Degradable in-vivo pressure-sensitive adhesive taking decellularized matrix material as base material and preparation method therefor

Abstract

The present application provides a degradable in-vivo pressure-sensitive adhesive taking a decellularized matrix material as a base material and a preparation method therefor. The degradable in-vivo pressure-sensitive adhesive comprises a biological base material layer and pressure-sensitive adhesive layers arranged on both sides of the biological base material layer. On the basis of the total mass of raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer comprise, by mass percentage, 5%-18% of a tissue-active material, 5%-25% of a base material, 10%-35% of a thickener, 10%-50% of a plasticizer, and 10%-60% of deionized water. The degradable in-vivo pressure-sensitive adhesive provided by the present application not only has good compatibility with human tissues, but also has adjustable viscosity. Moreover, the degradable in-vivo pressure-sensitive adhesive can be absorbed or completely discharged out of the body after degradation in vivo. Therefore, it is suitable for in-vivo wound closure, prevention of fluid (gas) leakage at suture sites, tissue repair, drug delivery, wound healing, and other applications.

Description

A biodegradable pressure-sensitive adhesive for in vivo use based on decellularized matrix material and its preparation method. Technical Field

[0001] This application belongs to the field of pressure-sensitive adhesive materials technology, specifically relating to a biodegradable in vivo pressure-sensitive adhesive based on decellularized matrix material and its preparation method. Background Technology

[0002] Pressure-sensitive adhesives are adhesives that are sensitive to pressure; they adhere when pressure is applied but not when no pressure is applied, making them a viable alternative to existing bio-adhesives. They have gained attention due to their ease of use and ability to quickly fix and bond desired items. Particularly in the medical field, medical pressure-sensitive adhesives are commonly used for suturing superficial wounds or securing bandages, reducing the risk of infection from non-biodegradable residues left on wounds by traditional adhesive tapes.

[0003] However, currently available medical pressure-sensitive adhesives cannot be used inside the body, and their internal application is limited to sealants, such as those with the Progel™ brand name. Sealant, such as those from Tisseel and Adherus, addresses specific surgical needs by sealing gaps between tissue surfaces, such as the lungs or dura mater. Clinically, its applications vary depending on the site of adhesion, including wound closure, prevention of fluid (gas) leakage from sutures, tissue repair, drug delivery, and wound healing. Current sealants cannot fulfill all these multiple purposes.

[0004] To address these issues, researchers have developed biodegradable pressure-sensitive adhesives that can connect similar or dissimilar surfaces, thus providing new insights for the development of internal adhesion materials suitable for various scenarios. For example, CN113908327A discloses a bioadhesive double-sided tape formed by adjusting the molecular weight and proportion of block polyesters and undergoing a series of complex processes to melt them into a film, coating it with adhesive, and then covering it with polytetrafluoroethylene. While these adhesives often use biodegradable materials synthesized through chemical modification and other production processes, their degradation products are prone to concentrated release in the body, potentially causing inflammatory reactions.

[0005] Furthermore, CN115895593A discloses a biodegradable pressure-sensitive adhesive, which allows adjustment of the overall glass transition temperature by regulating the ratio of hard monomers to soft monomers. Biodegradable pressure-sensitive tapes prepared using this adhesive exhibit advantages such as high initial tack, high peel strength, good holding power, and good biodegradability; however, it does not address its applicability to the human body.

[0006] Therefore, there is an urgent need in this field to develop a biodegradable pressure-sensitive adhesive that is not only suitable for various application scenarios, but also does not produce any repulsion reaction and has a simple and easy preparation method. Summary of the Invention

[0007] This application provides a biodegradable pressure-sensitive adhesive for in vivo use based on a decellularized matrix material and its preparation method. The biodegradable pressure-sensitive adhesive provided by this application not only exhibits good compatibility with human tissues and has adjustable viscosity, but also can be absorbed or completely excreted after degradation in vivo. Therefore, it is suitable for applications such as wound closure, prevention of fluid (gas) leakage from sutures, tissue repair, and wound healing.

[0008] In a first aspect, this application provides a biodegradable pressure-sensitive adhesive for in vivo use with a decellularized matrix material as the substrate, the biodegradable pressure-sensitive adhesive for in vivo use comprising a bio-substrate layer and a pressure-sensitive adhesive layer disposed on both sides of the bio-substrate layer;

[0009] Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 5%-18% tissue-active material, 5%-25% base material, 10%-35% thickener, 10%-50% plasticizer and 10%-60% deionized water by mass percentage.

[0010] This application provides a biodegradable bio-pressure-sensitive adhesive for in vivo use. On one hand, it uses a biomaterial as the substrate layer. This biomaterial exhibits good biocompatibility and will not cause rejection, inflammation, or other bodily reactions after application. In contrast, some biodegradable materials synthesized through physical or chemical modification processes in the prior art, such as bio-adhesives based on caprolactone, glycolide, or lactide, are prone to causing inflammatory reactions after the concentrated release of their degradation products. On the other hand, the biodegradable bio-pressure-sensitive adhesive does not require complex chemical modification and synthesis processes and partially incorporates biologically derived tissue-active ingredients. This not only endows the adhesive with good flowability and water retention but also promotes wound healing and repair of damaged tissues. Furthermore, the other components of the adhesive are also biodegradable and biocompatible raw materials, ensuring high safety for in vivo use and avoiding the inflammatory reactions associated with adhesives prepared through chemical synthesis and modification.

[0011] The biodegradable intracellular pressure-sensitive adhesive provided in this application has an adjustable viscosity to meet the bonding needs of different scenarios. For example, for scenarios such as hemostasis, sealing, and reducing fluid exchange and infectious contamination between different areas, a biodegradable medical pressure-sensitive adhesive with higher viscosity can be used. For scenarios requiring only temporary bonding, such as transferring patch material from outside the body to tissues or organs, a biodegradable medical pressure-sensitive adhesive with lower viscosity can be used. Furthermore, the aforementioned pressure-sensitive adhesive is completely biodegradable after implantation, leaving no foreign body residue and not forming capsules or lumps. It does not produce shadow structures, especially during subsequent imaging examinations after the removal of cancerous tissue. Optionally, drug components can be added to the pressure-sensitive adhesive components. When applied to the skin or tissue, the drug is gradually released as the degradation reaction occurs, thereby achieving drug delivery.

[0012] In this application, the mass percentage of the tissue-active material is 5%-18%, for example, it can be 5%, 8%, 10%, 12%, 15% or 18%, etc.

[0013] In this application, by controlling the mass percentage content of tissue-active materials, the biodegradable in vivo pressure-sensitive adhesive can have tissue or wound repair functions; if the content is too low, it will not achieve a good repair effect; if the content is too high, the viscosity of the biodegradable in vivo pressure-sensitive adhesive will decrease after irradiation sterilization.

[0014] In this application, the mass percentage of the base material is 5%-25%, for example, it can be 5%, 8%, 10%, 12%, 15%, 18%, 20%, 22% or 25%, etc.

