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, and the first bonding layer comprises an amphiphilic polymer. 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] This application relates to the field of medical devices, and in particular to a left atrial appendage closure device with an anticoagulant composite coating. Background Technology

[0002] Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and thromboembolism is a leading cause of death in AF patients. Clinical data shows that more than 90% of thrombus formation in AF patients is related to the left atrial appendage. Currently, left atrial appendage occlusion is a well-established method for preventing thromboembolism.

[0003] After implantation of a left atrial appendage occluder, complete endothelialization takes at least 4-6 weeks. Therefore, continuous anticoagulation therapy is necessary during this period. Applying an anticoagulant coating to the surface of the occluder can effectively reduce the risk of coagulation and some complications. Among the many complications of left atrial appendage occlusion, thrombosis on the occluder surface is a very common long-term complication. Its causes are complex and varied, related to factors such as the patient's own coagulation disorders, postoperative anticoagulation medication, the shape of the left atrial appendage and the occluder, and the occlusion itself. Furthermore, thrombosis carries a very high risk of embolism. Therefore, thrombosis seriously affects the safety of device use, making anticoagulant treatment of device surfaces that are in prolonged contact with blood essential.

[0004] However, the current main strategy for managing anticoagulation problems in clinical practice is to use systemic antibiotics and anticoagulants as adjunctive therapy. However, long-term use of antibiotics and anticoagulants inevitably leads to a series of side effects, such as antibiotic resistance and thrombocytopenia, and may even cause bleeding. Therefore, the best approach is to directly apply an anticoagulant coating to the surface of the medical device. However, most existing methods use heparin coatings for anticoagulation, which are chemically grafted onto the device surface. This process involves surface modification, is complex, requires repeated surface pretreatment, and involves toxic chemical reagents, raising safety concerns. In particular, the coating is prone to peeling and cannot maintain a long-term anticoagulant effect.

[0005] It should be noted that the information disclosed in the background section of this application is intended only to enhance the understanding of the general background of this application, and should not be construed as an admission or in any way implying that the information constitutes prior art known to those skilled in the art. Summary of the Invention

[0006] In view of this, the purpose of this 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 objectives, this application provides a left atrial appendage closure device, comprising: a frame; a membrane disposed along at least a portion of the outer surface of the frame; and an anticoagulant composite coating disposed on at least a portion of the outer surface of the membrane; the anticoagulant composite coating comprising a first adhesive layer and a second anticoagulant layer disposed from the inside to the outside along the thickness direction of the membrane, wherein the first adhesive layer comprises an amphiphilic polymer.

[0008] Optionally, the coating comprises a fiber bundle, the fiber bundle comprising a plurality of filaments, and the anti-coating composite coating is disposed on the surface of the outer filaments exposed in the fiber bundle and in the gaps between the outer filaments.

[0009] Optionally, the coating material is at least 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 comprises at least one of polyamide, polycarbonate, polydimethylsiloxane, polycaprolactone, methylcellulose, ethylcellulose, and polybutylene adipate / terephthalate.

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

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

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

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

[0016] The second anticoagulant layer comprises a fluoropolymer.

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

[0018] Optionally, a connecting structure is also included, which is disposed at the proximal end of the frame and is used for a detachable connection with the conveying system; neither the surface of the connecting structure nor the surface of the frame is provided with the anti-condensation composite coating.

[0019] And / or, the coating has a proximal portion and a distal portion axially disposed from the proximal end to the distal end of the frame, the proximal portion extending from the proximal end of the frame and covering the maximum outer diameter of the frame, the anti-condensation composite coating being disposed on the entire outer surface of the proximal portion and extending beyond the maximum outer diameter of the frame.

[0020] Optionally, the membrane is configured to have the anticoagulant composite coating applied only to at least a portion of its outer surface, and the membrane is further configured such that, apart from the surface with the anticoagulant composite coating, the other surfaces are non-anticoagulant areas.

