Mussel-imitating strong-adhesion anti-fouling marker as well as preparation method and application thereof

Abstract

The invention provides a mussel-imitating strong-adhesion anti-fouling marker as well as a preparation method and application thereof, and belongs to the technical field of biomedical materials. The invention provides a mussel-imitating strong-adhesion anti-fouling marker. The mussel-imitating strong-adhesion anti-fouling marker is prepared from the following components: a thixotropic temperature-sensitive physical crosslinking matrix and catechol modified chitosan nanoparticles loaded with surgical dye, the thixotropic temperature-sensitive physical crosslinking matrix comprises the following raw materials: poloxamer, a tannic acid solution, a rheology modifier and a solvent. According to the invention, poloxamer is taken as a temperature-sensitive element, tannic acid is introduced to construct a physical crosslinking enhanced network, catechol modified chitosan nanoparticles are taken as a color carrying and adhesion core, and a rheological modifier is supplemented, so that a system can be endowed with a remarkable shear thinning thixotropic characteristic, the viscosity of a marker can be instantaneously reduced when the marker is subjected to writing shear force, and the marker smoothly flows out; meanwhile, the adhesion and anti-pollution performance of the marker is improved.

Description

A mussel-like strong adhesion and antifouling marker, its preparation method and application Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a mussel-inspired strong adhesion and antifouling marker, its preparation method, and its application. Background Technology

[0002] In gastrointestinal surgery, accurate marking of lesion edges or anastomoses is crucial. However, the complex environment of the abdominal cavity, characterized by moisture, bleeding, peristalsis, and fat encapsulation, presents significant challenges to existing marking techniques: inaccurate marking and positioning. Existing liquid markers (such as methylene blue solution or common thermosensitive gel precursors) are prone to dripping or spreading under gravity when applied to the curved, moist surface of the intestine, resulting in blurred or displaced marking lines, failing to achieve "what you draw is what you get".

[0003] Unable to cope with "flushing, blood staining and adhesion": Liquid markers lack strong interfacial binding mechanisms and anti-fouling design, making them easy to be washed away by peritoneal fluid, covered by blood infiltration, or cause postoperative omental adhesions.

[0004] Poor user experience: Unable to write smoothly.

[0005] Therefore, how to improve the markers to achieve strong adhesion, anti-fouling properties, and smooth flow has become a pressing technical challenge in the field. Summary of the Invention

[0006] The purpose of this invention is to provide a mussel-inspired, highly adhesive, and anti-fouling marker, its preparation method, and its application. The mussel-inspired, highly adhesive, and anti-fouling marker provided by this invention can prevent sagging, allows for smooth flow, and possesses strong waterproof, bloodproof, and oil-resistant properties.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The present invention provides a mussel-like strong adhesion and antifouling marker, comprising the following components: a thixotropic thermosensitive physical crosslinking matrix and catechol-modified chitosan nanoparticles loaded with surgical dyes; the thixotropic thermosensitive physical crosslinking matrix comprises the following raw materials: poloxamer, tannic acid solution, rheology modifier, and solvent.

[0008] Preferably, the concentration of poloxamer in the thixotropic thermosensitive physical crosslinking matrix is ​​16~25g / 100mL.

[0009] Preferably, the concentration of tannic acid in the thixotropic thermosensitive physical crosslinking matrix is ​​0.2~1.8 g / 100 mL.

[0010] Preferably, the rheology modifier is at least one of nanocrystalline cellulose, layered silicate, and fumed silica.

[0011] Preferably, the concentration of the rheology modifier in the thixotropic thermosensitive physical crosslinking matrix is ​​0.1~1.0 g / 100 mL.

[0012] Preferably, the solvent is a phosphate buffer solution.

[0013] Preferably, the catechol-modified chitosan nanoparticles loaded with surgical dye have a mass content of 0.5-3.0% in the mussel-like strong adhesion and antifouling marker.

