Anti-leakage strong-adhesion two-component medical adhesive and preparation method thereof

Abstract

The invention relates to the technical field of medical adhesives, in particular to an anti-leakage strong-adhesion two-component medical adhesive and a preparation method thereof.The medical adhesive comprises an isocyanate prepolymer containing a hydroxyl polyester soft segment and a star-shaped structure curing agent, the isocyanate prepolymer is obtained by synthesizing polyester through esterification of dibasic acid and polyhydric alcohol, and the star-shaped structure curing agent is obtained through esterification of dibasic acid and polyhydric alcohol. The invention provides a preparation method and a use method of a polyurethane prepolymer which is obtained by performing a prepolymerization reaction with polyisocyanate and then uniformly mixing with multi-arm PEG-NHS (Polyethylene Glycol-Nitrogen-Hydroxysuccinimide). According to the present invention, the excellent performance is represented in the anastomotic stoma reinforcement, the tissue adhesion strength can achieve 75 kPa, the peristaltic stress adaptability is provided, the elongation at break can achieve 180-240%, and the coating material is suitable for pancreatic operation, gastrointestinal operation, dura mater, pulmonary resection and the like to form the in-situ sealing layer through the coating of the laparoscopic instrument so as to prevent the postoperative fistula / leakage and other complications, wherein the coating material can be used for the pancreatic operation, the gastrointestinal operation, the dura mater, the pulmonary resection and the like.

Description

Technical Field

[0001] This invention relates to the field of medical adhesives, specifically to a two-component medical adhesive with strong anti-leakage adhesion and its preparation method. Background Technology

[0002] Anastomotic leakage refers to a complication following surgery where the anastomosis of organs such as the digestive or respiratory tract ruptures due to poor healing, causing contents (such as digestive juices, gas, and food residue) to leak into surrounding tissues or body cavities. It is one of the more serious postoperative complications, commonly seen after surgeries on the gastrointestinal tract, esophagus, and biliary tract. The incidence of anastomotic leakage varies considerably depending on the type of surgery, the anastomotic site, and the patient's underlying condition, generally accounting for 5-19% of postoperative complications, and once it occurs, the mortality rate can be as high as one-third. The course of postoperative anastomotic leakage is often insidious, with early symptoms lacking specificity. Patients may only present with atypical symptoms such as fever, abdominal pain, and elevated white blood cell count, which are easily confused with normal postoperative inflammatory responses, leading to delayed diagnosis. The average diagnosis time is usually 8-12 days postoperatively. As leaked digestive fluids and intestinal contents seep into the abdominal cavity or surrounding spaces, they can rapidly lead to serious conditions such as local or diffuse peritonitis and sepsis. This not only prolongs hospital stays and increases medical costs, but may even force some patients to undergo secondary surgical interventions (such as repair, drainage, or stoma bypass). Furthermore, it can severely impact the prognosis of cancer patients, leading to increased local recurrence rates and shortened survival. Despite continuous improvements in surgical techniques and anastomotic instruments, and increasingly standardized preoperative risk assessment and preparation, anastomotic leakage remains a challenging problem for surgeons. Its prevention remains a key focus and difficulty in clinical research, and more effective strategies are urgently needed to reduce its risk and improve patient outcomes.

[0003] Tissue adhesives are medical adhesives primarily used to replace surgical sutures and reinforce anastomoses. Currently, the most commonly used tissue adhesives in clinical practice are fibrin glue and α-cyanoacrylate. However, while fibrin glue is biocompatible, its adhesive strength is insufficient, and it degrades and detaches in highly corrosive digestive fluid environments, posing a risk of bloodborne infection transmission. Although α-cyanoacrylate cures quickly, the exothermic polymerization process can lead to tissue necrosis, and its degradation products (formaldehyde) can easily cause chronic inflammation. Furthermore, its high rigidity makes it unable to adapt to the dynamic stress caused by respiratory movements.

