 4 in terms of microscopic morphology. In other words, it is clarified that when the fiber mesh braided membrane is covered on the outer surface of the frame 1, the inner fiber filaments 202 and the fiber filaments 202 with unexposed surfaces are not coated with the anticoagulation composite coating 4.

[0056] When 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 formed into the fiber mesh structure of the covering membrane 2 by, for example, braiding, knitting, weaving, electrospinning, or other methods.

[0057] It should be noted that the anticoagulation composite coating 4 does not encapsulate every fiber filament 202 in the fiber bundle 201. Furthermore, the anticoagulation composite 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 internal fiber filaments 202 are not exposed to the anticoagulation composite coating 4, thereby achieving single-sided anticoagulation. Furthermore, the anticoagulation composite 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, thus not affecting the performance of the coating 2 itself, allowing the coating 2 to maintain its original pore structure (i.e., mesh).

[0058] Here, when the membrane 2 is a fiber mesh woven membrane, it provides excellent mechanical support. Furthermore, the pores of the fiber mesh woven membrane allow blood to flow through while preventing the passage of thrombi. Therefore, the membrane 2 itself has a porous structure. Preferably, the pore size of the membrane 2 is 50 μm to 300 μm; this pore size facilitates the passage of blood through the membrane 2 while effectively preventing the passage of thrombi.

[0059] Preferably, the anti-coagulation composite coating 4 is applied to the surface of the fiber filament 202 by ultrasonic spraying.

[0060] As mentioned above, the anticoagulant composite 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. In practice, the anticoagulant composite coating 4 needs to be provided at least on the sealing 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.

[0061] 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 frame 1; the proximal portion 210 and the distal portion 220 do not overlap, and both surround and cover the frame 1, so that the coating 2 covers the frame 1 on the circumferential side of the frame 1. The entire outer surface of the proximal portion 210 is covered with an anticoagulant composite coating 4, while the entire outer surface of the distal portion 220 is a non-anticoagulant area. The proximal portion 210 needs to extend from the proximal end of the frame 1 and cover the maximum outer diameter (Dmax) position of the 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.

[0062] The distal portion 220 is the anchoring area and needs to conform to the LAA wall to ensure the stability of the device after implantation, enabling the device 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.

[0063] Preferably, the anticoagulant composite coating 4 extends from the proximal end of the frame 1 and covers the maximum outer diameter (Dmax) of the frame 1. For example, the anticoagulant composite coating 4 extends beyond the maximum outer diameter (Dmax) of the frame 1 so that the anticoagulant composite coating 4 can fully cover the maximum outer diameter of the frame 1. The distance exceeding the maximum outer diameter can be 3 mm, 5 mm, or other dimensions. The area of ​​the coating 2 other than that covered by the anticoagulant composite coating 4 is a non-anticoagulant area.

[0064] It should also be understood that the left atrial appendage closure device often needs to be received 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 composite coating 4 is also beneficial 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 frame 1 has a smaller sheathing force, especially when the anticoagulant composite coating 4 adopts a fluoropolymer coating, a lower surface friction coefficient can be obtained, and the sheathing force is smaller. In addition, after the left atrial appendage closure device 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 on the coating 2, thereby enhancing the stability of the left atrial appendage closure device after implantation.

[0065] Therefore, the anticoagulant and non-anticoagulant regions 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 occlusion device. In this application, although the maximum outer diameter of the frame 1 is covered by the anticoagulant composite coating 4, the device's fixation is primarily ensured by anchoring in the non-anticoagulant region, and therefore, the anticoagulant composite coating 4 does not affect the stability of the entire device.

[0066] The first adhesive layer 41 may include a suitable amphiphilic polymer, for example, at least one of polyamide (PA), polycarbonate (PC), polydimethylsiloxane (PDMS), polycaprolactone (PCL), methylcellulose (MC), ethylcellulose (EC), and polybutylene adipate / terephthalate (PBAT). More preferably, at least one of polyacrylamide (PAM) and polyethylene glycol (PEG) may be selected. Preferably, the first adhesive layer 41 is composed solely of an amphiphilic polymer.

