Injection hydrogel wound dressing based on crosslinkable glucan

Abstract

The invention relates to an injection hydrogel wound dressing based on cross-linkable glucan, which is prepared by the following preparation method: dissolving divinyl sulfone in dimethyl sulfoxide, and dropwise adding mercapto acid for shading for esterification reaction; catalytic tertiary amine alkali and a condensing agent are added into reactants to activate carboxylic acid groups, then glucan is added for a reaction, and after the reaction is carried out for a period of time, precipitation is carried out in a precipitator to obtain modified glucan; dissolving the modified glucan in deionized water according to the concentration of 10w / v%; dissolving oligomeric chitosan or purified keratin in deionized water according to the concentration of 10w / v%; and mixing the two solutions for crosslinking to prepare the hydrogel injection wound dressing. The invention provides the high-performance injection hydrogel wound dressing prepared by a scientific and reasonable method, the stability and effectiveness of the product are ensured, and the clinical application requirements can be met.

Description

Technical Field

[0001] The invention relates to the technical field of lithium ion battery materials, and in particular to an injectable hydrogel wound dressing based on cross-linkable dextran. Background Art

[0002] With the continuous advancement of medical technology and the increasing demand for health care, the development and application of wound dressings has become an important research field. Although traditional wound dressings, such as gauze and bandages, can protect wounds to a certain extent, they still have many shortcomings in preventing infection, promoting healing and improving patient comfort. Therefore, a new type of wound dressing that can effectively promote wound healing, has antibacterial properties and can improve patient comfort is particularly important.

[0003] In situ gel is a type of preparation that can undergo a phase transition immediately at the site of administration after administration in a solution state, transforming from a liquid state to form a non-chemically cross-linked semi-solid gel. In recent years, researchers have explored in situ injectable hydrogels, that is, hydrogel biomaterials that can spontaneously gel under physiological conditions when applied locally to the wound surface. This type of biomaterial contains extracellular matrix components, and cells that promote wound repair can be added as needed. It can also serve as a controlled release carrier for active peptides such as growth factors, simulating the local microenvironment of the wound surface, thereby inducing repair and regeneration. Since in situ gels need to react and form under human physiological conditions, the reaction conditions are relatively harsh, organic solvents cannot be used, the raw materials must be non-toxic to human cells, and the reaction cannot produce harmful substances such as free radicals.

[0004] Chitosan is a natural alkaline polysaccharide with a positive charge. The hydrogel formed by chitosan has good biocompatibility, biodegradability, antibacterial and low cytotoxicity. Chitosan hydrogel has good biological application prospects and has been widely used in biomedical fields such as drug controlled release, tissue engineering, and biosensors. However, in application, chitosan cross-linking methods such as the use of cross-linking agents, photocatalysis and enzyme catalysis generally have disadvantages such as low efficiency and slow gelation rate, and cannot form in situ injectable hydrogels. Chitosan-based in situ injectable hydrogels can be achieved by Schiff base reaction or electrostatic action, but because this reaction is reversible and the electrostatic force of chitosan is weak, its stability after gelation is poor, which limits the application of chitosan-based in situ injectable hydrogels.

[0005] Keratin is a protein widely found in epidermal structures such as hair and nails of humans and animals, as well as brain gray matter, spinal cord, and retinal nerves. It has good biocompatibility and antioxidant properties. Since it contains more cystine, it can be easily formed into hydrogels through disulfide cross-linking, and has unique applications in the fields of cell regeneration and nerve fiber repair. However, since the formation of disulfide bonds requires strong oxidizing conditions, such as high concentrations of hydrogen peroxide oxidation and gamma-ray radiation, the application of keratin in in situ injection hydrogels is limited.

[0006] Therefore, the existing technology needs to be improved. Summary of the invention

[0007] In the prior art, the application of chitosan and keratin in in situ injectable hydrogels is still insufficient. Therefore, the present invention provides an injectable hydrogel wound dressing based on cross-linkable dextran to solve the above problems.

