A dual-network medical hydrogel with low swelling degree, and a preparation method and use thereof

Abstract

The application provides a double-network medical hydrogel with low swelling degree and a preparation method and application thereof, in the hydrogel, ion bond and covalent bond are simultaneously used to construct a hydrogel network with high adhesion and low swelling degree in situ, and the hydrogel network has great application prospect in the fields of tissue adhesion, closure, filling, sealing, hemostasis and bone repair. During the gelation process, the succinimidyl ester groups on the sodium alginate can react with the amine groups on the chitosan to generate covalent bonds, the carboxyl groups on the sodium alginate can generate ion bond with Ca 2+ The chitosan can generate coordination with the anions in the sodium salt and / or potassium salt, and the three actions occur simultaneously, so that the in-situ generated hydrogel has better mechanical properties, stronger tissue adhesion, and a swelling degree of about 50%, which is compared with the swelling of the existing in-situ polymerization gel which is usually several times or even dozens of times.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and specifically relates to a covalent-ionic dual-network medical hydrogel with low swelling degree, strong adhesion, good biocompatibility, in vivo degradation and absorption, and combined with tissue adhesion, filling, sealing and repair functions, as well as its preparation method and uses. Background Technology

[0002] As China's industrialization level increases year by year, accidental injuries are also on the rise. Besides war and natural disasters causing numerous casualties, injuries from various factors such as traffic accidents, falls, machinery accidents, sharp object injuries, sprains, and more are extremely common in daily work. All wounds (including external and internal wounds) require immediate closure and repair to prevent infection and promote healing.

[0003] Suturing is the most common technique for achieving wound closure and repair. However, common problems with suturing include unavoidable infiltration of surrounding tissues, nerve damage, and potential postoperative adhesions, as well as local tissue ischemia and necrosis caused by capillary damage. Due to urgent clinical needs, medical hydrogel adhesives have emerged to replace traditional suturing techniques or as a supplement to suturing.

[0004] In wound management, encompassing hemostasis, closure, and repair, numerous functional materials have been developed. However, pre-formed dressings cannot conform to irregular wounds and have poor absorbency, limiting their use to small areas of oozing. Cyanoacrylates, with their in-situ polymerization properties, are inexpensive and have strong adhesion, but their degradation performance is poor, and the resulting polymer film is rigid, easily scratching surrounding soft tissues and causing new wounds during in vivo application. In-situ molded hydrogels, represented by fibrin glue, are expensive, have low mechanical strength, and require stringent storage conditions. Another common type is polyethylene glycol gels (such as DuraSeal). TM , Like SprayGel, it is expensive and has a high degree of swelling, which can compress surrounding tissues and cause secondary damage during use. Existing hydrogels still face many challenges in complex practical applications, and the development of hydrogels with low swelling, high adhesion, ease of use, and optimized performance has significant clinical value.

[0005] Alginate and chitosan are two widely used ionic polymers in the biomedical field. The carboxylate anions on the alginate molecular chain and the amino cations on the chitosan molecular chain form macromolecular complexes in aqueous solution due to electrostatic attraction, making them a commonly used pair of hydrogel materials. In in-situ polymerized hydrogels used for tissue filling and sealing, alginate is chemically modified to form aldehyde groups (-CHO), polyphenolic groups such as dopamine, or succinimide ester groups (-NHS). These groups react with the amino groups on chitosan and tissue surface proteins to form hydrogels with high adhesion properties. However, these materials often exhibit excellent water absorption and retention properties, swelling several times or even tens of times after absorbing large amounts of water from the body, compressing wounds, tissues, and nerves. Excessive swelling is one of the key issues limiting the application of these polysaccharide hydrogels in tissue sealing and filling. Summary of the Invention

[0006] In order to overcome the shortcomings of the prior art, the purpose of this invention is to provide a covalent-ionic dual-network medical hydrogel with low swelling degree, strong adhesion, good biocompatibility, in vivo degradation and absorption, and tissue adhesion, filling, sealing and repair functions, as well as its preparation method and uses.

