Oral repair membrane and preparation method thereof

Abstract

The present invention provides an oral repair membrane and a preparation method thereof. The oral repair membrane comprises a first layer and a second layer having a porous structure, wherein the average pore size of the second layer is smaller than the average pore size of the first layer; the raw material forming the first layer includes a piezoelectric material; and the raw material forming the second layer includes a piezoelectric material and a synthetic polymer material. The oral repair membrane of the present invention has a soft texture and good adhesion, does not slip during use, and reduces the exposure infection rate; and has a suitable pore size, which can prevent surrounding tissues such as fibroblasts and epithelial cells from entering the bone defect area, while allowing nutrients to enter the bottom of the oral repair membrane to promote bone regeneration.

Description

Technical Field

[0001] The invention relates to an oral repair membrane and a preparation method thereof, and belongs to the field of medical implant materials. Background Art

[0002] Currently, oral tissue defects mainly include periodontal tissue loss, insufficient or missing attached gingiva, defects after maxillofacial tumor resection, wound dehiscence after GBR, donor site defects for connective tissue transplantation, maxillary sinus fistula, wound closure after mandibular impacted tooth extraction, gingival recession, exposed root surfaces, abnormal frenulum attachment position / shallow vestibule groove, etc. Oral tissue defects need to be repaired. With the continuous development of tissue engineering, membrane-guided bone regeneration (MGBR) was born, which has improved the treatment level of oral tissue repair.

[0003] The therapeutic advantage of oral repair membranes is that they establish a biological barrier between oral soft tissue and bone defects. This provides a good repair space for bone regeneration, selectively blocking the entry of rapidly migrating fibroblasts and epithelial cells into the bone defect area, while also promoting or even inducing bone regeneration and oral wound healing. Existing oral repair membrane materials typically incorporate natural hydrophilic materials such as collagen, gelatin, and polysaccharides with synthetic materials such as polylactic acid to form a composite membrane. This promotes the adhesion and growth of tissue cells to the membrane material, improving the biocompatibility and tissue repair performance of the oral repair membrane.

[0004] For example, Reference 1 discloses a method for preparing an oral biomembrane, in which collagen and chondroitin sulfate are mixed into a slurry, which is then freeze-dried and pressed into a collagen composite film. However, in the presence of a large amount of tissue fluid or other fluids (such as oral saliva) for a long time, the hydrophilic materials such as collagen, gelatin, and polysaccharides in the oral repair membrane will swell, leading to structural changes such as fiber slippage or membrane deformation. Such changes often result in poor adhesion of the membrane to the implant site, post-implantation displacement, or loss of its original pore barrier function, leading to exposure and infection.

[0005] Furthermore, researchers have discovered that multilayered fiber networks fabricated using electrospinning can mimic the structural characteristics of natural extracellular matrix and are increasingly being used to create oral prosthetic membranes. Oral prosthetic membranes typically consist of two or three layers, one of which has smaller pores to prevent soft tissue ingrowth. However, using conventional materials such as polycaprolactone, polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid alone, it is difficult to create multilayered oral prosthetic membranes with varying pore sizes. Consequently, their barrier properties and bone regeneration-promoting effects are less than ideal.

[0006] References:

[0007] Reference 1: CN110038169A Summary of the Invention

[0008] Problems to be solved by the invention

[0009] In view of the technical problems existing in the prior art, for example, to solve the problems of poor adhesion of oral repair membranes and easy slippage and deformation of oral repair membranes, and to improve the problem that it is difficult to prepare oral repair membranes that meet the requirements using conventional raw materials using the current electrospinning process, the present invention first provides an oral repair membrane, which has good adhesion, will not slip during use, and reduces the exposure infection rate.

[0010] Furthermore, the oral repair membrane of the present invention has a suitable pore size, which can prevent surrounding tissues such as fibroblasts and epithelial cells from entering the bottom of the oral repair membrane to affect bone growth, and allow nutrients to enter the bottom of the oral repair membrane to promote bone growth.

[0011] Furthermore, the present invention also provides a method for preparing an oral repair membrane. The preparation method is simple and easy, the raw materials are easy to obtain, and the product can be industrially produced with high efficiency and low cost.

[0012] Solutions for solving problems

[0013] The present invention provides an oral repair membrane, which comprises a first layer and a second layer having a porous structure, wherein:

[0014] The average pore size of the second layer is smaller than the average pore size of the first layer;

[0015] The raw material forming the first layer includes piezoelectric material;

[0016] The raw materials for forming the second layer include piezoelectric material and synthetic polymer material.

[0017] Furthermore, the synthetic polymer material includes an elastomeric material and / or a low-melting-point material; the low-melting-point material has a lower thermal melting point than the piezoelectric material.

[0018] Furthermore, in the second layer, the mass ratio of the piezoelectric material to the synthetic polymer material is 1:1 to 4:1.

[0019] Furthermore, the oral restoration membrane further comprises a third layer having a porous structure, the third layer being located on a side of the second layer opposite to the first layer; the average pore size of the third layer being greater than the average pore size of the second layer;

[0020] Preferably, the raw material for forming the third layer contains piezoelectric material.

[0021] Furthermore, the average pore size of the oral restoration membrane is 0.1-5 μm; and / or the tensile strength of the oral restoration membrane is 1-5 MPa; and / or the softness of the oral restoration membrane is 200-700 mN.

[0022] Furthermore, the piezoelectric material includes one or a combination of two or more of polyhydroxyalkanoate and polyvinylidene fluoride;

[0023] Preferably, the polyhydroxyalkanoate includes one or a combination of two or more of a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate, poly-3-hydroxybutyrate, and a copolymer of 3-hydroxybutyrate and 4-hydroxybutyrate.

[0024] Furthermore, the low melting point material is polycaprolactone.

[0025] Furthermore, the elastomeric material includes one or a combination of two or more of polytrimethylene carbonate, polyurethane elastomer, polyethylene elastomer, polyurea elastomer, and polyamide elastomer.

[0026] Furthermore, the raw materials for forming the first layer and / or the third layer also contain a hydrophilic substance; preferably, the mass of the hydrophilic substance is less than 1 / 10 of the mass of the piezoelectric material.

[0027] The present invention also provides a method for preparing the oral repair membrane according to the present invention, comprising the steps of preparing the first layer, the second layer and an optional third layer of the oral repair membrane and compounding them to obtain a preform; preferably, the preform is prepared using an electrospinning process.

[0028] Furthermore, the preparation method of the present invention further comprises the following steps:

[0029] performing an elution treatment on the preform to obtain a formed body;

[0030] The molded body is subjected to heat treatment or not subjected to heat treatment and subjected to irradiation sterilization treatment to obtain an oral repair membrane.