[0008] To achieve the above object, the present invention provides an injectable hydrogel wound dressing based on cross-linkable glucan, which comprises the following specific steps: S1, dissolving divinyl sulfone in dimethyl sulfoxide, and adding mercapto acid dropwise to perform esterification reaction under light shielding; S2, adding a catalytic tertiary amine base and a condensing agent to the reactant to activate the carboxylic acid group, then adding dextran to react, and after a period of reaction, precipitating in a precipitant to obtain a modified dextran; S3, dissolving the modified glucan in deionized water at a concentration of 10 w / v%; S4, dissolving oligo-chitosan or purified keratin in deionized water at a concentration of 10 w / v%; S5. Mix the two solutions in S3 and S4 and cross-link them to prepare an injectable hydrogel wound dressing.

[0009] In one implementation, in S4, it further includes adding an antimicrobial cationic polymer and / or an antioxidant and dissolving them in deionized water.

[0010] In one implementation, in S4, the antimicrobial cationic polymer includes any one of a cationic polypeptide, a cationic polysaccharide, and a synthetic cationic polymer; and the antioxidant includes any one of a thiol antioxidant, a vitamin, and a natural extract.

[0011] In one implementation, in S1, the mercapto acid is a molecule containing both a carboxylic acid group and a mercapto group and connected by a carbon chain, and the mercapto acid is mercaptoacetic acid or mercaptopropionic acid.

[0012] In one implementation, in S2, the catalytic tertiary amine base includes any one of triethylamine, trimethylamine, N,N-dimethylethanolamine, N-methyldiethanolamine, triethanolamine, bis(dimethylaminoethyl)ether, benzyldimethylamine, N,N-dimethylpiperazine, 1,4-diazabicyclo[2.2.2]octane, N,N-diisopropylethylamine, tetramethylethylenediamine, tri-n-butylamine, N,N-dimethylcyclohexylamine, N-methylmorpholine, N,N-diisopropylethylamine and 4-dimethylaminopyridine.

[0013] In one implementation, in S2, the condensing agent is any one of ethylcarbodiimide hydrochloride, 1,3-dicyclohexylcarbodiimide, benzotriazol-1-yl-oxytripyrrolidinophosphorus hexafluorophosphate, bis(2-oxo-3-oxazolidinyl)phosphoryl chloride, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N'-diisopropylcarbodiimide.

[0014] In one implementation, in S2, the precipitant is any one of alcohol, acetone, ether, dichloromethane and tetrahydrofuran, and the volume ratio of dimethyl sulfoxide to the precipitant during the precipitation process is 1: (3-10).

[0015] In one implementation, in S3, the molecular weight of dextran is 6000Da-1200000Da; and the concentration of the modified dextran is 5%-30%.

[0016] In one implementation, in S4, the molecular weight of the oligosaccharide chitosan is less than 20,000 Da, and the keratin is human keratin.

[0017] Beneficial effects: The present invention prepares an injectable hydrogel wound dressing with excellent mechanical properties, antibacterial properties and biocompatibility by chemically modifying dextran and combining it with oligosaccharide chitosan or purified keratin. The hydrogel dressing can not only provide a moist healing environment, but also has excellent antibacterial and antioxidant properties, which can effectively prevent wound infection, promote wound healing and improve patient comfort; the synthesis method has simple steps, easy reaction conditions, easy storage, and great industrialization potential; the present invention provides a high-performance injectable hydrogel wound dressing prepared by a scientific and reasonable method, which ensures the stability and effectiveness of the product and can meet the needs of clinical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is a flow chart of the preparation steps of the injectable hydrogel wound dressing based on cross-linkable glucan provided by the present invention; Figure 2is the synthesis route of the cross-linkable glucan provided in Example 1; Figure 3 is a hydrogen nuclear magnetic resonance (NMR) characterization diagram of the modified dextran provided in Example 1; Figure 4 is a comparison diagram of the modified glucan provided in Examples 1 and 2 and the injectable hydrogel wound dressing based on cross-linkable glucan; Figure 5 is an electron microscopic comparison of the injectable hydrogel wound dressing based on cross-linkable dextran provided in Examples 1 and 2; Figure 6 is a comparison chart of contact sterilization performance of injectable hydrogel wound dressings based on cross-linkable dextran provided in the examples; Figure 7 It is a comparison chart of the recovery effect of the cross-linkable dextran-based injectable hydrogel wound dressing provided in the examples on the treatment of mouse wound models.

