Spraying type anti-adhesion Janus heterogeneous hydrogel film used after cholecystectomy and preparation method of spraying type anti-adhesion Janus heterogeneous hydrogel film
By utilizing the electrostatic self-assembly of spray-applied Janus heterogeneous hydrogel membranes, combined with both cationic and anionic functional sides, the problem of adhesions caused by bile leakage and allergic reactions after cholecystectomy is solved. This achieves instant molding, precise coverage, and efficient bile adsorption, reducing the risk of postoperative adhesions and allergies.
Patent Information
- Application Number
- CN202511621573.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-31
- Publication Date
- 2026-01-02
AI Technical Summary
Existing materials used after cholecystectomy are not effective in preventing adhesions when faced with bile leakage and allergic reactions. They are also difficult to mold and cover precisely. Conventional materials are prone to displacement or degrade too quickly, and cannot effectively prevent adhesions and allergic reactions.
Janus heterogeneous hydrogel membranes are sprayed and formed through electrostatic self-assembly, possessing both cationic and anionic functional sides. The cationic side contains sulfonated betaine-grafted quaternized chitosan and thermosensitive liposomes, while the anionic side contains carboxybetaine methacrylate and microspheres. Diphenhydramine and cholestyramine are loaded onto the membranes to achieve wet adhesion and lubrication, actively capturing bile sensitizers and controlling the release of antihistamines.
It achieves instant molding and precise fit, efficiently absorbs bile, significantly reduces the risk of adhesion and allergies, and improves the treatment effect after cholecystectomy.
Smart Images
Figure CN121243500A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical technology, specifically to a spray-on anti-adhesion Janus heterogeneous hydrogel membrane for use after cholecystectomy and its preparation method. Background Technology
[0002] Cholecystectomy is an important treatment for biliary system diseases, especially with the widespread use of laparoscopic techniques, which offer significant advantages such as minimal surgical trauma and rapid recovery. However, postoperative tissue adhesions and allergic reactions are common complications. Intraoperative tissue damage, bile leakage, and inflammatory reactions are the main causes of adhesion formation, while bile itself is also an important allergen: components such as bile salts and bilirubin in bile can act as antigens, inducing or exacerbating local and systemic allergic reactions, manifesting as skin erythema, itching, and even systemic inflammatory reactions, thereby further activating immune cells and promoting tissue fibrosis and abnormal healing. Adhesions are commonly found on the visceral surface of the liver lobe, duodenal ligament, and surrounding intestinal segments, which can lead to chronic right upper quadrant abdominal pain, digestive disorders, and even biliary or intestinal obstruction, seriously affecting the patient's postoperative quality of life and posing significant difficulties and risks to potential secondary surgeries.
[0003] Currently, clinical strategies for preventing adhesion after cholecystectomy mainly rely on absorbable barrier membranes (such as cellulose-based and hyaluronic acid-based materials) and liquid anti-adhesion agents, which reduce tissue contact by creating a physical barrier at the wound site. However, in the actual environment of biliary surgery, existing materials still have significant shortcomings. On the one hand, bile leakage is common, and its strong chemical irritant nature easily triggers sensitization reactions. Conventional materials lack the ability to adsorb and neutralize bile, failing to effectively alleviate bile-induced allergic and inflammatory reactions, and are prone to functional failure due to bile flushing or penetration. Even the Janus anti-adhesion bilayer membrane, which has emerged in recent years and possesses wet adhesion capabilities, while improving tissue adhesion, still primarily relies on a hydrated physical barrier formed by zwitterionic materials. It neither integrates bile adsorption components nor actively intervenes in the leakage of bile and the resulting histamine release process. On the other hand, due to the moist surgical wound and complex anatomical structure (such as the irregular shape of the liver bed), most membrane materials have poor adhesion and are prone to displacement. Liquid materials, on the other hand, suffer from uneven distribution and rapid degradation, making it difficult to achieve continuous and effective wound coverage. Existing products mostly rely on preparation methods such as ultraviolet light polymerization, which makes it difficult to achieve instant molding and precise coverage during surgery, further limiting their clinical application. In addition, conventional materials are often unable to cope with surgical trauma and allergic reactions caused by bile and drugs. Some materials also have poor mechanical properties (such as being too brittle or too soft), degradation cycles that do not match the tissue healing process, or may trigger foreign body reactions, potentially increasing the risk of adhesion and allergies. Summary of the Invention
[0004] The purpose of this invention is to address the aforementioned technical problems by providing a sprayable anti-adhesion Janus heterogeneous hydrogel membrane for use after cholecystectomy and its preparation method.
