Composite absorbable porous repair membrane as well as preparation method and application thereof

Abstract

The invention provides a composite absorbable porous repair membrane and a preparation method and application thereof. The porous repair membrane comprises a first substrate layer, a barrier layer and a second substrate layer which are stacked, the first substrate layer and the second substrate layer are made of a lactide-glycolide copolymer, a polyethylene glycol-polylactic acid copolymer and a lactide-caprolactone copolymer; through the specific three-layer structural design and the electrostatic spinning preparation process, the obtained porous repair film has a bionic structure and also has the characteristics of good biocompatibility, stable mechanical properties, excellent waterproof and anti-adhesion effects and the like; the artificial dura mater overcomes the defects that the artificial dura mater made of a traditional biological material easily causes human body rejection reaction, allograft infectious transmission, easy pollution and the like, and can be used as an optional dura mater for overall repair of the dura mater.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical materials, and particularly relates to a composite absorbable porous repair membrane, a preparation method thereof, and an application thereof. Background Art

[0002] The repair of the dura mater after craniocerebral and spinal neurosurgery is currently a technical challenge. At the end of many routine surgeries, and even more often during surgeries in the posterior cranial fossa and skull base, surgeons face the high risk of non-repairable dura mater and cerebrospinal fluid (CSF) leakage. Dural defects are caused by bipolar coagulation, attenuation of the dura mater, or contraction due to tearing during exposure, especially during meningioma surgery, where the dura mater usually needs to be resected or damaged to obtain normal tumor resection and achieve the expected surgical results. Generally speaking, tension-free is relatively infeasible, and dural patch transplantation is required. There are various options for repairing dural defects, including autologous transplantation, such as pericranial or fascia, usually xenotransplantation from human or bovine fascia, where skin and commercially processed graft materials are usually prepared from bovine collagen sources or human tissues. Autologous graft materials have many advantages, including biocompatibility, availability, and cost; however, they usually require additional or enlarged incisions, along with surgical risks, as well as postoperative pain and discomfort.

[0003] To overcome these problems, it is urgent to explore other repair approaches. The development of artificial dura mater substitutes from non-biological materials has become an ideal measure. Non-biological materials include absorbable polymers, such as those commonly used in sutures, and non-absorbable inert polymers, such as aliphatic polyurethanes. However, most of the existing traditional artificial dura mater repair patches are made entirely of high molecular polymers, resulting in poor waterproofing effects and insufficient mechanical support, and are prone to cause inflammatory reactions and have a certain risk of infection when used.

[0004] Therefore, the development of a porous repair membrane with a bionic structure, good biocompatibility, stable mechanical properties, and excellent waterproof and anti-adhesion effects is still a technical problem urgently to be solved in this field. Summary of the Invention

[0005] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide a composite absorbable porous repair membrane, a preparation method thereof, and an application thereof. The porous repair membrane has a bionic structure, and also has characteristics such as good biocompatibility, stable mechanical properties and mechanical performance, and good waterproof and anti-adhesion effects, which can effectively make up for the defects such as human rejection reactions, infectious transmission of allogeneic grafts, and easy contamination easily caused by artificial dura mater made of traditional biological materials.

[0006] To achieve the purpose of this invention, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a composite absorbable porous repair membrane, which comprises a first matrix layer, a barrier layer and a second matrix layer stacked on top of each other;

[0008] The materials of the first matrix layer and the second matrix layer both include lactide-glycolide copolymer, polyethylene glycol-polylactic acid copolymer and lactide-caprolactone copolymer.

[0009] The porous repair membrane provided by the present invention has a sandwich structure. The upper and lower layers are both matrix layers, and the materials include lactide-glycolide copolymer (PLGA), polyethylene glycol-polylactic acid copolymer (PELA) and lactide-caprolactone copolymer (PLCL). The above three materials are combined and made into the matrix layer by electrospinning, aiming to provide a matrix for tissue growth and graft replacement and an environmental medium or channel for cell growth and reproduction; the middle layer is a barrier layer, which can provide a watertight barrier during the absorption process, and the material of the barrier layer is soft, not fragile, compliant, smooth and absorbable; through the combination of the above three-layer structure, the obtained porous repair membrane has the advantages of high fiber density and controllable pore size in structure, and has the characteristics of being completely degradable (or completely absorbed by the human body), stable mechanical properties and mechanical properties, and excellent waterproof and anti-adhesion effects in performance, making up for the defects of the traditional biological material dura mater patch such as human rejection reaction, infectious transmission of allogeneic grafts, and easy contamination.