[0015] In this application, by controlling the mass percentage content of the base material, biodegradable pressure-sensitive adhesives can exhibit good bonding properties. Since the base material is the main component that binds two adhered materials together, it determines the basic properties of the adhesive. If the content is too low, the viscosity will be low, making it unsuitable for some applications requiring high strength. Conversely, if the content is too high, the adhesive viscosity may be too high, making it difficult to effectively coat the surfaces to be bonded, affecting its flowability and coating performance.

[0016] In this application, the addition of a base material endows the pressure-sensitive adhesive with good bonding properties.

[0017] In this application, the mass percentage of the thickener is 10%-35%, for example, it can be 10%, 15%, 20%, 22%, 25%, 30% or 35%, etc.

[0018] In this application, by adjusting the mass percentage content of the thickener, the viscosity and flowability meet the application requirements. If the content is too low, the adhesive may become too fluid, making it difficult to control and apply. This may result in the adhesive being too thin during application, affecting its adhesion performance. Conversely, if the content is too high, the viscosity of the adhesive will increase significantly, making it too viscous. This may result in the adhesive being difficult to apply and adhere effectively during application.

[0019] In this application, the addition of a thickener can give the pressure-sensitive adhesive good viscosity, thereby meeting the needs of specific surgical situations such as wound closure, tissue repair, drug delivery, tissue reinforcement, or wound healing.

[0020] In this application, the plasticizer has a mass percentage content of 10%-50%, for example, it can be 10%, 17%, 20%, 22%, 27%, 30%, 32%, 37%, 40%, 42%, 45%, 48% or 50%, etc.

[0021] In this application, the flexibility of the adhesive is adjusted by controlling the mass percentage content of the plasticizer, making it more adaptable to and resistant to surface deformation, vibration, or temperature changes. Too low a content may result in insufficient adhesive adhesion, making it difficult to adapt to objects with different shapes, structures, or surface properties; conversely, too high a content of plasticizer may make the adhesive too viscous, resulting in poor flowability, which may affect the uniformity of coating and application.

[0022] In this application, the addition of plasticizers imparts flexibility, extensibility, and plasticity to the pressure-sensitive adhesive. These effects make the adhesive easier to form elastic, flexible bonds on different surfaces and improve its applicability.

[0023] In this application, the mass percentage of the deionized water is 10%-60%, for example, it can be 10%, 20%, 30%, 40%, 50% or 60%, etc.

[0024] More preferably, based on the total mass of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 8%-15% base material, 10%-16% tissue-active material, 20%-30% thickener, 15%-20% plasticizer and 19%-45% deionized water by mass percentage.

[0025] Preferably, the tissue-active material comprises any one or a combination of at least two decellularized matrix gels selected from mammalian skin, pericardium, amnion, submucosa of the small intestine, or bladder basement membrane.

[0026] The preparation of the decellularized matrix gel involves decellularizing the aforementioned biological material followed by digestion. Existing methods can be used for this process. Specific decellularization methods can be found in paragraphs [0076-0082] of CN115006597B, which describe methods for preparing extracellular matrix. Similarly, specific digestion methods for preparing the decellularized matrix gel can be found in paragraphs [0091-0093] of the same patent, which describe methods for preparing collagen gel.

[0027] Preferably, the base material comprises biodegradable natural polymers and / or biodegradable modified natural polymers.

[0028] Preferably, the biodegradable natural polymeric compound includes any one or a combination of at least two of starch, dextrin, gum arabic, gum arabic, bone glue, hide glue, gelatin, fish glue, shellac, plant protein, or casein.

[0029] Preferably, the biodegradable modified natural polymer compound includes any one or a combination of at least two of carboxymethyl cellulose, modified starch, and polyvinyl alcohol.

[0030] Preferably, the thickener comprises any one or a combination of at least two of the following: starch, modified starch, xanthan gum, maltitol, fructooligosaccharides, sorbitol, xylitol, lactitol, mannitol, erythritol, hydrogenated starch hydrolysate, gelatin, cellulose, methylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, gum arabic, tamarind gum, guar gum, agar, sodium alginate, carrageenan, pectin, or β-cyclodextrin.

[0031] Preferably, the plasticizer comprises a polyol compound.

[0032] Preferably, the polyol compound includes any one or a combination of at least two of glycerol, sorbitol, or ethylene glycol.

[0033] Preferably, the base material, thickener, and plasticizer are of different types.

[0034] More preferably, the base material comprises carboxymethyl cellulose, with a degree of substitution ranging from 0.59 to 1.0, such as 0.59, 0.6, 0.7, 0.8, 0.9, or 1.0; and a viscosity ranging from 600 to 1000 mPa·s, such as 600 mPa·s, 650 mPa·s, 700 mPa·s, 750 mPa·s, 800 mPa·s, 850 mPa·s, 900 mPa·s, 950 mPa·s, or 1000 mPa·s.

[0035] More preferably, the thickener comprises gum arabic.

[0036] More preferably, the plasticizer comprises glycerin.

[0037] Preferably, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer further include 0.1%-21.6% of a humectant and 2.5%-5.2% of an antioxidant.

[0038] In this application, the humectant has a mass percentage content of 0.1%-21.6%, for example, it can be 0.1%, 0.5%, 1%, 2.5%, 5%, 8%, 10%, 12%, 15%, 18%, 20%, 21%, 21.6%, etc.

[0039] In this application, controlling the mass percentage of the humectant can prevent the pressure-sensitive adhesive from drying and curing in the container, ensuring that it maintains good flowability and application performance during storage and use. If the content is too low, it will not be able to prevent the pressure-sensitive adhesive from drying and curing; if the content is too high, it will change the viscosity of the pressure-sensitive adhesive and will likely affect its weather resistance, such as the product being affected in high humidity environments.

[0040] In this application, the antioxidant has a mass percentage content of 2.5%-5.2%, for example, it can be 2.5%, 2.8%, 3%, 3.5%, 4%, 4.5%, 5% or 5.2%, etc.

[0041] In this application, by controlling the mass percentage content of the antioxidant, the color change of pressure-sensitive adhesives due to oxidation can be reduced or prevented, which is crucial for applications requiring consistent appearance. Too low a content will fail to prevent oxidation and discoloration, while too high a content may lead to product instability, affecting its performance during storage and increasing production costs.

[0042] Preferably, the humectant includes polyol humectants and / or sugar humectants.

[0043] In this application, the moisturizer may also include a pseudo-natural moisturizing factor, such as any one or a combination of at least two of sodium lactate or trehalose.

[0044] Preferably, the antioxidant includes any one or a combination of at least two of vitamin E, vitamin C, flavonoids, tea polyphenols, phytic acid, glucosamine, lactone, or sodium hyaluronate.

[0045] In this application, the thickness of the pressure-sensitive adhesive layer is 0.2-2 mm, for example, it can be 0.2 mm, 0.5 mm, 0.8 mm, 1 mm, 1.2 mm, 1.5 mm, 1.8 mm or 2 mm, etc.

[0046] In this application, the viscosity of the pressure-sensitive adhesive can be selectively adjusted by controlling the thickness of the pressure-sensitive adhesive layer. A thinner coating may result in insufficient adhesion, failing to meet application requirements. A thicker coating may increase internal stress, thereby affecting its stability and durability, while also increasing production costs.