[0005] This invention provides a sprayable anti-adhesion Janus heterogeneous hydrogel membrane for use after cholecystectomy, characterized in that the Janus heterogeneous hydrogel membrane comprises a cationic functional side and an anionic functional side:
[0006] The cationic functional side comprises an amphoteric polymer formed by grafting sulfonate betaine onto quaternized chitosan, and a thermosensitive liposome loaded with diphenhydramine and clotting peptide.
[0007] The anionic functional side comprises an anionic polymer formed by copolymerizing carboxybetaine methacrylate and acrylic acid, and microspheres loaded with cholestyramine.
[0008] This invention provides a sprayable anti-adhesion Janus heterogeneous hydrogel membrane for use after cholecystectomy, characterized in that the Janus heterogeneous hydrogel membrane is formed by electrostatic self-assembly after simultaneous spraying of solutions A and B using a dual-cylinder spraying device, wherein:
[0009] The solution in tube A contains a cationic functional component, which can impart wet tissue adhesion to one side of the Janus heterogeneous hydrogel membrane and load a tissue response modifier.
[0010] The solution in tube B contains anionic functional components, which can impart lubricity to the other side of the Janus heterogeneous hydrogel membrane and load bile adsorbents.
[0011] The tissue response modifier includes diphenhydramine and clotting peptide, and the bile adsorbent includes cholestyramine. Both work together to block the formation of postoperative adhesions and allergic reactions from the pathological source.
[0012] This invention also provides a sprayable anti-adhesion Janus heterogeneous hydrogel membrane for use after cholecystectomy and its preparation method, specifically including the following steps:
[0013] (4) Preparation of Solution A (Cat Functional Side): First, sulfonated betaine (SBMA) monomer was grafted onto the quaternized chitosan (QCS) backbone and reacted for 6 h to obtain the zwitterionic polymer QCS-SB. Subsequently, drug-loaded thermosensitive liposomes (TSL) were prepared using a thin-film hydration-extrusion method: 16 mM bisphosphatidylcholine (DPPC), 4 mM bispalmitoylphosphatidylcholine (DSPC), 3 mM cholesterol, diphenhydramine, and thrombin were dissolved in chloroform to prepare an organic phase, which was then hydrated and extruded after film formation. Finally, purified QCS-SB was dissolved in PBS to prepare a 4% (w / v) solution, and TSL was incorporated to a final lipid concentration of 10 mg / mL to obtain Solution A.
[0014] (5) Preparation of Solution B (Anionic Functional Side): First, anionic polymer PCB-AA was synthesized by free radical polymerization: carboxybenzene methacrylate (CBMA) and acrylic acid (AA) were used as monomers, and 1% AIBN was used as an initiator. The reaction was carried out at 70℃ under nitrogen protection for 12 h. Subsequently, functionalized microspheres were prepared by emulsification crosslinking: cholestyramine powder was dispersed in 10 mL of 2% sodium alginate solution as the aqueous phase, and added dropwise through a 22G needle at a rate of 5 mL / h to the oil phase containing 100 mL of 2% CaCl2 solution. The mixture was stirred at 500 rpm for 30 min to solidify, generating calcium alginate microspheres, which were then collected by sieving. Finally, PCB-AA was dissolved in deionized water to prepare a 5% (w / v) solution, and microspheres were added to a final concentration of 50 mg / mL. After mixing, solution B was obtained.