[0010] Preferably, the thickness of the porous repair membrane is 0.2 to 0.4 mm, such as 0.2 mm, 0.22 mm, 0.24 mm, 0.26 mm, 0.28 mm, 0.3 mm, 0.32 mm, 0.34 mm, 0.36 mm, 0.38 mm or 0.4 mm, etc.

[0011] Preferably, the thicknesses of the first matrix layer and the second matrix layer are each independently 0.05 to 0.1 mm, such as 0.05 mm, 0.055 mm, 0.06 mm, 0.065 mm, 0.07 mm, 0.075 mm, 0.08 mm, 0.085 mm, 0.09 mm, 0.095 mm or 0.1 mm, etc.

[0012] Preferably, the mass ratio of the lactide-glycolide copolymer, the polyethylene glycol-polylactic acid copolymer and the lactide-caprolactone copolymer is (1 to 4):(6 to 15):(1 to 3), such as 1:6:1, 1.5:8:1.3, 2:9:1.5, 2.5:11:1.8, 3:12:2.1, 3.5:13:2.5 or 4:15:3, etc.

[0013] Preferably, the thickness of the barrier layer is 0.1 to 0.2 mm, such as 0.1 mm, 0.11 mm, 0.12 mm, 0.13 mm, 0.14 mm, 0.15 mm, 0.16 mm, 0.17 mm, 0.18 mm, 0.19 mm or 0.2 mm, etc.

[0014] Preferably, the material of the barrier layer comprises any one or a combination of at least two of polyglycolic acid, polydioxanone or polydioxane.

[0015] In a second aspect, the present invention provides a method for preparing the porous repair membrane as described in the first aspect, and the preparation method comprises the following steps:

[0016] (1) Dissolve a lactide-glycolide copolymer, a polyethylene glycol-polylactic acid copolymer and a lactide-caprolactone copolymer in an organic solvent A to obtain an electrospinning stock solution A;

[0017] Dissolve the material of the barrier layer in an organic solvent B to obtain an electrospinning stock solution B;

[0018] (2) Perform electrospinning on the electrospinning stock solution A obtained in step (1), the electrospinning stock solution B obtained in step (2) and the electrospinning stock solution A obtained in step (1) in sequence, and perform heat setting to obtain the composite absorbable porous repair membrane.

[0019] Preferably, the organic solvent A and the organic solvent B are each independently any one or a combination of at least two of N,N-dimethylformamide, acetone, hexafluoroisopropanol or dichloromethane.

[0020] Preferably, the mass percentage content of the lactide-glycolide copolymer in the electrospinning stock solution A is 1 to 4%, such as 1%, 1.5%, 2%, 2.5%, 3%, 3.5% or 4%, etc.

[0021] Preferably, the mass percentage content of the polyethylene glycol-polylactic acid copolymer in the electrospinning stock solution A is 6 to 15%, such as 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14% or 15%, etc.

[0022] Preferably, the mass percentage content of the lactide-caprolactone copolymer in the electrospinning stock solution A is 1 to 3%, such as 1%, 1.2%, 1.4%, 1.6%, 1.8%, 2%, 2.2%, 2.4%, 2.6%, 2.8% or 3%, etc.

[0023] Preferably, the mass percentage content of the material of the barrier layer in the electrospinning stock solution B is 8 to 26%, such as 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24% or 26%, etc.

[0024] Preferably, the spinning time of the electrospinning is 5 - 15 min, such as 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 11 min, 12 min, 13 min, 14 min or 15 min, etc.

[0025] Preferably, the receiving distance of the electrospinning is 20 - 40 cm, such as 20 cm, 22 cm, 24 cm, 26 cm, 28 cm, 30 cm, 32 cm, 34 cm, 36 cm, 38 cm or 40 cm, etc.

[0026] Preferably, the applied voltage of the electrospinning is 10 - 30 kV, such as 10 kV, 12 kV, 14 kV, 16 kV, 18 kV, 20 kV, 22 kV, 24 kV, 26 kV, 28 kV or 30 kV, etc.

