Instant-adhesive strong-tough wet tissue tape and preparation method thereof

Abstract

The present invention discloses an instant-adhesive strong-tough wet tissue tape and a preparation method thereof. The preparation of the instant-adhesive strong-tough wet tissue tape comprises the following steps: S1, reacting 3,4-dihydroxyphenylacetic acid with glycidyl methacrylate to synthesize 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate; S2, dissolving chitosan in an acrylic acid aqueous solution, then adding 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate and a photoinitiator to obtain a mixed solution; S3, applying the mixed solution to the surface of a polymer film treated with a plasma cleaner, and then curing under ultraviolet light to obtain the instant-adhesive strong-tough wet tissue tape. This invention designs and synthesizes novel catechol compounds with long alkyl side chains and uses them to manufacture an instantly adhesive, strong, and resilient wet tissue tape. This tape is thin, flexible, and optically transparent, conforming to various substrates and allowing visual inspection of the substrate's state. Prior to use, the tape is dry and non-sticky, but upon contact with water or blood, it rapidly bonds to wet biological tissue. The tape exhibits exceptionally strong interfacial toughness and adhesion strength to wet biological tissue, far exceeding existing commercial adhesives and some other wet tissue adhesives. Therefore, the instantly adhesive, strong, and resilient wet tissue tape can be used for wound closure and hemostasis.

Description

Technical Field

[0001] The invention belongs to the field of tissue adhesive materials, and particularly relates to an instant-adhesive strong-tough wet tissue tape and a preparation method thereof. Background Art

[0002] Adhesives are widely used in various fields, including light industry, electronics, and medical devices. Most adhesives bond well to dry adherends but not to wet / underwater adherends. This is because the hydration layer hinders interfacial interaction between the adhesive and the adherend, leading to adhesion failure. However, underwater work and biomedical applications (such as wound closure) often require wet / underwater adhesion. In nature, marine organisms such as mussels and barnacles can firmly adhere to static and dynamic underwater objects, such as coral reefs, ships, and whales. Adhesive proteins secreted by these organisms disrupt the hydration layer, forming a variety of adhesive interactions (such as covalent bonds, hydrogen bonds, electrostatic interactions, π-π, cation-π, and hydrophobic interactions), resulting in strong and durable underwater adhesion.

[0003] Inspired by the abundant 3,4-dihydroxyphenylalanine adhesive groups in the structure of mussel byssus proteins, numerous catechol-containing wet / underwater adhesives have been reported. For biocompatibility and biosafety considerations, catechol groups have been chemically grafted onto biopolymers to create bioadhesives, such as polyethylene glycol-catechol, hyaluronic acid-catechol, alginic acid-catechol, polyvinyl alcohol-catechol, polyacrylic acid-catechol, and chitosan-catechol. Compared to the robust and durable adhesion of mussels to underwater surfaces, the adhesion strength and durability of these catechol-containing artificial adhesives are significantly inferior. This is primarily due to their chemical structure primarily mimicking the catechol groups of mussel byssus proteins while ignoring other structural details. To date, 3,4-dihydroxyphenylethylamine or 3,4-dihydroxyphenylpropionic acid has been commonly used as modification reagents. In most catechol-functionalized polymers, the linkage between the catechol groups and the polymer backbone is typically four carbon atoms. In this context, attempts to improve the bond strength simply by increasing the content of catechol groups in the adhesive have not yielded satisfactory results.

[0004] Therefore, achieving instant strong bonding of underwater adhesives remains a great challenge due to the continuous interference of water. Summary of the Invention

[0005] The present invention aims to provide an instantly adhesive, strong, and tough wet tissue tape and its preparation method. This invention utilizes a novel, self-produced catechol compound containing long aliphatic side chains, 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate, which is copolymerized with acrylic acid via UV light initiation and then incorporated with the cationic polymer chitosan. This reaction produces a thin, optically transparent (>80%), instantly adhesive wet / underwater tissue tape. This tape exhibits excellent interfacial toughness, adhesion strength, and resistance to burst pressure on wet / underwater biological tissues.

[0006] The present invention is achieved through the following technical solutions:

[0007] A method for preparing an instant-adhesive, strong-tough wet tissue tape comprises the following steps:

[0008] S1. reacting 3,4-dihydroxyphenylacetic acid (a monomer containing a catechol compound) with glycidyl methacrylate to synthesize 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate;

[0009] S2. dissolving chitosan in an acrylic acid aqueous solution, then adding 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate and a photoinitiator, and stirring uniformly to obtain a mixed solution;

[0010] S3. Apply the mixed solution on the surface of the polymer film treated by a plasma cleaner, and then cure it under 365nm ultraviolet light to obtain an instant-adhesive strong wet tissue tape.

