High-strength anti-adhesion hydrogel sealant as well as preparation method and application thereof

Abstract

The invention discloses a high-strength anti-adhesion hydrogel sealant and a preparation method and application thereof.The preparation method comprises the steps that citric acid, a polyethylene glycol polypropylene glycol polyethylene glycol segmented copolymer and lauryl alcohol are subjected to a heating reaction under vacuum, double-bond modification is conducted to obtain double-bond CPLA, and the double-bond CPLA is dissolved in a solvent to obtain a first solution; heating citric acid, a polyethylene glycol polypropylene glycol polyethylene glycol block copolymer and dopamine hydrochloride under vacuum to react, carrying out double-bond modification to obtain a double-bond CPLD, and dissolving the double-bond CPLD into a solvent to obtain a second solution; and mixing the first solution and the second solution in equal proportion, adding a photoinitiator, and carrying out photo-crosslinking to obtain the high-strength anti-blocking hydrogel sealant. The sealant can effectively prevent postoperative exudation and postoperative adhesion, and has excellent mechanical properties, adhesive strength, swelling resistance, biocompatibility and biodegradability.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials, specifically relating to a high-strength anti-adhesion hydrogel sealant, its preparation method, and its application. Background Technology

[0002] Colorectal diseases, including colorectal cancer and inflammatory bowel disease, often require surgical intervention for treatment. During surgery, surgeons typically remove the diseased portion of the intestine and then suture the remaining portion to restore intestinal continuity. This process, known as colorectal anastomosis, is a common and crucial step in surgery. Sutures and staplers, as traditional tools, play a vital role in colorectal anastomosis. Meanwhile, in the field of abdominal surgery, preventing postoperative adhesions is also an important issue that surgeons must address. Postoperative abdominal adhesions are a common complication after colorectal surgery, with an incidence rate as high as 50% to 90%, leading to many serious consequences for patients, such as intestinal obstruction, chronic pelvic pain, and even infertility, often requiring a second surgery to resolve.

[0003] In colorectal anastomosis, sutures and staplers are indispensable, but they also bring a series of problems. Tissue damage caused by needle puncture and leakage of contents are the two most prominent challenges. Suture leakage, where contents seep into the abdominal cavity, is one of the most serious complications after colorectal surgery, and in severe cases, it can even lead to patient death. Preventing postoperative adhesions in abdominal surgery also presents challenges. After peritoneal injury, a large number of inflammatory cells are released with the peritoneal fluid. The pro-inflammatory factors and reactive oxygen species (ROS) they secrete can damage tissue, leading to increased vascular permeability and exudate leakage, thereby exacerbating the inflammatory response. Furthermore, leakage through the suture joint can increase the risk of infection and even purulent peritonitis, further prolonging the inflammatory process. Persistent inflammation can lead to excessive fibrin deposition and an imbalance in fibrinolysis, ultimately resulting in abdominal adhesions.

[0004] To address these issues, researchers and doctors are constantly exploring new solutions. Tissue adhesives and sealants, as promising alternatives to sutures, are gradually gaining attention. For example, fibrin glue has been approved as an adjunct to hemostasis in cardiovascular, thoracic, liver, and pancreatic surgeries. Fibrin glue primarily promotes wound healing and reduces bleeding and leakage by mimicking the body's natural clotting process. However, despite its excellent performance in certain surgeries, fibrin glue has not significantly reduced the incidence of anastomotic leakage in some animal experiments or clinical studies due to its poor mechanical properties and low adhesive strength. This indicates that relying solely on existing technologies such as fibrin glue is still insufficient to completely solve the problems of leakage and adhesion in colorectal anastomosis and abdominal surgeries.

[0005] Despite the significant efforts made by researchers and physicians in preventing leakage at colorectal suture sites and postoperative adhesions, current technologies still have significant limitations. While tissue adhesives such as fibrin glue reduce bleeding and leakage to some extent, their mechanical properties and adhesive strength limitations prevent them from completely replacing sutures and staplers. Furthermore, existing technologies have limited effectiveness in preventing postoperative adhesions, failing to effectively block the inflammatory response and fibrin deposition process. Therefore, developing a novel material or technology that possesses both good mechanical properties and adhesive strength while effectively preventing leakage and adhesions remains a pressing issue. Summary of the Invention

