Injectable temperature-sensitive hydrogel material containing zwitterions as well as preparation method and application of injectable temperature-sensitive hydrogel material

Abstract

The invention belongs to the technical field of biomedical materials, and particularly relates to an injectable temperature-sensitive hydrogel material containing zwitterions as well as a preparation method and application of the injectable temperature-sensitive hydrogel material. The invention provides an injectable temperature-sensitive hydrogel material containing zwitter-ions. The injectable temperature-sensitive hydrogel material is prepared from the following raw materials: a temperature-sensitive biopolymer derivative and a zwitter-ion monomer, the thermo-sensitive biopolymer derivative comprises a thermo-sensitive chitin derivative and / or a thermo-sensitive cellulose derivative; the mass ratio of the thermo-sensitive biopolymer derivative to the zwitterionic monomer is (5 / 1)-(1 / 20). The injectable temperature-sensitive hydrogel material containing zwitter-ions provided by the invention forms a completely physical cross-linked dual-network structure, is applied to a temperature-sensitive anti-adhesion material, can effectively resist non-specific adhesion of various proteins and bacteria, and is very suitable for resisting postoperative adhesion; and meanwhile, the wound dressing is not easy to lose at the wound and is biodegradable.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials, and in particular relates to an injectable temperature-sensitive hydrogel material containing zwitterions, a preparation method and an application thereof. Background Art

[0002] Internal soft tissue injuries are often caused by surgical trauma, removal of primary or secondary tumors, traumatic injuries such as the abdominal wall and chest wall, and soft tissue infections. Such tissue injuries are difficult to suture and can cause postoperative adhesions. In clinical practice, postoperative adhesions usually involve tissues such as tendons, dura mater sacs, intestines, peritoneum, pericardium, and uterus. In addition to conventional symptoms such as pain and movement disorders, adhesions of specific organs such as the uterine cavity and fallopian tubes can lead to organ-specific symptoms such as menopause and reproductive dysfunction. Adhesions of the intestines and pericardium can lead to life-threatening diseases such as intestinal obstruction and heart failure. Adequate removal of residual foreign matter such as debris and blood clots, adequate hemostasis, and reduced inflammation can reduce the occurrence of adhesions from the source. However, due to the long time for wound healing and adhesion formation, effective drugs and biomedical materials are still needed for anti-adhesion intervention during the postoperative healing process.

[0003] At present, some polymer materials for anti-adhesion have been commercialized. However, the existing anti-adhesion polymer materials have weak ability to resist the nonspecific adhesion of various proteins and bacteria, and are less effective in preventing postoperative adhesion. Summary of the invention

[0004] The purpose of the present invention is to provide an injectable thermosensitive hydrogel material containing zwitterions, a preparation method and an application thereof. The injectable thermosensitive hydrogel material containing zwitterions provided by the present invention is applied as an anti-adhesion material, can effectively resist the nonspecific adhesion of various proteins and bacteria, and is very suitable for preventing postoperative adhesion; at the same time, it has the characteristics of not being easily lost at the wound site and being biodegradable.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] The invention provides an injectable thermosensitive hydrogel material containing zwitterions. The preparation raw materials include: a thermosensitive biopolymer derivative and a zwitterion monomer; the thermosensitive biopolymer derivative includes a thermosensitive chitin derivative and / or a thermosensitive cellulose derivative; the mass ratio of the thermosensitive biopolymer derivative to the zwitterion monomer is 5 / 1 to 1 / 20.

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

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

[0009] The present invention provides a method for preparing an injectable thermosensitive hydrogel material containing zwitterions according to the above technical solution, comprising the following steps:

[0010] Mixing a thermosensitive biopolymer derivative, a zwitterionic monomer and a first solvent at low temperature at ≤10° C. to obtain a mixed solution, wherein the first solvent comprises water;

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

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

[0013] Dissolving the temperature-sensitive biopolymer derivative in a first solvent at ≤10° C. to obtain a temperature-sensitive biopolymer derivative solution, wherein the mass percentage of the temperature-sensitive biopolymer derivative in the temperature-sensitive biopolymer derivative solution is 0.05 to 0.5%;

[0014] Then, the temperature-sensitive biopolymer derivative solution is mixed with the zwitterionic monomer at a temperature of ≤10° C. to obtain a mixed solution.

[0015] Preferably, the reaction temperature is 25-70° C. and the insulation time is 12-48 hours.

