Anastomotic stoma reinforcing assembly and preparation method and application thereof

Abstract

The invention relates to an anastomotic stoma reinforcing assembly and a preparation method and application thereof. The anastomotic stoma reinforcing assembly comprises a reinforcing layer, and an elastic self-adhesive adhesive film is arranged on one side of the reinforcing layer. The anastomotic stoma reinforcing assembly with a brand-new structure and components is designed, the elastic self-adhesive adhesive film with specific components is designed, the anastomotic stoma reinforcing assembly has specific viscosity, viscosity retention time, hemostasis performance and anti-leakage performance and can be effectively matched with an anastomat to be used for reinforcing the anastomotic stoma (especially the anastomotic stoma obtained after lung tissue resection), meanwhile, the reinforcing layer with the specific structure is designed, and the reinforcing effect is good. The anastomat has proper supporting and fixing performance, realizes effective reinforcement of an anastomotic stoma through cooperation, can be more suitable for cutting and anastomosis of lung tissues, remarkably reduces the risk of leakage of the anastomotic stoma, and can realize painless separation of the reinforcing assembly and the anastomat.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical devices, and relates to an anastomotic stoma reinforcing assembly, a preparation method therefor, and an application thereof. BACKGROUND

[0002] In lung resection surgery, an anastomosis device has become a commonly used tool for resecting bronchial and lung tissue, which realizes tissue connection through mechanical stapling, significantly shortening the operation time and improving the degree of operation standardization. However, the anastomosis device still has problems that are difficult to overcome in clinical use: due to the soft, fragile, elastic and contractile nature of lung tissue, after stapling, due to the pressure and cutting of the staple legs on the lung tissue, and the elastic recoil of the lung tissue itself, micro gaps are easily formed at the stapling site, leading to gas leakage; and for lung lesion tissue with a fragile texture, the tissue cannot tightly wrap the staple legs after stapling, and a persistent bleeding channel is easily formed. Clinical data shows that the incidence of anastomotic leakage in lung tissue resection surgery is as high as 20%-30%, of which about 10% of patients will develop a series of complications due to severe gas leakage, increasing the treatment cost, and even endangering life.

[0003] In existing solutions for reinforcing lung anastomotic stoma (such as CN118903559A, CN119344799A, etc.), a physical plugging strategy is generally adopted, the core technology of which is to cover the anastomotic stoma with a single patch layer to disperse the stapling pressure by using the mechanical strength of the material itself. However, the single patch can only fill the gap between the tissue and the staple legs, and cannot actively plug the blood vessel end and the gas leakage channel, and has basically no effect on stopping the leakage of small blood vessels and small gas leakage points; moreover, the patch made of biological material, such as pig small intestine decellularized matrix, becomes light, thin and transparent after hydration, and gaps are easily formed after the postoperative resolution of tissue edema, leading to postoperative gas / liquid leakage. In organs with activity such as lung tissue, the gap problem is more prominent.

[0004] In addition, although some existing technical solutions (such as CN108348242A) involve the combination of a reinforcing sheet and an adhesive, the adhesive in the solution is only used to realize the temporary combination of the reinforcing sheet and the anastomosis device jaw, and the purpose is to prevent the displacement of the reinforcing sheet during the stapling operation, and does not have the function of actively stopping leakage. More importantly, the adhesion of the adhesive cannot be controlled and adjusted, and if the adhesion is too strong, the anastomotic stoma tissue will be pulled when the anastomosis device is removed, which may cause tissue damage; when the adhesion is too weak, the reinforcing sheet is easily detached from the anastomosis device, increasing the risk of surgery. CN117065078A proposes an anastomotic stoma reinforcing film, which contains an adhesive and an antibacterial hemostatic component, and can form an anastomotic stoma reinforcing effect after being attached to the anastomotic stoma. However, this solution is attached after the anastomosis device is fired, cannot seal the micro leakage channel in time, and cannot achieve the effect of adhering on one side and not adhering on the other side, and is extremely easy to adhere to the surrounding organ tissue in the clinical process.

[0005] Currently, the mainstream anastomosis reinforcement products on the market are suture-based designs. These products connect the reinforcement plate to the backing via sutures. When used with a stapler, the process involves multiple steps: "stapler holding the tissue – manually pulling the sutures to detach from the backing – confirming complete detachment of the backing – initiating cutting and anastomosis." This design has significant drawbacks: First, it is time-consuming, with the "pulling the sutures to detach the backing" step alone taking 10-30 seconds. Second, it is highly dependent on operator skill; pulling the sutures requires precise control of force (too light and the backing cannot be detached, too heavy and the reinforcement plate may shift or the sutures may break), demanding a high level of surgeon experience. Third, it poses a significant safety hazard; if the surgeon pulls suddenly with excessive force, the sutures may break, leaving the backing plate inside the body. In this case, the surgeon must use surgical forceps, scissors, or other instruments to precisely cut the connection between the backing plate and the reinforcement plate within a limited surgical field (especially in thoracoscopic minimally invasive surgery, where the field of view is only 3-5 cm in diameter) to remove the backing plate. The target tissues, such as lung tissue, are fragile. Even a slight deviation during the cutting operation can easily scratch the surrounding tissues, causing lung contusion, alveolar rupture, and bleeding.

[0006] Moreover, existing anastomosis reinforcement solutions for dynamically moving organs such as the lungs still have an unresolved fundamental contradiction: the reinforcement material needs to be firmly and temporarily fixed to the anastomosis device, but it must also be able to be safely and without damage separated from the anastomosis device after firing, avoiding tearing of fragile tissues.

[0007] Specifically, existing technologies, such as the anastomosis reinforcement assembly disclosed in CN106821438A, fix the reinforcement layer to the stapler through an "adhesive layer" (such as protein glue). While this adhesive layer solves the problem of temporary fixation, its adhesiveness cannot be adjusted during operation: if the adhesiveness is too strong, it can easily cause tissue damage during separation; if the adhesiveness is insufficient, there is a risk of dislodgement during surgery. More importantly, this type of adhesive layer only serves as a fixation medium and does not improve dynamic leakage caused by postoperative organ (such as lung) respiratory movement; its function is singular and passive. Furthermore, another type of technology, such as CN117942420A, focuses on developing biodegradable in vivo pressure-sensitive adhesives with good biocompatibility and durable adhesion. However, the characteristic of durable adhesion directly contradicts the requirement for safe separation after temporary fixation in anastomosis reinforcement scenarios.

[0008] In summary, there is a lack of existing technologies for a solution specifically designed to reinforce dynamic organ anastomoses. Summary of the Invention

[0009] To address the shortcomings of existing technologies and practical needs, this invention provides an anastomosis reinforcement component, its preparation method, and its application. It develops an anastomosis reinforcement component that simplifies operation and is particularly suitable for lung tissue resection, making it more adaptable to lung tissue cutting and anastomosis. This solves the contradiction in existing anastomosis reinforcement components that cannot simultaneously achieve secure fixation during surgery, safe separation after surgery, and long-term dynamic sealing.