[0015] (6) Formation of Janus heterogeneous hydrogel membrane: The solutions in tube A and tube B are simultaneously sprayed onto the tissue wound using a dual-tube spray gun, and a Janus heterogeneous hydrogel membrane with a cationic adhesion side and an anionic lubrication side is formed instantaneously through electrostatic interaction.
[0016] Furthermore, the molar ratio of SBMA to QCS in step (1) is 3:1.
[0017] Furthermore, the concentration of diphenhydramine in step (1) is 5 mM.
[0018] Furthermore, the concentration of the clotting peptide in step (1) is 0.5 mM.
[0019] Furthermore, the molar ratio of CBMA to AA in step (2) is 85:15.
[0020] Furthermore, the mass of the cholestyramine powder in step (2) is 200 mg.
[0021] Furthermore, the particle size of the calcium alginate microspheres screened in step (2) is 50-100 μm.
[0022] The present invention also provides the use of a sprayable anti-adhesion Janus heterogeneous hydrogel membrane for use after cholecystectomy in the preparation of products for preventing or reducing adhesions after cholecystectomy.
[0023] Furthermore, the product can conform to the shape of irregular wounds.
[0024] The advantages of this invention are:
[0025] 1. This invention constructs a Janus heterogeneous hydrogel membrane through electrostatic self-assembly of zwitterions, achieving synergy between strong wet adhesion on the QCS-SB side and super-lubricity on the PCB-AA side, accurately covering irregular wound surfaces and blocking fibroblast infiltration, realizing instant molding and precise adhesion, and solving the problem of poor adhesion of pre-formed membranes.
[0026] 2. This invention relies on bile acid adsorbents to actively capture bile sensitizers and thermosensitive liposomes to control the release of antihistamines, and for the first time introduces a synergistic chemical intervention mechanism of bile adsorption and allergy blocking, which reduces the risk of adhesion and allergy from the root.
[0027] 3. This invention is specifically designed for laparoscopic cholecystectomy, and significantly reduces the rate of hepato-intestinal adhesions through efficient bile adsorption and antihistamine release. Attached Figure Description
[0028] Figure 1 This is a morphological characterization diagram of the spray-applied anti-adhesion Janus heterogeneous hydrogel film prepared according to the present invention.
[0029] Figure 2 This is a characterization of the wet adhesion strength of the Janus heterogeneous hydrogel membrane of the present invention.
[0030] Figure 3 This is a characterization of the surface lubrication properties of the Janus heterogeneous hydrogel film of the present invention.
[0031] Figure 4 This is a characterization of the bile acid adsorption performance of the Janus heterogeneous hydrogel membrane of the present invention.
[0032] Figure 5 This invention relates to a study on the drug release behavior of the Janus heterogeneous hydrogel membrane.
[0033] Figure 6 This invention relates to a study on the in vivo anti-adhesion properties of the Janus heterogeneous hydrogel membrane. Detailed Implementation
[0034] The technical solutions described in this invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of this invention. Obviously, the embodiments described in this specification are only some feasible technical solutions of this invention. Other implementation methods obtained by those skilled in the art based on the embodiments of this invention without any creative effort should be considered to fall within the scope of protection of this invention.
[0035] Example 1: Preparation of Spray-applied Anti-adhesion Janus Heterogeneous Hydrogel Membrane
[0036] (1) Preparation of Solution A (Cat Functional Side): First, the cationic polymer QCS-SB was synthesized: SBMA was grafted onto the QCS backbone at a molar ratio of 3:1 via quaternization and graft copolymerization, and reacted for 6 hours to obtain the zwitterionic polymer QCS-SB. Subsequently, TSL was prepared using a thin-film hydration-extrusion method: 16 mM DPPC, 4 mM DSPC, 3 mM cholesterol, 5 mM diphenhydramine, and 0.5 mM thrombin were dissolved in chloroform to prepare an organic phase with a total lipid concentration of 20 mM. After film formation, the phase was hydrated and extruded. Finally, purified QCS-SB was dissolved in PBS to prepare a 4% (w / v) solution, and TSL was incorporated to a final lipid concentration of 10 mg / mL to obtain Solution A.