[0014] Preferably, the loading of the surgical dye on the catechol-modified chitosan nanoparticles is 1.0~5.0%.

[0015] The present invention also provides a method for preparing the mussel-like strong adhesion and antifouling marker described in the above technical solution, comprising: mixing a thixotropic thermosensitive physical crosslinking matrix and catechol-modified chitosan nanoparticles loaded with surgical dyes to obtain the mussel-like strong adhesion and antifouling marker.

[0016] The present invention also provides the application of the mussel-like strong adhesion and antifouling marker described in the above technical solution or the mussel-like strong adhesion and antifouling marker prepared by the preparation method described in the above technical solution in surgical serous membrane surface marking.

[0017] This invention provides a mussel-inspired, highly adhesive, and stain-resistant marker, comprising the following components: a thixotropic, temperature-sensitive, physically crosslinked matrix and catechol-modified chitosan nanoparticles loaded with surgical dyes; the thixotropic, temperature-sensitive, physically crosslinked matrix comprises the following raw materials: poloxamer, tannic acid solution, rheology modifier, and solvent. This invention uses poloxamer as the temperature-sensitive unit, introduces tannic acid to construct a physically crosslinked enhanced network, uses catechol-modified chitosan nanoparticles as the color carrier and adhesion core, and supplements it with a rheology modifier to impart significant shear-thinning thixotropic properties to the system. This allows the marker to instantly reduce viscosity when subjected to writing shear force, ensuring smooth flow and simultaneously improving the marker's adhesive and stain-resistant properties. The results of the embodiments show that the mussel-like strong adhesion and antifouling marker provided by the present invention recovers its viscosity to 15 Pa·s (more than 85% of the initial value) within 0.5 seconds after the shear force is removed (simulating the pen tip leaving the tissue); the width of the marking line on the surface of a pig small intestine tilted at 90° remains at 1 mm ± 0.1 mm, with no displacement within 5 minutes; when the marking site is continuously rinsed with simulated whole blood for 30 seconds, the integrity of the marking remains >95%, and a clear blood-repellent layer is formed on the surface. Detailed Implementation

[0018] This invention provides a mussel-like strong adhesion and antifouling marker, comprising the following components: a thixotropic thermosensitive physical crosslinking matrix and catechol-modified chitosan nanoparticles loaded with surgical dyes; the thixotropic thermosensitive physical crosslinking matrix comprises the following raw materials: poloxamer, tannic acid solution, rheology modifier, and solvent.

[0019] The present invention does not have any special limitations on the source of the raw materials, and commercially available products known to those skilled in the art can be used.

[0020] The mussel-inspired strong adhesion and antifouling marker provided by this invention comprises a thixotropic, temperature-sensitive, physically crosslinked matrix; the thixotropic, temperature-sensitive, physically crosslinked matrix comprises the following raw materials: poloxamer, tannic acid solution, rheology modifier, and solvent. In this invention, a supramolecular network structure with yield stress is formed through hydrogen bonding and physical entanglement assembly.

[0021] In this invention, the poloxamer is preferably poloxamer 407; the concentration of the poloxamer in the thixotropic temperature-sensitive physical crosslinking matrix is ​​preferably 16-25 g / 100 mL. As one embodiment, the concentration of the poloxamer in the thixotropic temperature-sensitive physical crosslinking matrix can be 17 g / 100 mL, 18 g / 100 mL, 19 g / 100 mL, 20 g / 100 mL, 21 g / 100 mL, 22 g / 100 mL, 23 g / 100 mL, or 24 g / 100 mL. This invention uses poloxamer as the temperature-sensitive building block.

[0022] In this invention, the solvent used for the tannic acid solution is preferably deionized water. This invention does not impose a specific limitation on the concentration of the tannic acid solution, as long as the concentration of tannic acid in the thixotropic, temperature-sensitive, physically crosslinked matrix meets the required requirements.