[0031] Furthermore, in the preparation method of the present invention, the temperature of the heat treatment is 70-110° C., and the time of the heat treatment is 5-30 minutes.

[0032] Effects of the Invention

[0033] The oral restoration membrane of the present invention has a soft texture and utilizes the potential of the piezoelectric material to attract the potential of cells to generate a good adhesion force. No slippage occurs during use, thereby reducing the exposure infection rate.

[0034] The oral cavity repair membrane of the present invention utilizes the piezoelectric property of the piezoelectric material to rapidly induce cell generation, and the piezoelectric material of the present invention can effectively avoid the problem of the oral cavity repair membrane swelling, leading to slippage and deformation during use.

[0035] The oral repair membrane of the present invention has a porous structure with an appropriate pore size, which can selectively block the surrounding tissues such as fibroblasts and epithelial cells with a faster migration speed from entering the bone defect area, while promoting or even inducing bone regeneration and oral wound healing.

[0036] The preparation method of the oral repair membrane of the present invention is simple and easy, the raw materials are easy to obtain, and the membrane is suitable for mass production. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 The specific experimental process of the oral restoration membrane of Example 1 of the present invention for evaluation of an animal model of a tooth extraction socket is shown; wherein, the four corners of the sample on the left are fixed with bone screws, while the sample on the right is not fixed with bone screws after bonding.

[0038] Figure 2 A comparison chart shows the wound healing conditions of Example 1 of the present invention after the oral repair membrane was used in an animal model of a tooth extraction socket on the first day; wherein, the four corners of the sample on the left were fixed with bone screws, while the sample on the right was not fixed with bone screws after bonding.

[0039] Figure 3 A comparison chart showing the wound healing conditions of the oral repair membrane of Example 1 of the present invention on the third day after being used in an animal model of a tooth extraction socket; wherein, the four corners of the sample on the left were fixed with bone screws, while the sample on the right was not fixed with bone screws after being attached.

[0040] Figure 4 A comparison chart showing the wound healing status of the oral repair membrane of Example 1 of the present invention on the sixth day after being used in an animal model of a tooth extraction socket; wherein, the four corners of the sample on the left were fixed with bone screws, while the sample on the right was not fixed with bone screws after being attached.

[0041] Figure 5 A comparison chart showing the wound healing status after the seventh day after the sutures were removed after the oral repair membrane of Example 1 of the present invention was used in an animal model of a tooth extraction socket; wherein, the four corners of the sample on the left were fixed with bone screws, while the sample on the right was not fixed with bone screws after bonding.

[0042] Figure 6 A comparative diagram showing the wound healing status of Example 1 of the present invention after the oral repair membrane was used in an animal model of a tooth extraction socket on the fourteenth day; wherein, the four corners of the sample on the left were fixed with bone screws, while the sample on the right was not fixed with bone screws after bonding.

[0043] Figure 7The figure shows a comparison of the gingival healing conditions of an animal model of tooth extraction socket site where the oral repair membrane of Example 1 of the present invention is used for wound healing, and an anatomical observation is made; wherein, the four corners of the sample on the left are fixed with bone screws, while the sample on the right is not fixed with bone screws after being attached.

[0044] Figure 8 The figure shows a comparison of the bone growth after the oral repair membrane of Example 1 of the present invention is used in an animal model of a tooth extraction socket and the wound is healed by anatomical observation; wherein, the four corners of the sample on the left are fixed with bone screws, while the sample on the right is not fixed with bone screws after bonding.

[0045] Figure 9 The figure shows the pathological observation of the implantation site after the oral restoration membrane of Example 1 of the present invention is used in an animal model of tooth extraction socket after wound healing and dissection.

[0046] Figure 10 The figure shows the wound healing condition on the fourteenth day after the oral repair membrane of Comparative Example 1 was used in the tooth extraction socket animal model.

[0047] Figure 11 The oral restoration membranes of Comparative Example 1 and Comparative Example 2 are used in an animal model of tooth extraction sockets, and pathological observations of tissue cell penetration at the implantation site after wound healing are shown. DETAILED DESCRIPTION

[0048] The following describes the technical features of the present invention in detail. The technical features described below are described based on representative embodiments and specific examples of the present invention, but the present invention is not limited to these embodiments and specific examples.

[0049] It should be noted that:

[0050] In this specification, the numerical range expressed using "a numerical value A to a numerical value B" means a range including the endpoints A and B.

[0051] In this specification, “substantially does not have / contains” means that during a certain method or step, a certain operation is not actually performed so as not to actually cause the operation object to have a certain characteristic, or, for a certain substance, the above description means that it is below the detection limit of the detector.

[0052] In this specification, unless otherwise specified, "%" means percentage by weight.

[0053] In this specification, the use of "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

[0054] As used herein, "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event occurs and instances where it does not.

[0055] In this specification, references to "some specific / preferred embodiments," "other specific / preferred embodiments," "embodiments," etc., mean that the specific elements (e.g., features, structures, properties, and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any appropriate manner.

[0056] <First Aspect>

[0057] A first aspect of the present invention provides an oral restoration film, comprising a first layer and a second layer having a porous structure, wherein:

[0058] The average pore size of the second layer is smaller than the average pore size of the first layer;

[0059] The raw material forming the first layer includes piezoelectric material;

[0060] The raw materials for forming the second layer include piezoelectric material and synthetic polymer material.

[0061] Furthermore, the first layer and the second layer are in contact.

[0062] The average pore size of the oral restoration membrane of the present invention is 0.1-5 μm, for example: 0.2 μm, 0.5 μm, 0.8 μm, 1 μm, 1.2 μm, 1.5 μm, 1.8 μm, 2 μm, 3 μm, 4 μm, etc.; and / or the tensile strength of the oral restoration membrane is 1-5 MPa, for example: 1.5 MPa, 2 MPa, 2.5 MPa, 3 MPa, 3.5 MPa, 4 MPa, 4.5 MPa, etc.; and / or the softness of the oral restoration membrane is 200-700 mN, for example: 250 mN, 300 mN, 350 mN, 400 mN, 450 mN, 500 mN, 550 mN, 600 mN, 650 mN, etc.

[0063] When the average pore size of the oral repair membrane of the present invention is 0.1-5 μm, the oral repair membrane can selectively block surrounding tissues such as fibroblasts and epithelial cells with faster migration speed from entering the bone defect area, while promoting or even inducing bone regeneration and oral wound healing.

[0064] When the tensile strength of the oral cavity repair membrane of the present invention is 1-5 MPa, the mechanical properties thereof are appropriate and the membrane is suitable for use as an oral cavity repair membrane.

