Injectable temperature-sensitive hydrogel material containing zwitterions and its preparation method and application

Abstract

The application belongs to the technical field of biomedical materials, and particularly relates to an injectable temperature-sensitive hydrogel material containing zwitterions and a preparation method and application thereof. The application provides an injectable temperature-sensitive hydrogel material containing zwitterions, and preparation raw materials include: temperature-sensitive biological polymer derivatives and zwitterionic monomers; the temperature-sensitive biological polymer derivatives include temperature-sensitive chitin derivatives and / or temperature-sensitive cellulose derivatives; and the mass ratio of the temperature-sensitive biological polymer derivatives to the zwitterionic monomers is 5 / 1-1 / 20. The injectable temperature-sensitive hydrogel material containing zwitterions provided by the application forms a completely physically cross-linked double network structure, is applied to temperature-sensitive anti-adhesion materials, can effectively resist non-specific adhesion of various proteins and bacteria, is very suitable for resisting postoperative adhesion, and simultaneously has the characteristics of not being easy to flow away at a wound and being biodegradable.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to an injectable thermosensitive hydrogel material containing zwitterions, its preparation method, and its application. Background Technology

[0002] Internal soft tissue injuries are often caused by surgical trauma, resection of primary or secondary tumors, traumatic injuries to the abdominal wall or chest wall, and soft tissue infections. These injuries are difficult to suture and can lead to postoperative adhesions. In clinical practice, postoperative adhesions typically involve tendons, the dural sac, intestines, peritoneum, pericardium, and uterus. Besides routine symptoms such as pain and movement disorders, adhesions to specific organs such as the uterine cavity and fallopian tubes can lead to organ-specific symptoms, such as menopausal symptoms and reproductive dysfunction. Adhesions to the intestines and pericardium can even lead to life-threatening conditions such as intestinal obstruction and heart failure. Thorough removal of residual foreign bodies such as debris and blood clots, adequate hemostasis, and reduction of inflammation can reduce the occurrence of adhesions at their source. However, due to the long time required for wound healing and adhesion formation, effective medications and biomedical materials are still needed for anti-adhesion intervention during the postoperative healing process.

[0003] Currently, some polymer materials for anti-adhesion have been commercialized. However, existing anti-adhesion polymer materials have weak resistance to non-specific adhesion of various proteins and bacteria, resulting in poor efficacy in preventing postoperative adhesions. Summary of the Invention

[0004] The purpose of this invention is to provide an injectable thermosensitive hydrogel material containing zwitterions, its preparation method, and its application. The injectable thermosensitive hydrogel material containing zwitterions provided by this invention is an anti-adhesion material that can effectively resist the non-specific adhesion of various proteins and bacteria, making it very suitable for anti-postoperative adhesion. At the same time, it has the characteristics of not easily flowing out at the wound site and being biodegradable.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] This invention provides an injectable thermosensitive hydrogel material containing zwitterions, the raw materials for which include: thermosensitive biopolymer derivatives and zwitterionic monomers; the thermosensitive biopolymer derivatives include thermosensitive chitin derivatives and / or thermosensitive cellulose derivatives; the mass ratio of the thermosensitive biopolymer derivatives to the zwitterionic monomers is 5 / 1 to 1 / 20.

[0007] Preferably, the thermosensitive biopolymer derivative includes one or more of thermosensitive carboxymethyl chitosan, thermosensitive hydroxyethyl chitosan, thermosensitive hydroxypropyl chitosan, thermosensitive hydroxybutyl chitosan, thermosensitive hydroxypropyl cellulose, and thermosensitive hydroxypropyl methyl cellulose.

[0008] Preferably, the zwitterionic monomer is 2-methacryloyloxyethylphosphorylcholine.