[0023] In this invention, the concentration of tannic acid in the thixotropic thermosensitive physical crosslinking matrix is ​​preferably 0.2~1.8 g / 100 mL. As one embodiment, the concentration of tannic acid in the thixotropic thermosensitive physical crosslinking matrix can be 0.3 g / 100 mL, 0.4 g / 100 mL, 0.5 g / 100 mL, 0.6 g / 100 mL, 0.7 g / 100 mL, 0.8 g / 100 mL, 0.9 g / 100 mL, 1.0 g / 100 mL, 1.1 g / 100 mL, 1.2 g / 100 mL, 1.3 g / 100 mL, 1.4 g / 100 mL, 1.5 g / 100 mL, 1.6 g / 100 mL, or 1.7 g / 100 mL. This invention introduces tannic acid to construct a physically cross-linked enhanced network; by limiting the concentration of tannic acid within the above-mentioned range, it is possible to ensure the mechanical strength and hemostatic properties of the gel while avoiding the risk of increased brittleness or phase separation caused by high concentration.

[0024] In this invention, the rheology modifier is preferably at least one of nanocrystalline cellulose (CNC), layered silicate, and fumed silica; the layered silicate is preferably lithium saponite; and the concentration of the rheology modifier in the thixotropic temperature-sensitive physical crosslinking matrix is ​​preferably 0.1~1.0 g / 100 mL. As one embodiment, the concentration of the rheology modifier in the thixotropic temperature-sensitive physical crosslinking matrix can be 0.2 g / 100 mL, 0.3 g / 100 mL, 0.4 g / 100 mL, 0.5 g / 100 mL, 0.6 g / 100 mL, 0.625 g / 100 mL, 0.7 g / 100 mL, 0.8 g / 100 mL, or 0.9 g / 100 mL. In this invention, the rheology modifier is used to impart thixotropy to the matrix at low temperatures.

[0025] In this invention, the length of the nanocrystalline cellulose is preferably 100-200 nm; the diameter of the nanocrystalline cellulose is preferably 5-10 nm; the thickness of the layered silicate is preferably 1-2 nm; the lateral dimension of the layered silicate is preferably 100-1000 nm; and the average particle size of the fumed silica is preferably 5-50 nm.

[0026] In this invention, the solvent is preferably phosphate buffered saline (PBS). There is no particular limitation on the amount of solvent used, as long as the concentration of each raw material meets the required specifications.

[0027] In one embodiment, the concentration of the phosphate buffer solution can be 0.01M; the pH value of the phosphate buffer solution can be 7.4.

[0028] In this invention, the preferred method for preparing the thixotropic temperature-sensitive physical crosslinking matrix is ​​to mix poloxamer, a rheology modifier, and a solvent, and then add a tannic acid solution to obtain the thixotropic temperature-sensitive physical crosslinking matrix.

[0029] In this invention, the mixing temperature of the poloxamer, rheology modifier, and solvent is preferably 2-8°C. As one embodiment, the mixing temperature of the poloxamer, rheology modifier, and solvent can be 3°C, 4°C, 5°C, 6°C, or 7°C.

[0030] The present invention does not have any special limitations on the operation of adding tannic acid solution, and any technical solution for preparing mixtures that is well known to those skilled in the art can be used.

[0031] The mussel-like strong adhesion and antifouling marker provided by this invention comprises catechol-modified chitosan nanoparticles loaded with surgical dyes; the mass content of the catechol-modified chitosan nanoparticles loaded with surgical dyes in the mussel-like strong adhesion and antifouling marker is preferably 0.5-3.0%. As one embodiment, the mass content of the catechol-modified chitosan nanoparticles loaded with surgical dyes in the mussel-like strong adhesion and antifouling marker can be 1.0%, 1.5%, 2.0%, or 2.5%. In this invention, the catechol-modified chitosan nanoparticles serve as the color carrier and adhesion core, used to improve the strong adhesion and antifouling performance of the surgical dyes; limiting the mass content of the catechol-modified chitosan nanoparticles loaded with surgical dyes within the above range can further improve the adhesion and antifouling performance.