[0047] Preferably, the material of the biological substrate layer includes a decellularized matrix material.

[0048] Preferably, the decellularized matrix material comprises any one or a combination of at least two of mammalian skin, pericardium, amnion, submucosa of the small intestine, or bladder basement membrane.

[0049] The specific decellularization process can be prepared using existing methods, such as the preparation method of extracellular matrix mentioned in paragraphs [0076-0082] of CN115006597B.

[0050] In a second aspect, this application provides a method for preparing a biodegradable in vivo pressure-sensitive adhesive based on a decellularized matrix material according to the first aspect, the method comprising the following steps:

[0051] The active material, base material, thickener, plasticizer and deionized water are mixed according to the formula to obtain a pressure-sensitive adhesive slurry. The pressure-sensitive adhesive slurry is then coated on both sides of the bio-based substrate layer and dried to obtain the biodegradable in vivo pressure-sensitive adhesive with decellularized matrix material as the substrate.

[0052] In this application, a humectant and an antioxidant may also be added before mixing.

[0053] In this application, the specific mixing process is as follows: the thickener and humectant are mixed once according to the formula amount, then deionized water is added and stirred at room temperature for 1 hour, then tissue active material is slowly added and stirred for another 1 hour, then plasticizer and base material heated to 65-75°C are added and stirred for another 1 hour, and finally antioxidant is added and stirred at room temperature for another 1 hour.

[0054] Preferably, the drying temperature is 20-50℃, for example, 20℃, 30℃, 40℃ or 50℃; the time is 4-24h, for example, 4h, 8h, 12h, 14h, 18h, 20h or 24h.

[0055] In this application, the specific process of coating the pressure-sensitive adhesive on both sides of the bio-based substrate layer and drying it to obtain the biodegradable pressure-sensitive adhesive is as follows: the pressure-sensitive adhesive is coated on both sides of the bio-based substrate layer, dried at 20-50℃ for 4-24 hours, and covered with release paper for later use.

[0056] Preferably, the thickness of the pressure-sensitive adhesive layer formed after drying is 0.2-2 mm, for example, it can be 0.2 mm, 0.5 mm, 0.8 mm, 1 mm, 1.2 mm, 1.5 mm, 1.8 mm or 2 mm.

[0057] In this application, the biodegradable pressure-sensitive adhesive for in vivo use is suitable for purposes such as wound closure, tissue repair, tissue reinforcement, and wound healing. It exhibits good biocompatibility and does not cause rejection, inflammation, or other bodily reactions after application. Furthermore, the pressure-sensitive adhesive provided in this application can restore tissue integrity rapidly, precisely, and non-invasively, and can provide support for tissue remodeling and healing, significantly improving surgical wound healing.

[0058] Compared with the prior art, this application has the following advantages:

[0059] Existing biodegradable pressure-sensitive adhesives often use materials such as paper, cellulose film, or polylactic acid as their substrate. However, these adhesives typically only degrade in vitro and cannot complete the degradation process within the complex human body. In contrast, this application proposes a biodegradable in vivo pressure-sensitive adhesive based on a decellularized matrix material, which can achieve complete degradation under the action of in vivo enzymes. Both the decellularized matrix material and the decellularized matrix gel component are biodegradable in vivo, and all other components of the biodegradable in vivo pressure-sensitive adhesive provided in this application are also biodegradable in vivo.

[0060] Furthermore, this application proposes a biodegradable pressure-sensitive adhesive for in vivo use based on decellularized matrix material, incorporating a tissue-active material—decellularized matrix gel. The decellularized matrix gel is obtained by digesting decellularized matrix and is rich in collagen and active factors, such as fibroblast growth factor (FGF), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF). These growth factors can regulate cell proliferation, differentiation, and migration, promoting tissue regeneration and repair. Compared to decellularized matrix, the matrix gel obtained after digestion has a smaller molecular weight and is more easily absorbed by the body; therefore, it can more effectively promote wound healing at the wound site.

[0061] This application provides a biodegradable pressure-sensitive adhesive for in vivo use. Firstly, it uses a biomaterial as the substrate layer, which provides structural support. This biomaterial exhibits good biocompatibility and possesses certain tensile strength and tear resistance, ensuring the adhesive is not easily broken or damaged during use and preventing rejection, inflammation, or other bodily reactions after application. In contrast, some biodegradable materials synthesized through physical or chemical modifications in existing technologies, such as bioadhesives based on caprolactone, glycolide, or lactide, tend to release concentrated degradation products that can easily cause inflammatory reactions. Secondly, the biodegradable pressure-sensitive adhesive for in vivo use does not require complex chemical modification and synthesis processes and incorporates some biologically derived tissue-active ingredients. This not only endows the adhesive with good flowability and water retention but also promotes wound healing and repair of damaged tissues. Furthermore, the other components of the pressure-sensitive adhesive are also biodegradable and biocompatible raw materials, ensuring high safety for in vivo use and avoiding the inflammatory reactions associated with adhesives prepared through chemical synthesis and modification.

[0062] The biodegradable intracellular pressure-sensitive adhesive provided in this application has an adjustable viscosity to meet the bonding needs of different scenarios. For example, for scenarios such as hemostasis, sealing, and reducing fluid exchange and infectious contamination between different areas, a biodegradable medical pressure-sensitive adhesive with higher viscosity can be used. For scenarios that only require temporary bonding, such as the transfer of patch materials from outside the body to tissues and organs, a biodegradable medical pressure-sensitive adhesive with lower viscosity can be used. In addition, the above-mentioned pressure-sensitive adhesive can be completely degraded after implantation, leaving no foreign body residue and not forming capsule tissue or lumps. Especially when imaging is performed again after the removal of cancerous tissue, no shadow structure is produced. Optional pressure-sensitive adhesive components can also be added with drug ingredients. When applied to the skin or tissue, the drug is gradually released as the degradation reaction occurs, thereby achieving the function of drug delivery. Attached Figure Description

[0063] Figure 1 is a schematic diagram of the biodegradable in vivo pressure-sensitive adhesive provided in Example 1 of this application. Detailed Implementation

[0064] The technical solution of this application will be further described below with reference to the accompanying drawings and specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of this application and should not be construed as specific limitations thereof.

[0065] The raw material composition of the pressure-sensitive adhesive layer of the biodegradable in vivo pressure-sensitive adhesive provided in the embodiments and comparative examples of this application is shown in Table 1:

[0066] Table 1

[0067] Example 1

[0068] This embodiment provides a biodegradable pressure-sensitive adhesive for in vivo use with a decellularized matrix material as the substrate, as shown in Figure 1. The biodegradable pressure-sensitive adhesive for in vivo use includes a decellularized porcine small intestinal submucosa substrate layer and pressure-sensitive adhesive layers disposed on both sides of the decellularized porcine small intestinal submucosa substrate layer.

[0069] The substrate layer was obtained from the submucosa of porcine small intestine through virus inactivation, decellularization, freeze-drying, defatting, and secondary freeze-drying. The porcine small intestinal submucosa was derived from boars fed a closed diet of plant-based feed, weighing 150 kg. The small intestine was harvested within half an hour of death, and the mucosa, muscle layer, and serosa of the small intestine were removed within 12 hours, leaving only the submucosa.