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

[0022] This configuration has several advantages. First, the anticoagulant composite coating, which includes a second anticoagulant layer, is applied to the outer surface of the membrane. This allows the membrane surface to function as an anticoagulant through the second anticoagulant layer, thereby reducing the risk of thrombus formation on the device surface and accelerating the endothelialization process. Second, the first adhesive layer has both hydrophilic and hydrophobic properties, allowing it to bond well with the membrane and the second anticoagulant layer. This increases the overall strength of the coating, reduces the risk of coating detachment, and maintains a long-term anticoagulant effect. Furthermore, since the anticoagulant composite coating is applied to the membrane surface through physical coating, the process is simple and safe. Attached Figure Description

[0023] Those skilled in the art will understand that the accompanying drawings are provided to better understand this application and do not constitute any limitation on the scope of this application. Wherein:

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

[0025] Figure 2 This is a schematic diagram of a structure in which an anti-coating composite coating is provided on at least a portion of the outer surface of the membrane according to an embodiment of this application;

[0026] Figure 3 This is a schematic diagram of the cross-section of the woven mesh film with anti-coating composite coating and its fiber bundles according to an embodiment of this application;

[0027] Figure 4 This is a schematic diagram of the left atrial appendage closure device described in Embodiment 1 of this application;

[0028] Figure 5 This is a schematic diagram of the left atrial appendage closure device described in Embodiment 2 of this application;

[0029] Figure 6 This is a schematic diagram of the left atrial appendage closure device described in Embodiment 3 of this application.

[0030] In the attached image:

[0031] 1-Frame; 11-Distal tail; 2-Cover; 201-Fiber bundle; 202-Fiber filament; 21-Outer surface of the cover; 22-Inner surface of the cover; 210-Proximal portion; 220-Distal portion; 3-Connecting structure; 4-Anticoagulant composite coating; 41-First adhesive layer; 42-Second anticoagulant layer. Detailed Implementation

[0032] The following specific examples illustrate the implementation of this application. Those skilled in the art can easily understand other advantages and effects of this application from the content disclosed in this specification. This application can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of this application. It should be noted that the illustrations provided in this embodiment are only schematic representations of the basic concept of this application. Therefore, the drawings only show components related to this application and are not drawn according to the actual number, shape, and size of components in the implementation. In actual implementation, the type, quantity, and proportion of each component can be arbitrarily changed, and the component layout may also be more complex.

[0033] Furthermore, while each embodiment described below possesses one or more technical features, this does not imply that users of this application must simultaneously implement all technical features in any embodiment, or can only separately implement some or all technical features in different embodiments. In other words, where implementation is possible, those skilled in the art can selectively implement some or all of the technical features in any embodiment, or selectively implement a combination of some or all of the technical features in multiple embodiments, based on the disclosure of this application and depending on design specifications or implementation requirements, thereby increasing the flexibility in implementing this application.

[0034] As used herein, the singular forms “a,” “an,” and “the” include plural objects, the plural form “multiple” includes two or more objects, and “a number” is used to indicate an indefinite quantity unless otherwise specified. As used herein, the term “or” is generally used to include the meaning of “and / or” unless otherwise specified, and the terms “installed,” “connected,” and “linked” should be interpreted broadly, for example, as a fixed connection, a detachable connection, or an integral connection. Connections can be mechanical, direct, or indirect via an intermediate medium, and can represent internal communication or interaction between two elements. Relational terms such as “first,” “second,” etc., are used merely to distinguish one entity or operation from another, 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 specify the quantity of the indicated technical features. It should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "axial," "radial," and "circumferential," etc., indicating orientation or positional relationships, are based on the orientation or positional relationships shown in the accompanying drawings and are used 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, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances.

[0035] In this application, the term "axial" 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 diametrical direction of the left atrial appendage closure device, i.e., the direction perpendicular to the axial direction. The term "lateral" generally refers to the direction away from the central axis of the left atrial appendage closure device, and "medial" refers to the direction closer to the central axis of the left atrial appendage closure device. The terms "distal" and "proximal" are described based on the relative orientation and position of the various components and elements of the left atrial appendage closure device. Although not restrictive, "distal" generally refers to the end of the left atrial appendage closure device that first enters the patient's body during normal use, and "proximal" is the end opposite to "distal," i.e., the end of the left atrial appendage closure device closer to the operator. In this document, "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 surface coagulation in medical devices in existing related technologies. The following description refers to the accompanying drawings.

[0037] Figure 1 The structural configuration of the left atrial appendage closure device in some embodiments is illustrated schematically. For example... Figure 1 As shown, the left atrial appendage closure device includes: an expandable frame 1; a membrane 2 disposed on the frame 1; and a connection structure 3 that can be connected to and disconnected from the delivery system.