[0011] The present invention designs and synthesizes a novel long alkyl side chain catechol compound and uses it to manufacture an instantly adhesive, strong and tough wet tissue tape. The tape is thin, soft and optically transparent, can conform to adhesive substrates of different morphologies, and the state of the adhesive substrate can be visually inspected. The tape is non-sticky before use, but when it comes into contact with water or blood, it can quickly adhere to wet biological tissue. The tape has very strong interfacial toughness and adhesion strength with wet biological tissue, far exceeding existing commercial adhesives and some other reported wet tissue adhesives. Therefore, the instantly adhesive, strong and tough wet tissue tape can be used for wound closure and hemostasis.

[0012] In step S1, the ratio of 3,4-dihydroxyphenylacetic acid to glycidyl methacrylate is 3.5-4 g: 2.6-3.0 mL.

[0013] Furthermore, in step S1, the reaction conditions are 60-80° C. and the reaction time is 6-12 hours.

[0014] Furthermore, in step S2, the concentration of acrylic acid in the mixed solution is 91.0 to 98.0 wt%, the content of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate is 0.5 to 4.0 wt%, and the concentration of chitosan is 1.0 to 5.0 wt%.

[0015] Furthermore, in step S2, the photoinitiator is 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone, and the concentration of the photoinitiator in the mixed solution is 0.1 to 0.3 wt%.

[0016] Furthermore, in step S3, the polymer film is a polypropylene, polyurethane, cellulose or chitosan film.

[0017] Furthermore, in step S3, the UV curing time is 2 to 5 minutes, and the thickness of the adhesive layer after curing is 0.05 to 0.2 mm.

[0018] In the instant, strong, and resilient wet tissue tape prepared using the above technical solution, the polyacrylic acid units not only destroy interfacial water through water absorption but also form interfacial hydrogen bonds with tissue surface groups. The poly-2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate units form didentate hydrogen bonds with the tissue surface. Chitosan generates electrostatic and cationic-π interactions with the polyacrylic acid and poly-2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate units, strengthening the adhesive matrix. This results in strong adhesion and interfacial toughness between the tape and wet tissue. Its wet tissue adhesion exceeds that of existing commercial tissue adhesives. This tissue tape effectively seals damaged tissue.

[0019] Compared with the prior art, the present invention also has the following beneficial effects:

[0020] 1. The tape is made of thin, soft, and optically transparent material. It uses a small amount of raw materials and can conform to substrates of varying shapes. The state of the substrate can be visually inspected.

[0021] 2. The tape preparation process is simple and the preparation time is short.

[0022] 3. The tape is dry and non-sticky before use, and has water-triggered wet tissue adhesion after contact with water or blood.

[0023] 4. The tape has strong wet tissue interface toughness and adhesion strength, which far exceeds existing commercial adhesives and other reported wet tissue adhesives. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1Design and synthesis of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate.

[0025] Figure 2 This is the H NMR spectrum of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate.

[0026] Figure 3 This is the infrared spectrum of the instant-adhesive strong-tough wet tissue adhesive prepared in Example 3.

[0027] Figure 4 This is a physical picture of the instant-adhesive strong-tough wet tissue tape prepared in Example 3.

[0028] Figure 5 This is an optically transparent image of the instant-adhesive, strong-tough wet tissue tape prepared in Example 3.

[0029] Figure 6 This is an example of stretching the instant-sticky, strong-tough wet tissue adhesive prepared in Example 3.

[0030] Figure 7 The instant-adhesive strong-tough wet tissue tape prepared in Example 3 was bonded to underwater pigskin.

[0031] Figure 8 The interface toughness and adhesion strength between the instant-adhesive strong wet tissue tape prepared in Example 3 of the present invention and Comparative Example 1 and wet pigskin.

[0032] Figure 9 The adhesion strengths of the instant-adhesive strong wet tissue tape prepared in Example 3 to tissues wetted with blood and simulated body fluids, respectively.

[0033] Figure 10 This is a diagram showing the cell compatibility of the instant-adhesive, strong, and tough wet tissue adhesive prepared in Example 3.