[0010] To achieve the above objectives, the present invention adopts the following technical solution:

[0011] In a first aspect, the present invention provides an anastomosis reinforcement component, which is used to be disposed on the anvil and / or staple cartridge of a stapler. The anastomosis reinforcement component includes a reinforcement layer, and an elastic self-adhesive film is disposed on one side of the reinforcement layer. The elastic self-adhesive film is configured to have the characteristics of fluid-responsive adhesion reduction (meaning that the elastic self-adhesive film provides the initial adhesion required for fixation in a dry state, and when it comes into contact with body fluids such as blood and tissue fluid, the viscous substance dissolves, resulting in a significant reduction in the overall adhesion of the film to the surface of the stapler, thereby achieving non-destructive separation), and is elastic, capable of dynamically adapting to tissue activity to seal the anastomosis (meaning that the elastic / viscoelastic substance and crosslinking agent in the elastic self-adhesive film work together to form an elastic three-dimensional network structure, which can adapt to physiological activities such as respiration and peristalsis of organs such as lung tissue and recover, so as to continuously maintain the seal of the anastomosis).

[0012] The reinforcing layer is made of at least one of collagen, gelatin, chitosan, silk fibroin, glycosaminoglycans, or decellularized matrix; the elastic self-adhesive film is made of water-soluble adhesive substances, elastic / viscoelastic substances, crosslinking agents, and water; the water-soluble adhesive substances are made of at least one of modified starch, maltitol, water-soluble collagen, water-soluble gelatin, or pullulan and its salts; the elastic / viscoelastic substances are made of at least one of gellan gum, sodium carboxymethyl cellulose, sodium alginate, hyaluronic acid, polyethylene glycol, collagen, gelatin, low-methoxyl pectin (LM pectin), polycaprolactone, poly(3-hydroxybutyrate), or poloxamer and its derivatives; the crosslinking agent is made of at least one of aldehyde crosslinking agents, carbodiimide crosslinking agents, epoxy compounds, diamine crosslinking agents, or metal ion crosslinking agents.

[0013] This invention designs a novel anastomosis reinforcement component with a novel structure and composition, including a specially designed elastic self-adhesive film. A water-soluble adhesive substance provides the film's adhesion. This water-soluble adhesive substance is composed of water-soluble materials. When the reinforcement component comes into contact with tissue fluid or blood, this substance dissolves in water, reducing its viscosity and enabling smooth separation of the reinforcement material from the anastomosis device. The addition of elastic / viscoelastic substances gives the film good elasticity, allowing it to adapt to tissue activity and deformation, such as respiratory movements in the lungs and peristalsis in the digestive tract. This prevents the patch from separating from the tissue due to tissue activity and avoids postoperative anastomosis leakage caused by tissue movement. Overall synergy ensures that the final obtained film possesses specific adhesive properties. The adhesive retention time and leak-proof performance effectively complement the stapler for anastomotic reinforcement (especially in lung resection anastomoses). The specially designed reinforcement layer possesses suitable support and fixation properties, working synergistically to achieve effective anastomotic reinforcement, particularly suitable for complex lung resections. It significantly reduces the risk of anastomotic leakage. Furthermore, the viscosity is controllable. When the reinforcement component is not in use, the elastic self-adhesive film has strong adhesion, firmly fixing the reinforcement material to the stapler. Upon entering the body and contacting tissue fluid and blood, the viscosity slowly decreases. When the stapler is detached, the viscosity drops to a certain level (similar to the adhesion of a No. 3 steel ball), thus achieving painless separation of the reinforcement component from the stapler. The reinforcement component provided by this invention uses a self-adhesive film to simplify operation, significantly shorten instrument usage time, and fundamentally avoid the risks of backing residue and tissue damage caused by suture breakage.

[0014] Preferably, the elastic / viscoelastic material is collagen, sodium carboxymethyl cellulose, gellan gum, or hyaluronic acid. Collagen hydrogel is more similar to the elasticity of human tissue; its triple helix structure retains network strength while providing good flexibility. Gellan gum is a linear polysaccharide chain composed of glucose, rhamnose, and glucuronic acid. The chains can form a dense and flexible cross-linked network through a "double helix structure," which has strong resistance to deformation. Sodium carboxymethyl cellulose enhances its elastic properties through physical entanglement and chemical cross-linking. Compared with other substances, its advantage is that it also has good adhesive properties, strengthening the viscosity of the hydrogel. Hyaluronic acid is the material with the best balance between elasticity and biocompatibility among natural polysaccharides. After cross-linking, it can form a highly elastic network with strong flexibility, and can quickly return to its original shape after being pressed.

[0015] In this invention, a crosslinking agent is used to provide chemical bonding within the elastic / viscoelastic material or between the elastic / viscoelastic material and the water-soluble viscous material, thereby enhancing the structural stability of the adhesive film system. The crosslinked components can construct a "chemical-physical" dual crosslinking network through active groups such as hydrogen bonds, covalent bonds, disulfide bonds, and hydrazide groups, thereby enhancing the elastic properties of the adhesive film system.

[0016] In this invention, the type of crosslinking agent can be selected according to the actual situation (specific components of water-soluble viscous substances and elastic / viscoelastic substances). Specifically, metal ion crosslinking agents can be used for gellan gum, sodium carboxymethyl cellulose, sodium alginate, hyaluronic acid, etc.; epoxy compounds can be used for polycaprolactone; epoxy compounds can be used for poly(3-hydroxybutyrate); and aldehyde crosslinking agents and epoxy compounds can be used for poloxamer.

[0017] Preferably, the metal ion crosslinking agent includes at least one of iron ions, aluminum ions, magnesium ions, calcium ions, sodium ions, or potassium ions. Preferably, salts of the corresponding ions are used, such as calcium chloride, magnesium chloride, zinc gluconate, etc. Calcium ions, magnesium ions, and zinc ions have high biocompatibility, and calcium ions also have biological activity, while zinc ions have antibacterial properties, which can reduce the risk of infection.

[0018] Preferably, the decellularized matrix comprises decellularized mammalian skin and / or hollow organ membranes.

[0019] Preferably, the hollow organ covering includes at least one of the pericardium, amnion, submucosa of the small intestine, or bladder basement membrane.

[0020] Preferably, the raw material of the elastic self-adhesive film further includes hemostatic components.

[0021] In this invention, hemostatic components are added to the elastic self-adhesive film to further improve the hemostatic performance of the film.

[0022] Preferably, the hemostatic component includes at least one of chitosan, fibrin glue, oxidized cellulose, or tissue particles;

[0023] Preferably, the tissue particles are micron-sized particles of decellularized matrix.

[0024] Preferably, the particle size range of the micron-sized particles in the decellularized matrix is ​​100~500 μm.

[0025] Preferably, the raw material of the elastic self-adhesive film may further include a layered decellularized matrix.

[0026] Preferably, the layered decellularized matrix comprises a monolayer of decellularized matrix.

[0027] In this invention, the term "monolayer decellularized matrix" is a concept relative to "multilayer decellularized matrix". After preparing the decellularized matrix, multiple decellularized matrices are stacked together to form a multilayer decellularized matrix, while those not stacked together are a monolayer decellularized matrix.

[0028] This invention introduces a monolayer decellularized matrix into an elastic self-adhesive film, which can further enhance the repair-promoting effect of the film and make the shape of the film easier to fix. The adhesive is coated on both sides of the monolayer decellularized matrix, which facilitates the use and cutting of the film and allows for the preparation of films of different sizes and shapes.

[0029] Preferably, the elastic self-adhesive film is further provided with a release layer.

[0030] Preferably, the material of the release layer includes release paper.

[0031] In this invention, a release layer is provided on the elastic self-adhesive film to prevent unused elastic self-adhesive film from being contaminated by external factors.

