A biomedical adhesive and its preparation method and application

Abstract

The application discloses a biomedical adhesive as well as a preparation method and application thereof, and belongs to the technical field of bio-based polymer adhesives and preparation thereof. The application solves the problems of limited use shape and harsh storage conditions of the existing biomedical adhesives. In the polymerization process of thioctic acid and an adhesion enhancer, an NHS ester structure is separated in the form of a monomer in the system or is introduced into a polymer chain segment by polymerization, so that a thioctic acid-NHS ester biomedical adhesive with strong stability, good biocompatibility, no tissue toxicity, implantability in the body or adhesion to a body surface wound, isolation of the wound, adhesion and fixation of tissues, and the functions of helping wound healing and repair is prepared. The adhesion performance of the biomedical adhesive does not decrease with the change of time, has good room temperature storage stability, can realize long-time effective adhesion to tissues, and has high adhesion performance to various tissues and various polymer materials.

Description

TECHNICAL FIELD

[0001] The present application relates to a biomedical adhesive and its preparation method and application, belonging to the field of bio-based polymer adhesives and their preparation technology. BACKGROUND

[0002] Adhesive is a substance that can bond two or more components or materials together through interfacial adhesion and cohesion, and is widely used in biomedical, aerospace, cultural relic restoration and daily office work and many other fields. With the development of the times economy and the progress of living standards, the requirements for adhesives used in biomedical applications are becoming higher and higher, and single-function adhesives can no longer meet market demand. Nowadays, biomedical adhesives are developing towards multifunctionalization. For example, they can not only achieve adhesion but also promote wound healing, have antibacterial, anti-inflammatory and antioxidant functions (Sci. Transl. Med., 2013, 5, 205ec161; J. Biomed. Mater. Res. B, 2016, 104, 626-639). In order to realize the multifunctionalization of adhesives, many natural polymer substances with antibacterial and antioxidant properties have been introduced into the preparation of adhesives, such as chitosan, cellulose, hyaluronic acid and gelatin (Adv. Healthc. Mater., 2019, 8, 1801568; Sci. Adv., 2023, 9, eadh4327; Biomaterials, 2023, 301, 122239; Adv. Mater., 2024, 2401745; Adv. Mater., 2024, 2404811;).

[0003] In addition, adhesives used in biomedical applications should also have wet adhesion ability, which is the key to replacing surgical sutures to achieve wound hemostasis and wound healing. However, traditional adhesives can only adhere to dry substrates in air, and when the substrate surface is wet, the adhesion performance of the adhesive will decrease sharply or even disappear, which is not conducive to the application of adhesives on wet tissue surfaces (Nature, 2019, 575, 169; Chem. Soc. Rev., 2020, 49, 433-464; Science, 2017, 357, 378-381). In order to enable adhesives to adhere to wet tissue surfaces, a common treatment method is to prepare the adhesives into the form of hydrogels, but the formation of gel networks limits the contact between the adhesives and the tissue surface, which leads to generally low adhesion performance of gel-based adhesives. Moreover, gel-state adhesives often have the problems of limited use shape and harsh storage conditions. SUMMARY

[0004] The present application aims at the above-mentioned defects and deficiencies of the existing biomedical adhesive, and provides a biomedical adhesive based on lipoic acid and an NHS ester compound and a preparation method thereof.

[0005] The technical scheme of the present application is as follows:

[0006] One of the purposes of the present application is to provide a preparation method of a biomedical adhesive, which comprises the following steps: taking lipoic acid, a compound containing an NHS ester structure, and an adhesion enhancer as raw materials, and performing a heating reaction in the presence of solvent anhydrous ethanol or without solvent to obtain the biomedical adhesive.

[0007] Further limitation, the structural general formula of the compound containing the NHS ester structure is as follows:

[0008]

[0009] In the formula, R is hydrogen, a linear alkyl group, an alkenyl group, a branched alkyl group, or a cyclic alkyl group.

[0010] Further limitation, the adhesion enhancer is one or a mixture of several of coffee acid, dopamine, levodopa, and dihydrocaffeic acid.

[0011] Further limitation, the mass ratio of lipoic acid to the compound containing the NHS ester structure is 10:1 to 2:1.

[0012] Further limitation, the mass ratio of lipoic acid to the adhesion enhancer is 10:0 to 2:1.

