A multi-stage unfolded self-assembly heart defect occluder and preparation method thereof

Abstract

The present invention provides a multi-stage unfolding self-assembling heart defect occluder and a preparation method thereof, and relates to the technical field of medical devices. The present invention sets a support frame including a disc body, a support frame, and a connecting belt to support a flow-blocking membrane, and uses shape memory materials with different transition temperatures for the connecting belt and the support frame, thereby producing shape changes under multiple temperature stimuli, realizing the graded recovery of the double discs and the "waist" of the occluder, so that the two can be unfolded autonomously in sequence, and the stability and uniformity of the unfolding process are increased. Compared with traditional occluders, the occluder of the present invention has a higher locking efficiency, can reduce the wear on the lesion caused by the uneven deformation of the double discs of the occluder, and reduce the erosion to the heart. At the same time, the shape memory polymer composite material also has good biocompatibility and degradability. Compared with traditional metal occluders, it can reduce the risks of cardiovascular abrasion perforation, allergies, arrhythmias, occluder shedding and other hidden dangers.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a multi-stage unfolded self-assembled heart defect occluder and a preparation method thereof. Background Art

[0002] With the continuous development of modern medical technology, cardiovascular disease has become one of the major health challenges worldwide. Structural heart disease is a type of heart disease characterized by abnormalities in the structure of the heart and large blood vessels, including congenital heart disease, valvular heart disease and cardiomyopathy. Interventional therapy has become an important means of treating structural heart disease. Interventional treatment methods mainly include the application of various occluders and the implantation of different metal stents. Taking the occluder as an example, it is usually a double-disc structure, consisting of a double disc and a "waist" connecting the double discs. The double discs are like two opposite umbrella pieces, and the "waist" is a short cylindrical shape. The occluder is implanted in the heart and fixed to the defect site to block the left-to-right shunt of blood, allowing the heart to restore normal blood circulation.

[0003] The raw materials of occluders have always been mainly nickel-titanium alloy and ceramic-coated alloy. Some patients may be at risk of complications such as allergies, erosion, infection, and embolism. Shape memory degradable occluders, due to their advantage of being degradable in the body, reduce complications such as allergies and embolism caused by metal occluders, and gradually replace metal occluders. The preparation of occluders that can change shape through external stimulation using shape memory materials can achieve minimally invasive treatment with preoperative shaping and intraoperative deployment. However, the deployment of the double discs and the "waist" of the shape memory occluder is usually carried out at the same time, which may cause the occluder to be subjected to uneven mechanical pressure distribution inside the heart, increase the possibility of friction with heart tissue, and have the risk of cardiovascular abrasion and perforation; and the simultaneous deployment of the double discs and the "waist" may also cause the occluder to be unstable in the fixed position at the implantation site, thereby affecting the electrical activity of the heart, leading to the occurrence of arrhythmias, or due to insufficient fixation, increase the risk of the occluder falling off. Summary of the invention

[0004] The problem that the present invention solves is that the double discs and waist of traditional metal occluders and primary shape memory occluders are deployed simultaneously, which may cause the cardiac occluder to be deployed before it is in place, resulting in inaccurate defect occlusion, tissue expansion, wear and tear, and even risks such as cardiovascular abrasion and perforation, arrhythmia, and occluder detachment.

[0005] In order to solve the above problems, the present invention provides a multi-stage unfolded self-assembled heart defect occluder and a preparation and use method thereof.

[0006] In a first aspect, the present invention provides a multi-stage unfolded self-assembled heart defect occluder, comprising a support frame and a flow-blocking membrane arranged on the support frame;

[0007] The support frame comprises two disc-shaped structures arranged opposite to each other and a support frame arranged between the two disc-shaped structures;

[0008] The disc-shaped structure includes a disc body and a connecting belt arranged on the circumference of the disc body, the support frame is connected between two opposite disc bodies, and the two ends of the support frame are staggeredly connected to the two disc bodies, so that the support frame can be rotated to extend or shorten under temperature stimulation; the flow-blocking film is connected to the connecting belt, and can be expanded or folded under the drive of the connecting belt. When the flow-blocking film is expanded, the disc-shaped structure is a planar structure, and when the flow-blocking film is folded, the disc-shaped structure is a platform structure;

[0009] The support frame is made of a first shape memory material, the connecting belt is made of a second shape memory material, and the first shape memory material and the second shape memory material have different transition temperatures.

[0010] Optionally, a plurality of the connecting belts are arranged at intervals along the circumference of the disk body, one end of the connecting belt is connected to the disk body, and the other end extends in a direction away from the disk body, and the plane where the disk body is in a planar structure is taken as the projection plane, and the projection of the connecting belt on the projection plane in the unfolded state is a straight line, a broken line, a curve or a combination thereof;

[0011] And / or, the cross-sectional shape of the disk body is circular, elliptical, quasi-circular or polygonal.

[0012] Optionally, the distance between the two disc-shaped structures can be customized according to the type of heart defect and the patient's condition;

[0013] And / or, the distance between the two disc-shaped structures is 3 mm-5 mm smaller than the height of the heart defect.

[0014] Optionally, the cross-sectional shape of the disk body is a polygon, the number of the connecting belts is the same as the number of sides of the disk body, and each of the connecting belts is respectively connected to the midpoint of each side of the disk body.

[0015] Optionally, the number of the blocking films is the same as the number of the connecting strips, and each blocking film is connected to each connecting strip respectively.