[0027] Preferably, the liquid injection speed of the electrospinning is 10 - 30 μL / min, such as 10 μL / min, 12 μL / min, 14 μL / min, 16 μL / min, 18 μL / min, 20 μL / min, 22 μL / min, 24 μL / min, 26 μL / min, 28 μL / min or 30 μL / min, etc.

[0028] Preferably, the heat setting is carried out by covering with a glass plate.

[0029] Preferably, the temperature of the heat setting is 25 - 45 °C, such as 25 °C, 27 °C, 29 °C, 31 °C, 33 °C, 35 °C, 37 °C, 39 °C, 41 °C, 43 °C or 45 °C, etc.

[0030] Preferably, the time of the heat setting is 30 - 80 min, such as 30 min, 35 min, 40 min, 45 min, 50 min, 55 min, 60 min, 65 min, 70 min, 75 min or 80 min, etc.

[0031] As a preferred technical solution of the present invention, the preparation method comprises the following steps:

[0032] (1) Dissolve the lactide - glycolide copolymer, polyethylene glycol - polylactic acid copolymer and lactide - caprolactone copolymer in organic solvent A to obtain electrospinning stock solution A;

[0033] Dissolve the material of the barrier layer in organic solvent B to obtain electrospinning stock solution B;

[0034] (2) Inject the electrospinning stock solution A obtained in step (1) into a syringe, and perform electrospinning under the action of a syringe pump. The spinning time is 5 - 15 min, the injection speed is 10 - 30 μL / min, the applied voltage is 10 - 30 kV, use a metal rotating receiver, the rotating receiving speed is 1000 - 3500 r / h, and the receiving distance is 20 - 40 cm to obtain the first matrix layer;

[0035] (3) Replace the syringe, inject the electrospinning stock solution B obtained in step (1) into the syringe, and perform secondary electrospinning under the action of a syringe pump. The spinning time is 5 - 15 min, the injection speed is 10 - 30 μL / min, the applied voltage is 10 - 30 kV, use a metal rotating receiver to receive, the rotating receiving speed is 1000 - 3500 r / h, and the receiving distance is 20 - 40 cm to form a barrier layer on the first matrix layer;

[0036] (4) Replace the syringe, inject the electrospinning stock solution A obtained in step (1) into the syringe, and perform electrospinning under the action of a syringe pump. The spinning time is 5 - 15 min, the injection speed is 10 - 30 μL / min, the applied voltage is 10 - 30 kV, use a metal rotating receiver to receive, the rotating receiving speed is 1000 - 3500 r / h, and the receiving distance is 20 - 40 cm to form a second matrix layer on the barrier layer to obtain the primary repair membrane;

[0037] (5) After unloading the primary repair membrane obtained in step (4) from the metal rotating receiver, perform post - covering heat - setting on a glass plate. The heat - setting temperature is 25 - 45 °C and the time is 30 - 80 min to obtain the porous repair membrane.

[0038] In the third aspect, the present invention provides an application of the porous repair membrane as described in the first aspect as an artificial dura mater.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] (1) The porous repair membrane provided by the present invention can be completely degraded (or completely absorbed) in the human body, has a bionic structure, stable mechanical properties and mechanical performance, good biocompatibility, waterproof and anti - adhesion, etc., making up for the defects such as human rejection reaction, infectious transmission of allogeneic grafts, and easy contamination brought by traditional biological material dura mater patches;

[0041] (2) The porous repair membrane provided by the present invention can prevent adhesion during the overall repair of the dura mater, has a certain tissue permeability, can absorb essential substances such as oxygen and nutrients, act locally on the affected area, and can greatly reduce a series of inflammatory reactions caused by dura mater damage during the long - term self - repair process of the body;

[0042] (3) The porous repair membrane provided by the present invention replaces the dura mater and can be completely degraded within 90 to 270 days after being implanted into the human body, thereby avoiding foreign body rejection reaction and secondary surgery. The degradation rate of the absorbable porous repair membrane can be controlled by changing the ratio of the matrix layer and the barrier layer and adjusting the spinning density. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 A schematic diagram of the overall structure of the porous repair membrane provided by the present invention;

[0044] Figure 2 This is a scanning electron microscope image of the porous repair membrane provided in Example 1. DETAILED DESCRIPTION

[0045] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0046] Unless otherwise specified, the raw materials involved in the following examples and comparative examples are conventional materials in the art and can be purchased from commercial products. In particular, the information of some raw materials involved is as follows:

[0047] (1) Lactide-glycolide copolymer: PLGA, purchased from Evonik Specialty Chemicals (Shanghai) Co., Ltd., model LG D1.75, wherein the molar ratio of lactide units to glycolide units is 85:15;

[0048] (2) Polyethylene glycol-polylactic acid copolymer: PELA, purchased from Xi'an Qiyue Biotechnology Co., Ltd., with a weight average molecular weight of 6000, wherein the molar ratio of lactic acid unit to ethylene glycol unit is 40:60;

[0049] (3) Lactide-caprolactone copolymer: PLCL, purchased from Merck KGaA, Darmstadt, Germany, with a weight average molecular weight of 150,000, wherein the molar ratio of lactide unit to caprolactone unit is 67:27;

[0050] (4) Polydioxanone: PDS, purchased from Evonik Specialty Chemicals (Shanghai) Co., Ltd., model X D1.75.

[0051] Example 1

[0052] A composite absorbable porous repair membrane, the overall structure of which is shown in the figure Figure 1 As shown, it comprises a first substrate layer 1, a barrier layer 2 and a second substrate layer 3 which are stacked;

[0053] Among them, the thicknesses of the first matrix layer 1 and the second matrix layer 3 are both 0.08 mm, and the materials include PLGA, PELA, and PLCL with a mass ratio of 3:10:2;

[0054] The thickness of the barrier layer 2 is 0.15 mm, and the material is PDS;

[0055] The preparation method of the porous repair membrane provided in this embodiment includes the following steps:

[0056] (1) Dissolve PLGA, PELA, and PLCL in a mixed solution of hexafluoroisopropanol and dichloromethane (the mass ratio of hexafluoroisopropanol to dichloromethane is 70:30), so that the mass percentage content of PLGA in the mixed solution is 3%, the mass percentage content of PELA is 10%, and the mass percentage content of PLCL is 2%. After heating to 50 °C and stirring evenly, obtain electrospinning stock solution A;

[0057] Dissolve PDS in a mixed solution of hexafluoroisopropanol and dichloromethane (the mass ratio of hexafluoroisopropanol to dichloromethane is 80:20), so that the mass percentage content of PDS in the mixed solution is 25%, and obtain electrospinning stock solution B;

[0058] (2) Inject the electrospinning stock solution A obtained in step (1) into the syringe of the electrospinning device, adjust the injection speed to 15 μL / min, the applied voltage to 20 kV, carry out electrospinning under the action of a propulsion pump, adjust the rotational receiving speed to 1800 r / h, the receiving distance to 30 cm, and the spinning time to 8 min, and use a metal rotating receiver for receiving to obtain the first matrix layer;

[0059] (3) Replace the syringe, and use the electrospinning stock solution B obtained in step (1) for the second electrospinning. Adjust the injection speed to 20 μL / min, the applied voltage to 30 kV, the rotational receiving speed to 2000 r / h, the receiving distance to 30 cm, and the spinning time to 15 min. Use a metal rotating receiver for receiving to form a barrier layer on the first matrix layer;

[0060] (4) Continue to replace the syringe, and use the electrospinning stock solution A obtained in step (1) for the third electrospinning. Adjust the injection speed to 15 μL / min, the applied voltage to 20 kV, adjust the rotational receiving speed to 1800 r / h, the receiving distance to 30 cm, and the spinning time to 8 min. Use a metal rotating receiver for receiving to form a second matrix layer on the barrier layer to obtain a primary repair membrane;

[0061] (5) After unloading the primary repair membrane obtained in step (4) from the metal rotating receiver, perform heat setting by covering it with a glass plate. The heat setting temperature is 40 °C and the time is 45 min. After complete drying, perform ethylene oxide sterilization and aseptic packaging to obtain the porous repair membrane.