[0032] In this invention, the loading amount of the surgical dye on the catechol-modified chitosan nanoparticles is preferably 1.0 to 5.0%. As one embodiment, the loading amount of the surgical dye on the catechol-modified chitosan nanoparticles can be 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, or 4.5%.

[0033] In this invention, the average particle size of the catechin-modified chitosan nanoparticles is preferably 50-200 nm.

[0034] This invention does not specifically limit the type of surgical dye; any well-known surgical dye may be used. As one embodiment, the surgical dye may be methylene blue. In this invention, the surgical dye is encapsulated within catechol-modified chitosan nanoparticles and complexed with tannins in a thixotropic, temperature-sensitive, physically crosslinked matrix network.

[0035] In this invention, the grafting rate of catechins in the catechin-modified chitosan nanoparticles is preferably 5-30%. As one embodiment, the grafting rate of catechins in the catechin-modified chitosan nanoparticles can be 10%, 15%, 20%, or 25%.

[0036] The present invention does not impose any special limitations on the preparation method of the catechin-modified chitosan nanoparticles. Any preparation method well known to those skilled in the art can be used to ensure that the grafting rate of catechin is within the above-mentioned range.

[0037] This invention does not impose any specific limitations on the preparation method of the catechol-modified chitosan nanoparticles loaded with surgical dyes, as long as the loading amount of surgical dyes meets the required requirements. As one embodiment, the preparation method of the catechol-modified chitosan nanoparticles loaded with surgical dyes can be as follows: First, chitosan is dissolved in acetic acid solution, and 3,4-dihydroxybenzaldehyde (as a catechol source) is added to perform a Schiff base reaction to obtain a modified chitosan solution; then, the modified chitosan solution is mixed with a methylene blue solution, and self-assembly is induced to form nanoparticles using an ionic crosslinking agent (such as sodium tripolyphosphate), and methylene blue is loaded onto these nanoparticles; finally, the nanoparticles are purified by centrifugation and washing to obtain the catechol-modified chitosan nanoparticles loaded with surgical dyes.

[0038] This invention uses poloxamer as a temperature-sensitive unit, introduces tannic acid to construct a physical cross-linking enhanced network, uses catechin-modified chitosan nanoparticles as a color carrier and adhesion core, and supplements it with a rheology modifier to endow the system with significant shear-thinning thixotropic properties, which can make the viscosity of the marker instantly decrease when subjected to writing shear force, allowing it to flow smoothly, while improving the adhesion and anti-fouling performance of the marker.

[0039] The mussel-inspired, highly adhesive, and stain-resistant marker provided by this invention possesses shear-thinning thixotropic rheological properties. In a static state, it is a high-viscosity semi-solid, preventing sagging. When subjected to writing shear force, its viscosity decreases instantaneously, allowing for smooth flow. After shearing ceases, it recovers its high viscosity within milliseconds and utilizes catechol to achieve rapid anchoring within 5 seconds. This invention achieves an ultimate surgical marking experience on moist, bleeding, and peristaltic intestinal surfaces—"draw and stop instantly, remain perfectly still, and be clear and durable"—solving the clinical pain points of traditional markers, such as easy displacement, sagging, and easy obscuring by blood.

[0040] The mussel-like strong adhesion and antifouling marker provided by this invention exhibits the following rheological behavior at 20°C: viscosity at rest >10 Pa·s, and viscosity within 10 s... -1 The apparent viscosity at the shear rate rapidly decreases to <1 Pa·s, and recovers to more than 80% of the initial viscosity within 1 second after the shear force is removed. At 37℃ (body temperature), the system further exhibits significant thermosensitive gel properties: the storage modulus (G') in the static state significantly increases to >100 Pa (more than 5 to 10 times higher than at 20℃), while the loss modulus (G'') relatively decreases, exhibiting overall solid gel behavior, with the viscosity further increasing to >50 Pa·s, suitable for stable anchoring and anti-sagging in vivo. This thermosensitive transition originates from the micelle self-assembly mechanism of poloxamer 407, and with the enhancement of the tannic acid hydrogen bond network, a faster and more stable sol-gel transition (gelation time <1 min) is achieved, ensuring rapid shaping of the marker after contact with tissue during surgery.