[0037] (2) Preparation of Solution B (Anionic Functional Side): First, anionic polymer PCB-AA was synthesized by free radical polymerization: CBMA and AA were used as monomers in a molar ratio of 85:15, and 1% AIBN was used as an initiator. The reaction was carried out at 70℃ under nitrogen protection for 12 h. Subsequently, functionalized microspheres were prepared by emulsification crosslinking: 200 mg of cholestyramine powder was dispersed in 10 mL of 2% sodium alginate solution as the aqueous phase. This aqueous phase was added dropwise to an oil phase containing 100 mL of 2% CaCl2 solution at a rate of 5 mL / h using a 22G needle. The mixture was stirred at 500 rpm for 30 min to solidify, generating calcium alginate microspheres. The 50-100 μm particle size fraction was collected by sieving. Finally, PCB-AA was dissolved in deionized water to prepare a 5% (w / v) solution, and microspheres were added to a final concentration of 50 mg / mL. After mixing, Solution B was obtained.
[0038] (3) Formation of Janus heterogeneous hydrogel membrane: The solutions in tube A and tube B are simultaneously sprayed onto the tissue wound through a dual-tube spray gun, and a Janus heterogeneous hydrogel membrane with a cationic adhesion side and an anionic lubrication side is formed instantaneously through electrostatic interaction.
[0039] Comparative Example 1: Preparation of electrospun Janus fiber membrane
[0040] The difference between this comparative example and Example 1 is that a Janus fiber membrane with macroscopic layering was formed by physical stacking, and it did not contain the drugs diphenhydramine, clotting peptide, and cholestyramine.
[0041] First, QCS was dissolved in an 80% aqueous acetic acid solution to prepare a spinning solution with a mass-to-volume fraction of 8%, which served as the raw material for the A-side adhesive layer. Simultaneously, polysulfobetaine was dissolved in trifluoroethanol to prepare a spinning solution with a mass-to-volume fraction of 12%, which served as the raw material for the B-side lubricating layer. Under conditions of 15 kV voltage, a feed rate of 0.8 mL / h, and a receiving distance of 15 cm, the two raw materials were deposited sequentially through a nozzle for 2 hours each, forming a bilayer fiber membrane on the receiving plate. Notably, this membrane material was not loaded with any drugs (diphenhydramine, thrombin, or cholestyramine). Subsequently, the resulting membrane material was dried at room temperature for 12 hours to completely remove the solvent and then crosslinked using epichlorohydrin vapor for 6 hours. The final product was an electrospun fiber membrane with a certain Janus structure but without any active functional components.
[0042] Comparative Example 2: Preparation of Spray-coated Cationic-Free Functional Side Hydrogel Membrane
[0043] The difference between this comparative example and Example 1 is that the solution in cylinder A without the cation functional side is directly sprayed onto the solution in cylinder B.
[0044] Comparative Example 3: Preparation of Spray-coated Non-anionic Functional Side Hydrogel Membrane
[0045] The difference between this comparative example and Example 1 is that the solution in cylinder B without the cation functional side is directly sprayed onto the solution in cylinder A.
[0046] Comparative Example 4: Preparation of Spray-coated Janus zwitterionic drug-free hydrogel membrane
[0047] The difference between this comparative example and Example 1 is that it does not contain the drugs diphenhydramine, clotting peptide, and cholestyramine.
[0048] Experimental Example 1: Morphological characterization of the spray-applied anti-adhesion Janus heterogeneous hydrogel film prepared in Example 1
[0049] The lyophilized hydrogel membrane prepared in Example 1 was plated with gold, and its microstructure was characterized using scanning electron microscopy (SEM). The results are as follows: Figure 1 As shown in (a), the porosity of the cationic functional side is small, exhibiting a dense structure. This is due to the electrostatic interactions and hydrogen bonds between the cationic polymer chains, as well as the filling effect of the liposomes; Figure 1As shown in (b), the anion-functional side has a larger porosity and exhibits porosity. This is attributed to the high hydration of the zwitterionic polymer PCB-AA, which leaves numerous pores due to water sublimation during freeze-drying. In summary, the hydrogel membrane prepared in Example 1 exhibits different structures on both sides, providing a basis for its different properties.
