A multi-stage degradation absorbable occlusion device tubular mesh and method of making same

Abstract

The application relates to a multi-stage degradation absorbable occluder tubular mesh and a preparation method thereof. The preparation method is as follows: at least two primary wires are woven into secondary wires, and the secondary wires are woven into a tubular mesh, so that the multi-stage degradation absorbable occluder tubular mesh is obtained; the primary wire is a monofilament, a multifilament or a woven yarn made of a biodegradable polymer; the complete degradation time of the at least two primary wires is different; the prepared multi-stage degradation absorbable occluder tubular mesh is a tubular mesh woven by the secondary wires; the secondary wire is a wire woven by the two or more primary wires; and the complete degradation time of the at least two primary wires is different. The preparation method has strong processability; the occluder tubular mesh prepared by the application has multi-stage gradient degradation, can reduce adverse reactions such as inflammation, can provide a moderate cell growth space for endothelialization of the surface of the occluder, and is beneficial to further inducing tissue regeneration.

Description

Technical Field

[0001] This application belongs to the field of medical device technology and relates to a multi-stage degradable absorbable occluder tubular mesh and its preparation method. Background Technology

[0002] Minimally invasive interventional techniques are widely used in clinical practice as an effective means of treating congenital heart disease. Occluders, as one of the main medical devices used in this field, can be used to treat atrial septal defects, ventricular septal defects, patent foramen ovale, and patent ductus arteriosus.

[0003] Currently, most occluders used in clinical practice are made of nickel-titanium alloy metal materials. Once implanted, the occluder will remain in the heart for life. Since the metal material is non-degradable, long-term contact with human tissue may cause postoperative complications such as delayed endothelialization, thrombosis, atrioventricular block, and nickel allergy.

[0004] After the occluder is implanted in the human body, it will form an endothelial membrane. Subsequently, the surface of the occluder will be gradually covered by autologous tissue. This process usually takes 3 to 6 months. Once the defect is completely repaired, the occluder does not need to remain in the body for a long time. Therefore, the occluder has a time window of effect. Ideally, the occluder should degrade on its own after complete endothelialization, providing space for further growth and embedding of autologous tissue, thereby avoiding a series of long-term complications.

[0005] Currently, bioresorbable materials commonly used in the preparation of biodegradable tubular mesh occluders include polylactic acid (PLA), polycaprolactone (PCL), poly(p-dioxanone) (PPDO), polyglycolic acid (PGA), and blends of these materials. Among them, PLA has good thermal stability and strong processability, but its poor toughness is not conducive to meeting the weaving conditions required for occluders. PLLA is the left-handed conformation of PLA, possessing strong tensile strength, and its complete degradation time exceeds 24 months, with degradation products being carbon dioxide and water. PCL has a low glass transition temperature, is soft and highly ductile at room temperature, and has a long degradation cycle, with a complete degradation time of 36–60 months. PPDO has excellent toughness and tensile strength, moderate strength and elasticity, strong weaving processability, and a high retention rate of mechanical properties during degradation, making it suitable for preparing woven support structures. Its complete degradation time is approximately 9 months, with decomposition products being carbon dioxide and water. PGA has high mechanical strength... High strength, poor flexibility, and excessively rapid degradation (complete degradation within 3 months) make it unsuitable for the self-repair speed of cardiac defects. Polylactic acid-glycolic acid copolymer (PLGA) can be produced using different monomer ratios. PGA's rapid degradation rate leads to excessively fast mechanical property decay, while PLA's poor hydrophilicity results in slow degradation. By adjusting the molecular weight and structural composition of both monomers, the final mechanical properties and degradation rate of PLGA can be improved to meet clinical needs. It has good processability and can be used for weaving. Its degradation products are carbon dioxide and water. Polylactide-caprolactone copolymer (PLC) is a polymer of PLA and PCL, possessing superior mechanical strength and material flexibility. The material stability of this copolymer can be maintained for 3 months. Polyglycolic acid-caprolactone copolymer (PGCL) is usually copolymerized from 75% PGA and 25% PCL, exhibiting good elasticity and toughness. It is also absorbed through hydrolysis, with a complete degradation time of approximately 5 months.

