Injectable, adhesive and antioxidant granular hydrogel as well as preparation method and application thereof
A new hydrogel material was prepared by modifying chitosan, which solved the shortcomings of existing hydrogel materials in terms of mechanical properties, adhesion and antioxidant activity, and achieved wound protection and self-healing effects, which were suitable for clinical emergency treatment.
Patent Information
- Application Number
- CN202311772573.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-21
- Publication Date
- 2025-06-24
AI Technical Summary
The existing natural hydrogel materials have limited performance in terms of mechanical properties, adhesion, shaping properties, and antioxidant activity, and the use and configuration process is cumbersome, making it difficult to meet the convenience and stability requirements of clinical applications.
Using gallic acid modified chitosan and phenylboric acid modified chitosan as substrates, a novel tissue repair hydrogel material is prepared by modification, which has injectable, self-healing, adhesion and antioxidant properties.
It realizes effective protection of wounds, has good biocompatibility and biological activity, can fit any tissue, seal the wounds, and has good self-healing, shaping and antioxidant properties, and is suitable for clinical applications in emergency treatment of wounds.
Smart Images
Figure CN120189546A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of hydrogel dressings, and relates to an injectable, adhesive, and antioxidant particulate hydrogel and its preparation method and application. Background Art
[0002] Skin tissue defects caused by accidents, disasters, burns, etc. are common. Among them, wound repair materials are key functional materials for achieving wound closure, reducing infection, and promoting the regeneration and repair of damaged tissues. Hydrogels have been widely used in wound repair due to their high water content, adjustable active ingredients, mechanical properties similar to natural soft tissues, and extracellular matrix topology. In particular, natural hydrogels represented by chitosan, gelatin, and hyaluronic acid are a class of natural hydrogel materials with the most application potential and clinical recognition due to their high biocompatibility, degradability, and tissue induction activity. However, conventional natural hydrogels have poor mechanical properties and stability, and limited tissue adhesion and wound closure effects. In addition, for clinical use, how to improve the convenience, stability, and operability of material storage and use is another important aspect.
[0003] For clinical applications, the existing hydrogel materials are cumbersome in the use and configuration process, and the traditional natural hydrogel materials have limited mechanical properties, adhesiveness, plasticity, and antioxidant activity. Therefore, there is an urgent need for an injectable, adhesive, and antioxidant particulate hydrogel. Summary of the Invention
[0004] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide an injectable, adhesive, and antioxidant particulate hydrogel and its preparation method and application.
[0005] To achieve the purpose of the present invention, the following technical solutions are adopted:
[0006] In the first aspect, the present invention provides an injectable, adhesive, and antioxidant particulate hydrogel, and the raw materials for preparing the hydrogel include gallic acid-modified chitosan and phenylboronic acid-modified chitosan.
[0007] The present invention uses chitosan as a matrix and prepares a novel tissue repair hydrogel material through modification with phenylboronic acid and gallic acid. This hydrogel has excellent injectability, self-healing ability, adhesiveness, and antioxidant properties, and can effectively protect wounds. Neither chitosan modified alone nor unmodified chitosan can form a gel. At the same time, this hydrogel can be prepared into micron-sized particulate hydrogels by freeze-drying, shearing, and ball milling, which can be rapidly dissolved in physiological saline, shaped arbitrarily, and used by direct injection. It is a wound repair material that is convenient for storage and use, has high biosecurity, and antioxidant properties. It not only has good biocompatibility and bioactivity of natural hydrogel materials, but also can conform to any tissue to close the wound, and has good self-healing ability, plasticity, and antioxidant properties. In addition, this material can be prepared into solid particulate materials by freeze-drying and grinding, which can be efficiently dissolved and rapidly used, especially having good clinical application value for wounds that need to be emergently treated. The prepared CSPBA / CSGA hydrogel can be prepared into granulated fixed particles by freeze-drying, grinding, and shearing, and can be dissolved and gelled again, still having good properties.
[0008] Preferably, the hydrogel comprises 0.5 - 5 parts by mass of gallic acid-modified chitosan and 0.5 - 5 parts by mass of phenylboronic acid-modified chitosan.
