A hydrogel patch for gastric perforation repair and a preparation method thereof

Abstract

This invention discloses a hydrogel patch for repairing gastric perforation and its preparation method, belonging to the field of biomedical materials technology. The preparation method is as follows: Acryloylvaline, acrylic acid, methylenebisacrylamide, compound A, and a photoinitiator are dissolved in an alcohol solvent, and after defoaming, a precursor solution is obtained. The precursor solution is then placed in a mold and cured by ultraviolet light. The resulting hydrogel is immersed in a hydrochloric acid solution to displace the alcohol solvent, yielding the hydrogel patch for repairing gastric perforation. The hydrogel patch provided by this invention has advantages such as resistance to strong acid corrosion, good biocompatibility, low swelling rate, and stable adhesion under fluctuating pH conditions. This strong and stable adhesion ensures that the hydrogel can adhere reliably and persistently to the gastric perforation site in a dynamic gastric acid environment, providing a stable platform for drug delivery, thereby potentially shortening surgical time and promoting wound healing.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to a hydrogel patch for repairing gastric perforation that is resistant to swelling and has stable adhesion under dynamic pH conditions of gastric juice, and its preparation method. Background Technology

[0002] Gastric perforation, such as ruptured gastric ulcers and gastric cancer, is one of the most acute abdominal conditions. Severe gastric perforation can lead to peritonitis, septic shock, and even multiple organ failure syndrome. Surgical treatment remains the most reliable clinical approach to date. Sutures made from biodegradable polymers (such as polyglycolic acid, polylactic acid, polylactic acid-copolyglycolic acid, or polyester polyurethane) have been widely used to repair gastric perforations; however, they are often associated with deep punctures and severe damage to gastric tissue due to ischemia, as well as inflammation of the biological tissue. Furthermore, sealing with decellularized tissue matrix carries a high risk of immune responses, especially in cases of acute injury or infection. Given these drawbacks, bioadhesive materials have emerged as one of the most promising alternatives or adjuncts to sutures and staples in the sealing and repair of gastric wounds.

[0003] Hydrogels are soft, moist materials with a similar flexibility and microenvironment to biological soft tissue. They are typically composed of cross-linked polymers with a three-dimensional network structure, capable of swelling in water and retaining a large amount of water without completely dissolving. As a soft, moist material, they are widely used in medical bioadhesive materials. However, due to the presence of gastric juice and its pH variations (pH 1-3), hydrogels exhibit swelling and pH responsiveness (volume responsiveness and adhesive responsiveness). Swelling of hydrogels can cause them to stretch at the wound site, hindering wound healing, while their responsiveness can lead to unstable adhesive properties, resulting in gel detachment and failure to achieve the desired therapeutic effect.

[0004] Chinese invention patent application number CN202410790727.8 discloses a hydrogel for repairing gastric perforation. This hydrogel can be rapidly injected and gelled through the esterification reaction between multi-arm PEG-NH2 and multi-arm PEG-NHS, and has a good adhesion effect to the outer wall of the stomach, making it suitable for the treatment of gastric perforation. However, the adhesion of this hydrogel is achieved by covalently bonding the amino functional groups on the stomach wall with the succinimide functional groups in the hydrogel. In the acidic environment of the stomach, the amino groups are easily protonated and cannot react with the succinimide functional groups, making it difficult for the gel to adhere to the inner wall of the stomach. Furthermore, the gel will still swell in an acidic environment, which will cause the gel to increase in volume after adhering to the stomach wall, thereby enlarging the wound and hindering perforation healing. Summary of the Invention

[0005] The purpose of this invention is to solve the problems of swelling of hydrogels in the gastric juice environment and adhesion response in the dynamic gastric acid environment in the prior art, and to provide a hydrogel patch for repairing gastric perforation and its preparation method. The hydrogel patch provided by this invention has the advantages of resistance to strong acid corrosion, good biocompatibility, low swelling rate, and stable adhesion performance in fluctuating pH environments.

