Esophageal hiatus hernia repair patch as well as preparation method and application thereof

Abstract

The invention provides an esophageal hiatus hernia repair patch as well as a preparation method and application thereof. The hiatus hernia repair patch comprises a main body layer, an adsorption structure, a dissolving film and a smooth layer, the adsorption structure is arranged on one side of the main body layer, and the dissolving film covers the adsorption structure and the side, where the adsorption structure is located, of the main body layer and is used for facing and / or making contact with hiatus hernia peripheral tissue. The adsorption structure, the main body layer and the smooth layer are all prepared from biodegradable materials; and the soluble film is prepared from a water-fast-dissolving material. The hiatus hernia repair patch disclosed by the invention is easy to flatten and fix in an operation, is not easy to adhere to other visceral organs in vivo, has a degradation period meeting clinical requirements, and is good in biocompatibility and excellent in mechanical property.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical biomaterials, and relates to esophageal hiatus hernia repair, in particular to a degradable esophageal hiatus hernia repair patch, a preparation method and application thereof. BACKGROUND

[0002] Esophageal hiatus hernia is a disease of normal tissue structure variation, which refers to the upward displacement of the stomach or other organs into the thoracic cavity through the diaphragmatic hiatus. With the deepening of the pathophysiological cognition of esophageal hiatus hernia disease, the surgical method is also constantly improved. Previous studies have found that the postoperative recurrence rate is high for esophageal hiatus hernia only with diaphragmatic muscle suture reinforcement. In laparoscopic esophageal hiatus hernia repair, the recurrence rate of esophageal hiatus hernia is 30% in the short term, and the long-term follow-up recurrence rate is 66% in patients without patch placement. Esophageal hiatus hernia patch is more and more widely used in esophageal hiatus hernia surgery. In the repair of esophageal hiatus hernia, the principle of tension-free repair is followed, and the esophageal hiatus hernia patch can reduce the tension during repair and reduce the mechanical disturbance of the diaphragm. When the tissue is subjected to tension caused by coughing, force, vomiting and obesity, the patch can provide support.

[0003] The first generation of surgical patches is mainly made of non-degradable materials, such as pp and polytetrafluoroethylene (PTFE), which are biologically inert and designed to produce a verified response, resulting in fibrosis and scar formation, and can be divided into three types according to the hole type, large hole, microporous, and large hole with multifilament. With the application of non-degradable synthetic patches such as polypropylene patches, the recurrence rate of esophageal hiatus hernia has been significantly reduced, but complications such as dysphagia, patch erosion, fibrosis, esophageal erosion and stenosis, patch extrusion, intestinal erosion, gastrointestinal fistula, patch infection, etc. began to appear. In addition to the possible occurrence of the above complications, non-degradable synthetic patches also have many disadvantages, such as poor tissue compatibility, and easy internal organ adhesion with adjacent organs.

[0004] The second generation of surgical patches is made of non-degradable biological materials, such as medical-grade PP, polyester and e-PTFE, but at the same time, a coating is covered on the surface of the non-degradable biological material to increase biocompatibility, reduce inflammatory response, mesh contraction and patch adhesion.

[0005] The third generation of surgical patch is a degradable patch. The biodegradable patch can reduce the recurrence of esophageal hiatal hernia and reduce the incidence of serious complications related to the patch. Most of the recurrence of esophageal hiatal hernia using degradable patch is small and the patient has no obvious symptoms, and the reoperation rate is very low. The difficulty of degradable patch is that the structural integrity changes with the absorption and degradation of the patch, and the effectiveness and safety of different materials are questioned. The commonly used Bio-A™ patch is completely degraded in about 7 months. The degradation rate of the degradable patch is too fast, which can cause the elasticity and strength of the newly built tissue to be low and prone to recurrence. At the same time, the existing degradable patch also has the disadvantages of high cost and poor biomechanical strength.

[0006] In addition, since the esophageal hiatus is surrounded by important organs such as liver lobes, spleen, and pericardium, and there are blood vessels such as abdominal aorta in the deep tissue, there is a great risk of suture fixation; the space for placing the esophageal hiatal hernia patch during surgery is extremely small, making it extremely difficult to flatten and fix the esophageal hiatal hernia patch, which requires a long operation time and high requirements for the operator. If the patch is attached to the surface of the diaphragm muscle and not flattened well, a gap between the tissue can easily cause fluid accumulation, which can further cause postoperative inflammation. If there is an esophageal hiatal hernia patch that can be easily flattened and fixed during surgery, the operation time will be greatly shortened, and the patient will have a better prognosis. SUMMARY

[0007] In view of the deficiencies of the prior art and actual needs, the purpose of the present application is to provide an esophageal hiatal hernia repair patch that can be easily flattened and fixed during surgery, is not easily adhered to other organs in the body, has a degradation period that meets clinical needs, good biocompatibility, and good mechanical properties.

[0008] Another purpose of the present application is to provide a preparation method for the esophageal hiatal hernia repair patch.

[0009] Another purpose of the present application is to provide the use of the esophageal hiatal hernia repair patch or the esophageal hiatal hernia repair patch prepared by the preparation method in the preparation of a product for promoting tissue repair in the body.

[0010] In order to achieve the above purpose, the present application improves the structure of the existing patch, as follows:

[0011] (1) In order to make the patch easy to adsorb and fix during surgery and not easy to slip off, an adsorption structure is designed, which is directly fixed around the hiatal hernia, so that the suture operation can be avoided, or the difficulty of patch fixation such as patch displacement, warping, and poor adhesion to the tissue during the suture operation can be avoided, and the mutual interference of surgical instruments during the suture operation is reduced, thereby reducing the difficulty of suture operation and the operation time.

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

[0013] (3) In order to make the patch not easy to adhere to other organs, a smooth layer is made, which is a non-porous film layer directly made by a flow casting method of degradable biological materials, and the anti-adhesion effect is remarkable.

[0014] (4) In order to make the degradation period of the patch meet the clinical needs, the degradation speed will not be too fast, and before the tissue repair is successful and the elasticity and strength of the new tissue reach enough resistance to the pressure in the abdominal cavity, the patch can always provide sufficient mechanical support. Through the selection of the material of the main layer, the molecular weight of the material, the internal molecular structure of the material, combined with the design and control of the thickness, pore size and porosity of the layer, the degradation period of the esophageal hiatus hernia patch of the present application is 9-12 months.