[0041] The mussel-inspired, highly adhesive, and stain-resistant marker provided by this invention has the following characteristics: rapid and stable anchoring and anti-sagging: upon contact with tissue, it instantly physical shapes due to thixotropy and generates irreversible chemical anchoring within 5 seconds (physical shaping and chemical adhesion work synergistically), preventing sagging on vertically wetted surfaces; strong blood resistance: a surface barrier film is formed through tannic acid interfacial complexation to prevent blood infiltration; underwater superoleophobicity: a highly hydrated surface is constructed, and contact angle tests show underwater superoleophobicity (>150°); ultimate writing experience: through rheological control, it achieves smooth writing, instant shaping, and no sagging; three strong anti-interference features: strong waterproof erosion resistance, strong blood penetration resistance, and strong oil adhesion resistance.

[0042] This invention achieves the above objectives through a strategy of "chemical matrix upgrade + physical rheology optimization": Chemical matrix upgrade: mussel-tannic acid dual-enhanced network; using catechin-modified chitosan nanoparticles, utilizing the quinone groups after oxidization of catechins to form rapid covalent bonds with amino groups on the tissue surface for anchoring (<5 seconds).

[0043] Tannic acid is introduced to form a dense hydrogen bond network with poloxamer to improve mechanical strength; the protein complexing ability of tannic acid is used to form a blood-repellent film on the surface; and a highly hydrated surface is used to achieve underwater superoleophobic and anti-adhesion.

[0044] Physico-rheological optimization: a shear-thinning thixotropic system was constructed; a rheology modifier was introduced into the system, and a weak physical network with yield stress at low temperature was constructed by finely controlling the interaction between high-concentration tannic acid and poloxamer.

[0045] The principle of the mussel-inspired strong adhesion and stain-resistant marker provided by this invention (draw and stop instantly): When at rest (stored in the pen or just drawn on the tissue), it exhibits a high-viscosity semi-solid state, sufficient to resist gravity and prevent sagging. When subjected to writing shear force (pen tip stroke), the physical network is instantly disrupted, and the viscosity drops sharply, becoming a flowable liquid. Once the pen tip leaves, the shearing stops, and the network is rebuilt within milliseconds to seconds, restoring the high-viscosity solid state, achieving precise shaping.

[0046] The present invention also provides a method for preparing the mussel-like strong adhesion and antifouling marker described in the above technical solution, comprising: mixing a thixotropic thermosensitive physical crosslinking matrix and catechol-modified chitosan nanoparticles loaded with surgical dyes to obtain the mussel-like strong adhesion and antifouling marker.

[0047] The present invention does not have any special limitations on the operation of mixing the thixotropic thermosensitive physical crosslinking matrix and the catechol-modified chitosan nanoparticles loaded with surgical dyes; any technical solution for preparing the mixture well known to those skilled in the art can be used.

[0048] The present invention also provides the application of the mussel-like strong adhesion and antifouling marker described in the above technical solution or the mussel-like strong adhesion and antifouling marker prepared by the preparation method described in the above technical solution in surgical serous membrane surface marking.

[0049] The present invention does not impose any special limitations on the operation of the mussel-like strong adhesion and antifouling marker in surgical serous membrane marking; the application operation of the marker well known to those skilled in the art can be used.