[0067] The thickness of the first adhesive layer 41 is preferably no more than 0.1 μm; this thickness does not increase the thickness of the entire anti-coagulation composite coating 4, while ensuring the coating's firmness and having good film-forming properties. Furthermore, the thickness of the first adhesive layer 41 is no less than 0.05 μm.

[0068] Preferably, the second anti-coagulation layer 42 comprises a fluoropolymer, such as one fluoropolymer or a combination of multiple fluoropolymers.

[0069] When the second anticoagulation layer 42 includes a fluoropolymer, the presence of fluoro groups causes the surface of the second anticoagulation layer 42 to exhibit a relatively high hydrophobicity overall, resulting in a better anticoagulation effect. At the same time, the hydrophobicity of the surface of the second anticoagulation layer 42 makes it difficult for fibrinogen and platelets that induce thrombosis to adhere to the surface of the coating 2, thereby not causing a coagulation reaction, thereby achieving an anticoagulant effect. In addition, the surface hydrophobicity of the second anticoagulation layer 42 allows albumin to be firmly adsorbed on the surface of the second anticoagulation layer 42, promoting the migration and crawling of endothelial cells, thereby accelerating the endothelialization of the material surface to effectively reduce complications. In addition, the fluoropolymer also has good film-forming properties, which can enable the second anticoagulation layer 42 to be evenly coated on the outer surface 21 of the coating 2 and quickly solidified into a film, and firmly bonded to the first adhesive layer 41, 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 have a long-term and stable anticoagulant effect.

[0070] The second anti-coagulation layer 42 may include, for example, 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 second anti-coagulation layer 42 is composed of polyvinylidene fluoride-hexafluoropropylene copolymer. This type of anti-coagulation coating is relatively more effective and safe, is not easily detached, and has a good long-term anti-coagulation effect.

[0071] The second anti-coagulation layer 42 may also include a non-fluorine-containing polymer, specifically, a polymer (non-fluorine-containing polymer) with better hydrophobicity than the cover 2. The second anti-coagulation layer 42 includes, for example, polystyrene, polyurethane, polyester, and combinations thereof.

[0072] The second anti-coagulation layer 42 can be a single polymer coating or a combination coating of at least two polymers.

[0073] The thickness of the second anti-coagulation layer 42 should not be too large or too small. Preferably, the thickness of the second anti-coagulation layer 42 does not exceed 1 μm; this ensures the anti-coagulation effect of the second anti-coagulation layer 42 while preventing it from falling off, thus improving safety and effectiveness and not affecting the insertion of the device into the sheath.

[0074] Preferably, the surface contact angle of the second anticoagulation layer 42 is 100° to 130°, such as 100°, 110°, 120° or 130°. This surface contact angle is beneficial for both efficient anticoagulation and better promotion of endothelialization.

[0075] Furthermore, the non-anticoagulant region on the covering 2 can be directly formed of a covering material without any coating. That is, the portion of the covering 2 not provided with the anticoagulant composite coating 4 is exposed to directly form the non-anticoagulant region. Furthermore, the exposed portion of the covering 2 can be further provided with a non-anticoagulant coating, forming the non-anticoagulant region from the non-anticoagulant coating. Therefore, the non-anticoagulant region can include both the non-anticoagulant coating and the exposed portion of the covering 2.

[0076] 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, generally, the non-anticoagulant coating is less hydrophobic than the coating 2, facilitating rapid coagulation within the closure device and filling and blocking the internal area. Alternatively, the non-anticoagulant coating may be made of a non-anticoagulant polymer material with hydrophilic groups.

[0077] 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 of 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 device after implantation.

[0078] Optionally, the non-anticoagulant coating includes at least one of polyacrylamide (PAM), polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), and polyetherimide (PEI).

[0079] Optionally, the thickness of the non-anticoagulant coating is less than or equal to 0.1 mm thick. 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°.

[0080] The left atrial appendage closure device provided by 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.