[0016] Optionally, the support frame includes a plurality of ligaments, the number of the ligaments is the same as the number of sides of the disc body, and two ends of the ligaments are respectively connected to two opposite disc-shaped structures.

[0017] Optionally, when the baffle films are in an unfolded state, there is an overlapping area between adjacent baffle films, and the baffle films are stacked in sequence along the circumference of the disk body.

[0018] Optionally, at a first preset temperature, the multi-stage unfolded self-assembled heart defect occluder is shaped into a temporary shape, the flow blocking membrane is retracted toward the center line of the disk body until the disk-shaped structure becomes the platform structure, and the support frame is rotated and extended to a first state;

[0019] At a second preset temperature, the disc-shaped structure remains as the platform structure, and the support frame is rotated and shortened from the first state to a second state;

[0020] At a third preset temperature, the support frame is maintained in the second state, and the flow-blocking film is expanded in a direction away from the center line of the disk body until the disk-shaped structure becomes a planar structure.

[0021] In a second aspect, the present invention provides a method for preparing a multi-stage unfolded self-assembled heart defect occluder, which is used to prepare the multi-stage unfolded self-assembled heart defect occluder as described in any one of the above items, comprising:

[0022] The first shape memory material and the second shape memory material are respectively made into molded wires; wherein the first shape memory material is a blend of a first gradient material and a second gradient material mixed in a first ratio, and the second shape memory material is a blend of a first gradient material and a second gradient material mixed in a second ratio; the first gradient material is selected from at least one of polylactic acid, polyurethane, polycaprolactone, polyhydroxyalkanoate, polybutylene succinate, polytrimethylene carbonate, and polydodecanoic acid glyceride, and the second gradient material is at least one of p-dioxanone and polyethylene glycol;

[0023] The support frame is prepared by a printing molding method or a wire drawing and weaving molding method; a flow-blocking film is covered on the support frame to obtain a multi-stage unfolded self-assembled heart defect occluder.

[0024] Optionally, the method for preparing the flow-blocking film comprises:

[0025] Polyethylene mixed particles, ethylene-co-vinyl alcohol particles, polylactic acid and polyvinyl acetate mixed particles are dissolved in dichloromethane or dimethyl sulfoxide, heated and stirred to obtain a mixed solution, and the mixed solution is spread on a glass plate to obtain the flow-blocking film.

[0026] The beneficial effects of the multi-stage unfolded self-assembled heart defect occluder of the present invention are:

[0027] The present invention provides a support frame including a disc body, a support frame, and a connecting belt to support the flow-blocking membrane, and uses shape memory materials with different transition temperatures for the connecting belt and the support frame, thereby gradually producing shape changes under multiple temperature stimuli, thereby avoiding the double discs and the "waist" of the occluder from being unfolded at the same time. Instead, different temperature stimuli are used to achieve graded deformation of the double discs and the "waist" of the occluder, so that the two are unfolded autonomously in sequence, thereby increasing the stability of the unfolding process. At the same time, the distance between the two disc-shaped structures is designed to be an interference fit with the heart defect site, so that the multi-stage unfolded self-assembled heart defect occluder is fixed at the defect site, thereby avoiding the problem of loose locking of the occluder due to incomplete shape unfolding. The design of sequential and autonomous unfolding can also ensure that the shape change of the occluder is more uniform during the unfolding process, thereby avoiding wear on the lesion caused by uneven deformation. Therefore, compared with traditional occluders, the occluder of the present invention has a higher locking efficiency, can reduce the wear on the lesion caused by the uneven deformation of the double discs of the occluder, and reduce the corrosiveness to the heart. At the same time, the shape memory material also has good biocompatibility and degradability, which can reduce the risks of cardiovascular abrasion perforation, arrhythmia, occluder detachment and other hidden dangers. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a structural schematic diagram of a multi-stage unfolded self-assembled heart defect occluder in an unfolded state (at a third preset temperature) according to an embodiment of the present invention;

[0029] Figure 2 It is a structural schematic diagram of a multi-stage unfolded self-assembled heart defect occluder in an embodiment of the present invention in a collapsed state (at a first preset temperature);

[0030] Figure 3 It is a structural schematic diagram of a multi-stage unfolded self-assembled heart defect occluder in an intermediate state (at a second preset temperature) in an embodiment of the present invention;

[0031] Figure 4 Schematic diagram of the structure of the disc-shaped structure and the flow-blocking film in an embodiment of the present invention;

[0032] Figure 5 It is a schematic diagram of another perspective of the multi-stage unfolded self-assembled heart defect occluder in an embodiment of the present invention;

[0033] Figure 6 This is a flow chart of a method for preparing a multi-stage self-assembled cardiac defect occluder according to an embodiment of the present invention.

[0034] Description of reference numerals:

[0035] 1. Disk body; 2. Connecting belt; 3. Support frame; 31. Ligament; 4. Flow-blocking membrane; 5. Overlapping area. DETAILED DESCRIPTION

[0036] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. Although certain embodiments of the present invention are shown in the accompanying drawings, it should be understood that the present invention can be implemented in various forms and should not be interpreted as being limited to the embodiments described herein. On the contrary, these embodiments are provided to provide a more thorough and complete understanding of the present invention. It should be understood that the drawings and embodiments of the present invention are only for exemplary purposes and are not intended to limit the scope of protection of the present invention.