[0070] Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of polyvinyl alcohol base, 24% of maltitol thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, 18% of sorbitol plasticizer, and the balance being deionized water.

[0071] This application provides a method for preparing the above-mentioned decellularized porcine small intestinal submucosa substrate, which includes the following steps:

[0072] (1) Virus inactivation: The treated porcine small intestinal submucosa material was soaked in 0.5% PAA solution for 30 minutes and the residual PAA solution was washed with purified water.

[0073] (2) Decellularization: Wash with a mixture of 0.1% trypsin and 0.1% SDS for 2 hours, and wash with purified water to remove residual solvent.

[0074] (3) Freeze-drying: Freeze-dry the decellularized matrix material.

[0075] (4) Degreasing: The lyophilized material was placed in a degreasing reactor containing ether solution and the equipment was run for 16 hours. The sample was then removed and analyzed in a fume hood for 2 hours, followed by rinsing with purified water to remove any remaining ether solution.

[0076] (5) Secondary freeze drying: The defatted matrix material is put back into the freeze dryer for freeze drying until a single layer of decellularized porcine small intestinal submucosa matrix is ​​obtained.

[0077] This embodiment also provides a method for preparing the above-mentioned biodegradable pressure-sensitive adhesive, which includes the following steps:

[0078] (1) Prepare the necessary raw materials and reagents:

[0079] ① 40 mg / mL decellularized porcine small intestinal submucosal matrix gel: The decellularized porcine small intestinal submucosal matrix was pulverized into powder with a particle size of 250 μm. 2 g of the powder was dissolved together with 200 mg of pepsin (activity 3450 U / mg, Sigma P6887-5G, derived from porcine gastric mucosa) in 25 mL of 0.01 mol / L HCl and digested for 40 h. Then, 2.8 mL of 10-fold concentrated PBS solution, 2.5 mL of 0.01 mol / L NaOH solution, and 19.7 mL of 1-fold concentrated PBS solution were added to the digestion solution, stirred thoroughly, and set aside for later use. ② Polyvinyl alcohol: A solution with a concentration range of 0.5 g / mL was prepared by dissolving polyvinyl alcohol in deionized water and heating to 90 °C until completely dissolved.

[0080] (2) Mix in proportion

[0081] Take 40g of maltitol, and weigh out trehalose, sorbitol, and vitamin E according to the component ratio. Also weigh out decellularized porcine small intestinal submucosal matrix gel, polyvinyl alcohol solution, and deionized water according to the component ratio. Mix maltitol, trehalose, and deionized water, and stir at room temperature for 1 hour. Slowly add the decellularized porcine small intestinal submucosal matrix gel and continue stirring for 1 hour. Then add sorbitol and polyvinyl alcohol solution and continue stirring for 1 hour. Finally, add vitamin E and stir at room temperature for 1 hour to obtain the pressure-sensitive adhesive.

[0082] (3) Apply pressure-sensitive adhesive to biomaterial substrate.

[0083] A pressure-sensitive adhesive was coated on one side of a decellularized porcine small intestinal submucosa substrate with a substrate thickness of 50 μm and a coating thickness of 500 μm. The substrate was dried at 26°C for 5 hours. After covering with release paper, the pressure-sensitive adhesive was coated on the other side of the decellularized porcine small intestinal submucosa substrate and dried at 26°C for 5 hours. After covering with release paper, the biodegradable pressure-sensitive adhesive was obtained.

[0084] (4) Packaging and sterilization

[0085] The prepared biodegradable pressure-sensitive adhesive was packaged in an aluminum foil bag and sterilized at 25 kGy.

[0086] Example 2

[0087] This embodiment provides a biodegradable in vivo pressure-sensitive adhesive with a decellularized matrix material as the substrate. The biodegradable in vivo pressure-sensitive adhesive includes a decellularized porcine small intestinal submucosa substrate layer and pressure-sensitive adhesive layers disposed on both sides of the decellularized porcine small intestinal submucosa substrate layer.

[0088] The substrate layer was obtained from porcine small intestinal submucosa material through virus inactivation, decellularization, freeze-drying, defatting, and secondary freeze-drying. The porcine small intestinal submucosa was derived from boars fed a closed diet of plant-based feed, weighing 150 kg. The small intestine was harvested within half an hour of death, and the mucosa, muscle layer, and serosa of the small intestine were removed within 12 hours, leaving only the small intestinal submucosa.

[0089] Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of polyvinyl alcohol base, 24% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, 18% of sorbitol plasticizer, and the balance being deionized water.

[0090] This application provides a method for preparing the above-mentioned decellularized porcine small intestinal submucosa substrate, which includes the following steps:

[0091] (1) Virus inactivation: The treated porcine small intestinal submucosa material was immersed in 0.5% polyacrylic acid (PAA) solution for 30 min, and the residual PAA solution was washed with purified water.

[0092] (2) Decellularization: Wash with a mixture of 0.1% trypsin and 0.1% sodium dodecyl sulfate (SDS) for 2 hours, and wash with purified water to remove residual solvent.

[0093] (3) Freeze-drying: Freeze-dry the decellularized matrix material.

[0094] (4) Degreasing: The lyophilized material was placed in a degreasing reactor containing ether solution and the equipment was run for 16 hours. The sample was then removed and analyzed in a fume hood for 2 hours, followed by rinsing with purified water to remove any remaining ether solution.

[0095] (5) Secondary freeze drying: The defatted matrix material is put back into the freeze dryer for freeze drying until a single layer of decellularized porcine small intestinal submucosa matrix is ​​obtained.

[0096] This embodiment also provides a method for preparing the above-mentioned biodegradable in vivo pressure-sensitive adhesive, which includes the following steps:

[0097] (1) Prepare the necessary raw materials and reagents:

[0098] ① 40 mg / mL decellularized porcine small intestinal submucosal matrix gel: The decellularized porcine small intestinal submucosal matrix was pulverized into powder with a particle size of 250 μm. 2 g of the powder was dissolved together with 200 mg of pepsin (activity 3450 U / mg, Sigma P6887-5G, derived from porcine gastric mucosa) in 25 mL of 0.01 mol / L HCl and digested for 40 h. Then, 2.8 mL of 10-fold concentrated PBS solution, 2.5 mL of 0.01 mol / L NaOH solution, and 19.7 mL of 1-fold concentrated PBS solution were added to the digestion solution, stirred thoroughly, and set aside for later use. ② Polyvinyl alcohol: A solution with a concentration range of 0.5 g / mL was prepared by dissolving polyvinyl alcohol in deionized water and heating to 90 °C until completely dissolved.

[0099] (2) Mix in proportion

[0100] Take 40g of gum arabic, and weigh out trehalose, sorbitol, and vitamin E according to the component ratio. Also weigh out decellularized porcine small intestinal submucosal matrix gel, polyvinyl alcohol solution, and deionized water according to the component ratio. Mix the gum arabic, trehalose, and deionized water, and stir at room temperature for 1 hour. Then slowly add the decellularized porcine small intestinal submucosal matrix gel and continue stirring for 1 hour. Next, add the sorbitol and polyvinyl alcohol solution and continue stirring for 1 hour. Finally, add vitamin E and stir at room temperature for 1 hour to obtain the pressure-sensitive adhesive.

