An esophageal hiatal hernia repair patch, its preparation method and application

Abstract

This invention provides an esophageal hiatal hernia repair patch, its preparation method, and its application. The esophageal hiatal hernia repair patch includes a main body layer, an adsorption structure, a soluble membrane, and a smooth layer. The adsorption structure is disposed on one side of the main body layer, and the soluble membrane covers the adsorption structure. The side of the main body layer containing the adsorption structure is positioned to face and / or contact the tissue surrounding the hiatal hernia. The adsorption structure, main body layer, and smooth layer are all made of biodegradable materials; the soluble membrane is made of a water-soluble material. The esophageal hiatal hernia repair patch of this invention is easy to flatten and fix during surgery, does not easily adhere to other organs in vivo, has a degradation period that meets clinical needs, good biocompatibility, and excellent mechanical properties.

Description

Technical Field

[0001] This invention belongs to the field of medical biomaterials technology, and relates to esophageal hiatal hernia repair, specifically to a biodegradable esophageal hiatal hernia repair patch, its preparation method, and its application. Background Technology

[0002] Hiatal hernia is a disease characterized by a variation in normal tissue structure, where the stomach or other organs protrude upwards into the thoracic cavity through the hiatus of the diaphragm. As our understanding of the pathophysiology of hiatal hernia deepens, surgical techniques are constantly being improved. Previous studies have found that diaphragmatic crura suture reinforcement alone results in a high recurrence rate for hiatal hernias. In laparoscopic hiatal hernia repair, the short-term recurrence rate for patients without a mesh placement is 30%, and the long-term recurrence rate is 66%, while the recurrence rate is low for patients with a mesh placement. Hiatal hernia meshes are increasingly widely used in hiatal hernia surgery. The principle of tension-free repair is followed in hiatal hernia repair. The hiatal hernia mesh, acting as a support, reduces tension during repair and minimizes mechanical disturbance to the diaphragm. It also provides support when the tissue is subjected to tension from coughing, straining, vomiting, or obesity.

[0003] First-generation surgical patches were primarily made of non-degradable materials, such as PP and polytetrafluoroethylene (PTFE), which were bio-inert and designed to induce a reaction leading to fibrosis and scarring. They were also classified into three types based on the type of pores: macroporous, microporous, and macroporous with multifilaments. With the application of non-degradable synthetic patches, such as polypropylene patches, the recurrence rate of hiatal hernias has significantly decreased. However, complications such as dysphagia, patch erosion, fibrosis, esophageal erosion and stricture, patch compression, intestinal erosion, gastrointestinal fistula, and patch infection have begun to appear. Besides the potential for these complications, non-degradable synthetic patches also have several drawbacks, such as poor tissue compatibility and a tendency to cause visceral adhesions to adjacent organs.

[0004] Second-generation surgical patches are made of non-degradable biomaterials, such as medical-grade PP, polyester, and e-PTFE, but with a coating on the surface of the non-degradable biomaterials to increase biocompatibility and reduce inflammation, mesh shrinkage, and patch adhesion.

[0005] The third generation of surgical patches is the biodegradable patch. Biodegradable patches can reduce the recurrence of hiatal hernias while also decreasing the incidence of serious patch-related complications. Most recurrent hiatal hernias treated with biodegradable patches have small hernial sacs, and patients experience minimal symptoms, resulting in a low reoperation rate. The challenge with biodegradable patches lies in the change in structural integrity as the patch degrades, and the effectiveness and safety of different materials are questionable. Commercially available Bio-A™ patches degrade completely in approximately 7 months. Rapid degradation of biodegradable patches can lead to low elasticity and strength in newly formed tissue, making recurrence more likely. Furthermore, existing biodegradable patches also suffer from high cost and poor biomechanical strength.

[0006] Furthermore, because the esophageal hiatus is surrounded by vital organs such as the liver, spleen, and pericardium, and also contains deep tissues containing blood vessels like the abdominal aorta, there is a significant risk associated with suturing and fixation. The space available for placing the hiatal hernia mesh during surgery is extremely limited, making its flattening and fixation very difficult, requiring a longer operation time, and placing higher demands on the surgeon. If the mesh attached to the diaphragm is not properly flattened, the resulting gap between it and the tissue can easily lead to fluid accumulation and postoperative inflammation. A hiatal hernia mesh that is easy to flatten and fix during surgery would significantly shorten the operation time and lead to better patient outcomes. Summary of the Invention

[0007] In view of the shortcomings of existing technologies and practical needs, the purpose of this invention is to provide an esophageal hiatal hernia repair patch that is easy to flatten and fix during surgery, does not easily adhere to other organs in the body, has a degradation cycle that meets clinical needs, has good biocompatibility, and excellent mechanical properties.

[0008] Another object of the present invention is to provide a method for preparing the aforementioned hiatal hernia repair patch.

[0009] Another object of the present invention is to provide the application of the above-mentioned hiatal hernia repair patch or the hiatal hernia repair patch prepared by the above-mentioned preparation method in the preparation of products that promote in vivo tissue repair.

[0010] To achieve the above objectives, the present invention improves the existing patch structure as follows:

[0011] (1) In order to make the patch easy to be absorbed and fixed during the operation and not easy to slip off, an adsorption structure was designed to be directly fixed around the hiatal hernia. This can eliminate the need for suturing, or avoid the difficulty of patch fixation such as patch displacement, warping, and poor adhesion to tissue during the suturing operation. At the same time, it reduces the mutual interference of surgical instruments during the suturing operation, and reduces the difficulty of suturing operation and operation time.

[0012] (2) In order to make the patch with the fixation structure easy to flatten and move before being placed in the appropriate surgical site, a soluble film is covered on the outside of the adsorption structure; and after the patch is placed in the appropriate site, the fixation structure can quickly play a fixing role, and the soluble film needs to be able to dissolve quickly.

[0013] (3) In order to prevent the patch from adhering to other organs, a smooth layer was made. This layer is a non-porous membrane layer, which is made directly by the casting method of biodegradable biomaterials, and the anti-adhesion effect is significant.

[0014] (4) In order to ensure that the degradation period of the patch meets clinical needs and that the degradation rate is not too fast, the patch of the present invention can always provide sufficient mechanical support before the tissue repair is successful and the elasticity and strength of the newly formed tissue are sufficient to resist the pressure in the abdominal cavity. By selecting the main layer material, the molecular weight of the material, the internal molecular structure of the material, and designing and controlling the thickness, pore size, and porosity of the layer, the degradation period of the hiatal hernia patch of the present invention is 9 to 12 months.