[0065] When the softness of the oral repair membrane of the present invention is 200-700 mN, it has appropriate softness, firm adhesion and excellent operability.

[0066] Cell membranes contain electrical potentials, including resting potential and action potential. The resting potential is the potential difference between the two sides of the membrane when the tissue cell is at rest. The action potential is the change in potential from the resting potential that occurs when the cell is stimulated. The oral prosthetic membrane of the present invention utilizes the potential attraction between the piezoelectric material and the cell's potential to generate a strong adhesion force, reducing the risk of infection through exposure.

[0067] First floor

[0068] The raw materials forming the first layer include autologous absorbable or non-absorbable piezoelectric materials; by using piezoelectric materials to prepare the first layer of the oral restoration membrane, the properties of the piezoelectric materials can be used to quickly induce cell generation, promote bone growth, and have good adhesion, will not shift, and do not require fixation with bone screws.

[0069] In the present invention, the first layer has a porous structure with an average pore size of 1-5 μm, for example, 1.5 μm, 2 μm, 2.5 μm, 3 μm, 3.5 μm, 4 μm, 4.5 μm, etc. The porous structure facilitates cell crawling and growth. The first layer of the present invention is preferably a first fiber layer.

[0070] The piezoelectric material of the present invention can be a hydrophobic material that does not swell. In addition, the piezoelectric coefficient of the piezoelectric material of the present invention is closer to that of human cells and natural components in the body, which is more conducive to promoting cell growth.

[0071] The present invention does not specifically limit the piezoelectric material of the first layer, and it can be some piezoelectric materials commonly used in the art. Specifically, the piezoelectric material includes one or a combination of two or more of polyhydroxyalkanoates and polyvinylidene fluoride (PVDF); preferably, the polyhydroxyalkanoates include one or a combination of two or more of a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV), poly-3-hydroxybutyrate (P3HB), and a copolymer of 3-hydroxybutyrate and 4-hydroxybutyrate (P34HB).

[0072] Furthermore, in the present invention, the thickness of the first layer may be 0.1 mm to 0.2 mm, for example, 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, etc.; preferably 0.1 mm to 0.15 mm.

[0073] Second floor

[0074] The second layer has a porous structure, and the average pore size of the second layer is smaller than the average pore size of the first layer, so that the second layer can prevent surrounding tissues such as fibroblasts and epithelial cells from entering the first layer of the oral repair membrane to affect bone growth. However, since it still has a porous structure, it can allow small molecule nutrients to pass through and enter the first layer to promote bone growth. Specifically, in the present invention, the average pore size of the second layer can be 0.1-1μm, for example: 0.2μm, 0.3μm, 0.4μm, 0.5μm, 0.6μm, 0.7μm, 0.8μm, 0.9μm, etc. The second layer of the present invention is preferably a second fiber layer.

[0075] Furthermore, the raw materials for forming the second layer include a piezoelectric material and a synthetic polymer material. The synthetic polymer material includes an elastomeric material and / or a low-melting-point material; the low-melting-point material has a lower melting point than the piezoelectric material. By using the elastomeric material and / or the low-melting-point material, a second layer with a smaller pore size can be produced.

[0076] The inventors discovered that due to the unique properties of elastomeric materials, the resulting oral prosthetic membrane shrinks, reducing the pore size of the second layer. This acts as a barrier, preventing the in-growth of surrounding tissues such as fibroblasts and epithelial cells, while allowing the passage of small molecule nutrients. Furthermore, they discovered that the combined use of elastomeric materials and piezoelectric materials can enhance the mechanical properties of the oral prosthetic membrane.

[0077] In addition, when using low-melting-point materials as synthetic polymer materials, heat treatment can make the low-melting-point materials melt and fill part of the pore space, and can also reduce the pore size of the second layer, thereby playing a shielding role, isolating fibroblasts and epithelial cells and other surrounding tissues from growing in, but allowing small molecule nutrients to pass through.

[0078] In some specific embodiments, in the second layer, the mass ratio of the piezoelectric material to the synthetic polymer material is 1:1 to 4:1, for example: 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.8:1, 2:1, 2.1:1, 2.5:1, 3.5:1, etc.

[0079] If the second layer uses a combination of piezoelectric material and elastomeric material as raw materials, the mass ratio of the piezoelectric material to the elastomeric material can be 1:1 to 7:3, for example: 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.8:1, 2:1, 2.1:1, etc.; when the content of the elastomeric material is too high or too low, the pore size of the second layer will be affected.

[0080] If the second layer uses a combination of piezoelectric material and low-melting-point material as raw materials, the mass ratio of the piezoelectric material to the low-melting-point material can be 1:1 to 3:2, for example, 1.1:1, 1.2:1, 1.3:1, 1.4:1, etc. If the content of the low-melting-point material is too low, the second layer cannot be reduced to an appropriate pore size, thus failing to provide a good shielding effect. If the content of the low-melting-point material is too high, the pores of the entire oral restoration membrane may be blocked during the hot-melt process, thereby affecting the penetration and supply of nutrients.

[0081] If the second layer uses a combination of piezoelectric material, elastomeric material and low-melting-point material as raw materials, the mass ratio of piezoelectric material to synthetic polymer material (the sum of the mass of elastomeric material and low-melting-point material) is 1:1 to 4:1. There is no limitation on the mass ratio of elastomeric material and low-melting-point material in synthetic polymer material. During the research process, the inventor found that when using piezoelectric material, elastomeric material and low-melting-point material to prepare the second layer, when the mass ratio of elastomeric material and low-melting-point material is greater than 1:4, the final oral restoration membrane has both optimal mechanical properties and suitable pore size. For example: the mass ratio of elastomeric material and low-melting-point material is 1:3, 1:2, 1:1, 1:0.5, etc.

[0082] The piezoelectric material of the second layer may be the same as or different from the piezoelectric material of the first layer. Specifically, the piezoelectric material of the second layer and the piezoelectric material of the first layer may each include one or a combination of two or more of polyhydroxyalkanoate and polyvinylidene fluoride (PVDF); the polyhydroxyalkanoate is preferably any one of a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV), poly-3-hydroxybutyrate (P3HB), and a copolymer of 3-hydroxybutyrate and 4-hydroxybutyrate (P34HB).

