Modified isocyanate prepolymer, preparation method thereof and degradable biological adhesive

Abstract

The invention discloses a modified isocyanate prepolymer, a preparation method thereof and a degradable biological adhesive, and belongs to the technical field of medical adhesives. The preparation method comprises the following steps: firstly, continuously reacting alcohol with polyhydroxy acid at a certain temperature to obtain a polyester soft segment containing part of hydroxyl and carboxyl functional groups; and adding isocyanate or isocyanate and alcohol into the prepolymer, and reacting to obtain the modified isocyanate prepolymer. And mixing the modified isocyanate prepolymer with a curing agent to obtain the polyurethane biological adhesive. The curing agent is an unsaturated carbonyl compound modified amine curing agent or a polyamine modified polyphenol curing agent. The polyurethane adhesive is applied to adhesion of a wet tissue interface, and during application, the polyurethane biological adhesive is smeared to a tissue part needing to be adhered and sealed, and in-situ curing is realized. The process for preparing the isocyanate prepolymer is simple, and the polyurethane biological adhesive obtained by utilizing the isocyanate prepolymer is easy to degrade and good in wet adhesion.

Description

Technical Field

[0001] The invention relates to the technical field of medical adhesives, and in particular to a modified isocyanate prepolymer and a preparation method thereof, and a degradable bioadhesive. Background Art

[0002] With the continuous progress of clinical medicine, medical adhesives can achieve rapid hemostasis and adhesion closure of tissues, which is beneficial to improve the effect of surgical treatment and has been widely studied in the medical field. Polyurethane adhesives have excellent mechanical properties, high bonding strength, clear molecular structure and easy design and modification, and have great potential in the field of medical adhesives.

[0003] At present, polyurethane adhesives usually use non-degradable diols or polyols as the flexible chain segments of the polymer. Although this gives the adhesive good flexibility, it also has problems such as difficult degradation and difficult absorption of degradation products. The preparation of most polyurethane adhesives requires the participation of organic solvents and catalysts, and the complex synthesis and purification processes are difficult to industrialize. Polyurethane adhesives often need to be used in a moist tissue environment, making it difficult to achieve effective adhesion to the wet tissue interface.

[0004] Patent CN 113150239 A uses polyethylene glycol, diisocyanate, tetrahydrofuran and terminal hydroxyl chain extender to prepare a polyurethane adhesive with controllable curing time, but it is difficult to degrade; Patent CN 116712595 A uses polyhydroxy compounds, N,N-dimethylformamide, lysine diisocyanate, tertiary amine compounds, catalysts and stabilizers to obtain a degradable adhesive, but its preparation involves organic solvents and catalysts, and the synthesis and purification processes are complicated.

[0005] In order to achieve rapid clinical application of polyurethane adhesives, polyurethane adhesives need to have the following properties: degradable, with a degradation rate that matches the tissue regeneration cycle; simple preparation process and easy industrialization; wettable adhesion, used for moist tissue interfaces; fast curing time; good biocompatibility; and matching the mechanical properties of the target tissue. Summary of the invention

[0006] In order to solve the problems of existing polyurethane adhesives being difficult to degrade, having a complicated preparation process, and having poor wet adhesion, the present invention aims to provide a modified isocyanate prepolymer, a preparation method thereof, and a degradable polyurethane bioadhesive. The preparation process of the isocyanate prepolymer is simple, and the polyurethane bioadhesive obtained therefrom is easily degraded and has good wet adhesion.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] A method for preparing a modified isocyanate prepolymer comprises the following steps (1)-(2):

[0009] (1) In a protective atmosphere, alcohols and polyhydroxy acids are continuously reacted at a certain temperature to obtain a polyester soft segment containing partial hydroxyl and carboxyl functional groups; wherein: the reaction temperature is 40-150° C., the reaction time is 1-72 hours; the molar ratio of the alcohol hydroxyl group of the alcohol to the carboxyl group of the polyhydroxy acid is 1:(0.01-10);

[0010] (2) adding isocyanate or adding isocyanate and alcohol to the reaction product obtained in step (1), and continuing the reaction at a certain temperature for a period of time to obtain the modified isocyanate prepolymer; wherein the reaction temperature is 40-150° C. and the reaction time is 1-72 hours.