[0081] [Example 1]

[0082] Please refer to Figure 4 , Example 1 of the present application provides a left atrial appendage closure device, wherein the frame 1 is formed by cutting a nickel-titanium tube, and a portion of the outer surface of the frame 1 is covered with a layer of PET knitted film 2.

[0083] The proximal portion 210 of the PET knitted coating 2 is a sealing disk. At this time, the entire outer surface of the proximal portion 210 is first coated with a first adhesive layer 41 by ultrasonic spraying. The component of the first adhesive layer 41 is polydimethylsiloxane, and then the second anti-coagulation layer 42 is continuously coated by ultrasonic spraying. The component of the second anti-coagulation layer 42 is polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP).

[0084] It should be understood that, except for the surface provided with the anticoagulant composite coating 4, the other surfaces of the PET knitted film 2 are all non-anticoagulant areas, and the non-anticoagulant areas here are directly made of PET knitted film material.

[0085] 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.

[0086] Table 1: Contact angles of anticoagulated blood and non-anticoagulated blood (°)

[0087] area Contact angle (°) Double-layer composite anti-coagulation coating area 101.99 Uncoated PET film 78.24

[0088] In Table 1, the contact angle of the double-layer composite anticoagulation coating region composed of polydimethylsiloxane and polyvinylidene fluoride-hexafluoropropylene copolymer is greater than 90°, therefore, the hydrophobicity of this double-layer composite anticoagulation coating region is good, while the contact angle of the uncoated PET film is less than 90°, indicating that the hydrophobicity is worse than that of the double-layer composite anticoagulation coating region.

[0089] 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.

[0090] Table 2: Clotting time (min) of anticoagulated blood and non-anticoagulated blood

[0091] area Coagulation time (min) Double-layer composite anti-coagulation coating area 35min Uncoated PET film 10min

[0092] In Table 2, the double-layer composite anticoagulant coating region composed of polydimethylsiloxane and polyvinylidene fluoride-hexafluoropropylene copolymer showed a significant difference in coagulation time compared with the uncoated PET film, confirming that the double-layer composite anticoagulant coating region can effectively play a single-sided anticoagulant effect.

[0093] [Example 2]

[0094] Please refer to Figure 5 , Example 2 of the present application provides a left atrial appendage closure device, wherein the frame 1 is formed by cutting a nickel-titanium tube, and a portion of the outer surface of the frame 1 is covered with a layer of PET knitted film 2.

[0095] The proximal portion 210 of the PET knitted coating 2 is a sealing disk, so that the entire outer surface of the proximal portion 210 is first coated with a first adhesive layer 41 by ultrasonic spraying, and the first adhesive layer 41 is composed of polyamide (PA), and then the second anti-coagulation layer 42 is continuously coated by ultrasonic spraying, and the second anti-coagulation layer 42 is composed of polytetrafluoroethylene (PTFE).

[0096] 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.

[0097] Table 3: Contact angles of anticoagulated blood area and non-anticoagulated blood (°)

[0098] area Contact angle (°) Double-layer composite anti-coagulation coating area 108.42 Uncoated PET film 78.24

[0099] In Table 3, the contact angle of the double-layer composite anticoagulation coating region composed of polyamide and polytetrafluoroethylene is greater than 90°, therefore, the hydrophobicity of this double-layer composite anticoagulation coating region is also good, while the contact angle of the uncoated PET film is less than 90°, therefore, the hydrophobicity of the uncoated PET film is worse than that of the double-layer composite anticoagulation coating region.

[0100] 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.

[0101] Table 4: Clotting time (min) of anticoagulated blood and non-anticoagulated blood

[0102] area Coagulation time (min) Double-layer composite anti-coagulation coating area 40min Uncoated PET film 10min

[0103] In Table 4, the double-layer composite anticoagulation coating region composed of polyamide and polytetrafluoroethylene and the uncoated PET film also showed obvious differences in coagulation time, confirming that the double-layer composite anticoagulation coating region can effectively achieve a single-sided anticoagulation effect.