[0006] To address the problems existing in the prior art, this invention provides a high-strength anti-adhesion hydrogel sealant, its preparation method, and its application, in order to solve the problems of poor mechanical strength, low adhesive strength, poor wound sealing, and adhesion in the prior art.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing a high-strength anti-adhesion hydrogel sealant, comprising the following steps: Citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol were heated under vacuum to react and double bonded to obtain double bonded CPLA. The double bonded CPLA was dissolved in a solvent to obtain the first solution. Citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and dopamine hydrochloride were heated under vacuum and double-bonded to obtain double-bonded CPLD. The double-bonded CPLD was dissolved in a solvent to obtain a second solution. The first solution and the second solution were mixed in equal proportions, and a photoinitiator was added. Photocrosslinking was then performed to obtain a high-strength anti-adhesion hydrogel sealant.

[0008] Furthermore, the molar ratio of citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and lauryl alcohol is 1.2 : 1.0 : 0.3; The molar ratio of citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and dopamine hydrochloride is 1.2:1.0:0.3.

[0009] Furthermore, the preparation process of the polymer CPLA is as follows: Under a protective atmosphere, citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol are mixed and heated to 160°C until the reactants are completely melted and the entire reaction system is clear. The temperature of the reaction system was lowered to 140°C, a vacuum was drawn, and the reaction continued to obtain the polymer CPLA.

[0010] Furthermore, the preparation process of double-bonded CPLA is as follows: the polymer CPLA is dissolved in anhydrous tetrahydrofuran in an ice-water bath, triethylamine is added after dissolution, acryloyl chloride is added dropwise after stirring, the reaction is carried out, the product is centrifuged, the supernatant is collected and directly evaporated to dryness to obtain double-bonded CPLA.

[0011] Furthermore, the preparation process of the polymer CPLD is as follows: Under a protective atmosphere, citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and dopamine hydrochloride are mixed and heated to 160°C until the reactants are completely melted and the entire reaction system is clear. The temperature of the reaction system was lowered to 140°C, a vacuum was drawn, and the reaction continued to obtain the polymer CPLD.

[0012] Furthermore, the preparation process of double-bonded CPLD is as follows: the polymer CPLD is dissolved in anhydrous tetrahydrofuran in an ice-water bath, triethylamine is added after dissolution, acryloyl chloride is added dropwise after stirring, the reaction is carried out, the product is centrifuged, the supernatant is collected and directly evaporated to dryness to obtain double-bonded CPLD.

[0013] Furthermore, the solution is a 2% hyaluronic acid PBS solution, with the hyaluronic acid having molecular weights of 0, 200,000-400,000, 400,000-600,000, 600,000-800,000, and 800,000-1,200,000, respectively.

[0014] Furthermore, the concentrations of both the first and second solutions are 500 mg / mL.

[0015] Furthermore, the photoinitiator is lithium phenyl-2,4,6-trimethylbenzoyl phosphate with a concentration of 100 μg / mL.

[0016] The present invention also provides a high-strength anti-adhesion hydrogel sealant, which is prepared by the above-described preparation method.

[0017] The present invention also provides a sealant for sealing and suturing wounds after colorectal anastomosis, the sealant comprising the above-mentioned high-strength anti-adhesion hydrogel sealant.

[0018] Compared with the prior art, the present invention has at least the following beneficial effects: This invention discloses a method for preparing a high-strength anti-adhesion hydrogel sealant. First, two raw materials, CPLA (polymerization of citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol) and CPLD (polymerization of citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and dopamine hydrochloride), are prepared by esterification reaction. The two raw materials are then modified by double bond modification. Subsequently, the two raw materials are dissolved in hyaluronic acid PBS solution and mixed. The high-strength anti-adhesion hydrogel sealant is prepared by photocrosslinking.

[0019] Furthermore, citric acid and polyethylene glycol-polypropylene glycol block copolymers were introduced into the hydrogel system. Citric acid is bioactive, improving the biocompatibility of the hydrogel. The polyethylene glycol-polypropylene glycol block copolymers are amphiphilic, enhancing the hydrogel's anti-swelling properties.

[0020] Furthermore, lauryl alcohol and dopamine hydrochloride were introduced into the hydrogel system. Lauryl alcohol enhanced the anti-swelling ability of the hydrogel system. Dopamine hydrochloride has antioxidant properties, which can scavenge ROS in the microenvironment, and at the same time, it can also bring adhesion, enhancing the adhesion ability of the hydrogel system.