[0016] The present invention provides the use of the injectable thermosensitive hydrogel material containing zwitterions 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] The present invention provides an injectable thermosensitive anti-adhesion hydrogel, comprising the injectable thermosensitive hydrogel material containing zwitterions 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 temperature-sensitive anti-adhesion hydrogel is 0.5-5%.

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

[0020] The present invention provides an injectable thermosensitive hydrogel material containing zwitterions, and the preparation 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 the present invention forms a completely physically cross-linked double network structure, which is composed 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, the present invention has the following beneficial effects:

[0021] The raw materials for preparing the injectable thermosensitive hydrogel material containing zwitterions provided by the present invention include: thermosensitive biopolymer derivatives and zwitterionic monomers. The thermosensitive biopolymer derivatives (including thermosensitive chitin derivatives and / or thermosensitive cellulose derivatives) have a large number of intermolecular and intramolecular hydrogen bonds, a highly crystalline structure and a high cohesive energy. The zwitterionic monomers have superhydrophilicity. The injectable thermosensitive hydrogel material obtained by the present invention with the above two raw materials contains a physical cross-linked double network structure formed by electrostatic interaction cross-linking and hydrophobic interaction cross-linking; at the same time, zwitterionic monomer segments with anionic and cationic groups are introduced into the gel, which helps the gel material to produce a hydration layer, thereby giving the hydrogel antibacterial properties, which can effectively resist the nonspecific adhesion of various proteins and bacteria, and is very suitable for anti-postoperative adhesion, and can create a moist microenvironment at the wound surface, reduce the temperature near the wound surface, and relieve the patient's pain.

[0022] The injectable thermosensitive hydrogel material containing zwitterions provided by the present invention forms a fluid state under low temperature conditions, has excellent injectability, and can quickly gel under body temperature conditions, and can spread over the entire postoperative wound surface with the peristalsis of the organ, so that when used as an anti-adhesion material, the coverage of the wound surface can be improved, and the operation time and difficulty can be reduced. At the same time, according to actual needs, the injectable thermosensitive hydrogel material containing zwitterions provided by the present invention can be further made into an anti-adhesion sponge material with tissue adhesion, which can be rehydrated into a gel structure, will not be quickly lost at the wound, is biodegradable, and is easy to operate when used, and is suitable for use as a postoperative anti-adhesion material.

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

[0024] The present invention provides a method for preparing an injectable thermosensitive hydrogel material containing zwitterions as described in the above technical solution, comprising the following steps: mixing a thermosensitive biopolymer derivative, a zwitterion 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 and an initiator to react to obtain a reaction material; and dialyzing and drying the reaction material in sequence to obtain the injectable thermosensitive hydrogel material containing zwitterions. The raw materials of the preparation method provided by the present invention are easy to obtain, the synthesis method is simple, and it is suitable for industrial production and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a sol-gel change diagram of the injectable temperature-sensitive hydrogel material containing zwitterions prepared in Example 1 of the present invention;

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

[0027] Figure 3 This is a diagram showing the swelling performance of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of the present invention;

[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 performance of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0030] The invention provides an injectable thermosensitive hydrogel material containing zwitterions. The preparation raw materials include: a thermosensitive biopolymer derivative and a zwitterion monomer; the thermosensitive biopolymer derivative includes a thermosensitive chitin derivative and / or a thermosensitive cellulose derivative; the mass ratio of the thermosensitive biopolymer derivative to the zwitterion monomer is 5 / 1 to 1 / 20.

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

[0032] The raw materials for preparing the injectable thermosensitive hydrogel material containing zwitterions provided by the present invention include thermosensitive biopolymer derivatives. In the present invention, the thermosensitive biopolymer derivatives include thermosensitive chitin derivatives and / or thermosensitive cellulose derivatives, preferably including one or more of thermosensitive carboxymethyl chitin, thermosensitive hydroxyethyl chitin, thermosensitive hydroxypropyl chitin (HPCH), thermosensitive hydroxybutyl chitin, thermosensitive hydroxypropyl cellulose and thermosensitive hydroxypropyl methylcellulose. In the embodiment, it can be HPCH or thermosensitive carboxymethyl chitin.

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

[0034] In the present 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. The present invention can obtain a structurally stable fully physically cross-linked double network structure by controlling the mass ratio of the thermosensitive biopolymer derivative to the zwitterionic monomer, and can form a hydration layer, thereby more effectively resisting the nonspecific adhesion of various proteins and bacteria.