[0006] Due to their unique design, biodegradable occluders allow for significant contact between the defect site, surrounding tissue, and the biodegradable material on the occluder surface. Biodegradable occluders, especially braided ones, often use a single biodegradable material for their tubular mesh portion. After implantation, these biodegradable filaments, due to their polymer degradation characteristics, undergo concentrated degradation. The large amount of degradation products produced in a short period may exceed the body's absorption capacity. Furthermore, the continuous pressure exerted on the tissue by the waist and end discs of the biodegradable occluder under hemodynamic influence can further induce inflammatory responses. The impact of blood flow also accelerates the reduction of the mechanical strength of the occluder filaments, potentially leading to filament rupture. Surface fragments of the filaments peel off in large quantities during the concentrated degradation process, further triggering severe inflammation and other adverse reactions. Therefore, designing a biodegradable occluder that does not cause severe inflammation and thrombosis due to concentrated degradation in a short period is of great significance.

[0007] Patent CN108273142A employs a method of adding a biocompatible coating with a longer degradation cycle to the surface of the wire to regulate the degradation rate of the wire, thereby avoiding early detachment or fragment embolism of the occluder. This method is used to delay the degradation cycle of the occluder and does not address the inflammatory problems caused by concentrated degradation of polymers. Patent CN106491240A prepares a biodegradable polymer material with a wide molecular weight distribution for weaving occluders. The dispersion coefficient of the polymer material is 3-8, which can reduce the concentration of degradation products released per unit time and avoid severe tissue inflammation caused by concentrated degradation. Its degradation cycle is as long as 4-5 years. Patent CN107970493A introduces the use of melt blending to prepare biodegradable filaments containing stereocomplex crystals for weaving occluders. The stereocomplex crystallinity of this biodegradable polymer material ranges from 5% to 80%, resulting in a more uniform degradation process and preventing severe tissue inflammation caused by concentrated degradation. Its degradation cycle is as long as 5-6 years.

[0008] However, while existing technologies can avoid severe tissue inflammation caused by concentrated degradation, they cannot leave gaps after the wires degrade to facilitate tissue ingrowth. Therefore, there is an urgent need to study a tubular mesh occluder that can both avoid concentrated degradation and facilitate tissue ingrowth and promote endothelial cell embedding. Summary of the Invention

[0009] The purpose of this application is to solve the problems existing in the prior art and provide a multi-stage degradable absorbable occluder tubular network, its preparation method, and the occluder itself, which can avoid concentrated degradation, facilitate tissue ingrowth, and promote endothelial cell embedding.

[0010] To achieve the above objectives, the technical solution adopted in this application is as follows:

[0011] A method for preparing a multi-stage degradable absorbable occluder tubular mesh involves first cross-winding at least two primary wires to form secondary wires; then weaving the secondary wires into a tubular mesh, thus forming a multi-stage degradable absorbable occluder tubular mesh; the primary wires are monofilaments, multifilaments, or woven yarns of biodegradable polymers, and the complete degradation times of at least two primary wires are different.

[0012] This application achieves the technical effect of effectively alleviating inflammatory response and inducing tissue ingrowth into the interior of the wires by cross-winding primary wires with different degradation rates, and then weaving them into a tubular mesh for the occluder. It has superior weaving operability and certain tensile strength.

[0013] Since the secondary wires of the tubular mesh of the occluder in this application are woven from primary wires at different rates, the occluder made from the tubular mesh has a gradient degradation characteristic, which can ensure that the occluder can be degraded one by one, uniformly and orderly according to the degradation cycle of the selected raw materials throughout the entire degradation cycle, and will not generate and accumulate a large amount of degradation products in a short period of time, which can effectively alleviate the inflammatory response.

[0014] Existing methods for weaving primary wires into secondary wires often employ parallel weaving, resulting in independent primary wires and a loose, flat secondary wire structure. This leads to a large contact area between the primary wires and tissue, causing rapid degradation and compromising the structural stability of the secondary wires during degradation. Furthermore, the tight contact with tissue leaves insufficient space for tissue ingrowth. To overcome these shortcomings, this application employs a cross-wound method for weaving primary wires into secondary wires. The primary wires interlock, creating a tighter structure that makes the secondary wire structure more three-dimensional and nearly cylindrical. This allows for more spatial gaps for tissue ingrowth, promoting endothelial cell embedding. Compared to the parallel weaving structure of primary wires, cross-wound weaving reduces the contact area between the secondary wires and tissue, allowing for better control of the degradation rate. Moreover, during the degradation of the primary wires, a small amount of polymers with a faster degradation rate degrades first, while the remaining components maintain their original weaving trajectory, preserving the overall structure of the occluder and maintaining a certain level of support strength in the early stages of degradation. The remaining weave patterns after material degradation provide more space for cell growth, which is conducive to tissue ingrowth into the gaps inside the secondary wire, promotes endothelialization of the occluder surface, and induces tissue to grow and fill the interior of the occluder.