[0004] Polyurethane, as a new generation of tissue bonding material, has shown potential for reinforcing anastomoses in complex surgeries with high fistula risk due to its controllable degradation rate and excellent mechanical adaptability. However, existing technologies still face the challenge of balancing curing kinetics and biocompatibility, requiring breakthroughs through molecular design and process innovation. Patent CN120082317A uses a polyethylene glycol-isoflurone diisocyanate prepolymer (NCO content 6.8%) combined with sodium 2-[(2-aminoethyl)amino]ethanesulfonate chain extender to achieve a natural degradation rate of >80% within 180 days. However, its tensile strength decays too quickly (decreasing to 45% of the initial value after 21 days), making it difficult to meet the mechanical maintenance requirements of pancreaticojejunostomies for 6-8 weeks. Patent CN119662185A develops a urea-containing isocyanate prepolymer (85% peel strength retention at -40°C) and achieves environmental curing at -20°C using a latent curing agent (p-toluenesulfonylaminourea). However, this system requires the addition of 0.5-1.5 parts of a water-absorbing agent (such as molecular sieve powder), which may cause local tissue dehydration at the anastomosis site. Patent CN119144267A achieves spontaneous cross-linking of components A / B by adjusting the CPR value (0.1-3), thus eliminating the need for traditional tin catalysts. Its shear strength reaches 4.2 MPa (tested in porcine pancreatic tissue), but its initial viscosity is as high as 5200 cP, which is not conducive to minimally invasive surgical injection applications. In summary, high-performance medical soft tissue adhesives need to meet various clinical application scenarios and possess the following characteristics: (1) Immediate sealing: initial adhesion ≥2N / cm² (formed within 5 minutes), capable of sealing tissue gaps ≤0.5mm, curing shrinkage <3%; (2) Dynamic mechanical compatibility: initial modulus 0.01-0.1MPa, elongation at break >200%; (3) Mechanical compatibility with the adhered tissue: adhesion to sutures and staples ≥2N / cm²; (4) Appropriate swelling rate to minimize tissue compression, resistance to digestive fluid corrosion, and biodegradability; (5) User-friendly operation, facilitating precise injection and application under laparoscopy; (6) Biocompatibility. Currently, although several medical adhesives have been approved for market launch, there is still no universal adhesive product that can simultaneously meet the requirements of immediate sealing, corrosion resistance, dynamic mechanical compatibility, and long-term biocompatibility. Summary of the Invention

[0005] To address the problems in existing technologies, this invention provides a two-component medical adhesive that provides leak-proof and strong adhesion. It offers immediate sealing, is biodegradable, and exhibits good mechanical adaptability, excellent adhesive properties, and sealing effect. It can be applied to anastomoses in pancreatic surgery, gastrointestinal surgery, dural surgery, and lung resection to reinforce anastomoses, isolate body fluids, and protect important blood vessels. Furthermore, it provides a solvent-free and catalyst-free adhesive preparation method that is simple to manufacture and avoids potential residual toxicity issues.

[0006] To achieve the above technical objectives, the technical solution of the present invention is as follows: A two-component medical adhesive that prevents leakage and has strong adhesion, comprising component A and component B; Component A is an isocyanate prepolymer containing hydroxyl polyester soft segments; Component B is a star-shaped curing agent, and its molecular branch ends contain active groups; After component A and component B are mixed, they are gradually cured within 90-120 seconds. After complete curing, a cross-linked network is formed. The tissue adhesion strength of the cured adhesive is ≥40kPa.

[0007] The isocyanate prepolymer contains 4.5-7.5% NCO and is obtained by esterifying a polyester with a dicarboxylic acid and a polyol, followed by a prepolymerization reaction with a polyisocyanate. Then, it is uniformly mixed with multi-arm PEG-NHS. The esterification synthesis temperature is 110-140℃. The molar ratio of alcohol hydroxyl groups to isocyanate functional groups in the raw material is 1:1-3.

[0008] The dicarboxylic acid is one or more of L-tartaric acid, L-malic acid, DL-malic acid, 3-hydroxyglutaric acid, 2-hydroxyadipic acid, 2,3-dihydroxymalonic acid, 2,3,4-trihydroxyglutaric acid, octanoic acid, and sebacic acid.