[0037] Unless otherwise defined, all technical and scientific terms used in this application have the same meanings as those commonly understood by those skilled in the art to which this application belongs; the terms used in the specification of this application are only for the purpose of describing specific implementation methods and are not intended to limit this application;

[0038] The term "including" and its variations used in this article are open inclusions, that is, "including but not limited to"; the term "based on" is "based at least in part on"; the term "one embodiment" means "at least one embodiment"; the term "another embodiment" means "at least one other embodiment"; the term "some embodiments" means "at least some embodiments"; the term "optionally" means "optional embodiments". The relevant definitions of other terms will be given in the following description. It should be noted that the concepts such as "first" (at the first preset temperature) and "second" mentioned in the present invention are used to distinguish different objects, rather than to describe a specific order or a primary and secondary relationship. In addition, the terms "first" and "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of this application, unless otherwise specified, the meaning of "multiple" is two or more.

[0039] like Figure 1 As shown, a multi-stage unfolded self-assembled heart defect occluder (hereinafter also referred to as an occluder) provided in an embodiment of the present invention comprises a support frame and a flow-blocking membrane 4 arranged on the support frame;

[0040] The support frame includes two disc-shaped structures arranged opposite to each other and a support frame 3 arranged between the two disc-shaped structures;

[0041] The disc-shaped structure includes a disc body 1 and a connecting belt 2 arranged on the circumference of the disc body 1, the support frame 3 is connected between two opposite disc bodies 1, and the two ends of the support frame 3 are staggeredly connected to the two disc bodies 1, so that the support frame 3 can be rotated to extend or shorten under temperature stimulation; the flow-blocking film 4 is connected to the connecting belt 2, and can be expanded or retracted under the drive of the connecting belt 2. When the flow-blocking film 4 is expanded, the disc-shaped structure is a planar structure, and when the flow-blocking film 4 is retracted, the disc-shaped structure is a platform structure;

[0042] The support frame 3 is made of a first shape memory material, and the connecting belt 2 is made of a second shape memory material. The first shape memory material and the second shape memory material have different transition temperatures.

[0043] In this embodiment, the occluder has a disc-shaped structure arranged relatively, which can be called a double disc-shaped structure. The flow-blocking membrane 4 is arranged on the two disc-shaped structures, and the flow-blocking membrane 4 is used to load drugs to assist in the repair of the defective part. The disc-shaped structure includes a disc body 1, and the two disc bodies 1 are connected by a support frame 3. The support frame 3 is equivalent to the "waist" of the occluder. The support frame 3 is made of shape memory material, and the two ends of the support frame 3 are staggered and connected with the two disc bodies 1, that is, the connecting line of the connecting positions of the two ends of the support frame 3 on the two disc bodies 1 is not parallel to the central connecting line of the two disc bodies 1, showing a spiral line, thereby, the rotation deformation of the support frame 3 can be achieved by external stimulation, for example, the support frame 3 can be rotated and extended or shortened by temperature stimulation, so as to realize the switching of the occluder between the slender state and the short and thick state. It can be understood that since the support frame 3 is staggered and connected on the two disc bodies 1, it is helpful for the support frame 3 to rotate or twist when deformed, generate a spiral force, and achieve a deformation of lengthening or shortening. The disc-shaped structure also includes a connecting belt 2 arranged on the circumference of the disc body 1, the connecting belt 2 is used to support the flow-blocking membrane 4, and the connecting belt 2 is also made of shape memory material, so that the deformation of the connecting belt 2 can also be achieved through external stimulation, thereby driving the deformation of the flow-blocking membrane 4 connected to the connecting belt 2. Here, since the connecting belt 2 is arranged on the circumference of the disc body 1 and connected to the disc body 1, it also belongs to the "disc body" of the occluder as a whole, and it is in a different position from the support frame 3. Therefore, in this embodiment, the connecting belt 2 and the support frame 3 are respectively made of shape memory materials with different transition temperatures, so that they can be connected at different positions. The temperature stimulation drives the two to deform, thereby avoiding the simultaneous expansion of the double discs and the "waist" of the occluder, but through different temperature stimulations, the "waist" and the double discs are autonomously expanded in sequence, which can increase the stability of the expansion process. First, the expansion of the waist can provide a stable support point, so that the subsequent expansion of the double disc can cover the lesion area more smoothly and accurately, avoiding the problem of loose locking of the occluder due to incomplete expansion of the shape. In addition, the design of autonomous expansion in sequence can also ensure that the shape of the occluder changes more evenly during the expansion process, avoiding the wear of the lesion caused by uneven deformation. Therefore, compared with the traditional occluder, the occluder of this embodiment has a higher locking efficiency, which can reduce the wear of the lesion caused by the uneven deformation of the double discs of the occluder, and reduce the erosion to the heart. At the same time, the shape memory material also has good biocompatibility and degradability, which can reduce the risk of cardiovascular abrasion perforation, arrhythmia, occluder shedding and other hidden dangers.