[0015] This application selects biodegradable polymer wires with different degradation rates as primary wires, so that the secondary wires have good mechanical properties and can withstand a series of braiding operations such as bending, torsion, tension, and extrusion. They can be used to directly prepare tubular mesh for occluders. This method is achieved through mechanical control and does not require other physicochemical means. The preparation method is simple, the molding method is fast and effective, and the braiding processability is strong.

[0016] As a preferred technical solution:

[0017] The preparation method of the multi-stage degradable absorbable plug tubular network as described above includes the following specific steps:

[0018] (1) Design the number and position of the yarn spindles of the two or more primary yarns on the braiding machine so that the two or more primary yarns can be intertwined with each other along the rotation trajectory of the yarn spindles;

[0019] (2) Braid the two or more primary wires into secondary wires;

[0020] (3) Design the trajectory and weaving method of the secondary wire along the tubular mold;

[0021] (4) The secondary wires are woven into a tubular network, which is a multi-stage degradable absorbable plug tubular network.

[0022] The preparation method of the multi-stage degradable absorbable plug tubular mesh described above uses the biodegradable polymer PLA, PCL, PPDO, PGA, PLGA, PGLA, PLC or PGCL.

[0023] In the method for preparing a multi-stage degradable absorbable plug tubular mesh as described in any of the preceding claims, the diameter of the primary wire is 0.02–0.15 mm. A primary wire diameter exceeding this range will be detrimental to subsequent weaving. It should be noted that when the cross-sectional shape of the primary wire is non-circular, the diameter here is understood as the equivalent diameter.

[0024] The method for preparing a multi-stage degradable absorbable plug tubular mesh as described above, wherein the primary wire consists of wire A with a complete degradation time of 1-9 months, wire B with a complete degradation time of 2-18 months, and wire C with a complete degradation time of 8-45 months; and in the secondary wire, the volume content of wire A is 10%-50%, the volume content of wire B is 10%-80%, and wire C is the balance.

[0025] In the preparation method of the multi-stage degradable absorbable plug tubular mesh described above, when the two or more primary wires are woven into secondary wires, the weaving method is one or a combination of two of the following: diamond weaving, regular weaving, three-strand weaving, and axial yarn weaving.

[0026] In the method for preparing a multi-stage degradable absorbable occluder tubular mesh as described above, the diameter of the secondary wire is 0.2–0.5 mm. The diameter of the secondary wire should not be too large, otherwise it will affect the subsequent weaving process and prevent proper forming. It should be noted that when the cross-sectional shape of the secondary wire is non-circular, the diameter here is understood as the equivalent diameter.

[0027] The preparation method of the multi-stage degradable absorbable plug tubular mesh described above has a secondary wire tensile strength of 300–550 MPa.

[0028] As described above, in the preparation method of the multi-stage degradable absorbable occluder tubular mesh, the secondary wires are braided into a tubular mesh using a diamond braid, regular braid, or Hercules braid, with a braiding pitch of 0.5–1.0 mm. A pitch within this range helps to obtain a more uniform braided tube; furthermore, the smaller the braiding pitch of the secondary wires, the tighter the winding of the primary wires, making it more difficult for blood to enter the interior of the secondary wires, and resulting in a longer degradation cycle.

[0029] This application also provides a multi-stage degradable absorbable occluder tubular network prepared using a method described in any of the preceding claims.

[0030] This application also provides a multi-stage degradable absorbable plug, comprising the multi-stage degradable absorbable plug tubular network as described above.

[0031] The tubular mesh occluder prepared by the method of this application has good mechanical properties and good tissue compatibility. It also has multiple degradation cycles and the overall degradation rate of the wire can be controlled. It provides new gaps during the stepwise degradation of polymer materials, which is conducive to tissue ingrowth and promotes the embedding of endothelial cells into the occluder.

[0032] Compared with the prior art, this application has the following beneficial effects:

[0033] (1) The unique primary braiding (i.e., braiding two or more primary wires into secondary wires) and secondary braiding (i.e., braiding secondary wires into a tubular network) structure of the occluder in this application allows the biodegradable polymers to be uniformly dispersed on the surface of the occluder tubular network, and to undergo gradual and uniform gradient degradation one by one. This prevents the generation of a large number of degradation products due to the concentrated degradation of a certain polymer, which could lead to adverse reactions such as inflammation.

[0034] (2) In this application, the tubular mesh is degraded one by one according to its degradation cycle of the primary wires in the secondary wires. The small amount of polymers with faster degradation rate degrades first, and the remaining components still maintain the original weaving track, without destroying the overall structure of the occluder. The occluder still has a certain supporting strength in the early stage of degradation. After the material is degraded, the empty weaving track provides more space for cell growth, which is conducive to tissue growth into the gaps inside the secondary wires, promotes endothelialization of the occluder surface, and induces tissue to grow and fill into the occluder.