[0038] Frame 1 is preferably a self-expanding structure. Frame 1 can be made of any suitable material, with nickel-titanium alloy being the most preferred. Optionally, frame 1 is made by cutting nickel-titanium tubing. Frame 1 has a compressed state and an expanded state, and can freely switch between the two states. Specifically, during the delivery of the left atrial appendage closure device via the delivery system, frame 1 is in a compressed state; once frame 1 is released from the delivery system, frame 1 autonomously expands to the expanded state (i.e., the usage state).

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

[0040] After at least a portion of the outer surface of the frame 1 is covered by the cladding 2, an occlusion disc is formed, which can be used to isolate blood flow. In some embodiments, the cladding 2 can prevent thrombi (i.e., blood clots, etc.) from passing through the cladding 2 and leaving the left atrial appendage to enter the blood flow. In some embodiments, the cladding 2 can also promote endothelial cell growth, reduce the risk of restenosis, etc.

[0041] Specifically, the covering 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 covering 2 may be disposed along a portion of the outer surface of the frame 1, exposing the distal tail 11 of the frame 1 to the outside of the covering 2, forming a skirt. The skirt is generally bent inward to prevent the skirt of the frame 1 from causing damage to the tissue structure during and after implantation. However, those skilled in the art will understand that the covering 2 may extend along the outer surface of the frame 1 to any extent, for example, extending to cover almost the entire outer surface of the frame 1.

[0042] The coating 2 can be a knitted material, fiber, fabric, nonwoven fabric, braid, or other suitable structure, preferably a fibrous mesh woven film. The coating 2 can be made of suitable materials, such as polyethylene (PE), polypropylene (PP), polyester, polyurethane (PU), polyethylene terephthalate (PET), or other materials, and the coating 2 can include one material or a combination of multiple materials.

[0043] The height of the overlay 2 may not exceed 2 / 3 of the total height of the frame 1, but is not limited to this in practice. 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 overlay 2 refers to the distance that the overlay 2 extends from the proximal end to the distal end of the frame 1.

[0044] The connecting structure 3 is located at the proximal end of the frame 1 and can be releasably connected to the distal end of the conveying system using a suitable structure. For example, the connecting structure 3 has an internal thread, which allows for threaded connection to the distal end of the conveying system. However, the threaded connection is not limiting; in practice, the connecting structure 3 can be releasably connected to the distal end of the conveying system by various means.

[0045] It should also be understood that although the membrane 2 itself has good mechanical properties, biological stability, and safety, the anticoagulation effect of the membrane material is generally poor. Therefore, it is necessary to select a material with better hydrophobicity for anticoagulation treatment. Therefore, the membrane 2 needs to be equipped with an anticoagulation coating.

[0046] like Figures 1 to 3 As shown in various embodiments of this 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 cover 2. This anticoagulant composite coating 4 has an anticoagulant effect, reducing the risk of thrombus formation on the device surface and accelerating the endothelialization process. Preferably, the cover 2 is only provided with the anticoagulant composite coating 4 on its outer surface 21; the other surfaces are non-anticoagulant areas. Specifically, the connecting structure 3 typically does not require the cover 2, therefore, the anticoagulant composite coating 4 is not required at the connecting structure 3; if it were, the anticoagulant composite coating 4 would easily detach. The frame 1 primarily provides support; if the anticoagulant composite coating 4 were provided on the frame 1, it would easily detach during device compression and release. Therefore, the frame 1 does not require the anticoagulant composite coating 4. Thus, the anticoagulant and non-anticoagulant descriptions in this application refer specifically to the cover 2.

[0047] More in detail, such as Figure 2 and Figure 3As shown, the anticoagulant composite coating 4 has a two-layer structure, comprising a first adhesive layer 41 and a second anticoagulant layer 42 disposed 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 is both hydrophilic and hydrophobic, specifically a high molecular weight polymer containing both hydrophilic and hydrophobic groups. In addition to including the amphiphilic polymer, the first adhesive layer 41 may contain other components or may not 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 membrane 2 to form an anticoagulant outer surface through the outermost second anticoagulant layer 42. This anticoagulant outer surface can effectively inhibit thrombus formation, thereby accelerating the endothelialization process, thus speeding up the closure process and reducing autoreaction. Furthermore, because the second anticoagulant layer 42 has hydrophobic properties, this hydrophobic outer surface can also effectively prevent tissue adhesion during implantation, improve instrument operability, reduce tissue damage caused by instrument manipulation, and increase surgical safety.