[0019] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the accompanying drawings and examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the description of the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" described below means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms is not necessarily for the same embodiment or example. Moreover, the technical features involved in each embodiment of the present invention can be combined with each other as long as they do not conflict with each other.

[0021] See also Figure 1 , Figure 1 The present invention provides an injectable hydrogel wound dressing based on cross-linkable glucan, which is prepared by the following preparation method, which includes the following specific steps: S1, dissolving divinyl sulfone in dimethyl sulfoxide, and adding mercapto acid dropwise to perform esterification reaction under light shielding; S2, adding a catalytic tertiary amine base and a condensing agent to the reactant to activate the carboxylic acid group, then adding dextran to react, and after a period of reaction, precipitating in a precipitant to obtain a modified dextran; S3, dissolving the modified glucan in deionized water at a concentration of 10 w / v%; S4, dissolving oligo-chitosan or purified keratin in deionized water at a concentration of 10 w / v%; S5. Mix the two solutions in S3 and S4 and cross-link them to prepare an injectable hydrogel wound dressing.

[0022] The present invention dissolves divinyl sulfone in dimethyl sulfoxide, then drips mercapto acid to shade for esterification, then adds catalytic tertiary amine base and condensation agent to activate carboxylic acid group, then adds dextran to react, and precipitates with precipitant to obtain modified dextran. Finally, the modified dextran is cross-linked with oligomeric chitosan or keratin to prepare injectable hydrogel. This method can prepare hydrogel wound dressing with good biocompatibility and injectability.

[0023] In S1, the thiol acid is a molecule containing both a carboxylic acid group and a thiol group and connected by a carbon chain, and the thiol acid is thioglycolic acid or mercaptopropionic acid (MPA). By using thioglycolic acid or mercaptopropionic acid as the thiol acid, the esterification reaction can be efficiently carried out, thereby obtaining a modified dextran with good reactivity, and improving the mechanical properties and stability of the hydrogel.

[0024] In S2, the catalytic tertiary amine base includes any one of triethylamine, trimethylamine, N,N-dimethylethanolamine, N-methyldiethanolamine (MDEA), triethanolamine, bis(dimethylaminoethyl)ether, benzyldimethylamine, N,N-dimethylpiperazine, 1,4-diazabicyclo[2.2.2]octane (DABCO), N,N-diisopropylethylamine (DIPEA), tetramethylethylenediamine (TMEDA), tri-n-butylamine, N,N-dimethylcyclohexylamine, N-methylmorpholine, N,N-diisopropylethylamine and 4-dimethylaminopyridine (DMAP). By adding the catalytic tertiary amine base, the activation reaction of the carboxylic acid group can be effectively promoted, and the reaction efficiency and product purity can be improved. Preferably, the catalytic tertiary amine base is 4-dimethylaminopyridine (DMAP).

[0025] Specifically, the condensing agent is any one of ethylcarbodiimide hydrochloride (EDC), 1,3-dicyclohexylcarbodiimide, benzotriazol-1-yl-oxytripyrrolidinophosphine hexafluorophosphate (PyBOP), bis(2-oxo-3-oxazolidinyl)phosphine chloride (BOP-Cl), O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), and N,N'-diisopropylcarbodiimide. By adding the condensing agent, the activation effect of the carboxylic acid group can be further improved, the modification of dextran can be promoted, and the performance of the hydrogel can be improved. Preferably, the condensing agent is ethylcarbodiimide hydrochloride (EDC).