[0007] The objective of this invention is achieved through the following technical solution:

[0008] A medical hydrogel comprising a first component and a second component: the first component comprises chitosan and calcium salt; the second component comprises sodium alginate containing succinimide ester groups and sodium and / or potassium salts.

[0009] According to an embodiment of the present invention, the first component is composed of chitosan and calcium salt; the second component is composed of sodium alginate containing succinimide ester groups and sodium and / or potassium salts.

[0010] According to an embodiment of the present invention, the mass ratio of the first component and the second component is 1:5 to 5:1, such as 3:1, 2:1, 1:1, 1:2 or 1:3.

[0011] According to an embodiment of the present invention, the chitosan is selected from one or more of chitosan hydrochloride, hydroxypropyl chitosan, methyl chitosan, ethyl chitosan, carboxymethyl chitosan, chitosan phosphate, and chitosan perchlorate.

[0012] According to an embodiment of the present invention, the calcium salt is selected from one or a combination of calcium chloride, calcium acetate, calcium lactate, calcium gluconate, and calcium nitrate.

[0013] According to an embodiment of the present invention, the mass ratio of the calcium salt to chitosan is 1:50 to 5:1, such as 1:50, 1:40, 1:30, 1:20, 1:10, 1:2, 1:1, 3:2, 2:1, 5:4, 5:2, 3:1, 7:2 or 4:1.

[0014] According to an embodiment of the present invention, the sodium salt is selected from one or more of sodium chloride, sodium sulfate, sodium phosphate, and sodium citrate; the potassium salt is selected from one or more of potassium chloride, potassium sulfate, potassium phosphate, and potassium citrate.

[0015] According to an embodiment of the present invention, the mass ratio of the sodium salt and / or potassium salt to sodium alginate containing succinimide ester groups is 1:50 to 5:1, such as 1:50, 1:40, 1:30, 1:20, 1:10, 1:3, 1:1, 3:2, 2:1, 5:2, 3:1, 7:2 or 4:1.

[0016] According to an embodiment of the present invention, the viscosity (1% aqueous solution) of the sodium alginate containing succinimide ester groups is 20-200 mPa·s, for example 20-50 mPa·s, 50-100 mPa·s, or 100-200 mPa·s.

[0017] According to an embodiment of the present invention, the degree of substitution of the succinimide ester group in the sodium alginate containing the succinimide ester group is 10-35%.

[0018] According to an embodiment of the present invention, the sodium alginate containing succinimide ester groups is prepared by the following method:

[0019] (a) Sodium alginate was dissolved in a buffer solution, and then N-hydroxysuccinimide and a dehydrating agent were added to carry out an esterification reaction to obtain sodium alginate containing succinimide ester groups.

[0020] According to an embodiment of the present invention, the method further includes the following steps:

[0021] (b) After the esterification reaction, a precipitant is added to the solution to separate the white solid, thus obtaining sodium alginate containing succinimide ester groups.

[0022] According to an embodiment of the present invention, the method further includes the following steps:

[0023] (c) Dissolve the above white solid in water, add a precipitant, and separate the white solid by centrifugation or vacuum filtration;

[0024] (d) Repeat step (c) 3-4 times, and vacuum dry the white solid separated in the last step to obtain the sodium alginate containing succinimide ester groups.

[0025] According to an embodiment of the present invention, in step (a), the buffer solution is a buffer solution known in the art, such as Mes buffer, and the pH of the buffer solution is 4 to 7, preferably 4 to 5.5.

[0026] According to an embodiment of the present invention, in step (a), the amount of sodium alginate added accounts for 0.5% to 10% of the total mass of the mixed system (sodium alginate and buffer solution).

[0027] According to an embodiment of the present invention, in step (a), the dehydrating agent is selected from 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[0028] According to an embodiment of the present invention, in step (a), the molar ratio of the N-hydroxysuccinimide to the carboxyl group in sodium alginate is 1:10 to 3:1, for example, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1 or 3:1; the molar ratio of the dehydrating agent to the N-hydroxysuccinimide is 1:1 to 5:1, for example, 1:1, 2:1, 3:1, 4:1 or 5:1.