[0006] The specific technical solution adopted in this invention is as follows:

[0007] In a first aspect, the present invention provides a method for preparing a hydrogel patch for repairing gastric perforation, comprising:

[0008] S1: Acrylylvaline, acrylic acid, methylenebisacrylamide, compound A, and photoinitiator are dissolved in an alcohol solvent and defoamed to obtain a precursor solution;

[0009] The structural formula of the acryloylvaline is: ;

[0010] The structural formula of compound A is:

[0011] ;

[0012] S2: The precursor solution is placed in a mold and cured by UV light. The resulting hydrogel is then immersed in hydrochloric acid solution to displace the alcohol solvent, resulting in a hydrogel patch for repairing gastric perforation.

[0013] As a preferred embodiment of the first aspect above, the molar concentration ratio of acryloylvaline, acrylic acid, methylenebisacrylamide, compound A and photoinitiator in the precursor solution is (0.6~0.8): (1.2~1.4): (0.003~0.007): (0.008~0.012):0.1.

[0014] As a preferred embodiment of the first aspect above, the photoinitiator is photoinitiator 2959 or α-ketoglutarate.

[0015] As a preferred embodiment of the first aspect above, the alcohol solvent is anhydrous ethanol.

[0016] As a preferred embodiment of the first aspect above, the method for preparing acryloylvaline is as follows: a sodium hydroxide solution of valine is added dropwise to acryloyl chloride, and after the reaction is complete under stirring, hydrochloric acid is added to the preliminary reaction product for acidification and the reaction is continued under stirring. The reaction product is extracted with ethyl acetate and then evaporated to dryness to obtain a solid product of acryloylvaline.

[0017] As a preferred embodiment of the first aspect above, the preparation method of compound A is as follows: triethanolamine and 4-hydroxymethylphenylboronic acid are added to dimethylformamide solvent for a condensation reaction, and the intermediate compound 2-(2-(4-(hydroxymethyl)phenyl)-1,3,6,2-dioxaborane-6-yl)ethyl-1-ol is separated; then the intermediate compound, isocyanate ethyl acrylate and dibutyltin dilaurate are added to dimethylformamide solvent for an addition reaction, and the reaction product is separated, purified and freeze-dried to obtain solid compound A.

[0018] As a preferred embodiment of the first aspect above, the defoaming treatment employs ultrasonic defoaming.

[0019] As a preferred embodiment of the first aspect above, the method of UV-induced curing is as follows: placing the precursor solution in the mold under UV irradiation for 8 to 10 hours, wherein the UV wavelength used is 365 nm and the UV irradiation power is 40 to 50 W.

[0020] As a preferred embodiment of the first aspect above, the hydrochloric acid solution has a pH of 1 to 3, and the hydrogel is soaked in the hydrochloric acid solution for 2 to 4 days.

[0021] In a second aspect, the present invention provides a hydrogel patch for repairing gastric perforation prepared by the preparation method described in any of the first aspects above.

[0022] Compared with the prior art, the present invention has the following advantages:

[0023] 1. This invention introduces the hydrophobic monomer acryloylvaline (NAV), which significantly inhibits acidic swelling. This improvement effectively solves the problem of severe swelling of existing polyacrylic acid hydrogels in the acidic environment of the stomach. Within the pH range of 1-3, the swelling rate of the hydrogel of this invention is less than 10%, significantly lower than the swelling rate of up to 360% of polyacrylic acid hydrogels without NAV and compound A at pH=3. Therefore, the low swelling characteristics of the hydrogel prepared by this invention ensure that it maintains structural integrity and dimensional stability in the stomach, laying the foundation for subsequent functional realization.

[0024] 2. This invention utilizes the synergistic effect of NAV and compound A to significantly enhance acidic adhesion strength. The synergistic effect of NAV and compound A in this improvement allows the hydrogel to overcome the weakness of existing polyacrylic hydrogels under strong acid conditions. The hydrogel of this invention shows an adhesion performance improvement of over 350% in hydrochloric acid solution at pH=1, and an improvement of up to 1280% in solution at pH=3 (based on polyacrylic hydrogels without NAV and compound A). This significantly enhanced adhesion strength provides a strong guarantee for achieving firm fixation of the hydrogel at gastric perforation sites.