[0083] The present invention does not make any special restrictions on the elastomer material of the second layer, and it can be some commonly used polymer elastomer materials in the art. The low melting point material only needs to satisfy the requirement that its thermal melting point is lower than that of the piezoelectric material. Specifically, the elastomer material includes one or more combinations of polytrimethylene carbonate (PTMC), polyurethane elastomer (TPU), polyethylene elastomer (TPE), polyurea elastomer, polyamide elastomer, etc., preferably one or more combinations of polytrimethylene carbonate (PTMC), polyurethane elastomer (TPU), etc., more preferably polytrimethylene carbonate (PTMC). Polytrimethylene carbonate has good biocompatibility and biodegradability, and has certain elasticity at low temperatures; the low melting point material is preferably polycaprolactone (PCL), which has a lower melting point. The heat treatment temperature required in the preparation process of the oral film is lower, which avoids the influence of high temperature on other materials, and it also has excellent biocompatibility, memory and biodegradability.

[0084] Furthermore, in the present invention, the thickness of the second layer may be 0.05 mm to 0.15 mm, for example, 0.06 mm, 0.07 mm, 0.08 mm, 0.09 mm, 0.1 mm, 0.11 mm, 0.12 mm, 0.13 mm, 0.14 mm, etc.

[0085] Third floor

[0086] The oral restoration membrane of the present invention may further include a third layer having a porous structure. The third layer is located on the side of the second layer opposite the first layer, and the average pore size of the third layer is larger than that of the second layer. Preferably, the third layer is a third fiber layer. The provision of the third layer can further promote gum healing.

[0087] In some specific embodiments, the raw material forming the third layer includes a piezoelectric material. The piezoelectric material of the third layer is the same as or different from the piezoelectric material of the first layer. Specifically, the piezoelectric material of the third layer can also include one or a combination of two or more of polyhydroxyalkanoates and polyvinylidene fluoride (PVDF); the polyhydroxyalkanoates are preferably one or a combination of two or more of a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV), poly-3-hydroxybutyrate (P3HB), and a copolymer of 3-hydroxybutyrate and 4-hydroxybutyrate (P34HB).

[0088] More preferably, the average pore size of the third layer is 1-5 μm, for example, 1.5 μm, 2 μm, 2.5 μm, 3 μm, 3.5 μm, 4 μm, 4.5 μm, etc.

[0089] Furthermore, in the present invention, the thickness of the third layer may be 0.1 mm-0.2 mm, for example, 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, etc., preferably 0.1 mm-0.15 mm.

[0090] hydrophilic substances

[0091] In some specific embodiments of the present invention, in order to improve the hydrophilicity of the oral restoration membrane, the raw materials forming the first layer and / or the third layer may further contain a hydrophilic substance; preferably, in order to ensure that the oral restoration membrane does not swell, the mass of the hydrophilic substance is less than 1 / 10 of the mass of the piezoelectric material, for example: the mass of the hydrophilic substance is 1 / 12, 1 / 15, 1 / 18, 1 / 20, etc. of the mass of the piezoelectric material.

[0092] Specifically, the hydrophilic substances include: nitrogen-containing compounds and their derivatives, cellulose compounds and their derivatives, alcohol compounds and their derivatives, chitosan compounds and their derivatives.

[0093] For example, the nitrogen-containing compounds and their derivatives include protein compounds, such as one or both of collagen and gelatin; the cellulose compounds and their derivatives include one or both of hydroxyethyl cellulose, carboxymethyl cellulose, and hydroxypropyl methyl cellulose; the alcohol compounds and their derivatives include 1,3-propylene glycol, etc.; the chitosan compounds and their derivatives include one or both of carboxymethyl chitosan and hydroxypropyl chitosan.

[0094] <Second Aspect>

[0095] The second aspect of the present invention provides a method for preparing the oral repair membrane according to the first aspect of the present invention, which includes the steps of preparing the first layer, the second layer and the optional third layer of the oral repair membrane and compounding them to obtain a preform; preferably, the preform is prepared by an electrospinning process.

[0096] electrospinning

[0097] The principle of electrospinning is to apply a high voltage to a polymer liquid during the electrospinning process, introducing electric charges into the liquid. When the charge in the liquid accumulates to a certain level, the liquid forms a Taylor cone at the nozzle. The applied electric field overcomes surface tension to form a liquid jet. Subsequently, electrostatic repulsion, Coulomb force, and surface tension combine to cause the polymer jet to move along an irregular spiral trajectory. The polymer jet is stretched and pulled in a very short time, and as the solvent evaporates or heat dissipates, it eventually solidifies to form micron / nanofibers.

[0098] During the electrospinning process of the present invention, the process parameters will affect the preform obtained by electrospinning. By controlling the process parameters, preforms with different morphologies and structures can be prepared. The present invention has no particular requirements for the electrospinning method, and it can be an electrospinning method commonly used in the art. Specifically, the present invention dissolves a polymer material in a suitable solvent to prepare a spinning solution of the polymer material; then, electrospinning is used to spin the spinning solution into a preform composed of interwoven fiber filaments. Preferably, the preform has a porous structure.

[0099] In the present invention, the electrospinning may include the following steps: preparing a fiber raw material in advance, dissolving the fiber raw material in a suitable solvent, and preparing a spinning solution of a certain concentration of fiber raw material. Wherein, the fiber raw material may be the piezoelectric material and / or synthetic polymer material in the first embodiment. There is no particular limitation on the specific concentration of the type of solvent used to form the solution, as long as it can meet the requirements of the subsequent electrospinning process. For example, a suitable solvent may be one or more combinations of trifluoroethanol, hexafluoroisopropanol, trifluoroacetic acid, N,N-dimethylformamide, cyclohexanone, acetone, butanone, tetrahydrofuran, chloroform, glacial acetic acid, formic acid, propionic acid or water.

[0100] The fiber membrane obtained by the present invention through the electrostatic spinning process using piezoelectric materials has good mechanical properties, and is not easy to break when high concentration of piezoelectric materials are used for spinning in the spinning process, and is easy to form into filaments.

[0101] In some specific embodiments, the electrospinning process comprises the following steps:

[0102] dissolving a piezoelectric material and an optional hydrophilic substance in a solvent to obtain a piezoelectric material solution;

[0103] dissolving the synthetic polymer material in a solvent to obtain a synthetic polymer material solution;

[0104] The piezoelectric material solution and the synthetic polymer material solution are placed in different electrospinning syringes respectively;

[0105] Electrospinning a piezoelectric material solution to prepare a first layer;

[0106] Then, while continuing to use the piezoelectric material solution for electrospinning, the synthetic polymer material solution is used for electrospinning to prepare a second layer, thereby obtaining a preform.

[0107] When preparing the second layer, the present invention uses a piezoelectric material solution for electrospinning and a synthetic polymer material solution for electrospinning at the same time. That is, there is no interruption when the first and second layers are electrospun using the piezoelectric material solution. Only the use of the synthetic polymer material solution for electrospinning is added simultaneously when preparing the second layer, thereby ensuring the continuity between the first and second layers and making it difficult for the first and second layers to be delaminated.