[0021] Furthermore, hyaluronic acid was introduced into the hydrogel system. The hyaluronic acid macromolecules will move away from the wound as the network in the system gradually cross-links, thereby achieving the anti-adhesion properties of the hydrogel sealant.

[0022] Furthermore, the two raw materials are prepared into solutions separately and then mixed in equal proportions. A photoinitiator is then added for photocrosslinking. This process is relatively simple, easy to operate and control, and ensures the stability and consistency of the product, providing a feasible solution for large-scale production. This sealant effectively prevents postoperative leakage and adhesion, and also possesses excellent mechanical properties, adhesive strength, anti-swelling properties, biocompatibility, and biodegradability.

[0023] In this invention, the molar ratio of citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, lauryl alcohol, and dopamine hydrochloride is precisely defined as 1.2:1.0:0.3. This precise ratio ensures a complete reaction, allowing each component to fully exert its function and guaranteeing the hydrogel's performance. The preparation process is meticulous and rigorous. Under a protective atmosphere, the reactants are heated to a specific temperature until they melt and become clear. The reaction is then continued under vacuum after cooling to ensure smooth polymerization. The double bond modification process is performed under conditions such as an ice-water bath to ensure reaction stability and obtain high-quality double bonded products. A 2% (w / w) hyaluronic acid-PBS solution is used as the solution, and hyaluronic acid with various molecular weights is available to meet different needs. The concentrations of the first and second solutions are both 500 mg / mL, and the photoinitiator concentration is 100 μg / mL. This appropriate concentration setting is beneficial for the photocrosslinking reaction, forming a high-performance hydrogel sealant.

[0024] The high-strength anti-adhesion hydrogel sealant provided by this invention can be used as a sealant for sealing sutured wounds after colorectal anastomosis. It acts on the wound in an in-situ gel-forming form, adapting well to complex wound morphologies, facilitating wound healing, achieving rapid healing, and providing a new solution for wound management. This sealant effectively seals sutured wounds, prevents postoperative adhesions, avoids leakage of intestinal contents, reduces inflammation, prevents potential infection, and promotes wound healing in multiple ways. It possesses excellent tissue adhesion strength and mechanical strength, adapting to intestinal peristalsis without being damaged, ensuring a long-lasting and stable sealing effect. Simultaneously, the movement of hyaluronic acid macromolecules reduces the adhesion strength on one side of the hydrogel, achieving anti-adhesion properties, meeting various needs for wound healing after colorectal surgery, and has broad prospects and significant value in clinical application. Attached Figure Description

[0025] Figure 1 In the image, (a) shows the 1H NMR spectrum of the polymer CPLA. 1 (a) 1H NMR spectrum; (b) 1H NMR spectrum of double-bonded CPLA; Figure 2 In the image, (a) is the 1H NMR spectrum of the polymer CPLD. 1 (a) H NMR spectrum; (b) double-bonded CPLD. 1 H NMR spectrum; Figure 3 The tensile stress-strain curve of CPLA+CPLD+HA hydrogel; Figure 4 The axial compressive stress-strain curves of the CPLA+CPLD+HA hydrogel are shown. Figure 5 The swelling curve of the CPLA+CPLD+HA hydrogel is shown. Figure 6 The in vitro degradation curves of the CPLA+CPLD+HA hydrogel are shown. Figure 7 In the study, the hemolysis rate of CPLA+CPLD+HA hydrogel and Triton X-100 positive control group upon contact with blood cells was compared. Figure 8 The shear adhesion strength of CPLA+CPLD+HA hydrogel to moist pigskin; Figure 9 Adhesion test on the anti-adhesion side of CPLA+CPLD+HA hydrogel; Figure 10 Live / dead staining images of L929 cells after co-incubation with CPLA+CPLD+HA hydrogel for 24 hours; Figure 11 Tests were conducted on the reactive oxygen species scavenging performance of the CPLA+CPLD+HA hydrogel. Figure 12 Anti-cell adhesion test for CPLA+CPLD+HA hydrogel. Detailed Implementation

[0026] To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions used in the specification and claims are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.

[0027] In this article, unless otherwise specified, “contains,” “includes,” “containing,” “has,” or similar terms cover the meanings of “composed of” and “mainly composed of,” for example, “A contains a” covers the meanings of “A contains a and others” and “A contains only a.”