[0011] Furthermore, the molar ratio of the total amount of alcoholic hydroxyl groups of the alcohols used in step (1) and step (2) to the isocyanate functional groups of the isocyanate is 1:(0.1-10).

[0012] Furthermore, in steps (1)-(2), the alcohol is a diol or a polyol, and the molecular weight of the alcohol is 62 to 10000 Da; the alcohol is selected from one or more of ethylene glycol, 1,2-propylene glycol, 1,4-butanediol, polyethylene glycol, polytetrahydrofuran, polycaprolactone diol and castor oil.

[0013] Furthermore, in step (1), the polyhydroxy acid has a hydroxyl functionality of ≥1 and a carboxyl functionality of ≥1.

[0014] Furthermore, the polyhydroxy acid is selected from one or more of 2,2-dihydroxymethylpropionic acid, 2,2-dihydroxymethylbutyric acid, tartaric acid, malic acid, lactic acid, citric acid, glucaric acid, threonic acid, gulonic acid, mucic acid, glyceric acid, okadaic acid and bile acid.

[0015] Furthermore, in step (2), the isocyanate functionality of the isocyanate is ≥ 2, and the isocyanate is an aliphatic isocyanate or an alicyclic isocyanate.

[0016] Furthermore, the isocyanate is selected from one or more of L-lysine diisocyanate, L-lysine triisocyanate, hexamethylene diisocyanate, isophorone diisocyanate and 4,4'-dicyclohexylmethane diisocyanate.

[0017] A modified isocyanate prepolymer is prepared by the method, and the prepolymer can be used to further prepare a degradable polyurethane adhesive; the preparation process of the degradable polyurethane adhesive is: the modified isocyanate prepolymer and a curing agent are mixed in a certain volume ratio to obtain the polyurethane bioadhesive; the volume ratio of the modified isocyanate prepolymer and the curing agent is 1: (0.1-10); the curing agent is an unsaturated carbonyl compound modified amine curing agent or a polyamine modified polyphenol curing agent.

[0018] Furthermore, the preparation process of the unsaturated carbonyl compound modified amine curing agent is as follows: in a protective atmosphere, a polyamine compound and an unsaturated carbonyl compound are continuously reacted at a certain temperature, and an unsaturated carbonyl compound modified amine curing agent is obtained by an addition reaction between an unsaturated olefin and a primary amine group; wherein the reaction temperature is 20 to 100° C., and the reaction time is 12 to 48 hours; and the molar ratio of the unsaturated olefin in the unsaturated carbonyl compound to the primary amine group in the polyamine compound is 1:(0.1 to 10);

[0019] Furthermore, the preparation process of the polyamine-modified polyphenol curing agent is as follows: in a protective atmosphere, continuously reacting the polyphenol compound and the alcohol compound at a certain temperature until they are completely dissolved; further adding a polyamine compound and continuously reacting at a certain temperature, utilizing the phenolic hydroxyl functional group and the primary amine group to undergo an addition reaction to obtain the polyamine-modified polyphenol curing agent; wherein the reaction temperature is 10 to 100° C., and the reaction time is 1 to 24 hours; the functional group molar ratio of the polyphenol compound to the polyamine compound is 1:(0 to 1), and the mass ratio of the polyphenol compound to the alcohol compound is 1:(0.1 to 10);