[0104] [Example 3]

[0105] Please refer to Figure 6 , Example 2 of the present application provides a left atrial appendage closure device, wherein the frame 1 is formed by cutting a nickel-titanium tube, and a portion of the outer surface of the frame 1 is covered with a layer of PET knitted film 2.

[0106] The proximal portion 210 of the PET knitted coating 2 is a sealing disk. The entire outer surface of the proximal portion 210 is first coated with a first adhesive layer 41 by ultrasonic spraying. The first adhesive layer 41 is composed of polycaprolactone (PCL), and then a second anti-coagulation layer 42 is coated by ultrasonic spraying. The second anti-coagulation layer 42 is composed of fluorinated ethylene propylene copolymer (FEP).

[0107] 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.

[0108] Table 5: Contact angles of anticoagulated area and non-anticoagulated blood (°)

[0109] area Contact angle (°) Double-layer composite anti-coagulation coating area 112.95 Uncoated PET film 78.24

[0110] In Table 5, the contact angle of the double-layer composite anticoagulation coating region composed of polycaprolactone and fluorinated ethylene propylene copolymer is also greater than 90°. Therefore, this double-layer composite anticoagulation coating region has good hydrophobicity, while the contact angle of the uncoated PET film is less than 90°, and its hydrophobicity is worse than that of the double-layer composite anticoagulation coating region.

[0111] 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.

[0112] Table 6: Coagulation time (min) of anticoagulated blood and non-anticoagulated blood

[0113]

[0114]

[0115] In Table 6, the double-layer composite anticoagulation coating area composed of polycaprolactone and fluorinated ethylene propylene copolymer showed a significant difference in clotting time compared with the uncoated PET film, confirming that fluorinated ethylene propylene copolymer (FEP) can effectively achieve a single-sided anticoagulation effect.

[0116] [Comparative Example]

[0117] The comparative embodiment is a left atrial appendage closure device, wherein the frame 1 is formed by cutting a nickel-titanium tube, and a portion of the outer surface of the frame 1 is covered with a layer of PET knitted film 2.

[0118] The proximal portion 210 of the PET knitted coating 2 is an occluding disk. At this time, the entire outer surface of the proximal portion 210 is only coated with a second anti-coagulation layer 42 by ultrasonic spraying. The component of the second anti-coagulation layer 42 is polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP).

[0119] 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.

[0120] Table 7: Contact angles of anticoagulated blood area and non-anticoagulated blood (°)

[0121] area Contact angle (°) Single layer anticoagulant coating area 108.72 Uncoated PET film 78.24

[0122] In Table 7, the contact angle of the single-layer anticoagulation coating region formed by polyvinylidene fluoride-hexafluoropropylene copolymer is greater than 90°. Therefore, the hydrophobicity of this double-layer composite anticoagulation coating region is good, while the contact angle of the uncoated PET film is less than 90°, indicating that the hydrophobicity is worse than that of the double-layer composite anticoagulation coating region.

[0123] 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 8 below.

[0124] Table 8: Clotting time (min) of anticoagulated blood and non-anticoagulated blood

[0125] area Coagulation time (min) Single layer anticoagulant coating area 35min Uncoated PET film 10min

[0126] In Table 8, the single-layer anticoagulation coating area formed by polyvinylidene fluoride-hexafluoropropylene copolymer showed obvious difference in coagulation time with the uncoated PET film, confirming that the double-layer composite anticoagulation coating area can effectively play a single-sided anticoagulation effect.

[0127] In another separate set of coating firmness tests, the left atrial appendage closure devices prepared in different embodiments and comparative examples were loaded into a delivery sheath and subjected to multiple in vitro insertion and removal tests for a fixed number of times. The surface coating morphology was observed by scanning electron microscopy to evaluate the firmness of the coatings prepared in different schemes.