[0026] Specifically, the precipitant is any one of alcohol, acetone, ether, dichloromethane and tetrahydrofuran, and the volume ratio of dimethyl sulfoxide to the precipitant during the precipitation process is 1: (3-10). By selecting the precipitant and its volume ratio, the precipitation process of the modified dextran can be effectively controlled to improve the purity and yield of the product. Preferably, the precipitant is ethanol.

[0027] Through the esterification reaction, reactive thiol (-SH) and carboxyl (-COOH) functional groups are introduced, increasing the reactivity and functionality of dextran. Modified dextran (DVP) is generated, which has higher reactivity and better physical and chemical properties, and is suitable for subsequent cross-linking reactions. After the mercapto acid reacts with divinyl sulfone, a modified dextran containing thiol and carboxyl groups is generated, which can further undergo cross-linking reactions with other materials (such as oligochitosan or keratin) to form a stable hydrogel network structure.

[0028] In S3, the molecular weight of dextran is 6000Da-1200000Da; the concentration of the modified dextran (DVP) is 5-30%. By controlling the molecular weight of dextran between 6000Da and 1200000Da, and the concentration of the modified dextran between 5% and 30%, the mechanical properties and degradation rate of the hydrogel can be adjusted to make it suitable for different types of wounds.

[0029] In S4, the molecular weight of the oligomeric chitosan is less than 20,000 Da, and the keratin is human keratin. By using oligomeric chitosan with a molecular weight of less than 20,000 Da and human keratin, the biocompatibility and biodegradability of the hydrogel can be further improved, making it more suitable for healing human wounds. Preferably, the human keratin is human hair.

[0030] In S4, it also includes adding antibacterial cationic polymers and / or antioxidants dissolved in deionized water. Specifically, the antibacterial cationic polymer includes any one of cationic polypeptides, cationic polysaccharides and synthetic cationic polymers. The cationic polypeptides are such as polylysine and nisin; the cationic polysaccharides are such as chitosan quaternary ammonium salts; the synthetic cationic polymers are such as polydiallyldimethylammonium chloride. Further, the antioxidant includes any one of thiol antioxidants, vitamins and natural extracts. The thiol antioxidants are such as acetylcysteine; the vitamins are such as sodium ascorbate; the natural extracts are such as anthocyanins. By using hydrogel as a carrier and adding functional antibacterial and antioxidant components, the antibacterial and antioxidant properties of the hydrogel can be enhanced, thereby promoting wound healing and reducing the risk of infection, thereby improving the practicality of the hydrogel and the possibility of wide application.

[0031] The injectable hydrogel wound dressing prepared by the above method has good biocompatibility, antibacterial properties, antioxidant properties and injectability, can effectively promote wound healing, reduce the risk of infection, and has broad application prospects.

[0032] Example 1: Preparation of injectable hydrogel based on cross-linkable dextran: S1. Dissolve 32.85 g of divinyl sulfone (DVP) in 90 ml of dimethyl sulfoxide (DMSO) and dropwise add 1.2 ml of mercaptopropionic acid (MPA) to react overnight (12 hours) in a dark environment, and use UV detection to confirm that the reaction is complete; S2, 0.2562g of dimethylaminopyridine (DMAP) and 4.0g of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were added to the reactants to activate the carboxylic acid groups. After 30 minutes, 5.0g of dextran was added to react overnight, and then precipitated in ethanol to obtain modified dextran (DVP); S3, dissolving the modified dextran in deionized water at a concentration of 10 w / v%; S4, dissolving oligosaccharide chitosan at a concentration of 10 w / v% in deionized water; S5. Mix the two solutions and wait for 10 seconds to prepare the injectable hydrogel, which is recorded as CS-Dex.