[0015] Based on this, the specific technical solution of the present invention is as follows:

[0016] In a first aspect, the present invention provides a hiatal hernia repair patch, comprising a main body layer, an adsorption structure, and a soluble membrane. The adsorption structure is disposed on one side of the main body layer, and the soluble membrane covers the adsorption structure. The side of the main body layer where the adsorption structure is located is used to face and / or contact the tissue surrounding the hiatal hernia. The thickness of the main body layer is 0.1~0.5mm, and the main body layer has a porous structure with a pore size range of 1~100 μm and a porosity of 5-20%. The thickness of the soluble membrane is 0.01~0.03mm, and the soluble membrane is prepared from a water-soluble material. The height of the adsorption structure when unfolded is 1~8 times the thickness of the main body layer.

[0017] Furthermore, the water-soluble material includes any one or more combinations of pullulan, starch, or carboxymethyl cellulose.

[0018] Furthermore, the water-soluble material includes any one or more combinations of pullulan, starch, or carboxymethyl cellulose.

[0019] Furthermore, the outer edge diameter of the suction cup is 1.5mm-3mm, and the distance between two adjacent suction cups is 1.5-3 times the diameter of the suction cup.

[0020] Furthermore, the esophageal hiatal hernia repair patch provided by the present invention also includes a smooth layer, which is a non-porous membrane layer made by casting. The smooth layer is located on the side of the main layer away from the adsorption structure and has a thickness of 0.02~0.1mm.

[0021] Furthermore, the main body layer, adsorption structure, and smooth layer are prepared from biodegradable materials.

[0022] The biodegradable materials include any one or more copolymers or combinations of biodegradable polyurethane, polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol, polyvinyl alcohol, polycarbonate, polyhydroxyalkanoates, PHB / PHV copolymers, polyanhydrides, polydioxanone, and bacterial cellulose.

[0023] Preferably, the biodegradable materials used to make the adsorption structure, the smooth layer, and the main body layer are all preferably copolymers of polycaprolactone and polyethylene glycol, with molecular weights of 3~18W, 20~55W, and 25~55W, respectively.

[0024] In a second aspect, the present invention provides a method for preparing an esophageal hiatal hernia repair patch as described in the first aspect, comprising the following steps:

[0025] A. Using the aforementioned biodegradable material, prepare biodegradable material solution one and biodegradable material solution two for fabricating the main layer and adsorption structure, respectively. Use a water-soluble material to prepare a water-soluble material solution for fabricating the film.

[0026] B. The main layer is prepared using a solution of biodegradable materials through casting or electrospinning, followed by drying.

[0027] C. Prepare the adsorption structure on one side of the main layer using spinning, 3D printing, or by using a mold, and then dry it.

[0028] D. Coat the surface of the main layer with the adsorption structure with a water-soluble material solution, and dry to obtain the hiatal hernia repair patch.

[0029] In the fabrication of the main layer, a porogen is added to the biodegradable material solution one. The porogen has a particle size of 1-100 μm. The biodegradable material solution one consists of the following components by mass percentage: 10-30% biodegradable material, 3-12% porogen, and the remainder is solvent.

[0030] No pore-forming agent is added to the biodegradable material solution two.

[0031] A water-soluble material solution is a saturated solution obtained by dissolving a water-soluble material in water.

[0032] Furthermore, the method also includes preparing a smooth layer, which is prepared on the side of the host layer away from the adsorption structure. The preparation steps of the smooth layer include:

[0033] E. Prepare a biodegradable material solution for making the smooth layer. Then, use a casting method to create the smooth layer on the other side of the main layer where no adsorption structure is present.

[0034] Preferably, the dried main body layer is placed under a coating applicator with the side not used for setting the adsorption structure facing upwards. The height of the coating applicator is adjusted, and an automatic coating machine is used to spread the biodegradable material solution on the surface of the main body layer for drying.

[0035] Thirdly, the present invention provides the application of an esophageal hiatal hernia repair patch as described in the first aspect or an esophageal hiatal hernia repair patch prepared by the preparation method described in the second aspect in the preparation of products that promote in vivo tissue repair.

[0036] Compared with the prior art, the patch of the present invention has the following advantages:

[0037] (1) The hiatal hernia patch of the present invention is attached and fixed to the tissue around the hernia orifice by an adsorption structure such as burrs, cilia or suction cups, which can achieve seamless fixation of the patch or avoid patch displacement, warping, poor adhesion to tissue and other difficulties in patch fixation during suturing. It solves the problems of the surrounding organs of the hiatus in the prior art, the inconvenience of suturing and fixation operation and the high risk. In addition, compared with suturing, the fixation method of puncture or adsorption helps to improve the tightness of the bond between the patch and the tissue, which helps to reduce the probability of fluid accumulation and reduce the incidence of postoperative inflammatory response.

[0038] (2) The adsorption structure of the hiatal hernia repair patch of the present invention facilitates the fixation of the patch onto the tissue after it is unfolded at the site to be repaired, and it is not easy to slip off. The surface of the dissolution membrane outside the adsorption structure is smooth and easy to move at the tissue contact surface, so that the patch will not be hindered from flattening and moving during surgery due to the adsorption structure being initially adsorbed and fixed, thus affecting the placement of the patch in the appropriate position. The dissolution membrane facilitates the folding of the patch into the tissue to be repaired and makes the patch easy to flatten on the tissue surface. The dissolution membrane dissolves rapidly after the patch is flattened. For example, it will dissolve after pressing the patch on the tissue surface for more than 15 seconds, exposing the adsorption structure. The dissolution membrane dissolves rapidly due to the water environment present in the tissue. The part that is not completely dissolved forms a gel. The formed gel helps to improve the adhesion between the adsorption structure and the tissue, which is beneficial to the fixation of the patch. It can also form a sealing ring on the edges of the adsorption structure such as burrs, cilia or suction cups, preventing the accumulation of fluid in the gaps at the edges of the adsorption structure, reducing the risk of inflammatory reaction and promoting tissue repair.