[0044] It can be understood that when the connecting belt 2 is deformed by external stimulation, since the connecting belt 2 is arranged in the circumference of the disc body 1, and the blocking film 4 is arranged on the connecting belt 2, the blocking film 4 can realize the enlargement of the area of ​​the disc structure by unfolding, thereby realizing effective blocking, and the area of ​​the entire disc structure is reduced by the folding of the blocking film 4, thereby reducing the volume of the occluder during implantation. Therefore, in this embodiment, the blocking film 4 can be unfolded or folded under the drive of the connecting belt 2, and the blocking film 4 is located in the circumference of the disc body 1. Therefore, as the blocking film 4 is unfolded or folded, the shape of the disc structure will also change. For ease of understanding, the disc structure can be compared to a flower, wherein the disc body 1 is equivalent to the pistil, the blocking film 4 is equivalent to the petal, and the unfolding and folding of the blocking film 4 is equivalent to the unfolding and folding of the petal; or the disc structure can be compared to an umbrella, wherein the disc body 1 is equivalent to the connection between the umbrella pole and the umbrella surface, the blocking film 4 is equivalent to the umbrella surface, and the connecting belt 2 is equivalent to the steel wire supporting the umbrella surface. Specifically, when the baffle film 4 is fully unfolded, the disk body 1 and the baffle film 4 are located in the same plane or substantially in the same plane. Here, considering the thickness of the disk body 1 and the baffle film 4, strictly speaking, the two are in parallel planes to each other, but compared with the angle relationship between the baffle film 4 and the disk body 1 when it is not fully unfolded, it is regarded as being substantially in the same plane. When the baffle film 4 is folded, the disk-shaped structure as a whole presents a table structure. The so-called table is a cone cut by a plane parallel to the bottom surface of the cone, and the part between the bottom surface and the cross section is called the table, and the table includes a prism and a frustum. For example, a plane parallel to the bottom surface of a pyramid is used to cut the pyramid, and the part between the bottom surface and the cross section is called a prism; a plane parallel to the bottom surface of a cone is used to cut the cone, and the part between the bottom surface and the cross section is called a frustum. Here, the disk body 1 is equivalent to the bottom surface of the cone. When the baffle film 4 is retracted under the drive of the connecting belt 2, it is impossible to retract the baffle film 4 around the disk body 1 to one point due to the limited driving force of the connecting belt 2. Therefore, the overall disk-shaped structure is similar to the structure of a table.

[0045] In summary, the occluder of this embodiment is provided with a support frame including a disc body 1, a support frame 3, and a connecting belt 2 to support the flow-blocking membrane 4, and the disc surface part and the "waist" of the support frame are respectively made of shape memory materials with different transition temperatures, so that the shape changes can be produced step by step under multiple temperature stimulations, and the graded deformation of the disc surface part and the "waist" of the occluder is realized, so that the flow-blocking membrane 4 is gathered and stacked in a petal shape in a temporary state, and the overall configuration of the occluder is a slender narrow cross-section shape, so as to facilitate implantation in the defective part, and during the unfolding process, the support frame 3 used to support the disc body 1 is spirally unfolded, shortened and thickened to better adapt to the defective part, and the flow-blocking membrane 4 is unfolded and flattened to achieve the occlusion of the defective part. At the same time, since the two disc-shaped structures are in an interference fit with the heart defective part after unfolding, the multi-stage unfolded self-assembled heart defect occluder is fixed at the defective position, avoiding the problem of the occluder being locked loosely due to incomplete shape unfolding. Therefore, the occluder of this embodiment is more suitable for the heart defect site and produces less wear, thereby reducing the risks of cardiovascular abrasion perforation, arrhythmia, occluder detachment and other hidden dangers.

[0046] Optionally, a plurality of the connecting belts 2 are arranged at intervals along the circumference of the disk body 1, one end of the connecting belt 2 is connected to the disk body 1, and the other end extends in a direction away from the disk body 1, and the plane where the disk body 1 is located when it is a planar structure is taken as the projection plane. In the unfolded state, the projection of the connecting belt 2 on the projection plane is a straight line, a broken line, a curve or a combination thereof.

[0047] One end of the connecting belt 2 made of shape memory material is fixed on the disk body 1, and the other end extends away from the disk body 1 and is arranged at intervals along the circumference of the disk body. Therefore, on the one hand, after the connecting belt is deformed by external stimulation, it can drive the flow-blocking film 4 connected to it to deform, and on the other hand, it also plays a role in supporting the flow-blocking film 4. Therefore, the shape of the connecting belt 2 can be designed as a straight line, a broken line, a curve or any combination thereof, such as an arc, an S-shaped ( Figure 4 ), Z-shaped, etc. The angle and structure of the connecting belt 2 can be adjusted and changed. Preferably, the connecting belt 2 is designed to be wavy in shape, which can be greatly deformed during the deformation process to meet the demand of driving the flow-blocking film 4.

[0048] Optionally, the cross-sectional shape of the disk body 1 is circular, elliptical, quasi-circular or polygonal.

[0049] The disc body 1 is used to support the connecting belt 2, and then support the flow-blocking film 4. The shape of the disc body 1 is not particularly limited, and it can be adapted to defective parts of different sizes and shapes. For example, the cross-sectional shape of the disc body 1 can be a regular or irregular shape such as a circle or a polygon. Of course, a regular shape is preferred, such as a regular polygon (such as a regular hexagon, octagon, decagon, dodecagon, hexadecagon), a circle, a honeycomb, and other easily deformable structures.

[0050] Optionally, the distance between the two disc-shaped structures can be customized according to the type of heart defect and the patient's condition.