[0009] The polyol is one or more of polyethylene glycol, polypropylene glycol, glycerol, pentaerythritol, mannitol, sorbitol, polycaprolactone diol, polycaprolactone triol, polyglycerol, and polyether polyol.

[0010] The polyisocyanate is selected from one or more of L-lysine diisocyanate, L-lysine triisocyanate, aspartic acid diisocyanate, furan diisocyanate and hexamethylene diisocyanate.

[0011] The multi-armed PEG-NHS is one or more of two-armed PEG-NHS, four-armed PEG-NHS, and eight-armed PEG-NHS, with a molecular weight range of 2K-40K.

[0012] The star-shaped curing agent is an amine compound, which is a mixture of polyamines and Michael addition products of α,β-unsaturated carbonyl compounds.

[0013] The polyamine compound is one or more of polyethyleneimine, 1,6-hexanediamine, bis(hexamethylene)triamine, tris(2-aminoethyl)amine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, spermine, spermidine, decanediamine, and dodecylamine.

[0014] The α,β-unsaturated carbonyl compound is one or more of diethyl maleate, acrylate, and acrylamide.

[0015] The molar ratio of the α,β-unsaturated carbonyl compound to the polyamine is 1:0.1-1.2.

[0016] The star-shaped curing agent is a thiol compound, specifically a mixture of polythiols and Michael addition products of difunctional α,β-unsaturated carbonyl compounds.

[0017] The molar ratio of the bifunctional α,β-unsaturated carbonyl compound to the polythiol is 1:0.8-1.5.

[0018] The bifunctional α,β-unsaturated carbonyl compound is one or more selected from 2-(acryloyloxy)methacrylate, ethylene glycol dimethacrylate, diethylene glycol diacrylate, diethylene glycol dimethacrylate, 1,6-hexanediol diacrylate, 1,6-hexanediol dimethacrylate and 2,5-dimethyl-2,5-hexanediol dimethacrylate.

[0019] The polythiols are one or more of the following: trimethylolpropane tris(3-mercaptopropionate), bis(3-mercaptopropionic acid) ethylene glycol, ethoxylated trimethylolpropane tris(3-mercaptopropionate), pentaerythritol tetra-3-mercaptopropionate, and hexa(3-mercaptopropionic acid) dipentaerythritol ester.

[0020] The method for preparing the leak-proof, strong-adhesion two-component medical adhesive includes the preparation of isocyanate prepolymer and star-shaped curing agent.

[0021] The isocyanate prepolymer is prepared by esterifying a diacid and a polyol to obtain a hydroxyl-terminated esterified product. This product is then mixed with a polyisocyanate under a protective atmosphere and polymerized with stirring to obtain an isocyanate-terminated prepolymer. Finally, the prepolymer is blended with multi-arm PEG-NHS at room temperature to obtain component A. The molar ratio of hydroxyl to carboxyl groups in the esterification reaction is 1:0-1; the esterification temperature is 110-140 h; the polymerization temperature is 40-100 °C; the reaction time is 5-48 h; and the mass of PEG-NHS is 0.1-7% of the mass of component A. No catalyst is required for this reaction system.

[0022] The star-shaped curing agent is prepared by adding an unsaturated carbonyl compound dropwise to a polyamine or polythiol, stirring thoroughly to induce a Michael addition reaction, thereby obtaining a curing agent containing a secondary amine or thiol-terminated group. The reaction temperature is 30-90℃; the reaction time is 24-48 hours, and no catalyst is required for this system.

[0023] The adhesive is used for sealing anastomotic joints. During use, the prepolymer and curing agent are thoroughly mixed and then applied to the tissue area to be sealed to achieve in-situ curing. The volume ratio of the prepolymer to the curing agent is 1:0.2-0.5.