[0039] (3) The hiatal hernia repair patch of the present invention provides sufficient mechanical support required during the repair of hiatal hernia, with the main body layer playing a major mechanical support role. The tensile strength of the hiatal hernia repair patch reaches 35.53 N / cm or above, the elastic modulus reaches 327.33 MPa or above, the elongation at break reaches 803.62% or above, the suture strength reaches 22.96 N or above, the tear strength reaches 45.74 N or above, and the burst strength reaches 403.34 kPa or above. It has excellent mechanical properties, strong pressure resistance, and helps to resist the complex environment inside the human body. In particular, the hiatal hernia repair patch prepared by the present invention has an elastic modulus of 327.33 MPa or above, which is elastic and soft, and can greatly reduce tissue damage during implantation, reduce patient discomfort, and improve patient acceptance. The burst strength reaches 403.34 kPa or above, which can fully withstand the physiological pressure and mechanical stress (such as abdominal pressure and tissue traction) during the repair of hiatal hernia.

[0040] (4) The degradation cycle of the hiatal hernia patch of the present invention is 9 to 12 months, which provides sufficient time for tissue repair. Before the tissue repair is successful and the elasticity and strength of the new tissue are sufficient to resist pressure, the patch of the present invention always provides sufficient mechanical support to prevent hernia recurrence.

[0041] (5) The porous structure of the main layer facilitates the flow of nutrients and promotes tissue repair. At the same time, its pore size is smaller than the diameter of the repair cells, so even if the smooth layer degrades, the repair cells are less likely to grow into the layer and are less likely to adhere.

[0042] (6) The hiatal hernia patch in this invention is made of biodegradable material, which is gradually absorbed by the human body, avoiding long-term foreign body residue and greatly reducing the risk of chronic inflammation or infection that may be caused by traditional non-degradable materials. In addition, this patented product is made of non-animal-derived material, has good biocompatibility, and is non-immunogenic.

[0043] (7) Regarding the prevention of adhesion, the smooth layer of the esophageal hiatal hernia repair patch of the present invention is a non-porous membrane layer with a dense structure, which can block the ingrowth of fibroblasts, muscle and vascular tissue cells, etc., and play a role in preventing adhesion, so that the patch does not adhere to the surrounding organs. Attached Figure Description

[0044] Figure 1 The diagram shows the adsorption structure of the hiatal hernia repair patch in Embodiment 1 of the present invention.

[0045] Figure 2 A schematic diagram of the structure of the hiatal hernia repair patch in Embodiment 2 of the present invention is shown.

[0046] Figure 3A schematic diagram of a mold for preparing the adsorption structure in Example 1 of the present invention is shown. A is a cross-sectional view of the mold; B is a top view of the mold.

[0047] Figure 4 A schematic diagram of mold two for preparing the adsorption structure in Example 2 of the present invention is shown. A is a cross-sectional view of mold two; B is a top view of mold two. Detailed Implementation

[0048] The following embodiments and experimental examples further illustrate the present invention and should not be construed as limiting the invention. The embodiments do not include a detailed description of conventional methods, which are well known to those skilled in the art and described in numerous publications.

[0049] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention, and the preferred embodiments and materials described in the specific implementation are for illustrative purposes only.

[0050] According to one aspect of the present invention, a hiatal hernia repair patch includes a main body layer, an adsorption structure, and a dissolution film. The adsorption structure is disposed on one side of the main body layer, and the dissolution film covers the adsorption structure. The side of the main body layer in which the adsorption structure is located is positioned to face and / or contact the tissue surrounding the hiatal hernia.

[0051] The thickness of the main body layer is 0.1~0.5mm, and the main body layer has a porous structure with a pore size ranging from 1~100 μm and a porosity of 5-20%.

[0052] The film thickness is 0.01–0.03 mm, and the film is prepared from a water-soluble material.

[0053] The height of the adsorption structure when it unfolds is 1 to 8 times the thickness of the main layer.

[0054] The hiatal hernia repair patch provided by this invention has good mechanical properties and a degradation period of 9 to 12 months, providing sufficient repair time for the tissue around the esophageal hiatus. Before the tissue repair is successful and the elasticity and strength of the newly formed tissue reach a level sufficient to resist pressure, the patch of this invention always provides sufficient mechanical support to prevent hernia recurrence.

[0055] The main body layer provides the primary mechanical support; at the same time, the porous structure of the main body layer facilitates the flow of nutrients and promotes tissue repair; the pore size range is smaller than the diameter of the repair cells, so even if there is no smooth layer or the smooth layer is degraded, the repair cells are not easy to grow into this layer and are not easy to adhere to the surrounding organs.

[0056] The hiatal hernia patch of the present invention is attached and fixed to the tissue around the hernia orifice through an adsorption structure, which can achieve fixation without sutures. It can also be used to avoid patch displacement, warping, poor adhesion to tissue and other difficulties in patch fixation during suturing operations. It can reduce the interference between surgical instruments during suturing operations, and reduce the difficulty of suturing operations and operation time.

[0057] Before the soluble membrane dissolves, it separates the adsorbed structure from the tissue, preventing the structure from being temporarily fixed to the tissue. This facilitates the movement of the hiatal hernia repair patch at the tissue contact surface, allowing the patch to flatten and move to the appropriate position. Furthermore, the soluble membrane dissolves rapidly upon contact with the water environment present in the tissue. The undissolved portion forms a gel, which helps improve the adhesion between the adsorbed structure and the tissue, aiding in patch fixation. It also forms a sealing layer around the edges of adsorbed structures such as burrs, cilia, or suction cups, preventing fluid accumulation at these edges, reducing the risk of inflammatory reactions, and further promoting tissue repair.

[0058] The thickness of the main layer is 0.1~0.5mm, specifically, but not limited to, 0.1mm, 0.2mm, 0.3mm, 0.4mm, 0.45mm, and 0.5mm;

[0059] The pore size ranges from 1 to 100 μm, and may include, but is not limited to, 1 μm, 5 μm, 7 μm, 10 μm, 20 μm, 35 μm, 50 μm, 65 μm, 75 μm, 85 μm, 90 μm, and 100 μm.

[0060] The porosity is 5-20%, specifically, but not limited to, 5%, 7%, 9%, 10%, 12%, 14%, 16%, 18%, and 20%.