[0050] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0051] Example 1: A mussel-inspired strong adhesion and antifouling marker consists of the following components: a thixotropic thermosensitive physical crosslinking matrix and methylene blue-loaded catechin-modified chitosan nanoparticles; the thixotropic thermosensitive physical crosslinking matrix is ​​prepared from the following raw materials: poloxamer 407, tannic acid solution, nanocrystalline cellulose, and solvent; the solvent is PBS, concentration is 0.01M, pH value is 7.4; the nanocrystalline cellulose has a length of 100~200nm and a diameter of 5~10nm; the concentration of poloxamer 407 in the thixotropic thermosensitive physical crosslinking matrix is ​​25g / 100mL; the concentration of tannic acid in the thixotropic thermosensitive physical crosslinking matrix is ​​1.2g / 100mL; the concentration of nanocrystalline cellulose in the thixotropic thermosensitive physical crosslinking matrix is ​​0.625g / 100mL; the mass content of the methylene blue-loaded catechin-modified chitosan nanoparticles in the mussel-inspired strong adhesion and antifouling marker is... The amount of methylene blue loaded on the catechin-modified chitosan nanoparticles is 3.0%; the loading amount of methylene blue on the catechin-modified chitosan nanoparticles is 5.0%; the grafting rate of catechin in the catechin-modified chitosan nanoparticles is 15%; the average particle size of the catechin-modified chitosan nanoparticles is 50~200nm; the preparation method of the methylene blue-loaded catechin-modified chitosan nanoparticles is as follows: first, chitosan is dissolved in acetic acid solution, and 3,4-dihydroxybenzaldehyde is added to carry out a Schiff base reaction to obtain a modified chitosan solution; then, the modified chitosan solution is mixed with a methylene blue solution, and self-assembly is induced to form nanoparticles by sodium tripolyphosphate as an ionic crosslinking agent, and methylene blue is loaded; finally, the catechin-modified chitosan nanoparticles loaded with methylene blue are obtained by centrifugation and washing purification; the preparation method of the mussel-like strong adhesion antifouling marker is as follows: at 4℃, poloxamer 407 powder and nanocrystalline cellulose are added to 80mL In PBS, the mixture was vigorously stirred and ultrasonically dispersed at low temperature until a uniform milky white dispersion was formed. Under vigorous vortex stirring, 5 mL of a 20 g / 100 mL tannic acid solution with deionized water as solvent was quickly added to obtain a thixotropic thermosensitive physical crosslinking matrix. The thixotropic thermosensitive physical crosslinking matrix was then resuspended with methylene blue-loaded catechol-modified chitosan nanoparticles to obtain a mussel-like strong adhesion and antifouling marker.

[0052] Example 2: A mussel-like strong adhesion and antifouling marker is composed of the following components: a thixotropic thermosensitive physical crosslinking matrix and methylene blue-loaded catechol-modified chitosan nanoparticles; the thixotropic thermosensitive physical crosslinking matrix is ​​prepared from the following raw materials: poloxamer 407, tannic acid solution, layered silicate, and solvent; the solvent is PBS, concentration is 0.01M, pH value is 7.4; the layered silicate is lithium saponite, thickness is 1~2nm, lateral dimension is 100~1000nm; the concentration of poloxamer 407 in the thixotropic thermosensitive physical crosslinking matrix is ​​20g / 100mL; the tannic acid... The concentration of acid in the thixotropic thermosensitive physical crosslinking matrix is ​​0.8 g / 100 mL; the concentration of the layered silicate in the thixotropic thermosensitive physical crosslinking matrix is ​​0.4 g / 100 mL; the mass content of the methylene blue-loaded catechin-modified chitosan nanoparticles in the mussel-like strong adhesion antifouling marker is 1.5%; the loading of methylene blue in the catechin-modified chitosan nanoparticles is 3.0%; the grafting rate of catechin in the catechin-modified chitosan nanoparticles is 20%; the average particle size of the catechin-modified chitosan nanoparticles is 50~200 nm; other operations are the same as in Example 1.

