An absorbable cardiac occluder choke membrane and its preparation method

Abstract

This invention belongs to the field of medical device technology and relates to an absorbable cardiac occluder flow-blocking membrane and its preparation method. The flow-blocking membrane is a multilayer biodegradable polymer composite membrane structure, which sequentially includes: a first hydrophilic layer, a first transition layer, a dense layer, a second transition layer, and a second hydrophilic layer. The first hydrophilic layer, the first transition layer, the second transition layer, and the second hydrophilic layer are all loose and porous layered structures, while the dense layer is a dense layered structure. The first and second hydrophilic layers are made of natural polymers, the first and second transition layers are made of a mixture of natural and synthetic polymers, and the dense layer is made of synthetic polymers. This absorbable cardiac occluder flow-blocking membrane has good hydrophilicity, anti-inflammatory properties, and mechanical properties, which can effectively accelerate endothelialization and reduce post-implantation inflammatory responses, thus enabling its application in cardiac occluders.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology and relates to an absorbable cardiac occluder choke membrane and its preparation method. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Congenital heart disease (CHD) is a common birth defect in newborns, mainly including atrial septal defect (ASD), ventricular septal defect (VSD), patent foramen ovale (PFO), and patent ductus arteriosus (PDA). Traditional treatment methods often involve open-heart surgery, which brings great pain and risks to patients. With the development of interventional medicine, interventional treatment for CHD has now entered a mature and widespread stage. A cardiac occluder is a Class III implantable medical device for treating CHD. Its structure mainly consists of a mesh stent and a choke membrane, where the choke membrane functions to seal the defect and block blood flow shunting.

[0004] According to the inventor's research, existing occluder membranes mainly fall into two categories: one is made of non-absorbable materials, which need to remain permanently in the body, forming a foreign body and easily causing long-term inflammatory reactions; the other is made of absorbable materials, which are further divided into natural absorbable materials and synthetic absorbable materials. Natural absorbable materials have good hydrophilicity and biocompatibility, but poor mechanical properties. Synthetic polymer materials have good mechanical properties and biocompatibility, but are mostly hydrophobic polymers, lacking cell affinity and hindering cell adhesion and growth. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide an absorbable choke membrane for cardiac occluders and its preparation method. This membrane possesses excellent hydrophilicity, anti-inflammatory properties, and mechanical properties, effectively accelerating endothelialization and reducing post-implantation inflammatory responses, thus enabling its application in cardiac occluders.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows:

[0007] On one hand, there is an absorbable cardiac occluder flow-blocking membrane, wherein the flow-blocking membrane is a multilayer biodegradable polymer composite membrane structure, the multilayer biodegradable polymer composite membrane structure comprising, in sequence: a first hydrophilic layer, a first transition layer, a dense layer, a second transition layer, and a second hydrophilic layer, wherein the first hydrophilic layer, the first transition layer, the second transition layer, and the second hydrophilic layer are all loose and porous layered structures, the dense layer is a dense layered structure, the first hydrophilic layer and the second hydrophilic layer are made of natural polymers, the first transition layer and the second transition layer are made of a mixture of natural polymers and synthetic polymers, and the dense layer is made of synthetic polymers; the natural polymers are chitosan, hyaluronic acid, silk fibroin, or one or more hydrophilic polymers, and the synthetic polymers are polylactic acid, polyglycolic acid, polydioxanone, polycaprolactone, polycarbonate, or one or two copolymers or blends thereof.

[0008] This invention employs both natural and synthetic polymers, coupling the properties of the two materials to create a flow-blocking membrane that simultaneously possesses excellent hydrophilicity, mechanical properties, and biocompatibility. However, the flow-blocking membrane also needs to promote endothelialization. From a structural perspective, a loosely porous membrane (layered structure) is beneficial for cell adhesion and growth, promoting endothelialization, but it also leads to a decrease in mechanical properties. While a dense membrane has good mechanical properties, it lacks cell adhesion. Therefore, this invention employs a five-layer structure. The middle layer is a dense layered structure made of synthetic polymer to ensure the overall mechanical properties of the membrane. Then, the surface of the middle layer is provided with a loosely porous layered structure to absorb and ensure cell adhesion and growth, thereby promoting endothelialization. In addition, the different hydrophilic properties of natural and synthetic polymers lead to a decrease in the bonding performance between the hydrophilic layer and the dense layer, resulting in a reduction in membrane life. To address this, the present invention provides a transition layer prepared by mixing natural and synthetic polymers between the hydrophilic layer and the dense layer, thereby increasing the bonding performance between the layers and improving the membrane life.