[0015] Based on this, the technical scheme of the present application is as follows:

[0016] In a first aspect, the present application provides an esophageal hiatus hernia repair patch, comprising a main layer, an adsorption structure and a dissolving film, the adsorption structure is arranged on one side of the main layer, the dissolving film covers the adsorption structure, the side of the main layer where the adsorption structure is located is used to face and / or contact the tissue around the hiatus hernia, the thickness of the main layer is 0.1-0.5mm, the main layer is a porous structure, the pore size range is 1-100μm, and the porosity is 5-20%, the thickness of the dissolving film is 0.01-0.03mm, the dissolving film is made of a water-soluble material, and the height of the adsorption structure when it is unfolded is 1-8 times the thickness of the main layer.

[0017] Further, the water-soluble material includes any one or a combination of pullulan, starch or carboxymethyl cellulose.

[0018] Further, the water-soluble material includes any one or a combination of pullulan, starch or carboxymethyl cellulose.

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

[0020] Further, the esophageal hiatus hernia repair patch provided by the present application further comprises a smooth layer, which is a non-porous film layer made by a flow casting method, and the smooth layer is located on the other side of the main layer away from the adsorption structure, and the thickness is 0.02-0.1mm.

[0021] Further, the body layer, the adsorption structure and the smooth layer are prepared from a degradable material. The degradable material includes any one or more of copolymerization or combination of degradable polyurethane, polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol, polyvinyl alcohol, polycarbonate, polyhydroxyalkanoate, PHB / PHV copolymer, polyanhydride, poly-p-dioxanone and bacterial cellulose.

[0022] Preferably, the degradable material used to make the adsorption structure, the smooth layer and the body layer is preferably a polycaprolactone and polyethylene glycol copolymer, with molecular weights of 3-18W, 20-55W and 25-55W, respectively.

[0023] In a second aspect, the present application provides a method for preparing an esophageal hiatus hernia repair patch as described in the first aspect, comprising the following steps:

[0024] A. Using the degradable material to prepare a degradable material solution I and a degradable material solution II for making the body layer and the adsorption structure, respectively, using a water-soluble material to prepare a water-soluble material solution for making the film,

[0025] B. Using a casting method or an electrospinning method, using the degradable material solution I to make the body layer, and drying,

[0026] C. Using a spinning method, a 3D printing method or a mold to prepare the adsorption structure on one side of the body layer, and drying,

[0027] D. Coating the water-soluble material solution on the surface of the body layer with the adsorption structure, and drying to obtain an esophageal hiatus hernia repair patch,

[0028] Wherein, when making the body layer, the degradable material solution I is added with a pore-forming agent, the particle size of the pore-forming agent is 1-100 μm, and the degradable material solution I is composed of the following components by mass percentage: 10-30% of the degradable material and 3-12% of the pore-forming agent, with the balance being a solvent,

[0029] The degradable material solution II does not add a pore-forming agent,

[0030] The water-soluble material solution is a saturated solution prepared by dissolving the water-soluble material in water.

[0031] Further, it further includes preparing a smooth layer, which is prepared on the other side of the body layer away from the adsorption structure, and the preparation steps of the smooth layer include:

[0032] E. Preparing a degradable material solution III for making the smooth layer, and using a casting method to make the smooth layer on the other side of the body layer without the adsorption structure,

[0033] Preferably, the main body layer after drying is placed under a film coater with the side not provided with the adsorption structure facing upward, the height of the film coater is adjusted, and the solution of the degradable material is pushed out on the surface of the main body layer by an automatic film coater, and dried.

[0034] In a third aspect, the present application provides use of the hiatal hernia repair patch according to the first aspect or prepared by the method according to the second aspect in the preparation of a product for promoting tissue repair in vivo.

[0035] Compared with the prior art, the patch of the present application has the following advantages:

[0036] (1) The esophageal hiatus patch of the present application is attached and fixed to the tissue around the hernia hole through the adsorption structure such as the burr, cilium or suction cup, so that the seamless fixation of the patch can be realized, or the difficulty in fixation of the patch such as displacement, warping, poor adhesion to the tissue and the like during the suturing operation can be avoided, and the problems of the prior art such as the encirclement of the organs around the hiatus, the inconvenience and high risk of the suturing fixation operation are solved. In addition, compared with the suturing operation, the fixation mode of piercing or adsorption helps to improve the tightness between the patch and the tissue, and helps to reduce the probability of fluid accumulation and the incidence of postoperative inflammatory reaction.

[0037] (2) The adsorption structure provided on the esophageal hiatus repair patch of the present application is convenient for fixing the patch on the tissue after the patch is unfolded at the tissue repair site and is not easy to slip off. The surface of the dissolving film outside the adsorption structure is smooth, which is easy to move on the tissue contact surface, so that the patch will not hinder the unfolding and moving of the patch during the operation because of the initial adsorption and fixation of the adsorption structure, and further affect the placement of the patch to the appropriate position. The dissolving film is convenient for folding the patch into the tissue repair site and easy to unfold the patch on the tissue surface. The dissolving film dissolves rapidly after the patch is unfolded, for example, it can be dissolved after being pressed on the tissue surface for more than 15 seconds, and the adsorption structure is exposed. The dissolving film dissolves rapidly due to the water environment in the tissue, and the part not completely dissolved forms a gel. The gel helps to improve the adhesion between the adsorption structure and the tissue, is beneficial to the fixation of the patch, and can form a sealing ring layer around the edge of the adsorption structure such as the burr, cilium or suction cup, prevent the accumulation of fluid in the gap between the edges of the adsorption structure, reduce the risk of inflammatory reaction, and promote tissue repair.