[0108] Furthermore, the electrospinning process further includes, after forming the second layer, stopping the electrospinning using the synthetic polymer material solution and only using the piezoelectric material solution for electrospinning to prepare the third layer.

[0109] Specifically, in the present invention, during the electrospinning process, the rate of the microinjection pump is adjusted to 1-15 mL / h, the voltage of the high-voltage generator is adjusted to 10-36 kV, and the receiving distance of the receiving device is adjusted to 5-30 cm.

[0110] In addition, it is possible to consider loading drugs into the spinning solution or during the electrospinning process. The drugs may include one or a combination of coagulation factors, growth factors, etc. This can not only improve the hemostatic properties of the material, but also promote rapid wound healing and prevent adhesion.

[0111] Elution treatment

[0112] The preparation method of the present invention also includes the step of eluting the preform to obtain a molded body. The purpose of eluting is to remove the solvent. Specifically, the elution step may include: eluting the preform with an eluent to remove the solvent. The eluent includes a mixture of alcohols and water, preferably a mixture of ethanol and water, and more preferably, the mass fraction of ethanol in the mixture of ethanol and water is above 70%, for example: 75%, 80%, 85%, 90%, 95%, etc. Specifically, in the present invention, the mixture of ethanol and water can be used for repeated soaking and elution to remove the solvent as completely as possible.

[0113] Heat treatment

[0114] When the second layer is made of piezoelectric material and low melting point material, the preparation method of the present invention further comprises the step of heat-treating the molded body to obtain the oral repair membrane.

[0115] When the second layer uses three materials: piezoelectric material, elastomeric material and low-melting-point material, if the mass ratio of the elastomeric material to the low-melting-point material is less than or equal to 1:4, the preparation method also includes heat treating the molded body; if the mass ratio of the elastomeric material to the low-melting-point material is greater than 1:4, there is no need to heat treat the molded body.

[0116] The low melting point material is melted by heat treatment to reduce the pore size of the second layer. Specifically, the heat treatment temperature is 70-110° C. and the heat treatment time is 5-30 minutes.

[0117] In addition, the cut oral restoration film can be sealed and packaged, and sterilized by Co-60 gamma ray irradiation. Specifically, the sealed packaging requires rapid packaging in a dry environment with an ambient humidity below 30%; the Co-60 gamma ray irradiation dose is 15 to 30 kGY.

[0118] Example

[0119] The embodiments of the present invention will be described in detail below with reference to the examples. However, it will be understood by those skilled in the art that the following examples are only intended to illustrate the present invention and should not be construed as limiting the scope of the invention. Where specific conditions are not specified in the examples, the methods were performed according to conventional conditions or the conditions recommended by the manufacturer. Unless otherwise specified, the materials or instruments used were commercially available conventional products.

[0120] Example 1

[0121] (1) dissolving a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate in a hexafluoroisopropanol solvent at a mass volume ratio of 16 g / 100 mL and stirring uniformly to obtain a copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate;

[0122] (2) dissolving polycaprolactone in hexafluoroisopropanol solvent at a mass volume of 8 g / 100 mL and stirring uniformly to obtain a polycaprolactone solution;

[0123] (3) The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was loaded into 8 syringes, and the polycaprolactone solution was loaded into another 4 syringes. The rate of the microinjection pump was adjusted to 8 mL / h (only the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was pushed forward), the voltage difference of the high-voltage generator was adjusted to 24 kV, and the receiving distance of the receiving device was adjusted to 20 cm. The interwoven copolymer fiber membrane of 3-hydroxybutyrate and 3-hydroxyvalerate was prepared by electrospinning, which was the first layer.

[0124] (4) When the thickness of the first layer reaches 0.1 mm, the polycaprolactone solution is pushed at a rate of 12 mL / h, and the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate is pushed at a rate of 8 mL / h. The copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and the polycaprolactone solution are electrospun simultaneously to prepare the second layer, wherein the mass ratio of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate to polycaprolactone is 1:1;

[0125] (5) When the electrospinning reaches a thickness of about 0.2 mm, the electrospinning of the polycaprolactone solution is stopped to obtain a second layer having a thickness of 0.1 mm; then, the electrospinning of the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is continued to prepare a third layer until the thickness reaches 0.3 mm, i.e., the thickness of the third layer is 0.1 mm; then, the electrospinning is stopped to obtain a preform.

[0126] (6) The preformed body in step (5) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol, and then dried to obtain a molded body.

[0127] (7) The molded article prepared in step (6) is heat-treated at 80° C. for 20 minutes to melt the polycaprolactone fibers and reduce the pore size of the second layer, thereby producing an oral prosthetic membrane having large pores in the upper and lower layers and small pores in the second layer. The oral prosthetic membrane is sealed and packaged, and sterilized by Co-60 gamma ray irradiation.

[0128] Example 2

[0129] (1) dissolving a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate in a hexafluoroisopropanol solvent at a mass volume ratio of 16 g / 100 mL and stirring uniformly to obtain a copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate;

[0130] (2) dissolving the polyurethane elastomer in an acetone-N,N-dimethylformamide mixed solvent at a mass volume concentration of 18 g / 100 mL, wherein the volume ratio of acetone to N,N-dimethylformamide in the solvent is 3:2, and stirring uniformly to obtain a polyurethane elastomer solution;

[0131] (3) The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was loaded into 8 syringes, and the polyurethane elastomer solution was loaded into another 4 syringes. The rate of the microinjection pump was adjusted to 10 mL / h (only the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was pushed forward), the voltage difference of the high-voltage generator was adjusted to 24 kV, and the receiving distance of the receiving device was adjusted to 20 cm. The interwoven copolymer fiber membrane of 3-hydroxybutyrate and 3-hydroxyvalerate was prepared by electrospinning, which was the first layer.

[0132] (4) When the thickness of the first layer reaches 0.1 mm, the polyurethane elastomer solution is pushed at a rate of 12 mL / h. At the same time, the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is pushed at a rate of 8 mL / h. The voltage is adjusted to 30 kV. The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate and the polyurethane elastomer solution are electrospun simultaneously to prepare the second layer. The mass ratio of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate to the polyurethane elastomer is 1:1.

[0133] (5) When the electrospinning reaches a thickness of about 0.2 mm, a second layer is obtained, and the thickness of the second layer is 0.1 mm; then the electrospinning of the polyurethane elastomer solution is stopped, and the electrospinning of the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is continued to prepare the third layer until the thickness reaches 0.3 mm, that is, the thickness of the third layer is 0.1 mm; then the electrospinning is stopped to obtain a preform.