[0013] Further limitation, when the solvent anhydrous ethanol is present, the specific preparation process is as follows: lipoic acid, the compound containing the NHS ester structure, and the adhesion enhancer are dissolved in anhydrous ethanol, and then heated in an oil bath at 50-80 DEG C for 1-8 h under nitrogen protection.

[0014] Further limitation, after the heating is completed, the mass ratio of the solvent to the solute is 1:10 to 10:1.

[0015] Further limitation, when no solvent is present, the specific preparation process is as follows: lipoic acid, the compound containing the NHS ester structure, and the adhesion enhancer are mixed, and then heated in an oil bath at 90-150 DEG C for 1-8 h under nitrogen protection.

[0016] The second purpose of the present application is to provide a biomedical adhesive prepared by the above-mentioned method.

[0017] The third purpose of the present application is to provide an application of the above-mentioned biomedical adhesive, which is specifically used for medical dressings.

[0018] Beneficial effects:

[0019] The application introduces the NHS ester structure in the lipoic acid and the adhesion enhancer polymerization process, and a lipoic acid-NHS ester biomedical adhesive with strong stability, good biocompatibility, no organizational toxicity, which can be implanted in the body or attached to the body surface wound, plays the role of isolating the wound, adhering and fixing the tissue, helping the wound healing and repairing, etc. The adhesion performance of the biomedical adhesive does not decrease with the change of time, has good room temperature storage stability, can realize the effective adhesion of the tissue for a long time, and has high adhesion performance to various tissues and various polymer materials. In addition, the preparation process provided by the application is simple and environment-friendly, the synthesis steps are simple, the raw materials are cheap and easy to obtain, and the adhesive material can be obtained after mixing, and can be prepared at any time as needed. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The Fourier infrared spectra of lipoic acid and the compound containing the NHS ester structure of formula I-1 before and after heating in ethanol;

[0021] Figure 2 The G' and G'' of the adhesive prepared in examples 8-12 change with the frequency graph;

[0022] Figure 3 The complex viscosity of the adhesive prepared in examples 8-12 changes with the frequency graph;

[0023] Figure 4 The Fourier infrared spectra of the adhesive prepared in examples 8-12;

[0024] Figure 5 The comparison chart of the adhesive prepared in example 22 before and after storage at room temperature for one month;

[0025] Figure 6 The adhesive prepared in example 22 on the adhesion effect of pig kidney;

[0026] Figure 7 The adhesive prepared in example 22 on the adhesion effect of pig lung;

[0027] Figure 8 The adhesive prepared in example 22 on the adhesion and plugging effect of pig heart;

[0028] Figure 9 The adhesive prepared in example 22 on the adhesion and plugging effect of pig lung;

[0029] Figure 10 The cytotoxicity test chart of the adhesive prepared in example 24;

[0030] Figure 11 The adhesive prepared in example 24 on the wound healing effect of mice. DETAILED DESCRIPTION

[0031] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application will be described in detail below with reference to the embodiments of the present application.

[0032] In the following description, a large number of specific details are set forth in order to provide a thorough understanding of the present application, but the present application can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the concept of the present application, therefore the present application is not limited to the specific embodiments disclosed below.

[0033] Secondly, the "one embodiment" or "embodiment" referred to herein means that the specific features, structures or characteristics can be included in at least one implementation of the present application. "In one embodiment" appearing in different places in the specification does not mean the same embodiment, nor is it an embodiment that is separate or alternative to other embodiments.

[0034] The experimental methods used in the following embodiments are conventional methods unless otherwise specified. The materials, reagents, methods and instruments used are conventional materials, reagents, methods and instruments in the art unless otherwise specified, which can be obtained by commercial channels by those skilled in the art, and the purity of the solid and liquid reagents used is analytical pure.

[0035] The compounds with NHS ester structure of formula I-1 to formula I-9 used in the following embodiments are respectively:

[0036]

[0037] The compounds without NHS ester structure of formula II-1 to formula II-3 used in the following embodiments are respectively:

[0038]

[0039] Among them, the compound of formula II-1 has no NHS ester structure compared with the compound of formula I-5, the compound of formula II-2 has no NHS ester structure compared with the compound of formula I-8, and the compound of formula II-3 has no NHS ester structure compared with the compound of formula I-9.

[0040] Example 1

[0041] 0.50g of lipoic acid and 0.05g of the compound with NHS ester structure shown in formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, heated in a 70℃ oil bath under nitrogen protection for 3h, and after heating, the mass ratio of solvent to solute was 7:3.