[0038] (3) The esophageal hiatus repair patch can provide sufficient mechanical support required in the esophageal hiatus repair process, wherein the main layer plays a main mechanical support role. The tensile strength of the esophageal hiatus repair patch reaches 35.53 N / cm or more, the elastic modulus reaches 327.33 Mpa or more, the elongation at break reaches 803.62% or more, the suture strength reaches 22.96 N or more, the tear strength reaches 45.74 N or more, the bursting strength reaches 403.34 kPa or more, the mechanical properties are excellent, the pressure resistance is strong, and it is helpful to resist the complex environment in the human body. In particular, the esophageal hiatus repair patch prepared by the application has an elastic modulus of 327.33 Mpa or more, good elasticity and softness, can greatly reduce the damage to the tissue during implantation, can also reduce the discomfort of the patient, and improve the acceptance of the patient. The bursting strength reaches 403.34 kPa or more, and can completely withstand the physiological pressure and mechanical stress (such as abdominal pressure and tissue pulling force) in the esophageal hiatus repair process.

[0039] (4) The degradation period of the esophageal hiatus repair patch is 9 months to 12 months, which provides sufficient repair time for tissue repair. Before the elasticity and strength of the new tissue reach enough to resist pressure, the patch always provides sufficient mechanical support to prevent hernia recurrence.

[0040] (5) The porous structure of the main layer is beneficial to the flow of nutrients and the repair of tissues. At the same time, the pore size of the main layer is smaller than the diameter of the repair cells, so that even if the smooth layer degrades, the repair cells cannot easily grow into the main layer, and adhesion is not easy to occur.

[0041] (6) The esophageal hiatus repair patch in the application is made of biodegradable material, which is gradually absorbed by the human body, avoids long-term foreign body residue, and greatly reduces the risk of chronic inflammation or infection that may be caused by traditional non-degradable materials. And the product of the patent is made of non-animal source material, has good biocompatibility and no immunogenicity.

[0042] (7) In terms of anti-adhesion, the smooth layer of the esophageal hiatus repair patch is a non-porous membrane layer, which has a dense structure and can block the growth of fibroblasts, muscle and vascular tissue cells, etc., thereby playing an anti-adhesion role and preventing the patch from adhering to the surrounding organs. BRIEF DESCRIPTION OF DRAWINGS

[0043] Figure 1 The adsorption structure diagram of the esophageal hiatus repair patch in Example 1 of the application is shown.

[0044] Figure 2 The structure diagram of the esophageal hiatus repair patch in Example 2 of the application is shown.

[0045] 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.

[0046] Figure 4 The figure shows a schematic diagram of the second mold for preparing the adsorption structure in Example 2 of the present invention. A is a cross-sectional view of the second mold; B is a top view of the second mold. DETAILED DESCRIPTION

[0047] The following examples and experimental examples further illustrate the present invention and should not be construed as limiting the present invention. The examples do not include detailed descriptions of conventional methods, which are well known to those skilled in the art and are described in numerous publications.

[0048] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention, and the preferred implementation methods and materials described in the specific embodiments are for illustrative purposes only.

[0049] According to one aspect of the present invention, a hiatal hernia repair patch comprises a main body layer, an adsorption structure, and a dissolving film, wherein the adsorption structure is arranged on one side of the main body layer, the dissolving film covers the adsorption structure, and the side of the main body layer where the adsorption structure is located is used to face and / or contact the surrounding tissue of the hiatal hernia.

[0050] The thickness of the main layer is 0.1-0.5 mm, and the main layer is a porous structure with a pore size range of 1-100 μm and a porosity of 5-20%;

[0051] The thickness of the dissolving film is 0.01 to 0.03 mm, and the dissolving film is made of a material that dissolves quickly in water;

[0052] The height of the adsorption structure when unfolded is 1 to 8 times the thickness of the main body layer.

[0053] The hiatal hernia repair patch provided by the present invention has good mechanical properties and a degradation period of 9 to 12 months, which provides sufficient repair time for the tissue around the esophageal hiatus. Before the tissue is successfully repaired and the elasticity and strength of the new tissue reach sufficient resistance to pressure, the patch of the present invention always provides sufficient mechanical support to prevent hernia recurrence.

[0054] The main layer plays a major role in mechanical support; at the same time, the porous structure of the main layer facilitates the flow of nutrients and is beneficial to tissue repair; the pore size range is smaller than the diameter of the repair cells. Even if there is no smooth layer or the smooth layer is degraded, it is not easy for the repair cells to grow into this layer and not easy to adhere to the surrounding organs.

[0055] The esophageal hiatus hernia patch of the present application is attached and fixed to the tissue around the hernia hole through the adsorption structure, and can be fixed without suturing. Of course, it can also be used to avoid the displacement, warping and poor fitting of the patch during the suturing operation, reduce the mutual interference of surgical instruments during the suturing operation, and reduce the difficulty of the suturing operation and the operation time.

[0056] Before the dissolving film is dissolved, the dissolving film separates the adsorption structure from the tissue, so that the adsorption structure is temporarily not fixed to the tissue, facilitating the movement of the esophageal hiatus hernia repair patch on the tissue contact surface, so as to flatten the patch and move it to a suitable position. In addition, the dissolving film dissolves quickly in the water environment existing in the tissue, and the part that has not completely dissolved forms a gel. The gel helps to improve the adhesion between the adsorption structure and the tissue, facilitates the fixation of the patch, and forms a sealing ring layer around the edges of the adsorption structure such as burrs, cilia or suction cups, prevents the accumulation of fluid in the gap between the edges of the adsorption structure, reduces the risk of inflammation, and further promotes tissue repair.

[0057] The thickness of the main layer is 0.1-0.5mm, and specifically can be but is not limited to 0.1mm, 0.2mm, 0.3mm, 0.4mm, 0.45mm, 0.5mm;

[0058] The pore size is 1-100 μm, and specifically can be 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, 100 μm;

[0059] The porosity is 5-20%, and specifically can be but is not limited to 5%, 7%, 9%, 10%, 12%, 14%, 16%, 18%, 20%;

[0060] The thickness of the dissolving film is 0.01-0.03mm, and specifically can be but is not limited to 0.01mm, 0.02mm, 0.03mm;

[0061] The height of the adsorption structure when it is unfolded is 1-8 times the thickness of the main layer, and specifically can be but is not limited to 1 times, 1.5 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times.

[0062] In a preferred embodiment of the present application, the water-soluble material includes any one or a combination of pullulan, starch or carboxymethyl cellulose.

