A bioabsorbable magnesium alloy oral film and a preparation method thereof

Abstract

The application relates to a bioabsorbable magnesium alloy oral cavity film and a preparation method thereof, and belongs to the technical field of biomedical devices. The magnesium alloy oral cavity film comprises a first polymer film, a magnesium alloy sheet and a second polymer film which are sequentially stacked. The materials of the first polymer film and the second polymer film both comprise a first polymer and a second polymer. The first polymer comprises a polylactic acid-glycolic acid copolymer. The second polymer comprises any one or a combination of at least two of polylactic acid, polycaprolactone, polylactic acid-caprolactone copolymer or polytrimethylene carbonate. The magnesium alloy sheet can give the oral cavity film certain mechanical strength to maintain the space for bone regeneration and protect the formation of bone tissue during the degradation process. Meanwhile, the alkaline ions generated by the degradation of the magnesium alloy sheet and the acidic ions generated by the hydrolysis of the polymer film can realize acid-base neutralization, greatly avoiding local inflammatory reactions caused by changes in the surrounding pH environment.

Description

Technical Field

[0001] This invention relates to the field of biomedical device technology, and in particular to a bioabsorbable magnesium alloy oral membrane and its preparation method. Background Technology

[0002] Dental implantology often faces the challenge of insufficient alveolar bone volume. Inflammation, periodontal disease, or congenital defects can all lead to a decrease in bone mass, thereby limiting the stable placement of implants. To address this bottleneck, guided bone regeneration (GBR) technology has been widely adopted and has become the standard method for pre-implantation bone augmentation.

[0003] The core principle of GBR (Glass Regeneration Bioreactor) is to utilize a biological barrier membrane to create a closed space between the bone defect area and the soft tissue. Soft tissue (epithelial cells or fibroblasts) migrate much faster than osteoblasts; without a barrier, they would rapidly occupy the defect area, inhibiting bone growth. The barrier membrane, through mechanical isolation, allows the slower-migrating osteoblasts to enter first and, supported by the blood clot, form new bone, thus achieving a bone regeneration effect from nothing.

[0004] Several invention studies have been conducted on the above-mentioned technologies, including the following two types of oral membranes: First, there are non-degradable oral membranes, mainly including polymer (non-degradable polymer raw materials) oral membranes and titanium alloy oral membranes. These non-degradable oral membranes have excellent mechanical properties and can play a good barrier role, but they require a second surgery to remove them, which carries a high risk of exposure and can easily lead to infection.

[0005] Secondly, there are biodegradable oral films, mainly including collagen oral films, polymer oral films (based on biodegradable polymer raw materials), and pure magnesium oral films. These types of oral films do not require secondary removal and can be gradually absorbed by the body, reducing the risk of exposure. However, they generally have poor mechanical properties and weak space maintenance capabilities. Collagen oral films also pose risks related to raw material sources and immune reactions, while the acidic environment created by the degradation of polymer oral films can irritate surrounding soft tissues and cause inflammation. Although the mechanical properties of magnesium alloy oral films can meet the requirements for use, the local accumulation of hydrogen gas generated during degradation and the increase in pH of the surrounding environment can easily cause temporary swelling, discomfort, and local inflammation. These reasons make magnesium films less than ideal in practical applications.

[0006] Based on the above problems, there is an urgent need to develop a bioabsorbable magnesium alloy oral membrane that has a certain mechanical strength, minimal impact on the surrounding oral environment, and excellent bone tissue integration ability. Summary of the Invention

[0007] To address the aforementioned technical problems, this invention provides a bioabsorbable magnesium alloy oral membrane and its preparation method. The magnesium alloy sheet provides the oral membrane with a certain mechanical strength to maintain space for bone regeneration and protect the formation of bone tissue during degradation. Simultaneously, the alkaline ions generated by the degradation of the magnesium alloy sheet and the acidic ions generated by the hydrolysis of the polymer membrane can achieve acid-base neutralization, greatly avoiding local inflammatory reactions caused by changes in the surrounding pH environment.

[0008] To achieve this objective, the present invention adopts the following technical solution: In a first aspect, the present invention provides a bioabsorbable magnesium alloy oral membrane, the magnesium alloy oral membrane comprising a first polymer membrane, a magnesium alloy sheet and a second polymer membrane stacked sequentially. The materials of both the first polymer membrane and the second polymer membrane include the first polymer and the second polymer; The first polymer comprises polylactic acid-glycolic acid copolymer; The second polymer includes any one or a combination of at least two of polylactic acid, polycaprolactone, polylactic acid-caprolactone copolymer, or polytrimethylene carbonate, wherein typical but non-limiting combinations include: a combination of polylactic acid and polycaprolactone, a combination of polylactic acid and polylactic acid-caprolactone copolymer, a combination of polylactic acid and polytrimethylene carbonate, a combination of polycaprolactone and polylactic acid-caprolactone copolymer, a combination of polylactic acid, polycaprolactone and polylactic acid-caprolactone copolymer, and a combination of polycaprolactone, polylactic acid-caprolactone copolymer, and polytrimethylene carbonate.