[0009] On the other hand, a method for preparing the above-mentioned absorbable cardiac occluder choke membrane includes the following steps:

[0010] The synthetic polymer is made into a dense layer using a solution casting method;

[0011] Electrospinning is used to form a first transition layer on one side of a dense layer by combining natural and synthetic polymers.

[0012] Electrospinning was used to form a first hydrophilic layer on the surface of the first transition layer from natural polymers.

[0013] Electrospinning was used to create a second transition layer on the other side of the dense layer by combining natural and synthetic polymers.

[0014] Electrospinning was used to form a second hydrophilic layer on the surface of the second transition layer from natural polymers.

[0015] Vacuum molding.

[0016] Solution casting involves dissolving the desired material in a suitable solvent, pouring the solution into a mold, and allowing it to solidify to obtain the desired material. This invention utilizes solution casting to achieve a denser layered structure, thus creating a dense layer. Electrospinning utilizes the special form of electrostatic atomization of polymeric fluids to form microjet streams that travel a considerable distance and ultimately solidify into fibers. These fibers form a layered structure composed of polymeric fibers, containing numerous pores, thus enabling the creation of a loose and porous layered structure. Furthermore, by selecting the materials for each layer, the desired material and structure of the absorbable cardiac occluder membrane can be ultimately produced.

[0017] Thirdly, the application of the above-mentioned absorbable cardiac occluder choke membrane in the preparation of cardiac occluders.

[0018] The beneficial effects of this invention are as follows:

[0019] This invention, through the combination of natural and synthetic polymers, the setting of a multi-layer structure, and the coordination of each layer's structure and materials, provides an absorbable cardiac occluder membrane with good hydrophilicity, biocompatibility, anti-inflammatory properties, and mechanical properties. It can accelerate cell endothelialization and play a role in blocking blood shunting, showing good application prospects. Attached Figure Description

[0020] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0021] Figure 1 The stress-strain curves of the absorbable cardiac occluder choke membrane provided in Embodiment 1 and Comparative Example 3 of the present invention;

[0022] Figure 2 The tear force-displacement curves of the absorbable cardiac occluder dam provided in Embodiment 1 and Comparative Example 3 of the present invention;

[0023] Figure 3 This is a cytotoxicity experiment diagram of the absorbable cardiac occluder choke membrane provided in Embodiment 1 of the present invention.

[0024] Figure 4 This is a diagram showing the cytotoxicity experiment status of the absorbable cardiac occluder choke membrane provided in Comparative Example 4 of the present invention. Detailed Implementation

[0025] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0026] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0027] Given that existing cardiac occluder choke membranes are difficult to balance in terms of hydrophilicity, anti-inflammatory properties, mechanical properties, biocompatibility, and cell affinity, this invention proposes an absorbable cardiac occluder choke membrane and its preparation method.

[0028] In a typical embodiment of the present invention, an absorbable cardiac occluder flow-blocking membrane is provided. The flow-blocking membrane is a multilayer biodegradable polymer composite membrane structure, which sequentially includes: a first hydrophilic layer, a first transition layer, a dense layer, a second transition layer, and a second hydrophilic layer. The first hydrophilic layer, the first transition layer, the second transition layer, and the second hydrophilic layer are all loose and porous layered structures, while the dense layer is a dense layered structure. The first and second hydrophilic layers are made of natural polymers, the first and second transition layers are made of a mixture of natural and synthetic polymers, and the dense layer is made of synthetic polymers. The natural polymers are one or more hydrophilic polymers such as chitosan, hyaluronic acid, and silk fibroin, while the synthetic polymers are one or two copolymers or blends of polylactic acid, polyglycolic acid, polydioxanone, polycaprolactone, and polycarbonate.

[0029] In some embodiments, the synthetic polymer is polylactic acid (PLA). Compared to other synthetic polymers, PLA has better biocompatibility and its mechanical properties meet the requirements, making it a better choice.

