Biomedical adhesive as well as preparation method and application thereof

Abstract

The invention 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 invention solves the problems of limited use shape and harsh storage conditions of the existing biomedical adhesive. In the polymerization process of lipoic acid and the adhesion enhancer, an NHS ester structure is dissociated in a system in the form of a monomer or introduced into a chain segment of a polymer through polymerization, and the preparation method has the advantages of high stability, good biocompatibility and no tissue toxicity, and can be implanted into a body or attached to a body surface wound. And the lipoic acid-NHS ester biomedical adhesive has the effects of isolating wounds, bonding and fixing tissues, helping the wounds to heal and repair and the like. The bonding performance of the biomedical adhesive cannot be attenuated along with the change of time, and the biomedical adhesive has good room-temperature storage stability and can effectively bond tissues for a long time; and the adhesive has high-strength adhesive property on various tissues and various polymer materials.

Description

Technical Field

[0001] The invention relates to a biomedical adhesive and a preparation method and application thereof, belonging to the technical field of bio-based polymer adhesives and preparation thereof. Background Art

[0002] Adhesive is a substance that can bond two or more components or materials together through interfacial adhesion and cohesion. It is widely used in many fields such as biomedicine, aerospace, cultural relic restoration and daily office. With the development of the economy and the improvement of living standards, the requirements for adhesives used in biomedicine are getting higher and higher. Single-function adhesives can no longer meet market demand. Now biomedical adhesives are developing in the direction of multifunctionality. For example, while achieving adhesion, they also have the functions of promoting wound healing, antibacterial, anti-inflammatory, and antioxidant (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 polymers 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 biomedicine should also have wet adhesion ability, which is the key to adhesives replacing surgical sutures to achieve wound hemostasis and wound healing. However, traditional adhesives can only adhere to dry substrates in the air. When there is water on the substrate surface, the adhesive's adhesive properties will drop 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 the adhesive to adhere to the wet tissue surface, a more common treatment method is to prepare the adhesive in the form of a hydrogel, but the formation of a gel network limits the contact between the adhesive and the tissue surface, which leads to the generally low adhesive properties of gel adhesives. Not only that, adhesives in a gel state often have problems such as limited use shape and harsh storage conditions. Summary of the invention

[0004] In view of the above defects and shortcomings of existing biomedical adhesives, the present invention provides a biomedical adhesive based on lipoic acid and NHS ester structure compounds and a preparation method thereof.

[0005] The technical solution of the present invention:

[0006] One of the purposes of the present invention is to provide a method for preparing a biomedical adhesive, which comprises the following steps: using 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 anhydrous ethanol or without a solvent to obtain the biomedical adhesive.

[0007] It is further defined that the general structural formula of the compound containing the NHS ester structure is:

[0008]

[0009] Wherein R is hydrogen, a straight-chain alkyl group, an alkenyl group, a branched-chain alkyl group or a cyclic alkyl group.

[0010] It is further defined that the adhesion enhancer is one or a mixture of caffeic acid, dopamine, levodopa, and dihydrocaffeic acid.

[0011] It is further defined that the mass ratio of lipoic acid to the compound containing an NHS ester structure is 10:1 to 2:1.

[0012] It is further defined that the mass ratio of lipoic acid to the adhesion enhancer is 10:0 to 2:1.

[0013] It is further defined that in the presence of anhydrous ethanol as a solvent, the specific preparation process is: dissolving lipoic acid, a compound with an NHS ester structure and an adhesion enhancer in anhydrous ethanol, and heating in an oil bath at 50-80° C. for 1-8 hours under nitrogen protection.

[0014] It is further defined that the mass ratio of the solvent to the solute after the heating is completed is 1:10 to 10:1.

[0015] It is further defined that, in the absence of a solvent, the specific preparation process is: mixing lipoic acid, a compound containing an NHS ester structure and an adhesion enhancer, and heating in an oil bath at 90 to 150° C. for 1 to 8 hours under nitrogen protection.

[0016] The second object of the present invention is to provide a biomedical adhesive prepared by the above method.