[0042] Example 2

[0043] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath for 3 h under nitrogen protection. After the heating was completed, the mass ratio of the solvent to the solute was 7:3.

[0044] Example 3

[0045] 0.50 g of lipoic acid and 0.15 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath for 3 h under nitrogen protection. After the heating was completed, the mass ratio of the solvent to the solute was 7:3.

[0046] Example 4

[0047] 0.50 g of lipoic acid and 0.20 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath for 3 h under nitrogen protection. After the heating was completed, the mass ratio of the solvent to the solute was 7:3.

[0048] Example 5

[0049] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath for 3 h under nitrogen protection. After the heating was completed, the mass ratio of the solvent to the solute was 4:1.

[0050] Example 6

[0051] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath for 3 h under nitrogen protection. After the heating was completed, the mass ratio of the solvent to the solute was 3:2.

[0052] Example 7

[0053] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath for 3 h under nitrogen protection. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0054] Example 8

[0055] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath for 1 h under nitrogen protection. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0056] Example 9

[0057] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 2 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0058] Example 10

[0059] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 4 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0060] Example 11

[0061] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0062] Example 12

[0063] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 8 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0064] Example 13

[0065] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-2 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0066] Example 14

[0067] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-3 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0068] Example 15

[0069] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-4 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0070] Example 16

[0071] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-5 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0072] Example 17

[0073] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-6 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0074] Example 18

[0075] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-7 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0076] Example 19

[0077] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-8 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0078] Example 20

[0079] 0.50 g of lipoic acid and 0.10 g of a compound having an NHS ester structure represented by Formula I-9 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0080] Example 21

[0081] 0.50 g of lipoic acid, 0.05 g of a compound having an NHS ester structure represented by Formula I-1, and 0.05 g of caffeic acid (adhesion enhancer) were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in a 70°C oil bath under nitrogen protection for 6 h. After the heating was completed, the mass ratio of the solvent to the solute was 1:1.

[0082] Example 22

[0083] 0.50 g of lipoic acid, 0.05 g of a compound having an NHS ester structure represented by Formula I-3, and 0.05 g of caffeic acid (adhesion enhancer) were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in an oil bath at 70°C for 6 hours under nitrogen protection. After the end of heating, the mass ratio of solvent to solute was 1:1.

[0084] Example 23

[0085] 0.50 g of lipoic acid, 0.05 g of a compound having an NHS ester structure represented by Formula I-4, and 0.05 g of caffeic acid (adhesion enhancer) were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in an oil bath at 70°C for 6 hours under nitrogen protection. After the end of heating, the mass ratio of solvent to solute was 1:1.

[0086] Example 24

[0087] 0.50 g of lipoic acid, 0.05 g of a compound having an NHS ester structure represented by Formula I-3, and 0.05 g of caffeic acid (adhesion enhancer) were placed in a round-bottom flask and heated in an oil bath at 120°C for 6 hours under nitrogen protection.

[0088] Comparative Example 1

[0089] 0.60 g of lipoic acid was placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in an oil bath at 70°C for 6 hours under nitrogen protection. After the end of heating, the mass ratio of solvent to solute was 1:1.

[0090] Comparative Example 2

[0091] 0.50 g of lipoic acid and 0.10 g of dihydrocaffeic acid represented by Formula II-1 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in an oil bath at 70°C for 6 hours under nitrogen protection. After the end of heating, the mass ratio of solvent to solute was 1:1.

[0092] Comparative Example 3

[0093] 0.50 g of lipoic acid and 0.10 g of 6-heptenoic acid represented by Formula II-2 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in an oil bath at 70°C for 6 hours under nitrogen protection. After the end of heating, the mass ratio of solvent to solute was 1:1.

[0094] Comparative Example 4

[0095] 0.50 g of lipoic acid and 0.10 g of 10-undecenoic acid represented by Formula II-3 were placed in a round-bottom flask and dissolved with anhydrous ethanol, and heated in an oil bath at 70°C for 6 hours under nitrogen protection. After the end of heating, the mass ratio of solvent to solute was 1:1.