[0063] In addition to the need to be dissolved in the water environment on the tissue contact surface, the material for making the dissolving film also needs to be non-toxic and have better biocompatibility, and be suitable for implantation into human tissues. Pullulan, starch and carboxymethyl cellulose can meet the requirements, and pullulan and / or pharmaceutical-grade carboxymethyl cellulose (CMC) are more preferred.

[0064] In a preferred embodiment of the present application, the adsorption structure is a plurality of burrs, a plurality of cilia, a plurality of suction disc structures, or a composite structure of at least two of the above.

[0065] In the above preferred embodiment, the adsorption structure is not limited to burrs, cilia or suction disc structures, but can also be other shape structures that can facilitate adsorption on the tissue. The adsorption structure fixes the patch and the tissue by piercing or adsorption, etc., to tightly combine the patch and the tissue, thereby not only strengthening the fixation between the patch and the tissue, but also greatly reducing the gap space between the patch and the tissue, reducing the probability of fluid accumulation, and reducing the occurrence of inflammatory reactions.

[0066] In a preferred embodiment of the present application, the outer edge diameter of the suction disc is 1.5-3 mm, and the spacing between adjacent two suction discs is 1.5-3 times the diameter of the suction disc.

[0067] In the preferred embodiment of the present application, the outer edge diameter of the suction disc is 1.5-3 mm, and the spacing between adjacent two suction discs is 1.5-3 times the diameter of the suction disc.

[0068] In a preferred embodiment of the present application, a smooth layer is further included, the smooth layer is a non-porous membrane layer made by a flow casting method, and the smooth layer is located on the other side of the main body layer away from the adsorption structure, and has a thickness of 0.02-0.1 mm.

[0069] The smooth layer is a non-porous membrane layer, which has a dense structure and can block the growth of fibroblasts, muscle and vascular tissue cells, etc., thereby preventing adhesion and preventing the patch from adhering to the surrounding organs. The thickness of the smooth layer is 0.02-0.1 mm, and can be but is not limited to 0.02 mm, 0.04 mm, 0.06 mm, 0.08 mm or 0.1 mm.

[0070] In a preferred embodiment of the present application, the main body layer, the adsorption structure and the smooth layer are prepared from a degradable material, and the degradable material includes any one or a combination of degradable polyurethane, polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol, polyvinyl alcohol, polycarbonate, polyhydroxyalkanoate, PHB / PHV copolymer, polyanhydride, poly-p-dioxanone and bacterial cellulose, etc.

[0071] In the above preferred embodiment, the degradable material can be any one or a combination of more than one of degradable polyurethane (PUR), polylactic acid (PLA), polyglycolic acid (PGA, also known as polyglycolic acid), polycaprolactone (PCL), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polycarbonate (PPC), polyhydroxyalkanoate (PHA), polyhydroxybutyrate-hydroxyvalerate copolymer (PHB / PHV copolymer), polyanhydride, polydioxanone (PDO), bacterial cellulose, etc., and can also be a copolymer of a plurality of the above, such as polycaprolactone (PCL)-polyethylene glycol (PEG) copolymer, polylactic acid (PLA)-polyglycolic acid (PGA) copolymer.

[0072] The above degradable material is gradually degraded in the biological body under the action of body fluids, acids, nucleic acids, etc., through hydrolysis, enzymatic degradation or cell metabolism, etc., and is continuously degraded and absorbed by the body, or is discharged out of the body, and finally the implanted material is completely replaced by new tissue. The above degradable material is used to manufacture the esophageal hiatus hernia patch of the application, which can avoid secondary surgery and reduce the pain of the patient.

[0073] In a preferred embodiment of the application, the degradable material used to make the adsorption structure, the smooth layer and the main body layer is preferably a polycaprolactone-polyethylene glycol copolymer, and the molecular weight is 3-18W, 20-55W and 25-55W, respectively.

[0074] Specifically, the molecular weight of the polycaprolactone-polyethylene glycol copolymer used for the adsorption structure is 3W, 5W, 7W, 10W, 12W, 14W, 16W or 18W, but is not limited to these values; the molecular weight of the polycaprolactone-polyethylene glycol copolymer used for the smooth layer is 20W, 25W, 30W, 35W, 40W, 45W, 50W or 55W, but is not limited to these values; and the molecular weight of the polycaprolactone-polyethylene glycol copolymer used for the main body layer is 25W, 30W, 35W, 40W, 45W, 50W or 55W, but is not limited to these values.

[0075] According to one aspect of the application, a preparation method of the esophageal hiatus hernia repair patch is characterized by comprising the following steps:

[0076] A. The degradable material is used to prepare a degradable material solution one for making the main body layer and a degradable material solution two for making the adsorption structure, and a water-soluble material solution for making the dissolving film is prepared by using a water-soluble material;

[0077] B. The degradable material solution one is used to make the main body layer by using a flow casting method or an electrospinning method, and the main body layer is dried;

[0078] C. Preparing the adsorption structure on one side of the main layer by a spinning method, a 3D printing method or using a mold, and drying;

[0079] D. Coating the water-fast dissolving material solution on the surface of the main layer provided with the adsorption structure, and drying to obtain the esophageal hiatus repair patch.

[0080] In the preparation of the main layer, the porogen is added in the degradable material solution I, the particle size of the porogen is 1-100 μm, and the degradable material solution I consists of 10-30% of degradable material and 3-12% of porogen by mass percentage, and the balance is solvent;

[0081] The degradable material solution II does not add the porogen;

[0082] The water-fast dissolving material solution is a saturated solution prepared by dissolving the water-fast dissolving material in water.

[0083] The particle size of the porogen used in the preparation of the main layer ranges from 1-100 μm, and specifically can be 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.

[0084] In order for the porosity of the main layer to reach a certain range, the mass percentage of the porogen in the degradable material solution needs to reach a corresponding range. In the preparation of the main layer, the degradable material solution by mass percentage, the degradable material accounts for 10-30%, specifically can be but is not limited to 10%, 12%, 15%, 18%, 20%, 22%, 25%, 28%, and 30%, and the porogen accounts for 3-12%, specifically can be but is not limited to 3%, 5%, 7%, 9%, 10%, 11%, and 12%.