[0030] In one or more embodiments, the natural polymer of the first and second hydrophilic layers is chitosan. Chitosan not only has hydrophilicity and anti-inflammatory properties, but also has a certain degree of alkalinity, which can neutralize the acidity generated during the degradation process of synthetic absorbable materials such as polylactic acid, thereby reducing the adverse reactions of the barrier membrane in vivo.

[0031] In some embodiments, the thickness of the dense layer is 0.01 to 0.05 mm.

[0032] In some embodiments, the thickness of the first hydrophilic layer is 0.01 to 0.05 mm.

[0033] In some embodiments, the thickness of the first transition layer is 0.01 to 0.05 mm.

[0034] In some embodiments, the thickness of the second transition layer is 0.01 to 0.05 mm.

[0035] In some embodiments, the thickness of the second hydrophilic layer is 0.01 to 0.05 mm.

[0036] Another embodiment of the present invention provides a method for preparing the above-mentioned absorbable cardiac occluder flow-blocking membrane, comprising the following steps:

[0037] The synthetic polymer is made into a dense layer using a solution casting method;

[0038] Electrospinning is used to form a first transition layer on one side of a dense layer by combining natural and synthetic polymers.

[0039] Electrospinning was used to form a first hydrophilic layer on the surface of the first transition layer from natural polymers.

[0040] Electrospinning was used to create a second transition layer on the other side of the dense layer by combining natural and synthetic polymers.

[0041] Electrospinning was used to form a second hydrophilic layer on the surface of the second transition layer from natural polymers.

[0042] Vacuum molding.

[0043] In some embodiments, the solvent used in the solution casting method to form a dense layer of the synthetic polymer is one or a mixture of two solvents such as dichloromethane, trichloromethane, N,N-dimethylformamide, hexafluoroisopropanol, trifluoroacetic acid, dimethyl sulfoxide, and ethanol.

[0044] In some embodiments, during electrospinning, the solvent used to dissolve and synthesize the polymer is one or a mixture of two solvents such as dichloromethane, trichloromethane, N,N-dimethylformamide, hexafluoroisopropanol, trifluoroacetic acid, dimethyl sulfoxide, and ethanol.

[0045] In some embodiments, during electrospinning, the solvent for dissolving the natural polymer is one or a mixture of two solvents such as water, ethanol, acetic acid, dichloromethane, chloroform, N,N-dimethylformamide, hexafluoroisopropanol, trifluoroacetic acid, and dimethyl sulfoxide.

[0046] In some embodiments, during the electrospinning process of preparing the first or second transition layer, natural and synthetic polymers are electrospinned simultaneously along different axes.

[0047] In some embodiments, after all electrospinning is completed, the fibers are first dried, then soaked in anhydrous ethanol, then dried a second time, and finally vacuum-pressed into a film. Specifically, the soaking time is 0.5–4 hours. Specifically, the first drying is vacuum drying; more specifically, the vacuum drying temperature is 30–60°C and the time is 6–48 hours. Specifically, the second drying is forced-air drying; more specifically, the forced-air drying temperature is 30–60°C and the time is 1–8 hours.

[0048] In some embodiments, the temperature for vacuum molding is 20–60°C, and the molding time is 0.5–10 min.

[0049] In some embodiments, vacuum molding includes packaging and sterilization. Specifically, aluminum-plastic bags are used for sealed packaging. Specifically, gamma ray sterilization is used.

[0050] A third embodiment of the present invention provides an application of the above-mentioned absorbable cardiac occluder choke membrane in the preparation of a cardiac occluder.

[0051] Specifically, the cardiac occluder is a ventricular septal defect occluder, an atrial septal defect occluder, a left atrial appendage occluder, a patent ductus arteriosus occluder, or a patent foramen ovale occluder, etc.

[0052] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments and comparative examples.

[0053] Example 1

[0054] An absorbable cardiac occluder choke membrane is prepared by the following steps:

[0055] Step 1: Prepare a dense layer:

[0056] Solution preparation: Polylactic acid (PLLA) was dissolved in dichloromethane (DCM) to prepare a synthetic polymer solution. PLLA has a weight-average molecular weight of 113,000 and a molecular weight distribution of 1.57. 2g of PLLA was weighed and placed in a 25mL volumetric flask, and DCM was added to the mark. The solution was allowed to dissolve for 16 hours.

