A polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds and its preparation method and application

Abstract

The present invention relates to the technical field of polymer material preparation, and relates to a polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds, and a preparation method and application thereof. The gelatin is cross-linked by gelatin and a cross-linking agent through the formation of imino bonds, and the cross-linking agent is a curcumin-modified polyether urethane terminated with a tetraaldehyde group, and its molecular structure is as follows: The polyurethane cross-linked modified gelatin medical hydrogel based on imino groups of the present invention contains a reversible Schiff base bond, so it has excellent mechanical properties and self-repairing properties, and can maintain more than 85% of the mechanical properties after repair at room temperature for 1 hour; at the same time, the hydrogel has degradability, antibacterial properties and high biocompatibility, so it can play a huge role in the field of biomedical materials.

Description

Technical Field

[0001] The invention relates to the technical field of polymer material preparation, and relates to a polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds, and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Hydrogel is a new type of material with a three-dimensional structure formed by cross-linking of hydrophilic polymer chains in an aqueous environment. It can maintain a certain shape and absorb a large amount of water. In the actual application of hydrogel materials, tiny cracks are generated inside or outside the material due to external squeezing and bending, and the generation of microcracks often leads to the failure of the hydrogel material. In order to give the hydrogel certain mechanical properties and special functions such as self-repair and environmental response, polymer segments can be used, the degree of cross-linking of polymer segments can be controlled, and other functional substances can be doped. In addition, hydrogels with structures can be used as transport carriers, and are often used in medicine to transport drugs and make drug dressings and other applications.

[0004] According to the inventors' research, in polymer materials, aldehyde groups and amino groups can react to form imine bonds, which can achieve dynamic self-repair under different acid-base conditions. However, the inventors found that the existing hydrogels that form imine bonds have low mechanical properties, which is not conducive to the use of medical hydrogels. After further research, it was found that the high mechanical strength hydrogels currently prepared have problems such as hydrogel cost, poor antibacterial properties, and weak degradation ability. Summary of the invention

[0005] In order to solve the shortcomings of the prior art, the purpose of the present invention is to provide a polyurethane cross-linked modified gelatin medical hydrogel based on imine bonds and its preparation method and application, which not only has good mechanical properties, antibacterial properties, and self-repairing properties, but also has high biocompatibility and biodegradable properties, and can act as a medical hydrogel.

[0006] In order to achieve the above object, the technical solution of the present invention is:

[0007] In a first aspect of the present invention, a tetraaldehyde-terminated curcumin-modified polyether urethane (CPEU-CHO) is provided, and its molecular structure is as follows:

[0008]

[0009] Among them, R1 is for n=natural number from 45 to 227; R2 is The mass content of the polyether chain segment in the tetraaldehyde-terminated curcumin-modified polyether urethane is 50-90%.

[0010] The second aspect of the present invention provides a method for preparing the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane, wherein polyether diol, curcumin (Cur), and diisocyanate are used as monomer raw materials to perform an addition reaction of isocyanate groups and hydroxyl groups to obtain an isocyanate-terminated curcumin-modified polyether urethane prepolymer (CPEU-NCO), and then a monohydroxy alkyl dialdehyde compound is added to continue the addition reaction of isocyanate groups and hydroxyl groups to obtain the obtained product.

[0011] The third aspect of the present invention provides a use of the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane in the preparation of modified gelatin medical hydrogel.

[0012] In a fourth aspect of the present invention, a polyurethane cross-linked modified gelatin medical hydrogel (CPEU-WG) based on imino bonds is provided, which is formed by cross-linking gelatin with a cross-linking agent through the formation of imino bonds, and the cross-linking agent is the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane.

[0013] The fifth aspect of the present invention provides a method for preparing a polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds, comprising uniformly mixing an aqueous gelatin solution with an aqueous solution of the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane, and allowing the mixture to stand for a cross-linking reaction to obtain the hydrogel.