[0085] In a preferred embodiment of the present application, a smooth layer is also prepared, which is prepared on the other side of the main layer away from the adsorption structure, and the preparation steps of the smooth layer include:

[0086] E. Preparing the degradable material solution III for preparing the smooth layer, and preparing the smooth layer on the other side of the main layer not provided with the adsorption structure by a casting method,

[0087] Preferably, the dried main layer is placed under a film coater with the side not provided with the adsorption structure upward, the height of the film coater is adjusted, and the degradable material solution III is pushed away on the surface of the main layer by an automatic film coater, and dried.

[0088] The esophageal hiatus hernia repair patch of the present application comprises a main body layer, an adsorption structure, and a dissolving film. In a further preferred embodiment, in addition to the main body layer, the adsorption structure, and the dissolving film, there is also a smooth layer. Through comprehensive design of the molecular weight of the degradable material structure, the thickness of each layer, the pore size and porosity, and the manufacturing process, the degradation period of the esophageal hiatus hernia repair patch is achieved to be 9-12 months, the dissolving film is dissolved during the operation process, and the adsorption structure degrades slightly earlier than the smooth layer and the main body layer.

[0089] According to one aspect of the present application, the esophageal hiatus hernia repair patch or the esophageal hiatus hernia repair patch prepared by the above preparation method is used in the preparation of a product for promoting tissue repair in the body.

[0090] The esophageal hiatus hernia repair patch in the present application can be used as an independent product alone, or can be used as a complete product in a set with other devices used in esophageal hiatus hernia repair surgery.

[0091] In the following specific examples, the degradable material used to make the main body layer, the adsorption structure, and the smooth layer of the esophageal hiatus hernia repair patch is PCL-PEG copolymer (also a kind of degradable polyurethane) made by copolymerization of polycaprolactone (PCL) and polyethylene glycol (PEG). The preparation method is referred to the preparation method in the example of patent document CN202111122492.8. Other materials used in the examples can be directly purchased from the market.

[0092] The esophageal hiatus hernia repair patch of the present application has good biocompatibility, especially the esophageal hiatus hernia repair patch made of PCL-PEG copolymer, which has excellent biocompatibility, no immune rejection reaction after implantation into the human body, no toxicity of degradation products, small pH change, greatly reducing the risk of inflammation caused by esophageal hiatus hernia repair patch implantation, stable local microenvironment, and conducive to tissue regeneration.

[0093] Example 1

[0094] A preparation method of an esophageal hiatus hernia repair patch, the preparation method comprising the following steps:

[0095] 1. Preparation of solution

[0096] (1) Preparation of degradable material solution one for making the main body layer: grind sodium chloride (porogen), and sieve out sodium chloride particles with a particle size of 1-100 μm with a sieve. Dissolve the degradable material PCL-PEG copolymer (weight average molecular weight Mw is 250 kDa) in tetrahydrofuran (THF), then add sodium chloride, and magnetically stir until the sodium chloride is uniformly dispersed in the solution to prepare the degradable material solution one. The solution consists of the following components by mass percentage: degradable material 25%, sodium chloride 10%, and the balance is tetrahydrofuran.

[0097] (2) Preparation of a degradable material solution two for making the adsorption structure: a degradable material PCL-PEG copolymer (weight average molecular weight Mw is 180 kDa) is dissolved in tetrahydrofuran (THF) to prepare a degradable material solution two. The solution: 25% of the degradable material, and the balance is tetrahydrofuran (by mass percent).

[0098] (3) Preparation of a water-soluble material solution for making the film: a commercially available pharmaceutical grade carboxymethyl cellulose (CMC) is dissolved in water for injection to prepare a saturated solution, which is a water-soluble material solution.

[0099] (4) Preparation of a degradable material solution three for making the smooth layer: a degradable material PCL-PEG copolymer (weight average molecular weight Mw is 200 kDa) is dissolved in tetrahydrofuran (THF) to prepare a degradable material solution two. The solution: 25% of the degradable material, and the balance is tetrahydrofuran (by mass percent).

[0100] 2, Making the smooth layer-main body layer

[0101] The degradable material solution three is poured on a glass plate, and a film applicator with a height adjusted to 0.1 mm is placed, and then pushed away by an automatic film applicator, and dried under a laminar flow hood.

[0102] After the above smooth layer is dried and formed, the degradable material solution one is poured on the surface of the smooth layer, a film applicator with a height adjusted to 0.5 mm is placed, and then pushed away by an automatic film applicator, and dried under a laminar flow hood, to obtain a smooth layer-main body layer.

[0103] 3, Making the adsorption structure

[0104] (1) Making a mold one as shown in Figure 3 The mold one can be used to make a burr-shaped adsorption structure.

[0105] (2) The degradable material solution two is poured into the mold one as shown in Figure 3 When the adsorption structure is dried and formed, the smooth layer-main body layer which has been integrated is placed thereon, and the side of the main body layer away from the smooth layer is in contact with the mold one (so that the adsorption structure is arranged on the main body layer), and after drying and forming, a smooth layer-main body layer-adsorption structure connected with the mold one is obtained.

[0106] (3) The smooth layer-main body layer-adsorption structure connected with the mold one is placed in water for soaking, until the smooth layer-main body layer-adsorption structure is peeled off from the mold one.

[0107] 4, Impurity removal and drying

[0108] (1) Solvent removal: soak the above smooth layer-main layer-absorbing structure in water for injection for at least 7 days, and change the water twice a day. Clean every two days. Until the total amount of solvent residue in the patch is ≦0.1%;

[0109] (2) Drying: rinse the above smooth layer-main layer-absorbing structure with water for injection cooled to 30°C, and lay it flat on the shelf of the oven. Set the oven temperature to 35°C until the moisture content in the patch is ≦0.5%;

[0110] (3) Cut off the rough edges or uneven thickness of the smooth layer-main layer-absorbing structure after drying, and confirm that there are no bubbles, no damage, no foreign matter, and uniform thickness.

[0111] 5. Dissolve the film

[0112] Coat the absorbing structure of the smooth layer-main layer-absorbing structure obtained in the previous step with a water-soluble material solution, and dry it under a laminar flow hood. Thus, an esophageal hiatus repair patch is obtained. Then cut it to the required size, package, and sterilize it by irradiation.