[0025] 3. This invention improves the adhesive stability under gastric juice pH fluctuations through the combination of NAV and compound A. This invention significantly improves the problem of the sensitivity of existing hydrogel adhesive properties to gastric juice pH fluctuations (the adhesive properties of existing polyacrylic acid hydrogels can decrease by up to 70% with increasing pH). The hydrogel of this invention maintains stable interfacial toughness of approximately 265 J / m within a pH range of 1-3. 2 Furthermore, it exhibits excellent stability. This strong and stable adhesive property ensures that the hydrogel can adhere reliably and persistently to the gastric perforation site in a dynamic gastric acid environment, providing a stable platform for drug delivery, which is expected to shorten surgical operation time and promote wound healing. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the dynamic ring-opening and ring-closing of compound A;

[0027] Figure 2 A comparison chart showing the effect of the presence or absence of NAV monomers on the swelling rate of hydrogels;

[0028] Figure 3 A comparative graph showing the effect of the presence or absence of NAV monomers on the uniaxial tensile mechanical properties of hydrogels;

[0029] Figure 4 A schematic diagram illustrating the adhesion mechanism of hydrogel patches to the gastric wall during the repair of gastric perforation.

[0030] Figure 5 A comparison of the effects of NAV monomers and compound A on the toughness of the hydrogel adhesion interface;

[0031] Figure 6 A comparison of interfacial toughness before and after treatment with sodium bicarbonate solution;

[0032] Figure 7 This image shows the biocompatibility test of hydrogel patches with GES-1 gastric parietal cells in vitro (green represents live cells, and red represents dead cells).

[0033] Figure 8 A statistical graph showing the cell mortality rate of GES-1 gastric parietal cells cultured in vitro on hydrogel patches;

[0034] Figure 9 Cumulative drug release curve for hydrogel patches;

[0035] Figure 10 This is a comparison of the results of in vitro repair of gastric perforation using hydrogel patches prepared in embodiments of the present invention and polyacrylic acid hydrogel. Detailed Implementation

[0036] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of the present invention. However, the present invention can be practiced in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below. Technical features in various embodiments of the present invention can be combined accordingly without mutual conflict.

[0037] It should be noted that the structural formula of acryloylvaline (NAV) used in this invention is as follows:

[0038]

[0039] The synthetic route for the above NAV is as follows:

[0040]

[0041] In subsequent embodiments of the present invention, the NAV is synthesized and prepared by the following specific synthesis methods:

[0042] 46.8 g of valine, 32 g of NaOH, and 180 ml of H₂O were stirred at 2-8°C for 30 min. Then, 32.5 ml of acryloyl chloride was added dropwise to a beaker using a dropping funnel, and the mixture was stirred at 2-8°C for 2 h, followed by stirring at room temperature for one day. After one day, 32 ml of HCl was slowly added to the beaker, and the mixture was acidified and stirred for 1 h. Finally, the mixture was extracted with 500 ml of ethyl acetate. The washings from the ethyl acetate solution were collected, and the ethyl acetate solution was evaporated to dryness using a rotary evaporator to obtain a white or pale yellow solid, which is acryloylvaline.

[0043] Furthermore, the structural formula of compound A used in this invention is:

[0044] .

[0045] The synthetic route for compound A is as follows:

[0046]

[0047] In subsequent embodiments of the present invention, compound A is synthesized and prepared by the following specific synthetic methods:

[0048] At room temperature, 20 g of 4-hydroxymethylphenylboronic acid and 20 g of triethanolamine were weighed separately using an electronic balance and added to a dry 300 mL wide-mouth glass reaction flask. Then, 200 mL of ultra-dry dimethylformamide (DMF) solvent was added, and the mixture was magnetically stirred until fully dissolved. The reaction flask was placed in an oil bath at 40 °C, and the reaction was continued with stirring. After the reaction was complete, the flask was removed and cooled to room temperature. Precipitation was carried out using 5 times the volume of diethyl ether. This precipitation process was repeated three times to obtain white solid particles. Finally, the particles were washed three times with acetone three times the volume of the white particles to obtain pure 2-(2-(4-(hydroxymethyl)phenyl)-1,3,6,2-dioxaborane-6-yl)ethyl-1-ol. The intermediate compound was dried in a vacuum at 40 °C for three days to obtain the dried intermediate compound. Subsequently, 12 g of the intermediate compound and 15.4 g of isocyanate methyl acrylate were accurately weighed and added to a dry 300 mL wide-mouth glass reaction flask. Simultaneously, 90 mL of ultra-dry DMF solvent was added, and the mixture was stirred until the solution became clear. 20 µL of dibutyltin dilaurate (DBTL) was added, and the mixture was stirred in the dark under nitrogen atmosphere until the reaction was complete. Then, the product was precipitated and washed three times with 15 times the volume of diethyl ether to obtain a pale yellow viscous solid 2-((((4-(6-(2-((((2-(methacryloyloxy)ethyl)carbamateoxy)ethyl)-1,3,6,2-dioxaborane-2-yl)phenyl)oxy)carbamate)amino)ethyl methacrylate (i.e., compound A). This solid was then freeze-dried for three days to obtain dried compound A. Finally, compound A was stored in an inert gas atmosphere at −20 °C for future use.

[0049] Compound A exhibits reversible dynamic ring-opening and ring-closing changes during acidic conditions, as illustrated in the diagram below. Figure 1 As shown.

[0050] It should be noted that the specific synthesis methods of NAV and compound A described above are merely preferred embodiments of the present invention, and theoretically, compounds with the same structure can also be synthesized through other methods. In the following embodiments, except for NAV and compound A which are synthesized using the above preparation methods, all other materials and reagents can be commercially available and are not limited thereto.

[0051] Example 1

[0052] In this embodiment, a hydrogel patch for repairing gastric perforation was prepared. The specific preparation steps are as follows:

[0053] Step 1: Acryloylvaline (NAV), acrylic acid, methylenebisacrylamide, compound A, and photoinitiator 2959 were dissolved in anhydrous ethanol and stirred at room temperature for 15 min to ensure complete dissolution of all components, yielding a precursor solution. In this precursor solution, the molar concentrations of acryloylvaline, acrylic acid, methylenebisacrylamide, compound A, and photoinitiator 2959 were 0.7:1.3:0.005:0.01:0.1, respectively.

[0054] Step 2: Place the homogeneous precursor solution obtained in Step 1 into an ultrasonic defoamer and sonicate for 10 minutes to remove bubbles.

[0055] Step 3: Pour the defoamed precursor solution obtained in Step 2 into the curing mold and wait for curing.

[0056] Step 4: Place the cured mold from Step 3 in an ultraviolet curing chamber and irradiate the precursor solution with ultraviolet light at a wavelength of 365 nm and a power of 45 W for 8 hours.

[0057] Step 5: Demold the solid obtained inside the mold after UV irradiation in Step 4, and immerse it in a hydrochloric acid solution with a pH of 2 for 72 hours to displace the anhydrous ethanol in the solid. Then remove it from the hydrochloric acid solution as a hydrogel for subsequent gastric perforation repair.

[0058] Comparative Example 1

[0059] In this comparative example, compared to Example 1, acryloylvaline (NAV) in step 1 was replaced with an equimolar amount of acrylic acid, while the rest of the process remained consistent with steps 1 to 5 of Example 1. Therefore, the hydrogel prepared in Comparative Example 1 is a hydrogel that does not contain NAV but contains compound A.

[0060] Comparative Example 2

[0061] In this comparative example, compared to Example 1, compound A in step 1 was replaced with an equimolar amount of methylenebisacrylamide, while the rest of the procedures remained the same as steps 1 to 5 in Example 1. Therefore, the hydrogel prepared in Comparative Example 2 is a hydrogel that does not contain compound A but contains NAV.

[0062] Comparative Example 3

[0063] In this comparative example, compared to Example 1, acryloylvaline (NAV) in step 1 was replaced with an equimolar amount of acrylic acid, and compound A in step 1 was replaced with an equimolar amount of methylenebisacrylamide. All other procedures remained the same as steps 1-5 in Example 1. Therefore, the hydrogel prepared in Comparative Example 2 was a hydrogel that did not contain NAV or compound A.