[0034] Figure 11 is the synthesis formula of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate, i.e., the polymer component of the sticky and tough wet tissue adhesive and its interfacial adhesion bond with wet tissue. DETAILED DESCRIPTION

[0035] The present invention will be described in detail below with reference to specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those skilled in the art, several variations and improvements can be made without departing from the scope of the present invention. These all fall within the scope of protection of the present invention. Example 1

[0036] Synthesis of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate

[0037] 3.636 g of 3,4-dihydroxyphenylacetic acid monomer was weighed and added to an acetonitrile solution (60 mL) containing 2.86 mL of glycidyl methacrylate. 1.29 g of tetrabutylammonium bromide was then added. The mixture was reacted at 80°C for 12 hours and purified by column chromatography (PE / EA = 1:2). The filtrate was rotary evaporated to remove the solvent to obtain a light yellow liquid 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate, which was stored in a refrigerator at -20°C. The reaction process was as follows: Figure 1 According to the NMR spectrum, it was proved that the compound was successfully synthesized (Figure 2). Example 2

[0038] Preparation of instant-adhesive strong wet tissue tape

[0039] 0.3 g of chitosan was dissolved in 10 g of acrylic acid (AA) and 0.21 mL of deionized water and stirred for 30 minutes. Then, 0.1 g of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate synthesized in Example 1 was added and stirring continued for 10 minutes. After dissolution, 0.050 g of a photoinitiator (2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone) was added and stirred to obtain a clear solution. The solution was coated onto a polypropylene film treated with a plasma cleaner and cured under a 365 nm UV lamp for 5 minutes. The prepared sample was placed in a ziplock bag and stored in a desiccator until further use. This was designated as catechol tissue tape. The IR spectrum ( ) confirmed the successful synthesis of catechol tissue tape. Example 3

[0040] Preparation of instant-adhesive strong wet tissue tape

[0041] 0.4 g of chitosan was weighed and dissolved in AA (10 g) and deionized water (0.21 mL) and stirred for 30 minutes. Then, 0.1 g of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate synthesized in Example 1 was added and stirred for 10 minutes. After dissolution, 0.050 g of photoinitiator (2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone) was added and stirred to obtain a clear solution. The solution was coated on the surface of a polypropylene film treated with a plasma cleaner and then cured under a 365 nm ultraviolet lamp for 5 minutes. The prepared sample was placed in a ziplock bag and stored in a desiccator for use, and was recorded as catechol tissue tape. According to the infrared spectrum ( Figure 3 ), demonstrating the successful synthesis of catechol tissue tape. Example 4

[0042] Preparation of instant-adhesive strong wet tissue tape

[0043] 0.5 g of chitosan was dissolved in 10 g of AA and 0.21 mL of deionized water and stirred for 30 minutes. Then, 0.1 g of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate synthesized in Example 1 was added and stirring continued for 10 minutes. After dissolution, 0.050 g of a photoinitiator (2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone) was added and stirred to obtain a clear solution. The solution was coated on a polypropylene film treated with a plasma cleaner and cured under a 365 nm UV lamp for 5 minutes. The prepared sample was placed in a ziplock bag and stored in a desiccator until further use. This was designated as catechol tissue tape. Infrared spectroscopy confirmed the successful synthesis of catechol tissue tape. Example 5

[0044] Preparation of instant-adhesive strong wet tissue tape

[0045] 0.4 g of chitosan was dissolved in 10 g of AA and 0.21 mL of deionized water and stirred for 30 minutes. Then, 0.1 g of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate synthesized in Example 1 was added and stirring continued for 10 minutes. After dissolution, 0.025 g of a photoinitiator (2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone) was added and stirred to obtain a clear solution. The solution was coated onto a polypropylene film treated with a plasma cleaner and cured under a 365 nm UV lamp for 5 minutes. The prepared sample was placed in a ziplock bag and stored in a desiccator until further use. This was designated as catechol tissue tape. Infrared spectroscopy confirmed the successful synthesis of catechol tissue tape. Example 6

[0046] Preparation of instant-adhesive strong wet tissue tape

[0047] 0.4 g of chitosan was dissolved in 10 g of AA and 0.21 mL of deionized water and stirred for 30 minutes. Then, 0.1 g of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate synthesized in Example 1 was added and stirring continued for 10 minutes. After dissolution, 0.015 g of a photoinitiator (2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone) was added and stirred to obtain a clear solution. The solution was coated onto a polypropylene film treated with a plasma cleaner and cured under a 365 nm UV lamp for 5 minutes. The prepared sample was placed in a ziplock bag and stored in a desiccator until further use. This was designated as catechol tissue tape. Infrared spectroscopy confirmed the successful synthesis of catechol tissue tape. Example 7