[0024] The application of the adhesive during the procedure is as follows: (1) Preoperative preparation stage: Assemble the two-component adhesive tooling, including: (2) Intraoperative curing stage: Use a two-component adhesive tool to mix the prepolymer and curing agent evenly and apply it to the anastomosis. It should be continuous and uniform to form a dynamic stress buffer interface. The modulus after curing is 10-200 kPa, the elongation at break is 180-240%, and the adhesion loss is ≤20% within 7 days.

[0025] The adhesive in this technical solution achieves synergistic performance regulation through a polyester-polyurethane hybrid network. The isocyanate groups and secondary amine / thiol groups in the two components undergo nucleophilic addition reactions to form a polyurethane crosslinking network. Irregular polyester in the main chain segment provides a degradable backbone, which can regulate the degradation rate to match the healing cycle. The ratio of functional groups in the curing agent and prepolymer is controlled to form a polyurethane adhesive with a gradient crosslinking density, thus influencing mechanical properties. Regarding the adhesion mechanism, to improve the density of adhesive groups and the degree of entanglement with the network, multi-arm PEG-NHS is selected. In this system, succinimidyl ester bonds rapidly covalently bind to the amino groups in the tissue, while residual isocyanate groups continuously penetrate collagen fibers, forming an "instant-long-term" two-stage adhesion. The liquid-phase two-component system is instantly blended using tooling, applied and cured in situ, and after penetrating the tissue micropores, forms a mechanically interlocking structure, further enhancing the adhesion effect and resisting corrosion from digestive fluids and cyclic stress.

[0026] As can be seen from the above description, the present invention has the following advantages: 1. This invention addresses the shortcomings of existing tissue adhesives by employing a polyester-polyurethane hybrid network. Through the synergistic effect of succinimide ester bonds (rapid adhesion) and isocyanate groups (long-lasting reinforcement), it achieves an initial tack of ≥2 N / cm² within 5 minutes and a strength of 75 kPa within 30 minutes.

[0027] 2. This invention uses a solvent-free and catalyst-free system, which simplifies the preparation process and avoids potential residual toxicity issues.

[0028] 3. The adhesive of this invention has outstanding resistance to the corrosion of digestive fluids, and the degradation process does not form fragment particles, thus reducing the occurrence of chronic inflammation.

[0029] 4. The two-component injection system of the present invention is compatible with standard laparoscopic instruments, with an operation time window of 5-8 minutes, high tooling injection stability, and screw propulsion to prevent hydraulic backflow. Attached Figure Description

[0030] Figure 1 This is a schematic diagram of the two-component syringe structure in Example 5. Detailed Implementation

[0031] Combination Figure 1 This article describes a specific embodiment of the present invention in detail, but does not limit the scope of the claims of the present invention in any way.

[0032] The raw materials for preparing the polyurethane adhesive in this embodiment are: polyethylene glycol (Mn=600), L-tartaric acid, L-lysine diisocyanate, bis(hexamethylene)triamine, and diethyl maleate.

[0033] The process for preparing the polyurethane adhesive in this embodiment is as follows: (1) Preparation of prepolymer: 15g of polyethylene glycol (Mn=600) and 1.75g ​​of L-tartaric acid were added to a three-necked flask and reacted at 140℃, 250r / min stirring speed and vacuum for 16h. The mixture was then transferred to another three-necked flask, cooled to room temperature, and 15g of polyethylene glycol (Mn=600) and 18.38g of L-lysine diisocyanate were added. The mixture was reacted at 75℃, 250r / min stirring speed and nitrogen atmosphere for 10h to obtain the prepolymer.

[0034] (2) Preparation of curing agent: 10g of dihexamethylenetriamine was added to a three-necked flask, and 17.59g of diethyl maleate was placed in a constant pressure funnel. The reaction was carried out at a speed of 6 drops / min and at a stirring speed of 300r / min under a nitrogen atmosphere for 24h to obtain the curing agent.

[0035] The application of polyurethane adhesive in this embodiment: The prepared prepolymer and curing agent are mixed at a volume ratio of 3:1 and then applied to the tissue parts to be bonded and sealed to achieve in-situ curing.