[0014] The present invention first prepares a tetraaldehyde-terminated curcumin-modified polyether urethane, and then uses it as a crosslinking agent to crosslink gelatin to prepare a multifunctional hydrogel. The crosslinking reaction of the hydrogel can occur at room temperature, and the crosslinking degree is high, so that it has good mechanical properties; the crosslinking bond is a dynamically reversible imine bond, thereby giving the hydrogel self-healing properties; the hydrogel contains a natural antibacterial material curcumin, so the hydrogel has certain antibacterial properties. The hydrogel is based on natural gelatin, curcumin materials and polyethylene glycol with good biocompatibility and degradability, and the hard segment degradation product of its polyurethane component is aliphatic diamine, so the hydrogel has high biocompatibility and biodegradability at the same time, so it can be used as a filling material for medical soft tissue in the medical field, etc., and has great application potential.

[0015] The hydrogel of the present invention is cross-linked by generating imine bonds through the reaction of -CHO and -NH2 groups, and the cross-linking degree is high, thereby giving the hydrogel excellent mechanical properties. At the same time, the imine bonds are dynamically reversible bonds, thereby giving the hydrogel good self-healing properties.

[0016] The tensile strength of the hydrogel prepared in the embodiment is 0.3-0.5 MPa, and the elongation at break is 500-600%. After repairing at room temperature for 1 hour, the tensile strength can be restored to more than 80% of the original gel.

[0017] It is also biodegradable, with a degradation time of 60 to 90 days in PBS buffer at 37°C; it has a significant inhibitory effect on both Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria).

[0018] The beneficial effects of the present invention are:

[0019] 1) The medical hydrogel provided by the present invention has a simple and convenient preparation method, readily available raw materials, strong practicability, and is easy to promote and apply.

[0020] 2) The medical hydrogel provided by the present invention is prepared by reacting a tetraaldehyde-terminated polyurethane crosslinker CPEU-CHO with gelatin (GE) to generate imide bond crosslinking, which has higher reaction efficiency and faster reaction rate, and the obtained product has excellent mechanical properties and can achieve self-repair at room temperature.

[0021] 3) The main raw materials of the medical hydrogel provided by the present invention are biocompatible polyethylene oxide and natural biological material gelatin, so the hydrogel finally prepared has excellent biocompatibility and biodegradability; the high degree of cross-linking of the hydrogel makes it have a slow degradation rate, and it can be used in organisms as a medium- to long-term implant material (1 to 3 months).

[0022] 4) The present invention embeds the natural antibacterial material curcumin into polyurethane and then introduces it into the hydrogel. At the same time, the remaining primary amino groups of gelatin also have certain antibacterial ability. The superposition of the two gives the hydrogel good broad-spectrum antibacterial properties, which provides a guarantee for the antibacterial property of the hydrogel.

[0023] 5) The medical hydrogel provided by the present invention can be directly freeze-dried into a sponge shape, and the sponge can be soaked in water to regenerate the hydrogel. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0025] Figure 1 The present invention is a schematic structural diagram of the preparation process of the polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds.

[0026] Figure 2 The stress-strain curve of CPEU-WG-1 in the embodiment of the present invention and the stress-strain curve after repair at room temperature for 1 hour.

[0027] Figure 3 This is a graph showing the degradation weight loss over time of CPEU-WG-1 according to an embodiment of the present invention.

[0028] Figure 4 This is a diagram showing the antibacterial zone effect of CPEU-WG-1 of the present invention on Escherichia coli and Staphylococcus aureus; the left is Staphylococcus aureus; the right is Escherichia coli. DETAILED DESCRIPTION

[0029] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0030] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0031] In view of the fact that it is difficult for existing hydrogels to take into account mechanical properties, antibacterial properties, self-repairing properties, biocompatibility and degradation properties, the present invention proposes a polyurethane cross-linked modified gelatin medical hydrogel based on imine bonds, and a preparation method and application thereof.

[0032] A typical embodiment of the present invention provides a tetraaldehyde-terminated curcumin-modified polyether urethane, the molecular structure of which is shown below:

[0033]

[0034] Among them, R1 is for n=natural number from 45 to 227; R2 is The mass content of the polyether chain segment in the tetraaldehyde-terminated curcumin-modified polyether urethane is 50-90%.

[0035] Another embodiment of the present invention provides a method for preparing the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane, wherein polyether diol, curcumin, and diisocyanate are used as monomer raw materials to perform an addition reaction between an isocyanate group and a hydroxyl group to obtain an isocyanate-terminated curcumin-modified polyether urethane prepolymer, and then a monohydroxy alkyl dialdehyde compound is added to continue the addition reaction between the isocyanate group and the hydroxyl group to obtain the obtained product.