[0050] Experimental Example 2: Characterization of the wet adhesion strength of the spray-applied anti-adhesion Janus heterogeneous hydrogel film prepared in Example 1.
[0051] To evaluate the wet adhesion strength of the materials prepared in Example 1 and Comparative Examples 1-4, an overlap-shear test was conducted using a universal testing machine in accordance with ASTM F2258. Each group of samples was bonded between fresh, detached pigskin samples moistened with PBS. After applying pre-compression, shear peeling was performed at a fixed rate, and the maximum stress value was recorded and the adhesion strength was calculated.
[0052] The results are as follows Figure 2 As shown, Example 1 exhibited the highest adhesion strength, reaching 27.4 kPa; Comparative Examples 1 and 4 showed adhesion strengths of 15.2 kPa and 6.2 kPa, respectively. It is noteworthy that Comparative Examples 2 and 3 were not included in the quantitative comparison because their single-component solutions could not form a continuous and stable hydrogel film through electrostatic self-assembly, resulting in measurable effective samples. However, Comparative Example 3 showed a noticeably sticky QCS-SB side, indicating a certain adhesion tendency. Example 1 demonstrated the highest adhesion strength, primarily attributed to the strong electrostatic interaction between its quaternary ammonium groups on the QCS-SB side and the tissue surface, as well as the resulting dense hydrogen bond network. In contrast, although Comparative Example 1 possessed a bilayer structure, its adhesion performance was limited due to the lack of an effective wet binding mechanism. Comparative Example 4 used empty liposomes instead of drug-loaded liposomes, which contained no clotting peptides and could not effectively dissipate the interfacial hydration layer on moist wound surfaces, severely hindering direct contact between the polymer and the tissue surface, thus leading to a significant decrease in adhesion performance. In summary, the hydrogel film prepared in Example 1 exhibited good wet adhesion strength.
[0053] Experimental Example 3: Characterization of the surface lubrication properties of the spray-applied anti-adhesion Janus heterogeneous hydrogel film prepared in Example 1.
[0054] To evaluate the surface lubrication properties of the materials prepared in Example 1 and Comparative Examples 1-4, a friction and wear testing machine was used to test the surface lubrication of each group of samples. Fresh peritoneal tissue was fixed as the grinding surface, and friction tests were conducted under lubrication conditions simulating physiological environment, with constant load and rate. Friction force data during the steady-state phase were collected, and the dynamic friction coefficient was calculated.
[0055] The results are as follows Figure 3As shown, the Janus hydrogel film in Example 1 exhibits excellent superlubricating properties, with a friction coefficient as low as 0.026. This is mainly attributed to the formation of a stable low-shear molecular layer by the highly hydrated zwitterionic brush on the PCB-AA side in a wet environment. In contrast, Comparative Example 1, due to its rough fiber surface, could not form a continuous hydrated layer, resulting in a friction coefficient of 0.085; while Comparative Example 4 showed a similar low friction coefficient to Example 1, reaching 0.047, further indicating that the superlubricating properties of the material are entirely derived from the PCB-AA component itself, and this performance is not significantly affected by the Janus structure or the absence of active ingredients. Furthermore, during the experiment, it was found that Comparative Examples 2 and 3 could not form a continuous and stable hydrogel film through electrostatic self-assembly of single-component solutions, thus failing to form measurable effective samples, and therefore no test results could be obtained. However, Comparative Example 3 exhibited a sticky surface due to the inherent adhesion of the QCS-SB side. In summary, the hydrogel film prepared in Example 1 possesses good lubricating properties.
[0056] Experimental Example 4: Characterization of bile acid adsorption performance of the spray-applied anti-adhesion Janus heterogeneous hydrogel membrane prepared in Example 1.