[0009] The mass fraction of the gallic acid-modified chitosan can be selected as 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, etc. The mass fraction of the phenylboronic acid-modified chitosan can be selected as 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0010] Preferably, the molecular weight of the gallic acid-modified chitosan is 5000 - 500000 Da, such as 5000 Da, 10000 Da, 20000 Da, 50000 Da, 100000 Da, 200000 Da, 300000 Da, 400000 Da, 500000 Da, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0011] Preferably, the molecular weight of the phenylboronic acid-modified chitosan is 5000 - 500000 Da, such as 5000 Da, 10000 Da, 20000 Da, 50000 Da, 100000 Da, 200000 Da, 300000 Da, 400000 Da, 500000 Da, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0012] Second aspect, the present invention provides a preparation method of the hydrogel according to the first aspect, and the preparation method includes:
[0013] Mix the aqueous solution of phenylboronic acid-modified chitosan with the aqueous solution of gallic acid-modified chitosan, centrifuge, and let stand to obtain the product.
[0014] Preferably, the rotation speed of the centrifugation is 800 - 4000 rpm, and the time is 3 - 30 minutes.
[0015] The rotation speed can be selected as 800 rpm, 1000 rpm, 1500 rpm, 2000 rpm, 2500 rpm, 3000 rpm, 3500 rpm, 4000 rpm, etc., and the time can be selected as 3 min, 5 min, 10 min, 15 min, 20 min, 25 min, 30 min, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0016] Preferably, the preparation method of the phenylboronic acid-modified chitosan includes:
[0017] (1) Mix 3-carboxyphenylboronic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide with methanol to obtain a first mixed solution;
[0018] Mix chitosan with an aqueous acetic acid solution to obtain a second mixed solution;
[0019] (2) Dropwise add the first mixed solution into the second mixed solution and stir to obtain a third mixed solution;
[0020] (3) Dialyze the third mixed solution and freeze-dry to obtain the product.
[0021] Preferably, the mass ratio of 3-carboxyphenylboronic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide to methanol is (0.5 - 2):(0.5 - 2):(0.2 - 2):(30 - 80).
[0022] Among them, the specific point values in (0.5 - 2) can be selected as 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.4, 1.6, 1.8, 2, etc., the specific point values in (0.2 - 2) can be selected as 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.4, 1.6, 1.8, 2, etc., and the specific point values in (30 - 80) can be selected as 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0023] Preferably, the mass percentage content of chitosan in the first mixed solution is 0.5-5%, such as 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0024] Preferably, the mass percentage content of acetic acid in the aqueous acetic acid solution is 0.3-2%, such as 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0025] Preferably, the volume ratio of the first mixed solution to the second mixed solution is (0.2-1):(0.5-2).
[0026] Specific point values in (0.2-1) can be selected as 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0027] Preferably, the stirring time is 10-24h, such as 10h, 12h, 14h, 16h, 18h, 20h, 22h, 24h, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0028] Preferably, the pH of the third mixed solution is 5.5-6.5, such as 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0029] Preferably, the dialysis time is 3-7 days, such as 3 days, 4 days, 5 days, 6 days, 7 days, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0030] Preferably, the preparation method of gallic acid-modified chitosan includes:
[0031] (1) Mix gallic acid with ethanol to obtain a first mixed solution;
[0032] Mix chitosan with an aqueous acetic acid solution to obtain a second mixed solution;
[0033] (2) Mix the first mixed solution, an aqueous solution of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and an aqueous solution of N-hydroxysuccinimide to obtain a third mixed solution;
[0034] (3) Add the third mixture dropwise to the second mixture and stir to obtain a fourth mixture;
[0035] (3) Dialyze the fourth mixture and freeze-dry it to obtain the product.
[0036] Preferably, the mass ratio of gallic acid to ethanol is (0.5 - 2):(1 - 5).