[0057] Ultrasonic and degassing treatment: First, place the volumetric flask in an ultrasonic cleaner to accelerate the homogeneity of the solution. The treatment conditions are: ultrasonic temperature 40℃, time 30min, and frequency 45Hz. Then, perform ultrasonic degassing treatment. The treatment conditions are: temperature room temperature, time 30min, and frequency 30Hz.

[0058] Casting and film formation: The synthetic polymer solution after the above degassing treatment is cast into a mold. The mold material is polytetrafluoroethylene plate and the mold size is 10*10cm. Then, the thickness of the film is adjusted to 0.02mm using a film scraper. The mold is then placed on a water platform in a fume hood and dried for 24 hours to obtain a dense PLLA film.

[0059] Step 2: Prepare the first transition layer:

[0060] Preparation of PLLA solution: PLLA has a weight-average molecular weight of 113,000 and a molecular weight distribution of 1.57. Measure 40 mL of chloroform (CF) and 10 mL of dimethylformamide (DMF) into 100 mL brown ground glass stoppered bottles, then weigh 5.28 g of PLLA into the same bottle and dissolve for 16 hours.

[0061] Prepare chitosan (CS) solution: Measure 25 mL of acetic acid (HAc) and 25 mL of water into a 100 mL ground glass bottle, then weigh 4.12 g of CS into the brown ground glass bottle and dissolve for 16 h.

[0062] Ultrasonic and degassing treatment: First, place the ground glass bottle in an ultrasonic cleaner to accelerate the homogeneity of the solution mixing. The treatment conditions are: ultrasonic temperature 30℃, time 30min, and frequency 45Hz. Then, perform ultrasonic degassing treatment. The treatment conditions are: temperature room temperature, time 30min, and frequency 30Hz.

[0063] Use the first syringe (20mL) to draw 10mL of PLLA solution and then install it on the Y-axis of the electrospinning machine; use the second syringe (20mL) to draw 20mL of CS solution and then install it on the Z-axis of the electrospinning machine.

[0064] The dense layer prepared in step 1 was wrapped around the collecting roller of an electrospinning machine. The spinning environment was set as follows: spinning temperature 40℃, spinning chamber humidity 25%; the electrospinning parameters were set as follows: positive spinning voltage 20KV, negative voltage 500V, receiving roller distance 14cm, roller speed 600RPM, Y-axis and Z-axis feed speeds both 0.01mm / s, X-axis distance 10cm, X-axis scanning speed 5mm / s, and nozzle size 0.8mm. Simultaneous spinning along the Y and Z axes was set, with a Y-axis and Z-axis advance distance of 5cm. PLLA and CS nanofibers were collected and covered on the PLLA dense layer, forming the first transition layer.

[0065] Step 3: Prepare the first hydrophilic layer:

[0066] In step 2, the Y-axis feed rate is set to 0, the Y-axis advance distance is 0, and other parameters remain unchanged. Electrospinning continues, and CS nanofibers are collected and covered on the first transition layer, which is the first hydrophilic layer.

[0067] Step 4: Prepare the second transition layer:

[0068] Remove the electrospun membrane from step 3. Attach the first hydrophilic layer close to and wrap it around the collecting roller of the electrospinning machine. Set the spinning environment as follows: spinning temperature 40℃, spinning chamber humidity 25%. Set the electrospinning parameters as follows: positive spinning voltage 20KV, negative voltage 500V, receiving roller distance 14cm, roller speed 600RPM, Y-axis and Z-axis feed speeds both 0.01mm / s, X-axis distance 10cm, X-axis scanning speed 5mm / s, and nozzle size 0.8mm. Set the Y-axis and Z-axis to spin simultaneously, with a Y-axis and Z-axis advance distance of 5cm. Cover and collect PLLA and CS nanofibers on the dense PLLA layer; this forms the second transition layer.

[0069] Step 5: Prepare the second hydrophilic layer:

[0070] In step 4, the Y-axis feed rate is set to 0, the Y-axis advance distance is 0, and other parameters remain unchanged. Electrospinning continues, and CS nanofibers are collected and covered on the second transition layer, which is the second hydrophilic layer.