[0032] Preferably, the mass ratio of water-soluble adhesive material to elastic / viscoelastic material in the elastic self-adhesive film is 1:(0.05~5), for example, it can be 1:0.06, 1:0.08, 1:0.1, 1:0.2, 1:0.5, 1:1, 1:2, 1:3 or 1:4, etc.

[0033] In this invention, controlling the mass ratio of a specific water-soluble viscous substance to an elastic / viscoelastic substance can precisely regulate the initial viscosity of the reinforcement component and the viscosity retention time in the solution, adapting to actual application scenarios. If the proportion of elastic substance is too low, the elasticity may not be able to adapt to the expansion and contraction changes of tissue, resulting in leakage risk; if the proportion of water-soluble viscous substance is too low, the reinforcement sheet may not be firmly bonded to the stapler, resulting in the risk of falling off.

[0034] Preferably, the mass ratio of elastic / viscoelastic material to crosslinking agent in the elastic self-adhesive film is 1:(1~10), for example, it can be 1:1, 1:2, 1:4, 1:5, 1:6, 1:7, 1:8 or 1:9, etc.

[0035] This invention controls the mass ratio of elastic / viscoelastic material to crosslinking agent, which can further improve the anti-leakage performance. If the crosslinking agent concentration is too low, the elasticity is insufficient and there is a risk of air leakage. If the crosslinking agent concentration is too high, the gel stiffness will be too strong and the elastic properties of the gel will be lost.

[0036] Preferably, the mass percentage of tissue particles in the raw material of the elastic self-adhesive film is 0.1% to 15%, for example, it can be 0.6%, 0.8%, 1%, 2%, 3%, 5%, 8%, 10%, 11%, 12%, 13% or 14%, etc., so as to reasonably control the hemostatic performance and adhesive and elastic properties of the film.

[0037] Preferably, the water-soluble adhesive substance in the elastic self-adhesive film has a mass percentage of 0.5% to 60%, for example, it can be 0.6%, 0.7%, 0.8%, 0.9%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 55%, 56%, 57%, 58%, or 59%, etc.

[0038] In this invention, controlling the concentration of water-soluble adhesive substances in the elastic self-adhesive film allows for reasonable control of the film's adhesive properties, making it suitable for practical applications. If the adhesiveness is too low, it will not bond firmly to the anastomosis device and may fall off during use. If the adhesiveness is too high, the adhesion will remain for too long upon contact with tissue fluid, potentially damaging the tissue during tearing. The concentration can be adjusted according to the adhesive substance; for example, 60% is primarily for low-molecular-weight adhesive components, such as maltitol.

[0039] Preferably, the thickness of the elastic self-adhesive film is 60 μm to 800 μm, for example, it can be 70, 75, 80, 90, 100, 150, 200, 300, 400, 500, 600, 650, 700, 750, 780 or 790 μm.

[0040] In this invention, controlling the thickness of the elastic self-adhesive film allows for precise regulation of the initial tack and tack retention time of the reinforcement component, adapting to actual application scenarios. If the film thickness is too low, it cannot effectively fill the gap between the tissue and the staple, resulting in limited shrinkage and rebound of the reinforcement sheet. If the film thickness is too high, the reinforcement sheet may become too thick overall, making it difficult to fire the stapler. On the other hand, the film thickness also directly affects the actual application of the adhesive and elastic properties. A thin film results in weak adhesion and elasticity, while a thick film results in excessively strong adhesion.

[0041] Preferably, the thickness of the reinforcing layer is 0.05 mm to 0.6 mm, for example, it can be 0.06, 0.07, 0.08, 0.1, 0.2, 0.3, 0.4, 0.5, 0.55, 0.56, 0.58 or 0.59 mm.

[0042] In this invention, controlling the thickness of the reinforcing layer can balance the anti-leakage performance and the difficulty of operation. The thicker the reinforcing component, the stronger the suture strength. However, if the thickness exceeds 0.6 mm, the staples will have difficulty penetrating the reinforcing sheet during use, and the tissue will not be able to be fixed.

[0043] Preferably, the thickness of the anastomosis reinforcement component is 0.1 mm to 1 mm.

[0044] In a second aspect, the present invention provides a method for preparing the anastomosis reinforcement component described in the first aspect, the method comprising:

[0045] The reinforcing layer is prepared using the raw materials of the reinforcing layer; the water-soluble viscous substance, elastic / viscoelastic substance, crosslinking agent and water are mixed to obtain an adhesive solution, the adhesive solution is coated on one side of the reinforcing layer, and after drying, the anastomosis reinforcement component is obtained.

[0046] Preferably, the adhesive can be first coated on both sides of a single layer of decellularized matrix and dried to obtain an elastic self-adhesive film; the elastic self-adhesive film is fixed to one side of the reinforcing layer to obtain an anastomosis reinforcement component.

[0047] Preferably, the method for preparing the reinforcing layer includes: taking a skin or hollow organ membrane from a mammal and subjecting it to virus inactivation, decellularization, defatting, and freeze-drying to obtain a single-layer decellularized matrix; then stacking the single-layer decellularized matrix and freeze-drying it to obtain the reinforcing layer.

[0048] Preferably, tissue particles are also added to the adhesive solution.

[0049] Preferably, the method for preparing the tissue particles includes: taking decellularized matrix (the same method as the preparation method of monolayer decellularized matrix, the main difference being that a complete layer is not required) and pulverizing it into micron-sized particles.

[0050] Preferably, during the process of applying the adhesive to one side of the reinforcing layer, the thickness of the adhesive film is 90 μm to 1000 μm (the overall thickness after gelation will decrease slightly to about 60 μm to 800 μm), and more preferably 120 μm to 800 μm.

[0051] Preferably, the adhesive solution can also be coated on both sides of a single-layer decellularized matrix, with a coating thickness of 45 μm to 500 μm on one side (the overall thickness after coating is about 90 μm to 1020 μm, and the overall thickness after gelation will decrease slightly to about 60 μm to 820 μm), preferably 100 μm to 420 μm.

[0052] Preferably, at least two monolayer decellularized matrix layers can be stacked together for use.

[0053] Preferably, the monolayer decellularized matrix may undergo surface treatment.

[0054] Preferably, the treatment includes treatment with an alkaline solution.

[0055] Preferably, the alkaline solution includes a NaOH solution.

[0056] Preferably, the concentration of the NaOH solution is 1% to 5%.

[0057] Preferably, the processing time is 20 to 40 minutes.

[0058] In this invention, by controlling the surface treatment conditions, effective surface treatment is achieved without damaging the decellularized matrix structure. This indicates that the treatment can activate the originally relatively closed structure of the decellularized matrix, exposing / introducing more active groups. These active groups can provide binding anchors for cell adhesion and proliferation, and can also activate tissue repair-related signaling pathways through specific interactions with growth factors in the tissue fluid, thereby accelerating the regeneration process of damaged tissues.

[0059] Thirdly, the present invention provides the application of the anastomosis reinforcement component described in the first aspect in the preparation of anastomosis repair products.

[0060] Fourthly, the present invention provides a surgical device comprising a stapler and the anastomosis reinforcement assembly described in the first aspect, the anastomosis reinforcement assembly being disposed on the anvil and / or staple cartridge of the stapler.