[0101] (3) Apply pressure-sensitive adhesive to biomaterial substrate.

[0102] Pressure-sensitive adhesive was coated on one side of a decellularized porcine small intestinal submucosa substrate with a substrate thickness of 50 μm and a coating thickness of 500 μm. After drying at 26°C for 5 hours and covering with release paper, pressure-sensitive adhesive was coated on the other side of the decellularized porcine small intestinal submucosa substrate. After drying at 26°C for 5 hours and covering with release paper, the substrate was cut to obtain the biodegradable pressure-sensitive adhesive.

[0103] (4) Packaging and sterilization

[0104] The prepared biodegradable pressure-sensitive adhesive was packaged in an aluminum foil bag and sterilized at 25 kGy.

[0105] Example 3

[0106] This embodiment provides a biodegradable in vivo pressure-sensitive adhesive with a decellularized matrix material as the substrate. The biodegradable in vivo pressure-sensitive adhesive includes a decellularized porcine small intestinal submucosa substrate layer and pressure-sensitive adhesive layers disposed on both sides of the decellularized porcine small intestinal submucosa substrate layer.

[0107] The substrate layer was obtained from porcine small intestinal submucosa material through virus inactivation, decellularization, freeze-drying, defatting, and secondary freeze-drying. The porcine small intestinal submucosa was derived from boars fed a closed diet of plant-based feed, weighing 150 kg. The small intestine was harvested within half an hour of death, and the mucosa, muscle layer, and serosa of the small intestine were removed within 12 hours, leaving only the small intestinal submucosa.

[0108] Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of sodium carboxymethyl cellulose base (degree of substitution 0.86, viscosity 800 mPa·s), 24% of maltitol thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 18% of sorbitol plasticizer, with the balance being deionized water.

[0109] This application provides a method for preparing the above-mentioned decellularized porcine small intestinal submucosa substrate, which includes the following steps:

[0110] (1) Virus inactivation: The treated porcine small intestinal submucosa material was soaked in 0.5% PAA solution for 30 minutes and the residual PAA solution was washed with purified water.

[0111] (2) Decellularization: Wash with a mixture of 0.1% trypsin and 0.1% SDS for 2 hours, and wash with purified water to remove residual solvent.

[0112] (3) Freeze-drying: Freeze-dry the decellularized matrix material.

[0113] (4) Degreasing: The freeze-dried material is placed in a degreasing reactor containing ether solution. The equipment is run for 16 hours. The sample is taken out and analyzed in a fume hood for 2 hours. The residual ether solution is then washed with purified water.

[0114] (5) Secondary freeze drying: The defatted matrix material is put back into the freeze dryer for freeze drying until a single layer of decellularized porcine small intestinal submucosa matrix is ​​obtained.

[0115] This embodiment also provides a method for preparing the above-mentioned biodegradable pressure-sensitive adhesive, which includes the following steps:

[0116] (1) Prepare the necessary raw materials and reagents:

[0117] ① 40 mg / mL Decellularized Porcine Small Intestinal Submucosal Matrix Gel: The decellularized porcine small intestinal submucosal matrix was pulverized into powder with a particle size of 250 μm. 2 g of the powder was dissolved together with 200 mg of pepsin (activity 3450 U / mg, Sigma P6887-5G, derived from porcine gastric mucosa) in 25 mL of 0.01 mol / L HCl and digested for 40 h. Then, 2.8 mL of 10x concentration PBS solution, 2.5 mL of 0.01 mol / L NaOH solution, and 19.7 mL of 1x concentration PBS solution were added to the digestion solution, stirred thoroughly, and set aside for later use.

[0118] (2) Mix in proportion

[0119] Take 40g of maltitol, and weigh out trehalose, sodium carboxymethyl cellulose, sorbitol, and vitamin E according to the component ratio. Also weigh out decellularized porcine small intestinal submucosal matrix gel and deionized water according to the component ratio. Mix maltitol, trehalose, and deionized water, and stir at room temperature for 1 hour. Slowly add the decellularized porcine small intestinal submucosal matrix gel and continue stirring for 1 hour. Then add sorbitol and sodium carboxymethyl cellulose and continue stirring for 1 hour. Finally, add vitamin E and stir at room temperature for 1 hour to obtain the pressure-sensitive adhesive.

[0120] (3) Apply pressure-sensitive adhesive to biomaterial substrate.

[0121] A pressure-sensitive adhesive was coated on one side of a decellularized porcine small intestinal submucosa substrate with a substrate thickness of 50 μm and a coating thickness of 500 μm. The substrate was dried at 26°C for 5 hours. After covering with release paper, the pressure-sensitive adhesive was coated on the other side of the decellularized porcine small intestinal submucosa substrate and dried at 26°C for 5 hours. After covering with release paper, the biodegradable pressure-sensitive adhesive was obtained.

[0122] (4) Packaging and sterilization

[0123] The prepared biodegradable pressure-sensitive adhesive was packaged in an aluminum foil bag and sterilized at 25 kGy.

[0124] Example 4

[0125] This embodiment provides a biodegradable in vivo pressure-sensitive adhesive with a decellularized matrix material as the substrate. The biodegradable in vivo pressure-sensitive adhesive includes a decellularized porcine small intestinal submucosa substrate layer and pressure-sensitive adhesive layers disposed on both sides of the decellularized porcine small intestinal submucosa substrate layer.

[0126] The substrate layer was obtained from porcine small intestinal submucosa material through virus inactivation, decellularization, freeze-drying, defatting, and secondary freeze-drying. The porcine small intestinal submucosa was derived from boars fed a closed diet of plant-based feed, weighing 150 kg. The small intestine was harvested within half an hour of death, and the mucosa, muscle layer, and serosa of the small intestine were removed within 12 hours, leaving only the small intestinal submucosa.

[0127] Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of sodium carboxymethyl cellulose base (degree of substitution 0.86, viscosity 800 mPa·s), 24% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, 18% of sorbitol plasticizer, and the balance being deionized water.

[0128] This application provides a method for preparing the above-mentioned decellularized porcine small intestinal submucosa substrate, which includes the following steps:

[0129] (1) Virus inactivation: The treated porcine small intestinal submucosa material was soaked in 0.5% PAA solution for 30 minutes, and the residual PAA solution was washed off with purified water.

[0130] (2) Decellularization: Wash with a mixture of 0.1% trypsin and 0.1% SDS for 2 hours, and wash with purified water to remove residual solvent.

[0131] (3) Freeze-drying: Freeze-dry the decellularized matrix material.

[0132] (4) Degreasing: The lyophilized material was placed in a degreasing reactor containing ether solution and the equipment was run for 16 hours. The sample was then removed and analyzed in a fume hood for 2 hours, followed by rinsing with purified water to remove any remaining ether solution.