[0009] The magnesium alloy oral membrane of the present invention has a three-layer structure, consisting of a first polymer membrane, a magnesium alloy sheet, and a second polymer membrane. The polymer membrane can achieve flexible fit after implantation, while the magnesium alloy sheet provides rigid support. All three layers are biodegradable materials, which can avoid infection caused by exposure during use and eliminates the need for secondary surgery, thus reducing medical costs. Specifically, the magnesium alloy sheet can provide the oral membrane with a certain mechanical strength to maintain space for bone regeneration and protect bone tissue formation during degradation. At the same time, the magnesium ions generated during the degradation of the magnesium alloy can promote bone tissue repair to a certain extent and reduce bacterial infection. Furthermore, the alkaline ions generated by the degradation of the magnesium alloy sheet and the acidic ions generated by the hydrolysis of the polymer membrane can achieve acid-base neutralization, which greatly avoids local inflammatory reactions caused by changes in the surrounding pH environment.

[0010] The polymer membrane comprises at least two polymer materials. Compared to a single polymer system, the first and second polymers exhibit a significant synergistic effect, thereby achieving comprehensive optimization of the material's tensile strength, degradation rate, flexibility, and barrier properties. Introducing only the first polymer only partially improves the material's tensile strength and flexibility; similarly, introducing only the second polymer only partially improves its flexibility. Both polymers have performance limitations when used alone and cannot simultaneously meet the stringent requirements of polymer membranes in terms of comprehensive mechanical properties, processability, and controllable degradation.

[0011] As a preferred embodiment of the present invention, the magnesium alloy sheet has a hollow structure.

[0012] The magnesium alloy sheet in this invention has a hollow structure to reduce the release of hydrogen gas while providing as much support performance as possible, and to avoid excessive gas release leading to local hydrogen accumulation and displacement of the filling bone powder.

[0013] It should be noted that, in the magnesium alloy oral membrane of the present invention, a first polymer membrane and a second polymer membrane are provided on both sides of the hollow structure of the magnesium alloy sheet.

[0014] Preferably, the hollow structure is an axisymmetric structure.

[0015] Preferably, the ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.1 to 0.5, for example, it can be 0.1, 0.2, 0.3, 0.4 or 0.5, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0016] This invention limits the proportion of the hollow structure area to reduce the amount of hydrogen released while providing as much support performance as possible. This avoids excessive gas release that could lead to local hydrogen accumulation and displacement of the filling bone powder. If the proportion of the hollow structure area is too small, it will cause local hydrogen accumulation and displacement of the filling bone powder. If the proportion of the hollow structure area is too large, it will result in insufficient mechanical strength of the magnesium alloy oral membrane.

[0017] It should also be noted that the present invention does not specifically limit the structure of the hollow structure. This is because, when the area of ​​the magnesium alloy sheet is determined, for hollow structures of different shapes, as long as the ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is the same, the effect achieved will be the same.

[0018] Preferably, the magnesium alloy sheet includes any one of the following: AE series alloys, AS series alloys, WE series alloys, AZ series alloys, AM series alloys, ZK series alloys, ZM series alloys, Mg-Li series alloys, or Mg-Ca series alloys.

[0019] Preferably, the magnesium alloy sheet contains zinc and manganese.

[0020] Preferably, the thickness of the magnesium alloy sheet is 50~100μm, for example, it can be 50μm, 60μm, 70μm, 80μm, 90μm or 100μm, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0021] This invention limits the thickness of the magnesium alloy sheet to 50~100μm to avoid hydrogen accumulation through rapid and uniform degradation. If the thickness of the magnesium alloy sheet is too large, the degradation cycle will be too long and uneven, and the local hydrogen generation rate will exceed the tissue diffusion capacity, thereby forming an air sac at the implantation site, causing inflammation or hindering tissue repair.

[0022] As a preferred technical solution of the present invention, the mass ratio of the first polymer and the second polymer in the first polymer membrane is (1~20):1, for example, it can be 1:1, 5:1, 10:1, 15:1 or 20:1, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0023] Preferably, the mass ratio of the first polymer and the second polymer in the second polymer membrane is (1~20):1, for example, it can be 1:1, 5:1, 10:1, 15:1 or 20:1, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0024] Preferably, the second polymer is polytrimethylene carbonate.