[0035] (3) This application selects biodegradable polymer primary wires with different degradation rates, so that the secondary wires have good mechanical properties and can withstand a series of weaving operations such as bending, torsion, stretching, and extrusion. They can be used to directly prepare tubular mesh for occluders. This method is achieved through mechanical control and does not require other physical and chemical means. The preparation method is simple, the molding method is fast and effective, and the weaving processability is strong. Attached Figure Description

[0036] Figure 1 This is a diagram of the secondary wire braiding track for Example 1;

[0037] Figure 2 This is an appearance diagram of the secondary wire in Example 1;

[0038] Figure 3 This is a diagram of the secondary wire braiding track for Example 2;

[0039] Figure 4This is an appearance diagram of the secondary wire in Example 2;

[0040] Figure 5 This is a diagram of the secondary wire braiding track for Example 3;

[0041] Figure 6 The graphs show the mass loss due to degradation of the secondary wires in Examples 1 and 2.

[0042] Figure 7 The diagram shows the support strength loss of the occluder bracket in Examples 1 and 2.

[0043] Figure 8 The graphs show the degradation mass loss of the secondary wire in Example 4 and Comparative Example 1.

[0044] Figure 9 Masson staining results (10×4) of subcutaneous rat occluder stent implantation in Example 4 and Comparative Example 1;

[0045] Figure 10 This is a weaving path diagram for the secondary wires woven into a net in Example 1. Detailed Implementation

[0046] The present application is further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the application. Furthermore, it should be understood that after reading the teachings of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the scope defined by the appended claims.

[0047] 1 Experimental Methods

[0048] 1.1 Degradation Test

[0049] The degradation test of the sample was carried out using a high-temperature accelerated method in a constant-temperature shaker (KYC-1102C, Shanghai Xiangfan Instrument Co., Ltd.). The temperature of the constant-temperature shaker was 50℃ and the rotation frequency was 60r / min.

[0050] Mass loss rate: The mass loss rate is calculated based on the difference in mass before and after the degradation test. The calculation formula is as follows:

[0051] K = (W0 - W) D ) / W0

[0052] In the formula, W0 refers to the mass of the sample before the degradation test, W D K represents the sample mass at the sampling time point corresponding to this degradation test, and K represents the mass loss rate.

[0053] Quality retention rate: S = 1 - K;

[0054] In the formula, S is the quality retention rate and K is the quality loss rate.

[0055] 1.2 Shedding force test

[0056] Referring to the requirements for the fixation effectiveness of occluders in YY / T 1553-2017 "Cardiovascular Implants - Cardiac Occluders", a digital push-pull tester (SH-20, Shanghai Siwei Instrument Co., Ltd.) was used to push the left disc of the biodegradable occluder stent out of a VSD defect model with a diameter of 6mm, and the maximum force value when the occluder was dislodged was recorded.

[0057] The formula for calculating the support strength loss rate is:

[0058] R = (F0 - F D ) / F0

[0059] Wherein, F0 refers to the shedding force of the sample before the degradation test, F D R represents the sample shedding force at the sampling time point corresponding to the degradation test, and R is the support strength loss rate.

[0060] Support strength retention rate: Y = 1 - R;

[0061] In the formula, Y is the support strength retention rate, and R is the support strength loss rate.

[0062] Example 1

[0063] A method for preparing a multi-stage degradable absorbable occluder tubular mesh, the specific steps of which are as follows:

[0064] (1) Preparation of primary wire;

[0065] Wire A: PPDO monofilament, 0.05mm in diameter, with a complete degradation time of 9 months;

[0066] Wire B: PLLA monofilament, 0.05mm in diameter, with a complete degradation time of 18 months;

[0067] Wire C: PCL monofilament, 0.03mm in diameter, with a complete degradation time of 30 months;

[0068] (2) Select two cables A, two cables B, and one cable C, such as... Figures 1-2As shown, the triangle indicates the location of the yarn carrier that holds the yarn spindle, and the arrow points in the direction of the yarn carrier's movement. The black arrow represents yarn A (PPDO monofilament), and the white arrow represents yarn B (PLLA monofilament). In the 8-spindle vertical braiding machine, the track on the track plate is processed into a composite figure-eight shape. The yarn carrier controls the two sets of yarns to move in opposite directions, so that yarn A (PPDO monofilament) and yarn B (PLLA monofilament) are woven in a diamond pattern around yarn C (PCL monofilament) to form a secondary yarn with a diameter of 0.25 mm and a breaking strength of 550 MPa.