[0020] Further, in the preparation process of the unsaturated carbonyl compound modified amine curing agent, the unsaturated carbonyl compound is selected from one or more of maleic acid, dimethyl maleate, diethyl maleate, dibutyl maleate, diallyl maleate, dioctyl maleate, fumaric acid, diethyl fumarate, dimethyl fumarate and dibutyl fumarate; the polyamine compound is selected from one or more of 1,2-propylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,6-hexanediamine, 1,8-octanediamine, bis(hexamethylene)triamine, spermine, spermidine, n-propylamine, n-butylamine, polyetheramine, polyethyleneimine with a molecular weight of 300-25000Da, diethylenetriamine, triethylenetetramine, tetraethylenepentamine and polyethylenepolyamine;

[0021] Furthermore, in the preparation process of the polyamine-modified polyphenol curing agent, the polyphenol compound is selected from one or more of tannic acid, gallic acid, gallic acid ester compounds (such as propyl gallate, lauryl gallate, etc.), tea polyphenols, gallol, lignin, catechol and ellagic acid, and the polyamine compound is selected from 1,2-propylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,6-hexanediamine, 1,8-octanediamine, bis(hexamethylene)triamine, spermine, spermidine, n-propylamine, n-butylamine, polyetheramine, molecular weight The present invention relates to one or more polyethyleneimine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine and polyethylenepolyamine with a molecular weight of 300-25000Da; the alcohol compound is selected from glycerol, ethylene glycol, diethylene glycol, triethylene glycol, 1,2-propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, 2,4-pentanediol, 2,5-hexanediol, dipropylene glycol, castor oil, diol or polyol polymer with a molecular weight of 200-1000Da (such as polyethylene glycol, polytetrahydrofuran, polycaprolactone diol, polycaprolactone triol, etc.).

[0022] The degradable polyurethane adhesive is used for bonding wet tissue interfaces. When used, the polyurethane bioadhesive is applied to the desired bonding and sealing tissue site and cured in situ.

[0023] The design mechanism and beneficial effects of the present invention are as follows:

[0024] 1. The present invention utilizes polyhydroxy acid to modify the polymer flexible chain segment, and further combines it with isocyanate to obtain a modified isocyanate prepolymer containing ester bonds and carboxylic acid functional groups. The introduction of ester bonds can improve the degradation performance of polyurethane adhesives; the introduction of carboxylic acids can enhance the hydrophilicity of adhesives and improve the adhesive's adhesion performance to wet tissue interfaces.

[0025] 2. The modified isocyanate prepolymer and curing agent of the present invention have a simple synthesis process, safe and reliable raw materials, and the reaction does not require a catalyst and an organic solvent, which can effectively avoid potential toxic risks.

[0026] 3. The polyurethane adhesive prepared by the present invention has good flexibility and matches the tissue modulus, which can avoid problems such as stress concentration caused by being too hard and resulting in bonding failure, and being too soft and easily damaged and failing.

[0027] 4. The polyurethane adhesive prepared by the present invention is degradable, simple to operate, has a fast curing time, good wet bonding performance, good biocompatibility, and is easy to industrialize. DETAILED DESCRIPTION

[0028] The technical solution of the present invention will be further described below through specific examples. Obviously, the examples are only for illustration and to help understand the nature, and should not be regarded as specific limitations on the application of the present invention.

[0029] Embodiment 1:

[0030] This embodiment provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=600), L-tartaric acid, polyethylene glycol (Mn=1500), L-lysine diisocyanate, 1,6-hexanediamine, diethyl maleate. The preparation of the polyurethane adhesive is as follows:

[0031] (1) Preparation of prepolymer: Under a nitrogen atmosphere, 10 g of polyethylene glycol (Mn=600) and 1.25 g of L-tartaric acid were reacted at 140°C with continuous stirring for 8 h to obtain a polyester soft segment. Then, 12.5 g of polyethylene glycol (Mn=1500) and 11.31 g of L-lysine diisocyanate were added in sequence and the mixture was reacted at 75°C with continuous stirring for 12 h to obtain a modified isocyanate prepolymer.

[0032] (2) Preparation of curing agent: Under nitrogen atmosphere, 10 g of 1,6-hexanediamine was added dropwise to 29.63 g of diethyl maleate, and the mixture was stirred at 60° C. for 24 h to obtain an unsaturated carbonyl compound-modified amine curing agent.