[0064] To compare and demonstrate the synergistic effect of acryloylvaline (NAV) introduced in this invention and compound A, the hydrogels (all with dimensions of 10 cm × 10 cm × 1 mm) prepared in Example 1, Comparative Examples 1 and 2 were subjected to performance tests. The specific test procedures are as follows:

[0065] 1) Swelling rate test

[0066] The two hydrogels prepared in Example 1 and Comparative Example 1 (the difference being whether they contain NAV) were cut into circular patches with a diameter of 8 mm and a thickness of 1 mm. Four groups of each type of hydrogel circular patch were taken and immersed in hydrochloric acid solutions at pH=1, pH=2, pH=3, and pH=4 for 48 h, respectively. The volume (V2) of each circular patch sample after immersion in solutions at different pH values ​​was then measured, and the swelling ratio (SR) was calculated using the formula: SR = (V1 / V2) × 100%, where V1 is the initial volume after immersion in an HCl aqueous solution at pH=2 for 72 h. The final swelling ratio test results for the two types of hydrogel circular patches are as follows: Figure 2 As shown.

[0067] 2) Uniaxial tensile test

[0068] The two hydrogels prepared in Example 1 and Comparative Example 1 (the difference between them being whether or not they contain NAV) were cut into standard dumbbell-shaped specimens and subjected to tensile tests using a universal testing machine (Instron 5965) at a tensile rate of 60 mm / min. The stress-strain curves were recorded, and the test results are shown below. Figure 3 As shown.

[0069] 3) 180° peel test (interface toughness test)

[0070] The hydrogel prepared in Example 1 of this invention can adhere to the gastric wall through hydrogen bonds. Figure 4This study demonstrates the adhesion mechanism between the hydrogel and the gastric wall when used as a patch for repairing gastric perforation. To test the toughness of the adhesion interface, four groups of hydrogels were prepared from each of the following samples: the hydrogel prepared in Example 1 (containing NAV and compound A), the hydrogel prepared in Comparative Example 1 (without NAV but containing compound A), and the hydrogel prepared in Comparative Example 2 (containing NAV but without compound A). These samples were immersed in hydrochloric acid solutions at pH 1, pH 2, pH 3, and pH 4 for 48 h, respectively. The immersed hydrogel samples were then cut into strips with a width (w) of 1 cm for subsequent testing. For each type of hydrogel strip, the testing procedure was as follows: Freshly slaughtered porcine gastric mucosa tissue was taken and cut into two strips, each 1 cm wide and 15 cm long. One strip of porcine gastric tissue was fixed to the testing platform, and the hydrogel strip was smoothly adhered to it. The other strip of porcine gastric tissue was then smoothly placed over the hydrogel, forming a "sandwich" structure to hold the hydrogel. A 180° peel test was conducted using an Instron 5965 universal testing machine at a peel rate of 120 mm / min. The peel force (F) was recorded, and the interfacial toughness (G) was calculated based on the width w and peel force F using the following formula: G = 2F / w. Finally, the adhesion interfacial toughness test results for hydrogel strips with different NAV monomers and compound A are as follows: Figure 5 As shown.

[0071] 4) Controllable adhesion test

[0072] Following the method described in section 3) of the above-mentioned 180° peel test (interface toughness test), the hydrogel strip was adhered to porcine gastric tissue to form a "sandwich" structure (the hydrochloric acid solution used for the second 48 h soaking of the hydrogel was only a pH=2 hydrochloric acid solution). Subsequently, this "sandwich" structure was divided into two groups: one group received no treatment, and the other group was treated with sodium bicarbonate solution. The treatment method was as follows: 2 mL of 0.01 mol / L sodium bicarbonate (NaHCO3) aqueous solution (pH 8.75) was dropped around the hydrogel-tissue interface area, and the mixture was allowed to stand for 10 min. Afterwards, following the method described in section 3) of the above-mentioned 180° peel test (interface toughness test), a universal testing machine was used to perform a 180° peel test on the "sandwich" structure samples before and after the sodium bicarbonate solution treatment. The results are as follows... Figure 6 As shown, the adhesion of hydrogels can be controlled by treating them with sodium bicarbonate solution.