[0048] Preparation of instant-adhesive strong wet tissue tape

[0049] 0.4 g of chitosan was dissolved in 10 g of AA and 0.21 mL of deionized water and stirred for 30 minutes. Then, 0.1 g of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate synthesized in Example 1 was added and stirring continued for 10 minutes. After dissolution, 0.015 g of a photoinitiator (2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone) was added and stirred to obtain a clear solution. The solution was coated onto a polypropylene film treated with a plasma cleaner and then cured under a 365 nm UV lamp for 3 minutes. The prepared sample was placed in a ziplock bag and stored in a desiccator until further use. This was designated as catechol tissue tape. Infrared spectroscopy confirmed the successful synthesis of catechol tissue tape. Comparative Example 1

[0050] This comparative example is a wet tissue tape prepared by replacing chitosan with gelatin, recorded as catechol gelatin tissue tape ( Figure 8 ).

[0051] Applications of the instant-adhesive, strong-tough wet tissue tape prepared by the present invention include bonding to wet / underwater tissue and wound closure. The following experiments were conducted using the instant-adhesive, strong-tough wet tissue tape (catechol tissue tape) prepared in Example 3.

[0052] Application Example 1

[0053] Actual image and optical transmittance of catechol tissue tape

[0054] The instant adhesive strong wet tissue tape is a flexible tape with a liner. It can be wrapped around a cylindrical paper tube for multiple turns without the tape falling off the liner or the tape coating breaking, which shows that the tape has good flexibility ( Figure 4 When the tape is placed 5 cm in front of the succulent plant, the succulent plant behind the tape can still be clearly observed, indicating that the tape has good optical transparency, which is conducive to directly observing the adhesion of the substrate ( Figure 5 ).

[0055] Application Example 2

[0056] Tensile and mechanical adaptability of catechol tissue tape without polymer backing

[0057] The catechol tissue adhesive without polymer backing was stretched to twice its original length and recovered to its original length after being released. The adhesive did not crack or deform. Figure 6When the adhesive was pressed against wet pigskin tissue, it adapted to the tissue's bending and straightening movements without falling off. These two tests demonstrate that the catechol tissue adhesive, without a polymer film, possesses excellent elasticity, toughness, and shape recovery.

[0058] Application Example 3

[0059] Interfacial toughness and adhesion strength of catechol tissue tape bonded to wet pigskin

[0060] Catechol tissue tape was cut into pieces with a size of 40 × 10 mm. 2 Cut to 60 × 10 × 0.5 mm 3 The tape was bonded to fresh underwater pigskin and immediately formed a strong bond with the underwater pigskin. Even with a 200 g weight hanging from the bottom, it could be easily lifted (Figure 7). The interfacial toughness of the catechol tissue tape bonded to wet / underwater pigskin tissue was as high as 615 J / m 2 The adhesion strength is as high as 1.99 MPa (Figure 8), which is much higher than existing commercial adhesives, such as fibrin glue (32 J / m 2 , 5 kPa), polyethylene glycol-based adhesives (44 J / m 2 , 10 kPa), cyanoacrylate-based adhesives (60 J / m 2 , 32 kPa). Compared with existing wet / underwater tissue adhesives developed by other researchers, it still has excellent adhesion strength, such as polydopamine tissue adhesives (24 kPa), polyvinyl alcohol tissue adhesives (170 kPa), gelatin tissue adhesives (200 kPa), and chitosan tissue adhesives (211.4 kPa).

[0061] Application Example 4

[0062] Closure of damaged biological tissues by catechol tissue tape in different liquid environments

[0063] The size is 40 × 10 mm 2 Two pieces of the same size of 60 × 10 × 0.5 mm were bonded with catechol tissue tape. 3The catechol tissue tape was then tested for adhesion strength in a simulated wound closure model using a universal testing machine on porcine tissues (kidney, liver, heart, and skin) moistened with pig blood (Figure 9A) and simulated body fluids (Figure 9C). The adhesion strength was measured to determine the suitability of the catechol tissue tape for sealing and closing damaged tissues and emergency treatment in different liquid environments (Figures 9B and 9D). The test data in Figures 9B and 9D demonstrate that the catechol tissue tape can effectively seal and close different tissues in both liquid environments, demonstrating its excellent wet adhesion and wound closure capabilities, making it suitable for use in emergency treatment scenarios.