[0133] (5) Secondary freeze drying: The defatted matrix material is put back into the freeze dryer for freeze drying until a single layer of decellularized porcine small intestinal submucosa matrix is ​​obtained.

[0134] This embodiment also provides a method for preparing the above-mentioned biodegradable pressure-sensitive adhesive, which includes the following steps:

[0135] (1) Prepare the necessary raw materials and reagents:

[0136] ① 40 mg / mL Decellularized Porcine Small Intestinal Submucosal Matrix Gel: The decellularized porcine small intestinal submucosal matrix was pulverized into powder with a particle size of 250 μm. 2 g of the powder was dissolved together with 200 mg of pepsin (activity 3450 U / mg, Sigma P6887-5G, derived from porcine gastric mucosa) in 25 mL of 0.01 mol / L HCl and digested for 40 h. Then, 2.8 mL of 10x concentration PBS solution, 2.5 mL of 0.01 mol / L NaOH solution, and 19.7 mL of 1x concentration PBS solution were added to the digestion solution, stirred thoroughly, and set aside for later use.

[0137] (2) Mix in proportion

[0138] Take 40g of gum arabic, and weigh out trehalose, sodium carboxymethyl cellulose, sorbitol, and vitamin E according to the component ratio. Also weigh out decellularized porcine small intestinal submucosal matrix gel and deionized water according to the component ratio. Mix the gum arabic, trehalose, and deionized water, and stir at room temperature for 1 hour. Then slowly add the decellularized porcine small intestinal submucosal matrix gel and continue stirring for 1 hour. Next, add sorbitol and sodium carboxymethyl cellulose and continue stirring for 1 hour. Finally, add vitamin E and stir at room temperature for 1 hour to obtain the pressure-sensitive adhesive.

[0139] (3) Apply pressure-sensitive adhesive to biomaterial substrate.

[0140] A pressure-sensitive adhesive was coated on one side of a decellularized porcine small intestinal submucosa substrate with a substrate thickness of 50 μm and a coating thickness of 500 μm. The substrate was dried at 26°C for 5 hours. After covering with release paper, the pressure-sensitive adhesive was coated on the other side of the decellularized porcine small intestinal submucosa substrate and dried at 26°C for 5 hours. After covering with release paper, the biodegradable pressure-sensitive adhesive was obtained.

[0141] (4) Packaging and sterilization

[0142] The prepared biodegradable pressure-sensitive adhesive was packaged in an aluminum foil bag and sterilized at 25 kGy.

[0143] Example 5

[0144] This embodiment provides a biodegradable in vivo pressure-sensitive adhesive with a decellularized matrix material as the substrate. The biodegradable in vivo pressure-sensitive adhesive includes a decellularized porcine small intestinal submucosa substrate layer and pressure-sensitive adhesive layers disposed on both sides of the decellularized porcine small intestinal submucosa substrate layer.

[0145] The substrate layer was obtained from porcine small intestinal submucosa material through virus inactivation, decellularization, freeze-drying, defatting, and secondary freeze-drying. The porcine small intestinal submucosa was derived from boars fed a closed diet of plant-based feed, weighing 150 kg. The small intestine was harvested within half an hour of death, and the mucosa, muscle layer, and serosa of the small intestine were removed within 12 hours, leaving only the small intestinal submucosa.

[0146] Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of sodium carboxymethyl cellulose base (degree of substitution 0.86, viscosity 800 mPa·s), 24% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, 18% of glycerin plasticizer, and the balance being deionized water.

[0147] This application provides a method for preparing the above-mentioned decellularized porcine small intestinal submucosa substrate, which includes the following steps:

[0148] (1) Virus inactivation: Soak the treated pig small intestine material in 0.5% PAA solution for 30 minutes, and wash off the residual PAA solution with purified water.

[0149] (2) Decellularization: Wash with a mixture of 0.1% trypsin and 0.1% SDS for 2 hours, and wash with purified water to remove residual solvent.

[0150] (3) Freeze-drying: Freeze-dry the decellularized matrix material.

[0151] (4) Degreasing: The lyophilized material was placed in a degreasing reactor containing ether solution and the equipment was run for 16 hours. The sample was then removed and analyzed in a fume hood for 2 hours, followed by rinsing with purified water to remove any remaining ether solution.

[0152] (5) Secondary freeze drying: The defatted matrix material is put back into the freeze dryer for freeze drying until a single layer of decellularized porcine small intestinal submucosa matrix is ​​obtained.

[0153] This embodiment also provides a method for preparing the above-mentioned biodegradable pressure-sensitive adhesive, which includes the following steps:

[0154] (1) Prepare the necessary raw materials and reagents:

[0155] ① 40 mg / mL Decellularized Porcine Small Intestinal Submucosal Matrix Gel: The decellularized porcine small intestinal submucosal matrix was pulverized into powder with a particle size of 250 μm. 2 g of the powder was dissolved together with 200 mg of pepsin (activity 3450 U / mg, Sigma P6887-5G, derived from porcine gastric mucosa) in 25 mL of 0.01 mol / L HCl and digested for 40 h. Then, 2.8 mL of 10x concentration PBS solution, 2.5 mL of 0.01 mol / L NaOH solution, and 19.7 mL of 1x concentration PBS solution were added to the digestion solution, stirred thoroughly, and set aside for later use.

[0156] (2) Mix in proportion

[0157] Take 40g of gum arabic, and weigh out trehalose, sodium carboxymethyl cellulose, and vitamin E according to the component ratio. Also weigh out decellularized porcine small intestinal submucosal matrix gel, glycerin, and deionized water according to the component ratio. Mix the gum arabic, trehalose, and deionized water, and stir at room temperature for 1 hour. Then slowly add the decellularized porcine small intestinal submucosal matrix gel and continue stirring for 1 hour. Next, add glycerin and sodium carboxymethyl cellulose and continue stirring for 1 hour. Finally, add vitamin E and stir at room temperature for 1 hour to obtain the pressure-sensitive adhesive.

[0158] (3) Apply pressure-sensitive adhesive to biomaterial substrate.

[0159] A pressure-sensitive adhesive was coated on one side of a decellularized porcine small intestinal submucosa substrate with a substrate thickness of 50 μm and a coating thickness of 500 μm. The substrate was dried at 26°C for 5 hours. After covering with release paper, the pressure-sensitive adhesive was coated on the other side of the decellularized porcine small intestinal submucosa substrate and dried at 26°C for 5 hours. After covering with release paper, the biodegradable pressure-sensitive adhesive was obtained.

[0160] (4) Packaging and sterilization

[0161] The prepared biodegradable pressure-sensitive adhesive was packaged in an aluminum foil bag and sterilized at 25 kGy.

[0162] Example 6

[0163] The difference between this embodiment and Embodiment 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 36% sodium carboxymethyl cellulose, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. That is, gum arabic is not added as a thickener in the adhesive system; instead, sodium carboxymethyl cellulose is used as both a base material and a thickener. Everything else is the same as in Embodiment 5.

[0164] Example 7

[0165] The difference between this embodiment and Embodiment 1 is that, taking the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of polyvinyl alcohol base, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 42% of sorbitol, with the balance being deionized water. That is, maltitol thickener is not added to the adhesive system; instead, sorbitol is used as both a plasticizer and a thickener. Everything else is the same as in Embodiment 1.