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

[0018] Beneficial effects:

[0019] The present invention introduces an NHS ester structure during the polymerization of lipoic acid and an adhesion enhancer to prepare a lipoic acid-NHS ester biomedical adhesive with strong stability, good biocompatibility, and no tissue toxicity. The adhesive can be implanted in the body or attached to a wound on the body surface to isolate the wound, adhere and fix tissues, and help wound healing and repair. The adhesive performance of the biomedical adhesive will not decay over time, has good room temperature storage stability, and can achieve long-term effective adhesion to tissues; it has high-strength adhesion to a variety of tissues and a variety of polymer materials. In addition, the preparation process provided by the present invention is simple and environmentally friendly, the synthesis steps are simple, the raw materials are cheap and easy to obtain, and can be stored stably for a long time; the adhesive material can be obtained after mixing, and can be prepared on demand at any time. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0021] Figure 2 G′ and G″ of the adhesives prepared in Examples 8-12 vary with frequency;

[0022] Figure 3 The graph showing the composite viscosity of the adhesive prepared in Examples 8-12 as a function of frequency;

[0023] Figure 4 The Fourier transform infrared spectra of the adhesives prepared in Examples 8-12;

[0024] Figure 5 This is a comparison chart of the adhesive prepared in Example 22 before and after being stored at room temperature for one month;

[0025] Figure 6 This is a diagram showing the bonding effect of the adhesive prepared in Example 22 on pig kidney;

[0026] Figure 7 This is a diagram showing the bonding effect of the adhesive prepared in Example 22 on pig lungs;

[0027] Figure 8 This is a diagram showing the effect of the adhesive prepared in Example 22 on the adhesion and plugging of a pig heart;

[0028] Fig. 9 This is a diagram showing the effect of the adhesive prepared in Example 22 on the adhesion and plugging of pig lungs;

[0029] Fig.10 This is a cytotoxicity test chart of the adhesive prepared in Example 24;

[0030] Fig.11 This is a diagram showing the effect of the adhesive prepared in Example 24 on wound healing in mice. DETAILED DESCRIPTION

[0031] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0032] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0033] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0034] The experimental methods used in the following examples 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, and can be obtained through commercial channels by those skilled in the art, and the purity of the solid and liquid reagents used is analytically pure.

[0035] The structures of the compounds containing NHS ester structures of Formula I-1 to Formula I-9 used in the following examples are respectively:

[0036]

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

[0038]

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

[0040] Example 1

[0041] 0.50 g of lipoic acid and 0.05 g of a compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 3 h under nitrogen protection. After heating, the mass ratio of the solvent to the solute was 7:3.

[0042] Example 2

[0043] 0.50 g of lipoic acid and 0.10 g of the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 3 h under nitrogen protection. After the heating, 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 containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 3 h under nitrogen protection. After the heating, 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 the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 3 h under nitrogen protection. After the heating, 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 the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 3 h under nitrogen protection. After the heating, 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 the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 3 h under nitrogen protection. After the heating, 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 the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 3 h under nitrogen protection. After the heating, 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 containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 1 h under nitrogen protection. After the heating, 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 the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 2 h under nitrogen protection. After the heating, 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 the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 4 h under nitrogen protection. After the heating, the mass ratio of the solvent to the solute was 1:1.

[0060] Embodiment 11

[0061] 0.50 g of lipoic acid and 0.10 g of the compound containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 6 h under nitrogen protection. After the heating, 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 containing an NHS ester structure represented by formula I-1 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 8 h under nitrogen protection. After the heating, the mass ratio of the solvent to the solute was 1:1.

[0064] Embodiment 13

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

[0066] Embodiment 14

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

[0068] Embodiment 15

[0069] 0.50 g of lipoic acid and 0.10 g of a compound containing an NHS ester structure represented by formula I-4 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 6 h under nitrogen protection. After the heating, 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 containing an NHS ester structure represented by formula I-5 were placed in a round-bottom flask and dissolved in anhydrous ethanol. They were heated in an oil bath at 70° C. for 6 h under nitrogen protection. After the heating, the mass ratio of the solvent to the solute was 1:1.

[0072] Embodiment 17

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

[0074] Embodiment 18

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

[0076] Embodiment 19

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

[0078] Embodiment 20

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

[0080] Embodiment 21

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

[0082] Embodiment 22

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

[0084] Embodiment 23

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

[0086] Embodiment 24

[0087] 0.50 g of lipoic acid, 0.05 g of the compound containing 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 h under nitrogen protection.