[0062] Example 2

[0063] A composite absorbable porous repair membrane, whose overall structure is the same as that of Example 1, includes a first matrix layer, a barrier layer, and a second matrix layer which are stacked;

[0064] Among them, the thicknesses of the first matrix layer and the second matrix layer are both 0.06 mm, and the materials include PLGA, PELA, and PLCL with a mass ratio of 2:14:3;

[0065] The thickness of the barrier layer is 0.18 mm, and the material is PDS;

[0066] The preparation method of the porous repair membrane provided in this example includes the following steps:

[0067] (1) Dissolve PLGA, PELA, and PLCL in a mixed solution of hexafluoroisopropanol and dichloromethane (the mass ratio of hexafluoroisopropanol to dichloromethane is 70:30), so that the mass percentage content of PLGA in the mixed solution is 2%, the mass percentage content of PELA is 14%, and the mass percentage content of PLCL is 3%. After heating to 50 °C and stirring evenly, obtain electrospinning stock solution A;

[0068] Dissolve PDS in a mixed solution of hexafluoroisopropanol and dichloromethane (the mass ratio of hexafluoroisopropanol to dichloromethane is 80:20), so that the mass percentage content of PDS in the mixed solution is 20%, and obtain electrospinning stock solution B;

[0069] (2) Inject the electrospinning stock solution A obtained in step (1) into the syringe of the electrospinning device, adjust the injection speed to 12 μL / min, the applied voltage to 15 kV, carry out electrospinning under the action of a propulsion pump, adjust the rotational receiving speed to 2000 r / h, the receiving distance to 25 cm, and the spinning time to 10 min, and use a metal rotary receiver for receiving to obtain the first matrix layer;

[0070] (3) Replace the syringe, carry out the second electrospinning with the electrospinning stock solution B obtained in step (1), adjust the injection speed to 15 μL / min, the applied voltage to 15 kV, the rotational receiving speed to 3000 r / h, the receiving distance to 20 cm, and the spinning time to 10 min, and use a metal rotary receiver for receiving to form a barrier layer on the first matrix layer;

[0071] (4) Continue to replace the syringe and perform the third electrospinning with the electrospinning stock solution A obtained in step (1). Adjust the injection rate to 12 μL / min, the applied voltage to 15 kV, and perform electrospinning under the action of a syringe pump. Adjust the rotational receiving speed to 2000 r / h, the receiving distance to 25 cm, and the spinning time to 10 min. Use a metal rotating receiver for receiving to form a second matrix layer on the barrier layer, obtaining a primary repair membrane.

[0072] (5) After unloading the primary repair membrane obtained in step (4) from the metal rotating receiver, perform heat setting by covering it with a glass plate from behind. The heat setting temperature is 30 °C and the time is 65 min. After complete drying, perform ethylene oxide sterilization and aseptic packaging to obtain the porous repair membrane.

[0073] Example 3

[0074] A composite absorbable porous repair membrane, which is different from Example 1 in that polyglycolic acid is used to replace PDS as the material of the barrier layer, and other structures, materials, and preparation methods are the same as those in Example 1.

[0075] Example 4

[0076] A composite absorbable porous repair membrane, which is different from Example 1 in that the thicknesses of both the first matrix layer and the second matrix layer are 0.03 mm, and other structures, materials, and preparation methods are the same as those in Example 1.

[0077] Example 5

[0078] A composite absorbable porous repair membrane, which is different from Example 1 in that the thicknesses of both the first matrix layer and the second matrix layer are 0.15 mm, and other structures, materials, and preparation methods are the same as those in Example 1.

[0079] Example 6

[0080] A composite absorbable porous repair membrane, which is different from Example 1 in that the thickness of the barrier layer is 0.05 mm, and other structures, materials, and preparation methods are the same as those in Example 1.

[0081] Example 7

[0082] A composite absorbable porous repair membrane, which is different from Example 1 in that the thickness of the barrier layer is 0.3 mm, and other structures, materials, and preparation methods are the same as those in Example 1.

[0083] Comparative Example 1

[0084] A composite absorbable porous repair membrane, which is different from Example 1 in that neither PELA nor PLCL is added to the materials of the first matrix layer and the second matrix layer, and the mass ratio of PELA to PLCL is still 10:2. Other structures, materials, and preparation methods are the same as those in Example 1.

[0085] Comparative Example 2

[0086] A composite absorbable porous repair membrane, which is different from Example 1 in that neither PELA nor PLCL is added to the materials of the first matrix layer and the second matrix layer, and the mass ratio of PLGA to PLCL is still 3:10. Other structures, materials, and preparation methods are the same as those in Example 1.

[0087] Comparative Example 3

[0088] A composite absorbable porous repair membrane, which is different from Example 1 in that neither PLCL nor PELA is added to the materials of the first matrix layer and the second matrix layer, and the mass ratio of PLGA to PELA is still 3:2. Other structures, materials, and preparation methods are the same as those in Example 1.