[0049] Specifically, when the anticoagulant outer surface of the membrane 2 comes into contact with blood, the second anticoagulant layer 42 in the anticoagulant composite coating 4 effectively prevents blood from adhering to and coagulating on the instrument surface. In particular, the anticoagulant effect is even better when the second anticoagulant layer 42 is an inert hydrophobic polymer coating. Inert hydrophobic polymer coatings mainly refer to fluoropolymer coatings. Inert hydrophobic polymer coatings can prevent plasma components from adhering by utilizing hydrophobic properties, thereby achieving an anticoagulant effect.

[0050] Simultaneously, a first adhesive layer 41 (i.e., a coating interlayer) exists between the second anticoagulant layer 42 and the outer surface 21 of the covering 2. The first adhesive layer 41 is essentially completely covered by the second anticoagulant layer 42. Because the first adhesive layer 41 has both hydrophilic and hydrophobic properties, it can bond well with the covering 2 and the second anticoagulant layer 42, thereby increasing the overall coating's strength and reducing the risk of coating detachment. It is particularly resistant to detachment during repeated insertion within the sheath, thus enabling the coating to maintain a long-term anticoagulant effect.

[0051] The anti-condensation composite coating 4 can be applied to the outer surface 21 of the membrane 2 in a suitable manner, such as physical coating, including optional methods like ultrasonic spraying, dip coating, physical / chemical deposition, plasma coating, and atomized spraying. Ultrasonic spraying is a more suitable method. Here, since the anti-condensation composite coating 4 is applied to the outer surface 21 of the membrane 2 through physical coating, the process is simple and safe.

[0052] Furthermore, compared to other methods, ultrasonic spraying offers greater process stability and controllability. It is also suitable for single-sided anti-coating treatment and allows for easy adjustment and control of process parameters, resulting in a more stable and reliable process. Another advantage of ultrasonic spraying is its lower material consumption and cost. Ultrasonic spraying can be performed before or after the coating 2 is applied to the frame 1; preferably, it is performed after the coating 2 is applied to the frame 1, which provides greater control and better spraying results.

[0053] In practice, at least the outer surface 21 of the membrane 2, where it directly contacts the blood, needs to be coated with an anticoagulant composite coating 4. However, the interior of most medical devices is not significantly affected by thrombosis or surface endothelialization; therefore, the inner surface 22 of the membrane 2 does not require anticoagulant treatment. This single-sided anticoagulant treatment reduces material usage and costs, and also helps to secure the entire left atrial appendage closure device. Here, when the inner surface 22 of the membrane 2 is not treated with anticoagulant, after the left atrial appendage closure device is implanted, a blood clot can quickly form inside the frame 1, which helps to quickly fix the left atrial appendage closure device at the left atrial appendage, making the entire device more secure and less prone to displacement.

[0054] In this embodiment, the anti-coating 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 uniformly distributed along the outer surface 21 of the membrane 2, which can better achieve single-sided anti-coating.

[0055] refer to Figure 3 As shown, in a preferred embodiment, the membrane 2 is a fibrous mesh woven membrane, wherein the anti-condensation 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. Here, it is considered that, at the microscopic morphology level, the fiber filaments 202 with and without the anti-condensation composite coating 4 are distinguished; that is, it is clarified that after the fibrous mesh woven membrane covers the outer surface of the frame 1, the inner fiber filaments 202 and the fiber filaments 202 whose surfaces are not exposed are not coated with the anti-condensation composite coating 4.

[0056] When the coating 2 is a fibrous mesh woven membrane, it includes one or more fiber bundles 201. Each fiber bundle 201 may include a suitable number of fiber filaments 202. The fiber filaments 202 are individual fine filaments. After the suitable number of fiber filaments 202 are wound to form the fiber bundle 201, the one or more fiber bundles 201 are then formed into the fibrous mesh structure of the coating 2 by means of, for example, weaving, knitting, spinning, electrospinning or other methods.