[0037] Among them, the specific point values in (0.5 - 2) can be selected as 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0038] Preferably, the mass percentage content of chitosan in the second mixture is 0.5 - 5%, such as 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0039] Preferably, the mass percentage content of acetic acid in the aqueous acetic acid solution is 0.3 - 2%, such as 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0040] Preferably, the mass percentage content of 1-ethyl-(3-dimethylaminopropyl)carbodiimide in the aqueous 1-ethyl-(3-dimethylaminopropyl)carbodiimide solution is 0.5 - 4%, such as 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0041] Preferably, the mass percentage content of N-hydroxysuccinimide in the aqueous N-hydroxysuccinimide solution is 0.5 - 3%, such as 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, etc. Other specific point values within the above numerical range can be selected and will not be elaborated one by one here.
[0042] Preferably, the mass ratio of gallic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide is (0.5 - 5):(0.5 - 5):(0.2 - 2).
[0043] Among them, specific point values in (0.5 - 5) can all be selected as 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, etc., and specific point values in (0.2 - 2) can all be selected as 0.2, 0.4, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, etc. Other specific point values within the above numerical ranges can all be selected and will not be elaborated one by one here.
[0044] Preferably, the volume ratio of the second mixed solution to the third mixed solution is (0.5 - 2):(1 - 10).
[0045] Among them, specific point values in (0.5 - 2) can all be selected as 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, etc., and specific point values in (1 - 10) can all be selected as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc. Other specific point values within the above numerical ranges can all be selected and will not be elaborated one by one here.
[0046] Preferably, the stirring time is 10 - 24h, such as 10h, 12h, 14h, 16h, 18h, 20h, 22h, 24h, etc. Other specific point values within the above numerical ranges can all be selected and will not be elaborated one by one here.
[0047] Preferably, the pH of the third mixed solution is 5 - 6, such as 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, etc. Other specific point values within the above numerical ranges can all be selected and will not be elaborated one by one here.
[0048] Preferably, the dialysis time is 3 - 7 days, such as 3 days, 4 days, 5 days, 6 days, 7 days, etc. Other specific point values within the above numerical ranges can all be selected and will not be elaborated one by one here.
[0049] In the third aspect, the present invention provides an application of the hydrogel according to the first aspect in the preparation of a wound repair product.
[0050] Compared with the prior art, the present invention has the following beneficial effects:
[0051] The present invention uses chitosan as a matrix and prepares a novel tissue repair hydrogel material through modification with phenylboronic acid and gallic acid. This hydrogel has excellent injectability, self-healing ability, adhesiveness, and antioxidant properties, and can effectively protect the wound surface. At the same time, this hydrogel can be prepared into micron-sized particulate hydrogels by freeze-drying, shearing, and ball milling, which can be rapidly dissolved in physiological saline, shaped arbitrarily, and used by direct injection. It is a wound repair material with convenient storage and use, high biological safety, and antioxidant properties. It not only has good biocompatibility and biological activity of natural hydrogel materials, but also can conform to any tissue to close the wound surface, and has good self-healing ability, plasticity, and antioxidant properties. In addition, this material can be prepared into solid particulate materials by freeze-drying and grinding, which can be efficiently dissolved and rapidly used, especially having good clinical application value for wounds that need to be urgently treated. The prepared CSPBA / CSGA hydrogel can be prepared into granulated fixed particles by freeze-drying, grinding, and shearing, and can be dissolved and gelled again, still having good properties. Description of the Drawings
[0052] Figure 1 It is the result of infrared spectrum analysis.
[0053] Figure 2 It is the result of nuclear magnetic resonance hydrogen spectrum analysis, where Figure A is the nuclear magnetic resonance hydrogen spectrum analysis result of gallic acid-modified chitosan, and Figure B is the nuclear magnetic resonance hydrogen spectrum analysis result of phenylboronic acid-modified chitosan.
[0054] Figure 3 It is the result of the plasticity test of the hydrogel.
[0055] Figure 4 It is the result of the tensile and ductility tests of the hydrogel.
[0056] Figure 5 It is the result of the self-healing test of the hydrogel.
[0057] Figure 6 It is the result of the injectability test of the hydrogel.
[0058] Figure 7 It is the result of the tissue adhesiveness test of the hydrogel.
[0059] Figure 8 It is the result of the adhesiveness test of the hydrogel material.
[0060] Figure 9 It is the result of the plasticity and adhesiveness tests of the solid particulate hydrogel.