[0033] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 3:1 to prepare the adhesive.

[0034] The curing time of the adhesive prepared in this embodiment is 90s; the maximum load on pig skin is 17.43N, the shear lap strength is 69.72kPa; the gel elastic modulus is 0.28MPa, and the elongation at break is 191.10%.

[0035] To further test the sealing effect of the adhesive on tissue, the bursting strength of the adhesive was tested according to the ASTM F2392-04-2015 standard test method. The results showed that the bursting strength was 55.2 kPa, proving that the sealing performance of the adhesive was good.

[0036] To further test the bonding effect of the adhesive on wet tissue surfaces, the pig skin to be tested was wetted and soaked with PBS buffer. The maximum load on the pig skin was tested to be 18.58N, and the shear lap strength was 74.32kPa, which proved the effectiveness of the adhesive on wet tissue surfaces.

[0037] Embodiment 2:

[0038] This embodiment provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=600), L-tartaric acid, L-lysine diisocyanate, 1,6-hexanediamine, diethyl maleate. The preparation of the polyurethane adhesive specifically includes the following steps:

[0039] (1) Preparation of prepolymer: 10 g of polyethylene glycol (Mn=600) and 0.83 g of L-tartaric acid were reacted at 140° C. with continuous stirring for 8 h to obtain a polyester soft segment, and then 7.54 g of L-lysine diisocyanate was added and the mixture was reacted at 75° C. with continuous stirring for 12 h to obtain a modified isocyanate prepolymer.

[0040] (2) Preparation of curing agent: The preparation process and proportion are the same as those in Example 1.

[0041] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 3:1 to prepare the adhesive.

[0042] The curing time of the adhesive prepared in this embodiment is 80s; the maximum load on pig skin is 7.44N, the shear lap strength is 29.76kPa; the gel elastic modulus is 0.56MPa, and the elongation at break is 117.06%.

[0043] Embodiment 3:

[0044] This embodiment provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=1000), L-tartaric acid, polyethylene glycol (Mn=600), L-lysine diisocyanate, 1,6-hexanediamine, diethyl maleate. The preparation of the polyurethane adhesive specifically includes the following steps:

[0045] (1) Preparation of prepolymer: 10 g of polyethylene glycol (Mn=1000) and 0.75 g of L-tartaric acid were added to a three-necked flask, and the mixture was reacted at 140° C., 250 r / min, and a nitrogen atmosphere for 16 h, and then the water was removed for use. Then, 3 g of polyethylene glycol (Mn=600) and 6.79 g of L-lysine diisocyanate were added to the system, and the mixture was reacted at 75° C., 250 r / min, and a nitrogen atmosphere for 8 h to obtain a modified isocyanate prepolymer.

[0046] (2) Preparation of curing agent: The preparation process and proportion are the same as those in Example 1.

[0047] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 3:1 to prepare the adhesive.

[0048] The curing time of the adhesive prepared in this embodiment is 80s; the maximum load on pig skin is 5.87N, the shear lap strength is 23.48kPa; the gel elastic modulus is 0.29MPa, and the elongation at break is 177.86%.

[0049] Embodiment 4:

[0050] This embodiment provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=600), L-tartaric acid, polyethylene glycol (Mn=1500), L-lysine diisocyanate, 1,6-hexanediamine, diethyl maleate. The preparation of the polyurethane adhesive specifically includes the following steps:

[0051] (1) Preparation of prepolymer: Under a nitrogen atmosphere, 10 g of polyethylene glycol (Mn=600) and 1.25 g of L-tartaric acid were reacted at 140°C with continuous stirring for 16 h to obtain a polyester soft segment, and then 12.5 g of polyethylene glycol (Mn=1500) and 11.31 g of L-lysine diisocyanate were added in sequence, and the mixture was reacted at 75°C with continuous stirring for 8 h to obtain a modified isocyanate prepolymer.