[0134] (6) The preformed body in step (5) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol and acetone-N,N-dimethylformamide mixed solvent, and then dried to obtain a molded body.

[0135] (7) The molded body in step (6) is sealed and packaged, and sterilized by Co-60 gamma ray irradiation.

[0136] Example 3

[0137] (1) dissolving a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate in a hexafluoroisopropanol solvent at a mass volume ratio of 16 g / 100 mL and stirring uniformly to obtain a copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate;

[0138] (2) dissolving polytrimethylene carbonate and polycaprolactone in a hexafluoroisopropanol solvent at a mass ratio of 1:3, wherein the total mass volume concentration is 10 g / 100 mL, and stirring uniformly to obtain a mixed solution of polycaprolactone and polytrimethylene carbonate;

[0139] (3) The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was loaded into 8 syringes, and the mixed solution of polycaprolactone and polytrimethylene carbonate was loaded into another 4 syringes. The rate of the microinjection pump was adjusted to 10 mL / h (only the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was pushed forward), the voltage difference of the high-voltage generator was adjusted to 24 kV, and the receiving distance of the receiving device was adjusted to 20 cm. The interwoven copolymer fiber membrane of 3-hydroxybutyrate and 3-hydroxyvalerate was prepared by electrospinning, which was the first layer.

[0140] (4) When the thickness of the first layer reaches 0.1 mm, the mixed solution of polycaprolactone and polytrimethylene carbonate is pushed at a rate of 12 mL / h, and the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is pushed at a rate of 8 mL / h. The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate and the mixed solution of polycaprolactone and polytrimethylene carbonate are simultaneously electrospun to prepare the second layer, wherein the mass ratio of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate to the polymer material (the total mass of polycaprolactone and polytrimethylene carbonate) is 4:1;

[0141] (5) When the electrospinning reaches a thickness of about 0.2 mm, a second layer is obtained, and the thickness of the second layer is 0.1 mm; then the electrospinning of the mixed solution of polycaprolactone and polytrimethylene carbonate is stopped, and the electrospinning of the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is continued to prepare the third layer until the thickness reaches 0.3 mm, that is, the thickness of the third layer is 0.1 mm; then the electrospinning is stopped to obtain a preform.

[0142] (6) The preformed body in step (5) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol, and then dried to obtain a molded body.

[0143] (7) The oral restoration film in step (6) is sealed and packaged, and sterilized by Co-60 gamma ray irradiation.

[0144] Example 4

[0145] (1) dissolving a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate in a hexafluoroisopropanol solvent at a mass volume ratio of 14 g / 100 mL and stirring uniformly to obtain a copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate;

[0146] (2) dissolving polytrimethylene carbonate in hexafluoroisopropanol solvent at a mass volume ratio of 12 g / 100 mL and stirring uniformly to obtain a polytrimethylene carbonate solution;

[0147] (3) The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was loaded into 8 syringes, and the polytrimethylene carbonate solution was loaded into another 4 syringes. The rate of the microinjection pump was adjusted to 8 mL / h (only the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was pushed forward), the voltage difference of the high-voltage generator was adjusted to 24 kV, and the receiving distance of the receiving device was adjusted to 20 cm. The interwoven copolymer fiber membrane of 3-hydroxybutyrate and 3-hydroxyvalerate was prepared by electrospinning, which was the first layer.

[0148] (4) When the thickness of the first layer reaches 0.1 mm, the polytrimethylene carbonate solution is pushed at a rate of 12 mL / h, and the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is pushed at a rate of 6 mL / h. The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate and the polytrimethylene carbonate solution are electrospun simultaneously to prepare the second layer, wherein the mass ratio of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate to polytrimethylene carbonate is 7:3;

[0149] (5) When the electrospinning reaches a thickness of about 0.2 mm, a second layer is obtained, and the thickness of the second layer is 0.1 mm; then the electrospinning of the polytrimethylene carbonate solution is stopped, and the electrospinning of the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is continued to prepare the third layer until the thickness reaches 0.3 mm, that is, the thickness of the third layer is 0.1 mm; then the electrospinning is stopped to obtain a preform.

[0150] (6) The preformed body in step (5) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol, and then dried to obtain a molded body.

[0151] (7) The molded body in step (6) is sealed and packaged, and sterilized by Co-60 gamma ray irradiation.

[0152] Example 5

[0153] (1) dissolving a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate in a hexafluoroisopropanol solvent at a mass volume ratio of 14 g / 100 mL and stirring uniformly to obtain a copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate;

[0154] (2) dissolving polycaprolactone in hexafluoroisopropanol solvent at a mass volume of 10 g / 100 mL and stirring uniformly to obtain a polycaprolactone solution;

[0155] (3) The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was loaded into 8 syringes, and the polycaprolactone solution was loaded into another 4 syringes. The rate of the microinjection pump was adjusted to 8 mL / h (only the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was pushed forward), the voltage difference of the high-voltage generator was adjusted to 24 kV, and the receiving distance of the receiving device was adjusted to 20 cm. The interwoven copolymer fiber membrane of 3-hydroxybutyrate and 3-hydroxyvalerate was prepared by electrospinning, which was the first layer.

[0156] (4) When the thickness of the first layer reaches 0.15 mm, the polycaprolactone solution is pushed at a rate of 12 mL / h, and the copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate is pushed at a rate of 6 mL / h. The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate and the polycaprolactone solution are electrospun simultaneously to prepare the second layer, wherein the mass ratio of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate to polycaprolactone is 3:2;

[0157] (5) When the electrospinning reaches a thickness of about 0.3 mm, a second layer is obtained, and the thickness of the second layer is 0.15 mm; then the electrospinning is stopped to obtain a preform.

[0158] (6) The preformed body in step (5) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol, and then dried to obtain a molded body.

[0159] (7) The molded article from step (6) is heat-treated at 70° C. for 30 minutes to melt the polycaprolactone fibers and reduce the pore size of the second layer, thereby producing an oral prosthetic membrane having large pores in the first layer and small pores in the second layer. The oral prosthetic membrane is sealed and packaged, and sterilized by Co-60 gamma ray irradiation.

[0160] Example 6

[0161] (1) dissolving the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and gelatin particles in a hexafluoroisopropanol solvent at a total mass volume ratio of 16 g / 100 mL, wherein the mass of the gelatin particles is 1 / 10 of the mass of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate, and stirring uniformly to obtain a mixed solution of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and gelatin;

[0162] (2) dissolving polycaprolactone in hexafluoroisopropanol solvent at a mass volume concentration of 12 g / 100 mL and stirring uniformly to obtain a polycaprolactone solution;

[0163] (3) The mixed solution of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and gelatin was loaded into 8 syringes, and the polycaprolactone solution was loaded into another 4 syringes. The rate of the microinjection pump was adjusted to 6 mL / h (only the mixed solution of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and gelatin was pushed forward), the voltage difference of the high-voltage generator was adjusted to 32 kV, and the receiving distance of the receiving device was adjusted to 20 cm. The interwoven mixed copolymer fiber membrane of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and gelatin was prepared by electrospinning, which was the first layer.