[0089] Comparative Example 4

[0090] A composite absorbable porous repair membrane, which is different from Example 1 in that the barrier layer is not provided, and it only includes a first matrix layer and a second matrix layer arranged in a stacked manner. Other materials, parameters, and preparation methods are the same as those in Example 1.

[0091] Morphology characterization:

[0092] The porous repair membrane provided in Example 1 was observed using a scanning electron microscope, and the scanning electron microscope image of the porous repair membrane provided in Example 1 is as Figure 2 shown;

[0093] From Figure 2 it can be seen that the surface of the porous repair membrane provided in Example 1 is a porous structure, having a certain tissue permeability and being able to absorb essential substances such as oxygen and nutrients.

[0094] Performance test:

[0095] (1) Fiber pore size: The sample was photographed using a scanning electron microscope. The irregular polygon formed by the fiber intersections was regarded as the pore of the fiber, and the maximum distance between two points within the polygon was regarded as the fiber pore size. Randomly select no less than 10 positions and take the average value.

[0096] (2) Tensile strength: The sample was folded in half along the long side, and the distance between the two clamps was 1 / 2 of the width of the wide side. Carefully ensure that the test sample is not stretched, distorted, or damaged by the clamps, and it was stretched along the wide side direction at a stable speed of 200 mm / min until it broke. Measure the maximum load force Tmax, and calculate the tensile strength according to the following formula:

[0097] Rm = Tmax / (L' × δ × 2);

[0098] Wherein, Rm represents the tensile strength, with the unit of megapascal (MPa); Tmax represents the maximum load force, with the unit of newton (N); δ represents the film thickness of the unit product, with the unit of millimeter (mm); L' represents the length after folding the long side of the unit product in half, with the unit of millimeter (mm).

[0099] (3) Suture strength: Using PP6 - 0 suture, fold the sample in half along the long side, thread the suture 2 mm away from the long side edge, and pull it along the width direction at a pulling speed of 200 mm / min. Record the maximum pulling force when the suture is pulled out of the sample or it is damaged. If the suture breaks, record the maximum force value during the pulling process, which is the suture strength.

[0100] (4) Waterproof and anti - adhesion effect: Cut the sample into an appropriate size, place it in a solution containing simulated cerebrospinal fluid, soak it for a certain time (72 hours) under certain temperature (such as 37 °C, simulating human body temperature) and humidity conditions, then take out the patch and observe whether there is solution penetration and infiltration on the surface of the patch. Quantitatively evaluate its waterproof performance by comparing the weight change of the patch before and after soaking through the weighing method. If the weight increase is not obvious, it indicates a good waterproof effect.

[0101] Test the porous repair membranes provided in Examples 1 - 7 and Comparative Examples 1 - 4 according to the above - mentioned test methods, and the test results are shown in Table 1:

[0102] Table 1

[0103]

[0104] Among them, " / " represents that the test cannot be carried out.

[0105] It can be seen from the data in Table 1 that:

[0106] (1) The fiber pore size of the porous repair membranes provided in Examples 1 - 3 is 16 - 19 μm, the tensile strength is 4.89 - 5.34 MPa, the suture strength is 1.8 - 2.0 N, and the weight increase amount after the waterproof and anti - adhesion test is only 0.5 - 0.8 g, indicating that the porous repair membranes provided in Examples 1 - 3 have high tensile strength, suture strength, and excellent waterproof and anti - adhesion effects.

[0107] (2) Compared with Example 1, the matrix layer of the porous repair membranes provided in Comparative Examples 1 - 3 is only composed of two materials in combination, and the spinning effect is very poor, and a complete porous repair membrane cannot be obtained, thus it cannot be used normally; the porous repair membrane provided in Comparative Example 4 does not have a barrier layer, the overall porous repair membrane formed by spinning is relatively soft, and there is no waterproof and anti - adhesion effect, which is not suitable for future clinical applications.

[0108] (3) Further comparison between Example 1 and Examples 4 - 5 shows that for the porous repair membrane provided in Example 4, the film thickness of the matrix layer decreases, resulting in a decrease in the overall film thickness and a weakening of the mechanical properties. Specifically, both the tensile strength and suture strength decrease accordingly. For the porous repair membrane provided in Example 5, the thickness of the matrix layer increases, resulting in an excessively high film thickness of the entire porous repair membrane, which is likely to exceed the average thickness of the human dura mater (0.42 mm) during actual application and is not suitable for future clinical applications.