[0057] It should be noted that the anti-condensation composite coating 4 does not encapsulate each fiber filament 202 within the fiber bundle 201. Furthermore, the anti-condensation composite coating 4 is only applied to the outer side of the fiber bundle 201 and does not penetrate into the inner region of the fiber bundle 201. Therefore, the inner fiber filaments 202 do not have the anti-condensation composite coating 4, thus achieving one-sided anti-condensation. Simultaneously, the anti-condensation composite coating 4 does not obstruct the fiber bundles 201 on the coating 2 or the mesh formed by their interlacing, and does not affect the performance of the coating 2 itself, allowing the coating 2 to maintain its original porous structure (i.e., mesh).

[0058] Here, when the membrane 2 is made of a fibrous mesh woven membrane, it provides good mechanical support, and the mesh of the fibrous mesh woven membrane allows blood flow but prevents thrombus passage. Thus, the membrane 2 itself has a porous structure. Preferably, the pore size of the membrane 2 is 50μm to 300μm; this pore size facilitates blood flow through the membrane 2 but effectively prevents thrombus passage.

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

[0060] As described above, an anticoagulant composite coating 4 must be applied to at least the portion of the outer surface 21 of the membrane 2 that is in direct contact with blood. In practice, the anticoagulant composite coating 4 must therefore be applied at least to the occlusion plate of the left atrial appendage closure device (i.e., Figure 1 (The position of the mid-section line) can cover up to the entire outer surface of the coating 2.

[0061] Please refer to Figure 1 In this embodiment, the membrane 2 has a proximal portion 210 and a distal portion 220 axially disposed 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 membrane 2 covers the periphery 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 position of the maximum outer diameter (Dmax) of the frame 1. The distal portion 220 extends from the junction with the proximal portion 210 to cover the distal end of the membrane 2, that is, the area of ​​the membrane 2 other than the proximal portion 210 is the distal portion 220.

[0062] The distal portion 220 is the anchoring area, which needs to be in contact with the left atrial appendage wall to ensure the stability of the device after implantation in the left atrial appendage, enabling the device to stably and effectively occlude the left atrial appendage. The proximal portion 210 is basically not used for anchoring support. It faces the atrium and is positioned at the entrance of the left atrial appendage, in contact with blood, and does not require anchoring.

[0063] Preferably, the anticoagulant composite coating 4 extends from the proximal end of the frame 1 and covers the position of 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 position of the maximum outer diameter of the frame 1. The distance beyond the maximum outer diameter can be 3 mm, 5 mm, or other dimensions. The area of ​​the membrane 2 other than that covered with the anticoagulant composite coating 4 is a non-anticoagulant area.

[0064] It should also be understood that the left atrial appendage closure device frequently needs to be inserted into or withdrawn from the delivery sheath during delivery or withdrawal. During these insertions and withdrawals, the presence of the anticoagulant composite coating 4 helps reduce the friction between the diaphragm 2 and the sheath, resulting in a smaller insertion force for the diaphragm 2 at its maximum outer diameter (Dmax) position on the frame 1. In particular, when the anticoagulant composite coating 4 is made of a fluoropolymer, an even lower surface friction coefficient can be achieved, further reducing the insertion force. Furthermore, after implantation, the non-anticoagulant area on the diaphragm 2 can increase the friction between the diaphragm 2 and the left atrial appendage wall, thereby enhancing the stability of the left atrial appendage closure device after implantation.

[0065] Therefore, the anticoagulation and non-anticoagulation regions of the coating 2 can be used to balance sheath insertion and anchoring performance, achieving low sheath insertion 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 anticoagulation composite coating 4, the device's fixation is mainly ensured by anchoring in the non-anticoagulation region; therefore, the anticoagulation composite coating 4 does not affect the overall stability of the device.

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

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

[0068] Preferably, the second anticoagulant layer 42 comprises a fluoropolymer, such as a combination of one or more fluoropolymers.

[0069] When the second anticoagulant layer 42 includes a fluoropolymer, the presence of fluorine groups gives the surface of the second anticoagulant layer 42 a generally high degree of hydrophobicity, resulting in better anticoagulation. Simultaneously, the hydrophobic surface of the second anticoagulant layer 42 makes it difficult for fibrinogen and platelets, which induce thrombus formation, to adhere to the surface of the coating 2, thus preventing coagulation reactions and achieving an anticoagulant effect. Furthermore, the hydrophobic properties of the second anticoagulant layer 42 allow albumin to be firmly adsorbed onto its surface, promoting endothelial cell migration and migration, thereby accelerating endothelialization of the material surface and effectively reducing complications. In addition, the fluoropolymer has excellent film-forming properties, enabling the second anticoagulant layer 42 to uniformly coat the outer surface 21 of the coating 2 and rapidly solidify into a film, firmly bonding with the first adhesive layer 41, preventing detachment and particle shedding, and exhibiting good biocompatibility and stability. Of course, the fluoropolymer also has good biocompatibility and stable properties, providing a long-term stable anticoagulant effect.