[0069] (3) Select a tubular mold with 16 heads (the diameter of the tubular mold is 8mm and the length is 33.5mm), and use a diamond weaving method with a weaving pitch of 0.7mm. The weaving pattern is as follows: Figure 10 As shown, the heads are arranged from left to right. Starting from head 1', the weaving sequence is 1'→1→2' (indicated by the thick solid line in the figure) to complete one round trip. Then, 2'→2→3' (indicated by the dashed line in the figure) to complete one round trip. This pattern is repeated until the first head 1' is returned. That is, the head and tail ends of the secondary wire are connected together (i.e., woven into a tubular mesh), resulting in a tubular fabric (i.e., a multi-stage degradable absorbable plug tubular mesh) wrapped around the surface of the cylindrical mold.

[0070] One end of the prepared multi-stage biodegradable absorbable plug tubular mesh is narrowed using a monofilament slightly thinner than the primary wire (e.g., 0.1 mm diameter PPDO), denoted as the narrowed end. The other end is left untreated, denoted as the open end. The open end is fixed by wrapping copper wire for a length of 3 mm. The heating device is turned on, and only the biodegradable filament wrapped with copper wire is continuously heated at 180°C for 5 seconds until the biodegradable filament in the copper wire melts. The copper wire is then removed, forming a molten end with textured patterns. A shaping mold is then inserted into the tubular mesh with the molten end. The material undergoes heat treatment for shaping at 100℃ for 60 minutes. The mold is then removed to obtain a biodegradable occluder support. A biodegradable flow-blocking membrane is filled into the biodegradable occluder support to form a left disc (i.e., the constricted end, with a diameter of 13mm), a right disc (i.e., the open end, with a diameter of 13mm), and a waist section (7mm in diameter). The biodegradable flow-blocking membrane is then fixed with biodegradable sutures. Finally, the two free ends of a safety rope are inserted from top to bottom through any two points on the left disc and then through the waist section before exiting from the right disc, thus obtaining a multi-stage biodegradable absorbable occluder.

[0071] Example 2

[0072] A method for preparing a multi-stage degradable absorbable occluder tubular mesh, the specific steps of which are as follows:

[0073] (1) Preparation of primary wire;

[0074] Wire A: PGCL multifilament (PGA segment to PCL segment molar ratio of 3:1), diameter of 0.1mm, complete degradation time of 5 months;

[0075] Wire B: PLGA multifilament (molar ratio of PGA segments to PLA segments is 1:2), diameter is 0.1mm, and complete degradation time is 12 months;

[0076] Cable C: PLLA multifilament, 0.1mm in diameter, with a complete degradation time of 24 months;

[0077] (2) Select one cable A, one cable B, and one cable C; for example... Figures 3-4 As shown, a 3-spindle braiding machine is selected. The triangle indicates the location of the yarn carrier that loads the yarn spindles, and the arrow indicates the direction of movement. This allows the three yarns to intertwine and be braided into a three-strand braid, producing a secondary wire with a diameter of 0.25 mm and a breaking strength of 400 MPa.

[0078] (3) Using a diamond weaving method with a weaving pitch of 0.5 mm, the secondary wires are woven into a tubular mesh along a tubular mold (the diameter of the tubular mold is 8 mm and the length is 33.5 mm), thus forming a multi-stage degradable absorbable plug tubular mesh; wherein, the weaving pattern is the same as in Example 1 (i.e., according to...). Figure 10 (The weaving pattern is followed).

[0079] One end of the prepared multi-stage biodegradable absorbable plug tubular mesh is woven into a flat mesh structure using monofilaments slightly thinner than the primary wire (e.g., 0.1 mm diameter PPDO). The other end is left untreated and designated as the open end. The open end is then fixed by wrapping it with copper wire for a length of 3 mm. The heating device is turned on, and only the biodegradable filaments wrapped with copper wire are continuously heated at 230°C for 5 seconds until the biodegradable filaments in the copper wire melt. The copper wire is then removed, forming a molten end with textured patterns. A shaping mold is then inserted into the tubular mesh with the molten end for heat treatment. The molding process is carried out at 155℃ for 60 minutes. The mold is then removed to obtain a biodegradable occluder support. A biodegradable flow-blocking membrane is filled into the biodegradable occluder support to form a left disc (i.e., the end woven into a flat mesh structure, with a diameter of 13mm), a right disc (i.e., the open end, with a diameter of 13mm), and a waist section (7mm in diameter). The biodegradable flow-blocking membrane is then fixed with biodegradable sutures. Finally, the two free ends of a safety rope are inserted from top to bottom through any two points on the left disc and then through the waist section before exiting from the right disc to obtain a multi-stage biodegradable absorbable occluder.