[0036] The reaction formula is as follows:

[0037]

[0038] In some embodiments, the polyether glycol is polyethylene glycol (PEG) having a molecular weight of 1000 to 20000 g / mol, preferably 2000 to 10000 g / mol.

[0039] In some embodiments, the diisocyanate is an aliphatic diisocyanate, preferably hexamethylene diisocyanate, tetramethylene diisocyanate, isophorone diisocyanate or lysine diisocyanate (LDI), more preferably lysine diisocyanate.

[0040] In some embodiments, the molar ratio of polyether diol, curcumin, and diisocyanate is 1:1:3.

[0041] In some embodiments, the solvent used in the reaction system is N,N-dimethylformamide (DMF), and the concentration of the monomer in DMF is 0.3-0.8 g / mL.

[0042] In some embodiments, the catalyst used in the reaction system is a tin catalyst. Preferably, the tin catalyst is dibutyltin dilaurate or stannous octoate; the amount of the tin catalyst added is 0.1-0.2% of the total weight of the monomers.

[0043] In some embodiments, the reaction temperature is 70-90°C. The end point of the reaction of -NCO is measured by di-n-butylamine titration method. The -NCO content reaches the theoretical value in about 2-3 hours. The end point of the reaction of the curcumin-modified polyether urethane capped with tetraaldehyde is detected by infrared detection of the -NCO absorption peak (2250-2285cm -1 ) disappears in about 1.5 to 2.5 hours.

[0044] In some embodiments, the monohydroxyalkyl dialdehyde compound is hydroxymalondialdehyde, hydroxy 1,4-butanedialdehyde, or 3-hydroxyglutaraldehyde.

[0045] In some embodiments, the feeding amount of the monohydroxyalkyl dialdehyde compound is such that the molar amount of the aldehyde group is equal to the molar amount of -NCO in the isocyanate-terminated curcumin-modified polyether urethane prepolymer.

[0046] A third embodiment of the present invention provides a use of the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane in the preparation of modified gelatin medical hydrogel.

[0047] A fourth embodiment of the present invention provides a polyurethane cross-linked modified gelatin medical hydrogel (CPEU-WG) based on an imino bond, which is formed by cross-linking gelatin with a cross-linking agent through the formation of an imino bond, and the cross-linking agent is the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane.

[0048] The fifth embodiment of the present invention provides a method for preparing a polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds, wherein the gelatin aqueous solution and the aqueous solution of the above-mentioned tetraaldehyde-terminated curcumin-modified polyether urethane are evenly mixed, and the mixture is allowed to stand for a cross-linking reaction to obtain the hydrogel.

[0049] The reaction process is as follows Figure 1 shown.

[0050] In some embodiments, the concentration of the gelatin aqueous solution is 0.040-0.060 g / mL, the temperature is 40-50° C., and the pH is 10.0. The primary amine content of the gelatin aqueous solution under these conditions is 0.4-0.8 mmol / g.

[0051] In some embodiments, the aqueous solution of tetraaldehyde-terminated curcumin-modified polyether urethane has a concentration of 0.040-0.060 g / mL and a temperature of 40-50° C. Preferably, the temperature of the aqueous solution of tetraaldehyde-terminated curcumin-modified polyether urethane is consistent with the temperature of the gelatin aqueous solution.

[0052] In some embodiments, the added mass ratio of gelatin to tetraaldehyde-terminated curcumin-modified polyether urethane is 1:0.4-2.

[0053] In some embodiments, the cross-linking reaction is allowed to stand for 10 to 20 minutes.

[0054] A fifth embodiment of the present invention provides an application of the above-mentioned polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds in the field of biomedical engineering.

[0055] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0056] Example 1

[0057] 20.00 g of polyethylene glycol (M n =2000g / mol), 3.68g curcumin and 6.79g lysine diisocyanate were dissolved in 100mL N,N-dimethylformamide solvent, two drops of stannous octoate were added for catalysis, the temperature was raised to 75°C under mechanical stirring, the reaction was continued for 2h to obtain CPEU-NCO-1 solution, and 1.76g hydroxymalondialdehyde was added, the temperature was kept constant and the reaction was continued for 2h, and finally the DMF was removed by vacuum rotary evaporation to obtain viscous CPEU-CHO-1. 5g of CPEU-CHO-1 was dissolved in 100mL deionized water at 40°C to obtain a CPEU-CHO-1 aqueous solution.