[0164] (4) When the thickness of the first layer reaches 0.1 mm, the polycaprolactone solution is pushed at a rate of 12 mL / h. At the same time, the mixed solution of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and gelatin is pushed at a rate of 6 mL / h. The mixed solution of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and gelatin and the polycaprolactone solution are electrospun simultaneously to prepare the second layer, wherein the mass ratio of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate to polycaprolactone is 1:1;

[0165] (5) When the electrospinning reaches a thickness of about 0.2 mm, a second layer is obtained, and the thickness of the second layer is 0.1 mm; then the electrospinning of the polycaprolactone solution is stopped, and the electrospinning of the copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate and the gelatin mixed solution is continued to prepare the third layer until the thickness reaches 0.3 mm, that is, the thickness of the third layer is 0.1 mm; then the electrospinning is stopped to obtain a preform.

[0166] (6) The preformed body in step (5) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol, and then dried to obtain a molded body.

[0167] (7) The molded article prepared in step (6) is heat-treated at 80° C. for 20 minutes to melt the polycaprolactone fibers and reduce the pore size of the second layer, thereby producing an oral prosthetic membrane having large pores in the upper and lower layers and small pores in the second layer. The oral prosthetic membrane is sealed and packaged, and sterilized by Co-60 gamma ray irradiation.

[0168] Comparative Example 1

[0169] (1) dissolving L-polylactic acid in hexafluoroisopropanol solvent at a mass volume ratio of 8 g / 100 mL and stirring uniformly to obtain an L-polylactic acid solution;

[0170] (2) The poly(L-lactic acid) solution was loaded into 12 syringes, the rate of the microinjection pump was adjusted to 10 mL / h, the voltage difference of the high-voltage generator was adjusted to 24 kV, and the receiving distance of the receiving device was adjusted to 20 cm, and an interwoven poly(L-lactic acid) fiber membrane was prepared by electrospinning;

[0171] (3) When the electrospinning reaches a thickness of about 0.3 mm, the solution electrospinning is stopped to obtain a preform.

[0172] (4) The preformed body in step (3) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol, and then dried to obtain a molded body.

[0173] (5) The molded body in step (4) is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain an oral repair membrane.

[0174] Comparative Example 2

[0175] (1) dissolving a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate in a hexafluoroisopropanol solvent at a mass volume ratio of 16 g / 100 mL and stirring uniformly to obtain a copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate;

[0176] (2) The copolymer solution of 3-hydroxybutyrate and 3-hydroxyvalerate was loaded into 8 syringes, the rate of the microinjection pump was adjusted to 8 mL / h, the voltage difference of the high-voltage generator was adjusted to 24 kV, and the receiving distance of the receiving device was adjusted to 20 cm. Interwoven copolymer fiber membranes of 3-hydroxybutyrate and 3-hydroxyvalerate were prepared by electrospinning.

[0177] (3) When the electrospinning reaches a thickness of 0.3 mm, the electrospinning is stopped to obtain a preform.

[0178] (4) The preformed body in step (3) is repeatedly immersed in a 95% ethanol solution to remove residual hexafluoroisopropanol, and then dried to obtain a molded body.

[0179] (5) The molded body in step (4) is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain an oral repair membrane.

[0180] Performance Testing

[0181] The tensile strength was measured using the GB / T1040.3-2006 method.

[0182] Softness is measured according to the method of GB / T 8942-2002; the softness value is the sum of the bending resistance of the oral restoration membrane and the maximum vector of the friction force between the oral restoration membrane and the gap, expressed in millinewtons (mN). The smaller the softness value, the softer the oral restoration membrane and the better the adhesion.

[0183] The pore size was measured by the bubble point method using a capillary flow porosimeter with reference to GTT TM017-2012 “Test method for pore characteristics of textile nonwoven materials”.

[0184] 1. Mechanical properties test

[0185]

[0186] As shown in Table 1, the oral prosthetic films of Examples 1-6 of the present invention have approximately the same tensile strength as that of Comparative Example 1, and exhibit a more suitable degree of softness. Therefore, the oral prosthetic films of the present invention possess suitable tensile strength and softness. Furthermore, compared to conventional oral prosthetic films, the oral prosthetic films of the present invention are more flexible, adhere more securely, and exhibit excellent operability.

[0187] 2. Aperture

[0188]

[0189] As shown in Table 2, due to the presence of the second layer of the oral prosthetic membrane of the present invention, the average pore diameters of the oral prosthetic membranes of Examples 1-6 of the present invention are smaller than those of Comparative Examples 1-2, with the oral prosthetic membrane of Example 3 having the smallest average pore diameter. Therefore, the oral prosthetic membrane of the present invention exhibits superior tissue barrier properties.

[0190] 3. Animal experiments

[0191] The oral restoration membrane samples prepared in Example 1, Comparative Example 1, and Comparative Example 2 were irradiated and sterilized, and then used for evaluation in an animal model of tooth extraction sockets.

[0192] Two beagle dogs were selected and fasted for 12 hours before surgery. They were anesthetized with 3% sodium pentobarbital at 1 ml / kg intravenously. After anesthesia, the hair surrounding the mandibular surgical site was removed. The oral cavity and surrounding skin were disinfected with iodine and draped. The gingival flap surrounding the first, second, third, and fourth premolars was separated, ensuring the periosteum was intact. The first, second, third, and fourth premolars on both sides of the mandible were extracted.

[0193] Take one of the beagle dogs, place bone powder mixed with autologous blood in the tooth extraction socket, squeeze it appropriately to make the bone powder level with the defect surface, cover the bone powder with the repair membrane sample prepared in Example 1, and fix the four corners of one sample with bone screws. The other sample is fixed without bone screws after being attached. Then suture the gums. The specific operation process is as follows Figure 1 shown.

[0194] Another beagle dog was taken, and bone powder mixed with autologous blood was placed in the tooth extraction socket. The bone powder was squeezed appropriately to make the height of the bone powder flush with the defect surface. The repair membrane samples of Comparative Examples 1 and 2 were respectively covered at different positions above the bone powder. After the samples were attached, no bone screws were used to fix them, and then the gums were sutured.