[0051] In this optional embodiment, the distance between the two disc-shaped structures is adjustable. According to the changes in the distance between the heart defect and the atrial septum and ventricular septum and to adapt to the specific conditions of different patients, heart defect occluders of different heights are designed and selected. It can be understood that the length and torque of the support frame 3 will also change accordingly.

[0052] Optionally, the distance between the two disc-shaped structures is smaller than the height of the heart defect by 3 mm to 5 mm.

[0053] In this optional embodiment, the distance between the two disc-shaped structures is designed to be smaller than the heart defect, 3mm-5mm, so that the multi-stage self-assembled heart defect occluder can lock the defect after deployment, further fixing the occluder.

[0054] Optionally, the cross-sectional shape of the disk body 1 is a polygon, the number of the connecting belts 2 is the same as the number of sides of the disk body 1 , and each connecting belt 2 is connected to each side of the disk body 1 .

[0055] The number of connecting strips 2 is designed to be the same as the number of polygonal sides of the disk body 1, and a connecting strip 2 is set on each side of the disk body 1, so that the flow-blocking membrane 4 surrounding the disk body 1 can be driven to achieve uniform folding and unfolding of various parts of the flow-blocking membrane 4, avoiding partial incomplete folding or unfolding, which affects the smooth passage of the occluder through the defect site and the occluding effect on the defect site.

[0056] Optionally, the number of the blocking films 4 is the same as the number of the connecting belts 2 , and each blocking film 4 is connected to each connecting belt 2 , respectively.

[0057] The flow-blocking films 4 are connected to the connecting belts 2 to achieve a one-to-one driving effect, so as to avoid the blocking effect being affected by incomplete unfolding or folding of the flow-blocking films 4. The shape of the disk body 1 can be adaptively set according to the defective part, and accordingly, the angle, shape and number of the flow-blocking films 4 need to be adjusted.

[0058] For example, taking the disk body 1 whose cross-sectional shape is a regular hexagon as an example, Figure 4 As shown, each of the six sides of the disk body 1 is connected with a connecting belt 2 , the baffle membranes 4 are six pieces, each baffle membrane 4 is fan-shaped, the baffle membrane 4 is connected to the connecting belt 2 as a whole, and is connected to the disk body 1 by the connecting belt 2 .

[0059] Optionally, the flow-blocking film 4 and the connecting belt 2 can be connected by welding, gluing or sewing. The flow-blocking film 4 can be connected to the front and back sides of the connecting belt 2, or can be set through the connecting belt 2. For example, Figure 1 As shown in the figure, one end of the connecting belt 2 is connected to the disk body 1, and the other end is a free end. A groove extending from one end to the other end is provided on the connecting belt 2, and the flow-blocking film 4 passes through the groove. In this way, the connecting belt 2 is fixed on both the front and back sides of the flow-blocking film 4, which improves the linkage between the connecting belt 2 and the flow-blocking film 4, so that once the connecting belt 2 is deformed, it can drive the connecting belt 2 to deform, thereby improving the sensitivity of deformation.

[0060] Optionally, the area of ​​the unfolded flow-blocking membrane 4 can be customized according to the patient's condition, and the area can be set to 130%-150% of the defect area to better cover the defect.

[0061] Optionally, the support frame 3 includes a plurality of ligaments 31 , the number of the ligaments 31 is the same as the number of sides of the disc body 1 , and two ends of the ligaments 31 are respectively connected to two opposite disc-shaped structures.

[0062] The support frame 3 is used to support and connect the two disk bodies 1. The support frame 3 is designed to have the same number of ligaments 31 as the number of sides of the disk body 1, and the two ends of the ligament 31 are connected to two disk-shaped structures. For example, a ligament 31 is connected to each edge or each vertex of the disk body 1, which can improve the connection stability of the two disk bodies 1.

[0063] For example, Figure 1 , Figure 4 Taking the disk body 1 as an example, the cross-sectional shape of the disk body 1 is a regular hexagon. Figure 5 As shown, six ligaments 31 are used to connect the two disk bodies 1. The ligaments 31 can be connected to the edges or vertices of the disk bodies 1. Here, since the support frame 3 is staggered on the two disk bodies 1, the ligament 31 is spiral as a whole, and the six ligaments 31 intersect at one point between the two disk bodies 1.

[0064] In this optional embodiment, six ligaments 31 are spirally formed into a support frame 3. The spiral structure of the support frame 3 can support and block the blocked part when it is unfolded in the body, and the hollow structure of the support frame 3 is conducive to the growth of tissue inside, which helps to repair the defect and provide a support structure for tissue growth.

[0065] Optionally, when the baffle films 4 are in the unfolded state, there is an overlapping area 5 between adjacent baffle films 4 , and the baffle films 4 are sequentially stacked along the circumference of the disk body 1 .

[0066] The flow-blocking films 4 are overlapped and arranged, so that when the flow-blocking films 4 are in the unfolded state, there is no gap between them, so as to achieve complete blocking. It should be understood that since the flow-blocking films 4 are distributed along the circumference of the disk body 1, each flow-blocking film 4 can be stacked in sequence along the circumference of the disk body 1, with the clockwise direction as the rear, one side of the flow-blocking film 4 at the rear is pressed on one side of the flow-blocking film 4 in the front, and so on, to achieve the stacking of the layers of the flow-blocking films 4. When the flow-blocking films 4 are in the retracted state, they are stacked layer by layer like a flower, so that the occluder is an elongated narrow cross-section shape as a whole, which can be more easily implanted in the defective part, and in the process of unfolding the flow-blocking films 4, the flow-blocking films 4 are unfolded and stacked layer by layer, similar to the blooming of flowers, to achieve the blocking of the defective part.