[0029] According to an embodiment of the present invention, in step (a), the temperature of the esterification reaction is room temperature, and the time of the esterification reaction is 2 to 24 hours.

[0030] According to an embodiment of the present invention, in steps (b) and (c), the volume ratio of the precipitant to the polysaccharide solution containing succinimide ester groups is 1:1 to 5:1, for example, 1:1, 2:1, 3:1, 4:1 or 5:1.

[0031] According to an embodiment of the present invention, in steps (b) and (c), the precipitant is selected from at least one of methanol, ethanol, isopropanol, acetone and tetrahydrofuran.

[0032] According to an embodiment of the present invention, in step (d), the vacuum drying temperature is 30-70°C and the time is 4-24 hours.

[0033] The present invention provides a medical hydrogel, which is formed by the reaction of a first component and a second component. The first component includes chitosan and calcium salt; the second component includes sodium alginate containing succinimide ester groups and sodium and / or potassium salts.

[0034] According to an embodiment of the present invention, the medical hydrogel is a hydrogel polymerized in situ using a covalent-ionic dual network.

[0035] According to an embodiment of the present invention, the swelling degree of the medical hydrogel is less than or equal to 50% (swelling degree when placed in phosphate buffer at pH 7.4 at 37°C).

[0036] The present invention also provides a method for preparing the above-mentioned medical hydrogel, the method comprising:

[0037] The first component is dissolved in the first buffer solution, and the second component is dissolved in deionized water or the second buffer solution. After mixing and standing, the medical hydrogel is formed.

[0038] According to an embodiment of the present invention, the pH value of the first buffer solution is 7.5 to 12.0, for example, 7.6 to 11.0.

[0039] According to embodiments of the present invention, the first buffer solution includes, but is not limited to, phosphate buffer, sodium carbonate-sodium bicarbonate buffer, sodium tetraborate buffer, and Tris-HCl buffer.

[0040] According to an embodiment of the present invention, the mass ratio of the first buffer solution to the first component is 5:1 to 200:1, for example, 12:1 to 100:1.

[0041] According to an embodiment of the present invention, the pH value of the second buffer solution is 3.0 to 7.0, for example, 3.5 to 6.0.

[0042] According to embodiments of the present invention, the second buffer includes, but is not limited to, Mes buffer, phosphate buffer, disodium hydrogen phosphate-citric acid buffer, and citrate-sodium hydroxide-hydrochloric acid buffer.

[0043] According to an embodiment of the present invention, the mass ratio of the water or the second buffer solution to the second component is 5:1 to 200:1, for example, 12:1 to 100:1.

[0044] The present invention also provides the application of the above-mentioned medical hydrogel in tissue adhesion, filling, sealing, hemostasis and bone repair.

[0045] Beneficial effects:

[0046] This invention utilizes the simultaneous interaction of ionic and covalent bonds in a chitosan hydrogel system to construct an in-situ polymer network with high adhesion and low swelling properties, showing great promise for applications in tissue adhesion, occlusion, filling, sealing, hemostasis, and bone repair. During the gelation process, the succinimide ester groups on sodium alginate can react with the amine groups on chitosan to form covalent bonds, and the carboxyl groups on sodium alginate react with Ca... 2+Ionic bonding occurs between them, and chitosan coordinates with the anions in its sodium and / or potassium salts. This triple interaction results in in-situ hydrogels with superior mechanical properties, stronger tissue adhesion, and a swelling degree as low as approximately 50%. Compared to existing in-situ polymerized gels, which typically exhibit swelling several times or even tens of times greater, this low-swelling medical hydrogel effectively reduces pressure and damage to surrounding tissues and nerves during clinical applications. Furthermore, this invention employs a precipitant-separation-vacuum drying post-treatment method, replacing the common aqueous solution dialysis-freeze-drying method. This saves reaction time and costs, facilitating large-scale production. More importantly, this post-treatment method significantly reduces the exposure time of sodium alginate containing succinimide ester groups in the aqueous solution, effectively reducing the reverse hydrolysis reaction of the succinimide ester groups, thus yielding a highly substituted product. The increased covalent cross-linking sites during gelation also help suppress the swelling level of the hydrogel. Detailed Implementation

[0047] The present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0048] Unless otherwise specified, the experimental methods used in the following examples are conventional methods; unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0049] Example 1

[0050] Preparation of sodium alginate containing succinimide ester groups:

[0051] (1) Dissolve 2.0g sodium alginate in 80mL of Mes buffer at pH 5.5, then add 1.2g N-hydroxysuccinimide and 2.3g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and stop the reaction after stirring at room temperature for 12h.

