Slow-release dressing with antibacterial and hemostatic functions and preparation method thereof

Abstract

The invention relates to the technical field of biomedical materials, and discloses a slow-release dressing with antibacterial and hemostatic functions and a preparation method thereof.The preparation method comprises the following steps that modified chitosan, modified sodium alginate and carrageenan are dispersed in deionized water and stirred at the temperature of 40-50 DEG C until the materials are completely dissolved, then citric acid and glycerinum are added into the materials, magnetic stirring is conducted for 1-2 h, and the slow-release dressing with the antibacterial and hemostatic functions is obtained. And placing at room temperature for 12-24 hours to obtain the slow-release dressing with the antibacterial and hemostatic functions. The slow-release dressing disclosed by the invention has good antibacterial performance and hemostatic performance.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a sustained-release dressing with antibacterial hemostatic function and a preparation method thereof. BACKGROUND

[0002] In the medical field, wound infection and bleeding are common and serious problems. Open wounds are easily invaded by bacteria, causing infection, not only delaying healing, but also possibly leading to complications such as sepsis, threatening the lives of patients. Rapid and effective hemostasis can reduce blood loss and reduce the risk of shock, therefore, developing a dressing with antibacterial hemostatic function is crucial to improve wound treatment effect and reduce infection rate and mortality. Traditional medical dressings are mainly used to cover the wound surface and absorb exudate, but they cannot effectively inhibit wound infection, especially in open wounds or contaminated environments, which easily leads to bacterial infection. Therefore, how to avoid this phenomenon is the key to solving the problem. For example, patent CN119971132A discloses a medical dressing for promoting healing of diabetic wounds, which comprises the following raw materials by mass percentage: stem cell exosome 0.008-0.012%, forsythia flower 0.004-0.01%, oligopeptide-10.002-0.005%, modified CaSi2 nanosheet 0.03-0.07%, hydroxypropyl chitosan 2-6%, xanthan gum 0.1-0.5%, glycerol 0.5-5%, and the balance is water. The medical dressing of the invention not only can promote wound healing, but also is beneficial to the repair of scars after wound healing, but the antibacterial performance and hemostatic performance need to be improved. SUMMARY

[0003] (I) Technical problems solved

[0004] In view of the deficiencies of the prior art, the present application provides a sustained-release dressing with antibacterial hemostatic function and a preparation method thereof. The sustained-release dressing of the present application has good antibacterial performance and hemostatic performance.

[0005] (II) Technical solutions

[0006] To achieve the above-mentioned purpose, the present application provides the following technical solutions: A sustained-release dressing with antibacterial hemostatic function comprises the following components by weight: 4-6 parts by weight of modified chitosan, 3-5 parts by weight of modified sodium alginate, 1-2 parts by weight of carrageenan, 0.5-0.6 parts by weight of citric acid, 0.8-1 parts by weight of glycerol, and 8-10 parts by weight of deionized water.

[0007] Further, the preparation method of the modified chitosan is as follows:

[0008] Step one: add tetrahydrofuran solvent to the reactor, pre-cool in the cold hydrazine for 20-25 min at-8 to-12℃, then add ethylene glycol diglycidyl ether, 1,3-propanedithiol, lithium hydroxide to it, stir evenly, stir in the ice water bath at 0-5℃ for 5-8h, after the reaction is completed, centrifugal, rotary evaporation to remove the solvent, dry, to obtain intermediate 1;

[0009] Step two: under the protection of nitrogen gas, add intermediate 1, thioctic acid to the N,N-dimethylformamide solvent, stir and mix, then add 4-dimethylaminopyridine, N,N-dicyclohexyl carbodiimide, stir at room temperature for 20-24h, after the reaction is completed, rotary evaporation to remove the solvent, wash and dry, to obtain intermediate 2;