[0195] During operation, it was found that the oral repair membrane of the embodiment of the present invention 1 is soft. In the case of not using bone screws for fixation, adhesion is also very good, adheres firmly, and is excellent in operability. After suturing the gums, 800,000 units of penicillin sodium (intravenous infusion of penicillin sodium for the first 3 days) and 1 million units of streptomycin were injected intramuscularly every day for 7 days after operation to prevent infection. Fasting was carried out for 5 days after operation, and nutrition was supplemented by intravenous infusion every day (0.5 bottles / day of fat emulsion, 0.5 bottles / day of amino acids, 1 bottle / day of normal saline, and 1 bottle / day of glucose injection). On the 6th day, liquid food was fed every other day for 2 weeks. After feeding the liquid food, residual food in the wound was slowly rinsed with normal saline immediately to prevent infection.

[0196] For seven days after surgery, observe and record the surgical site daily. Use a cotton swab soaked in chlorhexidine disinfectant to gently roll the wound for disinfection. For wounds that have healed well, remove the sutures on the seventh or eighth day. If necessary, extend the disinfection period.

[0197] Continue observation for fourteen days, then dissect and euthanize the animal. After observing the condition of the gums, peel off the gums at the implant site and observe the condition of the implanted material. Use a hacksaw to remove the mandibular bone in the bone graft area, leaving both ends of the sample at least 2 cm away from the bone graft area to ensure the integrity of the bone graft area. Carefully lift the gingival flap and observe the bone formation in the bone graft area. After the observation is completed, carefully peel off the soft tissue (gingival tissue and implanted material) and alveolar bone in the bone graft area, fix, dehydrate, and embed the soft tissue to make pathological sections for histopathological section observation, and observe the growth of new bone components and tissue cell penetration.

[0198] Postoperative observation:

[0199] The wound healing results of the oral repair membrane of Example 1 after being used in the tooth extraction socket animal model are shown in FIG. Figure 2-6 As shown. Figure 2 As shown in the figure, on the first day after surgery, the wound was rosy, normal, and had little secretion. Figure 3 As shown, on the third day after surgery, the wound was rosy and normal; Figure 4 As shown, on the sixth day after surgery, healing was good; Figure 5 As shown, on the seventh day after surgery, the wound healed well and the sutures were removed; Figure 6 As shown, on the fourteenth day after surgery, complete healing was achieved.

[0200] In the anatomy experiment, Figure 7 As shown in the figure, it can be seen that after using the oral repair membrane of Example 1, the gums healed well, and the oral repair membrane was completely attached to the alveolar bone under the gums. The oral repair membrane without bone screw fixation did not slip, and the material was easily separated from the gum tissue, and the material did not show obvious thickening. Figure 8 As shown, it can be seen that there is a circle of bone tissue hyperplasia at the edge, and no bone powder is scattered around it.

[0201] Pathological results such as Figure 9 As shown, from Figure 9 (above) we can see obvious new bone tissue, which shows that the oral repair membrane of Example 1 has a significant effect in promoting bone growth; Figure 9 It can be seen from (bottom) that no tissue cells have penetrated and grown into the oral repair membrane in Example 1, indicating that Example 1 has a good tissue shielding effect.

[0202] The wound healing results of the oral repair membrane of comparative example 1 after being used in the tooth extraction socket animal model are as follows: Figure 10 As shown, fourteen days after surgery, the oral repair membrane was exposed and infected, and the wound healing was poor.

[0203] The oral repair membranes of Comparative Example 1 and Comparative Example 2 were used in the tooth extraction site animal model. After the wound healed, the pathological images after dissection were as follows: Figure 11 As shown, it was found that a large number of tissue cells had penetrated and grown into the oral repair membranes of Comparative Example 1 and Comparative Example 2, indicating that their tissue shielding effects were poor.

[0204] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. An oral repair membrane, characterized in that: The oral restoration film comprises a first layer and a second layer having a porous structure, wherein: The average pore size of the second layer is smaller than the average pore size of the first layer, and the average pore size of the second layer is 0.1-1 μm; The raw material forming the first layer includes piezoelectric material; The raw materials forming the second layer include a piezoelectric material and a synthetic polymer material, wherein the mass ratio of the piezoelectric material to the synthetic polymer material is 1:1 to 4:1, and the synthetic polymer material includes an elastomeric material and / or a low-melting-point material, and the low-melting-point material has a lower thermal melting point than the piezoelectric material; The low melting point material is polycaprolactone, and the elastomer material includes one or a combination of two or more of polytrimethylene carbonate, polyurethane elastomer, polyethylene elastomer, polyurea elastomer, and polyamide elastomer; The average pore size of the oral repair membrane is 0.1-5 μm.

2. The oral repair membrane according to claim 1, characterized in that The oral restoration film further comprises a third layer having a porous structure, wherein the third layer is present on a side of the second layer opposite to the first layer; The average pore size of the third layer is greater than the average pore size of the second layer.

3. The oral repair membrane according to claim 2, characterized in that: The raw material for forming the third layer contains piezoelectric material.

4. The oral repair membrane according to any one of claims 1 to 3, characterized in that: The tensile strength of the oral restoration film is 1-5 MPa; and / or the softness of the oral restoration film is 200-700 mN.

5. The oral repair membrane according to any one of claims 1 to 3, characterized in that: The piezoelectric material includes one or a combination of two or more of polyhydroxyalkanoate and polyvinylidene fluoride.

6. The oral repair membrane according to claim 5, characterized in that: The polyhydroxyalkanoate includes one or a combination of two or more of a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate, poly-3-hydroxybutyrate, and a copolymer of 3-hydroxybutyrate and 4-hydroxybutyrate.

7. The oral repair membrane according to any one of claims 1 to 3, characterized in that: The raw materials for forming the first layer and / or the third layer further include hydrophilic substances.

8. The oral repair membrane according to claim 7, characterized in that: The mass of the hydrophilic substance is less than 1 / 10 of the mass of the piezoelectric material.

9. A method for preparing the oral repair membrane according to any one of claims 1 to 8, characterized in that: The method comprises the steps of preparing the first layer, the second layer and the optional third layer of the oral repair film and compounding them to obtain a preform.

10. The preparation method according to claim 9, characterized in that The preform is prepared by utilizing an electrostatic spinning process.

11. The preparation method according to claim 9 or 10, characterized in that: The following steps are also included: performing an elution treatment on the preform to obtain a formed body; The molded body is subjected to heat treatment or not subjected to heat treatment and subjected to irradiation sterilization treatment to obtain an oral repair membrane.

12. The preparation method according to claim 11, characterized in that The heat treatment temperature is 70-110° C., and the heat treatment time is 5-30 minutes.

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