[0061] Compared with the prior art, the present invention has at least the following beneficial effects:

[0062] This invention designs an anastomosis reinforcement component with an elastic self-adhesive film. It features specific components and a structure, utilizing a multi-component synergy. The design incorporates water-soluble adhesive substances and elastic / viscoelastic materials, effectively preventing gaps between the tissue and staples caused by reduced thickness after hydration. It also allows for rebound and compression with tissue expansion and contraction. The film's adhesiveness can be adjusted during surgery, achieving strong adhesion when needed and easy separation when needed, significantly reducing the tearing force on the tissue during separation. The use of tissue particles increases the surface area of ​​contact between the biomaterial and the tissue, rapidly activating coagulation factors and quickly sealing bleeding points. The self-adhesive film design completely eliminates the "pulling sutures and peeling backing" steps of traditional suture-based products, shortening the instrument operation process and reducing instrument usage time per surgery by 40-60%. Furthermore, the "temporary adhesion-automatic detachment" mechanism ensures positioning and release, eliminating foreign body residue and greatly reducing patient safety risks due to instrument defects, significantly improving clinical safety. Attached Figure Description

[0063] Figure 1 This is a schematic diagram of the anastomosis reinforcement component structure. 1 is the reinforcement layer, 2 is the elastic self-adhesive film, and 3 is the release layer.

[0064] Figure 2 Typical photographs taken during animal experiments using the anastomosis reinforcement component prepared according to Example 1 of the present invention;

[0065] Figure 3 Gross anatomical diagram taken 4 weeks post-operation when the anastomosis reinforcement component prepared using Example 1 of the present invention was used for animal testing.

[0066] Figure 4 This is a schematic diagram of histopathology 4 weeks post-operation when the anastomosis reinforcement component prepared using Example 1 of the present invention was used for animal experiments.

[0067] Figure 5 This image shows a situation where the backing cannot be removed when cutting lung tissue using commercially available suture products. Detailed Implementation

[0068] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention is determined by the claims.

[0069] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased from legitimate channels.

[0070] In this invention, the collagen in the raw material of the reinforcing layer may include type I collagen and / or type III collagen, etc.

[0071] In this invention, the gelatin in the raw material of the reinforcing layer may include high Bloom value gelatin (200~300 Bloom).

[0072] In this invention, the chitosan in the raw material of the reinforcing layer may include medium-high degree of deacetylation (DD 70%~95%) + medium-high molecular weight (M). W Chitosan (50~300 kDa).

[0073] In this invention, the silk fibroin in the raw material of the reinforcing layer may include high molecular weight native silk fibroin (M... W >100kDa).

[0074] In this invention, the modified starch may include chemically modified (CMS, HPS), composite modified starch, and physically modified pregelatinized starch.

[0075] In this invention, the pectin may include LM pectin (which requires calcium ion crosslinking), which can form an elastic gel after crosslinking and has a certain adhesive force.

[0076] In this invention, the water-soluble collagen may include water-soluble collagen with a molecular weight range of 1000-10000 Da (such as enzymatically extracted fish collagen).

[0077] In this invention, the pullulan polysaccharide may include low molecular weight (1×10⁻⁶) polysaccharides. 4 ~1×10 5Da) pullulan polysaccharide is more conducive to regulating the viscosity of the film and avoiding excessive viscosity.

[0078] In this invention, the gellan gum in the elastic / viscoelastic material may include high-acyl gellan gum (acyl content 1.5~2.0%), which can serve as an elastic component to enhance the crack resistance of the adhesive layer.

[0079] In this invention, the sodium carboxymethyl cellulose may include sodium carboxymethyl cellulose with a degree of substitution ranging from 0.6 to 1.0.

[0080] Sodium alginate is composed of β-D-mannuronic acid (M unit) and α-L-guluronic acid (G unit) linked by 1,4-glycosidic bonds. "High M-type" specifically refers to a type where the M unit content is significantly higher than the G unit content, with an M / G ratio ≥ 1.5 (some industries classify M / G ≥ 2.0 as "extremely high M-type"). In this invention, the sodium alginate may include high M-type (M / G ratio ≥ 1.5) sodium alginate. High M-type sodium alginate has a highly flexible molecular chain, resulting in a flexible and elastic adhesive layer that improves the tensile recovery of self-adhesives.

[0081] In this invention, the hyaluronic acid may include high molecular weight (M... w ≥1×10 6 Da) Hyaluronic acid. The adhesive layer formed by this type of hyaluronic acid has good elasticity, moisturizing and adhesion properties, and can be used as an elastic component to improve the softness and durability of the adhesive layer.

[0082] In this invention, the polyethylene glycol may include high molecular weight (M... w PEG with a molecular weight of ≥10,000 Da can provide a certain degree of elasticity through molecular chain entanglement, thereby improving the flexibility of the adhesive layer.

[0083] In this invention, the collagen in the elastic / viscoelastic material may include natural unhydrolyzed / low-hydrolyzed collagen, which can serve as an elastic component to enhance the tensile strength and biocompatibility of the adhesive layer.

[0084] In this invention, the gelatin in the elastic / viscoelastic material may include high Bloom value (Bloom value ≥ 220g) gelatin.

[0085] In this invention, the polycaprolactone may include high molecular weight (M... n ≥40,000Da) PCL and PCL-PEG copolymers: High molecular weight PCL itself has good flexibility and elastic recovery; PCL-PEG copolymers, due to the introduction of PEG blocks, have further improved elasticity and water solubility, and can be used as elastic components.

[0086] In this invention, the poly(3-hydroxybutyrate) may include copolymerized PHB (such as PHBV, PHBH).

[0087] The main reagents used in the following examples include: pullulan (purchased from Furuida, catalog number 0069), collagen (purchased from Adamas Life, catalog number 046292806), calcium chloride (purchased from Greatent, catalog number 01585503), and sodium carboxymethyl cellulose (purchased from Huzhou Zhanwang Pharmaceutical Co., Ltd., viscosity 800). mPa·s), zinc gluconate (purchased from Adamas, catalog number 013473882), maltitol (purchased from Aladdin, catalog number 014652493), water-soluble collagen (purchased from JK, catalog number 101259), modified starch (purchased from Greatent, catalog number 01123387), sodium alginate (purchased from Mingyue Algae Group Co., Ltd., catalog number A00219), gellan gum (purchased from Zhejiang Tianwei Biotechnology Co., Ltd., catalog number TW-HGX), hyaluronic acid (purchased from Kewpie, catalog number O06003), polyethylene glycol (purchased from Adamas, catalog number 013685318).

[0088] Example 1

[0089] This embodiment provides an anastomosis reinforcement component, the structural schematic diagram of which is shown below. Figure 1 As shown, the reinforcement component consists of a reinforcement layer, an elastic self-adhesive film (hereinafter referred to as the elastic film) and a release layer, with the elastic film laid on one side of the reinforcement layer.

[0090] The reinforcing layer was obtained from the submucosa of the small intestine of pigs through virus inactivation, decellularization, freeze-drying, defatting, and secondary freeze-drying.

[0091] The raw materials for the elastic film include 10% tissue particles, 12% pullulan (viscous substance), 1% collagen (elastic substance), and 1% calcium chloride by mass, with the balance being deionized water. At this point, the mass ratio of viscous substance to elastic substance is 12:1, and the mass ratio of elastic substance to crosslinking agent is 1:1.

[0092] Preparation method of micron-sized tissue particles: Prepare freeze-dried decellularized porcine small intestinal submucosa, pulverize it into powder with a particle size of 300 μm, and set aside for later use.