[0035] The present invention provides a method for preparing an injectable thermosensitive hydrogel material containing zwitterions according to the above technical solution, comprising the following steps:

[0036] Mixing a thermosensitive biopolymer derivative, a zwitterionic monomer and a first solvent at low temperature at ≤10° C. to obtain a mixed solution, wherein the first solvent comprises water;

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

[0038] The present invention mixes a thermosensitive biopolymer derivative, a zwitterionic monomer and a first solvent at low temperature under the condition of ≤10°C to obtain a mixed solution, wherein the first solvent comprises water. In the present 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 temperature of the low-temperature mixing is preferably ≤5°C. In the present invention, the low-temperature mixing preferably includes the following steps: dissolving the thermosensitive biopolymer derivative in the first solvent under the condition of ≤10°C to obtain a thermosensitive biopolymer derivative solution. The mass percentage of the thermosensitive biopolymer derivative in the thermosensitive biopolymer derivative solution is 0.05-0.5%, more preferably 0.05-0.2%, and in the embodiment, it can be 0.1% or 0.2%. After obtaining the thermosensitive biopolymer derivative solution, the present invention mixes the thermosensitive biopolymer derivative solution with the zwitterionic monomer under the condition of ≤10°C to obtain a mixed solution. In the present invention, the low temperature mixing is followed by obtaining an initial mixed solution; the present invention preferably further comprises mixing the initial mixed solution with N 2 Degassing to obtain a mixed solution, the N 2 The degassing time is preferably 1 to 2 hours. 2 Degassing is preferably carried out under stirring conditions.

[0039] After obtaining the mixed solution, the present invention mixes the mixed solution and the initiator to react to obtain a reaction material; the reaction material is dialyzed and dried in sequence 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 that the zwitterionic monomer in the mixed solution undergoes a polymerization reaction 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 and the zwitterionic monomer. The temperature of the reaction is preferably 25 to 70°C, more preferably 37 to 60°C, and the embodiment can be 40°C or 60°C; the insulation time of the reaction is preferably 12 to 48h, more preferably 24 to 45h, and the embodiment can be 36h or 24h. The present invention provides control of the temperature and insulation time of the reaction, which can ensure the smooth progress of the polymerization reaction of the zwitterionic monomer. The reaction is carried out in a protective gas atmosphere, and the protective gas is specifically nitrogen. In the present invention, the dialysis is performed in deionized water, the molecular weight cutoff of the dialysis bag used in the dialysis is preferably 14000Da, the dialysis time is preferably 7 days, the drying is preferably freeze drying, and the freeze drying time is preferably 5 days.

[0040] The injectable temperature-sensitive hydrogel material containing zwitterions provided by the present invention is not easy to be lost at the wound site, is easy to use, and has the dual advantages of inhibiting fibrin deposition.

[0041] The present invention provides the use of the injectable thermosensitive hydrogel material containing zwitterions 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 the present invention, the temperature-sensitive anti-adhesion material includes an injectable temperature-sensitive anti-adhesion hydrogel or an anti-adhesion sponge material.

[0043] The present invention provides an injectable thermosensitive anti-adhesion hydrogel, comprising the injectable thermosensitive hydrogel material containing zwitterions 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 the present invention, the water is preferably deionized water. The buffer solution is preferably a PBS aqueous solution. The solid content of the injectable thermosensitive anti-adhesion hydrogel is preferably 0.5-5%.

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

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

[0048] The present 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 freeze-dried to obtain the anti-adhesion sponge material. In the present invention, the amount of the injectable thermosensitive hydrogel material containing zwitterions and the water is preferably 0.3g:10mL. The dissolution is preferably carried out under ice water bath conditions. The dissolution is preferably carried out under stirring conditions.

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

[0051] Example 1: Preparation of Hydroxypropyl Chitosan Containing Zwitterionic Phosphorylcholine

[0052] Hydroxypropyl chitosan (HPCH) was dissolved in deionized water at 5°C to prepare a 0.1 wt% hydroxypropyl chitosan aqueous solution, followed by the addition of zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC), wherein the mass ratio of HPCH to MPC was 1 / 10. 2 Degas for 1 hour. Add ammonium persulfate to the mixed solution, with the mass ratio of zwitterionic MPC to ammonium persulfate being 20 / 1. Gradually increase the temperature to 40°C, and then 2 The reaction was carried out under atmospheric conditions for 36 hours, and after dialysis and drying, an injectable thermosensitive hydrogel material containing zwitterions, namely hydroxypropyl chitosan containing zwitterion phosphorylcholine (referred to as HPCS-3), was obtained. The mass ratio of HPCH to MPC was adjusted to 1 / 5 and 1 / 7 to obtain HPCS-1 and HPCS-2, respectively.