[0052] (2) Add 120 mL of anhydrous ethanol to the reaction mixture, filter, and obtain a white solid.

[0053] (3) Dissolve the white solid in 80 mL of water, then add 120 mL of anhydrous ethanol, filter, and obtain the white solid.

[0054] (4) Repeat step (3) three times. The white solid separated in the last step is dried under vacuum at 60°C for 10 hours to obtain sodium alginate containing succinimide ester groups. The degree of substitution of the succinimide ester groups was measured to be 34%.

[0055] Preparation of dual-network hydrogels:

[0056] (1) Weigh 0.04 g of chitosan hydrochloride and 0.02 g of calcium chloride and dissolve them in 1 mL of Tris-HCl buffer solution at pH 8.5;

[0057] (2) Weigh 0.06 g of sodium alginate containing succinimide ester group and 0.02 g of sodium phosphate and dissolve them in 1 mL of Mes buffer;

[0058] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a double-network hydrogel is obtained.

[0059] Example 2

[0060] Preparation of dual-network hydrogels:

[0061] (1) Weigh 0.04 g of chitosan hydrochloride and 0.05 g of calcium chloride and dissolve them in 1 mL of Tris-HCl buffer solution at pH 8.5;

[0062] (2) Weigh 0.06 g of sodium alginate containing succinimide ester group and 0.05 g of sodium phosphate prepared in Example 1 and dissolve them in 1 mL of Mes buffer;

[0063] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a double-network hydrogel is obtained.

[0064] Example 3

[0065] Preparation of dual-network hydrogels:

[0066] (1) Weigh 0.04 g of chitosan hydrochloride and 0.08 g of calcium chloride and dissolve them in 1 mL of Tris-HCl buffer solution at pH 8.5;

[0067] (2) Weigh 0.06 g of sodium alginate containing succinimide ester group and 0.08 g of sodium phosphate prepared in Example 1 and dissolve them in 1 mL of Mes buffer;

[0068] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a double-network hydrogel is obtained.

[0069] Example 4

[0070] Preparation of sodium alginate containing succinimide ester groups:

[0071] (1) Dissolve 2.0g sodium alginate in 80mL of Mes buffer at pH 5.5, then add 0.7g N-hydroxysuccinimide and 1.2g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and stop the reaction after stirring at room temperature for 12h.

[0072] (2) Add 120 mL of anhydrous ethanol to the reaction mixture, filter, and obtain a white solid.

[0073] (3) Dissolve the white solid in 80 mL of water, then add 120 mL of anhydrous ethanol, filter, and obtain the white solid.

[0074] (4) Repeat step (3) three times. The white solid separated in the last step is dried under vacuum at 60°C for 10 hours to obtain sodium alginate containing succinimide ester groups. The degree of substitution of the succinimide ester groups was measured to be 12%.

[0075] Preparation of dual-network hydrogels:

[0076] (1) Weigh 0.05 g of carboxymethyl chitosan and 0.02 g of calcium lactate and dissolve them in 1 mL of sodium carbonate-sodium bicarbonate buffer solution at pH 9;

[0077] (2) Weigh 0.05g of sodium alginate containing succinimide ester group and 0.02g of sodium sulfate and dissolve them in 1mL of deionized water;

[0078] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a double-network hydrogel is obtained.

[0079] Example 5

[0080] Preparation of dual-network hydrogels:

[0081] (1) Weigh 0.05g of carboxymethyl chitosan and 0.05g of calcium lactate and dissolve them in 1mL of sodium carbonate-sodium bicarbonate buffer solution at pH 9;

[0082] (2) Weigh 0.05 g of sodium alginate containing succinimide ester group and 0.05 g of sodium sulfate prepared in Example 4 and dissolve them in 1 mL of deionized water;

[0083] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a double-network hydrogel is obtained.