[0025] It should be noted that when the mass ratio of the first polymer to the second polymer is (1~20):1, the synergistic effect of the first polymer and the second polymer can be fully utilized, avoiding the performance degradation of the oral membrane due to excessive amounts of one polymer. At the same time, the combination of poly(lactic-co-glycolic acid) copolymer and polytrimethylene carbonate has the best effect. This is because the hydrophilic segments in the poly(lactic-co-glycolic acid) (PLGA) molecular chain are prone to forming short-range ordered structures during crystallization. This structure leads to an increase in water absorption during the degradation stage after film formation, which in turn causes material embrittlement. After introducing polytrimethylene carbonate (PTMC) for blending modification, the flexible segments composed of carbonate bonds in the PTMC main chain can effectively improve the system performance. The physical entanglement formed between PTMC and the PLGA molecular chain significantly enhances the overall toughness of the composite film, thereby effectively inhibiting the embrittlement phenomenon of the material during degradation and achieving comprehensive optimization of the material's tensile strength, degradation rate, flexibility, and barrier properties.

[0026] In a second aspect, the present invention provides a method for preparing a bioabsorbable magnesium alloy oral membrane according to the first aspect, the method comprising the following steps: (1) According to the ratio of the first polymer membrane and the second polymer membrane, the polymer raw material powder and organic solvent are mixed respectively to obtain two parts of the first mixture. Then, the two parts of the first mixture are cast onto the substrate to prepare the first polymer membrane and the second polymer membrane respectively. The polymer raw material powder includes a first polymer powder and a second polymer powder; The material of the first polymer powder includes polylactic acid-glycolic acid copolymer; The material of the second polymer powder includes any one or a combination of at least two of polylactic acid, polycaprolactone, polylactic acid-caprolactone copolymer, or polytrimethylene carbonate; (2) Magnesium alloy sheet is obtained by extruding magnesium alloy raw materials; (3) The first polymer membrane, the magnesium alloy sheet and the second polymer membrane are stacked in sequence, and then hot-pressed to obtain the bioabsorbable magnesium alloy oral membrane. There is no specific order between steps (1) and (2).

[0027] This invention first prepares a first polymer membrane, a magnesium alloy sheet, and a second polymer membrane, and then prepares a bio-absorbable magnesium alloy oral membrane through hot-pressing composite technology. The preparation method provided by this invention is simple, convenient, and easy to industrialize.

[0028] As a preferred technical solution of the present invention, the preparation method further includes using laser cutting to prepare a hollow structure on a magnesium alloy sheet.

[0029] Preferably, the hollow structure is an axisymmetric structure.

[0030] Preferably, the ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.1 to 0.5, for example, it can be 0.1, 0.2, 0.3, 0.4 or 0.5, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0031] As a preferred technical solution of the present invention, the mass ratio of the first polymer powder and the second polymer powder in the polymer raw material powder is (1~20):1, for example, it can be 1:1, 5:1, 10:1, 15:1 or 20:1, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0032] As a preferred embodiment of the present invention, the material of the second polymer powder is polytrimethylene carbonate.

[0033] Preferably, the organic solvent includes dichloromethane and / or hexafluoroisopropanol.

[0034] Preferably, the substrate is made of any one of stainless steel, glass, or polytetrafluoroethylene.

[0035] As a preferred technical solution of the present invention, the concentration of the polymer raw material powder in the first mixture is 20~300mg / mL, for example, it can be 20mg / mL, 50mg / mL, 100mg / mL, 200mg / mL or 300mg / mL, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0036] Preferably, the mixing is carried out by stirring.

[0037] As a preferred technical solution of the present invention, the stirring speed is 200~1000 r / min, for example, it can be 200 r / min, 400 r / min, 600 r / min, 800 r / min or 1000 r / min, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0038] Preferably, the stirring time is 3 to 20 hours, for example, 3 hours, 5 hours, 10 hours, 15 hours or 20 hours, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0039] As a preferred technical solution of the present invention, the pressure of the hot pressing treatment is 0.1~20MPa, for example, it can be 0.1MPa, 0.5MPa, 1MPa, 5MPa, 10MPa or 20MPa, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0040] Preferably, the temperature of the hot pressing treatment is 30~200℃, for example, it can be 30℃, 50℃, 100℃, 150℃ or 200℃, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0041] The present invention limits the hot pressing temperature to 30~200℃, that is, the hot pressing temperature is slightly higher than the glass transition temperature of the polymer raw materials, so as to allow the polymer chains to diffuse into each other to form a strong bond similar to covalent bonds, and to avoid the thermal degradation of polymers caused by high temperature.