[0070] The second anticoagulant layer 42 includes, 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 one or more combinations of these fluoropolymers. Preferably, the second anticoagulant layer 42 is composed of polyvinylidene fluoride-hexafluoropropylene copolymer, which has relatively better effectiveness and safety, is less prone to peeling, and has good long-term anticoagulant effect.

[0071] The second anticoagulant layer 42 may also include a non-fluorinated polymer, specifically, a high molecular weight polymer (non-fluorinated polymer) with better hydrophobicity than the coating 2. The second anticoagulant layer 42 includes, for example, polystyrene, polyurethane, polyester, and combinations thereof.

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

[0073] The thickness of the second anticoagulant layer 42 should not be too large or too small. Preferably, the thickness of the second anticoagulant layer 42 does not exceed 1 μm; in this way, the anticoagulant effect of the second anticoagulant layer 42 can be guaranteed, and it is not easy to fall off, resulting in better safety and effectiveness, and it does not affect the insertion of the instrument sheath.

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

[0075] Furthermore, the non-anticoagulation areas on the membrane 2 can be the membrane material without any coating; that is, the portion of the membrane 2 without the anticoagulant composite coating 4 is exposed and directly forms a non-anticoagulation area. Alternatively, the exposed portion of the membrane 2 can be further coated with a non-anticoagulation coating, forming the non-anticoagulation area. Therefore, the non-anticoagulation area can include either the non-anticoagulation coating or the exposed portion of the membrane 2.

[0076] It should be understood that the non-anticoagulant coating is composed of a non-anticoagulant polymer material. Non-anticoagulant polymer materials have few hydrophobic groups and poor hydrophobicity of these groups. Therefore, under normal circumstances, the hydrophobicity of the non-anticoagulant coating is inferior to that of the membrane 2, which facilitates rapid coagulation inside the sealing device and fills and seals the internal area. Alternatively, the non-anticoagulant coating can also be made of a non-anticoagulant polymer material with hydrophilic groups.

[0077] The non-anticoagulant coating can be applied to either the inner surface 22 or the outer surface 21 of the membrane 2. When the non-anticoagulant coating is applied to the outer surface 21 of the membrane 2, it increases the coefficient of friction of the non-coagulation area on the outer surface of the membrane 2, thereby increasing the friction between the membrane 2 and the left atrial appendage wall, thus enhancing the stability of the device after implantation.

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

[0079] Optionally, the thickness of the non-anticoagulant coating is less than or equal to 0.1 mm. 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 following specific examples further illustrate the left atrial appendage closure device provided in this application. Of course, the following specific examples are only for illustrative purposes and are not intended to limit this application in any way.

[0081] Example 1

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

[0083] The proximal portion 210 of the PET knitted film 2 is a sealing plate. 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 composition of the first adhesive layer 41 is polydimethylsiloxane. Then, the second anticoagulant layer 42 is coated by ultrasonic spraying. The composition of the second anticoagulant layer 42 is polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP).

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

[0085] In a separate contact angle test, the contact angles of the anticoagulant and non-anticoagulant regions of the PET knitted film relative to pure water were tested, and the test results are shown in Table 1 below.

[0086] Table 1: Contact angle (°) between anticoagulated and non-anticoagulated blood regions

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

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

[0089] In a separate anticoagulation test, the coagulation properties of the anticoagulation and non-anticoagulation areas of the PET knitted film were characterized by immersion in whole blood of adult pig arterial blood (without heparin). The results are shown in Table 2 below.

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

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

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

[0093]

Example 2

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

[0095] The proximal portion 210 of the PET knitted film 2 is a sealing disc. Thus, the entire outer surface of the proximal portion 210 is first coated with a first adhesive layer 41 by ultrasonic spraying. The composition of the first adhesive layer 41 is polyamide (PA). Then, a second anticoagulant layer 42 is coated by ultrasonic spraying. The composition of the second anticoagulant layer 42 is polytetrafluoroethylene (PTFE).