[0061] The film thickness is 0.01–0.03 mm, specifically, but not limited to, 0.01 mm, 0.02 mm, and 0.03 mm;

[0062] The height of the adsorption structure when it unfolds is 1 to 8 times the thickness of the main layer, specifically, but not limited to, 1, 1.5, 3, 4, 5, 6, 7, and 8 times.

[0063] In a preferred embodiment of the present invention, the water-soluble material includes any one or more combinations of pullulan, starch, or carboxymethyl cellulose.

[0064] In addition to being able to dissolve in an aqueous environment at the tissue contact surface, the materials used to make the membrane also need to be non-toxic, have better biocompatibility, and be suitable for implantation into human tissue. Pullulan, starch, and carboxymethyl cellulose can meet these requirements, with pullulan and / or pharmaceutical-grade carboxymethyl cellulose (CMC) being preferred.

[0065] In a preferred embodiment of the present invention, the adsorption structure is a composite structure consisting of multiple burrs, multiple cilia, multiple suction cup structures, or at least two of the former three arranged in a cross pattern.

[0066] In the preferred embodiments described above, the adsorption structure is not limited to burrs, cilia, or suction cups; it can also be other shapes or structures that facilitate adsorption onto tissue. The adsorption structure, through methods such as insertion or adsorption, tightly binds the patch to the tissue, not only strengthening the fixation between the patch and the tissue but also significantly reducing the gap between them, thus lowering the likelihood of fluid accumulation and reducing the occurrence of inflammatory reactions.

[0067] In a preferred embodiment of the present invention, the outer edge diameter of the suction cup is 1.5mm-3mm, and the distance between two adjacent suction cups is 1.5-3 times the diameter of the suction cup.

[0068] The outer edge diameter of the suction cup is 1.5mm-3mm, specifically, but not limited to, 1.5mm, 1.8mm, 2mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, and 3mm; the distance between two adjacent suction cups is 1.5-3 times the diameter of the suction cup, specifically, but not limited to, 1.5 times, 1.8 times, 2 times, 2.2 times, 2.4 times, 2.6 times, 2.7 times, and 3 times.

[0069] In a preferred embodiment of the present invention, a smooth layer is further included. The smooth layer is a non-porous film layer made by casting. The smooth layer is located on the side of the main layer away from the adsorption structure and has a thickness of 0.02~0.1mm.

[0070] The smooth layer is a non-porous membrane with a dense structure that prevents the ingrowth of fibroblasts, muscle cells, and vascular tissue cells, thus preventing adhesion and ensuring that the patch does not adhere to surrounding organs. The thickness of the smooth layer is 0.02~0.1mm, specifically, but not limited to, 0.02mm, 0.04mm, 0.06mm, 0.08mm, and 0.1mm.

[0071] In a preferred embodiment of the present invention, the main body layer, the adsorption structure, and the smooth layer are prepared from biodegradable materials, including any one or more copolymers or combinations of biodegradable polyurethane, polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol, polyvinyl alcohol, polycarbonate, polyhydroxyalkanoates, PHB / PHV copolymers, polyanhydrides, polydioxanone, and bacterial cellulose.

[0072] In the preferred embodiments described above, the biodegradable material may be any one or a combination of biodegradable polyurethane (PUR), polylactic acid (PLA), polyglycolic acid (PGA, also known as polyhydroxyacetic acid), polycaprolactone (PCL), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polycarbonate (PPC), polyhydroxy fatty acid ester (PHA), polyhydroxybutyrate-hydroxyvalerate copolymer (PHB / PHV copolymer), polyanhydride, polydioxanone (PDO), and bacterial cellulose, or may be a copolymer of multiple of these materials, such as polycaprolactone (PCL)-polyethylene glycol (PEG) copolymer or polylactic acid (PLA)-polyglycolic acid (PGA) copolymer.

[0073] The aforementioned biodegradable materials, within a living organism, gradually degrade through hydrolysis, enzymatic hydrolysis, or cellular metabolism under the influence of body fluids, acids, and nucleic acids. These degradation processes lead to absorption by the body or excretion, with the implanted material ultimately being completely replaced by new tissue. The application of these biodegradable materials in the hiatal hernia patch of this invention avoids the need for secondary surgery, reducing patient suffering.

[0074] In a preferred embodiment of the present invention, the biodegradable materials used to make the adsorption structure, the smooth layer, and the main body layer are preferably copolymers of polycaprolactone and polyethylene glycol, with molecular weights of 3~18W, 20~55W, and 25~55W, respectively.

[0075] The adsorption structure preferably uses a copolymer of polycaprolactone and polyethylene glycol with a molecular weight of 3-18W, specifically, but not limited to, 3W, 5W, 7W, 10W, 12W, 14W, 16W, and 18W; the smooth layer preferably uses a copolymer of polycaprolactone and polyethylene glycol with a molecular weight of 20-55W, specifically, but not limited to, 20W, 25W, 30W, 35W, 40W, 45W, 50W, and 55W; the main body layer preferably uses a copolymer of polycaprolactone and polyethylene glycol with a molecular weight of 25-55W, specifically, but not limited to, 25W, 30W, 35W, 40W, 45W, 50W, and 55W.

[0076] According to one aspect of the present invention, a method for preparing a hiatal hernia repair patch as described above is characterized by comprising the following steps:

[0077] A. Using the aforementioned biodegradable material, prepare biodegradable material solution one and biodegradable material solution two for fabricating the main layer and adsorption structure, respectively. Use a water-soluble material to prepare a water-soluble material solution for fabricating the film.

[0078] B. The main layer is prepared using a solution of biodegradable materials through casting or electrospinning, followed by drying.

[0079] C. Prepare the adsorption structure on one side of the main layer using spinning, 3D printing, or by using a mold, and then dry it.

[0080] D. Coat the surface of the main layer with the adsorption structure with a water-soluble material solution, and dry to obtain the hiatal hernia repair patch.

[0081] In the fabrication of the main layer, a porogen is added to the biodegradable material solution one. The porogen has a particle size of 1-100 μm. The biodegradable material solution one consists of the following components by mass percentage: 10-30% biodegradable material, 3-12% porogen, and the remainder is solvent.

[0082] No pore-forming agent is added to the biodegradable material solution two.

[0083] A water-soluble material solution is a saturated solution obtained by dissolving a water-soluble material in water.