[0053] Example 3: A mussel-like strong adhesion and antifouling marker consists of the following components: a thixotropic thermosensitive physical crosslinking matrix and methylene blue-loaded catechol-modified chitosan nanoparticles; the thixotropic thermosensitive physical crosslinking matrix is ​​prepared from the following raw materials: poloxamer 407, tannic acid solution, fumed silica (average particle size 5-50 nm), and solvent; the solvent is PBS, concentration 0.01 M, pH 7.4; the concentration of poloxamer 407 in the thixotropic thermosensitive physical crosslinking matrix is ​​18 g / 100 mL; the concentration of tannic acid in the thixotropic thermosensitive physical crosslinking matrix... The concentration of the fumed silica in the matrix is ​​1.5 g / 100 mL; the concentration of the fumed silica in the thixotropic temperature-sensitive physical crosslinking matrix is ​​0.5 g / 100 mL; the mass content of the methylene blue-loaded catechin-modified chitosan nanoparticles in the mussel-like strong adhesion antifouling marker is 2.0%; the loading of methylene blue in the catechin-modified chitosan nanoparticles is 4.0%; the grafting rate of catechin in the catechin-modified chitosan nanoparticles is 25%; the average particle size of the catechin-modified chitosan nanoparticles is 50~200 nm; other operations are the same as in Example 1.

[0054] Comparative Example 1: Methylene blue aqueous solution is commonly used in clinical practice.

[0055] Comparative Example 2 omitted the tannic acid solution, nanocrystalline cellulose, and methylene blue-loaded catechin-modified chitosan nanoparticles from Example 1, and obtained ordinary poloxamer 407 thermosensitive gel.

[0056] In a clean environment, the markers prepared in Examples 1-3 and Comparative Examples 1-2 were injected into the reservoir of the marker pen, a spring valve core was installed, a porous pen tip was pressed in, and the pen was sealed. The following tests were then conducted: 1. Rheological and thixotropic testing instruments: rotational rheometer, equipped with a cone-plate clamp, with temperature settings of 20°C (simulating operating room room temperature) and 37°C (body temperature).

[0057] Thixotropic recovery test: Low shear (0.1s) -1 60 seconds, simulating a static state.

[0058] High shear (100s) -1 30 seconds, simulating writing.

[0059] Immediately resume low shear (0.1s) -1 180 seconds, record the time required for the viscosity to recover to the percentage of its initial state (metric: <recovery within 1 second>80%).

[0060] Experimental data show that at 20°C, after the shear force was removed (simulating the pen tip leaving the tissue), the viscosity of Example 1 recovered to 15 Pa·s (more than 85% of the initial value) within 0.5 seconds; Example 2 recovered to 14 Pa·s (more than 82% of the initial value) within 0.6 seconds; Example 3 recovered to 16 Pa·s (more than 88% of the initial value) within 0.4 seconds; and Comparative Example 2 required 15-20 seconds to slowly gel through temperature change.

[0061] At 37°C, this system exhibits stronger thermosensitive gel properties, with a significantly increased viscosity at rest (>50 Pa·s) and faster recovery after shear force removal: Example 1 recovered to 65 Pa·s (over 92% of the initial value) within 0.3 seconds; Example 2 recovered to 58 Pa·s (over 90% of the initial value) within 0.4 seconds; and Example 3 recovered to 72 Pa·s (over 94% of the initial value) within 0.25 seconds. Comparative Example 2, although it gelled slowly at 37°C, still required 10-15 seconds to recover, and its viscosity was only 30-40 Pa·s. This demonstrates that the present invention possesses extremely strong rapid thixotropic recovery and anti-sagging properties at body temperature, making it suitable for precise and durable marking on surgical serous surfaces.

[0062] 2. Anti-drip writing experience test (simulated clinical operation) model: a fresh, moist pig small intestine segment fixed vertically.

[0063] Procedure: Hold the marker pen and write "dots" and "lines" on the surface of the intestine.