[0009] This invention provides a method for preparing the injectable thermosensitive hydrogel material containing zwitterions as described above, comprising the following steps:

[0010] A temperature-sensitive biopolymer derivative, a zwitterionic monomer, and a first solvent are mixed at a low temperature of ≤10°C to obtain a mixed solution, wherein the first solvent contains water.

[0011] The mixed solution and the initiator are mixed and reacted to obtain the reaction material; the reaction material is then dialyzed and dried sequentially to obtain the injectable thermosensitive hydrogel material containing zwitterions.

[0012] Preferably, the low-temperature mixing includes the following steps:

[0013] A thermosensitive biopolymer derivative is dissolved in a first solvent at ≤10℃ to obtain a thermosensitive biopolymer derivative solution, wherein the mass percentage of the thermosensitive biopolymer derivative in the solution is 0.05-0.5%.

[0014] The thermosensitive biopolymer derivative solution was then mixed with the zwitterionic monomer at ≤10°C to obtain a mixed solution.

[0015] Preferably, the reaction temperature is 25–70°C and the holding time is 12–48 h.

[0016] This invention provides the application of the injectable thermosensitive hydrogel material containing zwitterions as described in the above technical solution or the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method described in the above technical solution in the preparation of anti-adhesion materials.

[0017] This invention provides an injectable thermosensitive anti-adhesion hydrogel, comprising the injectable thermosensitive hydrogel material containing zwitterions as described in the above technical solution or the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method described in the above technical solution, and a second solvent, wherein the second solvent is water or a buffer solution.

[0018] Preferably, the solid content of the injectable thermosensitive anti-adhesion hydrogel is 0.5% to 5%.

[0019] This invention provides an anti-adhesion sponge material, which is obtained by freeze-drying an aqueous solution of the zwitterionic injectable thermosensitive hydrogel material prepared by the above-described technical solution or the preparation method described above.

[0020] This invention provides an injectable thermosensitive hydrogel material containing zwitterions. The raw materials include: thermosensitive biopolymer derivatives and zwitterionic monomers; the thermosensitive biopolymer derivatives include thermosensitive chitin derivatives and / or thermosensitive cellulose derivatives; the mass ratio of the thermosensitive biopolymer derivatives to the zwitterionic monomers is 5 / 1 to 1 / 20. The injectable thermosensitive hydrogel material containing zwitterions provided by this invention forms a fully physically cross-linked dual-network structure, consisting of a zwitterionic monomer network cross-linked by electrostatic interactions and a thermosensitive biopolymer derivative network cross-linked by hydrophobic interactions. Compared with the prior art, this invention has the following beneficial effects:

[0021] The raw materials for preparing the injectable thermosensitive hydrogel material containing zwitterions provided by this invention include: thermosensitive biopolymer derivatives and zwitterionic monomers. The thermosensitive biopolymer derivatives (including thermosensitive chitin derivatives and / or thermosensitive cellulose derivatives) possess numerous intermolecular and intramolecular hydrogen bonds, exhibiting a highly crystalline structure and high cohesive energy. The zwitterionic monomers are superhydrophilic. The injectable thermosensitive hydrogel material obtained by this invention using the above two raw materials contains a physically cross-linked double network structure formed by electrostatic and hydrophobic interactions. Simultaneously, the introduction of zwitterionic monomer segments with anionic and cationic groups into the gel facilitates the formation of a hydration layer, thereby endowing the hydrogel with antibacterial properties. It effectively resists the non-specific adhesion of various proteins and bacteria, making it highly suitable for preventing postoperative adhesions. Furthermore, it can create a moist microenvironment at the wound site, reducing the temperature near the wound and alleviating patient pain.

[0022] The injectable thermosensitive hydrogel material containing zwitterions provided by this invention exhibits excellent injectability under low-temperature conditions and rapidly gels at body temperature, spreading throughout the postoperative wound surface with organ peristalsis. This improves wound coverage and reduces operation time and difficulty when used as an anti-adhesion material. Furthermore, based on practical needs, the injectable thermosensitive hydrogel material containing zwitterions provided by this invention can be further formulated into an anti-adhesion sponge material with tissue adhesion. This anti-adhesion sponge material can rehydrate into a gel structure, does not rapidly flow away at the wound site, is biodegradable, and is easy to use, making it suitable for postoperative anti-adhesion material application.