[0028] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0029] The following examples use instruments and equipment conventional in the art. Experimental methods in the following examples, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. All raw materials used in the following examples are conventional commercially available products with specifications conventional in the art. In this specification and the following examples, unless otherwise specified, "%" represents weight percentage, "parts" represents parts by weight, and "ratio" represents weight proportion.

[0030] The first aspect of this invention discloses a method for preparing a high-strength anti-adhesion hydrogel sealant, comprising the following steps: (1) The polymer CPLA was prepared by citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol. The specific process was as follows: citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol were placed in a single-necked round-bottom flask in a molar ratio of 1.2:1.0:0.3, nitrogen gas was purged for 15 min, and the flask was placed in a preheated 160℃ oil bath under nitrogen gas until complete melting was observed (approximately within 2 h). When the entire reaction system became clear, the temperature was lowered to 140℃, and after the cooling was completed, nitrogen gas purging was stopped, and a vacuum was started. The reaction continued under vacuum until the stir bar stopped rotating at 600 rpm.

[0031] (2) Double-bonded CPLA was prepared by polymer CPLA, triethylamine and acryloyl chloride. The specific process was as follows: 3 g of polymer CPLA was dissolved in 30 ml of anhydrous tetrahydrofuran in an ice-water bath. After dissolution, 164 μL of triethylamine was added, and the mixture was stirred for 5-6 min. Then, 80 μL of acryloyl chloride was added dropwise, and the reaction was carried out for 24 h. The product was centrifuged, and the supernatant was collected and directly evaporated to dryness to obtain double-bonded CPLA.

[0032] (3) A polymer CPLD was prepared by reacting citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and dopamine hydrochloride. Specifically, citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and dopamine hydrochloride were placed in a single-necked round-bottom flask at a molar ratio of 1.2:1.0:0.3. Nitrogen gas was introduced for 15 min, and the flask was placed in a preheated 160°C oil bath under nitrogen gas until complete melting was observed (approximately within 2 h). Once the entire reaction system was clear, the temperature was lowered to 140°C. After cooling, nitrogen gas was stopped, and a vacuum was drawn. The reaction continued under vacuum until the stir bar stopped rotating at 600 rpm.

[0033] (4) Double-bonded CPLD was prepared by polymer CPLD, triethylamine and acryloyl chloride. The specific process was as follows: 3 g of polymer CPLD was dissolved in 30 ml of anhydrous tetrahydrofuran in an ice-water bath. After dissolution, 205 μL of triethylamine was added and stirred for 5-6 min. Then, 100 μL of acryloyl chloride was added dropwise and the reaction was allowed to proceed for 24 h. The product was centrifuged and the supernatant was collected and directly evaporated to dryness to obtain double-bonded CPLD.

[0034] (5) Hyaluronic acid with molecular weights of 0 (without hyaluronic acid), 200,000-400,000, 400,000-600,000, 600,000-800,000 and 800,000-1,200,000 respectively was dissolved in PBS buffer at a mass concentration of 2% to obtain hyaluronic acid PBS solution.

[0035] (6) Both double-bonded CPLA and double-bonded CPLD were dissolved in hyaluronic acid PBS solution at a concentration of 500 mg / mL; the two solutions were mixed in equal proportions and photoinitiator lithium phenyl-2,4,6-trimethylbenzoyl phosphate was added to obtain a precursor solution; ultraviolet irradiation was performed, and the precursor solution was photocrosslinked to obtain a high-strength anti-adhesion hydrogel sealant, wherein the concentration of photoinitiator lithium phenyl-2,4,6-trimethylbenzoyl phosphate was 100 μg / mL.

[0036] The second aspect of this invention discloses a high-strength anti-adhesion hydrogel sealant prepared by the above-described method. This sealant effectively seals sutured wounds, prevents postoperative adhesions, and accelerates wound healing. The hydrogel forms rapidly in situ and seals the sutured wound to prevent leakage of intestinal contents. The antioxidant properties of the hydrogel reduce inflammation and prevent potential infection, thereby promoting wound healing. The hydrogel exhibits excellent tissue adhesion strength and mechanical strength, adapting to intestinal peristalsis without being damaged. The movement of hyaluronic acid macromolecules significantly reduces the adhesion strength on one side of the hydrogel, thus achieving its anti-adhesion properties. The characteristics of this material can meet various needs for wound healing after colorectal surgery.

[0037] The present invention will be further described in detail below with reference to specific embodiments. These descriptions are for explanation purposes only and are not intended to limit the scope of the invention.