[0073] 5) In vitro cell compatibility test

[0074] The gastric parietal cell line GES-1 was co-cultured with the hydrogel sample prepared in Example 1 according to standard cell culture methods. The cytotoxicity of the hydrogel was assessed by microscopic observation and quantitative cell viability assays. The biocompatibility results of the hydrogel and GES-1 gastric parietal cells in vitro culture observed under a microscope are as follows: Figure 7 As shown in the figure, green represents live cells and red represents dead cells. After quantitative assessment of cell viability, the statistical results of cell death rates in the hydrogel and GES-1 gastric parietal cells cultured in vitro are as follows: Figure 8 As shown, the control group did not have the hydrogel prepared in Example 1 added during the culture process.

[0075] 6) Drug loading and in vitro release test

[0076] Drug loading: The hydrogel prepared in Example 1 was immersed in a tetracycline hydrochloride aqueous solution (concentration: 5 mg / mL) at pH=2 for 168 h to complete drug loading and obtain a drug-loaded hydrogel patch.

[0077] In vitro release: The drug-loaded hydrogel was transferred to a release container (volume: 50 mL) containing fresh HCl aqueous solution at pH=2. At different predetermined time points, 5 mL of release medium (i.e., the liquid portion in the release container) was extracted, and an equal volume of fresh release medium at the same pH was immediately replenished. The concentration of tetracycline hydrochloride in the release medium extracted at different time points was measured using a UV-Vis spectrophotometer at the characteristic absorption wavelength of tetracycline hydrochloride, and the cumulative drug release was calculated. Finally, the cumulative drug release curve was plotted with the extraction time point as the x-axis and the tetracycline hydrochloride release amount as the y-axis, as shown below. Figure 9 As shown.

[0078] 7) In vitro gastric perforation repair simulation test

[0079] Fresh, isolated porcine stomach tissue was collected, cleaned, and a perforation of approximately 5 mm in diameter was created at the bottom of the stomach using surgical scissors. The drug-loaded hydrogel patch obtained in the drug loading and in vitro release test (section 6) above was used as the gastric perforation repair patch. Simultaneously, a piece of polyacrylic acid hydrogel (without NAV and compound A) of the same size prepared in Comparative Example 3 (without NAV and compound A) was used as a control, and both were adhered to the two identical perforation sites. Approximately 800 mL of pH 2 HCl aqueous solution was injected into the porcine stomach model to simulate the gastric acid environment. Liquid leakage of the hydrogel patch at the perforation site was observed and recorded at 2 h, 4 h, and 8 h. The final liquid leakage test results for the two hydrogels are as follows: Figure 10 As shown.

[0080] Based on the above performance test results, the hydrogel patch prepared in the embodiments of the present invention has the following significant advantages:

[0081] 1. Low swelling rate in acidic environments: This invention effectively suppresses the swelling of hydrogels in acidic environments by introducing the hydrophobic monomer NAV into the hydrogel. Within the pH range of 1-3, the swelling rate of the hydrogel prepared by this invention is less than 10%. In contrast, the polyacrylic acid hydrogel prepared in Comparative Example 3, which does not contain NAV and compound A, exhibits a swelling rate as high as 360% at pH 3.

[0082] 2. Strong and stable adhesion in acidic environments: In this invention, the synergistic effect of NAV and compound A significantly enhances the adhesion strength of the hydrogel system and reduces its responsiveness to pH fluctuations in gastric juice. Within an acidic range of pH 1-3, its interfacial toughness remains stably maintained at approximately 265 J / m. 2 Furthermore, the attenuation rate is less than 5%. This stable and robust adhesive property allows the hydrogel to adhere firmly to the gastric perforation site, providing a basis for drug delivery. This property is expected to shorten the surgical time for gastric perforation repair and promote wound healing.

[0083] 3. Excellent cell compatibility: The hydrogel of this invention exhibits excellent cell compatibility, with a cell death rate of less than 2% according to co-culture experiments with gastric parietal cells GES-1. This indicates that the hydrogel poses a low potential risk to human gastric parietal cells.