[0023] The raw materials for preparing the injectable thermosensitive hydrogel material containing zwitterions provided by this invention are readily available and have excellent biocompatibility. At the same time, the introduction of zwitterion monomers further improves the degree of cross-linking of the injectable thermosensitive hydrogel material, which can effectively prolong the residence time of the injectable thermosensitive hydrogel material in body fluids.

[0024] This invention provides a method for preparing the injectable thermosensitive hydrogel material containing zwitterions as described above, comprising the following steps: mixing a thermosensitive biopolymer derivative, a zwitterionic monomer, and a first solvent at a low temperature of ≤10°C to obtain a mixed solution, wherein the first solvent contains water; mixing the mixed solution with an initiator to react and obtain a reactant; and sequentially dialysis and drying the reactant to obtain the injectable thermosensitive hydrogel material containing zwitterions. The preparation method provided by this invention uses readily available raw materials, has a simple synthesis method, and is suitable for industrial production applications. Attached Figure Description

[0025] Figure 1 The sol-gel transformation diagram shows the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of this invention.

[0026] Figure 2 This is a gel time analysis diagram of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of the present invention;

[0027] Figure 3 The swelling properties of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of this invention are shown in the diagram.

[0028] Figure 4 This is a biocompatibility diagram of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of the present invention.

[0029] Figure 5 This is a graph showing the adhesion properties of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of this invention. Detailed Implementation

[0030] This invention provides an injectable thermosensitive hydrogel material containing zwitterions, the raw materials for which include: thermosensitive biopolymer derivatives and zwitterionic monomers; the thermosensitive biopolymer derivatives include thermosensitive chitin derivatives and / or thermosensitive cellulose derivatives; the mass ratio of the thermosensitive biopolymer derivatives to the zwitterionic monomers is 5 / 1 to 1 / 20.

[0031] In this invention, unless otherwise specified, all raw materials / components used in the preparation are commercially available products well known to those skilled in the art.

[0032] The raw materials for preparing the zwitterionic injectable thermosensitive hydrogel material provided by this invention include thermosensitive biopolymer derivatives. In this invention, the thermosensitive biopolymer derivatives include thermosensitive chitin derivatives and / or thermosensitive cellulose derivatives, preferably one or more of thermosensitive carboxymethyl chitin, thermosensitive hydroxyethyl chitin, thermosensitive hydroxypropyl chitin (HPCH), thermosensitive hydroxybutyl chitin, thermosensitive hydroxypropyl cellulose, and thermosensitive hydroxypropyl methyl cellulose. In the examples, HPCH or thermosensitive carboxymethyl chitin may be used.

[0033] The raw materials for preparing the injectable thermosensitive hydrogel material containing zwitterions provided by this invention include zwitterionic monomers. In this invention, the zwitterionic monomer is preferably 2-methacryloyloxyethylphosphorylcholine (MPC).

[0034] In this invention, the mass ratio of the thermosensitive biopolymer derivative to the zwitterionic monomer is 5 / 1 to 1 / 20, preferably 1 / 1 to 1 / 10, and in the embodiments it can be 1 / 10, 1 / 7 or 1 / 5. By controlling the mass ratio of the thermosensitive biopolymer derivative to the zwitterionic monomer, this invention can obtain a structurally stable, fully physically cross-linked double network structure, while also forming a hydration layer, thereby more effectively resisting the non-specific adhesion of various proteins and bacteria.

[0035] This invention provides a method for preparing the injectable thermosensitive hydrogel material containing zwitterions as described above, comprising the following steps:

[0036] A temperature-sensitive biopolymer derivative, a zwitterionic monomer, and a first solvent are mixed at a low temperature of ≤10°C to obtain a mixed solution, wherein the first solvent contains water.