[0093] The method for preparing the anastomosis reinforcement component includes the following steps:

[0094] (1) Preparation of the reinforcement layer:

[0095] Take the decellularized submucosa of porcine small intestine after freeze-drying, spray purified water on its surface to moisten it, lay six layers in a predetermined order, freeze-dry it, and cut it into 60 mm × 10 mm rectangles for later use, with a thickness of 0.13 mm.

[0096] (2) Preparation of elastic adhesive film and product assembly:

[0097] ① Preparation of collagen elastic substances: After pulverizing the decellularized porcine small intestinal submucosal matrix, 2 g of the decellularized porcine small intestinal submucosal matrix powder and 100 mg of pepsin were dissolved together in 25 mL of 0.01 mol / L HCl and digested for 48 h. Then, 2.8 mL of 10×PBS solution, 2.5 mL of 0.01 mol / L NaOH solution and 19.7 mL of 1×PBS solution were added to the digestion solution and stirred evenly for later use.

[0098] ② Preparation of pullulan polysaccharide viscous substance: Dissolve it in deionized water to prepare a 20% concentration solution, stir evenly and set aside for use.

[0099] ③ Preparation of elastic adhesive: Mix a certain proportion of pullulan polysaccharide solution with collagen solution to make the mass ratio of viscous substance to elastic substance = 12:1. Then add a certain amount of calcium chloride solution and micron-sized tissue particles in batches to make the mass ratio of elastic substance to crosslinking agent = 1:1. Stir evenly and set aside for use.

[0100] ④ Apply the elastic adhesive to one side of the reinforcing sheet with a coating thickness of 600 μm, and after gelling at 37℃ for 10 h, cover it with release paper.

[0101] (3) Sterilization and packaging:

[0102] The prepared reinforcement components were packaged in aluminum foil bags and sterilized by irradiation at 25 kgy.

[0103] Example 2

[0104] This embodiment provides an anastomosis reinforcement component, which consists of a reinforcement layer, an elastic adhesive film, and a release layer, with the elastic adhesive film laid on one side of the reinforcement layer.

[0105] The reinforcing layer was obtained from the submucosa of the small intestine of pigs through virus inactivation, decellularization, freeze-drying, defatting, and secondary freeze-drying.

[0106] The raw materials for the elastic film include 10% by weight of tissue particles, 12% pullulan, 1% sodium carboxymethyl cellulose (a viscoelastic substance), and 1% zinc gluconate, with the balance being deionized water. At this point, the mass ratio of the viscous substance to the viscoelastic substance is 12:1, and the mass ratio of the elastic substance to the crosslinking agent is 1:1.

[0107] Preparation method of micron-sized tissue particles: Prepare freeze-dried decellularized porcine small intestinal submucosa, pulverize it into powder with a particle size of 300 μm, and set aside for later use.

[0108] The method for preparing the reinforced component includes the following steps:

[0109] (1) Preparation of reinforcement materials:

[0110] The decellularized submucosa of porcine small intestine after freeze-drying was laid in six layers in a predetermined order, then freeze-dried and cut into rectangles of 60 mm × 10 mm for later use, with a thickness of 0.13 mm.

[0111] (2) Preparation of elastic adhesive film and product assembly:

[0112] ① Preparation of elastic adhesive: Take 20 g pullulan polysaccharide, weigh sodium carboxymethyl cellulose, zinc gluconate and deionized water according to the above component ratio, mix them evenly, add micron-sized tissue particles in batches, and continue stirring for 1 h to obtain elastic adhesive.

[0113] ② Apply the elastic adhesive to one side of the reinforcing sheet with a coating thickness of 600 μm, and after gelling at 39℃ for 10 h, cover it with release paper.

[0114] (3) Sterilization and packaging:

[0115] The prepared reinforcement components were packaged in aluminum foil bags and sterilized by irradiation at 25 kgy.

[0116] Example 3

[0117] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that pullulan polysaccharide in the elastic film is replaced with an equal amount of maltitol. All other aspects are the same as in Embodiment 1.

[0118] Example 4

[0119] This embodiment provides an anastomosis reinforcement component, which differs from Embodiment 1 only in that an elastic adhesive is applied to both sides of a surface-treated monolayer decellularized matrix:

[0120] ① Processing method of monolayer decellularized matrix: Prepare a piece of freeze-dried decellularized porcine small intestinal submucosa, immerse it in 0.1 mol / L NaOH solution for 30 min, rinse with a large amount of deionized water and freeze-dry to obtain the surface-modified decellularized matrix.

[0121] ② Preparation of elastic adhesive film: The elastic adhesive liquid is coated on one side of the surface-modified monolayer decellularized matrix with a coating thickness of 300 μm. After gelling at 37℃ for 10 h, release paper is covered. The adhesive liquid is then coated on the other side of the monolayer decellularized matrix with the same thickness. After treatment under the same gelling conditions, release paper is covered.

[0122] Cut the elastic film to the appropriate size to fit the nail cartridge / nail felt surface.

[0123] ③Product assembly: Peel off the release paper from one side of the elastic film, and flatten it in the middle of the reinforcing material, pressing the edges to keep it flat.

[0124] ④ Sterilization and packaging: The prepared reinforced components are packaged in aluminum foil bags and sterilized by irradiation at 25 kgy.

[0125] Example 5

[0126] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the concentration of pullulan polysaccharide in the raw material of the elastic adhesive film is adjusted to 20%, so that the mass ratio of viscous material to elastic material is 20:1. All other aspects are the same as in Embodiment 1.

[0127] Example 6

[0128] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the concentration of pullulan polysaccharide in the raw materials of the elastic film is adjusted to 1%, the concentration of collagen is adjusted to 5%, and the concentration of calcium chloride is adjusted to 5%, so that the mass ratio of viscous material to elastic material is 1:5 and the mass ratio of elastic material to crosslinking agent is 1:1. All other aspects are the same as in Embodiment 1.

[0129] Example 7

[0130] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the single-sided coating thickness of the elastic adhesive film is 450 μm, and all other aspects are the same as in Embodiment 1.

[0131] Example 8

[0132] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the single-sided coating thickness of the elastic adhesive film is 45 μm, while all other aspects are the same as in Embodiment 1.

[0133] Example 9

[0134] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the concentration of tissue particles in the raw material of the elastic film is adjusted to 15%, while all other aspects are the same as in Embodiment 1.

[0135] Example 10

[0136] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the concentration of tissue particles in the raw material of the elastic film is adjusted to 0.1%, while all other aspects are the same as in Embodiment 1.

[0137] Example 11

[0138] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that in step (1), 20 layers of decellularized porcine small intestinal submucosa are laid with a thickness of 0.55 mm. All other aspects are the same as in Embodiment 1.

[0139] Example 12

[0140] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that in step (1), three layers of decellularized porcine small intestinal submucosa are laid with a thickness of 0.06 mm. All other aspects are the same as in Embodiment 1.

[0141] Example 13

[0142] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the calcium chloride concentration in the raw material of the elastic film is adjusted to 10%, so that the mass ratio of elastic material to crosslinking agent is 1:10. All other aspects are the same as in Embodiment 1.

[0143] Example 14

[0144] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the calcium chloride concentration in the raw material of the elastic film is adjusted to 5%, so that the mass ratio of elastic material to crosslinking agent is 1:5. All other aspects are the same as in Embodiment 1.

[0145] Example 15

[0146] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the concentration of tissue particles in the raw material of the elastic film is adjusted to 0.05%, while all other aspects are the same as in Embodiment 1.