[0113] Example 2

[0114] The preparation method of an esophageal hiatus repair patch provided in this embodiment is different from that of Example 1 in that the main layer is prepared by electrospinning.

[0115] The preparation method comprises the following steps:

[0116] 1. Preparation of solution

[0117] (1) Preparation of degradable material solution for making main layer: grind sodium chloride (porogen) and sieve out sodium chloride particles of 1-100 μm in size. Dissolve the degradable material PCL-PEG copolymer (weight average molecular weight Mw is 250 kDa) in a mixture of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF), and then add sodium chloride. Stir until the 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: degradable material 25%, sodium chloride 10%, and the balance tetrahydrofuran.

[0118] The ratio of solvents: tetrahydrofuran (THF): N,N-dimethylformamide (DMF) = 1:1.

[0119] The specific preparation operation is as follows:

[0120] 1) Respectively take 150 mL of tetrahydrofuran and 150 mL of N,N-dimethylformamide into a three-necked flask, start the stirrer, and adjust the speed to (200±100) r / min for uniform stirring.

[0121] 2) Weigh 75 g of degradable material and add it to a three-necked flask. Different volumes of solution can be prepared according to the amount of solution used.

[0122] 3) Stir at room temperature for more than 4 h to completely dissolve the degradable material.

[0123] 4) Add 30 g of sodium chloride with a particle size of 1-100 μm, and stir until the sodium chloride is uniformly dispersed in the solution to prepare the first layer 1 electrospinning solution.

[0124] (2) Prepare degradable material solution two for making the adsorption structure: dissolve the degradable material PCL-PEG copolymer (weight average molecular weight Mw is 180 kDa) in tetrahydrofuran (THF) to prepare the degradable material solution two. The solution: 25% degradable material, the balance is tetrahydrofuran (by mass percentage).

[0125] (3) Prepare a water-soluble material solution for making a film: dissolve the commercially available pharmaceutical grade carboxymethyl cellulose (CMC) in water for injection to prepare a saturated solution, which is a water-soluble material solution.

[0126] (4) Prepare 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 the degradable material solution two. The solution: 25% degradable material, the balance is tetrahydrofuran (by mass percentage).

[0127] 2, Make the smooth layer-main body layer

[0128] Pour the degradable material solution three on the glass plate, place the coating film adjuster with the correct height (0.1 mm), push it away with the automatic coating film machine, and dry it under the laminar flow hood to obtain the smooth layer.

[0129] Fix the smooth layer on the receiving device of the electrospinning machine. Slowly draw the degradable material solution one for making the main body layer with a disposable syringe to avoid air bubbles. If air bubbles are generated, they must be removed before subsequent operations. Install a 22G needle (inner diameter is 0.41 mm), and fix the syringe (as the nozzle) in the electrospinning machine push injection pump buckle. Start electrospinning, set the electrospinning time to 4.5 h. After the electrospinning is completed, the smooth layer-main body layer is obtained, and it is taken off from the receiving device.

[0130] The electrospinning parameters are as follows:

[0131] The distance between the nozzle and the receiver is adjusted to 20±1 cm; the receiver receiving rotation speed is set to (380±100) rpm / min; the nozzle push injection speed is set to 0.4±0.05 ml / min; the nozzle translation speed is set to 420±50 mm / min, and the translation distance is set to 200±50 mm; the negative voltage is set to (-3±1) KV, and the positive voltage is set to (9±0.5) KV.

[0132] 4. Making the adsorption structure

[0133] (1) Making the mold two as shown in Figure 4 . The mold two can be used to make the adsorption structure in the shape of a suction cup.

[0134] (2) The degradable material solution two is injected into the mold two as shown in Figure 4 . When the adsorption structure is about to be dried and formed, the smooth layer-body layer that has been integrated is placed thereon, and the side of the body layer away from the smooth layer is in contact with the mold one (so that the adsorption structure is arranged on the body layer). After drying and forming, the smooth layer-body layer-adsorption structure connected with the mold two is obtained.

[0135] (3) The smooth layer-body layer-adsorption structure connected with the mold two is placed in water for soaking until the smooth layer-body layer-adsorption structure is separated from the mold two.

[0136] 5. Impurity removal and drying

[0137] (1) Solvent removal: The smooth layer-body layer-adsorption structure is soaked in water for injection for at least 7 days, and the water is changed twice a day. It is cleaned once every two days. Until the total amount of solvent residue in the patch is ≦0.1%;

[0138] (2) Drying: The smooth layer-body layer-adsorption structure is washed with water for injection cooled to 30°C, and is laid flat on the shelf of the oven. The oven is set to a temperature of 35°C until the water content in the patch is ≦0.5%;

[0139] (3) The rough edges or uneven thickness of the smooth layer-body layer-adsorption structure after drying are cut off, and it is confirmed to be free of bubbles, damage, foreign matter, and uniform thickness.

[0140] 6. Making the film solution

[0141] The water-soluble material solution is coated on the side of the smooth layer-body layer-adsorption structure obtained in the previous step, and is air-dried under the laminar flow hood, to obtain an esophageal hiatus repair patch. It is then cut to the required size, packaged, and sterilized by irradiation.

[0142] Example 3

[0143] The hiatal hernia repair patch prepared in this example is different from that in Example 1 in that the weight-average molecular weights of the degradable material PCL-PEG copolymer used in the main layer, adsorption structure, and smooth layer are different.

[0144] In this embodiment, the main layer is made of a degradable material PCL-PEG copolymer with a weight average molecular weight Mw of 330 kDa; the adsorption structure is made of a degradable material PCL-PEG copolymer with a weight average molecular weight Mw of 180 kDa; and the smooth layer is made of a degradable material PCL-PEG copolymer with a weight average molecular weight Mw of 300 kDa.

[0145] Example 4

[0146] The hiatal hernia repair patch prepared in this example is different from that in Example 1 in that the weight-average molecular weights of the degradable material PCL-PEG copolymer used in the main layer, adsorption structure, and smooth layer are different.

[0147] In this embodiment, the main layer is made of a degradable material PCL-PEG copolymer with a weight average molecular weight Mw of 550 kDa; the adsorption structure is made of a degradable material PCL-PEG copolymer with a weight average molecular weight Mw of 30 kDa; and the smooth layer is made of a degradable material PCL-PEG copolymer with a weight average molecular weight Mw of 550 kDa.