[0061] Figure 10 It is the result of the biocompatibility test of the hydrogel.
[0062] Figure 11 It is the result of the antioxidant test of the hydrogel. Detailed Description of the Invention
[0063] The technical solution of the present invention will be further described below by specific embodiments. Those skilled in the art should understand that the embodiments are only to help understand the present invention and should not be regarded as specific limitations on the present invention.
[0064] Preparation Example 1
[0065] This preparation example provides a gallic acid-modified chitosan, and the gallic acid-modified chitosan is prepared by the following preparation method:
[0066] (1) Dissolve 1 g of chitosan (CS, Sigma, 448877) in an acetic acid solution containing 1% (v / v) to obtain a chitosan solution with a mass fraction of 1% (w / v);
[0067] (2) Dissolve 1.37 g of gallic acid (GA, Aladdin, G131992) in 20 mL of ethanol solution, dissolve 1.54 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC, TCI, D1601) in 30 mL of ultrapure water, and dissolve 0.93 g of N-hydroxysuccinimide (NHS, Sigma, 130672) in 10 mL of ultrapure water. After mixing the three, add them dropwise to the solution in (1), control the pH of the system to 5.1, and stir at room temperature under anaerobic conditions for 12 h;
[0068] (3) Dialyze the reacted solution in (2) in deionized water in a dialysis bag with a molecular weight cut-off of MWCO 14000 Da for 7 d, freeze-dry for 72 h to obtain a gallic acid-modified chitosan (CSGA) product, and store it sealed at -20 °C.
[0069] Preparation Example 2
[0070] This preparation example provides a phenylboronic acid-modified chitosan, and the phenylboronic acid-modified chitosan is prepared by the following preparation method:
[0071] (1) Dissolve 1 g of chitosan (CS, Sigma, 448877) in an acetic acid solution containing 0.5% (v / v) to obtain a chitosan solution with a mass fraction of 1% (w / v);
[0072] (2) Dissolve 0.89 g of 3-carboxyphenylboronic acid (PBA, Aladdin, C103261), 1.03 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and 0.62 g of N-hydroxysuccinimide (NHS, Sigma, 130672) in 50 mL of methanol, and then add them dropwise to the solution in (1), control the pH of the system to 6, and stir at room temperature under anaerobic conditions for 12 h;
[0073] (3) The reacted solution (2) was dialyzed in deionized water for 5 days in a dialysis bag with a molecular weight cut-off of MWCO 14000 Da, and then freeze-dried for 72 h to obtain the product of phenylboronic acid-modified chitosan (CSPBA), which was stored sealed at -20 °C.
[0074] Example 1
[0075] This example provides a hydrogel, which is prepared by the following method:
[0076] (1) 0.2 g of CSPBA was dissolved in 10 mL of ultrapure water to obtain a 2% (w / v) CSPBA solution, and 0.2 g of CSPBA was dissolved in 10 mL of ultrapure water to obtain a 2% (w / v) CSGA solution. The CSPBA and CSGA solutions were centrifuged at 2000 rpm.
[0077] (2) 0.5 mL of the CSPBA solution was added to 0.5 mL of the CSGA solution, vortexed for 30 s, centrifuged at 2000 rpm for 10 s, and allowed to stand for 1 minute to obtain the CSPBA / CSGA hydrogel.
[0078] Test Example 1
[0079] The gallic acid-modified chitosan obtained in Preparation Example 1 and the phenylboronic acid-modified chitosan obtained in Preparation Example 2 were subjected to infrared spectroscopy analysis. The results are as Figure 1 shown: Comparing with the spectrum of unmodified chitosan (CS), the newly added absorption peak at 1527 cm -1 in the CSGA spectrum is the characteristic peak of the benzene ring of gallic acid, and the newly added absorption peak at 1545 cm -1 in the CSPBA spectrum is the characteristic peak of the benzene ring of phenylboronic acid, which confirms that the amino group of CS can condense with the carboxyl groups of gallic acid and phenylboronic acid, and the polyphenol and phenylboronic acid groups are successfully modified on the chitosan molecular chain.