[0037] The mixed solution and the initiator are mixed and reacted to obtain the reaction material; the reaction material is then dialyzed and dried sequentially to obtain the injectable thermosensitive hydrogel material containing zwitterions.

[0038] This invention involves low-temperature mixing of a thermosensitive biopolymer derivative, a zwitterionic monomer, and a first solvent at ≤10°C to obtain a mixed solution, wherein the first solvent contains water. In this invention, the first solvent is preferably water or an aqueous solution. The water is preferably deionized water. The aqueous solution is preferably a sodium hydroxide aqueous solution, and the molar concentration of the sodium hydroxide aqueous solution is preferably 0.1–0.5 mol / L. The low-temperature mixing temperature is preferably ≤5°C. In this invention, the low-temperature mixing preferably includes the following steps: dissolving the thermosensitive biopolymer derivative in the first solvent at ≤10°C to obtain a thermosensitive biopolymer derivative solution. The mass percentage of the thermosensitive biopolymer derivative in the solution is 0.05–0.5%, more preferably 0.05–0.2%, and in the examples, it can be 0.1% or 0.2%. After obtaining the thermosensitive biopolymer derivative solution, this invention mixes the thermosensitive biopolymer derivative solution with the zwitterionic monomer at ≤10°C to obtain a mixed solution. In this invention, the initial mixed solution is obtained after low-temperature mixing; the invention preferably further includes degassing the initial mixed solution with N2 to obtain a mixed solution, wherein the N2 degassing time is preferably 1 to 2 hours, and the N2 degassing is preferably carried out under stirring conditions.

[0039] After obtaining the mixed solution, the present invention mixes the mixed solution with an initiator to react and obtain the reactant; the reactant is then dialyzed and dried sequentially to obtain the injectable thermosensitive hydrogel material containing zwitterions. In the present invention, the initiator is preferably ammonium persulfate. The mass ratio of the initiator to the zwitterionic monomer is preferably 1 / 20. The reaction is a polymerization reaction of the zwitterionic monomer in the mixed solution under the action of the initiator to generate a zwitterionic polymer. The present invention can ensure the smooth progress of the polymerization reaction of the zwitterionic monomer by controlling the mass ratio of the initiator to the zwitterionic monomer. The reaction temperature is preferably 25-70°C, more preferably 37-60°C, and in the examples, it can be 40°C or 60°C; the reaction holding time is preferably 12-48 hours, more preferably 24-45 hours, and in the examples, it can be 36 hours or 24 hours. The present invention provides control over the reaction temperature and holding time to ensure the smooth progress of the polymerization reaction of the zwitterionic monomer. The reaction is carried out in a protective gas atmosphere, specifically nitrogen. In this invention, the dialysis is performed in deionized water, and the molecular weight cutoff of the dialysis bag used for the dialysis is preferably 14000 Da. The dialysis time is preferably 7 days, and the drying is preferably freeze-drying, with the freeze-drying time preferably being 5 days.

[0040] The injectable thermosensitive hydrogel material containing zwitterions provided by this invention is not easily lost at wound sites, is easy to use, and has the dual advantages of inhibiting fibrin deposition.

[0041] This invention provides the application of the injectable thermosensitive hydrogel material containing zwitterions as described in the above technical solution or the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method described in the above technical solution in the preparation of anti-adhesion materials.

[0042] In this invention, the temperature-sensitive anti-adhesion material includes injectable temperature-sensitive anti-adhesion hydrogel or anti-adhesion sponge material.

[0043] This invention provides an injectable thermosensitive anti-adhesion hydrogel, comprising the injectable thermosensitive hydrogel material containing zwitterions as described in the above technical solution or the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method described in the above technical solution, and a second solvent, wherein the second solvent is water or a buffer solution.