[0147] Example 16

[0148] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that pullulan polysaccharide in the elastic film is replaced with water-soluble collagen in equal amounts. All other aspects are the same as in Embodiment 1.

[0149] Example 17

[0150] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that pullulan polysaccharide in the elastic film is replaced with modified starch in an equal amount. All other aspects are the same as in Embodiment 1.

[0151] Example 18

[0152] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that the collagen in the elastic film is replaced with sodium alginate in an equal amount. All other aspects are the same as in Embodiment 1.

[0153] Example 19

[0154] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that collagen in the elastic adhesive film is replaced with gellan gum in equal amounts. All other aspects are the same as in Embodiment 1.

[0155] Example 20

[0156] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that collagen in the elastic film is replaced with hyaluronic acid in equal amounts. All other aspects are the same as in Embodiment 1.

[0157] Example 21

[0158] This embodiment provides an anastomosis reinforcement component. Compared with Embodiment 1, the only difference is that collagen in the elastic film is replaced with polyethylene glycol in equal amounts. All other aspects are the same as in Embodiment 1.

[0159] Comparative Example 1

[0160] This comparative example provides an anastomosis reinforcement component. Compared with Example 1, the only difference is that the concentration of pullulan polysaccharide in the raw materials of the elastic film is adjusted to 12%, the concentration of collagen is adjusted to 0.5%, and the concentration of calcium chloride is adjusted to 0.5%, so that the mass ratio of viscous material to elastic material is 24:1 and the mass ratio of elastic material to crosslinking agent is 1:1. All other aspects are the same as in Example 1.

[0161] Comparative Example 2

[0162] This comparative example provides an anastomosis reinforcement component. Compared with Example 1, the only difference is that the concentration of pullulan polysaccharide in the raw materials of the elastic film is adjusted to 2%, the concentration of collagen is adjusted to 10%, and the concentration of calcium chloride is adjusted to 12%, so that the mass ratio of viscous material to elastic material is 1:6 and the mass ratio of elastic material to crosslinking agent is 1:1. All other aspects are the same as in Example 1.

[0163] Comparative Example 3

[0164] This comparative example provides a joint reinforcement component. Compared with Example 1, the only difference is that the single-sided coating thickness of the elastic adhesive film is 550 μm, and all other aspects are the same as in Example 1.

[0165] Comparative Example 4

[0166] This comparative example provides a joint reinforcement component. Compared with Example 1, the only difference is that the single-sided coating thickness of the elastic adhesive film is 30 μm, while all other aspects are the same as in Example 1.

[0167] Comparative Example 5

[0168] This comparative example provides an anastomosis reinforcement component, which differs from Example 1 only in that the concentration of tissue particles in the raw material of the elastic film is adjusted to 20%, while all other aspects are the same as in Example 1.

[0169] Comparative Example 6

[0170] This comparative example provides an anastomosis reinforcement component, which differs from Example 1 only in that the tissue particles in the raw material of the elastic film are replaced with an equal amount of deionized water.

[0171] Comparative Example 7

[0172] This comparative example provides an anastomosis reinforcement component. Compared with Example 1, the only difference is that in step (1), 20 layers of decellularized porcine small intestinal submucosa are laid with a thickness of 0.62 mm. All other aspects are the same as in Example 1.

[0173] Comparative Example 8

[0174] This comparative example provides an anastomosis reinforcement component. Compared with Example 1, the only difference is that in step (1), two layers of decellularized porcine small intestinal submucosa are laid with a thickness of 0.04 mm. All other aspects are the same as in Example 1.

[0175] Comparative Example 9

[0176] This comparative example provides a joint reinforcement component, which differs from Example 1 only in that the reinforcement component consists only of a reinforcement layer and does not contain an elastic adhesive film.

[0177] Comparative Example 10

[0178] Compared with Example 1, the only difference is that the concentration of calcium chloride in the raw material of the elastic film is adjusted to 11%, so that the mass ratio of elastic material to crosslinking agent is 1:11. Everything else is the same as Example 1.

[0179] Comparative Example 11

[0180] Compared with Example 1, the only difference is that the calcium chloride concentration in the raw material of the elastic film is adjusted to 0.9%, so that the mass ratio of elastic material to crosslinking agent is 1:0.9. Everything else is the same as Example 1.

[0181] Test case

[0182] The anastomosis reinforcement components prepared in each embodiment and comparative example were subjected to the following tests:

[0183] (1) Initial tack: Tested according to GB / T 4852-2002. The experimental results are expressed as the maximum steel ball number that the elastic film can stick within the specified range. Three parallel samples are used for each group of samples, and the average value is taken.

[0184] (2) Adhesive retention time: The product was loaded onto the stapler and immersed in deionized water. Every 30 seconds, the product was removed and the reinforcing sheet was observed to see if it fell off. The time it took for the reinforcing sheet to fall off was recorded. Each group of samples was tested in triplicate, and the average value was taken.

[0185] (3) Suture strength: The test was conducted according to Appendix B of YY / T 1979-2021. Before the test, the staples and reinforcing strips attached to the dialysis paper were immersed in purified water for 10 minutes to hydrate, then removed and dried before testing. The stapler without the anastomotic reinforcing strip was used as a blank control group. Three replicates were made for each group of samples, and the minimum suture strength was taken as the test result.

[0186] (4) Pressure resistance: Fresh and structurally intact pig small intestine was taken, and one end of the small intestine was anastomosed and cut using a stapler with the reinforcement components assembled. The other end was connected to the water injection port of the anastomosis (suture) pressure tester and tied securely to prevent leakage. The water column pressure was gradually increased until liquid dripped from the anastomosis, and the pressure at this point was recorded as the maximum pressure resistance of the reinforcement sheet. A stapler without the anastomosis reinforcement sheet was used as a blank control group. Three samples were tested in each group, and the average pressure resistance was taken as the test result.

[0187] (5) Simulated use test: The product was loaded onto the stapler, and the fresh isolated pig lung tissue was held in the stapler and slid from left to right for 10 cm. After 6 sliding movements, the reinforcement sheet was observed to see if it fell off the stapler. Three parallel samples were made for each group of samples.

[0188] (6) In vitro hemostatic performance test: After mixing the anticoagulant with fresh rat blood in a certain proportion, the elastic membrane was placed at the bottom of the test tube, with the test tube without the reinforcement component as a blank control. Blood solution containing anticoagulant was added to each test tube and incubated for 5 min to ensure full contact between the reinforcement component and the blood. Then, 20 μL of CaCl2 solution was added to initiate coagulation. Deionized water was slowly added to the test tube at different coagulation times (5, 10, 20, 30 min). When the uncoagulated red blood cells came into contact with deionized water, hemolysis would occur. The absorbance of the supernatant was measured at 545 nm, and the coagulation index (%) was calculated.

[0189] Coagulation index (%) = (1-AS / AW)×100%. Where AS is the absorbance value of the hydrogel group and AW is the absorbance value of the blank control group.

[0190] (7) In vitro anti-leakage performance test: An isolated fragile pig lung tissue model was established by enzymatic hydrolysis and used as the test subject. The pig lung tissue was cut and anastomosed using an anastomosis device with pre-assembled reinforcement components. The cut pig lung was placed in a pre-prepared water tank to ensure that the tissue at the anastomosis site was completely submerged. The pig lung was inflated with a pressure pump, and the pressure was controlled to rise to 30 cm H2O. After maintaining the pressure for 60 s, the air was deflated. The inflation-deflation operation was repeated 5 times. The air bubbles were observed to see if any bubbles escaped from the anastomosis site. The leakage intensity was subjectively scored according to the 0-3 grading system (0: no bubbles; 1: countable single bubbles; 2: continuous bubbles; 3: aggregated bubbles).