[0148] Example 5

[0149] In this example, only the main layer was prepared by casting. The main layer was made of a biodegradable material PCL-PEG copolymer with a weight average molecular weight Mw of 330 kDa. The specific operation method was the same as the method for preparing the main layer in Example 1.

[0150] Example 6

[0151] In this example, only the main layer was prepared using electrospinning. The main layer was made of a biodegradable material, PCL-PEG copolymer, with a weight-average molecular weight (Mw) of 330 kDa. The specific operation method was the same as that used in Example 2.

[0152] Test example

[0153] 1. Mechanical properties test

[0154] The hiatal hernia repair patches in Examples 1 to 4 and the main body layers in Examples 5 to 6 were cut into a plurality of samples of appropriate sizes and lengths.

[0155] Experimental methods:

[0156] (1) Tensile strength, elastic modulus: open the tensile testing machine, set the parameters, and test the tensile strength of the sample, and process the data to obtain the elastic modulus.

[0157] (2) Elongation at break: open the tensile testing machine, set the parameters, and test the elongation at break, and process the data; elongation at break (%) = (sample elongation at break / sample original length) x 100%.

[0158] (3) Suture strength: use a selected size of suture to suture and knot at one end of the sample to be tested, and similarly suture multiple samples, 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 test the suture strength, and obtain the test data.

[0159] (4) Tear strength: cut the sample along the center with a sharp knife, and prepare a pant-shaped sample. The blade of the knife must be sharp and cannot have a curled edge or a notch. The cut is located at the center of the sample width. Use a thickness gauge to measure the thickness of three points in the tear zone of the sample, and the arithmetic mean is the thickness. Open the tensile testing machine, clamp the sample to be tested, and test the tear strength to obtain the test data.

[0160] (5) Burst strength: multiple square samples are used, and the thickness of each sample is tested with a thickness gauge, then the tensile testing machine is opened, the sample to be tested is clamped, and the burst strength is tested to obtain the test data.

[0161] The experimental results are shown in Table 1 below.

[0162] Table 1. Summary of mechanical property tests of Examples 1-6

[0163]

[0164] From the above results, it can be seen that the tensile strength of the esophageal hiatus repair patch in the examples of the present application reaches 35.53 N / cm or more, the elastic modulus reaches 327.33 Mpa or more, the elongation at break reaches 803.62% or more, the suture strength reaches 22.96 N or more, the tear strength reaches 45.74 N or more, and the burst strength reaches 403.34 kPa or more; the tensile strength of the main layer in the examples of the present application reaches 36.65 N / cm or more, the elastic modulus reaches 332.37 Mpa or more, the elongation at break reaches 836.41% or more, the suture strength reaches 24.35 N or more, the tear strength reaches 48.55 or more, and the burst strength reaches 435.11 kPa or more.

[0165] The mechanical strength of the esophageal hiatus repair patch of the application can well meet the mechanical performance requirements of the esophageal hiatus repair patch during the esophageal hiatus repair process. Meanwhile, the main body layer has good mechanical properties, and in the case that there is no smooth layer or the smooth layer has been degraded, the main body layer can also meet the mechanical support strength required during the esophageal hiatus repair process.

[0166] Meanwhile, the esophageal hiatus repair patch prepared by the application has an elastic modulus of 327.33 Mpa or more, is soft and has good elasticity, can greatly reduce the damage to the tissue during the implantation process, can also reduce the discomfort of the patient, and improves the acceptance of the patient; the esophageal hiatus repair patch prepared by the application has a burst strength of 403.34 kPa or more, and can fully withstand the physiological pressure and mechanical stress (such as abdominal pressure and tissue pulling force) during the esophageal hiatus repair process.

[0167] 2. Degradation experiment

[0168] Experimental method:

[0169] (1) Enzyme buffer preparation:

[0170] A solution containing potassium dihydrogen phosphate and sodium hydrogen phosphate is prepared with sterile double distilled water, 1.653 g of KH2PO4 and 7.744 g of NaH2PO4 are contained in each liter of buffer. The pH value of the buffer solution should be 7.4±0.2, and 0.2 g / L of lipase is added after sterilization. The salts used for preparation are analytical pure and are dried to constant weight.

[0171] (2) Degradation test:

[0172] The esophageal hiatus repair patches in Examples 1-4 and the main body layer in Examples 5-6 are cut into multiple samples of appropriate size, vacuum dried to constant weight at room temperature, and the weight of each sample is accurately measured. Each sample is placed in a glass container, the sample is covered with enzyme buffer and the container is sealed. The minimum volume of the buffer should be 10 mL, and the ratio of the volume (mL) of the buffer to the mass (g) of the sample should be greater than or equal to 30:1. The sample is maintained at 37±1℃ using a constant temperature water bath or oven.

[0173] (3) Degradation cycle determination:

[0174] The sample degradation test selects 38 weeks, 39 weeks, 41 weeks, 42 weeks, 51 weeks, and 52 weeks for sampling for mechanical property testing.

[0175] After wiping the surface liquid of the sample with a paper towel, the sample is loaded into the tensile testing machine clamp for direct testing. The test rate is set to 50 mm / min. When the sample cannot be tested for mechanical properties, the test is terminated, and the time node for stopping the test is the degradation cycle of the sample.

[0176] Experimental results:

[0177] Table 2. Summary of degradation time

[0178]

[0179] From the above data, it can be seen that the time for complete degradation of the esophageal hiatus repair patch prepared in each embodiment of the present application is 39-52 weeks, which provides sufficient repair time for esophageal hiatus repair. At the same time, it can be ensured that the esophageal hiatus repair patch provides sufficient mechanical support during esophageal hiatus repair, and does not degrade too early to affect esophageal hiatus repair, and gradually degrades after esophageal hiatus repair is completed, without causing additional discomfort or risk to the patient.

[0180] 3. Cell proliferation experiment

[0181] Experimental method:

[0182] The main body layer in Examples 5 and 6 was made into a circular sample with a size of 1 cm 2 ) by a puncher, and after 25 KGy irradiation sterilization, each sample was soaked in MEM medium containing 10% FBS, and soaked at 37°C, 60 rpm for 24 h.