[0166] Example 8

[0167] The difference between this embodiment and Embodiment 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 2.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Embodiment 5.

[0168] Example 9

[0169] The difference between this embodiment and Embodiment 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 5.2% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Embodiment 5.

[0170] Example 10

[0171] The difference between this embodiment and Embodiment 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 10% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Embodiment 5.

[0172] Example 11

[0173] The difference between this embodiment and Embodiment 5 is that, taking the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 16% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Embodiment 5.

[0174] Example 12

[0175] The difference between this embodiment and Embodiment 5 is that, taking the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of sodium carboxymethyl cellulose base, 20% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 18% of glycerin plasticizer, with the balance being deionized water. All other aspects are the same as in Embodiment 5.

[0176] Example 13

[0177] The difference between this embodiment and Embodiment 5 is that, taking the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of sodium carboxymethyl cellulose base, 30% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 18% of glycerin plasticizer, with the balance being deionized water. All other aspects are the same as in Embodiment 5.

[0178] Example 14

[0179] The difference between this embodiment and Embodiment 5 is that, taking the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 8% of sodium carboxymethyl cellulose base, 24% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 18% of glycerin plasticizer, with the balance being deionized water. All other aspects are the same as in Embodiment 5.

[0180] Example 15

[0181] The difference between this embodiment and Embodiment 5 is that, taking the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 15% of sodium carboxymethyl cellulose base, 24% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 18% of glycerin plasticizer, with the balance being deionized water. All other aspects are the same as in Embodiment 5.

[0182] Comparative Example 1

[0183] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of sodium carboxymethyl cellulose base, 5% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 18% of glycerin plasticizer, with the balance being deionized water. All other aspects are the same as in Example 5.

[0184] Comparative Example 2

[0185] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 40% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0186] Comparative Example 3

[0187] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 2% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0188] Comparative Example 4

[0189] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 30% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0190] Comparative Example 5

[0191] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 24% by mass of gum arabic thickener, 5% by mass of trehalose humectant, 3.5% by mass of vitamin E antioxidant, and 18% by mass of glycerin plasticizer, with the balance being deionized water. All other aspects are the same as in Example 5.

[0192] Comparative Example 6

[0193] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 3% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0194] Comparative Example 7

[0195] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 30% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% of sodium carboxymethyl cellulose base, 24% of gum arabic thickener, 5% of trehalose humectant, 3.5% of vitamin E antioxidant, and 18% of glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0196] Comparative Example 8

[0197] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0198] Comparative Example 9

[0199] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 1% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0200] Comparative Example 10

[0201] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include, by mass percentage, 14% decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 10% vitamin E antioxidant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0202] Comparative Example 11

[0203] The difference between this comparative example and Example 5 is that, based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 14% by mass of decellularized porcine small intestinal submucosa matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, and 18% glycerin plasticizer, with the balance being deionized water. Everything else is the same as in Example 5.

[0204] Test conditions

[0205] After being packaged with the biodegradable in vivo pressure-sensitive adhesive provided in Examples 1 to 15 and Comparative Examples 1 to 11, the products were sterilized and tested. The test methods are as follows:

[0206] (1) Initial tack: Tested according to GB / T 4852-2002. The experimental results are expressed as the maximum steel ball number that the pressure-sensitive tape can stick within the specified range. Three parallel samples are used for each group of samples, and the average value is taken.

[0207] (2) Tackiness: Tested according to GB 4851-1984 standard, with three parallel samples for each group and the average value taken.

[0208] (3) 180° peel strength: Tested according to GB / T 2792-1998 standard, with three parallel samples for each group and the average value taken.

[0209] (4) Color change: Place the sterilized pressure-sensitive adhesive in a test chamber at 50±2℃ for 5 days and observe the degree of yellowing. Evaluate the degree of color change within 24 hours according to the ASTM D1925 standard shown in Table 2.

[0210] Table 2: Classification Levels of Discoloration

[0211] (5) Elongation at break: The test was conducted according to the standard GB 6329-1986. Three parallel samples were used for each group of samples, and the average value was taken.

[0212] (6) Wound healing rate in mice: A mouse wound model was established using 6-8 week old mice (purchased from a qualified commercial animal testing company). The mice's backs were shaved, and the skin and subcutaneous membrane were removed from the back area between the neck and shoulder, creating a 1 cm diameter wound. A 0.5 mm thick circular silicone splint was sutured with 6-0 nylon sutures to prevent wound contraction. To observe differences in wound healing in mice, transparent tracing paper was used to cover the wound on days 3, 7, 10, 12, and 15 post-traumatic incision. A line was drawn along the outer edge of the wound, and the wound area was measured. The wound healing rate was calculated as (1 - incision area / initial incision area) × 100%.

[0213] (7) pH value test: The test was conducted in accordance with the standard GB / T 14518-1993. Three parallel samples were used for each group of samples, and the average value was taken.

[0214] (8) Cytotoxicity test: The MTT method was used to determine the cytotoxicity of medical devices in accordance with GB / T 16886.5-2017 Biological evaluation of medical devices Part 5: Results of in vitro cytotoxicity test.

[0215] (9) Pyrogen test: According to the Chinese Pharmacopoeia 2020 edition, Part IV: 1142 Pyrogen test method, the rabbit pyrogen test was used to evaluate the potential pyrogen reaction of the sample.

[0216] The test results are shown in Table 3:

[0217] Table 3

[0218] As can be seen from Table 3:

[0219] In Examples 1 and 2, maltitol and gum arabic were used as thickeners, respectively. The initial tack, holding tack, and peel strength of the biodegradable pressure-sensitive adhesives prepared with these components showed no significant difference. However, the addition of sodium carboxymethyl cellulose as a base material effectively improved the final viscosity characteristics of the product.

[0220] In Example 5, the formulation included 14% decellularized porcine small intestinal submucosal matrix gel, 12% sodium carboxymethyl cellulose base, 24% gum arabic thickener, 5% trehalose humectant, 3.5% vitamin E antioxidant, and 18% glycerol plasticizer, with the balance being deionized water. The prepared biodegradable pressure-sensitive adhesive for in vivo exhibited the best initial tack, holding power, and peel strength, and the lowest discoloration level. This indicates that the biodegradable pressure-sensitive adhesive for in vivo prepared in Example 5 demonstrated the strongest adhesion when bonding contact surfaces and showed better stability during storage.

[0221] Example 6 uses carboxymethyl cellulose as both a base material and a thickener, and its initial tack, holding tack, and peel strength are significantly lower than those of Examples 1-5. Example 7 uses sorbitol as both a thickener and a plasticizer, and its initial tack, holding tack, and peel strength are also significantly lower than those of Examples 1-5.