[0042] Preferably, the hot pressing time is 2 to 20 minutes, for example, 2 minutes, 5 minutes, 10 minutes, 15 minutes or 20 minutes, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0043] Preferably, the preparation method includes the following steps: (1) Mix the first polymer powder and the second polymer powder according to the mass ratio of the first polymer membrane and the second polymer membrane to obtain two parts of polymer raw material powder, wherein the mass ratio of the first polymer powder and the second polymer powder in the first polymer membrane and the second polymer membrane is (1~20):1, the material of the first polymer powder includes polylactic acid-glycolic acid copolymer; the material of the second polymer powder includes any one or at least two of polylactic acid, polycaprolactone, polylactic acid-caprolactone copolymer or polytrimethylene carbonate; then mix the polymer raw material powder and dichloromethane respectively, and stir at a speed of 200~1000r / min for 3~20h to obtain two parts of polymer raw material powder with a concentration of 20~300mg / mL. Then, cast the two parts of the first mixture onto the substrate respectively, and let them stand at 4~25℃ for 16~48h to prepare a first polymer membrane and a second polymer membrane with a thickness of 150~200μm respectively. (2) Extruding magnesium alloy raw materials to obtain magnesium alloy sheets with a thickness of 50~100μm; and using laser cutting to prepare an axisymmetric hollow structure on the magnesium alloy sheet; the ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.1~0.5; (3) The first polymer membrane, the magnesium alloy sheet and the second polymer membrane are stacked in sequence, and then hot-pressed at a pressure of 0.1~20MPa, a temperature of 30~200℃ and a time of 2~20min to obtain the bioabsorbable magnesium alloy oral membrane; There is no specific order between steps (1) and (2).

[0044] It should be noted that the method for removing the first polymer membrane and the second polymer membrane from the substrate in this invention includes: after standing, using tweezers to remove the first polymer membrane and the second polymer membrane from the substrate; Alternatively, after standing, a first composite structure formed by the substrate and the first polymer film and a second composite structure formed by the substrate and the second polymer film are obtained. The first composite structure and the second composite structure are immersed in anhydrous ethanol for 1-5 hours. Then, the first polymer film and the second polymer film are removed from the substrate using tweezers, and the first polymer film and the second polymer film are dried at 20-25°C for 1-5 hours.

[0045] Compared with the prior art, the present invention has at least the following beneficial effects: (1) The polymer membrane in the magnesium alloy oral membrane of the present invention can achieve flexible fit after implantation, while the magnesium alloy sheet can provide rigid support. All three layers are biodegradable materials, which can avoid the problem of infection caused by exposure during use, eliminate the need for secondary surgery, and reduce medical costs. (2) The tensile strength of the magnesium alloy oral membrane can reach more than 12.5N. After a 2-week degradation experiment, the bending performance test showed no breakage. This means that it can maintain the space for bone regeneration and protect the formation of bone tissue during the degradation process. At the same time, the magnesium ions generated during the degradation of magnesium alloy can promote the repair of bone tissue to a certain extent and reduce bacterial infection. (3) The alkaline ions produced by the degradation of magnesium alloy sheets and the acidic ions produced by the hydrolysis of polymer membranes can achieve acid-base neutralization, thus avoiding local inflammatory reactions caused by changes in the surrounding pH environment. (4) The present invention first prepares a first polymer membrane, a magnesium alloy sheet and a second polymer membrane respectively, and then prepares a bio-absorbable magnesium alloy oral membrane by hot pressing composite technology. The preparation method provided by the present invention is simple, convenient and easy to industrialize. Attached Figure Description

[0046] Figure 1 This is a schematic diagram of the structure of the bioabsorbable magnesium alloy oral membrane provided in Embodiment 1 of the present invention. Detailed Implementation

[0047] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention is determined by the claims.

[0048] The magnesium alloy sheet used in the following embodiments is ZM21 magnesium alloy. The above limitations are only for clearly illustrating the technical solution of the present invention and are not considered as further limitations on the present invention.

[0049] Example 1 This embodiment provides a bioabsorbable magnesium alloy oral membrane, such as... Figure 1 As shown, the magnesium alloy oral membrane comprises a first polymer membrane, a magnesium alloy sheet, and a second polymer membrane stacked sequentially. The first polymer membrane is made of polylactic acid-glycolic acid copolymer (molecular weight 10000) and polycaprolactone (molecular weight 2000) in a mass ratio of 85:15; wherein the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 75:25; the second polymer membrane is made of the same material as the first polymer membrane. The magnesium alloy sheet has a thickness of 80 μm; and the magnesium alloy sheet has an axisymmetric hollow structure, the ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.3.