[0033] See also Figure 2 , Figure 2 This is the synthesis route of the cross-linkable glucan provided in Example 1.

[0034] Example 2: In S4, oligomeric chitosan is replaced with 10 w / v% reduced keratin. The two solutions are mixed and waited for 10 seconds to prepare a hydrogel, which is recorded as Ker-Dex. The other steps are the same as in Example 1 and are not repeated here.

[0035] Example 3: In S4, 5 w / v% acetylcysteine ​​was added to the oligo-chitosan solution, and the two solutions were mixed and waited for 10 seconds to prepare a hydrogel, which was recorded as CS-Dex-N. The other steps were the same as those in Example 1 and will not be repeated here.

[0036] Example 4: In S4, oligomeric chitosan was replaced with 10 w / v% reduced keratin, and 5 w / v% acetylcysteine ​​was added. The two solutions were mixed and waited for 10 seconds to obtain a hydrogel, which was recorded as Ker-Dex-N. The other steps were the same as in Example 1 and will not be repeated here.

[0037] Example 5: In S4, 5 w / v% acetylcysteine ​​and 5 w / w% polylysine antibacterial agent were added to the oligo-chitosan solution. The two solutions were mixed and waited for 10 seconds to obtain a hydrogel, which was recorded as CS-Dex-NL. The other steps were the same as those in Example 1 and will not be repeated here.

[0038] Example 6: In S4, oligomeric chitosan was replaced with 10 w / v% reduced keratin, and 5 w / v% acetylcysteine ​​and 5 w / v% polylysine antibacterial agent were added. The two solutions were mixed and waited for 10 seconds to prepare a hydrogel, which was recorded as Ker-Dex-NL. The other steps were the same as in Example 1 and will not be repeated here.

[0039] Verification experiment of contact bactericidal performance of injectable hydrogel wound dressing: 5 μL of Staphylococcus aureus liquid was evenly applied to the surface of the hydrogel. The negative control group was a bacterial stock solution diluted to a concentration in 1 mL of solution, and the test group was an injectable hydrogel based on cross-linked dextran provided in Examples 1 to 6. After the test material coated with the bacterial liquid was cultured in an incubator at 37°C for 3 hours, the test material was immersed in a sterilized PBS buffer to wash the bacteria off the surface of the test material, and the plate was smeared for counting.

[0040] Mouse wound model test A 5 mm diameter circular wound was made on the back of the mouse using a puncher, and the injection hydrogel wound dressing (Examples 2, 4, and 6) was covered on the wound surface and fixed with a band-aid, and the wound healing status was observed every two days. Based on the needs of the true restoration of hydrogel in the wound recovery process, no bactericides other than hydrogels, such as alcohol, chlorhexidine, etc., were applied to the wound during the mouse wound recovery process; nor were additional sources of infection, such as fungi and bacteria, introduced.

[0041] Results Analysis See also Figure 3 , Figure 3 The hydrogen nuclear magnetic resonance (NMR) characterization diagram of the modified dextran provided in Example 1. The hydrogen nuclear magnetic resonance (NMR) characterization diagram of the modified dextran (DVP) provided in Example 1 is as follows: Figure 3 As shown, the characteristic peak signals of functional groups, such as the characteristic peak of vinyl group (5.0-6.5ppm) and the characteristic peak of dextran backbone (2.5-4.0ppm), indicate that the structure of the polymer synthesis is correct.