[0057] To evaluate the bile acid adsorption performance of the materials prepared in Example 1, Comparative Example 1, and Comparative Example 4, the adsorption capacity of each group of materials for bile acids was quantitatively evaluated using an enzyme-linked immunosorbent assay (ELISA) kit. Each group of materials was placed in phosphate-buffered saline (PBS) containing 100 μM of initial bile acid, incubated at 37°C with shaking for 2 hours, and then samples were collected. After centrifugation, the supernatant was collected, and the residual bile acid concentration was determined according to the kit instructions. The adsorption rate was then calculated.
[0058] The results are as follows Figure 4 As shown, the adsorption rates of bile acids in Example 1, Comparative Example 1, and Comparative Example 4 were 93%, 2.6%, and 3.3%, respectively, indicating that the hydrogel membrane prepared in Example 1 has excellent bile acid adsorption performance. Comparative Example 4, lacking a bile acid adsorbent, showed almost no adsorption capacity; Comparative Example 1 also showed no significant adsorption effect. These results indicate that the efficient adsorption function of the material for bile acids depends entirely on the active microspheres loaded with cholestyramine on the B side, highlighting the crucial role of functionalized microspheres in the active capture of sensitizers. In summary, the hydrogel membrane prepared in Example 1 exhibits good bile acid adsorption performance.
[0059] Experimental Example 5: Drug release behavior study of the spray-applied anti-adhesion Janus heterogeneous hydrogel membrane prepared in Example 1
[0060] To evaluate the drug release behavior of the hydrogel membrane prepared in Example 1, the release behavior of diphenhydramine was determined by high-performance liquid chromatography (HPLC). The material was placed in a dialysis bag and immersed in PBS release medium at 37°C (simulated body temperature) and 25°C, respectively. 3 mL samples of the test solution were taken at time points of 0.5, 1, 2, 4, 8, and 12 h, and an equal volume of fresh medium was added simultaneously. The concentration of diphenhydramine in the release medium was detected by HPLC, the cumulative release rate was calculated, and a release curve was plotted.
[0061] The results are as follows Figure 5 As shown, at 37°C, the cumulative release rate of diphenhydramine in Example 1 exceeded 50% within 30 minutes, exhibiting a significant burst release effect. Subsequently, the release behavior gradually slowed down, indicating that the system possesses good temperature-sensitive triggered drug release characteristics. However, at 25°C, the cumulative release rate was only 2.3% within 1 hour, further confirming that its drug release behavior is significantly temperature-dependent. These results indicate that the high-speed drug release characteristics triggered by body temperature are entirely dependent on the temperature-sensitive liposomes loaded on side A. Therefore, Example 1 successfully achieved good body temperature-triggered drug release performance.
[0062] Experimental Example 6: In vivo anti-adhesion performance study of the spray-applied anti-adhesion Janus heterogeneous hydrogel membrane prepared in Example 1.
[0063] A rat cecal abrasion model was used to evaluate the anti-adhesion efficacy of the material. Thirty male SD rats were randomly divided into 5 groups (n=6): Example 1 group; Comparative Example 1 group; Comparative Example 4 group; Sham-operated group; Model group. Surgery was performed under 1-1.5% isoflurane anesthesia, and the cecal serosa was abraded until petechiae appeared (approximately 1 cm). 2 After the wound was treated and the patients were grouped and given appropriate interventions, the abdomen was closed. Postoperatively, tissue samples were taken 7 days later, and the adhesions were assessed using a double-blind scoring method (0-4 points): 0 points indicated no adhesions; 1 point indicated 0-25% thin adhesions without blood vessels; 2 points indicated 25-50% similar tissue adhesions; 3 points indicated 50-75% thick, opaque adhesions with blood vessels; 4 points indicated 75-100% thick, dense vascular adhesions requiring sharp dissection.