[0036] The adhesive prepared in this embodiment has a curing time of 60s; an initial load (5min) of 6.57N on fresh pigskin, a shear overlap strength of 26.28kPa; a 30min load of 11.75N, a shear overlap strength of 47kPa; and a burst strength of 75.5kPa.

[0037] The bonding and sealing effects of the adhesive described in this embodiment were further tested: The sealing effect of the adhesive in this embodiment was tested according to ASTM F2392-04, "Standard Test Method for Bursting Strength of Surgical Sealants." A fresh pig stomach was used to simulate human biological tissue, and the bursting strength of the adhesive described in Example 1 was tested. The test results showed that the bursting strength was as high as 45.6 kPa; no leakage occurred after maintaining a constant pressure of 15 kPa for 48 hours, indicating that the adhesive described in this invention has good bonding and sealing effects.

[0038] Example 2 The raw materials for preparing the polyurethane adhesive in this embodiment are: glycerol, L-lysine diisocyanate, sebacic acid, polyethylene glycol (Mn=1000), tetraethylenepentamine, dodecylamine, and diethyl maleate.

[0039] The process for preparing the polyurethane adhesive in this embodiment is as follows: (1) Preparation of prepolymer: 1 mmol of glycerol and 1 mmol of sebacic acid were added to a three-necked flask and reacted at 160°C, 250 r / min stirring speed and vacuum for 7.5 h; then 2 mmol of polyethylene glycol and 3 mmol of L-lysine diisocyanate were added and reacted at 75°C, 250 r / min stirring speed and nitrogen atmosphere for 5 h to obtain the prepolymer.

[0040] (2) Preparation of curing agent: 10g of tetraethylenepentamine and 3g of dodecylamine were added to a three-necked flask, and 23.24g of diethyl maleate was placed in a constant pressure funnel. The reaction was carried out at a speed of 6 drops / min and at 40℃, 300r / min stirring speed and nitrogen atmosphere for 24h to obtain curing agent.

[0041] The application of polyurethane adhesive in this embodiment: The prepared prepolymer and curing agent are mixed at a volume ratio of 2:1 and then applied to the tissue parts to be bonded and sealed to achieve in-situ curing.

[0042] The adhesive prepared in this embodiment has a curing time of 120s; an initial load (5min) on fresh pigskin of 5.75N; a shear overlap strength of 23kPa; and a burst strength of 50kPa.

[0043] Example 3 The raw materials for preparing the polyurethane adhesive in this embodiment are: polyethylene glycol (Mn=1000), L-malic acid, L-lysine diisocyanate, bis(hexamethylene)triamine, dodecylamine, and diethyl maleate.

[0044] The process for preparing the polyurethane adhesive in this embodiment is as follows: (1) Preparation of prepolymer: 10g of polyethylene glycol (Mn=1000) and 1.5g of L-malic acid were added to a three-necked flask and reacted at 140℃, 250r / min stirring speed and vacuum for 16h. The mixture was then transferred to another three-necked flask, cooled to room temperature, and 10g of polyethylene glycol (Mn=600) and 19.03g of L-lysine diisocyanate were added. The mixture was reacted at 75℃, 250r / min stirring speed and nitrogen atmosphere for 16h to obtain the prepolymer. Finally, 3% by mass of four-arm-PEG-NHS was added and stirred evenly at room temperature.

[0045] (2) Preparation of curing agent: 10g of bis(hexamethylene)triamine and 5g of dodecylamine were added to a three-necked flask, and 27.86g of diethyl maleate was placed in a constant pressure funnel. The reaction was carried out at a speed of 6 drops / min and at a stirring speed of 300r / min under a nitrogen atmosphere for 24h to obtain the curing agent.

[0046] The application of polyurethane adhesive in this embodiment: The prepared prepolymer and curing agent are mixed at a volume ratio of 3:1 and then applied to the tissue parts to be bonded and sealed to achieve in-situ curing.