[0052] (2) Preparation of curing agent: The preparation process and proportion are the same as those in Example 1.

[0053] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 3:1 to prepare the adhesive.

[0054] The curing time of the adhesive prepared in this embodiment is 80s; the maximum load on pig skin is 2.05N, the shear lap strength is 8.2kPa; the gel elastic modulus is 0.19MPa, and the elongation at break is 286.15%.

[0055] Embodiment 5:

[0056] This embodiment provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=600), L-tartaric acid, L-lysine diisocyanate, 1,6-hexanediamine, diethyl maleate. The preparation of the polyurethane adhesive specifically includes the following steps:

[0057] (1) Preparation of prepolymer: 10 g of polyethylene glycol (Mn=600) and 0.83 g of L-tartaric acid were reacted at 140° C. with continuous stirring for 16 h to obtain a polyester soft segment, and then 7.54 g of L-lysine diisocyanate was added and the mixture was reacted at 75° C. with continuous stirring for 8 h to obtain a modified isocyanate prepolymer.

[0058] (2) Preparation of curing agent: The preparation process and proportion are the same as those in Example 1.

[0059] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 3:1 to prepare the adhesive.

[0060] The curing time of the adhesive prepared in this embodiment is 90s; the maximum load on pig skin is 1.18N, the shear lap strength is 4.72kPa; the gel elastic modulus is 0.026MPa, and the elongation at break is 413.46%.

[0061] Comparative Example 1:

[0062] This comparative example provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=600), L-tartaric acid, polyethylene glycol (Mn=1500), L-lysine diisocyanate, polyethyleneimine (Mw=600), tannic acid, and glycerol. The preparation of the polyurethane adhesive specifically includes the following steps:

[0063] (1) Preparation of prepolymer: The preparation process and proportion are the same as those in Example 1.

[0064] (2) Preparation of curing agent: 7.5 g of tannic acid was fully dissolved in 20 ml of glycerol, and then 0.5 ml of polyethyleneimine (Mw=600) was added at room temperature. After sufficient stirring, the mixture was reacted at 55°C, 250 r / min, and nitrogen atmosphere for 2 h to obtain a polyamine-modified polyphenol curing agent.

[0065] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 4:1 to prepare the adhesive.

[0066] The curing time of the adhesive prepared in this comparative example is 15s; the maximum load on pig skin is 2.77N, the shear lap strength is 11.08kPa; the gel elastic modulus is 0.46MPa, and the elongation at break is 98.65%.

[0067] Comparative Example 2:

[0068] This comparative example provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=600), L-tartaric acid, L-lysine diisocyanate, polyethyleneimine (Mw=600), tannic acid, and glycerol. The preparation of the polyurethane adhesive specifically includes the following steps:

[0069] (1) Preparation of prepolymer: The preparation process and proportion are the same as those in Example 2.

[0070] (2) Preparation of curing agent: The preparation process and proportion are the same as those of Comparative Example 1.

[0071] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 4:1 to prepare the adhesive.

[0072] The curing time of the adhesive prepared in this comparative example is 15s; the maximum load on pig skin is 2.84N, the shear lap strength is 11.36kPa; the gel elastic modulus is 0.30MPa, and the elongation at break is 104.81%.

[0073] Comparative Example 3:

[0074] This comparative example provides a polyurethane adhesive, the raw materials for its preparation include: polyethylene glycol (Mn=1000), L-tartaric acid, polyethylene glycol (Mn=600), L-lysine diisocyanate, polyethyleneimine (Mw=600), tannic acid, and glycerol. The preparation of the polyurethane adhesive specifically includes the following steps:

[0075] (1) Preparation of prepolymer: The preparation process and proportion are the same as those in Example 3.

[0076] (2) Preparation of curing agent: The preparation process and proportion are the same as those of Comparative Example 1.