[0038] Example 1 (1) The polymer CPLA was prepared by citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol. The specific process was as follows: citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol were placed in a single-necked round-bottom flask in a molar ratio of 1.2:1.0:0.3, nitrogen gas was purged for 15 min, and the flask was placed in a preheated 160℃ oil bath under nitrogen gas until complete melting was observed (approximately within 2 h). When the entire reaction system became clear, the temperature was lowered to 140℃, and after the cooling was completed, nitrogen gas purging was stopped, and a vacuum was started. The reaction continued under vacuum until the stir bar stopped rotating at 600 rpm.

[0039] (2) Double-bonded CPLA was prepared by polymer CPLA, triethylamine and acryloyl chloride. The specific process was as follows: 3 g of polymer CPLA was dissolved in 30 ml of anhydrous tetrahydrofuran in an ice-water bath. After dissolution, 164 μL of triethylamine was added, and the mixture was stirred for 5-6 min. Then, 80 μL of acryloyl chloride was added dropwise, and the reaction was carried out for 24 h. The product was centrifuged, and the supernatant was collected and directly evaporated to dryness to obtain double-bonded CPLA.

[0040] (3) A polymer CPLD was prepared by reacting citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and dopamine hydrochloride. Specifically, citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and dopamine hydrochloride were placed in a single-necked round-bottom flask at a molar ratio of 1.2:1.0:0.3. Nitrogen gas was introduced for 15 min, and the flask was placed in a preheated 160°C oil bath under nitrogen gas until complete melting was observed (approximately within 2 h). Once the entire reaction system was clear, the temperature was lowered to 140°C. After cooling, nitrogen gas was stopped, and a vacuum was drawn. The reaction continued under vacuum until the stir bar stopped rotating at 600 rpm.

[0041] (4) Double-bonded CPLD was prepared by polymer CPLD, triethylamine and acryloyl chloride. The specific process was as follows: 3 g of polymer CPLD was dissolved in 30 ml of anhydrous tetrahydrofuran in an ice-water bath. After dissolution, 205 μL of triethylamine was added and stirred for 5-6 min. Then, 100 μL of acryloyl chloride was added dropwise and the reaction was allowed to proceed for 24 h. The product was centrifuged and the supernatant was collected and directly evaporated to dryness to obtain double-bonded CPLD.

[0042] (5) Dissolve hyaluronic acid with a molecular weight of 600,000 to 800,000 in PBS buffer at a mass concentration of 2% to obtain hyaluronic acid PBS solution.

[0043] (6) Both double-bonded CPLA and double-bonded CPLD were dissolved in hyaluronic acid PBS solution at a concentration of 500 mg / mL; the two solutions were mixed in equal proportions, and the photoinitiator lithium phenyl-2,4,6-trimethylbenzoyl phosphate was added to obtain a precursor solution; the precursor solution was subjected to ultraviolet irradiation, and a high-strength anti-adhesion hydrogel sealant was obtained by photocrosslinking, wherein the concentration of the photoinitiator lithium phenyl-2,4,6-trimethylbenzoyl phosphate was 100 μg / mL. The obtained hydrogel was named CPLA+CPLD+HA3.

[0044] Example 2 Unlike Example 1, the molecular weight of hyaluronic acid in step (5) was adjusted to 0 (no hyaluronic acid was added), and the resulting anti-adhesion hemostatic hydrogel was named CPLA+CPLD.

[0045] Example 3 Unlike Example 1, the molecular weight of hyaluronic acid in step (5) was adjusted to 200,000-400,000, and the resulting anti-adhesion hemostatic hydrogel was named CPLA+CPLD+HA1.

[0046] Example 4 Unlike Example 1, the molecular weight of hyaluronic acid in step (5) was adjusted to 400,000-600,000, and the resulting anti-adhesion hemostatic hydrogel was named CPLA+CPLD+HA2.

[0047] Example 5 Unlike Example 1, the molecular weight of hyaluronic acid in step (5) was adjusted to 800,000-1,200,000, and the resulting anti-adhesion hemostatic hydrogel was named CPLA+CPLD+HA4.

[0048] The substances obtained in Example 1 were analyzed. 1 H NMR spectrum ( Figure 1 ,2) The successful synthesis of polymer CPLA, double-bonded CPLA, polymer CPLD and double-bonded CPLD was confirmed. Figure 1The characteristic peaks at 2.3 and 6.2 ppm correspond to the -CO-O- group and the -CH=CH2 group, indicating the successful synthesis of polymer CPLA and double-bonded CPLA. Figure 2 The characteristic peaks at 6.7 and 6.2 ppm correspond to the protons and -CH=CH2 groups on the benzene ring of dopamine hydrochloride, indicating the successful synthesis of polymer CPLD and double-bonded CPLD.