[0044] In this invention, the water is preferably deionized water. The buffer solution is preferably an aqueous PBS solution. The solid content of the injectable temperature-sensitive anti-adhesion hydrogel is preferably 0.5% to 5%.

[0045] The present invention provides a method for preparing the injectable thermosensitive anti-adhesion hydrogel described in the above technical solution, preferably comprising the following steps: dissolving the injectable thermosensitive hydrogel material containing zwitterions in a second solvent to obtain the injectable thermosensitive anti-adhesion hydrogel.

[0046] This invention provides an anti-adhesion sponge material, which is obtained by freeze-drying an aqueous solution of the zwitterionic injectable thermosensitive hydrogel material prepared by the above-described technical solution or the preparation method described above.

[0047] In this invention, the aqueous solution of the injectable thermosensitive hydrogel material preferably includes the injectable thermosensitive hydrogel material and water, wherein the water is preferably deionized water.

[0048] This invention provides a method for preparing the anti-adhesion sponge material described in the above technical solution, preferably comprising the following steps:

[0049] The injectable thermosensitive hydrogel material containing zwitterions is dissolved in water to obtain an aqueous solution of the injectable thermosensitive hydrogel material containing zwitterions; the aqueous solution of the injectable thermosensitive hydrogel material containing zwitterions is then freeze-dried to obtain the anti-adhesion sponge material. In this invention, the preferred ratio of the injectable thermosensitive hydrogel material containing zwitterions to the water is 0.3 g: 10 mL. The dissolution is preferably carried out under ice-water bath conditions. The dissolution is preferably carried out under stirring conditions.

[0050] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0051] Example 1: Preparation of hydroxypropyl chitin containing zwitterionic phosphorylcholine

[0052] Hydroxypropyl chitin (HPCH) was dissolved in deionized water at 5°C to prepare a 0.1 wt% aqueous solution. Then, zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was added, with a HPCH to MPC mass ratio of 1 / 10. The solution was degassed with N2 for 1 hour under continuous stirring. Ammonium persulfate was added to the mixed solution, with a zwitterionic MPC to ammonium persulfate mass ratio of 20 / 1. The temperature was gradually increased to 40°C, and the reaction was carried out under N2 atmosphere for 36 hours. After dialyzing and drying, an injectable thermosensitive hydrogel material containing zwitterionic phosphorylcholine was obtained, namely hydroxypropyl chitin containing zwitterionic phosphorylcholine (denoted as HPCS-3). Adjusting the HPCH to MPC mass ratio to 1 / 5 and 1 / 7 yielded HPCS-1 and HPCS-2, respectively.

[0053] Example 2: Preparation of carboxymethyl chitin containing zwitterionic phosphorylcholine

[0054] Carboxymethyl chitin was dissolved in a 0.5M sodium hydroxide aqueous solution at 5°C to prepare a 0.2wt% carboxymethyl chitin solution. Then, zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was added, with a mass ratio of carboxymethyl chitin to MPC of 1 / 5. The mixture was degassed with N2 for 1 hour under continuous stirring. Ammonium persulfate was added to the mixed solution, with a mass ratio of zwitterionic MPC to ammonium persulfate of 20 / 1. The temperature was gradually increased to 60°C, and the reaction was carried out under N2 atmosphere for 24 hours. After dialyzing and drying, an injectable thermosensitive hydrogel material containing zwitterionic phosphorylcholine, i.e., carboxymethyl chitin containing zwitterionic phosphorylcholine, was obtained.

[0055] Example 3: Preparation of injectable thermosensitive anti-adhesion hydrogel

[0056] 0.2 g of HPCS-3 prepared in Example 1 was added to a centrifuge tube containing 10 mL of deionized water, and the mixture was continuously stirred in an ice bath until the HPCS-3 was completely dissolved. The centrifuge tube was then placed in a constant temperature and humidity chamber at 37°C to obtain an injectable thermosensitive anti-adhesion hydrogel. This hydrogel exhibits reversible thermosensitivity, good fluidity at low temperatures, and rapid gel formation at body temperature. Figure 1 (As shown).