[0077] (3) Preparation of adhesive: The prepolymer and the curing agent are fully mixed in a volume ratio of 4:1 to prepare the adhesive.

[0078] The curing time of the adhesive prepared in this comparative example is 15s; the maximum load on pig skin is 1.41N, the shear lap strength is 5.64kPa; the gel elastic modulus is 0.31MPa, and the elongation at break is 92.61%.

[0079] Performance Test The adhesives described in Examples 1-5 and Comparative Examples 1-3 were used as test objects to measure the curing time, lap-shear strength, elastic modulus and tensile strain.

[0080] (1) Curing time test

[0081] The curing time is tested with reference to GB / T13477.5-2002 "Test methods for building sealing materials Part 5: Determination of surface drying time".

[0082] (2) Lap-shear strength test

[0083] The test was carried out according to the standard YY / T 0729.1-2009 “Test method for bonding performance of tissue adhesives Part 1: Lap-shear tensile bearing strength”.

[0084] (3) Tensile elastic modulus test

[0085] The test was carried out according to GB / T 1040.1-2018 "Determination of tensile properties of plastics Part 1: General".

[0086] The above specific embodiments are only further descriptions of the technical solutions of the present invention and cannot be considered as specific limitations on the application of the present invention. Those skilled in the art can understand that equivalent replacements or changes based on the technical solutions of the present invention are all within the scope of protection claimed by the present invention.

Claims

1. A method for preparing a modified isocyanate prepolymer, characterized in that: The method comprises the following steps (1)-(2): (1) In a protective atmosphere, alcohols and polyhydroxy acids are continuously reacted at a certain temperature to obtain a polyester soft segment containing some hydroxyl and carboxyl functional groups; (2) adding isocyanate or adding isocyanate and alcohol to the reaction product obtained in step (1), and continuing the reaction at a certain temperature for a period of time to obtain the modified isocyanate prepolymer.

2. The method for preparing a modified isocyanate prepolymer according to claim 1, wherein: In steps (1)-(2), the reaction temperature is 40-150° C. and the reaction time is 1-72 h; In step (1), the molar ratio of the alcoholic hydroxyl group of the alcohol to the carboxyl group of the polyhydroxy acid is 1:(0.01-10); The molar ratio of the total amount of alcoholic hydroxyl groups of the alcohols used in step (1) and step (2) to the isocyanate functional groups of the isocyanate is 1:(0.1-10).

3. The method for preparing a modified isocyanate prepolymer according to claim 1, characterized in that: In steps (1)-(2), the alcohol is a diol or a polyol, and the molecular weight of the alcohol is 62 to 10000 Da; the alcohol is selected from one or more of ethylene glycol, 1,2-propylene glycol, 1,4-butanediol, polyethylene glycol, polytetrahydrofuran, polycaprolactone diol and castor oil.

4. The method for preparing a modified isocyanate prepolymer according to claim 1, characterized in that: In step (1), the hydroxyl functionality of the polyhydroxy acid is ≥1 and the carboxyl functionality is ≥1; the polyhydroxy acid is selected from one or more of 2,2-dihydroxymethylpropionic acid, 2,2-dihydroxymethylbutyric acid, tartaric acid, malic acid, lactic acid, citric acid, glucaric acid, threonic acid, gulonic acid, mucic acid, glyceric acid, okadaic acid and bile acid.

5. The method for preparing a modified isocyanate prepolymer according to claim 1, characterized in that: In step (2), the isocyanate has an isocyanate functionality of ≥2, and the isocyanate is an aliphatic isocyanate or an alicyclic isocyanate; the isocyanate is selected from one or more of L-lysine diisocyanate, L-lysine triisocyanate, hexamethylene diisocyanate, isophorone diisocyanate and 4,4'-dicyclohexylmethane diisocyanate.