[0084] The particle size range of the porogen used in the fabrication of the main layer is 1-100μm, specifically including but not limited to 1μm, 5μm, 7μm, 10μm, 20μm, 35μm, 50μm, 65μm, 75μm, 85μm, 90μm, and 100μm.

[0085] To achieve a certain porosity in the main layer, the mass percentage of the porogen in the biodegradable material solution needs to reach a corresponding range. When fabricating the main layer, the biodegradable material solution, by mass percentage, comprises 10-30% biodegradable material (specifically, but not limited to, 10%, 12%, 15%, 18%, 20%, 22%, 25%, 28%, and 30%), and 3-12% porogen (specifically, but not limited to, 3%, 5%, 7%, 9%, 10%, 11%, and 12%).

[0086] In a preferred embodiment of the present invention, a smooth layer is further prepared on the side of the host layer away from the adsorption structure. The preparation step of the smooth layer includes:

[0087] E. Prepare a biodegradable material solution for making the smooth layer. Then, use a casting method to create the smooth layer on the other side of the main layer where no adsorption structure is present.

[0088] Preferably, the dried main body layer is placed under a coating applicator with the side not used for setting the adsorption structure facing upwards. The height of the coating applicator is adjusted, and an automatic coating machine is used to spread the biodegradable material solution on the surface of the main body layer for drying.

[0089] The hiatal hernia repair patch of the present invention comprises a main body layer, an adsorption structure, and a dissolution membrane. In a further preferred embodiment, in addition to the main body layer, the adsorption structure, and the dissolution membrane, a smooth layer is also included. Through comprehensive design of the selection of molecular weight of the biodegradable material structure, the thickness of each layer, the pore size and porosity, and the manufacturing process, the degradation cycle of the hiatal hernia repair patch is achieved in 9-12 months, the dissolution membrane dissolves during the operation, and the adsorption structure degrades slightly earlier than the smooth layer and the main body layer.

[0090] According to one aspect of the present invention, the above-described hiatal hernia repair patch or the hiatal hernia repair patch prepared by the above-described preparation method is used in the preparation of products that promote in vivo tissue repair.

[0091] The hiatal hernia repair patch of this invention can be used as a standalone product or as a complete set of devices used in hiatal hernia repair surgery.

[0092] In the following specific embodiments, the biodegradable materials used for the main body layer, adsorption structure, and smoothing layer of the esophageal hiatal hernia patch are PCL-PEG copolymers (also a type of biodegradable polyurethane) formed by the copolymerization of polycaprolactone (PCL) and polyethylene glycol (PEG), prepared according to the manufacturing method described in the embodiment of patent document CN202111122492.8. Other materials used in the embodiments can be purchased directly from the market.

[0093] The hiatal hernia patch of this invention has good biocompatibility. In particular, the hiatal hernia patch made of PCL-PEG copolymer has excellent biocompatibility. After implantation in the human body, there is no immune rejection reaction. During the process of complete degradation and absorption in the body, the degradation products are non-toxic and the pH changes little, which greatly reduces the risk of inflammation caused by hiatal hernia patch implantation. The local microenvironment is stable and conducive to tissue regeneration.

[0094] Example 1

[0095] A method for preparing a hiatal hernia repair patch, the method comprising the following steps:

[0096] 1. Preparation of solution

[0097] (1) Preparation of the first biodegradable material solution for the main layer: Grind sodium chloride (porogen) and sieve out sodium chloride particles with a size of 1-100 μm. Dissolve the biodegradable material PCL-PEG copolymer (weight average molecular weight Mw of 250 kDa) in tetrahydrofuran (THF), then add sodium chloride and stir magnetically until sodium chloride is uniformly dispersed in the solution to prepare the first biodegradable material solution. The solution consists of the following components by mass percentage: 25% biodegradable material, 10% sodium chloride, and the balance is tetrahydrofuran.

[0098] (2) Preparation of degradable material solution two for making adsorption structure: Dissolve the degradable material PCL-PEG copolymer (weight average molecular weight Mw is 180 kDa) in tetrahydrofuran (THF) to prepare degradable material solution two. This solution: 25% degradable material, the balance is tetrahydrofuran (by mass percentage).

[0099] (3) Prepare a water-soluble material solution for making a soluble film: Dissolve commercially available pharmaceutical grade carboxymethyl cellulose (CMC) in water for injection to make a saturated solution, which is the water-soluble material solution.

[0100] (4) Preparation of degradable material solution three for making the smooth layer: Dissolve the degradable material PCL-PEG copolymer (weight average molecular weight Mw is 200 kDa) in tetrahydrofuran (THF) to prepare degradable material solution two. This solution: 25% degradable material, the balance is tetrahydrofuran (by mass percentage).

[0101] 2. Create a smooth layer - main layer

[0102] Pour the biodegradable material solution onto a glass plate, place a coating applicator with the height adjusted to 0.1 mm, spread it out with an automatic coating machine, and then air dry it under a laminar flow hood.

[0103] After the smooth layer has dried and formed, the biodegradable material solution is poured onto the surface of the smooth layer, and a coating applicator with the height adjusted (0.5 mm) is placed on it. After being spread by an automatic coating machine, it is air-dried under a laminar flow hood to obtain the smooth layer-main layer.

[0104] 3. Fabrication of adsorption structures

[0105] (1) Making such Figure 3 The mold shown is called Mold 1. Using Mold 1, a burr-shaped adsorption structure can be created.

[0106] (2) Inject the biodegradable material solution into the following: Figure 3 In the mold shown, when the adsorption structure is about to dry and take shape, the smooth layer-main body layer that has been integrated is placed on it, with the side of the main body layer away from the smooth layer in contact with the mold (so that the adsorption structure is set on the main body layer). After drying and taking shape, the smooth layer-main body layer-adsorption structure connected to the mold is obtained.

[0107] (3) Soak the smooth layer-main body layer-adsorption structure connected to the mold one in water until the smooth layer-main body layer-adsorption structure is separated from the mold one;

[0108] 4. Remove impurities and dry

[0109] (1) Solvent removal: Immerse the above-mentioned smooth layer-main layer-adsorption structure in water for injection for at least 7 days, changing the water twice a day. Clean every two days until the total amount of residual solvent in the patch is ≤0.1%;

[0110] (2) Drying: Rinse the smooth layer-main layer-adsorption structure thoroughly with water for injection cooled to 30°C, and lay it flat on the rack of the drying oven. Set the oven temperature to 35°C until the residual moisture in the initial patch is ≤0.5%;

[0111] (3) Remove the rough or uneven parts at the edges of the smooth layer-main layer-adsorption structure after drying, and confirm that there are no bubbles, no damage, no foreign matter, and that the thickness is uniform.