[0064] The results are as follows Figure 6As shown, the adhesion score of Example 1 group was significantly lower than that of the other groups (score 1), demonstrating excellent anti-adhesion efficacy. The sham surgery group scored 1 point, and Comparative Example 4 scored 3 points, which, although significantly lower than the model group (4 points), were still higher than that of Example 1 group. This indicates that the zwitterionic Janus structure itself provides a basic physical barrier function, while the loaded active ingredients (antihistamines, clotting peptides, and bile acid adsorbents) contribute additional efficacy enhancement, thereby significantly strengthening the anti-adhesion effect. Comparative Example 1 had a higher score (4 points) due to problems such as easy displacement, degradation, and mismatch between tissue repair, indicating poor anti-adhesion performance. Meanwhile, only slight thin-film adhesions were observed on the cecal wound in Example 1 group, further demonstrating that the hydrogel membrane prepared in Example 1 has excellent anti-adhesion ability.
[0065] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and additions without departing from the principle of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.
Claims
1. A sprayable anti-adhesion Janus heterogel film for use after cholecystectomy, characterized in that, The Janus heterogeneous hydrogel film comprises a cationic functional side and an anionic functional side: The cationic functional side comprises a zwitterionic polymer formed by grafting sulfobetaine onto quaternized chitosan, and temperature-sensitive liposomes loaded with diphenhydramine and thrombin peptide; The anionic functional side comprises an anionic polymer formed by copolymerization of carboxybetaine methacrylate and acrylic acid, and microspheres loaded with cholestyramine.
2. The Janus heterogel film of claim 1, wherein, The Janus heterogeneous hydrogel film is formed by synchronously spraying the barrel A solution and the barrel B solution through a double-barrel spraying device and then through electrostatic self-assembly, wherein: The barrel A solution comprises a cationic functional component capable of imparting one side of the Janus heterogeneous hydrogel film with wet tissue adhesion and loaded with a tissue reaction modulator; The barrel B solution comprises an anionic functional component capable of imparting the other side of the Janus heterogeneous hydrogel film with lubricity and loaded with a bile adsorbent; The tissue reaction modulator includes diphenhydramine and thrombin peptide, and the bile adsorbent includes cholestyramine, both of which jointly block the formation of postoperative adhesions and allergic reactions from the pathological source.
3. A method for the preparation of a sprayable anti-adhesion Janus heterogel film for post cholecystectomy, characterized by, The preparation method comprises the following steps: (1) Preparation of barrel A solution: the barrel A solution comprises a cationic polymer formed by grafting sulfobetaine onto quaternized chitosan, and temperature-sensitive liposomes loaded with diphenhydramine and thrombin peptide; (2) Preparation of barrel B solution: the barrel B solution comprises an anionic polymer formed by copolymerization of carboxybetaine methacrylate and acrylic acid, and microspheres loaded with cholestyramine; (3) Formation of Janus heterogeneous hydrogel film: the barrel A solution and the barrel B solution are synchronously sprayed to a tissue wound surface through a double-barrel spraying gun, and a Janus heterogeneous hydrogel film with a cationic adhesion side and an anionic lubrication side is instantaneously formed through electrostatic interaction.
4. The production method according to claim 3, wherein The molar feed ratio of sulfobetaine to quaternized chitosan in step (1) is 3:
1.
5. The production method according to claim 3, wherein In the temperature-sensitive liposomes loaded with diphenhydramine and thrombin peptide in step (1), the concentration of diphenhydramine is 5 mM, and the concentration of thrombin peptide is 0.5 mM.
6. The production method according to claim 3, wherein The molar ratio of carboxybetaine methacrylate to acrylic acid in step (2) is 85:
15.
7. The production method according to claim 3, wherein The microspheres loaded with cholestyramine in step (2) are prepared by emulsification crosslinking, wherein the mass of cholestyramine powder is 200 mg.
8. The production method according to claim 7, wherein The microspheres loaded with cholestyramine are calcium alginate microspheres, and the particle size is 50-100 μm.
9. The production method according to claim 3, wherein The anionic polymer is dissolved in deionized water to form a solution with a mass fraction of 5%, and the microspheres loaded with cholestyramine are added to a final concentration of 50 mg / mL.
10. Use of the Janus heterogel film according to claims 1-2 for the preparation of a product for preventing or reducing adhesions after cholecystectomy, characterized in that, The product can conform to the shape of irregular wounds.