6. A modified isocyanate prepolymer prepared by the method according to any one of claims 1 to 5.

7. A degradable polyurethane adhesive based on the modified isocyanate prepolymer according to claim 6, characterized in that: The preparation process of the degradable polyurethane adhesive is as follows: the modified isocyanate prepolymer and the curing agent are mixed in a certain volume ratio to obtain the polyurethane bioadhesive; the volume ratio of the modified isocyanate prepolymer and the curing agent is 1:(0.1-10); the curing agent is an unsaturated carbonyl compound modified amine curing agent or a polyamine modified polyphenol curing agent.

8. The degradable polyurethane adhesive according to claim 7, characterized in that: The preparation process of the unsaturated carbonyl compound modified amine curing agent is as follows: in a protective atmosphere, a polyamine compound and an unsaturated carbonyl compound are continuously reacted at a certain temperature, and an unsaturated carbonyl compound modified amine curing agent is obtained by an addition reaction between an unsaturated olefin and a primary amine group; wherein the reaction temperature is 20 to 100° C., and the reaction time is 12 to 48 hours; and the molar ratio of the unsaturated olefin in the unsaturated carbonyl compound to the primary amine group in the polyamine compound is 1:(0.1 to 10); The preparation process of the polyamine-modified polyphenol curing agent is as follows: in a protective atmosphere, continuously reacting a polyphenol compound with an alcohol compound at a certain temperature until the polyphenol compound is completely dissolved; further adding a polyamine compound and continuously reacting at a certain temperature, utilizing the phenolic hydroxyl functional group and the primary amine group to undergo an addition reaction to obtain a polyamine-modified polyphenol curing agent; wherein the reaction temperature is 10 to 100° C., and the reaction time is 1 to 24 hours; the functional group molar ratio of the polyphenol compound to the polyamine compound is 1:(0 to 1), and the mass ratio of the polyphenol compound to the alcohol compound is 1:(0.1 to 10).

9. The degradable polyurethane adhesive according to claim 8, characterized in that: In the preparation process of the unsaturated carbonyl compound modified amine curing agent, the unsaturated carbonyl compound is selected from one or more of maleic acid, dimethyl maleate, diethyl maleate, dibutyl maleate, diallyl maleate, dioctyl maleate, fumaric acid, diethyl fumarate, dimethyl fumarate and dibutyl fumarate; the polyamine compound is selected from one or more of 1,2-propylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,6-hexanediamine, 1,8-octanediamine, bis(hexamethylene)triamine, spermine, spermidine, n-propylamine, n-butylamine, polyetheramine, polyethyleneimine with a molecular weight of 300-25000Da, diethylenetriamine, triethylenetetramine, tetraethylenepentamine and polyethylenepolyamine; In the preparation process of the polyamine-modified polyphenol curing agent, the polyphenol compound is selected from one or more of tannic acid, gallic acid, gallic acid ester compounds (such as propyl gallate, lauryl gallate, etc.), tea polyphenols, gallol, lignin, catechol and ellagic acid, and the polyamine compound is selected from 1,2-propylenediamine, 1,3-propylenediamine, 1,4-butylenediamine, 1,6-hexanediamine, 1,8-octanediamine, bis(hexamethylene)triamine, spermine, spermidine, n-propylamine, n-butylamine, polyetheramine, a molecular weight of 30 One or more of 0-25000Da polyethyleneimine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine and polyethylenepolyamine; the alcohol compound is selected from glycerol, ethylene glycol, diethylene glycol, triethylene glycol, 1,2-propylene glycol, 1,3-butanediol, 1,4-butanediol, 2,4-pentanediol, 2,5-hexanediol, dipropylene glycol, castor oil, diol or polyol polymer with a molecular weight of 200-1000Da (such as polyethylene glycol, polytetrahydrofuran, polycaprolactone diol, polycaprolactone triol, etc.).

10. The use of the degradable polyurethane adhesive according to claim 7, characterized in that: The polyurethane adhesive is used for bonding wet tissue interfaces. When used, the polyurethane bioadhesive is applied to the desired tissue bonding and sealing position and cured in situ.