[0088] Comparative Example 1

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

[0096] Effect example

[0097] (1) 1 g of lipoic acid and the compound containing an NHS ester structure of formula I-1 were weighed and dissolved in ethanol, and heated in an oil bath at 70°C for 6 h under nitrogen protection. The Fourier infrared spectra before and after heating were compared. The results were as follows: Figure 1 As shown by Figure 1 It can be seen that lipoic acid polymerizes after being heated in ethanol, while Formula Ⅰ-1 does not change before and after being heated in ethanol.

[0098] (2) Comparative Examples 8-12 obtained the Fourier transform infrared spectra of the adhesive, the results are as follows Figure 4 As shown by Figure 4 It can be seen that heating lipoic acid and the compound containing NHS ester structure of formula Ⅰ-1 in ethanol will cause the disulfide bond in lipoic acid to break and generate sulfhydryl free radicals to initiate double bond polymerization of the compound in formula Ⅰ-1. The H-NHS (N-hydroxysuccinimide) in the figure is the product of the reaction of NHS ester with amino, hydroxyl, sulfhydryl and other groups. 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.

[0099] (3) The adhesives prepared in Examples 8-12 were tested and the G′ and G″ of the adhesives varied with frequency and the composite viscosity varied with frequency was calculated by a rotational rheometer. The test results are shown in Figure 2 and Figure 3 As shown, it indicates that the adhesive has shear thinning properties, indicating that the adhesive has injectable ability.

[0100] (4) Adhesion performance test

[0101] Fresh pig skin, pork, aorta, heart, liver, kidney, stomach, bladder and large intestine tissues were obtained from local supermarkets, and the adhesive prepared in Examples 1-23 was applied to two tissue surfaces and slightly pressed. The adhesive strength and toughness of the adhesive on different tissue surfaces were then tested using a universal mechanical testing machine. 3 to 5 samples were collected in each group, and the average value was taken as the final result.

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

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

[0104] Where F is the peak stress at the moment of pulling apart, in N; S is the bonding area, in mm 2 ; T is the lap shear strength, unit is kPa.

[0105] The bonding toughness test method is a T-type peel test mode. During the test, the sample is stretched in two opposite directions perpendicular to the bonding surface at a tensile rate of 50 mm / min. After the applied force is stable, the peel force F (N) is recorded and the bonding toughness of the sample is calculated according to formula (2).

[0106] τ=2F / L (2)

[0107] Where F is the peel force after stabilization, in N; L is the width of the bonding surface, in m; τ is the bonding toughness, in J / m 2 .

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

[0109] Table 1 Adhesion performance of the adhesives prepared in Examples 1-23 to pig skin

[0110]

[0111]

[0112] The following conclusions can be drawn from the results of the bonding of the adhesives prepared in the above examples and comparative examples to pigskin:

[0113] 1) The content of solute and solvent will affect the bonding strength of the adhesive. If the solute content is too high, the cohesive force of the adhesive will be too strong, making it difficult to apply. If the solute content is too low, the content of the active ingredient of the adhesive will be too low, which will lead to a decrease in bonding strength.

[0114] 2) The heating time will affect the adhesive properties within a certain range. This is because if the heating time is too short, the polymer chain segments in the adhesive will be shorter, which is not conducive to adhesion.

[0115] 3) Regardless of whether the NHS ester is free in the system in the form of a monomer or polymerized in the polymer chain segment through the double bond at the end, as long as the adhesive contains the NHS ester structure, its adhesive performance is much higher than that without the NHS ester structure. This is because the reason for the enhanced adhesive performance is that the NHS ester structure has a strong hydrogen bond interaction with the carboxyl group in lipoic acid, thereby enhancing the adhesive performance;

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

[0117] Table 2 Adhesion performance of the adhesive prepared in Example 22 to pork, aorta, heart, stomach, bladder and large intestine

[0118]

[0119] Table 3 Adhesion performance of the adhesive prepared in Example 22 to pig skin after being stored at room temperature for different periods of time

[0120]

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

[0122] Table 4 Adhesion performance of the adhesive prepared in Example 22 to pig skin at different times in simulated in vivo environment

[0123]

[0124] To simulate the moist environment in vivo, the bonded samples were placed in a sealed sample bag and kept in a constant temperature environment of 37°C, and 0.1 mol / L PBS buffer (pH 6.8-7.2) was sprayed regularly to keep the samples moist.