[0064] Application Example 5

[0065] Biocompatibility of catechol tissue adhesive without polymer film

[0066] The cytotoxicity of catechol tissue adhesive without a polymer film was evaluated using a direct contact method according to ISO 10993. A mouse embryonic fibroblast cell suspension cultured in a culture medium without adhesive tape served as a control. 0.1 g of catechol tissue adhesive without a polymer film was placed in a sterile culture dish, and the adhesive tape was rinsed with phosphate-buffered saline. The mouse embryonic fibroblast cell suspension was then incubated at 5 × 10 cells / well. 3 Cells were seeded into 24-well plates at a concentration of 100 cells / well and cultured at 37°C in a humidified atmosphere with 5% CO2 for 72 hours. The old culture medium was removed and 100 μL of 100 mg / mL catechol tissue adhesive extract (uncoated with a polymer film) was added. The cells were cultured for 24, 48, and 72 hours. 10 μL of phosphate-buffered saline (PBS) was added to each well and incubated at 37°C (5% CO2) for 4 hours. The absorbance at 450 nm was measured, using dimethyl sulfoxide as a control.

[0067] At the same time, live / dead cells were determined using a cell counting kit at 24, 48, and 72 hours. Cells were cultured in 24-well plates along with the samples. After incubation, the culture medium was removed, the cells were gently rinsed with phosphate-buffered saline, and 100 µL of staining reagent was added. The plates were then incubated at 37°C in the dark for 30 minutes before the staining reagent was removed. After gently rinsing the cells with phosphate-buffered saline, 100 µL of normal culture medium was added to the wells. Furthermore, the cells were stained with calcein and then propidium iodide and observed under a fluorescence microscope.

[0068] Fluorescence microscopy showed that mouse embryonic fibroblasts in the culture medium containing catechol tissue adhesive without polymer film proliferated well over time and exhibited a normal spindle shape, similar to the control group (Figure 10A). Compared with the control group, the survival rate of mouse embryonic fibroblasts in the tape culture medium was not significantly different at each time point ( Figure 10 B). These results indicate that catechol tissue adhesive without a polymer film is non-cytotoxic due to the good biocompatibility of its components. Therefore, catechol tissue adhesive without a polymer film is biosafe and has the potential to be used as a bioadhesive for wound closure.

Claims

1. A method for preparing an instant-adhesive, strong, wet tissue tape, characterized in that: The steps include: S1. reacting 3,4-dihydroxyphenylacetic acid with glycidyl methacrylate to synthesize 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate; S2. dissolving chitosan in an acrylic acid aqueous solution, then adding 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate and a photoinitiator, and stirring uniformly to obtain a mixed solution; S3. Applying the mixed solution on the surface of the polymer film treated by a plasma cleaner, and then curing it under ultraviolet light to obtain an instant-adhesive strong-tough wet tissue tape.

2. The method for preparing an instant-adhesive strong-tough wet tissue tape according to claim 1, wherein: In step S1, the ratio of 3,4-dihydroxyphenylacetic acid to glycidyl methacrylate is 3.5-4 g: 2.6-3.0 mL.

3. The method for preparing an instant-adhesive strong-tough wet tissue tape according to claim 1, characterized in that: In step S1, the reaction conditions are 60-80° C. and the reaction time is 6-12 hours.

4. The method for preparing an instant-adhesive strong-tough wet tissue tape according to claim 1, wherein: In step S2, the concentration of acrylic acid in the mixed solution is 91.0 to 98.0 wt %, the content of 2-(2-(3,4-dihydroxyphenyl)acetoxy)-3-hydroxypropyl methacrylate is 0.5 to 4.0 wt %, and the concentration of chitosan is 1.0 to 5.0 wt %.

5. The method for preparing the instant-adhesive strong-tough wet tissue tape according to claim 1, wherein: In step S2, the photoinitiator is 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone, and the concentration of the photoinitiator in the mixed solution is 0.1 to 0.3 wt%.

6. The method for preparing an instant-adhesive strong-tough wet tissue tape according to claim 1, characterized in that: In step S3, the polymer film is a polypropylene, polyurethane, cellulose or chitosan film.

7. The method for preparing an instant-adhesive strong-tough wet tissue tape according to claim 1, wherein: In step S3, the UV curing time is 2 to 5 minutes, and the thickness of the adhesive layer after curing is 0.05 to 0.2 mm.

8. An instant-adhesive, strong-tough wet tissue tape obtained by the preparation method according to any one of claims 1 to 7.

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