[0010] Step three: add chloroacetic acid in anhydrous ethanol solvent, ice bath cooling to 0-5℃, slowly drop 40% mass fraction sodium hydroxide aqueous solution, then add intermediate 2 to it, stir and mix, under the protection of nitrogen gas, warm up to 60-70℃ for 6-12h, after the reaction is completed, filter, purify, dry, to obtain intermediate 3;

[0011] Step four: swell chitosan in 3% mass fraction acetic acid solution for 1-2h, add intermediate 3, N,N-methylene bisacrylamide, silver nitrate to it, introduce nitrogen for 10-15min, then add azobisisobutyronitrile catalyst, oil bath at 65-75℃ for 6-8h, after the reaction is completed, dialyze the mixture in the dialysis bag with a molecular weight cut-off of 3300-3500 for 36-48h, wash and dry, to obtain modified chitosan.

[0012] Further, the amount ratio of tetrahydrofuran, ethylene glycol diglycidyl ether, 1,3-propanedithiol, lithium hydroxide in step one is 25-30mL:4.42-4.46g:2.58-2.62g:0.11-0.13g.

[0013] Further, the amount ratio of N,N-dimethylformamide, intermediate 1, thioctic acid, 4-dimethylaminopyridine, N,N-dicyclohexyl carbodiimide in step two is 10-15mL:3.84-3.88g:0.71-0.75g:0.48-0.52g:0.84-0.88g.

[0014] Further, the amount ratio of ethanol, chloroacetic acid, sodium hydroxide, intermediate 2 in step three is 12-15mL:3.12-3.16g:0.5-0.6g:2.14-2.18g.

[0015] Further, the amount ratio of the chitosan, acetic acid, intermediate 3, N,N-methylene bisacrylamide, silver nitrate, azobisisobutyronitrile in the step four is 1.61-1.63g: 15-18mL: 2.25-2.28g: 0.24-0.26g: 0.6-0.8g: 0.3-0.32g.

[0016] Further, the preparation method of the modified sodium alginate is:

[0017] S1: adding sodium alginate into deionized water, stirring magnetically until completely dissolved, passing nitrogen for 10-15min, then adding epichlorohydrin, N,N-dimethyldecylamine, stirring and mixing, reacting at 40-45℃ for 20-24h, after the reaction is completed, washing, suction filtration, drying to obtain intermediate 4;

[0018] S2: adding intermediate 4, cinnamic acid into ethanol solution, stirring uniformly, then adding N,N'-dicyclohexyl carbodiimide, reacting at 60-80℃ for 3-4h, after the reaction is completed, washing and drying to obtain modified sodium alginate.

[0019] Further, the amount ratio of the deionized water, sodium alginate, epichlorohydrin, N,N-dimethyldecylamine in the S1 is 78-82mL: 4.02-4.06g: 1.96-1.98g: 6.44-6.48mL.

[0020] Further, the amount ratio of the ethanol, intermediate 4, cinnamic acid, N,N'-dicyclohexyl carbodiimide in the S2 is 20-25mL: 2.33-2.37g: 2.04-2.08g: 0.3-0.4g.

[0021] Further, the preparation method of the slow-release dressing with antibacterial hemostatic function is: dispersing the modified chitosan, modified sodium alginate, carrageenan in deionized water, stirring at 40-50℃ until completely dissolved, then adding citric acid, glycerol, stirring magnetically for 1-2h, placing at room temperature for 12-24h to obtain the slow-release dressing with antibacterial hemostatic function.