[0112] 5. Making a film

[0113] A water-soluble material solution is coated onto the side containing the adsorption structure of the smooth layer-main layer-adsorption structure obtained in the previous step, and then air-dried under a laminar flow hood to obtain the esophageal hiatal hernia repair patch. It is then cut to the required size, packaged, and sterilized by irradiation.

[0114] Example 2

[0115] The method for preparing a hiatal hernia repair patch provided in this embodiment differs from that in Embodiment 1 in that the main body layer is prepared by electrospinning.

[0116] The preparation method includes the following steps:

[0117] 1. Preparation of solution

[0118] (1) Preparation of the first solution of biodegradable material for the main layer: Grind sodium chloride (porogen) and sieve out sodium chloride particles with a size of 1-100 μm. Dissolve the biodegradable material PCL-PEG copolymer (weight average molecular weight Mw of 250 kDa) in a mixed solution of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF), then add sodium chloride and stir until sodium chloride is uniformly dispersed in the solution to prepare the first layer electrospinning solution. The solution consists of the following components by mass percentage: 25% biodegradable material, 10% sodium chloride, and the balance is tetrahydrofuran.

[0119] Solvent ratio: Tetrahydrofuran (THF): N,N-dimethylformamide (DMF) = 1:1.

[0120] The specific preparation steps are as follows:

[0121] 1) Measure 150 mL of tetrahydrofuran and 150 mL of N,N-dimethylformamide into a three-necked flask, turn on the stirrer, adjust the speed to (200±100) r / min, and stir until homogeneous.

[0122] 2) Weigh 75g of the biodegradable material and add it to a three-necked flask. Different volumes of solution can be prepared depending on the amount of solution needed.

[0123] 3) Stir at room temperature for more than 4 hours to completely dissolve the biodegradable material.

[0124] 4) Add 30g of sodium chloride with a particle size of 1-100μm, stir with a stirrer until the sodium chloride is evenly dispersed in the solution, and prepare the first layer 1 electrospinning solution.

[0125] (2) Preparation of degradable material solution two for making adsorption structure: Dissolve the degradable material PCL-PEG copolymer (weight average molecular weight Mw is 180 kDa) in tetrahydrofuran (THF) to prepare degradable material solution two. This solution: 25% degradable material, the balance is tetrahydrofuran (by mass percentage).

[0126] (3) Prepare a water-soluble material solution for making a soluble film: Dissolve commercially available pharmaceutical grade carboxymethyl cellulose (CMC) in water for injection to make a saturated solution, which is the water-soluble material solution.

[0127] (4) Preparation of degradable material solution three for making the smooth layer: Dissolve the degradable material PCL-PEG copolymer (weight average molecular weight Mw is 200 kDa) in tetrahydrofuran (THF) to prepare degradable material solution two. This solution: 25% degradable material, the balance is tetrahydrofuran (by mass percentage).

[0128] 2. Create a smooth layer - main layer

[0129] The biodegradable material solution is poured onto a glass plate, and a coating applicator with the height adjusted to 0.1 mm is placed on it. After being spread by an automatic coating machine, the coating is air-dried under a laminar flow hood to obtain a smooth layer.

[0130] Secure the smooth layer to the receiving device of the electrospinning machine. Slowly draw up the biodegradable material solution used to make the main layer using a disposable syringe, avoiding the formation of air bubbles. If air bubbles are generated, they must be removed before proceeding to the next step. Attach a 22G needle (0.41mm inner diameter) and secure the syringe (which serves as the nozzle) to the electrospinning machine's injection pump latch. Begin electrospinning and set the electrospinning time to 4.5 hours. After this electrospinning cycle, the smooth layer-main layer is obtained and removed from the receiving device.

[0131] The parameters for electrospinning are as follows:

[0132] Adjust the distance between the nozzle and the receiver to 20±1 cm; set the receiver rotation speed to (380±100) rpm / min; set the nozzle injection speed to 0.4±0.05 ml / min; set the nozzle translation speed to 420±50 mm / min and the translation distance to 200±50 mm; set the negative voltage to (-3±1) KV and the positive voltage to (9±0.5) KV.

[0133] 4. Fabrication of adsorption structures

[0134] (1) Making such Figure 4 The second mold shown is used to create a suction cup-shaped adsorption structure.

[0135] (2) Inject the biodegradable material solution into the following: Figure 4 In the mold shown, when the adsorption structure is about to dry and take shape, the smooth layer-main body layer that has been integrated is placed on it, and the side of the main body layer away from the smooth layer contacts the mold (so that the adsorption structure is set on the main body layer). After drying and taking shape, the smooth layer-main body layer-adsorption structure connected to the mold is obtained.

[0136] (3) Soak the smooth layer-main body layer-adsorption structure connected to the mold two in water until the smooth layer-main body layer-adsorption structure is separated from the mold two;

[0137] 5. Remove impurities and dry

[0138] (1) Solvent removal: Immerse the above-mentioned smooth layer-main layer-adsorption structure in water for injection for at least 7 days, changing the water twice a day. Clean every two days until the total amount of residual solvent in the patch is ≤0.1%;

[0139] (2) Drying: Rinse the smooth layer-main layer-adsorption structure thoroughly with water for injection cooled to 30°C, and lay it flat on the rack of the drying oven. Set the oven temperature to 35°C until the residual moisture in the initial patch is ≤0.5%;

[0140] (3) Remove the rough or uneven parts at the edges of the smooth layer-main layer-adsorption structure after drying, and confirm that there are no bubbles, no damage, no foreign matter, and that the thickness is uniform.

[0141] 6. Making a film

[0142] A water-soluble material solution is coated onto the side containing the adsorption structure of the smooth layer-main layer-adsorption structure obtained in the previous step, and then air-dried under a laminar flow hood to obtain the esophageal hiatal hernia repair patch. It is then cut to the required size, packaged, and sterilized by irradiation.

[0143] Example 3

[0144] The esophageal hiatal hernia repair patch prepared in this embodiment differs from that in Example 1 in that the weight-average molecular weight of the biodegradable material PCL-PEG copolymer used in the main body layer, adsorption structure, and smoothing layer is different.