[0049] Figure 3 The tensile stress-strain curves of the CPLA+CPLD+HA hydrogel are shown. With the increase of HA molecular weight, the tensile strength and elongation at break of the hydrogel both show a trend of first increasing and then decreasing. The CPLA+CPLD+HA2 group has the highest tensile strength and elongation at break, which are 54.33 kPa and 218.8%, respectively.

[0050] Figure 4 The figures show the axial compressive stress-strain curves for the CPLA+CPLD+HA hydrogels. All five hydrogel groups can form a robust structure capable of resisting a certain amount of pressure. The CPLA+CPLD+HA group exhibits the highest compressive strength, reaching 35.95 kPa.

[0051] Figure 5 The swelling curves of the CPLA+CPLD+HA hydrogels are shown. The addition of HA molecules significantly increases the swelling rate of the hydrogels, with the CPLA+CPLD+HA1 group reaching a swelling rate of 450%. As the molecular weight of HA increases, the swelling rate of the hydrogels first decreases and then increases, with the CPLA+CPLD+HA3 group exhibiting the lowest swelling rate at 64%.

[0052] Figure 6 The in vitro degradation curves of the CPLA+CPLD+HA hydrogel are shown in the figure. As can be seen from the figure, approximately 80% of the five hydrogel materials degraded after 35 days. Therefore, while treating wounds, the CPLA+CPLD+HA hydrogel does not significantly affect the user's normal physiological activities. Furthermore, the material's slow degradation provides an effective physical barrier and protection during the vulnerable inflammatory and repair phases of the wound.

[0053] Figure 7 The hemolysis rate of CPLA+CPLD+HA hydrogel and Triton X-100 positive control group upon contact with blood cells was measured. The hemolysis rate of all five groups of CPLA+CPLD+HA hydrogel was less than 5%, indicating that these materials have good blood compatibility.

[0054] Figure 8The adhesion strength of CPLA+CPLD+HA hydrogel to pigskin was evaluated using an overlap shear test. As shown in the figure, even the lowest adhesion strength of CPLA+CPLD+HA3 hydrogel reached 11 kPa.

[0055] Figure 9 For the anti-adhesion test of CPLA+CPLD+HA hydrogel, the adhesion strength of the group with added HA (CPLD+CPLA+HA1 / HA2 / HA3 / HA4) was lower than that of the group without HA (CPLD+CPLA), indicating that the introduction of HA effectively reduced the adhesion between the material and the tissue, indirectly supporting its anti-adhesion function; the composite hydrogel containing HA is more suitable for postoperative anti-adhesion scenarios by reducing adhesion strength and synergistic bioactivity.

[0056] L929 cells were co-cultured with the material leachate to determine cell compatibility. CPLA+CPLD+HA hydrogel was co-cultured with L929 cells for 24 hours, with tissue culture plates (TCP) serving as a control group. Figure 10 As shown in Figure (a), the cell viability of each group exceeded 97%. Referring to Figure (b), the live / dead staining results are consistent with the cell viability results; the L929 cells in each group exhibited a green spindle shape with only a few dead cells in the field of view, similar to the TCP group. These results indicate that the CPLA+CPLD+HA hydrogel has good cell compatibility.

[0057] Figure 11 The reactive oxygen species (ROS) scavenging performance of CPLA+CPLD+HA hydrogels was tested. Compared with the control group, the CPLA+CPLD+HA hydrogel group effectively reduced the ROS content in cells, and the fluorescence intensity was significantly reduced. These results indicate that the CPLA+CPLD+HA hydrogels possess good antioxidant properties.

[0058] Figure 12 Anti-cell adhesion test of CPLA+CPLD+HA hydrogel. The fluorescence intensity of the CPLA+CPLD+HA hydrogel group was much lower than that of the hydrogel-free group, indicating that very few cells adhered to the hydrogel. The results show that the CPLA+CPLD+HA hydrogel has excellent anti-adhesion properties.