[0067] Exemplarily, the baffle film 4 is combined with the node connecting ligament 31 and is divided into six pieces. Each piece of baffle film 4 corresponds to a sector angle of 80°. The six baffle films 4 overlap with each other to achieve complete blocking in the unfolded state.

[0068] Exemplarily, the cross-section of the disk body 1 is a hexagon, the connecting belt 2 is formed by 180° and 300° arcs connected tangentially, the baffle membrane 4 is composed of six trapezoidal structures, each of which is connected by the connecting belt 2 as a supporting structure. The six trapezoidal structures are stacked on each other in the expanded state, so as to achieve complete sealing of the defects on the disk surface without gaps.

[0069] Optionally, at a first preset temperature, the flow-blocking film 4 is retracted toward the center line of the disk body 1 until the disk-shaped structure becomes the platform structure, and the support frame 3 is rotated and extended to a first state;

[0070] At a second preset temperature, the disc-shaped structure remains as the platform structure, and the support frame 3 is rotated and shortened from the first state to the second state;

[0071] At the third preset temperature, the support frame 3 is maintained in the second state, and the flow-blocking film 4 is expanded in a direction away from the center line of the disk body 1 until the disk-shaped structure becomes a planar structure.

[0072] In this optional embodiment, at the first preset temperature, the occluder is shaped into a temporary shape, that is, the flow blocking film 4 is stacked and gathered in a layered manner toward the center line of the disk body 1, so that the disk structure is a platform structure, and at the same time, the support frame 3 is rotated and extended to the first state, at which time the occluder is in a slender state (such as Figure 2 to facilitate implantation into the defect site.

[0073] Since the support frame 3 and the connecting belt 2 are made of shape memory materials with different glass transition temperatures, they can be deformed under different temperature stimuli. At the second preset temperature, the connecting belt 2 does not deform, so the flow-blocking film 4 does not deform either. At this time, the disc-shaped structure maintains the platform structure unchanged, while the support frame 3 rotates and shortens and deforms, and is in the second state. Figure 3 As shown. At this time, the occluder is in an intermediate state. It can be understood that when the occluder is in a temporary shape, the support frame 3 is rotated, stretched, thinned and elongated, so that the occluder can smoothly enter the defect. When the occluder is in an intermediate state, the support frame 3 is rotated and expanded, becomes thicker and shorter, and fits the defect more closely, achieving a better blocking effect on the defect.

[0074] At the third preset temperature, the support frame 3 remains in the second state, the connecting belt 2 is deformed, thereby driving the flow-blocking membrane 4 to expand away from the center line of the disk body 1, so that the disk-shaped structure is a planar structure. At this time, the occluder is in Figure 1 The expanded state shown is to facilitate the occlusion of the defect.

[0075] During specific use, the occluder with a temporary shape can be implanted in the defective part of the heart, and the temperature can be controlled to be adjusted to the second preset temperature to rotate and shorten the support frame 3 to achieve the first-level deployment of the occluder. At this time, the occluder is in an intermediate state. The temperature is then controlled to be adjusted to the third preset temperature to deform the connecting belt 2 of the occluder and drive the flow-blocking membrane 4 to expand to a planar shape, thereby achieving the second-level deployment of the occluder. At this time, the occluder is in the deployed state.

[0076] Exemplarily, the occluder is specifically deployed in vivo as follows:

[0077] Step 1: The occluder is shaped into a temporary shape in vitro at 60°C, so that the biodegradable flow-blocking membrane 4 is stacked in layers, and the support frame 3 is rotated and stretched for a certain distance, and the temporary shape of the occluder becomes thinner and longer;

[0078] Step 2: implant the occluder with a temporary shape into the heart defect, control the temperature to 40°C to achieve the first-level deployment of the occluder, rotate the support frame 3 to become thicker, and clamp the defect to make the occluder more compatible with the tissue. At the same time, the support frame 3 can provide a carrier for the growth of tissue in the heart defect to promote tissue repair;

[0079] Step 3: Raise the temperature to 45°C to achieve secondary expansion of the occluder, and the connecting belt 2 returns to a planar shape, and the biodegradable drug-loaded flow-blocking membrane 4 is expanded to achieve occlusion of the defect. At the same time, the biodegradable drug-loaded flow-blocking membrane 4 is loaded with drugs that promote tissue repair, and the drugs are slowly released during the degradation process, thereby achieving long-term direct repair of the defect.

[0080] like Figure 6 As shown, a method for preparing a multi-stage unfolded self-assembled heart defect occluder provided in an embodiment of the present invention is used to prepare the multi-stage unfolded self-assembled heart defect occluder as described in any one of the above items, comprising:

[0081] The first shape memory material and the second shape memory material are respectively made into a molded wire; wherein the first shape memory material is a blend of a first gradient material and a second gradient material mixed in a first ratio, and the second shape memory material is a blend of a first gradient material and a second gradient material mixed in a second ratio. The first gradient material is selected from at least one of shape memory materials such as polylactic acid, polyurethane, polycaprolactone, polyhydroxyalkanoate, polybutylene succinate, polytrimethylene carbonate, polydodecanoic acid glyceride, etc., and the second gradient material is at least one of p-dioxanone and polyethylene glycol. The second gradient material can achieve the adjustment of the transition temperature of the shape memory material by changing the ester bond of the polyester, changing the ratio of the carboxylic acid and polyol components, adding a plasticizer, and regulating the branch point and the molecular weight of the branch segment.