[0145] In this embodiment, the main body layer is made of PCL-PEG copolymer, a biodegradable material with a weight-average molecular weight (Mw) of 330 kDa; the adsorption structure is made of PCL-PEG copolymer, a biodegradable material with a weight-average molecular weight (Mw) of 180 kDa; and the smooth layer is made of PCL-PEG copolymer, a biodegradable material with a weight-average molecular weight (Mw) of 300 kDa.

[0146] Example 4

[0147] The esophageal hiatal hernia repair patch prepared in this embodiment differs from that in Example 1 in that the weight-average molecular weight of the biodegradable material PCL-PEG copolymer used in the main body layer, adsorption structure, and smoothing layer is different.

[0148] In this embodiment, the main body layer is made of PCL-PEG copolymer, a biodegradable material with a weight-average molecular weight (Mw) of 550 kDa; the adsorption structure is made of PCL-PEG copolymer, a biodegradable material with a weight-average molecular weight (Mw) of 30 kDa; and the smooth layer is made of PCL-PEG copolymer, a biodegradable material with a weight-average molecular weight (Mw) of 550 kDa.

[0149] Example 5

[0150] In this embodiment, only the main body layer is fabricated using a casting method. The material used to fabricate the main body layer is a biodegradable PCL-PEG copolymer with a weight-average molecular weight (Mw) of 330 kDa. The specific operation method is the same as that used for fabricating the main body layer in Example 1.

[0151] Example 6

[0152] In this embodiment, only the main body layer is fabricated using electrospinning. The material used to fabricate the main body layer is a biodegradable PCL-PEG copolymer with a weight-average molecular weight (Mw) of 330 kDa. The specific operation method is the same as that used for fabricating the main body layer in Example 2.

[0153] Test case

[0154] 1. Mechanical property testing

[0155] The hiatal hernia repair patches from Examples 1-4 and the main body layer from Examples 5-6 were cut into multiple samples of appropriate size and length.

[0156] Experimental methods:

[0157] (1) Tensile strength and elastic modulus: Turn on the tensile testing machine, set the parameters, test the tensile strength of the sample, and process the data to obtain the elastic modulus.

[0158] (2) Elongation at break: Turn on the tensile testing machine, set the parameters, test the elongation at break, and process the data; Elongation at break (%) = (Elongation at break of specimen / Original length of specimen) × 100%.

[0159] (3) Suture strength: Use the selected specification of suture thread to sew two stitches on one end of the sample to be tested and tie a knot to fix it. Suture multiple samples in the same way, and use a thickness gauge to test the thickness of each sample. Then use a tensile testing machine to clamp the sample to be tested and perform a suture strength test on the suture joint to obtain test data.

[0160] (4) Tear strength: Cut along the center of the sample with a cutter to prepare a trouser-shaped sample. The blade of the cutter must be sharp and free from burrs or nicks. The cut should be located at the center of the sample width. Use a thickness gauge to measure three points in the tear zone of the sample, and the arithmetic mean of these measurements is the thickness. Turn on the tensile testing machine, clamp the sample to be tested, and perform the tear strength test to obtain the test data.

[0161] (5) Bursting strength: Multiple square specimens are tested for thickness using a thickness gauge. Then, the tensile testing machine is turned on, the specimens to be tested are clamped, and the bursting strength test is performed to obtain the test data.

[0162] The experimental results are shown in Table 1 below.

[0163] Table 1. Summary of Mechanical Property Tests for Examples 1-6

[0164]

[0165] As can be seen from the above results, the tensile strength of the hiatal hernia repair patch in the embodiments of the present invention reaches 35.53 N / cm or above, the elastic modulus reaches 327.33 MPa or above, the elongation at break reaches 803.62% or above, the suture strength reaches 22.96 N or above, the tear strength reaches 45.74 N or above, and the burst strength reaches 403.34 kPa or above; the tensile strength of the main body layer in the embodiments of the present invention reaches 36.65 N / cm or above, the elastic modulus reaches 332.37 MPa or above, the elongation at break reaches 836.41% or above, the suture strength reaches 24.35 N or above, the tear strength reaches 48.55 N or above, and the burst strength reaches 435.11 kPa or above.

[0166] The mechanical strength of the hiatal hernia repair patch of this invention can well meet the mechanical performance requirements of the patch during the hiatal hernia repair process. At the same time, the main body layer of this invention has good mechanical properties; even in the absence of a smooth layer or when the smooth layer has degraded, the main body layer can still meet the mechanical support strength required during the hiatal hernia repair process.

[0167] Meanwhile, the esophageal hiatus hernia repair patch prepared by this invention has an elastic modulus of 327.33 MPa or higher. The esophageal hiatus hernia repair patch is soft and elastic, which can greatly reduce tissue damage during implantation, reduce patient discomfort, and improve patient acceptance. The rupture strength of the esophageal hiatus hernia repair patch prepared by this invention reaches 403.34 kPa or higher, which can fully withstand the physiological pressure and mechanical stress (such as abdominal pressure and tissue traction) during the esophageal hiatus hernia repair process.

[0168] 2. Degradation experiment

[0169] Experimental methods:

[0170] (1) Preparation of enzyme buffer:

[0171] Prepare a solution containing potassium dihydrogen phosphate and disodium hydrogen phosphate using sterile double-distilled water, with each liter of buffer containing 1.653 g KH₂PO₄ and 7.744 g NaH₂PO₄. The pH of this buffer solution should be 7.4 ± 0.2. After sterilization, add 0.2 g / L lipase. All salts used in the preparation are of analytical grade and dried to constant weight.

[0172] (2) Degradation test:

[0173] The hiatal hernia repair patches from Examples 1-4 and the main body layers from Examples 5-6 were cut into multiple samples of appropriate size and vacuum-dried to constant weight at room temperature. The weight of each sample was accurately measured. Each sample was placed in a glass container, covered with enzyme buffer, and the container was sealed. The minimum volume of the buffer should be 10 mL, and the ratio of buffer volume (mL) to sample mass (g) should be greater than or equal to 30:1. The samples were maintained at 37±1℃ using a constant temperature water bath or oven.

[0174] (3) Determination of degradation cycle:

[0175] Degradation tests were conducted at weeks 38, 39, 41, 42, 51, and 52 for mechanical property testing.