[0222] Comparative Example 1, containing less thickener, showed reduced initial tack and holding power of the pressure-sensitive adhesive, indicating that the thickener plays a crucial role in regulating the viscosity of biodegradable in-cell pressure-sensitive adhesives. When the thickener content increased to 40%, the surface fluidity of the biodegradable in-cell pressure-sensitive adhesive increased after irradiation sterilization, while holding power and peel strength experienced a sharp decline. This is because irradiation caused the glycosidic bonds in the thickener to break, generating new functional groups and altering the chemical bonds, reactive groups, and crystal structure of the thickener polysaccharide, thus changing the overall viscosity of the biodegradable in-cell pressure-sensitive adhesive. Comparative Example 3, containing less base material, showed reduced initial tack and holding power of the pressure-sensitive adhesive. Comparative Example 4, containing more base material, exhibited higher initial tack, holding power, and peel strength, but during actual coating, the poor fluidity of the adhesive system easily led to substrate curling, resulting in an uneven surface of the pressure-sensitive adhesive product. In Comparative Example 5, where no base material was added, the initial tack, holding tack, and peel strength of the pressure-sensitive adhesive were significantly reduced. This indicates that the base material plays an important role in the product formulation. Furthermore, comparing Examples 5 and 6 with Comparative Example 5 reveals that the thickener and base material provided in this application have a synergistic effect; both are indispensable, otherwise the overall performance of the biodegradable in vivo pressure-sensitive adhesive will be affected.

[0223] Comparative Example 6 contained less decellularized matrix gel, Comparative Example 7 contained more decellularized matrix gel, and Comparative Example 8 contained no decellularized matrix gel. The results showed that when excessive amounts of decellularized matrix gel were added, the adhesion of the pressure-sensitive adhesive decreased significantly. This is because the irradiation energy caused the water in the gel system to ionize, generating a large number of free radicals that reacted with proteins, leading to irreversible cross-linking reactions between amino and hydroxyl groups. During wound repair, the addition of decellularized matrix gel significantly promoted the wound healing rate (Table 4), indicating that decellularized matrix gel plays an important role in pressure-sensitive adhesives.

[0224] Table 4: Wound healing rate in mice (%)

[0225] Comparative Example 9 contained less vitamin E, Comparative Example 10 contained more vitamin E, and Comparative Example 11 contained no vitamin E. Although the viscosity results showed that the amount of vitamin E added had little effect on viscosity, the yellowing test showed that Comparative Examples 9 and 11 exhibited a higher degree of discoloration, indicating that the antioxidant vitamin E plays an important role in pressure-sensitive adhesives.

[0226] [Corrected according to Rule 91, 11.03.2026] Table 5

[0227] Table 5 shows the results of elongation at break, pH, cytotoxicity, and pyrogen reaction of a biodegradable pressure-sensitive adhesive for in vivo application, made by coating both sides with decellularized porcine small intestinal submucosa as the substrate and decellularized porcine small intestinal submucosa gel as the active substance, sodium carboxymethyl cellulose as the base material, gum arabic as the thickener, trehalose as the humectant, vitamin E as the antioxidant, and glycerin as the plasticizer. All results meet the national standard requirements.

[0228] The applicant declares that this application illustrates the process method through the above embodiments, but this application is not limited to the above process steps, that is, it does not mean that this application must rely on the above process steps to be implemented. Those skilled in the art should understand that any improvements to this application, equivalent substitutions of the raw materials used in this application, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this application.

Claims

1. A biodegradable pressure-sensitive adhesive for in vivo use based on a decellularized matrix material, comprising a bio-based substrate layer and a pressure-sensitive adhesive layer disposed on both sides of the bio-based substrate layer; Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 5%-25% base material, 5%-18% tissue-active material, 10%-35% thickener, 10%-50% plasticizer and 10%-60% deionized water by mass percentage.

2. The degradable in vivo pressure sensitive adhesive of claim 1, wherein, Based on the total mass of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer include 8%-15% base material, 10%-16% tissue-active material, 20%-30% thickener, 15%-20% plasticizer and 19%-45% deionized water by mass percentage.

3. The degradable in vivo pressure sensitive adhesive of claim 1 or 2, wherein, The tissue-active material includes any one or a combination of at least two decellularized matrix gels selected from mammalian skin, pericardium, amnion, submucosa of the small intestine, or bladder basement membrane.

4. The degradable in vivo pressure sensitive adhesive of claim 1, wherein, The base material includes biodegradable natural polymer compounds and / or biodegradable modified natural polymer compounds; The biodegradable natural polymeric compounds include any one or a combination of at least two of the following: starch, dextrin, peach gum, gum arabic, bone glue, hide glue, gelatin, fish glue, shellac, plant protein, or casein. The biodegradable modified natural polymeric compound includes any one or a combination of at least two of sodium carboxymethyl cellulose, modified starch, and polyvinyl alcohol.

5. The degradable in vivo pressure sensitive adhesive of claim 1, wherein, The thickener includes any one or a combination of at least two of the following: starch, modified starch, xanthan gum, maltitol, fructooligosaccharides, sorbitol, xylitol, lactitol, mannitol, erythritol, hydrogenated starch hydrolysate, gelatin, cellulose, methylcellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, gum arabic, tamarind gum, guar gum, agar, sodium alginate, carrageenan, pectin, or β-cyclodextrin.

6. The degradable in vivo pressure sensitive adhesive of claim 1, wherein, The plasticizer includes polyol compounds; The polyol compounds include any one or a combination of at least two of glycerol, sorbitol, or ethylene glycol.

7. The degradable in vivo pressure sensitive adhesive of any one of claims 4-6, wherein, The base material, thickener, and plasticizer are of different types.

8. The degradable, in vivo pressure sensitive adhesive of any one of claims 4-6, wherein, The base material includes sodium carboxymethyl cellulose; The thickener includes gum arabic; The plasticizer includes glycerin.

9. The degradable in vivo pressure sensitive adhesive of claim 1, wherein, Based on the total mass of the raw materials of the pressure-sensitive adhesive layer as 100%, the raw materials of the pressure-sensitive adhesive layer further include 0.1%-21.6% of a humectant and 2.5%-5.2% of an antioxidant; The humectant includes polyol humectants and / or sugar humectants; The antioxidants include any one or a combination of at least two of the following: vitamin E, vitamin C, flavonoids, tea polyphenols, phytic acid, glucosamine, lactone, or sodium hyaluronate.

10. The degradable in vivo pressure sensitive adhesive of claim 1, wherein, The material of the biological substrate layer includes decellularized matrix material; The decellularized matrix material includes any one or a combination of at least two of the following: mammalian skin, pericardium, amnion, submucosa of the small intestine, or bladder basement membrane.

11. A method for preparing a biodegradable in vivo pressure-sensitive adhesive based on a decellularized matrix material according to any one of claims 1-10, comprising the following steps: The active material, base material, thickener, plasticizer and deionized water are mixed according to the formula to obtain a pressure-sensitive adhesive slurry. The pressure-sensitive adhesive slurry is then coated on both sides of the bio-based substrate layer and dried to obtain the biodegradable in vivo pressure-sensitive adhesive with decellularized matrix material as the substrate.

12. The method of claim 11, wherein, The drying temperature is 20-50℃, and the time is 4-24h.

13. The method of claim 11, wherein, The thickness of the pressure-sensitive adhesive layer formed after drying is 0.2-2 mm.

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