[0080] Meanwhile, the above materials were subjected to NMR analysis, as Figure 2 shown: In the 1H NMR spectrum of CSGA, a new peak of the protons of the phenyl group appeared at 7.1 ppm, which was similar to the original GA spectrum; the characteristic peak of the benzene protons in CSPBA was obvious at 7.8 ppm, which was consistent with the proton peak of PBA. In summary, the gallic acid-modified chitosan and the phenylboronic acid-modified chitosan can be successfully prepared according to the experimental steps described in Preparation Example 1 and Preparation Example 2.
[0081] Test Example 2
[0082] The hydrogel prepared in Example 1 was analyzed for its plasticity, stretchability, injectability, self-healing ability, and tissue adhesion.
[0083] Figure 3It shows that the prepared hydrogel can be shaped by any mold.
[0084] Figure 4 It shows that the hydrogel has good tensile and ductile properties.
[0085] Figure 5 It shows that the prepared hydrogel can heal quickly. After 10 s, the healing interfaces can penetrate each other without separation.
[0086] Figure 6 It shows that the prepared hydrogel has good injectability and can be injected through a 26G needle.
[0087] Figure 7 It shows that the prepared hydrogel has excellent tissue adhesiveness and can seal any wound surface.
[0088] Figure 8 It shows that the hydrogel has high adhesiveness to both metal and plastic surfaces.
[0089] Test Example 3
[0090] The fixed particulate hydrogel material was prepared according to the experimental steps in the technical route section, and the properties of the hydrogel were observed. Figure 9 It shows that the prepared hydrogel can be quickly dissolved and gelled in normal saline (the mass ratio of the hydrogel to normal saline is 0.05:1), and has good plasticity and adhesiveness after redissolution.
[0091] Test Example 4
[0092] Biocompatibility test
[0093] Experimental setup: blank group and hydrogel group
[0094] Experimental sample: the hydrogel described in Example 1
[0095] Experimental method: Digest the fibroblast L929 cells, count them using a cell counting chamber, and aspirate the cell suspension and add it to the hydrogel material previously placed in a 24-well plate (the material is 0.2 g / well). In the blank group, cells are directly inoculated on the well plate without adding the material. Add 1×10 4 cells to each well and culture them in an incubator with 5% CO2, 37 °C, and 100% humidity for 5 d, and then characterize them using the Live / Dead viability / cytotoxicity staining kit (Thermo, L3224).
[0096] The results are as Figure 10 shown. The cells have a good growth state in the hydrogel and there are no dead cells. This result fully demonstrates that the hydrogel prepared in this patent has good biocompatibility.
[0097] Test Example 5
[0098] Antioxidant performance test
[0099] Experimental sample: the hydrogel prepared in Example 1
[0100] Experimental setup: PBS blank group and hydrogel groups with different concentrations (the concentrations of the hydrogel are set as: 0.05 mg / mL, 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL)
[0101] The specific operation is as follows: the antioxidant function of the hydrogel is evaluated by measuring the scavenging ability of the hydrogel on 1,1-diphenyl-2-picrylhydrazyl (DPPH, alpha Aesar, 44150) radicals. Take 100 μM of DPPH and different amounts of the hydrogel (12 mg, 9 mg, 6 mg, 3 mg, 1.5 mg) and co-incubate them in 3 mL of ethanol at 37 °C in the dark for 30 min, and measure the absorbance of the DPPH mixture at 517 nm with a UV-visible spectrophotometer. Calculate the radical scavenging efficiency ((1 - Ah / A0) × 100%), where A0 and Ah are the A517 values before and after the co-incubation of DPPH and the hydrogel respectively. The results are as Figure 11 shown, the hydrogel can effectively scavenge free radicals, and its antioxidant effect is positively correlated with its concentration.
[0102] The applicant declares that the present invention illustrates an injectable, adhesive, antioxidant particulate hydrogel and its preparation method and application through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement to the present invention, the equivalent substitution of each raw material of the product of the present invention, the addition of auxiliary components, the selection of specific methods, etc., all fall within the protection scope and the disclosure scope of the present invention.
[0103] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above-mentioned embodiments. Within the technical concept scope of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.