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

[0054] Carboxymethyl chitosan was dissolved in 0.5 M sodium hydroxide aqueous solution at 5°C to prepare a 0.2 wt% carboxymethyl chitosan solution, and then zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was added, wherein the mass ratio of carboxymethyl chitosan to MPC was 1 / 5, and N 2 Degas for 1 hour. Add ammonium persulfate to the mixed solution, with the mass ratio of zwitterionic MPC to ammonium persulfate being 20 / 1. Gradually increase the temperature to 60°C, and then 2 The reaction was carried out under atmospheric conditions for 24 hours, and after dialysis and drying, an injectable thermosensitive hydrogel material containing zwitterions was obtained, namely, carboxymethyl chitosan containing zwitterion phosphorylcholine.

[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 stirred continuously in an ice bath environment. After HPCS-3 was completely dissolved, the centrifuge tube was placed in a constant temperature and humidity chamber at 37°C to obtain an injectable thermosensitive anti-adhesion hydrogel. The hydrogel has reversible thermosensitivity, good fluidity at low temperatures, and can quickly form a gel at body temperature ( Figure 1 shown).

[0057] Figure 2 This is a gel time analysis chart of the injectable thermosensitive hydrogel material containing zwitterions prepared in Example 1 of the present invention. Weigh 0.06g of HPCH, HPCS-1, HPCS-2 and HPCS-3 respectively and add them into a centrifuge tube containing 3mL of deionized water. After they are completely dissolved at 2°C, place the centrifuge tubes in a constant temperature and humidity chamber at room temperature (25°C) and 37°C respectively. Invert the centrifuge tubes every 5 seconds to observe the fluidity of the solution until the solution forms a gel and record the gel time. Figure 2 It can be seen that HPCS with zwitterions has excellent temperature sensitivity and can form a gel within 30 seconds at body temperature. This means that after the HPCS solution is injected into a wound in the human body, the HPCS can quickly gel to form a barrier layer without 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 by weighing method. Columnar hydrogels of 5 mm in diameter (HPCS-1, HPCS-2 and HPCS-3) were immersed in a PBS buffer solution with a pH of 7.4 and placed in a shaker at 37°C at a rate of 60 rpm. At selected time intervals, excess water on the surface of the hydrogel was absorbed with filter paper, weighed, and the swelling rate of the hydrogel 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 infinitely, and is suitable for preventing postoperative adhesion.

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

[0061] The toxicity of the HPCS prepared in Example 1 to NIH 3T3 cells was tested by the extract method. The HPCS (HPCS-1, HPCS-2 and HPCS-3) prepared in Example 1 were soaked in DMEM culture medium according to a certain ratio. After obtaining the extract, it was filtered using a 0.22 μm filter head, and then the extract was used to replace the culture medium for culturing NIH 3T3 cells. After culturing for 24 hours, the proliferation rate of NIH 3T3 cells in the well plate was tested using a CCK-8 kit. 0.1 mL of DMEM culture medium was used as a negative control.

[0062] The anticoagulated rabbit whole blood was centrifuged at 3000rpm for 10min to prepare the red blood cell suspension. After washing the red blood cells three times with PBS, a 5% (v / v) red blood cell suspension was prepared. Then, HPCS was added to 500μL of the suspension at 0.5g / mL. After incubating the centrifuge tube at 37℃ for 1 hour, it was centrifuged at 3000rpm for 5min, and the absorbance of the supernatant was detected. 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] Add 0.3 g of HPCS (HPCS-1, HPCS-2 and HPCS-3) prepared in Example 1 into a centrifuge tube containing 10 mL of deionized water, and continue stirring in an ice bath environment. After the HPCS is completely dissolved, pour the HPCS solution into freeze drying to obtain an HPCS sponge. The tissue adhesion strength test was carried out using a lap shear test. Use a fresh pig skin piece (1 cm wide), remove the fat layer with a scalpel, and rinse with PBS (pH = 7.4) for 30 minutes before the test. Cut the HPCS sponge into 10×10 mm 2 size, cover the wet pigskin surface, and then use another piece of pigskin of the same size to bond the area of ​​10×10mm 2 After the two pieces of pig skin were gently pressed for 30 seconds at room temperature, the specimens were subjected to tensile shear strength tests. The sponge has a certain tissue adhesion ( Figure 5 ), and has excellent water absorption properties, and can slowly gel after hydration. HPCS sponges with tissue adhesion can stay in body fluids for a longer time without loss, and are suitable for use as a support barrier. HPCH sponges are prepared using the same method, and the sponges do not have tissue adhesion.