[0183] The whole process was operated in a clean bench to ensure aseptic operation. Mouse fibroblasts L-929 grown to the logarithmic growth phase were digested with 0.25% trypsin (containing EDTA), and after digestion, the cell suspension was centrifuged (1000 rpm, 5 min), and the supernatant was discarded. The cells were resuspended with MEM medium, counted to obtain a cell suspension of 5×10 4 Each sample was placed in a 48-well plate, and 3 samples were operated in parallel for each group.

[0184] The cell suspension of 5×10 4 was inoculated in the 48-well plate at 300 μL per well. Two other 48-well plates were operated in the same way, and were cultured in a cell incubator (37°C, 5% CO2, >90% humidity).

[0185] After 24h, 3d and 6d, the original culture medium in the 48-well plate was discarded, 100 μL of MTT (final concentration 1 mg / mL) was added into the corresponding holes of the 48-well plate, and the plate was placed in a carbon dioxide incubator for culture, after 2h, the supernatant was removed, 200 μL of isopropyl alcohol was added into each hole to dissolve the crystal, after the crystal was completely dissolved, the sample was taken out, the liquid in the hole was transferred into a 96-well plate, 100 μL per hole, the absorbance value at 570nm wavelength was determined on an enzyme-labeled instrument, and by comparing with the OD value of the blank group, whether the cell has proliferation effect on the material surface was determined, and the cell proliferation rate was calculated.

[0186] The specific test results are shown in Table 3 below:

[0187] Table 3. Cell proliferation experiment results

[0188]

[0189] From the above data, it can be seen that the main body layer prepared in the embodiment of the application has good cell proliferation rate effect.

[0190] The unexplained part in the application is the same as the prior art or is realized by using the prior art. The applicant declares that the application is illustrated by the above embodiment to explain the detailed method of the application, but the application is not limited to the above detailed method, that is, it does not mean that the application must rely on the above detailed method to be implemented. It should be understood by those skilled in the art that any improvement of the application, equivalent replacement of each raw material of the product of the application, addition of auxiliary ingredients, selection of specific methods, etc. fall within the protection scope and disclosure scope of the application.

Claims

1. A hiatal hernia repair patch, characterized in that: The invention comprises a main body layer, an adsorption structure, and a dissolving film, wherein the adsorption structure is arranged on one side of the main body layer, the dissolving film covers the adsorption structure, and the side of the main body layer where the adsorption structure is located is used to face and / or contact the surrounding tissues of the hiatal hernia. The thickness of the main layer is 0.1~0.5mm, and the main layer is a porous structure with a pore size range of 1~100μm and a porosity of 5-20%. The thickness of the dissolving film is 0.01 to 0.03 mm, and the dissolving film is made of a material that dissolves quickly in water. The height of the adsorption structure when unfolded is 1 to 8 times the thickness of the main body layer.

2. The hiatal hernia repair patch according to claim 1, characterized in that: The material that dissolves quickly in water includes any one or more combinations of pullulan, starch or carboxymethyl cellulose.

3. The hiatal hernia repair patch according to claim 1, characterized in that: The adsorption structure is a plurality of burrs, a plurality of cilia, a plurality of suction cup structures, or a composite structure of at least two of the foregoing three in a cross-arranged manner.

4. The hiatal hernia repair patch according to claim 3, characterized in that: 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.

5. The hiatal hernia repair patch according to claim 1, characterized in that: It also includes a smooth layer, which is a non-porous membrane layer made by a casting method. The smooth layer is located on the other side of the main layer away from the adsorption structure and has a thickness of 0.02 to 0.1 mm.

6. The hiatal hernia repair patch according to claim 5, characterized in that: The main layer, adsorption structure and smooth layer are made of degradable materials. The degradable material includes any one or more copolymers or combinations of degradable polyurethane, polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol, polyvinyl alcohol, polycarbonate, polyhydroxyalkanoate, PHB / PHV copolymer, polyanhydride, polydioxanone and bacterial cellulose.

7. The hiatal hernia repair patch according to claim 6, characterized in that: The degradable materials used to make the adsorption structure, the smooth layer, and the main layer are preferably copolymers of polycaprolactone and polyethylene glycol, with molecular weights of 3-18W, 20-55W, and 25-55W, respectively.

8. The method for preparing the hiatal hernia repair patch according to any one of claims 1 to 7, characterized in that: The steps include: A. Using the degradable material to prepare degradable material solution 1 and degradable material solution 2 for making the main layer and adsorption structure respectively, using a water-soluble material to prepare a water-soluble material solution for making a dissolving film, B. Use cast film method or electrospinning method to make the main layer using biodegradable material solution, dry it, C. Prepare an adsorption structure on one side of the main layer by spinning, 3D printing or using a mold, and dry it. D. Applying a solution of a material that dissolves quickly in water onto the surface of the main layer having the adsorption structure and drying the solution to obtain a hiatal hernia repair patch. When making the main layer, a porogen is added to the degradable material solution 1, and the particle size of the porogen is 1-100 μm. The degradable material solution 1 is composed of the following components by mass percentage: 10-30% of the degradable material and 3-12% of the porogen, and the balance is solvent. No porogen is added to the second degradable material solution. The solution of the material that dissolves rapidly in water is a saturated solution prepared by dissolving the material that dissolves rapidly in water in water.

9. The method for preparing the hiatal hernia repair patch according to claim 8, characterized in that: The invention also includes preparing a smooth layer, wherein the smooth layer is prepared on the other side of the main layer away from the adsorption structure, and the preparation steps of the smooth layer include: E. Prepare a solution of a degradable material for making a smooth layer. Third, use a casting method to make a smooth layer on the other side of the main layer where the adsorption structure is not provided. Preferably, the dried main layer is placed under a coater with the side not used for setting the adsorption structure facing upwards, the height of the coater is adjusted, and the degradable material solution is pushed on the surface of the main layer with an automatic coater and dried.

10. Use of the hiatal hernia repair patch according to any one of claims 1 to 7 or the hiatal hernia repair patch prepared by the preparation method according to any one of claims 8 to 9 in preparing a product that promotes tissue repair in vivo.

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