[0191] (8) Animal experiments: A model of complete lung resection of Bama miniature pig was established to investigate the effects of the anastomosis on the air leakage prevention ability, hemostasis ability and tissue healing ability of experimental animals 4 weeks after surgery.

[0192] Anastomotic air leakage: After the incision is completed and ventilation is restored, the degree of lung air leakage is assessed using the immersion test method. The anesthesiologist assists in inflating the lungs to a pressure of 20-30 cm H2O, observing whether air bubbles escape from the anastomosis site, and subjectively scoring the leakage intensity according to a 0-3 grading system (0: no air bubbles; 1: countable single air bubbles; 2: continuous air bubbles; 3: aggregated air bubbles).

[0193] Intraoperative bleeding: Observe and record the number of bleeding points per unit length requiring clinical hemostasis within 10 minutes after the stapler fires and the cutting and anastomosis is completed, the number of pulsating bleeding points, and the time required for hemostasis treatment of bleeding points. Observe and record the amount of bleeding at the anastomosis site within 3 minutes after the stapler fires and the hemostasis treatment is completed.

[0194] (9) Instrument usage time: The time from when the anastomosis device grasps the tissue to when it is removed (along with the reinforcement attachment) after firing. Fresh pig lungs with an ex vivo time of less than 24 hours were collected. The pig lung tissue was cut and anastomosed using an anastomosis device with the reinforcement components already assembled. The instrument usage time for each operation was recorded. Five replicates were performed for each group of samples, and the average value was taken as the final result. Commercially available suture products were used as the control group.

[0195] The test results (1)-(5) are shown in Table 1.

[0196] Table 1

[0197]

[0198] Note: A blank group was set only for the suture strength test and pressure resistance test: the stapler without the reinforcement plate was used as the blank control group; the reinforcement material of Comparative Example 7 was too thick, and the stapler could not be fired smoothly, so the pressure resistance test could not be performed; the reinforcement component of Comparative Example 9 did not contain adhesive film, so the initial tack, tack retention time and simulated use tests were not performed.

[0199] The results in Table 1 show that:

[0200] The initial tack of the reinforced components prepared in each embodiment is as low as 5, and the tack retention time is as low as 1 min. They will not fall off during use testing. According to literature, doctors can complete the assembly of the stapler from start to finish within 1 to 5 minutes. This indicates that the reinforced components designed and prepared in this invention meet the requirements of practical applications and match the operating habits of doctors.

[0201] Furthermore, as can be seen from the results of Examples 1-3, by adjusting the viscous and elastic / viscoelastic components, viscosity can be controlled and adjusted to meet the requirements of precision.

[0202] Furthermore, this invention discovered that the ratio of viscous material to elastic / viscoelastic material and the thickness of the elastic adhesive film significantly affect the initial tack and the retention time of the adhesive in water for the reinforcement component. Comparative Examples 2 and 4 show that when the proportion of viscous material is low or the coating thickness is thin, the reinforcement component cannot adhere well to the stapler, posing a risk of falling off during clinical surgery. Conversely, excessive viscous material (Comparative Example 1) or excessively thick adhesive coating on one side of the elastic adhesive film (Comparative Example 3) results in high tack and an excessively long adhesion time, which may not be compatible with the surgeon's operating habits.

[0203] The results of the various embodiments show that the main influencing parameter of the stitch strength is the thickness of the reinforcing sheet. Examples 1, 11, and 12 show that the stitch strength increases with the increase of the reinforcing sheet thickness. Comparative Example 8 shows that when the reinforcing sheet is thinner, the stitch strength is not significantly improved compared to the control group.

[0204] The pressure resistance results show that the ratio of elastic / viscoelastic material, the crosslinking agent ratio, and the thickness of the elastic film significantly affect the maximum pressure resistance of the reinforced component. Comparative Examples 1 and 4 indicate that when the elastic material ratio is low or the coating is thin, the elastic material cannot effectively fill the gap between the tissue and the staples, resulting in leakage even at low pressure. Comparative Example 10 shows that when the crosslinking agent concentration is too high, the elastic film becomes too rigid, and during pressurization, its insufficient flexibility makes it prone to rupture, leading to leakage.

[0205] Furthermore, when the reinforcing component lacked the adhesive film (Comparative Example 9), its pressure resistance was weaker than that of Example 1, which had the adhesive film. This is because after the biomaterial is hydrated, water molecules fill the voids in the matrix and enter the gaps between molecular chains, causing the "fluffy voids" that were originally supported by air to disappear, resulting in a significant reduction in overall thickness due to pore collapse. Measurements using calipers revealed that the thickness of Comparative Example 9 decreased from 0.15 mm before hydration to 0.09 mm (after hydration), a reduction of approximately 40%. This drastic reduction in thickness can easily lead to postoperative air leakage during surgery, and in severe cases, a second surgery may be required.

[0206] Furthermore, when the elastic adhesive film did not contain hemostatic components (Comparative Example 6), its initial tack, tack retention time, suture strength, pressure resistance, and simulated use test results were no different from those of Example 1, indicating that the addition or absence of hemostatic components does not affect the adhesiveness and mechanical properties of the reinforced component.

[0207] The results of the hemostatic performance test are shown in Table 2.

[0208] Table 2

[0209]

[0210] The higher the coagulation index, the better the coagulation performance. As shown in Table 2, the present invention controls the concentration of tissue particles in the elastic membrane, which can further improve the hemostatic performance. Excessive tissue particle content (Comparative Example 5) has a serious aggregation effect, making it difficult to disperse evenly in the adhesive solution and making it difficult to conduct tests. Without the addition of tissue particles (Comparative Example 6), the coagulation performance is significantly reduced, and the low tissue particle content leads to a certain degree of decrease in coagulation performance.

[0211] The results of the leak-proof performance test are shown in Table 3.

[0212] Table 3

[0213]

[0214] As shown in Table 3, controlling the thickness of the reinforcing layer in this invention can further improve the anti-leakage performance. When the reinforcing layer is too thick (Comparative Example 7), the staples cannot penetrate the reinforcing assembly to staple the tissue together, resulting in stapleing failure; therefore, no air leakage test was conducted. Conversely, when the reinforcing layer is too thin (Comparative Example 8), the elastic membrane on it cannot effectively fill the gap between the tissue and the staples, leading to air leakage. Furthermore, Comparative Example 9 shows that because the reinforcing assembly lacks an elastic membrane, it cannot adapt to the expansion and contraction of lung tissue. During the simulated breathing process, gaps gradually form between the tissue and the staples, leading to gas leakage.

[0215] This invention controls the crosslinking agent content, which can further improve the anti-leakage performance. When the crosslinking agent content is low (Comparative Example 11), the elastic / viscoelastic material cannot maintain its three-dimensional elastic structure well. As the lung tissue breathes and circulates, the elastic / viscoelastic material gel gradually breaks down, and gaps gradually form between the tissue and the anastomotic staple, leading to gas leakage. When the crosslinking agent content is too high (Comparative Example 10), the rigidity of the membrane system is too strong. As the stapler is fired, the membrane ruptures due to insufficient flexibility and cannot adapt to the periodic movement of the lung tissue, resulting in tiny gaps between the membrane and the lung tissue, ultimately leading to gas leakage at the anastomosis site.