[0058] Dissolve 10 g of gelatin in 200 mL of deionized water at 40° C., adjust the pH value to 10.0, add 100 mL of CPEU-CHO-1 aqueous solution and mix, quickly stir evenly, and allow the cross-linking reaction to stand for 15 minutes to obtain the hydrogel CPEU-WG-1.

[0059] Example 2

[0060] 30.00 g of polyethylene glycol (M n =3000g / mol), 3.68g curcumin and 6.79g lysine diisocyanate were dissolved in 100mL DMF solvent, two drops of stannous octoate were added for catalysis, the temperature was raised to 80°C under mechanical stirring, and the reaction was carried out for 2h to obtain CPEU-NCO-2 solution, and then 2.32g of 3-hydroxyglutaraldehyde was added, and the reaction was continued at a constant temperature for 2h, and finally the DMF was removed by vacuum rotary evaporation to obtain a viscous CPEU-CHO-2. 5g of CPEU-CHO-2 was dissolved in 100mL deionized water at 40°C to obtain a CPEU-CHO-2 aqueous solution.

[0061] Dissolve 10 g of gelatin in 200 mL of deionized water at 40° C., adjust the pH value to 10.0, add 100 mL of CPEU-CHO-2 aqueous solution and mix, quickly stir evenly, and allow the cross-linking reaction to stand for 15 minutes to obtain the hydrogel CPEU-WG-2.

[0062] Example 3

[0063] 40.00 g of polyethylene glycol (M n =4000g / mol), 3.68g curcumin and 6.79g lysine diisocyanate were dissolved in 100mL DMF solvent, two drops of stannous octoate were added for catalysis, the temperature was raised to 75°C under mechanical stirring, and the reaction was carried out for 2h to obtain CPEU-NCO-3 solution, and then 2.04g hydroxy 1,4-butanedialdehyde was added, and the reaction was continued at a constant temperature for 2.5h, and finally the DMF was removed by vacuum rotary evaporation to obtain a viscous CPEU-CHO-3. 5g of CPEU-CHO-3 was dissolved in 100mL deionized water at 40°C to obtain a CPEU-CHO-3 aqueous solution.

[0064] Dissolve 10 g of gelatin in 200 mL of deionized water at 45° C., adjust the pH value to 10.0, add 100 mL of CPEU-CHO-3 aqueous solution and mix, quickly stir evenly, and allow the cross-linking reaction to stand for 15 minutes to obtain the hydrogel CPEU-WG-3.

[0065] Example 4

[0066] 50.00 g of polyethylene glycol (M n=5000g / mol), 3.68g curcumin and 6.79g lysine diisocyanate were dissolved in 100mL DMF solvent, two drops of dibutyltin dilaurate were added for catalysis, the temperature was raised to 75°C under mechanical stirring, the reaction was continued for 2.5h to obtain CPEU-NCO-4 solution, and then 1.76g hydroxymalondialdehyde was added, the constant temperature was maintained and the reaction was continued for 2h, and finally the DMF was removed by vacuum rotary evaporation to obtain viscous CPEU-CHO-4. 5g of CPEU-CHO-4 was dissolved in 100mL deionized water at 40°C to obtain a CPEU-CHO-4 aqueous solution.

[0067] Dissolve 10 g of gelatin in 200 mL of deionized water at 40° C., adjust the pH value to 10.0, add 90 mL of CPEU-CHO-4 aqueous solution and mix, quickly stir evenly, and allow to stand for cross-linking reaction for 10 minutes to obtain hydrogel CPEU-WG-4.

[0068] Analytical and Interpretative Methods: The following analytical methods were used in all examples unless otherwise stated.