[0096] In the separate contact angle test, the contact angles of the anticoagulant and non-anticoagulant regions of the PET knitted film relative to pure water were tested, and the test results are shown in Table 3 below.

[0097] Table 3: Contact angle (°) between anticoagulated and non-anticoagulated blood regions

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

[0099] In Table 3, the contact angle of the double-layer composite anti-condensation coating area composed of polyamide and polytetrafluoroethylene is greater than 90°. Therefore, this double-layer composite anti-condensation coating area has good hydrophobicity. In contrast, 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 anti-condensation coating area.

[0100] In a separate anticoagulation test, the coagulation properties of the anticoagulation and non-anticoagulation areas of the PET knitted film were characterized by immersion in whole blood of adult pig arterial blood (without heparin). The results are shown in Table 4 below.

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

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

[0103] In Table 4, the double-layer composite anticoagulant coating area composed of polyamide and polytetrafluoroethylene also showed a significant difference in clotting time compared with the uncoated PET film, confirming that the double-layer composite anticoagulant coating area can effectively achieve the anticoagulant effect on one side.

[0104]

Example 3

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

[0106] The proximal portion 210 of the PET knitted film 2 is a sealing disc. 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). Then, a second anticoagulant layer 42 is coated by ultrasonic spraying. The second anticoagulant layer 42 is composed of fluorinated ethylene propylene copolymer (FEP).

[0107] In the separate contact angle test, the contact angles of the anticoagulant and non-anticoagulant regions of the PET knitted film relative to pure water were tested, and the test results are shown in Table 5 below.

[0108] Table 5: Contact angle (°) between anticoagulated and non-anticoagulated blood regions

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

[0110] In Table 5, the contact angle of the double-layer composite anti-condensation coating region composed of polycaprolactone and fluorinated ethylene propylene copolymer is also greater than 90°. Therefore, this double-layer composite anti-condensation 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 anti-condensation coating region.

[0111] In a separate anticoagulation test, the coagulation properties of the anticoagulation and non-anticoagulation areas of the PET knitted film were characterized by immersion in whole blood of adult pig arterial blood (without heparin). The results are shown in Table 6 below.

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

[0113] area Clotting time (min) Double-layer composite anti-condensation coating area 40min Uncoated PET film 10min

[0114] In Table 6, the double-layer composite anticoagulant 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 anticoagulant effect.

[0115] [Comparative Examples]

[0116] The comparative embodiment is a left atrial appendage closure device, wherein the frame 1 is formed by cutting a nickel-titanium tube, and a layer of PET knitted film 2 covers part of the outer surface of the frame 1.

[0117] The proximal portion 210 of the PET knitted film 2 is a sealing plate. At this time, the entire outer surface of the proximal portion 210 is coated with a second anticoagulant layer 42 by ultrasonic spraying. The composition of the second anticoagulant layer 42 is polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP).

[0118] In a separate contact angle test, the contact angles of the anticoagulant and non-anticoagulant regions of the PET knitted film relative to pure water were tested, and the test results are shown in Table 1 below.

[0119] Table 7: Contact angle (°) between anticoagulated and non-anticoagulated blood regions

[0120] area Contact angle (°) Single-layer anti-condensation coating area 108.72 Uncoated PET film 78.24

[0121] In Table 7, the contact angle of the single-layer anti-condensation coating area formed by polyvinylidene fluoride-hexafluoropropylene copolymer is greater than 90°. Therefore, this double-layer composite anti-condensation coating area has good hydrophobicity. In contrast, the contact angle of the uncoated PET film is less than 90°, indicating that its hydrophobicity is worse than that of the double-layer composite anti-condensation coating area.

[0122] In a separate anticoagulation test, the coagulation properties of the anticoagulation and non-anticoagulation areas of the PET knitted film were characterized by immersion in whole blood of adult pig arterial blood (without heparin). The results are shown in Table 8 below.

[0123] Table 8: Clotting time (min) of anticoagulated and non-anticoagulated blood

[0124]

[0125]

[0126] In Table 8, the monolayer anticoagulant coating area formed by polyvinylidene fluoride-hexafluoropropylene copolymer showed a significant difference in clotting time compared to the uncoated PET film, confirming that the bilayer composite anticoagulant coating area can effectively provide a single-sided anticoagulant effect.