[0042] See also Figure 4 , Figure 4It is a comparison diagram of the modified glucan provided in Examples 1 and 2 and the injectable hydrogel wound dressing based on cross-linkable glucan. Among them, I is the modified glucan provided in Example 1, II is the injectable hydrogel wound dressing based on cross-linkable glucan provided in Example 1, and III is the injectable hydrogel wound dressing based on cross-linkable glucan provided in Example 2. It can be seen that after the glucan is cross-linked with oligomeric chitosan and keratin respectively, the strength of the hydrogel formed by the cross-linking of glucan and keratin is higher than that formed by the hydrogel formed by glucan and oligomeric chitosan. This should be due to 1) the molecular weight of oligomeric chitosan is less than 20,000 Da, which is much smaller than the molecular weight of keratin, and its molecular skeleton strength is lower than that of keratin; 2) in the cross-linking process between oligomeric chitosan and glucan, the amino group participates in the Michael addition, and its nucleophilic reaction efficiency is much lower than that of the thiol group in keratin. Therefore, keratin can achieve a better cross-linking effect than oligomeric chitosan.

[0043] See also Figure 5 , Figure 5 This is a comparison of electron micrographs of the injectable hydrogel wound dressings based on cross-linkable dextran provided in Examples 1 and 2. Through observation under a scanning electron microscope, after freeze-drying, both the oligosaccharide chitosan / dextran hydrogel (left picture) and the keratin / dextran hydrogel (right picture) formed objective porous structures, which can be used as good carriers of functional molecules for further optimization of the hydrogel.

[0044] See also Figure 6 , Figure 6 : This is a comparison chart of the contact sterilization performance of the injectable hydrogel wound dressing based on cross-linkable dextran provided in the embodiment. The present invention further applies polylysine as an antibacterial agent and acetylcysteine ​​as an antioxidant in the hydrogel as an excellent antibacterial wound dressing. Since chitosan has a certain bactericidal effect, the hydrogels formed by cross-linking thereof all have a contact sterilization effect of greater than 90%. After adding antibacterial cationic polylysine, its sterilization effect is increased from 90% to greater than 99.999%. Similarly, although the keratin cross-linked hydrogel itself has no sterilization effect, after adding antibacterial cationic polylysine, its sterilization effect also reaches greater than 99.999%.

[0045] See also Figure 7 , Figure 7It is a comparison chart of the recovery effect of the cross-linkable dextran-based injectable hydrogel wound dressing on the mouse wound model provided in the embodiment. The antibacterial hydrogel dressing designed by the present invention has been further verified on the mouse wound model. In the control group, the wound was not treated in any way. It can be seen that after 13 days, there is still no sign of healing, and during the healing process from day 1 to day 7, the wound showed signs of infection. After 13 days of healing, the wound covered by Example 2, i.e. Ker-Dex, had a significant reduction in the area of ​​the wound, but it was still not completely healed. After 11 days of healing, the wound covered by Example 4, i.e. Ker-Dex-N, achieved the effect of covering 13 days in Example 2, but the wound was still not completely closed at the end of the experiment. The wound covered by Example 6, i.e. Ker-Dex-NL, which has both antibacterial and antioxidant agents, achieved the effect of healing for 13 days in the embodiment after the 9th day, and the wound was completely closed on the 11th day. On the 13th day, the surface of the wound was covered with mouse hair. Therefore, in the present invention, both antibacterial agents and antioxidants are beneficial to wound healing, and their combined use can greatly increase the speed of wound recovery.

[0046] In summary, the present invention dissolves divinyl sulfone in dimethyl sulfoxide, then drips mercapto acid to shade for esterification, then adds catalytic tertiary amine base and condensation agent to activate carboxylic acid group, then adds dextran to react, and precipitates by precipitant to obtain modified dextran; by cross-linking modified dextran with oligomeric chitosan or keratin, chemically modifying dextran, combining oligomeric chitosan or purified keratin, an injectable hydrogel wound dressing with excellent mechanical properties, antibacterial properties and biocompatibility is prepared. The Michael addition method is used for organic covalent bond linkage, and the reaction is irreversible and the chemical and mechanical properties are stable; the hydrogel dressing can not only provide a moist healing environment, but also has excellent antibacterial and antioxidant properties, can effectively prevent wound infection, promote wound healing, and improve patient comfort. In addition, the present invention can also realize the multifunctionality of the dressing by adding different antibacterial cationic polymers and antioxidants to meet the care needs of different types of wounds. The present invention provides a scientific and reasonable method for preparing a high-performance injectable hydrogel wound dressing, which ensures the stability and effectiveness of the product and can meet the needs of clinical application.