[0084] Example 6

[0085] Preparation of dual-network hydrogels:

[0086] (1) Weigh 0.05 g of carboxymethyl chitosan and 0.08 g of calcium lactate and dissolve them in 1 mL of sodium carbonate-sodium bicarbonate buffer solution at pH 9;

[0087] (2) Weigh 0.05 g of sodium alginate containing succinimide ester group and 0.08 g of sodium sulfate prepared in Example 4 and dissolve them in 1 mL of deionized water;

[0088] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a double-network hydrogel is obtained.

[0089] Comparative Example 1

[0090] Preparation of single-network hydrogels:

[0091] (1) Weigh 0.04 g of chitosan hydrochloride and dissolve it in 1 mL of Tris-HCl buffer at pH 8.5;

[0092] (2) Weigh 0.06 g of sodium alginate containing succinimide ester group prepared in Example 1 and dissolve it in 1 mL of Mes buffer;

[0093] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a single-network hydrogel is obtained.

[0094] Comparative Example 2

[0095] Preparation of single-network hydrogels:

[0096] (1) Weigh 0.05 g of carboxymethyl chitosan and dissolve it in 1 mL of sodium carbonate-sodium bicarbonate buffer solution at pH 9;

[0097] (2) Weigh 0.05 g of sodium alginate containing succinimide ester group prepared in Example 4 and dissolve it in 1 mL of deionized water;

[0098] (3) The solutions from steps (1) and (2) are uniformly mixed by an extrusion device and applied to the desired area. After standing, a single-network hydrogel is obtained.

[0099] Test Example 1

[0100] Determination of the swelling degree of hydrogels.

[0101] Prepare a disc-shaped hydrogel with a diameter of 10 mm and a height of 5 mm, and weigh it (W0). Place it in 50 mL of pH 7.4 phosphate buffer at 37°C until the weight no longer increases. Record the maximum weight as W. t Formula for calculating the swelling degree of hydrogels:

[0102] Swelling degree (%) = (Wt -W0) / W0×100%

[0103] The test results are shown in the table below.

[0104]

[0105]

[0106] Test Example 2

[0107] Pigskin was used to test the adhesive strength.

[0108] Pigskin was cut into two strips, each 30mm long and 10mm wide. The solutions obtained in steps (1) and (2) of the above-described examples and comparative examples were uniformly mixed using an extrusion device and extruded onto approximately 10mm x 10mm areas at one end of each pigskin strip. Finally, the coated areas of the two pigskin strips were joined together and placed in a humid environment under a pressure of 20N for 2 hours. The bonding strength of the medical adhesive to the pigskin was tested using a universal tensile testing machine, and the test results are shown in the table below.

[0109]

[0110] Test Example 3

[0111] The mechanical properties of the gel were tested using a universal tensile testing machine.

[0112] Cylindrical hydrogels with a diameter of 10 mm and a height of 5 mm were prepared in a cylindrical mold. The dimensions of each sample were accurately measured, and the compressive strength was tested using a universal tensile testing machine. The compression test speed was 1 mm / min, and the sample was compressed until it broke. The test results are shown in the table below.

[0113]

[0114] In Comparative Examples 1 and 2, no additional salt was added to the hydrogels; they were mono-network hydrogels formed solely by the covalent bonding between chitosan and sodium alginate containing succinimidyl ester groups. The swelling degree, adhesion, and mechanical properties of the hydrogels were mainly affected by the degree of substitution of the succinimidyl ester groups on the sodium alginate. The degree of substitution was adjusted by the amount of N-hydroxysuccinimidyl ester added during the reaction. A higher amount of N-hydroxysuccinimidyl ester added resulted in a higher degree of substitution, a greater cross-linking density of the gel, and consequently, lower swelling degree, stronger adhesion, and better mechanical properties. The mono-network hydrogels already exhibited lower swelling degree and comparable adhesion and compressive strength than commercially available gels.