[0064] Experimental data show that when marking on the surface of a pig small intestine tilted at 90°, Comparative Example 1 flowed instantly after being dropped, with a diffusion diameter >2cm; Comparative Example 2 showed a downward flow of about 1cm; the marking line width in Example 1 remained at 1mm ± 0.1mm, with no displacement within 5 minutes; the marking line width in Example 2 remained at 1.1mm ± 0.1mm, with no displacement within 5 minutes; and the marking line width in Example 3 remained at 0.9mm ± 0.1mm, with no displacement within 5 minutes.

[0065] 3. Strong anti-blood and anti-erosion performance: The marked area was continuously rinsed with simulated whole blood for 30 seconds. The color of the marks in Comparative Example 1 and Comparative Example 2 faded or even disappeared. In Example 1, due to the rapid physical / chemical anchoring of tannic acid and catechol, the mark integrity was maintained at >95%, and a clear blood-repellent layer was formed on the surface. In Example 2, the mark integrity was maintained at >93%. In Example 3, the mark integrity was maintained at >96%.

[0066] In addition, contact angle tests showed that the underwater superoleophobic contact angle of Example 1 was 152°; that of Example 2 was 150°; that of Example 3 was 155°; that of Comparative Example 1 was 85°; and that of Comparative Example 2 was 110°.

[0067] As can be seen from the above embodiments and comparative examples, the mussel-like strong adhesion anti-fouling marker can prevent dripping, flow smoothly, and has strong waterproof, bloodproof, and oil-proof adhesion properties.

[0068] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A mussel-like strong adhesion and antifouling marker, comprising the following components: a thixotropic thermosensitive physical crosslinking matrix and catechol-modified chitosan nanoparticles loaded with surgical dyes; wherein the thixotropic thermosensitive physical crosslinking matrix comprises the following raw materials: poloxamer, tannic acid solution, rheology modifier, and solvent.

2. The mussel-like strong adhesion and anti-fouling marker according to claim 1, characterized in that, The concentration of poloxamer in the thixotropic thermosensitive physical crosslinking matrix is ​​16~25g / 100mL.

3. The mussel-like strong adhesion and anti-fouling marker according to claim 1, characterized in that, The concentration of tannic acid in the thixotropic thermosensitive physical crosslinking matrix is ​​0.2~1.8 g / 100 mL.

4. The mussel-like strong adhesion and anti-fouling marker according to claim 1, characterized in that, The rheology modifier is at least one of nanocrystalline cellulose, layered silicate, and fumed silica.

5. The mussel-like strong adhesion and anti-fouling marker according to claim 1, characterized in that, The concentration of the rheology modifier in the thixotropic thermosensitive physical crosslinking matrix is ​​0.1~1.0 g / 100 mL.

6. The mussel-like strong adhesion and anti-fouling marker according to claim 1, characterized in that, The solvent is phosphate buffer.

7. The mussel-like strong adhesion and anti-fouling marker according to claim 1, characterized in that, The catechol-modified chitosan nanoparticles loaded with surgical dyes have a mass content of 0.5-3.0% in the mussel-like strong adhesion and antifouling marker.

8. The mussel-like strong adhesion and anti-fouling marker according to claim 1, characterized in that, The loading of the surgical dye on the catechol-modified chitosan nanoparticles is 1.0~5.0%.

9. A method for preparing the mussel-like strong adhesion and antifouling marker according to any one of claims 1 to 8, comprising: A mussel-like strong adhesion and antifouling marker was obtained by mixing a thixotropic, temperature-sensitive, physically crosslinked matrix with catechol-modified chitosan nanoparticles loaded with surgical dyes.

10. The application of the mussel-like strong adhesion and antifouling marker according to any one of claims 1 to 8 or the mussel-like strong adhesion and antifouling marker prepared by the preparation method according to claim 9 in surgical serous membrane surface marking.