[0069] Tensile performance test: The prepared CPEU-WG hydrogel was made into dumbbell-shaped splines using a rubber pneumatic slicer. The Z005 electronic universal material testing machine from Zwick / Roell of Germany was used to test the tensile properties of the specimens. The test results are shown in Table 1, and the tensile speed is 50 mm / min. A blade was used to cut the CPEU-WG-1 hydrogel in the middle and then spliced ​​together. The interfaces were aligned and repaired at room temperature for 1 hour before the tensile performance test was performed. The two curves and the maximum tensile strength were observed to judge the self-repair efficiency. The maximum tensile strength before repair was Pa0, and the maximum tensile strength after repair was Pa1. The tensile mechanical properties of the CPEU-WG-1 hydrogel are shown in Table 1. Figure 2 The calculation formula is as follows:

[0070] Repair efficiency (%) = Pa1 / Pa0×100%

[0071] Degradation performance test: The mass of CPEU-WG-1 hydrogel with an area of ​​1×1 cm was measured, recorded as M0, and then the test sample was placed in a conical flask containing PBS buffer with pH=7.4, and in vitro degradation was simulated in a biological incubator at 37±0.1℃. After a certain period of degradation, the hydrogel was taken out, the surface was dried with absorbent paper to a constant weight, and the mass of each hydrogel was weighed on an analytical balance and recorded, recorded as M n , until the hydrogel breaks. The remaining mass fraction at each time period is calculated using the following formula, and the remaining mass fraction of the material is used to represent the degradation performance of the material. Figure 3 shown.

[0072] Remaining mass fraction (%) = M n / M0×100%

[0073] Antibacterial performance test: Escherichia coli and Staphylococcus aureus were selected, and the antibacterial performance of CPEU-WG hydrogel was evaluated by the inhibition zone. Specific steps: Pre-cut the CPEU-WG-1 hydrogel into a size of 5mm in diameter and sterilize it under ultraviolet light for 30 minutes. Add about 20mL of agar culture medium to the culture dish, let it stand horizontally to solidify, inoculate 0.1mL of bacterial solution, and spread it evenly. Take the pre-sterilized CPEU-WG-1 hydrogel and inoculate it into the agar culture medium, culture it in a constant temperature incubator at 37°C for 18 hours, observe the results and measure the inhibition zone. Figure 4 shown.

[0074] Table 1. Mechanical properties and repair efficiency of CPEU-WG

[0075]

[0076] As shown in Table 1, the tensile test of CPEU-WG hydrogel showed that its tensile strength can reach 0.3-0.5MPa, and its elongation at break is 500-600%, which has excellent mechanical properties and can meet the requirements of the hydrogel in the daily application of medical materials. In addition, after the fracture is repaired at room temperature for 1 hour, the repair efficiency can reach up to 92%. Figure 1 As shown in the figure, the self-repairing efficiency of the hydrogel prepared in this embodiment gradually decreases with the reduction of the imine bond content, but it can also ensure that it has certain mechanical properties after repair, and the repair efficiency of the hydrogel in all embodiments can reach more than 85%.

[0077] like Figure 3 As shown in the figure, the degradation test of CPEU-WG-1 hydrogel shows that the degradation rate is less than 5% within 30 days after the initial degradation. Even after 70 days of degradation, the mass is only 64.3% of the original, and it can still maintain certain mechanical properties, which proves that the material has good degradation performance and can be used as a long-term implant material in the human body. The degradation products can be absorbed by the human body to avoid the harm of secondary trauma to the human body.

[0078] Figure 4 As shown in the antibacterial circle effect diagram, it can be intuitively observed that the diameters of the antibacterial circles of CPEU-WG-1 hydrogel against Staphylococcus aureus and Escherichia coli are 26mm and 25mm respectively, both of which have obvious antibacterial effects. Curcumin has broad-spectrum antibacterial properties, and gelatin also has certain antibacterial ability. The dual effects enhance the antibacterial ability, which can meet the needs of the field of medical materials.

[0079] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. Application of a tetraaldehyde-terminated curcumin-modified polyether urethane in the preparation of a modified gelatin medical hydrogel, characterized in that: The molecular structural formula of the tetraaldehyde-terminated curcumin-modified polyether urethane is as follows: Among them, R1 is , or ; for , n = 45 ~ 227 natural numbers; R2 is The mass content of the polyether chain segment in the tetraaldehyde-terminated curcumin-modified polyether urethane is 50-90%.