[0115] By comparing Comparative Example 1 with Examples 1-3, and Comparative Example 2 with Examples 4-6, under otherwise unchanged conditions, as the amount of salt added to the first and second components increases, the swelling degree decreases, while the adhesive strength and compressive strength increase. The swelling degree can be reduced to less than half of the initial value, as low as 44%. Higher adhesion and limited swelling degree offer significant advantages for hydrogels in applications such as nerve repair, tissue sealing, and bone repair.

[0116] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A medical hydrogel, wherein, The medical hydrogel comprises a first component and a second component: the first component comprises chitosan and calcium salt; the second component comprises sodium alginate containing succinimide ester groups and sodium and / or potassium salts; Wherein, the chitosan is selected from one or more of chitosan hydrochloride, hydroxypropyl chitosan, methyl chitosan, ethyl chitosan, carboxymethyl chitosan, chitosan phosphate, and chitosan perchlorate; the calcium salt is selected from one or more of calcium chloride, calcium acetate, calcium lactate, calcium gluconate, and calcium nitrate; the mass ratio of the calcium salt to chitosan is 1:50-5:1; In the sodium alginate containing succinimide ester groups, the degree of substitution of the succinimide ester groups is 10%-35%; the sodium salt is selected from one or more of sodium sulfate, sodium phosphate, and sodium citrate; the potassium salt is selected from one or more of potassium sulfate, potassium phosphate, and potassium citrate. The mass ratio of the sodium and / or potassium salts to sodium alginate containing succinimide ester groups is 1:50-5:

1.

2. The medical hydrogel according to claim 1, wherein, The mass ratio of the first component to the second component is 1:5-5:

1.

3. The medical hydrogel according to claim 1, wherein, The viscosity of the sodium alginate containing succinimide ester groups is 20-200 mPa•s.

4. A medical hydrogel, wherein the medical hydrogel is formed by reacting a first component and a second component, the first component comprising chitosan and calcium salt; the second component comprising sodium alginate containing succinimide ester groups and sodium and / or potassium salts; in, The chitosan is selected from one or more of chitosan hydrochloride, hydroxypropyl chitosan, methyl chitosan, ethyl chitosan, carboxymethyl chitosan, chitosan phosphate, and chitosan perchlorate; the calcium salt is selected from one or more of calcium chloride, calcium acetate, calcium lactate, calcium gluconate, and calcium nitrate; the mass ratio of the calcium salt to chitosan is 1:50-5:

1. Wherein, in the sodium alginate containing succinimide ester groups, the degree of substitution of the succinimide ester groups is 10%-35%; the sodium salt is selected from one or more of sodium sulfate, sodium phosphate, and sodium citrate; the potassium salt is selected from one or more of potassium sulfate, potassium phosphate, and potassium citrate; the mass ratio of the sodium salt and / or potassium salt to the sodium alginate containing succinimide ester groups is 1:50-5:

1.

5. The medical hydrogel according to any one of claims 1-4, wherein, The medical hydrogel is a covalent-ionic dual-network in-situ polymerized hydrogel. And / or, the swelling degree of the medical hydrogel is less than or equal to 50%.

6. A method for preparing the medical hydrogel according to any one of claims 1-5, the method comprising: The first component is dissolved in the first buffer solution, and the second component is dissolved in deionized water or the second buffer solution. After mixing and standing, the medical hydrogel is formed.

7. The preparation method according to claim 6, wherein, The pH value of the first buffer solution is 7.5-12.0; And / or, the first buffer includes phosphate buffer, sodium carbonate-sodium bicarbonate buffer, sodium tetraborate buffer, and Tris-HCl buffer; And / or, the mass ratio of the first buffer solution to the first component is 5:1 to 200:1; And / or, the pH of the second buffer solution is 3.0-7.0; And / or, the second buffer includes Mes buffer, phosphate buffer, disodium hydrogen phosphate-citrate buffer, and citrate-sodium hydroxide-hydrochloric acid buffer; And / or, the mass ratio of the water or second buffer solution to the second component is 5:1 to 200:

1.

8. The use of the medical hydrogel according to any one of claims 1-5 in the preparation of materials for tissue adhesion, filling, sealing, hemostasis and bone repair.

Images