[0050] This embodiment also provides a method for preparing the bioabsorbable magnesium alloy oral membrane, the method comprising the following steps: (1) Polylactic acid-glycolic acid copolymer (molecular weight 10000) and polycaprolactone (molecular weight 2000) were mixed in a mass ratio of 85:15 to obtain polymer raw material powder, wherein the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer was 75:25; then the polymer raw material powder and dichloromethane were mixed and stirred at a speed of 500 r / min for 16 h to obtain a first mixture with a polymer raw material powder concentration of 38.18 mg / mL; then two portions of the first mixture were cast onto glass substrates and left to stand at 4 °C for 48 h to prepare a first polymer film and a second polymer film with a thickness of 200 μm respectively. (2) Extruding magnesium alloy raw materials to obtain magnesium alloy sheets with a thickness of 80 μm; and using laser cutting to prepare an axisymmetric hollow structure on the magnesium alloy sheet, wherein the area of ​​the hollow structure is 0.3 times the area of ​​the magnesium alloy sheet. (3) The first polymer membrane, the magnesium alloy sheet and the second polymer membrane are stacked in sequence, and then hot-pressed at a pressure of 10 MPa, a temperature of 70°C and a time of 5 min to obtain the bioabsorbable magnesium alloy oral membrane. There is no specific order between steps (1) and (2).

[0051] Example 2 This embodiment provides a bioabsorbable magnesium alloy oral membrane, which includes a first polymer membrane, a magnesium alloy sheet, and a second polymer membrane stacked sequentially. The first polymer membrane is made of polylactic acid-glycolic acid copolymer (molecular weight 10,000) and polylactic acid (molecular weight 60,000) in a mass ratio of 1:1; wherein the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 75:25; and the material of the second polymer membrane is the same as that of the first polymer membrane. The magnesium alloy sheet has a thickness of 80 μm; and the magnesium alloy sheet has an axisymmetric hollow structure, the ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.2.

[0052] This embodiment also provides a method for preparing the bioabsorbable magnesium alloy oral membrane, the method comprising the following steps: (1) Polylactic acid-glycolic acid copolymer (molecular weight 10000) and polylactic acid (molecular weight 60000) were mixed in a mass ratio of 1:1 to obtain polymer raw material powder, wherein the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer was 75:25; then the polymer raw material powder and dichloromethane were mixed and stirred at a speed of 200 r / min for 20 h to obtain a first mixture with a polymer raw material powder concentration of 20 mg / mL; then the two portions of the first mixture were cast onto a stainless steel substrate and left to stand at 25 °C for 16 h to prepare a first polymer film and a second polymer film with a thickness of 200 μm respectively. (2) Extruding magnesium alloy raw materials to obtain magnesium alloy sheets with a thickness of 80 μm; and using laser cutting to prepare an axisymmetric hollow structure on the magnesium alloy sheet, wherein the area of ​​the hollow structure is 0.2 times the area of ​​the magnesium alloy sheet. (3) The first polymer membrane, the magnesium alloy sheet and the second polymer membrane are stacked in sequence, and then hot-pressed at a pressure of 0.1 MPa, a temperature of 30°C and a time of 20 min to obtain the bioabsorbable magnesium alloy oral membrane. There is no specific order between steps (1) and (2).

[0053] Example 3 This embodiment provides a bioabsorbable magnesium alloy oral membrane, which includes a first polymer membrane, a magnesium alloy sheet, and a second polymer membrane stacked sequentially. The first polymer membrane is made of polylactic acid-glycolic acid copolymer (molecular weight 10,000) and polylactic acid-caprolactone copolymer (molecular weight 90,000) in a mass ratio of 20:1; wherein the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 75:25, and the molar ratio of lactic acid to caprolactone in the polylactic acid-caprolactone copolymer is 70:30; and the material of the second polymer membrane is the same as that of the first polymer membrane. The magnesium alloy sheet has a thickness of 80 μm; and the magnesium alloy sheet has an axisymmetric hollow structure, the ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.4.