[0080] The trends of the quality loss curves of the secondary wires obtained in Examples 1 and 2 are as follows: Figure 6As shown, by selecting the type, quantity, and weaving method of materials, their degradation rate can be altered. Components with shorter degradation cycles will gradually degrade in the early stages, and the gaps between fibers provide new space for cell growth, which is beneficial for the growth of new tissue; for example... Figure 7 The diagram shows the loss of support strength of the biodegradable occluder stents prepared in Examples 1 and 2. During the first 24 days of accelerated degradation, the support strength can be maintained above 50%, during which the material plays a major supporting role. At the same time, the degradation cycle is relatively short, and the degradation of components allows for the formation of gaps between fibers, which is conducive to the ingrowth of tissue in vivo. Afterward, the support strength of the material decreases, and the newly grown tissue can provide support together with the remaining components until the material is completely degraded and the tissue is completely edged in.

[0081] Example 3

[0082] A method for preparing a multi-stage degradable absorbable occluder tubular mesh, the specific steps of which are as follows:

[0083] (1) Preparation of primary wire;

[0084] Wire A: PGA multifilament, 0.02mm in diameter, complete degradation time is 2 months;

[0085] Wire B: PLC multifilament (the molar ratio of PLA segments to PCL segments is 1:1), with a diameter of 0.02 mm and a complete degradation time of 12 months;

[0086] Cable C: PLLA multifilament, 0.02mm in diameter, with a complete degradation time of 24 months;

[0087] (2) Select three wires A, three wires B, and two wires C, such as Figure 5 As shown, all the triangles indicate the location of the yarn carriers that hold the yarn spindles, and the arrows point in the direction of the yarn carriers' movement. The yarn carriers control the yarn to move in a figure-eight pattern with the track disc, and the two sets of yarns are woven in a regular pattern of 2 up and 2 down to form a secondary yarn with a diameter of 0.2 mm and a breaking strength of 400 MPa.

[0088] (3) Using a regular weaving method with a weaving pitch of 1.0 mm, the secondary wires are woven into a tubular mesh along a tubular mold (the diameter of the tubular mold is 8 mm and the length is 33.5 mm), thus forming a multi-stage degradable absorbable plug tubular mesh; wherein, the weaving pattern is the same as in Example 1 (i.e., according to...). Figure 10 (The weaving pattern is followed).

[0089] One end of the prepared multi-stage biodegradable absorbable plug tubular mesh is narrowed using a monofilament slightly thinner than the primary wire (e.g., 0.1 mm diameter PPDO), denoted as the narrowed end. The other end remains untreated, denoted as the open end. The open end is fixed by wrapping it with copper wire for a length of 5 mm. The heating device is turned on, and only the biodegradable filament wrapped with copper wire is continuously heated at 170°C for 5 seconds until the biodegradable filament in the copper wire melts. The copper wire is then removed, forming a molten end with textured markings. A shaping mold is then inserted into the tubular mesh with the molten end. Heat treatment is performed at 150℃ for 60 minutes to set the shape. The mold is then removed to obtain a biodegradable occluder support. A biodegradable flow-blocking membrane is filled into the biodegradable occluder support to form a left disc (i.e., the constricted end, with a diameter of 13mm), a right disc (i.e., the open end, with a diameter of 13mm), and a waist section (7.5mm in diameter). The biodegradable flow-blocking membrane is then fixed with biodegradable sutures. Finally, the two free ends of a safety rope are inserted from top to bottom through any two points on the left disc and then through the waist section before exiting from the right disc to obtain a multi-stage biodegradable absorbable occluder.

[0090] Example 4

[0091] A method for preparing a multi-stage degradable absorbable occluder tubular mesh, the specific steps of which are as follows:

[0092] (1) Preparation of primary wire;

[0093] Wire A: PGA multifilament, diameter 0.09mm, complete degradation time is 3 months;

[0094] Wire B: PGLA (PGA segment to PLA molar ratio of 9:1) multifilament, diameter of 0.09mm, complete degradation time of 4 months;

[0095] Wire C: PPDO monofilament, 0.09mm in diameter, with a complete degradation time of 9 months;

[0096] (2) Select 1 wire A, 1 wire B, and 2 wires C, and use a diamond braiding method to braid them into a secondary wire with a diameter of 0.23mm and a breaking strength of 350MPa, namely multi-component braided yarn MBY.