2. A use of the tetraaldehyde-terminated curcumin modified polyether urethane according to claim 1 in the preparation of a medical hydrogel of modified gelatin, characterized in that: The preparation method of the tetraaldehyde-terminated curcumin-modified polyether urethane comprises the following steps: using polyether diol, curcumin and diisocyanate as monomer raw materials to carry out an addition reaction between isocyanate groups and hydroxyl groups to obtain an isocyanate-terminated curcumin-modified polyether urethane prepolymer; then adding a monohydroxy alkyl dialdehyde compound; and continuing to carry out an addition reaction between isocyanate groups and hydroxyl groups to obtain the tetraaldehyde-terminated curcumin-modified polyether urethane prepolymer.

3. The use of the tetraaldehyde-terminated curcumin modified polyether urethane as claimed in claim 2 in the preparation of a medical hydrogel of modified gelatin, characterized in that: The solvent used in the reaction system is N,N-dimethylformamide.

4. The use of the tetraaldehyde-terminated curcumin modified polyether urethane as claimed in claim 2 in preparing a medical hydrogel of modified gelatin, characterized in that: The molecular weight of the polyether diol is 1000-20000 g / mol.

5. The use of the tetraaldehyde-terminated curcumin modified polyether urethane as claimed in claim 2 in preparing a medical hydrogel of modified gelatin, characterized in that: The molecular weight of the polyether diol is 2000-10000 g / mol.

6. The use of the tetraaldehyde-terminated curcumin modified polyether urethane as claimed in claim 2 in preparing a medical hydrogel of modified gelatin, characterized in that: The concentration of the monomer in DMF was 0.3~0.8 g / mL.

7. The use of the tetraaldehyde-terminated curcumin modified polyether urethane as claimed in claim 2 in preparing a medical hydrogel of modified gelatin, characterized in that: The molar ratio of polyether diol, curcumin and diisocyanate is 1:1:3; Or, a tin catalyst is used in the reaction system; the amount of the tin catalyst added is 0.1-0.2% of the total mass of the monomer; Or, the reaction temperature is 70~90 ℃; Alternatively, the feeding amount of the monohydroxyalkyl dialdehyde compound is such that the molar amount of the aldehyde group is equal to the molar amount of -NCO in the curcumin-modified polyether urethane prepolymer terminated with isocyanate.

8. The use of the tetraaldehyde-terminated curcumin modified polyether urethane as claimed in claim 7 in preparing a medical hydrogel of modified gelatin, characterized in that: The tin catalyst is dibutyltin dilaurate or stannous octoate.

9. A polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds, characterized in that: The crosslinking agent is formed by crosslinking gelatin by forming an imine bond with gelatin, and the crosslinking agent is the tetraaldehyde-terminated curcumin-modified polyether urethane used in the application of claim 1.

10. A method for preparing a polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds, characterized in that: The gelatin aqueous solution and the aqueous solution of the tetraaldehyde-terminated curcumin-modified polyether urethane used in the application of claim 1 are uniformly mixed, and allowed to stand for cross-linking reaction to obtain the product.

11. The method for preparing the polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds as claimed in claim 10, characterized in that: The concentration of the gelatin aqueous solution was 0.040-0.060 g / mL, the temperature was 40-50 °C, and the pH was 10.0; Alternatively, the concentration of the aqueous solution of the tetraaldehyde-terminated curcumin-modified polyether urethane is 0.040-0.060 g / mL and the temperature is 40-50 °C.

12. The method for preparing the polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds as claimed in claim 11, characterized in that: The temperature of the aqueous solution of the tetraaldehyde-terminated curcumin-modified polyether urethane is consistent with the temperature of the gelatin aqueous solution.

13. The method for preparing the polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds as claimed in claim 10, characterized in that: The added mass ratio of gelatin to tetraaldehyde-terminated curcumin-modified polyether urethane is 1:0.4~2; Alternatively, the cross-linking reaction is allowed to stand for 10 to 20 minutes.

14. Use of the polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds as claimed in claim 9 or the polyurethane cross-linked modified gelatin medical hydrogel based on imino bonds obtained by any one of the preparation methods described in claims 10 to 13 in the preparation of biomedical engineering materials.

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