[0071] Step 6, Post-processing:

[0072] After removing the electrospun membrane from step 5 above, place it in a vacuum oven at 40°C and dry for 24 hours. Then, soak the dried membrane in anhydrous ethanol for 1 hour. Finally, remove the electrospun membrane and dry it in a forced-air oven at 40°C for 2 hours.

[0073] Step 7: Cutting and secondary shaping:

[0074] The membrane from step 6 above is laser-cut to a size of 5cm*5cm. The cut membrane is then placed in a vacuum laminator at 40℃ and laminated for 2 minutes before being removed.

[0075] Step 8: Packaging and sterilization:

[0076] The film from step 7 above is sealed and packaged, with the inner bag being a polyester bag and the outer bag being an aluminum-plastic bag. It is then heat-sealed for 0.5 minutes.

[0077] After packaging, the product is sterilized using gamma rays at a dose of 20 kGy.

[0078] Example 2

[0079] This embodiment provides an absorbable cardiac occluder cholangiography membrane, which differs from Embodiment 1 only in that the natural polymer is hyaluronic acid, while the other materials, reagents, and preparation methods are the same as in Embodiment 1.

[0080] Example 3

[0081] This embodiment provides an absorbable cardiac occluder choke membrane, which differs from Embodiment 1 only in that the natural polymer is silk fibroin, while the other materials, reagents, and preparation methods are the same as in Embodiment 1.

[0082] Example 4

[0083] This embodiment provides an absorbable cardiac occluder choke membrane, which differs from Embodiment 1 only in that the synthetic polymer is polyglycolic acid and the solvent is hexafluoroisopropanol (HFIP). Other materials, reagents, and preparation methods are the same as in Embodiment 1.

[0084] Example 5

[0085] This embodiment provides an absorbable cardiac occluder choke membrane, which differs from Embodiment 1 only in that the synthetic polymer is poly(p-dioxanone), the solvent is HFIP, and the other materials, reagents, and preparation methods are the same as in Embodiment 1.

[0086] Example 6

[0087] This embodiment provides an absorbable cardiac occluder choke membrane, which differs from Embodiment 1 only in that the synthetic polymer is a lactic acid-glycolic acid copolymer, the solvent is a blend of CF and DMF, and the other materials, reagents, and preparation methods are the same as in Embodiment 1.

[0088] Example 7

[0089] This embodiment provides an absorbable cardiac occluder choke membrane, which differs from Embodiment 1 only in that the synthetic polymer is a lactic acid-caprolactone copolymer, the solvent is a blend of CF and DMF, and the other materials, reagents, and preparation methods are the same as in Embodiment 1.

[0090] Comparative Example 1

[0091] This comparative example provides an absorbable cardiac occluder choke membrane, which differs from Example 1 only in that the choke membrane consists only of the PLLA dense membrane from step 1 and does not include the electrospun membrane.

[0092] Comparative Example 2

[0093] This comparative example provides an absorbable cardiac occluder choke membrane, which differs from Example 1 only in that the choke membrane does not include a first transition layer and a second transition layer. In the absorbable cardiac occluder choke membrane prepared in this comparative example, the first and second hydrophilic layers do not adhere well to the dense PLLA layer and are in a separated state.

[0094] Comparative Example 3

[0095] This comparative example provides an absorbable cardiac occluder choke membrane, which differs from Example 1 only in that the choke membrane does not include a PLLA dense membrane.

[0096] Comparative Example 4

[0097] This comparative example provides an absorbable cardiac occluder choke membrane, which differs from Example 1 only in that the choke membrane includes a PLLA dense membrane and a PLLA electrospun membrane, but does not include a CS electrospun membrane.