[0097] (3) Using the Hercules braiding method with a braiding pitch of 1.0 mm, the secondary wires are braided into a tubular mesh along a tubular mold (the diameter of the tubular mold is 8 mm and the length is 33.5 mm), thus forming a multi-stage degradable absorbable occluder tubular mesh; wherein, the braiding pattern is the same as in Example 1 (i.e., according to...). Figure 10 (The weaving pattern is followed).

[0098] One end of the prepared multi-stage biodegradable absorbable plug tubular mesh is narrowed using a monofilament slightly thinner than the primary wire (e.g., 0.1 mm diameter PPDO), denoted as the narrowed end. The other end remains untreated, denoted as the open end. The open end is fixed by winding copper wire for a length of 5 mm. The heating device is turned on, and only the biodegradable filaments of the copper wire section are continuously heated at 120°C for 10 seconds until the biodegradable filaments in the copper wire melt. The copper wire is then removed, forming a molten end with textured markings. A shaping mold is then inserted into the tubular mesh with the molten end. Heat treatment is performed at 90℃ for 60 minutes to set the shape. The mold is then removed to obtain a biodegradable occluder support. A biodegradable flow-blocking membrane is filled into the biodegradable occluder support to form a left disc (i.e., the constricted end, with a diameter of 13mm), a right disc (i.e., the open end, with a diameter of 12.5mm), and a waist (with a diameter of 7.5mm). The biodegradable flow-blocking membrane is then fixed with biodegradable sutures. Finally, the two free ends of a safety rope are inserted from top to bottom through any two points on the left disc and then through the waist before exiting from the right disc to obtain a multi-stage biodegradable absorbable occluder.

[0099] Comparative Example 1

[0100] A method for preparing a biodegradable absorbable plugging device tubular mesh is basically the same as in Example 4, except that...

[0101] (1) Preparation of primary wire;

[0102] Wire C: PPDO monofilament, 0.09mm in diameter, with a complete degradation time of 9 months;

[0103] (2) Select 4 wires C and use a diamond braiding method to braid them into a secondary wire with a diameter of 0.23mm and a breaking strength of 350MPa, which is denoted as single-component braided yarn OBY.

[0104] The biodegradable absorbable plug tubular mesh obtained in Comparative Example 1 was used to prepare a biodegradable absorbable plug in the same way as in Example 4.

[0105] The mass loss rates during the degradation process of the secondary wire in Example 4 and Comparative Example 1 are as follows: Figure 8 As shown, compared with Comparative Example 1, the secondary wire of Example 4 degrades at different times, that is, it has a gradient degradation trend, which avoids the accumulation of a large number of acidic products caused by concentrated degradation of materials in the same period of time, and may reduce the complications during the degradation cycle.

[0106] The biodegradable occluder stents of Example 4 and Comparative Example 1 were implanted subcutaneously into the backs of SD rats. Figure 9As shown in the section results obtained from subcutaneous implantation in rats, at 14 days, tissue grew into the MBY fibers, and inflammatory reactions were observed on the surface of each fiber. At 28 days, some fibers in the MBY fibers began to degrade, and new tissue further grew into the interior of the MBY fibers. Although the OBY fibers also have a braided structure, tissue could not grow into the gaps between the OBY fibers. At 56 days, the PGA component in the MBY fibers was basically degraded, and new fiber tissue grew into the gaps left by the degradation. Collagen tissue also grew into the interior of the MBY fibers. A small number of inflammatory cells still infiltrated the MBY fibers, but the inflammatory reaction on the outer layer of the MBY fibers subsided. A small amount of tissue grew into the external gaps of the OBY fibers, and inflammatory reactions were still present on the surface of the OBY fibers. This indicates that gradient degradation is beneficial for inducing tissue ingrowth into the interior of the fibers.

[0107] Example 5

[0108] A method for preparing a multi-stage degradable absorbable occluder tubular mesh, the specific steps of which are as follows:

[0109] (1) Preparation of primary wire;

[0110] Wire A: PGA multifilament, 0.2mm in diameter, with a complete degradation time of 9 months;

[0111] Wire B: PLC multifilament (the molar ratio of PLA segments to PCL segments is 1:1), with a diameter of 0.2 mm and a complete degradation time of 18 months;

[0112] Cable C: PLLA multifilament, 0.2mm in diameter, with a complete degradation time of 45 months;

[0113] (2) Select 3 yarns A, 3 yarns B, and 2 yarns C. All the triangles are the positions of the yarn carriers loaded into the spindles, and the arrows point in the direction of the yarn carriers' movement. The yarn carriers control the yarn to move in a figure-eight pattern with the track disc. The two sets of yarns are woven in a regular pattern of 2 up and 2 down to form a secondary yarn with a diameter of 2mm and a breaking strength of 600MPa.