[0057] Figure 2 This is a gel time analysis chromatogram of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of the present invention. 0.06 g of HPCH, HPCS-1, HPCS-2, and HPCS-3 were weighed and added to centrifuge tubes containing 3 mL of deionized water. After they were completely dissolved at 2°C, the centrifuge tubes were placed in constant temperature and humidity incubators at room temperature (25°C) and 37°C, respectively. The centrifuge tubes were inverted every 5 seconds to observe the solution flowability until the solution formed a gel, and the gel time was recorded. Figure 2 It is known that HPCS incorporating zwitterions possesses excellent thermosensitive properties, forming a gel within 30 seconds at body temperature. This allows HPCS solution to rapidly gel and form a barrier layer after being injected into a wound, preventing it from being lost from the wound.

[0058] Example 4: Swelling properties of HPCS prepared in Example 1

[0059] The swelling properties of the HPCS prepared in Example 1 were tested using a gravimetric method. Columnar HPCS hydrogels (HPCS-1, HPCS-2, and HPCS-3) with a diameter of 5 mm were immersed in PBS buffer at pH 7.4 and placed in a shaker at 37°C with a shaking rate of 60 rpm. At selected time intervals, excess water on the surface of the hydrogel was blotted off with filter paper, and the gels were weighed. The swelling ratio of the hydrogels was calculated. Figure 3 ).Depend on Figure 3 It can be seen that the HPCS prepared in Example 1 has good anti-swelling properties in body fluids and will not swell indefinitely, making it suitable for anti-postoperative adhesions.

[0060] Example 5: Biocompatibility of HPCS prepared in Example 1

[0061] The cytotoxicity of HPCS prepared in Example 1 against NIH 3T3 cells was tested using the extraction method. HPCS (HPCS-1, HPCS-2, and HPCS-3) prepared in Example 1 were immersed in DMEM medium at a specific ratio. After obtaining the extract, it was filtered through a 0.22 μm filter, and then the extract was used to replace the medium used to culture NIH 3T3 cells. After culturing for 24 h, the proliferation rate of NIH 3T3 cells in the wells was tested using a CCK-8 assay kit. 0.1 mL of DMEM medium was used as a negative control.

[0062] Red blood cell suspension was prepared by centrifuging anticoagulated rabbit whole blood at 3000 rpm for 10 min. The red blood cells were washed three times with PBS to prepare a 5% (v / v) red blood cell suspension. Then, HPCS was added to 500 μL of the suspension at 0.5 g / mL. The centrifuge tubes were incubated at 37°C for 1 hour, then centrifuged at 3000 rpm for 5 min, and the absorbance of the supernatant was measured. PBS and deionized water were used as negative and positive controls, respectively. Figure 4 It can be seen that HPCS thermosensitive hydrogel has good biocompatibility.

[0063] Example 6: Preparation of HPCS adhesive sponge prepared in Example 1

[0064] 0.3 g of the HPCS (HPCS-1, HPCS-2, and HPCS-3) prepared in Example 1 was added to a centrifuge tube containing 10 mL of deionized water. The mixture was stirred continuously in an ice bath until the HPCS was completely dissolved. The HPCS solution was then freeze-dried to obtain the HPCS sponge. Tissue adhesion strength was tested using an overlap shear test. Fresh pigskin (1 cm wide) was used, with the fat layer removed using a scalpel. The pigskin was rinsed with PBS (pH = 7.4) for 30 minutes before the test. The HPCS sponge was cut into 10 × 10 mm pieces. 2 The size is such that it covers the wet pigskin surface, and then another piece of pigskin of the same size is used to bond an area of ​​10×10mm. 2 Cover. After gently pressing the two pieces of pigskin at room temperature for 30 seconds, the tensile shear strength of the specimens was tested. The sponge has certain tissue adhesion ( Figure 5 It possesses excellent water absorption properties and slowly gels upon hydration. HPCS sponges, with their tissue-adhesive properties, can remain in body fluids for longer periods without leakage, making them suitable for use as a support barrier. HPCH sponges, which lack tissue-adhesive properties, were prepared using the same method.