[0059] In summary, this invention provides a high-strength, anti-adhesion hydrogel sealant. This sealant effectively seals sutured wounds, prevents postoperative adhesions, and accelerates wound healing. The hydrogel forms rapidly in situ and seals the sutured wound to prevent leakage of intestinal contents. The hydrogel's antioxidant properties reduce inflammation and prevent potential infection, thereby promoting wound healing. The hydrogel exhibits excellent tissue adhesion and mechanical strength, adapting to intestinal peristalsis without being damaged. The movement of hyaluronic acid macromolecules significantly reduces the adhesion strength on one side of the hydrogel, thus achieving its anti-adhesion properties. Furthermore, this sealant is biodegradable and biocompatible, allowing it to be safely integrated into the body and effectively promote wound healing. The characteristics of this material can meet various needs for wound healing after colorectal surgery and may become an indispensable part of colorectal surgery in the future, providing patients with rapid and effective treatment and healing opportunities.

[0060] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a high-strength anti-adhesion hydrogel sealant, characterized in that, Includes the following steps: Citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol were heated under vacuum to react and double bonded to obtain double bonded CPLA. The double bonded CPLA was dissolved in a solvent to obtain the first solution. Citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and dopamine hydrochloride were heated under vacuum and double-bonded to obtain double-bonded CPLD. The double-bonded CPLD was dissolved in a solvent to obtain a second solution. The first solution and the second solution were mixed in equal proportions, and a photoinitiator was added. Photocrosslinking was then performed to obtain a high-strength anti-adhesion hydrogel sealant.

2. The method for preparing a high-strength anti-adhesion hydrogel sealant according to claim 1, characterized in that, The molar ratio of citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and lauryl alcohol is 1.2 : 1.0 : 0.

3. The molar ratio of citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer, and dopamine hydrochloride is 1.2:1.0:0.

3.

3. A method for preparing a high-strength anti-adhesion hydrogel sealant according to claim 1 or 2, characterized in that, The preparation process of the polymer CPLA is as follows: Under a protective atmosphere, citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and lauryl alcohol are mixed and heated to 160°C until the reactants are completely melted and the entire reaction system is clear. The temperature of the reaction system was lowered to 140°C, a vacuum was drawn, and the reaction continued to obtain the polymer CPLA.

4. The method for preparing a high-strength anti-adhesion hydrogel sealant according to claim 3, characterized in that, The preparation process of double-bonded CPLA is as follows: the polymer CPLA is dissolved in anhydrous tetrahydrofuran in an ice-water bath, triethylamine is added after dissolution, and acryloyl chloride is added dropwise after stirring. After the reaction is complete, the product is centrifuged, and the supernatant is collected and directly evaporated to dryness to obtain double-bonded CPLA.

5. A method for preparing a high-strength anti-adhesion hydrogel sealant according to claim 1 or 2, characterized in that, The preparation process of the polymer CPLD is as follows: Under a protective atmosphere, citric acid, polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymer and dopamine hydrochloride are mixed and heated to 160°C until the reactants are completely melted and the entire reaction system is clear. The temperature of the reaction system was lowered to 140°C, a vacuum was drawn, and the reaction continued to obtain the polymer CPLD.

6. The method for preparing a high-strength anti-adhesion hydrogel sealant according to claim 5, characterized in that, The preparation process of double-bonded CPLD is as follows: polymer CPLD is dissolved in anhydrous tetrahydrofuran in an ice-water bath, triethylamine is added after dissolution, acryloyl chloride is added dropwise after stirring, the reaction is carried out, the product is centrifuged, the supernatant is collected and directly evaporated to dryness to obtain double-bonded CPLD.

7. The method for preparing a high-strength anti-adhesion hydrogel sealant according to claim 1, characterized in that, The solution is a 2% (w / w) hyaluronic acid PBS solution, with hyaluronic acid having molecular weights of 200,000-400,000, 400,000-600,000, 600,000-800,000, and 800,000-1,200,000, respectively; the concentration of both the first and second solutions is 500 mg / mL.

8. The method for preparing a high-strength anti-adhesion hydrogel sealant according to claim 1, characterized in that, The photoinitiator is lithium phenyl-2,4,6-trimethylbenzoyl phosphate with a concentration of 100 μg / mL.

9. A high-strength anti-adhesion hydrogel sealant, characterized in that, It is prepared by any one of claims 1 to 8.

10. A sealant for sealing and suturing wounds after colorectal anastomosis, characterized in that, The sealant includes the high-strength anti-adhesion hydrogel sealant as described in claim 9.

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