[0104] In addition, it should be noted that in the various specific technical features described in the above specific embodiments, they can be combined in any suitable way without contradiction. In order to avoid unnecessary repetition, the present invention will not separately describe various possible combination methods.
Claims
1. An injectable, adhesive, antioxidant particulate hydrogel, characterized in that, The raw materials for preparing the hydrogel include gallic acid-modified chitosan and phenylboronic acid-modified chitosan.
2. The hydrogel according to claim 1, characterized in that, The hydrogel includes 0.5 - 5 parts by mass of gallic acid-modified chitosan and 0.5 - 5 parts by mass of phenylboronic acid-modified chitosan.
3. The hydrogel according to claim 1 or 2, wherein The molecular weight of the gallic acid-modified chitosan is 5000 - 500000 Da; Preferably, the molecular weight of the phenylboronic acid-modified chitosan is 5000 - 500000 Da.
4. The preparation method of the hydrogel according to any one of claims 1-3, characterized in that, The preparation method includes: Mix the aqueous solution of phenylboronic acid-modified chitosan and the aqueous solution of gallic acid-modified chitosan, centrifuge, and let stand to obtain the product.
5. The preparation method according to claim 4, characterized in that, The rotation speed of the centrifugation is 800 - 4000 rpm, and the time is 3 - 30 min.
6. The preparation method according to claim 4 or 5, characterized in that, The preparation method of the phenylboronic acid-modified chitosan includes: (1) Mix 3-carboxyphenylboronic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide with methanol to obtain a first mixed solution; Mix chitosan with an aqueous acetic acid solution to obtain a second mixed solution; (2) Dropwise add the first mixed solution into the second mixed solution and stir to obtain a third mixed solution; (3) Dialyze the third mixed solution and freeze-dry to obtain the product.
7. The preparation method according to claim 6, characterized in that, The mass ratio of 3-carboxyphenylboronic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide to methanol is (0.5 - 2):(0.5 - 2):(0.2 - 2):(30 - 80); Preferably, the mass percentage of chitosan in the first mixed solution is 0.5 - 5%; Preferably, the mass percentage of acetic acid in the aqueous acetic acid solution is 0.3 - 2%; Preferably, the volume ratio of the first mixed solution to the second mixed solution is (0.2 - 1):(0.5 - 2); Preferably, the stirring time is 10 - 24 h; Preferably, the pH of the third mixed solution is 5.5 - 6.5; Preferably, the dialysis time is 3 - 7 days.
8. The preparation method according to any one of claims 4-7, characterized in that, The preparation method of the gallic acid-modified chitosan includes: (1) Mix gallic acid with ethanol to obtain a first mixed solution; Mix chitosan with an aqueous acetic acid solution to obtain a second mixed solution; (2) Mix the first mixed solution, an aqueous solution of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and an aqueous solution of N-hydroxysuccinimide to obtain a third mixed solution; (3) Dropwise add the third mixed solution into the second mixed solution and stir to obtain a fourth mixed solution; (3) Dialyze the fourth mixed solution and freeze-dry to obtain the product.
9. The preparation method according to claim 8, wherein The mass ratio of gallic acid to ethanol is (0.5 - 2):(1 - 5); Preferably, the mass percentage of chitosan in the second mixed solution is 0.5 - 5%; Preferably, the mass percentage of acetic acid in the aqueous acetic acid solution is 0.3 - 2%; Preferably, the mass percentage of 1-ethyl-(3-dimethylaminopropyl)carbodiimide in the aqueous solution of 1-ethyl-(3-dimethylaminopropyl)carbodiimide is 0.5 - 4%; Preferably, the mass percentage of N-hydroxysuccinimide in the aqueous solution of N-hydroxysuccinimide is 0.5 - 3%; Preferably, the mass ratio of gallic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and N-hydroxysuccinimide is (0.5-5):(0.5-5):(0.2-2); Preferably, the volume ratio of the second mixed solution to the third mixed solution is (0.5-2):(1-10); Preferably, the stirring time is 10-24 h; Preferably, the pH of the third mixed solution is 5-6; Preferably, the dialysis time is 3-7 days.
10. Use of the hydrogel according to any one of claims 1-3 in the preparation of a wound repair product.