[0128] Table 9: In vitro sheath insertion and removal test results of different embodiments

[0129] Number of insertions and extractions Example 1 Example 2 Example 3 Comparative Example 5 times No obvious damage No obvious damage No obvious damage No obvious damage 10 times No obvious damage No obvious damage No obvious damage Slight damage 15 times No obvious damage Slight damage Slight damage Visibly damaged and falling off 20 times Slight damage Slight damage Visibly damaged and falling off A lot of damage and falling off

[0130] According to Table 9, compared with Examples 1-3, there is no significant difference in the contact angle and coagulation time performance of the comparative example. However, the coating firmness results show that the coating prepared in the comparative example is more likely to fall off. In particular, as the number of insertion and removal of the sheath increases, the comparative example coating is obviously damaged and falls off, confirming that the double-layer composite anticoagulation coating has better firmness performance.

[0131] To summarize, the present application physically coats the anticoagulant composite coating 4 on the outer surface 21 of the coating 2. On the one hand, this enhances the anticoagulant properties of the outer surface of the coating 2, thereby reducing the possibility of thrombus formation on the device surface. On the other hand, the hydrophobic surface is conducive to cell adhesion and migration, thereby accelerating the endothelialization process on the device surface. On the other hand, the first adhesive layer 41 can be better combined with the coating 2 and the second anticoagulant layer 42, thereby increasing the firmness of the entire coating, reducing the risk of coating shedding, and maintaining a long-term anticoagulant effect. In addition, since the anticoagulant composite coating 4 is bonded to the surface of the coating 2 by physical coating, it also has the characteristics of simple process and good safety.

[0132] 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.

[0133] 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 closure device, characterized in that: include: A frame; a coating, which is arranged along at least a portion of the outer surface of the frame; and an anticoagulant composite coating, which is arranged on at least a portion of the outer surface of the coating; the anticoagulant composite coating includes a first adhesive layer and a second anticoagulant layer arranged from the inside to the outside along the thickness direction of the coating.

2. The left atrial appendage closure device according to claim 1, wherein: The coating includes a fiber bundle, which includes a plurality of fiber filaments. The anti-coagulation composite coating is arranged on the exposed surfaces of the outer fiber filaments in the fiber bundle and on the gaps between the outer fiber filaments.

3. The left atrial appendage closure device according to claim 2, wherein: The material of the coating is one of polyethylene, polypropylene, polyester, polyurethane and polyethylene terephthalate.

4. The left atrial appendage closure device according to claim 2, wherein: The pore size of the coating is 50 μm to 300 μm.

5. The left atrial appendage closure device according to claim 1, wherein: The first adhesive layer includes one of polyamide, polycarbonate, polydimethylsiloxane, polycaprolactone, methyl cellulose, ethyl cellulose, and polybutylene adipate / terephthalate.

6. The left atrial appendage closure device according to claim 1, wherein: The thickness of the first adhesive layer does not exceed 0.1 μm.

7. The left atrial appendage closure device according to claim 1, wherein: The second anti-coagulation layer has at least one of the following characteristics: The thickness of the second anticoagulant layer does not exceed 1 μm; The surface contact angle of the second anti-coagulation layer is 100° to 130°; The second anti-coagulation layer is composed of a fluorine-containing polymer.

8. The left atrial appendage closure device according to claim 1, wherein: The second anti-coagulation layer includes one of polytetrafluoroethylene, polyvinylidene fluoride, fluorinated ethylene propylene copolymer, and polyvinylidene fluoride-hexafluoropropylene copolymer.

9. The left atrial appendage closure device according to claim 1, wherein: It also includes a connecting structure, which is arranged at the proximal end of the frame and is used for detachable connection with the delivery system; the surface of the connecting structure and the surface of the frame are not provided with the anti-coagulation composite coating; And / or, the coating has a proximal portion and a distal portion axially arranged from the proximal end to the distal end of the frame, the proximal portion extends from the proximal end of the frame and covers the maximum outer diameter of the frame, and the anticoagulation composite coating is arranged on the entire outer surface of the proximal portion and extends beyond the maximum outer diameter of the frame.

10. The left atrial appendage closure device according to claim 1, wherein: The covering film is configured to have the anticoagulant composite coating only on at least a portion of its outer surface. The covering film is further configured so that except for the surface provided with the anticoagulant composite coating, all other surfaces are non-anticoagulant areas.

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