[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 environment. After the HPCS was completely dissolved, the HPCS solution was poured into freeze drying, and the HPCS powder was obtained after crushing. The powder formed a paste under the action of body fluids and could not self-gelate to form a complete gel network structure.

[0067] From the above examples, it can be seen that the preparation method of the injectable thermosensitive hydrogel material containing zwitterions provided by the present invention is to first mix the zwitterion monomer with the thermosensitive biopolymer at low temperature, and then raise the temperature to react to obtain the injectable thermosensitive hydrogel material containing zwitterions modified by zwitterions. The injectable thermosensitive hydrogel material containing zwitterions provided by the present invention has a simple preparation process, has a double network structure with complete physical cross-linking, has good fluidity at low temperatures, is injectable, and can quickly form a gel under body temperature. The injectable thermosensitive hydrogel material containing zwitterions provided by the present invention can be freeze-dried to form a sponge material, which has certain tissue adhesion, can quickly absorb water from the wound surface and adhere to the wound surface, has good biocompatibility and biodegradability, and is suitable for postoperative anti-adhesion.

[0068] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. An injectable thermosensitive hydrogel material containing zwitterions, characterized in that: The preparation 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.

2. The injectable thermosensitive hydrogel material containing zwitterions according to claim 1, characterized in that: The temperature-sensitive biopolymer derivative includes one or more of temperature-sensitive carboxymethyl chitosan, temperature-sensitive hydroxyethyl chitosan, temperature-sensitive hydroxypropyl chitosan, temperature-sensitive hydroxybutyl chitosan, temperature-sensitive hydroxypropyl cellulose and temperature-sensitive hydroxypropyl methyl cellulose.

3. The injectable thermosensitive hydrogel material containing zwitterions according to claim 1, characterized in that: The zwitterionic monomer is 2-methacryloyloxyethyl phosphorylcholine.

4. The method for preparing the injectable thermosensitive hydrogel material containing zwitterions according to any one of claims 1 to 3, characterized in that: The following steps are involved: Mixing a thermosensitive biopolymer derivative, a zwitterionic monomer and a first solvent at low temperature at ≤10° C. to obtain a mixed solution, wherein the first solvent comprises water; The mixed solution and the initiator are mixed and reacted to obtain a reaction material; the reaction material is dialyzed and dried in sequence to obtain the injectable thermosensitive hydrogel material containing zwitterions.

5. The preparation method according to claim 4, characterized in that: The low temperature mixing comprises the following steps: Dissolving the temperature-sensitive biopolymer derivative in a first solvent at ≤10° C. to obtain a temperature-sensitive biopolymer derivative solution, wherein the mass percentage of the temperature-sensitive biopolymer derivative in the temperature-sensitive biopolymer derivative solution is 0.05 to 0.5%; Then, the temperature-sensitive biopolymer derivative solution is mixed with the zwitterionic monomer at a temperature of ≤10° C. to obtain a mixed solution.

6. The preparation method according to claim 4 or 5, characterized in that: The reaction temperature is 25-70° C., and the insulation time is 12-48 hours.

7. Use of the injectable thermosensitive hydrogel material containing zwitterions according to any one of claims 1 to 3 or the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method according to any one of claims 4 to 6 in the preparation of anti-adhesion materials.

8. An injectable temperature-sensitive anti-adhesion hydrogel, characterized in that: The invention comprises the injectable thermosensitive hydrogel material containing zwitterions as claimed in any one of claims 1 to 3 or the injectable thermosensitive hydrogel material containing zwitterions prepared by the preparation method as claimed in any one of claims 4 to 6 and a second solvent, wherein the second solvent is water or a buffer solution.

9. The injectable temperature-sensitive anti-adhesion hydrogel according to claim 8, characterized in that: The solid content of the injectable temperature-sensitive anti-adhesion hydrogel is 0.5-5%.

10. An anti-adhesion sponge material, characterized in that: The aqueous solution of the injectable thermosensitive hydrogel material containing zwitterions prepared by the injectable thermosensitive hydrogel material containing zwitterions according to any one of claims 1 to 3 or the preparation method according to any one of claims 4 to 6 is freeze-dried to obtain the injectable thermosensitive hydrogel material containing zwitterions.

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