[0125] Figure 6 This is a diagram showing the bonding effect of the adhesive prepared in Example 22 on pig kidneys. Figure 6 It can be seen that the adhesive can easily stick to the detached part of the pig kidney and can replace the suture to repair the pig kidney.

[0126] Figure 7 This is a diagram showing the bonding effect of the adhesive prepared in Example 22 on pig lungs. Figure 7 It can be seen that the adhesive can easily stick to the torn part of the pig lung and can replace the sutures to repair the pig lung.

[0127] Figure 8 The figure is a graph showing the adhesion effect of the adhesive prepared in Example 22 on the pig heart. Figure 8 It can be seen that by coating the adhesive on the TPU film and sticking it on the leaking part of the pig's heart, the leak can be successfully repaired after half an hour.

[0128] Fig. 9 The figure is a graph showing the adhesion effect of the adhesive prepared in Example 22 on pig lungs. Fig. 9 It can be seen that by coating the adhesive on the TPU film and sticking it on the hole in the pig lung, the leak can be successfully repaired after half an hour.

[0129] Table 5 Adhesion performance of the adhesive prepared in Example 22 to different polymer materials

[0130]

[0131] Based on the above experimental results, it can be seen that the adhesive prepared by the present invention has high-strength adhesion properties to a variety of biological tissues and a variety of polymer materials, and the adhesion performance will not decay with the change of time, and has good room temperature storage stability; and it has adhesion stability, and can achieve long-term effective adhesion to tissues.

[0132] The adhesive prepared in Example 24 was subjected to a cytotoxicity test, and the results were as follows: Fig.10 As shown, the results showed that when the cells were cultured with adhesive extracts at concentrations of 20 mg / mL, 40 mg / mL, and 60 mg / mL for 12 h, 24 h, and 36 h, the cell survival rate was not less than 95%.

[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. The results are as follows: Fig.11 As shown by Fig.11 It can be seen that the wounds of mice coated with adhesive healed faster than those of mice not coated or coated with commercial dressings, indicating that adhesives have the effect of promoting wound healing.

[0134] Based on the above experimental results, it can be seen that the adhesive prepared by the present invention has good biocompatibility and no tissue toxicity. It can be implanted in the body or attached to wounds on the surface of the body to isolate wounds, bond and fix tissues, and help wound healing and repair, and can achieve long-term effective bonding of tissues.

[0135] Although the present invention has been disclosed as above in the preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A method for preparing a biomedical adhesive, characterized in that: The invention adopts lipoic acid, a compound containing an NHS ester structure and an adhesion enhancer as raw materials, and is obtained by heating reaction in the presence of anhydrous ethanol solvent or in the absence of a solvent.

2. The preparation method according to claim 1, characterized in that: The general structural formula of the compound containing NHS ester structure is: Wherein R is hydrogen, a straight-chain alkyl group, an alkenyl group, a branched-chain alkyl group or a cyclic alkyl group.

3. The preparation method according to claim 1, characterized in that: The adhesion enhancer is one or a mixture of caffeic acid, dopamine, levodopa and dihydrocaffeic acid.

4. The preparation method according to claim 1, characterized in that: The mass ratio of lipoic acid to the compound containing an NHS ester structure is 10:1 to 2:

1.

5. The preparation method according to claim 1, characterized in that: The mass ratio of lipoic acid to the adhesion enhancer is 10:0 to 2:

1.

6. The preparation method according to claim 1, characterized in that: When the solvent anhydrous ethanol is present, the specific preparation process is: dissolving lipoic acid, a compound with an NHS ester structure and an adhesion enhancer in anhydrous ethanol, and heating in an oil bath at 50-80° C. for 1-8 hours under nitrogen protection.

7. The preparation method according to claim 6, characterized in that: After heating, the mass ratio of solvent to solute is 1:10 to 10:

1.

8. The preparation method according to claim 1, characterized in that: In the absence of solvent, the specific preparation process is: lipoic acid, a compound containing an NHS ester structure and an adhesion enhancer are mixed, and heated in an oil bath at 90 to 150° C. for 1 to 8 hours under nitrogen protection.

9. A biomedical adhesive prepared by the method according to any one of claims 1 to 8.

10. A use of the biomedical adhesive according to claim 9, characterized in that: Used in medical dressings.

Images