[0098] Test Example 1

[0099] This test example provides mechanical property tests on the absorbable cardiac occluder choke membranes of Example 1 and Comparative Example 3. The tensile and tear properties of the choke membranes were tested using a Shimadzu AGS-H universal testing machine. The test load was 500 N, and the tensile rate was 100 mm / min. For the tensile property test, a 10 mm * 150 mm rectangular strip was used. Both ends of the strip were fixed to fixtures. The stress of the sample was calculated using the maximum tensile load, and the strain was calculated using displacement. The stress-strain curve of the sample was plotted. For the tear property test, a 10 mm * 25 mm rectangular strip was used. A 4-0 suture was passed through the sample 3 mm from the short edge. The suture was folded in half and knotted approximately 5 cm from the perforation to prevent suture slippage. The un-sutured end and the sutured end of the sample membrane were fixed to fixtures. The tear force of the sample was calculated as the maximum tensile load. The stress-strain curves of the samples are shown below. Figure 1 The tear force-displacement curve is shown below. Figure 2 The stress-strain curves and tear force-displacement curves of the flow-blocking membranes in Example 1 and Comparative Example 3 show that adding a dense layer can significantly improve their tensile strength and tear force.

[0100] Test Example 2

[0101] This test provides an antibacterial performance test of the absorbable cardiac occluder choke membranes in Example 1 and Comparative Example 4. Following standard ASTM E2180-07, the antibacterial activity of the choke membranes against *E. coli* was determined by plate culture counting, with three replicates for each sample. The choke membrane in Example 1 showed an 86.9% inhibition rate against *E. coli*, while the choke membrane in Comparative Example 4 showed a 3.8% inhibition rate. The experimental results indicate that chitosan itself possesses antibacterial properties and exhibits significant anti-inflammatory effects.

[0102] Test Example 3

[0103] This test example provides hydrophilicity tests on the choke membranes of the absorbable cardiac occluders in Example 1 and Comparative Example 4. The static contact angles of the choke membranes in Example 1 and Comparative Example 4 were measured using an XG-CAMC31 contact angle meter from Shanghai Xuanzhun Instruments Co., Ltd. Five points were tested for each sample, and the average value was taken. The static contact angle of the choke membrane in Example 1 was 39.8°, and the static contact angle of the choke membrane in Comparative Example 4 was 129.8°. The experimental results show that the hydrophilicity of the choke membrane with added CS is significantly improved.

[0104] Test Example 4

[0105] This test case provides an in vitro cytotoxicity assay of the absorbable cardiac occluder membranes from Examples 1 and 4. The extraction medium was serum-containing MEM medium, and the sample extracts were prepared at 6 cm⁻¹. 2 Add the prepared 1×10⁶ mL solution to the extraction medium. 5 100 μL of L929 cell suspension was seeded into each well of a 96-well plate. A blank control, negative control, positive control, and test sample group (the absorbable cardiac occluder membrane provided in Example 1 and Comparative Example 4) were included, with at least 6 wells in each group. The plates were incubated at 37°C for 24 hours using a 5% CO2 incubator. The original culture medium was discarded. Fresh cell culture medium was added to the blank control group, and 100 μL of the corresponding extraction solution was added to each of the negative control, positive control, and test sample groups. The plates were then incubated for another 24 hours using a 5% CO2 incubator.

[0106] 24 hours after changing the culture medium, cell morphology was observed under a microscope. The cell morphologies of Example 1 and Comparative Example 4 are shown in the figures below. Figure 3 and Figure 4 Add 20 μL of MTT solution (5 g / L) to each well, continue culturing for 4 h, then discard the liquid in the wells. Add 150 μL of LDMSO, shake for 10 min, and measure the absorbance at 570 nm (reference wavelength 650 nm) using a microplate reader. Calculate the cell viability (%). The viability of Example 1 was 96%, and the viability of Comparative Example 4 was 87%.

[0107] The photographs show that the cells in Example 1 are plump and growing well, while the cells in Comparative Example 4 exhibit apoptosis. The cell viability also indicates that increasing the CS hydrophilic layer effectively improves cell viability. This may be because the weak acidity of PLLA has a certain killing effect on cells, while the weak alkalinity of CS can neutralize the weak acidity of PLLA, thus promoting cell growth. The experimental results show that increasing the CS hydrophilic layer is beneficial for cell proliferation.