[0096] Effect Example

[0097] (1) Take 1 g of lipoic acid and the compound with NHS ester structure of Formula I-1 respectively, dissolve them in ethanol, heat them in a 70°C oil bath under nitrogen protection for 6 h, compare the Fourier infrared spectra before and after heating, and the results are shown in Figure 1 , from which it can be seen that lipoic acid will polymerize after heating in ethanol, and Formula I-1 does not change before and after heating in ethanol. Figure 1

[0098] (2) Compare the Fourier infrared spectra of the adhesives obtained in Examples 8-12, and the results are shown in Figure 4 , from which it can be seen that heating lipoic acid and the compound with NHS ester structure of Formula I-1 in ethanol will break the disulfide bond in lipoic acid to generate thiol free radicals to initiate the double bond polymerization of the compound in Formula I-1, and H-NHS (N-hydroxysuccinimide) in the figure is the product after the reaction of NHS ester with amino, hydroxyl, thiol and other groups, and from the infrared spectra of Examples 8-12, it can be seen that there is no characteristic peak of H-NHS, indicating that the NHS ester structure does not participate in the reaction, and the NHS ester structure is intact before and after heating. Figure 4

[0099] (3) The adhesives prepared in Examples 8-12 are tested by a rotary rheometer to calculate the changes of G' and G" of the adhesives with frequency and the changes of complex viscosity with frequency, and the test results are shown in Figure 2 and Figure 3 , indicating that the adhesives have shear thinning properties, indicating that the adhesives have injectability.

[0100] (4) Adhesion performance test

[0101] Fresh porcine skin, porcine meat, aorta, heart, liver, kidney, stomach, bladder and large intestine tissues are obtained from local supermarkets, the adhesives prepared in Examples 1-23 are applied to the surfaces of two tissues, slightly pressed, and then a universal mechanical testing machine is used to test the adhesion strength and adhesion toughness of the adhesives on the surfaces of different tissues, 3-5 samples per group, and the average value is the final result.

[0102] The adhesion strength test method is a single lap shear test mode. During the test, the two opposite directions parallel to the adhesive surface are stretched at a stretching rate of 50 mm / min, the stress peak value F (N) at the instant of pulling apart is tested, and the stress per unit adhesive area is calculated according to formula (1), which is the adhesion strength of the sample.

[0103] T = 1000F / S (1)

[0104] Wherein F is the stress peak value at the instant of pulling apart, unit: N; S is the adhesive area, unit: mm 2 ; T is the lap shear strength, unit: kPa.

[0105] ​​The adhesive toughness test method is T type peeling test mode. During the test, the two opposite directions perpendicular to the adhesive surface are stretched at a stretching rate of 50 mm / min, and after the action force is stable, the peeling force F (N) is recorded, and the adhesive toughness of the sample is calculated according to formula (2).

[0106] τ = 2F / L (2)

[0107] Wherein F is the peeling force after stabilization, the unit is N; L is the width of the adhesive surface, the unit is m; τ is the adhesive toughness, the unit is J / m 2 .

[0108] The performance test data are shown in the following table:

[0109] Table 1 Adhesive prepared by examples 1-23 to the adhesion performance of pigskin

[0110]

[0111]

[0112] From the above table, the adhesion results of the adhesives prepared from each example and each comparative example to pigskin can be concluded as follows:

[0113] 1) The content of solute and solvent will affect the adhesive strength of the adhesive, too high solute content will lead to too strong cohesive force of the adhesive, which will make it difficult to coat, and too low solute content will lead to too low content of effective components in the adhesive, which will all lead to the decrease of adhesive strength;

[0114] 2) The heating time within a certain range will affect the adhesive performance of the adhesive, because too short heating time will lead to shorter chain segments of the polymer in the adhesive, which is not conducive to adhesion;

[0115] 3) Whether the NHS ester is in the form of monomer free in the system or polymerized in the chain segment through the terminal double bond, as long as the adhesive contains NHS ester structure, its adhesive performance is much higher than that of the adhesive without NHS ester structure, because the reason for the enhancement of the adhesive performance is that the NHS ester structure has strong hydrogen bond interaction with the carboxyl group in thioctic acid, thereby enhancing the adhesive performance of the adhesive;

[0116] 4) The addition of the adhesion enhancer enriches the types of interactions of the adhesive, thereby improving the adhesive performance of the adhesive.

[0117] Table 2 Adhesive prepared by example 22 to the adhesion performance of pigskin, aorta, heart, stomach, bladder and large intestine

[0118]

[0119] Table 3 Adhesive prepared by example 22 to the adhesion performance of pigskin after storage at room temperature for different time

[0120]

[0121] Figure 5 The comparison chart of the adhesive prepared in Example 22 before and after storage at room temperature for one month is shown in Figure Figure 5 It can be seen that the adhesive still presents a uniform and transparent state after storage at room temperature for one month, indicating that the adhesive has good storage stability.