[0054] This embodiment also provides a method for preparing the bioabsorbable magnesium alloy oral membrane, the method comprising the following steps: (1) Polylactic acid-glycolic acid copolymer (molecular weight 10000) and polylactic acid-caprolactone copolymer (molecular weight 90000) were mixed at a mass ratio of 20:1 to obtain polymer raw material powder, wherein the molar ratio of lactic acid to glycolic acid in polylactic acid-glycolic acid copolymer was 75:25 and the molar ratio of lactic acid to caprolactone in polylactic acid-caprolactone copolymer was 70:30; then the polymer raw material powder and dichloromethane were mixed and stirred at a speed of 1000 r / min for 3 h to obtain a first mixture with a polymer raw material powder concentration of 300 mg / mL; then the two portions of the first mixture were cast onto glass substrates and left to stand at 25 °C for 24 h to prepare a first polymer film and a second polymer film with a thickness of 200 μm respectively. (2) Extruding magnesium alloy raw materials to obtain magnesium alloy sheets with a thickness of 80 μm; and using laser cutting to prepare an axisymmetric hollow structure on the magnesium alloy sheet, wherein the area of ​​the hollow structure is 0.4 times the area of ​​the magnesium alloy sheet. (3) The first polymer membrane, the magnesium alloy sheet and the second polymer membrane are stacked in sequence, and then hot-pressed at a pressure of 20 MPa, a temperature of 70 °C and a time of 3 min to obtain the bioabsorbable magnesium alloy oral membrane. There is no specific order between steps (1) and (2).

[0055] Example 4 This embodiment provides a bioabsorbable magnesium alloy oral membrane, which differs from Example 1 only in that polycaprolactone is replaced with the same mass of polytrimethylene carbonate (molecular weight 10,000), otherwise it is the same as Example 1.

[0056] Example 5 This embodiment provides a bioabsorbable magnesium alloy oral membrane, which differs from Embodiment 1 only in that the magnesium alloy sheet does not have a perforated structure, but is otherwise identical to Embodiment 1.

[0057] Example 6 This embodiment provides a bioabsorbable magnesium alloy oral membrane, which differs from Embodiment 1 only in that the ratio of the area of ​​the hollow structure in the magnesium alloy sheet to the area of ​​the magnesium alloy sheet is adjusted from 0.3 to 0.7, while all other aspects are the same as Embodiment 1.

[0058] Example 7 This embodiment provides a bioabsorbable magnesium alloy oral membrane, which differs from Embodiment 1 only in that the mass ratio of polylactic acid-glycolic acid copolymer and polycaprolactone is adjusted from 85:15 to 15:85, while all other aspects are the same as in Embodiment 1.

[0059] Example 8 This embodiment provides a bioabsorbable magnesium alloy oral membrane, which differs from Example 1 only in that the mass ratio of polylactic acid-glycolic acid copolymer and polycaprolactone is adjusted from 85:15 to 30:1, while all other aspects are the same as in Example 1.

[0060] Example 9 This embodiment provides a bioabsorbable magnesium alloy oral membrane. The only difference from Embodiment 1 is that the temperature of the hot pressing process in step (3) is adjusted from 70°C to 300°C. All other aspects are the same as in Embodiment 1.

[0061] Comparative Example 1 This comparative example provides a bioabsorbable magnesium alloy oral membrane, which differs from Example 1 only in that polycaprolactone is replaced with the same mass of polylactic acid-glycolic acid copolymer, i.e., both the first and second polymer membranes contain only one material. Otherwise, they are the same as Example 1.

[0062] Comparative Example 2 This comparative example provides a bioabsorbable magnesium alloy oral membrane, which differs from Example 1 only in that the polylactic acid-glycolic acid copolymer is replaced with the same mass of polycaprolactone, i.e., both the first and second polymer membranes contain only one material. Otherwise, they are the same as Example 1.

[0063] Comparative Example 3 This comparative example provides a bioabsorbable magnesium alloy oral membrane, which differs from Example 1 only in that the preparation method is adjusted to: first, prepare a magnesium alloy sheet with an axisymmetric hollow structure, then prepare a first mixture of polymer raw material powder with a concentration of 38.18 mg / mL, immerse the magnesium alloy sheet in the first mixture, air dry it naturally, and then perform hot pressing. Otherwise, it is the same as Example 1.

[0064] The tensile strength of the bioabsorbable magnesium alloy oral membranes in the above examples and comparative examples was tested using a mechanical tensile testing machine. Additionally, the bioabsorbable magnesium alloy oral membranes were immersed in PBS buffer (manufacturer: Biosharp, pH=7.4) for 4 weeks for degradation experiments. The pH value of the degradation system was tested at 1 week, 2 weeks, and 4 weeks. Bending performance tests were also conducted on the magnesium alloy oral membranes, simulating actual clinical use scenarios. During the tests, the oral membranes were bent to a point where the distance between its two ends was 10 mm to observe and evaluate whether the material fractured under this ultimate deformation. The test results are shown in Tables 1 and 2.