[0082] Exemplarily, the shape memory material components of the two transition temperatures may include the following components by weight ratio:

[0083]

[0084] Among them, polylactic acid, polycaprolactone, and polydodecanoic acid glyceride can be replaced by polyurethane, polyhydroxyalkanoate, polybutylene succinate, and polytrimethylene carbonate. After replacement, adjusting the ratio can achieve the control of transition temperature. In addition, the first gradient material and the second gradient material are not limited to the form of mixing the above components, and multiple materials can be mixed to prepare the required transition temperature material.

[0085] The support frame is prepared by a printing molding method or a wire drawing and weaving molding method; a flow blocking film 4 is covered on the support frame to obtain a multi-stage unfolded self-assembled heart defect occluder.

[0086] In this embodiment, by controlling the addition ratio of polyethylene glycol or diepoxyhexanone, etc., the ratio of the first shape memory polymer to the second shape memory polymer is changed, thereby adjusting the glass transition temperature of the shape memory material, and obtaining molded wires made of the first shape memory material and the second shape memory material respectively, and then using different molded wires to prepare different structures of the occluder, and finally covering it with a flow-blocking film 4 to obtain the occluder.

[0087] This embodiment is made of a double shape memory polymer, which can realize the function of the double disc part and the waist part of the occluder to unfold autonomously in sequence after being affected by environmental stimulation, and the preparation method has high designability and low cost.

[0088] Optionally, the method for preparing the flow-blocking film 4 includes:

[0089] Polyethylene mixed particles, ethylene-co-vinyl alcohol particles, polylactic acid and polyvinyl acetate mixed particles are dissolved in dichloromethane or dimethyl sulfoxide, heated and stirred to obtain a mixed solution, and the mixed solution is spread on a glass plate to obtain the flow-blocking film 4.

[0090] Optionally, the preparation of the formed wire material specifically includes:

[0091] Polylactic acid particles, polycaprolactone particles, and polylauryl glyceride particles were selected, and polyethylene glycol particles and p-dioxanone particles were added in different proportions to prepare polymer mixed particles. The polymer mixed particles were melt-blended using a twin-screw extruder, and then cooled and wound to obtain a modified dual shape memory polymer molding wire.

[0092] Optionally, the dissolution blending of the twin-screw extruder specifically includes: firstly setting the temperature of different sections of the twin-screw extruder, the temperature of the feeding section is set to be 15°C-25°C higher than the melting point of the polymer particle mixture, and the temperature set from the feeding section to the extrusion section should be successively reduced by 2-5°C for heating. Then, the feeder motor switch and the twin-screw extrusion switch are turned on, and the set temperature, feeding speed, and extrusion speed of the twin-screw extruder are fine-tuned to adjust the concentration of the extruded melt to ensure normal wire drawing.

[0093] Optionally, the preparation method further comprises: testing and screening the modified dual shape memory polymer to select the dual shape memory polymer with excellent performance, and then preparing the support frame by using 3D or 4D printing (additive manufacturing technology) molding technology or wire drawing and weaving molding technology.

[0094] Among them, the screening of dual shape memory polymers specifically includes: conducting DSC experiments on the polymer to determine its two recovery temperatures; conducting thermal recovery experiments on the polymer near the recovery temperature to test its recovery rate and recovery process; and conducting in vitro degradation tests on dual shape memory polymer samples.

[0095] Optionally, the preparation method further comprises: testing and screening the support frame.

[0096] Optionally, the preparation method further comprises: after covering the flow-blocking membrane 4, performing a blocking performance test on the occluder.

[0097] The screening of the occluder includes: combining disc bodies 1 and connecting belts 2 of different shapes to obtain corresponding component units, and periodically arraying the component units to obtain a planar structure, and performing a tensile test on the planar structure or woven structure prepared with the screened dual shape memory polymer under normal body temperature and life temperature conditions; performing a thermal recovery experiment on the occluder prepared with the screened dual shape memory polymer to test its recovery rate and recovery process; and performing a closure rate test on the occluder prepared with the screened dual shape memory polymer under normal body temperature and life temperature conditions.

[0098] The present invention is further described below in conjunction with specific embodiments.

[0099] Example 1

[0100] This embodiment provides a method for preparing a multi-stage self-assembled heart defect occluder, which is as follows:

[0101] First, two shape memory materials were prepared by a twin-screw extruder, and the occluder support frame was prepared by 4D printing. The disc 1 and the support frame 3 were prepared by materials with higher transition temperatures, and the connecting belt 2 was prepared by materials with lower transition temperatures. The disc 1 is a regular hexagon with an outer circle diameter of 10 mm and a thickness of 1 mm, and the support frame 3 is composed of six ligaments 31 with a height of 12 mm and a diameter of 1.2 mm. The preparation of the flow-blocking membrane 4 is as follows: 10 g of polylactic acid, 10 g of polyethylene glycol and 40 ml of dichloromethane are prepared into a solution, heated in a 33 ° C oil bath, stirred at a speed of 400 r / min for 1 hour, poured onto a 100*100 mm glass plate and allowed to stand for 1 hour to solidify, and the flow-blocking membrane 4 is obtained. The flow-blocking membrane 4 is cut into a suitable shape and connected to the connecting belt 2 of the occluder support frame by welding, gluing or suturing, so that the connecting belt 2 is in the center of the flow-blocking membrane 4.