[0065] Comparative Example 1: Preparation of HPCS powder prepared in Example 1

[0066] 0.3 g of HPCS-3 prepared in Example 1 was added to a centrifuge tube containing 10 mL of deionized water and stirred continuously in an ice bath until the HPCS was completely dissolved. The HPCS solution was then freeze-dried and pulverized to obtain HPCS powder. This powder forms a paste under the action of body fluids and cannot self-gelatinize to form a complete gel network structure.

[0067] As can be seen from the above embodiments, the preparation method of the zwitterionic injectable thermosensitive hydrogel material provided by the present invention involves first mixing zwitterionic monomers with thermosensitive biopolymers at low temperature, followed by raising the temperature to carry out the reaction, thereby obtaining a zwitterionic modified injectable thermosensitive hydrogel material. The preparation process of the zwitterionic injectable thermosensitive hydrogel material provided by the present invention is simple, possesses a fully physically cross-linked double network structure, exhibits good fluidity at low temperatures, is injectable, and can rapidly form a gel at body temperature. After freeze-drying, the zwitterionic injectable thermosensitive hydrogel material provided by the present invention can form a sponge material with certain tissue adhesion, which can quickly absorb water and adhere to the wound surface, exhibiting good biocompatibility and biodegradability, and is suitable for postoperative anti-adhesion.

[0068] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. Other embodiments can be obtained based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing an injectable thermosensitive hydrogel material containing zwitterions, characterized in that, Includes the following steps: A thermosensitive biopolymer derivative, a zwitterionic monomer, and a first solvent are mixed at a low temperature of ≤10°C to obtain a mixed solution. The first solvent is water or an aqueous sodium hydroxide solution. The thermosensitive biopolymer derivative includes thermosensitive carboxymethyl chitin or thermosensitive hydroxypropyl chitin. The zwitterionic monomer is 2-methacryloyloxyethyl phosphorylcholine. The mass ratio of the thermosensitive biopolymer derivative to the zwitterionic monomer is 1 / 1 to 1 / 10. The mixed solution and the initiator are mixed and reacted to obtain the reaction material. The initiator is ammonium persulfate. The mass ratio of the initiator to the zwitterionic monomer is 1 / 20. The reaction temperature is 25~70℃ and the reaction holding time is 12~48h. The reaction material is then dialyzed and dried sequentially to obtain the injectable thermosensitive hydrogel material containing zwitterions.

2. The preparation method according to claim 1, characterized in that, The low-temperature mixing includes the following steps: A thermosensitive biopolymer derivative is dissolved in a first solvent at ≤10℃ to obtain a thermosensitive biopolymer derivative solution, wherein the mass percentage of the thermosensitive biopolymer derivative in the solution is 0.05~0.5%. The thermosensitive biopolymer derivative solution was then mixed with the zwitterionic monomer at ≤10°C to obtain a mixed solution.

3. The application of the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method according to claim 1 or 2 in the preparation of anti-adhesion materials.

4. An injectable thermosensitive anti-adhesion hydrogel, characterized in that, The invention includes an injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method described in claim 1 or 2, and a second solvent, wherein the second solvent is water or a buffer solution.

5. The injectable thermosensitive anti-adhesion hydrogel according to claim 4, characterized in that, The solid content of the injectable thermosensitive anti-adhesion hydrogel is 0.5-5%.

6. An anti-adhesion sponge material, characterized in that, The solution of the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method described in claim 1 or 2 is obtained by freeze-drying.

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