[0122] Table 4 The adhesive properties of the adhesive prepared in Example 22 for different time of adhesion to pig skin in simulated in-vivo environment

[0123]

[0124] The simulation of in-vivo humid environment is to place the adhered sample in a sealed sample bag and in a constant temperature environment at 37°C, and to spray 0.1 mol / L PBS buffer (pH 6.8-7.2) regularly to keep the sample humid.

[0125] Figure 6 The adhesion effect of the adhesive prepared in Example 22 to pig kidney is shown in Figure Figure 6 It can be seen that the adhesive can easily adhere to the detached part of the pig kidney and can replace the suture thread to repair the pig kidney.

[0126] Figure 7 The adhesion effect of the adhesive prepared in Example 22 to pig lung is shown in Figure Figure 7 It can be seen that the adhesive can easily adhere to the cracked part of the pig lung and can replace the suture thread to repair the pig lung.

[0127] Figure 8 The adhesion effect of the adhesive prepared in Example 22 to pig heart is shown in Figure Figure 8 It can be seen that the adhesive coated on the TPU film and attached to the leakage of the pig heart can successfully repair the leakage after half an hour.

[0128] Figure 9 The adhesion effect of the adhesive prepared in Example 22 to pig lung is shown in Figure Figure 9 It can be seen that the adhesive coated on the TPU film and attached to the leakage of the pig lung can successfully repair the leakage after half an hour.

[0129] Table 5 The adhesive properties of the adhesive prepared in Example 22 to different high molecular materials

[0130]

[0131] From the above experimental results, it can be seen that the adhesive prepared by the present application has high adhesion to various biological tissues and various polymer materials, and the adhesion does not decay with time, has good room temperature storage stability, and has adhesion stability, so that long-term effective adhesion to tissues can be achieved.

[0132] The adhesive prepared in Example 24 was subjected to cytotoxicity test, and the results are shown in Table 3. Figure 10 The results show that the cell survival rate is not less than 95% when the cells are cultured with the adhesive extract solution with a concentration of 20 mg / mL, 40 mg / mL and 60 mg / mL for 12 h, 24 h and 36 h.

[0133] The adhesive prepared in Example 24 was used to treat the wounds of mice, and the healing conditions of the adhesive treatment group, the commercial dressing treatment group, the untreated group and the suture treatment group were compared, and the results are shown in Table 4. Figure 11 As can be seen from Table 4, Figure 11 the wound of the mouse coated with the adhesive heals faster than the wounds of the mice without coating or coated with commercial dressing, which indicates that the adhesive has the effect of promoting wound healing.

[0134] From the above experimental results, it can be seen that the adhesive prepared by the present application has good biocompatibility and no tissue toxicity, can be implanted into the body or attached to the wound on the body surface, plays the role of isolating the wound, adhering and fixing the tissue, helping the wound healing and repair, and can achieve long-term effective adhesion to the tissue.

[0135] Although the present application has been disclosed with the above preferred embodiments, it is not intended to limit the present application, and any person skilled in the art can make various modifications and modifications without departing from the spirit and scope of the present application, therefore the protection scope of the present application should be defined by the claims.

Claims

1. A method for preparing a biomedical adhesive, characterized by, The bioadhesive is prepared by heating lipoic acid, a compound containing NHS ester structure and a binding enhancer in the presence of solvent anhydrous ethanol. The structural general formula of the compound containing NHS ester structure is: In the formula, R is hydrogen, straight-chain alkyl, alkenyl, branched-chain alkyl or cyclic alkyl; The binding enhancer is one or a mixture of several of coffee acid, dopamine, levodopa and dihydrocaffeic acid; The mass ratio of lipoic acid to the compound containing NHS ester structure is 10:1 to 2:1; The mass ratio of lipoic acid to the binding enhancer is 10:0 to 2:1; In the presence of solvent anhydrous ethanol, the specific preparation process is as follows: lipoic acid, the compound containing NHS ester structure and the binding enhancer are dissolved in anhydrous ethanol, and then heated in an oil bath at 50-80℃ for 1-8h under nitrogen protection; After heating, the mass ratio of solvent to solute is 1:10 to 10:

1.

2. A bioadhesive prepared by the method of claim 1.

3. Use of the bio-medical adhesive according to claim 2, characterized in that, The bioadhesive is used for medical dressings.

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