[0176] After wiping the sample surface dry with a paper towel, place the sample into the tensile testing machine fixture and conduct the test directly. Set the test rate to 50 mm / min. The test will be terminated when the sample can no longer be tested for mechanical properties; the point at which the test stops is the sample's degradation cycle.

[0177] Experimental results:

[0178] Table 2. Summary of Degradation Time

[0179]

[0180] As can be seen from the above data, the hiatal hernia repair mesh prepared in the various embodiments of the present invention completely degrades in 39-52 weeks, providing sufficient repair time for hiatal hernia repair. Simultaneously, it ensures that the hiatal hernia repair mesh provides sufficient mechanical support during hiatal hernia repair, preventing premature degradation that could affect the repair process, and gradually degrades after complete repair without causing additional discomfort or risk to the patient.

[0181] 3. Cell proliferation experiment

[0182] Experimental methods:

[0183] The main layer in Examples 5 and 6 was made into a 48-hole plate with a bottom area of ​​1 cm using a punch. 2 The circular samples were sterilized by irradiation at 25 KGy, and then each sample was immersed in MEM medium containing 10% FBS at 37°C and 60 rpm for 24 h.

[0184] The entire procedure was performed in a clean bench to ensure aseptic operation. Mouse fibroblasts L-929 cells grown to the logarithmic growth phase were digested with 0.25% trypsin (containing EDTA). After digestion, the cell suspension was centrifuged (1000 rpm, 5 min), the supernatant was discarded, and the cells were resuspended in MEM medium. Cells were counted to obtain 5 × 10⁶ cells per cell. 4 Prepare a cell suspension of cells / mL; spread each soaked sample evenly in a 48-well plate, and perform three parallel operations on each group.

[0185] 5×10 4 Cell suspension of 300 μL per well was seeded into two other 48-well plates. The same procedure was performed on two other 48-well plates, and the plates were cultured in a cell culture incubator (37°C, 5% CO2, >90% humidity).

[0186] After 24 hours, 3 days, and 6 days, the original culture medium in the 48-well plates was discarded. 100 μL of MTT (final concentration 1 mg / mL) was added to the corresponding wells of each 48-well plate, and the plates were incubated in a CO2 incubator. After 2 hours, the supernatant was removed, and 200 μL of isopropanol was added to each well to dissolve the crystals. After the crystals were completely dissolved, the samples were removed, and the liquid in each well was transferred to a 96-well plate, 100 μL per well. The absorbance value at 570 nm was measured on a microplate reader, and the OD value was compared with that of the blank group to determine whether the cells had a proliferation effect on the material surface, and the cell proliferation rate was calculated.

[0187] The specific test results are shown in Table 3 below:

[0188] Table 3. Results of cell proliferation experiment

[0189]

[0190] As can be seen from the above data, the main body layer prepared in the embodiments of the present invention has a good cell proliferation rate effect.

[0191] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

Claims

1. A patch for repairing hiatal hernia, characterized in that, The system comprises a main body layer, an adsorption structure, a solvent film, and a smooth layer. The adsorption structure is disposed on one side of the main body layer, and the solvent film covers the adsorption structure. The side of the main body layer containing the adsorption structure is positioned to face and / or contact the tissue surrounding the hiatal hernia. The thickness of the main body layer is 0.1~0.5mm, and the main body layer has a porous structure with a pore size ranging from 1~100μm and a porosity of 5-20%. The film thickness is 0.01–0.03 mm, and the film is prepared from a water-soluble material, which includes any one or more combinations of pullulan, starch, or carboxymethyl cellulose. The height of the adsorption structure when it unfolds is 1 to 8 times the thickness of the main body layer. The adsorption structure can be a composite structure consisting of multiple suction cups, multiple suction cups and multiple burrs arranged in a cross pattern, multiple suction cups and multiple cilia arranged in a cross pattern, or a composite structure consisting of multiple suction cups, multiple burrs and multiple cilia arranged in a cross pattern. The outer edge diameter of the suction cup is 1.5mm-3mm, and the spacing between two adjacent suction cups is 1.5-3 times the diameter of the suction cup. The smooth layer is a non-porous film layer produced by a casting method. The smooth layer is located on the side of the main layer away from the adsorption structure, and its thickness is 0.02~0.1mm. The adsorption structure, smooth layer, and main body layer are all prepared from biodegradable materials, all of which are copolymers of polycaprolactone and polyethylene glycol with weight-average molecular weights of 30-180 kDa, 200-550 kDa, and 250-550 kDa, respectively. The degradation period of the hiatal hernia repair patch is 9 to 12 months.

2. The method for preparing the hiatal hernia repair patch according to claim 1, characterized in that, Includes the following steps: A. Using the aforementioned biodegradable material, prepare biodegradable material solution one and biodegradable material solution two for fabricating the main layer and adsorption structure, respectively. Use a water-soluble material to prepare a water-soluble material solution for fabricating the film. The first biodegradable material solution contains a porogen with a particle size of 1-100 μm. The first biodegradable material solution, by mass percentage, consists of: 10-30% biodegradable material and 3-12% porogen, with the remainder being solvent. The second biodegradable material solution does not contain a porogen. The water-soluble material solution is a saturated solution obtained by dissolving the water-soluble material in water. B. The main layer is prepared using a solution of biodegradable materials through casting or electrospinning, followed by drying. C. Prepare the adsorption structure on one side of the main layer using spinning, 3D printing, or by using a mold, and then dry it. D. Coat the surface of the main layer with the adsorption structure with a water-soluble material solution, and then dry. The process also includes preparing a smooth layer, which is prepared on the side of the host layer away from the adsorption structure. The preparation steps of the smooth layer include: E. Prepare a biodegradable material solution for making the smooth layer. Then, use a casting method to create the smooth layer on the other side of the main layer where no adsorption structure is present. The dried main body layer is placed under the coating applicator with the side not used for setting the adsorption structure facing upwards. The height of the coating applicator is adjusted, and the biodegradable material solution is spread on the surface of the main body layer using an automatic coating machine. After drying, the esophageal hiatal hernia repair patch is obtained.

3. The application of the hiatal hernia repair patch according to claim 1 or the hiatal hernia repair patch prepared by the preparation method according to claim 2 in the preparation of products that promote in vivo tissue repair.

Images