[0065] Table 1

[0066] Table 2

[0067] Note: The pH environment of the oral cavity is between 6.5 and 7.5. That is, the pH value of the magnesium alloy oral membrane should not exceed 7.5 during the degradation process, and the pH value should not change too much compared with the initial pH value. In other words, the absolute value of the change in pH value should not exceed 0.2.

[0068] The test results show that: (1) As can be seen from Examples 1 to 4, the magnesium alloy oral membrane of the present invention has a three-layer structure, namely a first polymer membrane, a magnesium alloy sheet and a second polymer membrane. The polymer membrane can achieve flexible fit after implantation, while the magnesium alloy sheet can provide rigid support. All three layers are biodegradable materials, which can avoid the problem of infection caused by exposure during use and eliminate the need for secondary surgery, thus reducing medical costs. Specifically, the magnesium alloy sheet can provide the oral membrane with a certain mechanical strength to maintain space for bone regeneration and protect the formation of bone tissue during degradation. At the same time, the magnesium ions generated during the degradation of the magnesium alloy can promote the repair of bone tissue to a certain extent and reduce bacterial infection. Furthermore, the alkaline ions generated by the degradation of the magnesium alloy sheet and the acidic ions generated by the hydrolysis of the polymer membrane can achieve acid-base neutralization, which greatly avoids the local inflammatory reaction caused by changes in the surrounding pH environment. Specifically, the tensile strength of the magnesium alloy oral membrane can reach more than 12.5N, and no breakage occurs after bending performance testing after a 2-week degradation experiment.

[0069] (2) As can be seen from Examples 1 and 5-6, in Example 1, the ratio of the area of ​​the hollow structure in the magnesium alloy sheet to the area of ​​the magnesium alloy sheet is 0.3, and its magnesium alloy oral membrane can withstand a tensile force of 12.5N. After a 2-week degradation experiment, the bending performance test does not show any breakage, and the pH value of the degradation system is 7.50 after a 4-week degradation experiment. In Example 5, the magnesium alloy sheet does not have a hollow structure, and the pH value of its magnesium alloy oral membrane is 7.61 after a 4-week degradation experiment. In Example 6, the ratio of the area of ​​the hollow structure in the magnesium alloy sheet to the area of ​​the magnesium alloy sheet is 0.7, and its magnesium alloy oral membrane can only withstand a tensile force of 10.4N. This shows that by setting a hollow structure on the magnesium alloy sheet and limiting the proportion of the hollow structure area, the present invention can reduce the amount of hydrogen released while providing support performance, and avoid excessive gas release leading to local hydrogen accumulation and displacement of the filling bone powder.

[0070] (3) As can be seen from Examples 1 and 7-8, in Example 1, the mass ratio of polylactic acid-glycolic acid copolymer to polycaprolactone is 85:15, and its magnesium alloy oral membrane can withstand a tensile force of 12.5N. After a 2-week degradation experiment, the bending performance test does not break, and the pH value of the degradation system is 7.50 after a 4-week degradation experiment. In Example 7, the mass ratio of polylactic acid-glycolic acid copolymer to polycaprolactone is 15:85, and its magnesium alloy oral membrane can only withstand a tensile force of 8.25N. After a 4-week degradation experiment, the pH value of the degradation system is 7.56. In Example 8, the mass ratio of polylactic acid-glycolic acid copolymer to polycaprolactone is 30:1. Although its magnesium alloy oral membrane can withstand a tensile force of 43N, after a 2-week degradation experiment, the flexibility of the material decreases significantly and is accompanied by obvious embrittlement, which leads to its failure in the bending performance test in the second week. This indicates that the present invention specifically limits the mass ratio of the first polymer and the second polymer to (1~20):1, which can achieve comprehensive optimization of the tensile strength, degradation rate, flexibility and barrier properties of the material.

[0071] (4) As can be seen from Examples 1 and 9, the hot pressing temperature of Example 1 is 70°C, and its magnesium alloy oral membrane can withstand a tensile force of 12.5N. After a 2-week degradation experiment, the bending performance test does not show any breakage. After a 4-week degradation experiment, the pH value of the degradation system is 7.50. In contrast, the hot pressing temperature of Example 9 is 300°C, and its magnesium alloy oral membrane can withstand a tensile force of 12.4N. After a 4-week degradation experiment, the pH value of the degradation system is 7.51. It can be seen that excessively high hot pressing temperature will lead to the thermal degradation of polymers, ultimately reducing the overall performance of the magnesium alloy oral membrane.