[0047] The adhesive prepared in this embodiment has a curing time of 90s; the initial load (5min) on fresh pigskin is 9.6N, the shear overlap strength is 38.4kPa, the load at 30min is 19N, the shear overlap strength is 76kPa, and the burst strength is 90kPa.

[0048] Example 4 The raw materials for preparing the polyurethane adhesive in this embodiment are: polycaprolactone diol (Mn=530), L-lysine diisocyanate, bis(3-mercaptopropionic acid) ethylene glycol, and ethyl 2-(acryloyloxy)methacrylate.

[0049] The process for preparing the polyurethane adhesive in this embodiment is as follows: (1) Preparation of prepolymer: 3.13 g of polycaprolactone diol (Mn=530) and 4.2 g of L-lysine diisocyanate were added to a three-necked flask and reacted at 75 °C, 250 r / min stirring speed and nitrogen atmosphere for 8 h to obtain the prepolymer.

[0050] (2) Preparation of curing agent: 2.38 g of bis(3-mercaptopropionic acid) ethylene glycol and 2.28 g of 2-(acryloyloxy) methacrylate ethyl ester were added to a three-necked flask and reacted at 40 °C, 300 r / min stirring speed and nitrogen atmosphere for 24 h to obtain curing agent.

[0051] The application of polyurethane adhesive in this embodiment: The prepared prepolymer and curing agent are mixed at a volume ratio of 2:1 and then applied to the tissue parts to be bonded and sealed to achieve in-situ curing.

[0052] The adhesive prepared in this embodiment has a curing time of 30 minutes; a maximum load on fresh pigskin of 5.6 N; a shear overlap strength of 29.2 kPa; and a burst strength of 35.6 kPa. Example 5 The prepolymer and curing agent prepared in Example 1 are uniformly mixed and applied using a two-component syringe, which can be used for real-time adhesion and sealing of wound tissue in laparoscopic surgery; wherein the prepolymer and curing agent are mixed in a volume ratio of 5:1 to 1:1. The mixing structure of the two-component syringe is only required to achieve uniform mixing of the two components in the specified ratio; the specific structure is not limited. Figure 1 The two-component syringe shown includes a screw-type injector A, two-component injection chambers B, an extension tube C, and a mixing head D. The volume ratio of the two injection chambers is 1:(1-5), which are used to dispense the prepolymer and the curing agent, respectively. The screw plays the role of stabilizing the extrusion of the prepolymer and the curing agent. After being fully mixed by the mixing head, the extruded adhesive is applied to the joint to achieve in-situ curing.

[0053] In the performance testing of the adhesives in Examples 1-4 above, the curing time test was performed in accordance with GB / T13477.5. The tests were conducted according to the 2002 standard "Test Methods for Building Sealing Materials - Part 5: Determination of Surface Drying Time"; the lap-shear strength test was performed according to YY / T0729.1. 2009 Test methods for adhesive properties of tissues - Part 1: Overlap Shear tensile strength was tested according to the standard; burst strength was tested according to ASTM F2392. 04. Standard Test Method for Burst Strength of Surgical Sealants.

[0054] It is understood that the above detailed description of the present invention is for illustrative purposes only and is not intended to limit the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that modifications or equivalent substitutions can still be made to the present invention to achieve the same technical effects; as long as the usage requirements are met, they are all within the protection scope of the present invention.

Claims

1. A two-component medical adhesive with strong anti-leakage adhesion, characterized in that: Includes component A and component B; Component A is an isocyanate prepolymer containing hydroxyl polyester soft segments; Component B is a star-shaped curing agent, and its molecular branch ends contain active groups; After component A and component B are mixed, they are gradually cured within 90-120 seconds. After complete curing, a cross-linked network is formed. The tissue adhesion strength of the cured adhesive is ≥40kPa.

2. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 1, characterized in that: The isocyanate prepolymer has an NCO content of 4.5-7.5%, and is obtained by esterifying a polyester with a dicarboxylic acid and a polyol, followed by a prepolymerization reaction with a polyisocyanate, and then uniformly mixing it with multi-arm PEG-NHS.

3. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 2, characterized in that: The dicarboxylic acid is one or more of L-tartaric acid, L-malic acid, DL-malic acid, 3-hydroxyglutaric acid, 2-hydroxyadipic acid, 2,3-dihydroxymalonic acid, 2,3,4-trihydroxyglutaric acid, octanoic acid, and sebacic acid.

4. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 2, characterized in that: The polyol is one or more of polyethylene glycol, polypropylene glycol, glycerol, pentaerythritol, mannitol, sorbitol, polycaprolactone diol, polycaprolactone triol, polyglycerol, and polyether polyol.

5. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 2, characterized in that: The polyisocyanate is selected from one or more of L-lysine diisocyanate, L-lysine triisocyanate, aspartic acid diisocyanate, furan diisocyanate and hexamethylene diisocyanate.

6. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 2, characterized in that: The multi-armed PEG-NHS is one or more of two-armed PEG-NHS, four-armed PEG-NHS, and eight-armed PEG-NHS, with a molecular weight range of 2K-40K.

7. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 1, characterized in that: The star-shaped curing agent is an amine compound, which is a mixture of polyamines and Michael addition products of α,β-unsaturated carbonyl compounds; the polyamine compound is one or more selected from polyethyleneimine, 1,6-hexanediamine, bis(hexamethylene)triamine, tris(2-aminoethyl)amine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, spermine, spermidine, decanediamine and dodecylamine; The α,β-unsaturated carbonyl compound is one or more of diethyl maleate, acrylate, and acrylamide.

8. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 1, characterized in that: The star-shaped curing agent is a thiol compound, specifically a mixture of polythiols and Michael addition products of difunctional α,β-unsaturated carbonyl compounds; The molar ratio of the bifunctional α,β-unsaturated carbonyl compound to the polythiol is 1:0.8-1.5; The bifunctional α,β-unsaturated carbonyl compound is one or more of 2-(acryloyloxy)methacrylate, ethylene glycol dimethacrylate, diethylene glycol diacrylate, diethylene glycol dimethacrylate, 1,6-hexanediol diacrylate, 1,6-hexanediol dimethacrylate and 2,5-dimethyl-2,5-hexanediol dimethacrylate; The polythiols are one or more of the following: trimethylolpropane tris(3-mercaptopropionate), bis(3-mercaptopropionic acid) ethylene glycol, ethoxylated trimethylolpropane tris(3-mercaptopropionate), pentaerythritol tetra-3-mercaptopropionate, and hexa(3-mercaptopropionic acid) dipentaerythritol ester.

9. The two-component medical adhesive with strong adhesion and leak-proof properties according to claim 1, characterized in that: The method for preparing the leak-proof, strong-adhesion two-component medical adhesive includes the preparation of isocyanate prepolymer and star-shaped curing agent; The isocyanate prepolymer is prepared by esterifying a diacid and a polyol to obtain a hydroxyl-terminated esterified product. This product is then mixed with a polyisocyanate under a protective atmosphere and polymerized with stirring to obtain an isocyanate-terminated prepolymer. Finally, the prepolymer is blended with multi-arm PEG-NHS at room temperature to obtain component A. The molar ratio of hydroxyl to carboxyl groups in the esterification reaction is 1:0-1; the esterification temperature is 110-140 h; the polymerization temperature is 40-100 °C; the reaction time is 5-48 h; and the mass of PEG-NHS is 0.1-7% of the mass of component A. No catalyst is required for this reaction system. The star-shaped curing agent is prepared by adding an unsaturated carbonyl compound dropwise to a polyamine or polythiol, stirring thoroughly to induce a Michael addition reaction, and obtaining a curing agent containing a secondary amine or thiol-terminated group.

10. The leak-proof, strong-adhesion two-component medical adhesive according to claim 9, characterized in that: The reaction temperature is 30-90℃; the reaction time is 24-48h; and no catalyst is required for this reaction system.

Images