[0084] 4. Long-lasting local drug delivery: The drug-loaded hydrogel patch of this invention can achieve continuous drug release for more than 168 hours (one week). Combined with its excellent adhesion properties, the drug-loaded hydrogel can firmly adhere to the site of gastric perforation lesions, achieving local drug delivery. This characteristic helps improve the utilization rate of drugs at the lesion site, reduce drug abuse, thereby helping to prevent the development of drug resistance in bacteria and promote wound healing.

[0085] It should be noted that, since the hydrogel of the present invention is used for the repair of gastric perforations, it needs to be designed in patch form considering its application environment. The specific patch shape and size can be adjusted by designing the inner cavity of the curing mold or by subsequent cutting. The inner cavity of the curing mold is preferably designed as a thin layer, so that the precursor solution inside can directly form a thin hydrogel patch after UV curing.

[0086] Example 2

[0087] In this embodiment, a hydrogel patch for repairing gastric perforation was prepared. The specific preparation steps are as follows:

[0088] Step 1: Acryloylvaline (NAV), acrylic acid, methylenebisacrylamide, compound A, and α-ketoglutaric acid were dissolved in anhydrous ethanol and stirred at room temperature for 15 min to ensure complete dissolution of all components, yielding a precursor solution. In this precursor solution, the molar concentrations of acryloylvaline, acrylic acid, methylenebisacrylamide, compound A, and α-ketoglutaric acid were 0.7:1.3:0.005:0.01:0.1, respectively.

[0089] Step 2: Place the homogeneous precursor solution obtained in Step 1 into an ultrasonic defoamer and sonicate for 10 minutes to remove bubbles.

[0090] Step 3: Pour the defoamed precursor solution obtained in Step 2 into the curing mold and wait for curing.

[0091] Step 4: Place the cured mold from Step 3 in an ultraviolet curing chamber and irradiate the precursor solution with ultraviolet light at a wavelength of 365 nm and a power of 45 W for 8 hours.

[0092] Step 5: After the solid obtained from the mold in Step 4 is cured by ultraviolet light, it is demolded and immersed in a hydrochloric acid solution with a pH of 2 for 72 hours to displace the anhydrous ethanol in the solid. Then it is removed from the hydrochloric acid solution and used as the hydrogel for subsequent repair of gastric perforation. Similarly, in this embodiment, the photoinitiator is replaced, and a hydrogel with similar properties to that in Example 1 can still be obtained.

[0093] Example 3

[0094] In this embodiment, a hydrogel patch for repairing gastric perforation was prepared. The specific preparation steps are as follows:

[0095] Step 1: Acryloylvaline (NAV), acrylic acid, methylenebisacrylamide, compound A, and photoinitiator 2959 were dissolved in anhydrous ethanol and stirred at room temperature for 15 min to ensure complete dissolution of all components, yielding a precursor solution. In this precursor solution, the molar concentrations of acryloylvaline, acrylic acid, methylenebisacrylamide, compound A, and photoinitiator 2959 were 0.6:1.4:0.003:0.012:0.1, respectively.

[0096] Step 2: Place the homogeneous precursor solution obtained in Step 1 into an ultrasonic defoamer and sonicate for 10 minutes to remove bubbles.

[0097] Step 3: Pour the defoamed precursor solution obtained in Step 2 into the curing mold and wait for curing.

[0098] Step 4: Place the cured mold from Step 3 in an ultraviolet curing chamber and irradiate the precursor solution with ultraviolet light at a wavelength of 365 nm and a power of 45 W for 8 hours.

[0099] Step 5: After the solid obtained from the mold in Step 4 is cured by ultraviolet light, it is demolded and immersed in a hydrochloric acid solution with a pH of 2 for 72 hours to displace the anhydrous ethanol in the solid. Then it is removed from the hydrochloric acid solution and used as the hydrogel for subsequent repair of gastric perforation. Similarly, this embodiment changes the proportion of raw materials, but still obtains a hydrogel with similar properties to that in Example 1.