[0072] (5) As can be seen from Example 1 and Comparative Examples 1-2, the polymer membrane of the present invention contains at least two polymer materials. Compared with a single polymer system, the first polymer and the second polymer can produce a significant synergistic effect, thereby achieving comprehensive optimization of the material's tensile strength, degradation rate, flexibility, and barrier properties. If only the first polymer is introduced, the tensile strength and flexibility of the material can only be partially improved; if only the second polymer is introduced, the flexibility of the material can also only be partially improved. Both have performance limitations when used alone and cannot simultaneously meet the stringent requirements of polymer membranes in terms of comprehensive mechanical properties, processability, and controllable degradation.

[0073] (6) As can be seen from Example 1 and Comparative Example 3, the present invention first prepares a first polymer membrane, a magnesium alloy sheet and a second polymer membrane respectively, and then prepares a bio-absorbable magnesium alloy oral membrane by hot pressing composite technology, which can keep the pH value of the magnesium alloy oral membrane below 7.50 during the degradation process to avoid local inflammatory reactions caused by changes in the surrounding pH environment.

[0074] In summary, the magnesium alloy oral membrane provided by this invention has a tensile strength of over 12.5N and does not break during bending performance testing after a 2-week degradation experiment. This means that it can maintain space for bone regeneration and protect the formation of bone tissue during the degradation process. At the same time, the alkaline ions generated by the degradation of the magnesium alloy sheet and the acidic ions generated by the hydrolysis of the polymer membrane can achieve acid-base neutralization, avoiding local inflammatory reactions caused by changes in the surrounding pH environment.

[0075] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A bioabsorbable magnesium alloy oral membrane, characterized in that, The magnesium alloy oral membrane comprises a first polymer membrane, a magnesium alloy sheet, and a second polymer membrane stacked in sequence. Both the first polymer membrane and the second polymer membrane are made of a first polymer and a second polymer; the mass ratio of the first polymer and the second polymer in the first polymer membrane is (1~20):1; the mass ratio of the first polymer and the second polymer in the second polymer membrane is (1~20):

1. The first polymer comprises polylactic acid-glycolic acid copolymer; The second polymer includes any one or a combination of at least two of polylactic acid, polycaprolactone, polylactic acid-caprolactone copolymer, or polytrimethylene carbonate; The magnesium alloy sheet has a hollow structure; the hollow structure is an axisymmetric structure. The ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.1 to 0.

5.

2. A method for preparing a bioabsorbable magnesium alloy oral membrane according to claim 1, characterized in that, The preparation method includes the following steps: (1) According to the ratio of the first polymer membrane and the second polymer membrane, the polymer raw material powder and organic solvent are mixed respectively to obtain two parts of the first mixture. Then, the two parts of the first mixture are cast onto the substrate to prepare the first polymer membrane and the second polymer membrane respectively. The polymer raw material powder includes a first polymer powder and a second polymer powder; The material of the first polymer powder includes polylactic acid-glycolic acid copolymer; The material of the second polymer powder includes any one or a combination of at least two of polylactic acid, polycaprolactone, polylactic acid-caprolactone copolymer, or polytrimethylene carbonate; (2) Magnesium alloy sheet is obtained by extruding magnesium alloy raw materials; (3) The first polymer membrane, the magnesium alloy sheet and the second polymer membrane are stacked in sequence, and then hot-pressed to obtain the bioabsorbable magnesium alloy oral membrane. There is no specific order between steps (1) and (2).

3. The preparation method according to claim 2, characterized in that, The preparation method also includes using laser cutting to prepare a hollow structure on a magnesium alloy sheet; The hollow structure is an axisymmetric structure; The ratio of the area of ​​the hollow structure to the area of ​​the magnesium alloy sheet is 0.1 to 0.

5.

4. The preparation method according to claim 2 or 3, characterized in that, The mass ratio of the first polymer powder to the second polymer powder in the polymer raw material powder is (1~20):

1.

5. The preparation method according to claim 2, characterized in that, The material of the second polymer powder is polytrimethylene carbonate; The organic solvents include dichloromethane and / or hexafluoroisopropanol.

6. The preparation method according to claim 2, characterized in that, The concentration of the polymer raw material powder in the first mixture is 20~300mg / mL; The mixing is carried out by stirring.

7. The preparation method according to claim 6, characterized in that, The stirring speed is 200~1000 r / min; The stirring time is 3 to 20 hours.

8. The preparation method according to claim 2, characterized in that, The pressure for the hot pressing process is 0.1~20MPa; The temperature of the hot pressing process is 30~200℃; The hot pressing process takes 2 to 20 minutes.

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