[0108] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. An absorbable heart occluder membrane, characterized in that, The flow-blocking membrane is a multilayer biodegradable polymer composite membrane structure, which sequentially includes: a first hydrophilic layer, a first transition layer, a dense layer, a second transition layer, and a second hydrophilic layer. The first hydrophilic layer, the first transition layer, the second transition layer, and the second hydrophilic layer are all loose and porous layered structures, while the dense layer is a dense layered structure. The first and second hydrophilic layers are made of natural polymers, the first and second transition layers are made of a mixture of natural and synthetic polymers, and the dense layer is made of synthetic polymers. The natural polymers are one or more hydrophilic polymers selected from chitosan, hyaluronic acid, and silk fibroin, while the synthetic polymers are one or a copolymer of two of the following: polylactic acid, polyglycolic acid, polydioxanone, polycaprolactone, and polycarbonate. The synthetic polymer is made into a dense layer using a solution casting method; Natural polymers are mounted on the Z-axis of an electrospinning machine, and synthetic polymers are mounted on the Y-axis of the same machine. Electrospinning is performed simultaneously on both the Z and Y axes to prepare a transition layer.

2. The absorbable cardiac occluder choke membrane as described in claim 1, characterized in that, The synthetic polymer is polylactic acid.

3. The absorbable cardiac occluder choke membrane as described in claim 2, characterized in that, The natural polymers of the first and second hydrophilic layers are chitosan.

4. The absorbable cardiac occluder choke membrane as described in claim 2, characterized in that, The thickness of the dense layer is 0.01~0.05 mm; Alternatively, the thickness of the first hydrophilic layer is 0.01~0.05 mm; Alternatively, the thickness of the first transition layer is 0.01~0.05 mm; Alternatively, the thickness of the second transition layer is 0.01~0.05 mm; Alternatively, the thickness of the second hydrophilic layer is 0.01~0.05 mm.

5. A method for preparing the absorbable cardiac occluder choke membrane according to claim 1, characterized in that, Includes the following steps: The synthetic polymer is made into a dense layer using a solution casting method; Electrospinning is used to form a first transition layer on one side of a dense layer by combining natural and synthetic polymers. Electrospinning was used to form a first hydrophilic layer on the surface of the first transition layer from natural polymers. Electrospinning was used to create a second transition layer on the other side of the dense layer by combining natural and synthetic polymers. Electrospinning was used to form a second hydrophilic layer on the surface of the second transition layer from natural polymers. Vacuum molding.

6. The method for preparing the absorbable cardiac occluder choke membrane as described in claim 5, characterized in that, The solvent used in the solution casting method to form a dense layer of synthetic polymer is one or a mixture of two of the following solvents: dichloromethane, trichloromethane, N,N-dimethylformamide, hexafluoroisopropanol, trifluoroacetic acid, dimethyl sulfoxide, and ethanol. Alternatively, in electrospinning, the solvent used to dissolve and synthesize the polymer is one or a mixture of two of the following: dichloromethane, trichloromethane, N,N-dimethylformamide, hexafluoroisopropanol, trifluoroacetic acid, dimethyl sulfoxide, and ethanol. Alternatively, in electrospinning, the solvent for dissolving natural polymers is one or a mixture of two of the following: water, ethanol, acetic acid, dichloromethane, chloroform, N,N-dimethylformamide, hexafluoroisopropanol, trifluoroacetic acid, and dimethyl sulfoxide.

7. The method for preparing the absorbable cardiac occluder choke membrane as described in claim 5, characterized in that, After all electrospinning is completed, the fibers are first dried, then soaked in anhydrous ethanol, then dried a second time, and finally vacuum pressed into a film. The soaking time is 0.5 to 4 hours. The first drying is vacuum drying. The temperature of vacuum drying is 30 to 60 ℃ and the time is 6 to 48 hours. The second drying is forced air drying. The temperature of forced air drying is 30 to 60 ℃ and the time is 1 to 8 hours.

8. The method for preparing the absorbable cardiac occluder choke membrane as described in claim 5, characterized in that, The temperature for vacuum molding is 20~60 ℃, and the molding time is 2~20 min; Alternatively, vacuum molding can be followed by packaging and sterilization; aluminum-plastic bags can be used for sealed packaging; or gamma-ray sterilization can be used.

9. The use of the absorbable cardiac occluder choke membrane according to any one of claims 1 to 4 in the preparation of a cardiac occluder.

10. The application as described in claim 9, characterized in that, The cardiac occluder is a ventricular septal defect occluder, an atrial septal defect occluder, a left atrial appendage occluder, a patent ductus arteriosus occluder, or a patent foramen ovale occluder.

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