[0047] The synthesis method provided by the present invention has simple steps, easy reaction conditions, easy storage, and great industrialization potential; through the cross-linking of modified dextran, chitosan and keratin can quickly form hydrogels, so that the application of these two materials in the field of in situ injection hydrogels has been expanded; the preparation process does not involve organic solvents, can be carried out under human physiological conditions, does not produce toxic byproducts, and the dextran cross-linking agent has good biocompatibility and safety, so it can be used in medical consumables application scenarios with high biosafety. In short, the present invention provides a new type of injectable hydrogel wound dressing based on cross-linkable dextran, which has broad application prospects and important clinical value.

[0048] The above description is only a preferred embodiment of the present invention, and does not limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made by using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. An injectable hydrogel wound dressing based on cross-linkable dextran, characterized in that: It is prepared by the following preparation method, which comprises the following specific steps: S1, dissolving divinyl sulfone in dimethyl sulfoxide, and adding mercapto acid dropwise to perform esterification reaction under light shielding; S2, adding a catalytic tertiary amine base and a condensing agent to the reactant to activate the carboxylic acid group, then adding dextran to react, and after a period of reaction, precipitating in a precipitant to obtain a modified dextran; S3, dissolving the modified glucan in deionized water at a concentration of 10 w / v%; S4, dissolving oligo-chitosan or purified keratin in deionized water at a concentration of 10 w / v%; S5. Mix the two solutions in S3 and S4 and cross-link them to prepare an injectable hydrogel wound dressing.

2. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 1, characterized in that: In S4, it also includes adding an antibacterial cationic polymer and / or an antioxidant and dissolving them in deionized water.

3. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 2, characterized in that: In S4, the antimicrobial cationic polymer includes any one of a cationic polypeptide, a cationic polysaccharide and a synthetic cationic polymer; and the antioxidant includes any one of a thiol antioxidant, a vitamin and a natural extract.

4. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 1, characterized in that: In S1, the mercapto acids are molecules containing both carboxylic acid groups and mercapto groups and connected by a carbon chain, and the mercapto acid is mercaptoacetic acid or mercaptopropionic acid.

5. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 1, characterized in that: In S2, the catalytic tertiary amine base includes any one of triethylamine, trimethylamine, N,N-dimethylethanolamine, N-methyldiethanolamine, triethanolamine, bis(dimethylaminoethyl)ether, benzyldimethylamine, N,N-dimethylpiperazine, 1,4-diazabicyclo[2.2.2]octane, N,N-diisopropylethylamine, tetramethylethylenediamine, tri-n-butylamine, N,N-dimethylcyclohexylamine, N-methylmorpholine, N,N-diisopropylethylamine and 4-dimethylaminopyridine.

6. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 1, characterized in that: In S2, the condensing agent is any one of ethylcarbodiimide hydrochloride, 1,3-dicyclohexylcarbodiimide, benzotriazol-1-yl-oxytripyrrolidinophosphorus hexafluorophosphate, bis(2-oxo-3-oxazolidinyl)phosphoryl chloride, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate and N,N'-diisopropylcarbodiimide.

7. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 1, characterized in that: In S2, the precipitant is any one of alcohol, acetone, ether, dichloromethane and tetrahydrofuran, and the volume ratio of dimethyl sulfoxide to the precipitant during the precipitation process is 1: (3-10).

8. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 1, characterized in that: In S3, the molecular weight of dextran is 6000Da~1200000Da; the concentration of the modified dextran is 5%~30%.

9. The injectable hydrogel wound dressing based on cross-linkable dextran according to claim 1, characterized in that: In S4, the molecular weight of the oligosaccharide chitosan is less than 20,000 Da, and the keratin is human keratin.

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