[0216] This invention can further improve the "dynamic following" capability of the reinforcement component by controlling the proportion of elastic / viscoelastic materials and the thickness of the elastic film. When the proportion of elastic material is low (Comparative Example 1) or the film thickness is thin (Comparative Example 4), the elastic film cannot effectively fill the gap between the tissue and the staple, resulting in air leakage.

[0217] Furthermore, when the elastic membrane lacked hemostatic components (Comparative Example 6), its leak-proof performance test showed no air leakage, consistent with Example 1, indicating that the addition or absence of hemostatic components does not affect the leak-proof performance of the reinforced component. Animal characterization was conducted using samples produced in Example 1; typical photographs of the test process are shown below. Figure 2 The results showed that no air leakage or rupture of the anastomosis was observed during or after the operation; no obvious bleeding points or pulsatile bleeding points were observed at the anastomosis during the operation, and there were 0 bleeding points within 10 minutes. The amount of blood loss at the anastomosis within 3 minutes after hemostasis was completed was 0 g.

[0218] Gross anatomical results 4 weeks postoperatively are shown in Figure 3 The results showed that the animals' local healing was good, and no obvious infection or complications were observed.

[0219] Histopathological results are shown in Figure 4 The results showed no obvious abnormalities at any time point, indicating a trend of tissue ingrowth and patch degradation.

[0220] The samples produced in Example 1 were compared with a commercially available suture product—absorbable tissue reinforcement material (National Medical Device Registration Number: 20243020621)—to test the device usage time. The results are shown in Table 4.

[0221] Table 4

[0222]

[0223] When using the commercially available product for the fifth time, the seams broke, and the backing could not be removed. Figure 5As shown, the operator carefully cuts off the backing with scissors and removes it; this process takes a total of 232 seconds. Table 4 shows that the average usage time of the product of this invention is only 11.8 seconds, which is only 17.5% of commercially available products. This is because the operation method is directly simplified to "clamping-firing," significantly improving surgical efficiency and reducing the patient's anesthesia exposure time. Furthermore, the design of this invention is seamless and backless, and no instrument defects were observed throughout the test, ensuring patient safety from the outset.

[0224] In summary, this invention designs an anastomosis reinforcement component with an elastic self-adhesive membrane. By designing specific components and structures and utilizing multi-component synergy, and employing both adhesive and elastic / viscoelastic materials, it effectively avoids gaps between the tissue and the staples caused by the reduction in thickness of the reinforcement material after hydration. It also allows for rebound and compression with tissue expansion and contraction, enabling the membrane to self-adjust its adhesiveness during surgery—achieving strong adhesion when needed and easy separation when needed—significantly reducing the tearing force on the tissue during separation. The use of tissue particles increases the surface area of ​​contact between the biomaterial and the tissue, rapidly activating coagulation factors to quickly seal bleeding points. Surface modification of the monolayer decellularized matrix allows for specific interaction with growth factors in the tissue fluid, accelerating the regeneration process of damaged tissue. Through its innovative self-adhesive membrane design, this invention surpasses commercially available suture-type products in terms of instrument usage time, operational portability, and clinical safety, better meeting the "high efficiency, safety, and ease of operation" requirements of minimally invasive surgery.

[0225] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. An anastomotic stoma reinforcement assembly for being disposed on a staple anvil and / or a staple cartridge of a stapler, the anastomotic stoma reinforcement assembly comprising: The anastomotic stoma reinforcing assembly comprises a reinforcing layer, one side of the reinforcing layer is provided with an elastic self-adhesive film; and the elastic self-adhesive film is provided with the characteristic of body fluid responsive adhesive force reduction and elasticity, and can dynamically adapt to tissue activities to seal the anastomotic stoma. The raw material of the reinforcing layer comprises at least one of collagen, gelatin, chitosan, silk fibroin, glycosaminoglycan or decellularized matrix. The raw material of the elastic self-adhesive film comprises water-soluble adhesive substance, elastic / viscoelastic substance, crosslinking agent and water. The water-soluble adhesive substance comprises at least one of modified starch, maltitol, pectin, water-soluble collagen, water-soluble gelatin or pullulan and its salt. The elastic / viscoelastic substance comprises at least one of gellan gum, sodium carboxymethyl cellulose, sodium alginate, hyaluronic acid, low methoxyl pectin, polyethylene glycol, collagen, gelatin, polycaprolactone, poly(3-hydroxybutyrate) or poloxamer and its derivatives. The crosslinking agent comprises at least one of aldehyde crosslinking agent, carbodiimide crosslinking agent, epoxy compound, diamine crosslinking agent or metal ion crosslinking agent. The metal ion crosslinking agent comprises at least one of iron ion, aluminum ion, magnesium ion, calcium ion, sodium ion or potassium ion. The mass ratio of the elastic / viscoelastic substance to the crosslinking agent in the elastic self-adhesive film is 1:(1-10); and the mass ratio of the water-soluble adhesive substance to the elastic / viscoelastic substance in the elastic self-adhesive film is 1:(0.05-5). The thickness of the elastic self-adhesive film is 60 μm-800 μm.

2. The anastomotic stapling assembly according to claim 1, wherein, The decellularized matrix comprises the skin and / or cavity organ covering membrane of a mammal after decellularization. The cavity organ covering membrane comprises at least one of pericardium, amniotic membrane, small intestinal submucosa or bladder basement membrane.

3. The anastomotic stapling assembly according to claim 1, wherein, The raw material of the elastic self-adhesive film further comprises a hemostatic component. The hemostatic component comprises at least one of chitosan, fibrin glue, oxidized cellulose or tissue particles.

4. The anastomotic stapling assembly according to claim 3, wherein, The tissue particles are micrometer-level particles of the decellularized matrix.

5. The anastomotic stapling assembly according to claim 3, wherein, The mass percentage of the tissue particles in the raw material of the elastic self-adhesive film is 0.1%-15%.

6. The anastomotic stapling assembly according to claim 1, wherein, The thickness of the reinforcing layer is 0.05 mm-0.6 mm. The thickness of the anastomotic stoma reinforcing assembly is 0.1 mm-1 mm.

7. A method of manufacturing an anastomosis reinforcing assembly according to any one of claims 1-6, characterized in that, The preparation method comprises: preparing the reinforcing layer by using the raw material of the reinforcing layer; mixing the water-soluble adhesive substance, the elastic / viscoelastic substance, the crosslinking agent and water to obtain glue solution, and coating the glue solution on one side of the reinforcing layer to obtain the anastomotic stoma reinforcing assembly.

8. The method of claim 6, wherein the anastomotic staple line reinforcement assembly is prepared by, The preparation method of the reinforcing layer comprises: taking the skin or cavity organ covering membrane of a mammal to perform virus inactivation, decellularization, defatting and freeze-drying treatment to obtain a single-layer decellularized matrix, and stacking and freeze-drying the single-layer decellularized matrix to obtain the reinforcing layer.

9. Use of the anastomotic stoma reinforcing assembly according to any one of claims 1-6 in the preparation of an anastomotic stoma repair product.

10. A surgical device, characterized by The surgical device comprises a stapler and the anastomotic stoma reinforcing assembly according to any one of claims 1-6, and the anastomotic stoma reinforcing assembly is arranged on the anvil and / or the cartridge of the stapler.

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