[0114] (3) A regular weaving method is adopted, with a weaving pitch of 1.2 mm. The secondary wires are woven into a tubular mesh along a tubular mold (the diameter of the tubular mold is 8 mm and the length is 33.5 mm), which is a multi-stage degradable absorbable plug tubular mesh; wherein, the weaving pattern is the same as in Example 1 (i.e., according to...). Figure 10 (The weaving pattern is followed).

[0115] One end of the prepared multi-stage biodegradable absorbable plug tubular mesh is woven into a flat mesh structure using monofilaments slightly thinner than the first-stage wire (e.g., 0.1 mm diameter PPDO). The other end is left untreated and designated as the open end. The open end is fixed by wrapping it with copper wire for a length of 5 mm. The heating device is turned on, and only the biodegradable filaments wrapped with copper wire are continuously heated at 170°C for 5 seconds until the biodegradable filaments in the copper wire melt. The copper wire is then removed, forming a molten end with textured patterns. A shaping mold is then inserted into the tubular mesh with the molten end for heat treatment. The mold is set at 150℃ for 60 minutes. The mold is then removed to obtain a biodegradable occluder support. A biodegradable flow-blocking membrane is filled into the support to form a left disc (the end woven into a flat mesh structure, with a diameter of 13mm), a right disc (the open end, with a diameter of 13mm), and a waist section (7.5mm in diameter). The biodegradable flow-blocking membrane is then secured with biodegradable sutures. Finally, the two free ends of a safety rope are inserted from top to bottom through any two points on the left disc and then through the waist section, exiting from the right disc to obtain a multi-stage biodegradable absorbable occluder.

Claims

1. A method for preparing a multi-stage degradable absorbable plugging device tubular mesh, characterized in that, Includes the following steps: S1: Design the number and position of spindles of two or more primary yarns on the braiding machine so that the two or more primary yarns intertwine with each other along the rotation trajectory of the spindles. The primary yarn is a biodegradable polymer woven yarn, and at least two primary yarns have different complete degradation times; the primary yarn consists of yarn A with a complete degradation time of 1-9 months, yarn B with a complete degradation time of 2-18 months, and yarn C with a complete degradation time of 8-45 months; and in the secondary yarn, the volume content of yarn A is 10%-50%, the volume content of yarn B is 10%-80%, and yarn C is the balance; S2: The two or more primary wires are braided into secondary wires, wherein the primary wires interweave with each other to form interlacing points; S3: Design the trajectory and weaving method for the secondary wires to be braided along the tubular mold; S4: The secondary wires are woven into a tubular network, which is a multi-stage degradable absorbable plug tubular network.

2. The method for preparing a multi-stage degradable absorbable plug tubular mesh according to claim 1, characterized in that, The biodegradable polymer is PLA, PCL, PPDO, PGA, PLGA, PGLA, PLC, or PGCL.

3. The method for preparing a multi-stage degradable absorbable plugging device tubular mesh according to any one of claims 1 to 2, characterized in that, The diameter of the primary wire is 0.02~0.15mm.

4. The method for preparing a multi-stage degradable absorbable plugging device tubular network according to claim 3, characterized in that, When two or more primary wires are braided into secondary wires, the braiding method is one or a combination of two of the following: diamond braiding, regular braiding, three-strand braiding, and axial yarn braiding.

5. The method for preparing a multi-stage degradable absorbable plugging device tubular mesh according to claim 4, characterized in that, The diameter of the secondary wire is 0.2~0.5mm.

6. The method for preparing a multi-stage degradable absorbable plugging device tubular mesh according to claim 5, characterized in that, The tensile strength of the secondary wire is 300~550MPa.

7. The method for preparing a multi-stage degradable absorbable plugging device tubular network according to claim 6, characterized in that, When the secondary wire is braided into a tubular mesh, the braiding method is diamond braiding, regular braiding, or Hercules braiding, and the braiding pitch of the secondary wire is 0.5~1.0mm.

8. A multi-stage degradable absorbable plugging device tubular mesh, characterized in that, It is prepared by the method described in any one of claims 1 to 7 for the preparation of a multi-stage degradable absorbable plug tubular mesh.

9. A multi-stage degradable absorbable plugging device, characterized in that, Includes the multi-stage degradable absorbable plug tubular mesh as described in claim 8.

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