[0102] After being formed into a temporary shape in hot water and then cooled and fixed, it is delivered to the designated part and heated to 38°C so that the support frame 3 rotates and unfolds to clamp the defective part, and then heated to 43°C again so that the connecting belt 2 unfolds, driving the flow-blocking membrane 4 to unfold and cover the defective part.

[0103] Although the present invention is disclosed as above, the protection scope of the present invention is not limited thereto. Those skilled in the art may make various changes and modifications without departing from the spirit and scope of the present invention, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. A multi-stage self-assembled heart defect occluder, characterized in that: It comprises a support frame and a flow-blocking membrane (4) arranged on the support frame; The support frame comprises two disc-shaped structures arranged opposite to each other and a support frame (3) arranged between the two disc-shaped structures; The disc-shaped structure comprises a disc body (1) and a connecting belt (2) arranged in the circumferential direction of the disc body (1); the support frame (3) is connected between two opposite disc bodies (1), and the two ends of the support frame (3) are staggeredly connected to the two disc bodies (1), so that the support frame (3) can be rotated to extend or shorten under temperature stimulation; the flow-blocking film (4) is connected to the connecting belt (2) and can be expanded or retracted under the drive of the connecting belt (2); when the flow-blocking film (4) is expanded, the disc-shaped structure is a planar structure, and when the flow-blocking film (4) is retracted, the disc-shaped structure is a platform structure; Wherein, the support frame (3) is made of a first shape memory material, the connecting belt (2) is made of a second shape memory material, and the first shape memory material and the second shape memory material have different transition temperatures; The cross-sectional shape of the disk body (1) is a polygon, the number of the connecting strips (2) is the same as the number of sides of the disk body (1), and each connecting strip (2) is connected to the midpoint of each side of the disk body (1); The number of the flow-blocking films (4) is the same as the number of the connecting strips (2), and each of the flow-blocking films (4) is connected to each of the connecting strips (2) respectively; The support frame (3) comprises a plurality of ligaments (31), the number of the ligaments (31) being the same as the number of sides of the disc surface body (1), and the two ends of the ligaments (31) being respectively connected to two opposite disc-shaped structures; When the flow-blocking films (4) are in an unfolded state, there is an overlapping area (5) between adjacent flow-blocking films (4), and the flow-blocking films (4) are stacked in sequence along the circumference of the disk body (1).

2. The multi-stage unfolded self-assembled heart defect occluder according to claim 1, characterized in that: A plurality of the connecting belts (2) are arranged at intervals along the circumference of the disk body (1); one end of the connecting belt (2) is connected to the disk body (1), and the other end extends in a direction away from the disk body (1); the plane where the disk body (1) is located when it is a planar structure is taken as the projection plane; in the unfolded state, the projection of the connecting belt (2) on the projection plane is a straight line, a broken line, a curve or a combination thereof; And / or, the cross-sectional shape of the disc body (1) is circular, quasi-circular or polygonal.

3. The multi-stage unfolded self-assembled heart defect occluder according to claim 1, characterized in that: The distance between the two disc-shaped structures can be customized according to the type of heart defect and the patient's condition; And / or, the distance between the two disc-shaped structures is 3 mm-5 mm smaller than the height of the heart defect.

4. The multi-stage unfolded self-assembled heart defect occluder according to claim 1, characterized in that: At a first preset temperature, the flow-blocking film (4) is retracted toward the center line of the disk body (1) until the disk-shaped structure becomes the platform structure, and the support frame (3) is rotated and extended to a first state; At a second preset temperature, the disc-shaped structure remains as the platform structure, and the support frame (3) is rotated and shortened from the first state to a second state; At a third preset temperature, the support frame (3) remains in the second state, and the flow-blocking film (4) is expanded in a direction away from the center line of the disk body (1) until the disk-shaped structure becomes a planar structure.

5. A method for preparing a multi-stage self-assembled heart defect occluder, characterized in that: A method for preparing a multi-stage unfolded self-assembled heart defect occluder as claimed in any one of claims 1 to 4, comprising: The first shape memory material and the second shape memory material are respectively made into formed wires; wherein the first shape memory material is a blend of a first gradient material and a second gradient material mixed in a first ratio, and the second shape memory material is a blend of a first gradient material and a second gradient material mixed in a second ratio; Wherein, the first gradient material is at least one of polylactic acid, polyurethane, polycaprolactone, polyhydroxyalkanoate, polybutylene succinate, polytrimethylene carbonate, and polydodecanoic acid glyceride, and the second gradient material is at least one of p-dioxanone and polyethylene glycol; The support frame is covered with a flow-blocking membrane (4) to obtain a multi-stage unfolded self-assembled heart defect occluder.

6. The method for preparing the multi-stage unfolded self-assembled heart defect occluder according to claim 5, characterized in that: The method for preparing the flow-blocking film (4) comprises: Polyethylene mixed particles, ethylene-co-vinyl alcohol particles, polylactic acid and polyvinyl acetate mixed particles are dissolved in dichloromethane or dimethyl sulfoxide, heated and stirred to obtain a mixed solution, and the mixed solution is spread on a glass plate to obtain the flow-blocking film (4).

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