[0100] Example 4

[0101] In this embodiment, a hydrogel patch for repairing gastric perforation was prepared. The specific preparation steps are as follows:

[0102] Step 1: Acryloylvaline (NAV), acrylic acid, methylenebisacrylamide, compound A, and photoinitiator 2959 were dissolved in anhydrous ethanol and stirred at room temperature for 15 min to ensure complete dissolution of all components, yielding a precursor solution. In this precursor solution, the molar concentrations of acryloylvaline, acrylic acid, methylenebisacrylamide, compound A, and photoinitiator 2959 were 0.8:1.2:0.007:0.008:0.1, respectively.

[0103] Step 2: Place the homogeneous precursor solution obtained in Step 1 into an ultrasonic defoamer and sonicate for 10 minutes to remove bubbles.

[0104] Step 3: Pour the defoamed precursor solution obtained in Step 2 into the curing mold and wait for curing.

[0105] Step 4: Place the cured mold from Step 3 in an ultraviolet curing chamber and irradiate the precursor solution with ultraviolet light at a wavelength of 365 nm and a power of 45 W for 8 hours.

[0106] Step 5: After the solid obtained from the mold in Step 4 is cured by ultraviolet light, it is demolded and immersed in a hydrochloric acid solution with a pH of 2 for 72 hours to displace the anhydrous ethanol in the solid. Then it is removed from the hydrochloric acid solution and used as the hydrogel for subsequent repair of gastric perforation. Similarly, this embodiment changes the proportion of raw materials, but still obtains a hydrogel with similar properties to that in Example 1.

[0107] The embodiments described above are merely some preferred implementations of the present invention and are not intended to limit the invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, all technical solutions obtained through equivalent substitution or transformation fall within the protection scope of the present invention.

Claims

1. A method for preparing a hydrogel patch for gastric perforation repair, characterized by, include: S1: Acrylylvaline, acrylic acid, methylenebisacrylamide, compound A, and photoinitiator are dissolved in an alcohol solvent, and after defoaming, a precursor solution is obtained; in the precursor solution, the molar ratio of acrylylvaline, acrylic acid, methylenebisacrylamide, compound A, and photoinitiator is (0.6~0.8): (1.2~1.4): (0.003~0.007): (0.008~0.012):0.1; The structural formula of the acryloylvaline is: ; The structural formula of compound A is: ； S2: The precursor solution is placed in a mold and cured by UV light. The resulting hydrogel is then immersed in hydrochloric acid solution to displace the alcohol solvent, resulting in a hydrogel patch for repairing gastric perforation.

2. The preparation method according to claim 1, characterized in that, The photoinitiator used is photoinitiator 2959 or α-ketoglutarate.

3. The preparation method according to claim 1, characterized in that, The alcohol solvent used is anhydrous ethanol.

4. The preparation method according to claim 1, characterized in that, The preparation method of acryloylvaline is as follows: a sodium hydroxide solution of valine is added dropwise to acryloyl chloride. After the reaction is complete under stirring, hydrochloric acid is added to the preliminary reaction product for acidification and the reaction is continued under stirring. The reaction product is extracted with ethyl acetate and then evaporated to dryness to obtain a solid product of acryloylvaline.

5. The preparation method according to claim 1, characterized in that, The preparation method of compound A is as follows: triethanolamine and 4-hydroxymethylphenylboronic acid are added to dimethylformamide solvent for condensation reaction, and the intermediate compound 2-(2-(4-(hydroxymethyl)phenyl)-1,3,6,2-dioxaborane-6-yl)ethyl-1-ol is separated; then the intermediate compound, isocyanate ethyl acrylate and dibutyltin dilaurate are added to dimethylformamide solvent for addition reaction, and the reaction product is separated, purified and freeze-dried to obtain solid compound A.

6. The preparation method according to claim 1, characterized in that, The defoaming process employs ultrasonic defoaming.

7. The preparation method according to claim 1, characterized in that, The method of UV-induced curing is as follows: the precursor solution in the mold is placed under UV light irradiation for 8 to 10 hours, wherein the UV light wavelength is 365 nm and the UV light irradiation power is 40 to 50 W.

8. The preparation method according to claim 1, characterized in that, The hydrochloric acid solution has a pH of 1 to 3, and the hydrogel is soaked in the hydrochloric acid solution for 2 to 4 days.

9. A hydrogel patch for repairing gastric perforation prepared by the preparation method according to any one of claims 1 to 8.

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