[0109] (4) Further comparison between Example 1 and Examples 6 - 7 shows that for the porous repair membrane provided in Example 6, the film thickness of the barrier layer decreases, resulting in a decrease in the overall film thickness and a weakening of the mechanical properties. Specifically, both the tensile strength and suture strength decrease accordingly. At the same time, the barrier layer has a waterproof function, and the corresponding waterproof effect will be greatly weakened with the reduction of the barrier layer film thickness. For the porous repair membrane provided in Example 7, the barrier layer is too thick. Although it may theoretically improve its waterproof effect, problems such as poor spinning forming effect and easy delamination of the overall porous repair membrane will occur.

[0110] The applicant declares that through the above - mentioned examples, the present invention illustrates a composite absorbable porous repair membrane and its preparation method and application. However, the present invention is not limited to the above - mentioned process steps, that is, it does not mean that the present invention must rely on the above - mentioned process steps to be implemented. Those skilled in the art should understand that any improvement to the present invention, equivalent substitution of the raw materials selected for the present invention, addition of auxiliary components, and selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A composite absorbable porous repair membrane, characterized in that, The porous repair membrane comprises a first matrix layer, a barrier layer and a second matrix layer which are stacked; The materials of the first matrix layer and the second matrix layer both include lactide-glycolide copolymer, polyethylene glycol-polylactic acid copolymer and lactide-caprolactone copolymer.

2. The porous repair membrane according to claim 1, wherein The thickness of the porous repair membrane is 0.2-0.4 mm; Preferably, the thicknesses of the first matrix layer and the second matrix layer are independently 0.05-0.1 mm each.

3. The porous repair membrane according to claim 1 or 2, characterized in that, The mass ratio of the lactide-glycolide copolymer, the polyethylene glycol-polylactic acid copolymer and the lactide-caprolactone copolymer is (1-4):(6-15):(1-3).

4. The porous repair membrane according to any one of claims 1 to 3, characterized in that, The thickness of the barrier layer is 0.1-0.2 mm; Preferably, the material of the barrier layer includes any one or a combination of at least two of polyglycolic acid, poly-p-dioxanone or polydioxane.

5. A method for preparing the porous repair membrane according to any one of claims 1 to 4, characterized in that, The preparation method comprises the following steps: (1) Dissolve the lactide-glycolide copolymer, the polyethylene glycol-polylactic acid copolymer and the lactide-caprolactone copolymer in organic solvent A to obtain electrospinning stock solution A; Dissolve the material of the barrier layer in organic solvent B to obtain electrospinning stock solution B; (2) Perform electrospinning on the electrospinning stock solution A obtained in step (1), the electrospinning stock solution B obtained in step (2) and the electrospinning stock solution A obtained in step (1) in sequence, and perform heat setting to obtain the composite absorbable porous repair membrane.

6. The preparation method according to claim 5, characterized in that, The organic solvent A and the organic solvent B independently include any one or a combination of at least two of N,N-dimethylformamide, acetone, hexafluoroisopropanol or dichloromethane.

7. The preparation method according to claim 5 or 6, characterized in that, The mass percentage content of the lactide-glycolide copolymer in the electrospinning stock solution A is 1-4%; Preferably, the mass percentage content of the polyethylene glycol-polylactic acid copolymer in the electrospinning stock solution A is 6-15%; Preferably, the mass percentage content of the lactide-caprolactone copolymer in the electrospinning stock solution A is 1-3%; Preferably, the mass percentage content of the material of the barrier layer in the electrospinning stock solution B is 8-26%.

8. The preparation method according to any one of claims 5 to 7, characterized in that, The spinning time of the electrospinning is 5-15 min; Preferably, the receiving distance of the electrospinning is 20-40 cm; Preferably, the applied voltage of the electrospinning is 10-30 kV; Preferably, the injection speed of the electrospinning is 10-30 μL / min.

9. The preparation method according to any one of claims 5 to 8, characterized in that, The heat setting is carried out by covering with a glass plate; Preferably, the temperature of the heat setting is 25-45 °C and the time is 30-80 min.

10. Application of a porous repair membrane as claimed in any one of claims 1-4 as an artificial dura mater.

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