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

[0128] Table 9: Results of in vitro sheath entry / exit tests for different embodiments

[0129] Number of times it enters and exits the sheath Example 1 Example 2 Example 3 Comparative Examples 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 Minor damage 15 times No obvious damage Minor damage Minor damage Obvious damage and detachment 20 times Minor damage Minor damage Obvious damage and detachment Extensive damage and detachment

[0130] As can be seen from Table 9, compared with Examples 1-3, there was no significant difference in the contact angle and clotting time performance of the comparative examples. However, the coating adhesion results showed that the coating prepared in the comparative examples was more likely to fall off. In particular, with the increase of the number of times the sheath was inserted and removed, the coating of the comparative examples showed obvious damage and peeling, which confirmed that the double-layer composite anticoagulant coating had better adhesion performance.

[0131] In summary, this application achieves several advantages by physically coating the outer surface 21 of the membrane 2 with an anticoagulant composite coating 4. Firstly, this enhances the anticoagulant properties of the outer surface of the membrane 2, thereby reducing the likelihood of thrombus formation on the device surface. Secondly, the hydrophobic surface facilitates cell adhesion and migration, accelerating the endothelialization process on the device surface. Furthermore, the first adhesive layer 41 can effectively bond with the membrane 2 and the second anticoagulant layer 42, increasing the overall coating's strength, reducing the risk of coating detachment, and maintaining a long-term anticoagulant effect. Additionally, since the anticoagulant composite coating 4 is physically applied to the surface of the membrane 2, it also features a simple process and good safety.

[0132] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above 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 embodiments described above are merely examples of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of this application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these modifications and improvements all fall within the protection scope of this application.

Claims

1. A left atrial appendage closure device, characterized by, The frame; a film disposed along at least a portion of an outer surface of the frame; and an anticoagulant composite coating disposed on at least a portion of an outer surface of the film; the anticoagulant composite coating comprising a first adhesive layer and a second anticoagulant layer disposed from inside to outside along a thickness direction of the film, the first adhesive layer comprising an amphiphilic polymer. The film comprises a fiber bundle comprising a plurality of fiber filaments, the anticoagulant composite coating being disposed on surfaces exposed by outer fiber filaments in the fiber bundle and interstices between the outer fiber filaments and the fiber filaments.

2. The LAA closure device of claim 1, wherein The material of the film is at least one of polyethylene, polypropylene, polyester, polyurethane, poly-p-xylylene glycol.

3. The LAA closure device of claim 2, wherein The pore size of the film is 50 μm to 300 μm.

4. The LAA closure device of claim 2, wherein, The first adhesive layer comprises at least one of polyamide, polycarbonate, polydimethylsiloxane, polycaprolactone, methyl cellulose, ethyl cellulose, polybutylene adipate / terephthalate.

5. The LAA closure device of claim 1, wherein The thickness of the first adhesive layer is not more than 0.1 μm.

6. The LAA closure device of claim 1, wherein, The second anticoagulant layer has at least one of the following characteristics:

7. The LAA closure device of claim 1, wherein The thickness of the second anticoagulant layer is not more than 1 μm; The surface contact angle of the second anticoagulant layer is 100° to 130° The second anticoagulant layer comprises a fluoropolymer. The second anticoagulant layer comprises at least one of polytetrafluoroethylene, polyvinylidene fluoride, fluorinated ethylene propylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer.

8. The LAA closure device of claim 1, wherein, Further comprising a connection structure disposed at a proximal end of the frame and configured to be releasably connected with a delivery system; the surface of the connection structure and the surface of the frame are both not provided with the anticoagulant composite coating; 9. The LAA closure device of claim 1, wherein, And / or, the film has a proximal portion and a distal portion disposed axially from the proximal end to the distal end of the frame, the proximal portion extending from the proximal end of the frame and covering to the maximum outer diameter of the frame, the anticoagulant composite coating being disposed on the entire outer surface of the proximal portion and extending beyond the maximum outer diameter of the frame. The film is configured to dispose the anticoagulant composite coating only on at least a portion of its outer surface, and the film is further configured to be a non-anticoagulant region on other surfaces except the surface provided with the anticoagulant composite coating.

10. The LAA closure device of claim 1, wherein, ​

Images