[0022] (Three) beneficial technical effects

[0023] The application synthesizes an intermediate 1 with a thioether bond and a plurality of hydroxyl groups by using ethylene glycol diglycidyl ether and 1,3-propanedithiol, then reacts a carboxyl in thioctic acid with a hydroxyl in the intermediate 1, grafts the thioctic acid to the main chain, the disulfide bond in the thioctic acid can be crosslinked with chitosan through N,N-methylene bisacrylamide, the disulfide bond has a fat-soluble property, can improve the hydrophobicity of the chitosan main chain, introduces a carboxyl by reacting chloroacetic acid with the intermediate 2, the existence of the carboxyl can reduce the pH value, causes the non-specific aggregation of blood platelets, thereby forming an artificial clot, improves the hemostatic effect of the dressing, and then reacts with silver nitrate, the thioether bond is easy to form coordination with silver ions, the silver ions can interfere with the activity of protease, at the same time, destroy the cell membrane of microorganisms, make the structure of microorganisms disorder, and improve the antibacterial effect of the dressing; the hydroxyl of sodium alginate and the epoxy group of epichlorohydrin are ring-opening reaction, cross-linking is formed at the same time, and a hydroxyl is generated, the chlorine atom of epichlorohydrin and the tertiary amine on N,N-dimethyl decylamine occur nucleophilic substitution, a quaternary ammonium salt group is generated, the sodium alginate is given a positive charge, and the antibacterial effect of the dressing is enhanced, the carboxyl on cinnamic acid can occur esterification reaction with the hydroxyl and be grafted to the sodium alginate main chain, the benzene propene structure of cinnamic acid can be inserted into the lipid bilayer of the bacterial cell membrane, increase the membrane permeability, cause the content to leak, and improve the antibacterial effect of the dressing. DETAILED DESCRIPTION

[0024] To make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the above technical scheme will be described in detail below with specific examples. Obviously, the described examples are some of the embodiments of the present application, rather than all the embodiments. Based on the examples in the present application, all other examples obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0025] Example 1

[0026] (1) 25 mL of tetrahydrofuran solvent was added to a reactor, and pre-cooled for 20 min in a cold hydrazine at-8 ℃, then 4.42 g of ethylene glycol diglycidyl ether, 2.58 g of 1,3-propanedithiol and 0.11 g of lithium hydroxide were added thereto, stirred uniformly, and stirred for 5 h under an ice water bath at 0 ℃, after the reaction was completed, centrifuged, removed the solvent by rotary evaporation, and dried to obtain the intermediate 1;

[0027] (2) 3.84 g of the intermediate 1 and 0.71 g of thioctic acid were added to 10 mL of N,N-dimethylformamide solvent under the protection of nitrogen gas, stirred and mixed, then 0.48 g of 4-dimethylaminopyridine and 0.84 g of N,N-dicyclohexyl carbodiimide were added, stirred for 20 h at normal temperature, after the reaction was completed, the solvent was removed by rotary evaporation, washed and dried to obtain the intermediate 2;

[0028] (3) 3.12 g of chloroacetic acid was added in 12 mL of anhydrous ethanol solvent, cooled to 0°C in an ice bath, 0.5 g of 40% mass fraction sodium hydroxide aqueous solution was slowly added dropwise, then 2.14 g of intermediate 2 was added, the mixture was stirred and mixed, warmed to 60°C for 6 h under nitrogen gas protection, after the reaction was completed, filtration, purification, drying, to obtain intermediate 3;

[0029] The synthesis reaction formula of intermediate 3 is as follows:

[0030] (4) 1.61 g of chitosan was swelled in 15 mL of 3% mass fraction acetic acid solution for 1 h, 2.25 g of intermediate 3, 0.24 g of N,N-methylene bisacrylamide, 0.6 g of silver nitrate were added, nitrogen was introduced for 10 min, then 0.3 g of azobisisobutyronitrile catalyst was added, oil bath at 65°C for 6 h, after the reaction was completed, the mixture was dialyzed in a dialysis bag with a molecular weight cut-off of 3300 for 36 h, washed and dried to obtain modified chitosan;

[0031] (5) 4.02 g of sodium alginate was added to 78 mL of deionized water, magnetically stirred until completely dissolved, nitrogen was introduced for 10 min, then 1.96 g of epichlorohydrin, 6.44 mL of N,N-dimethyldecylamine was added, stirred and mixed, reacted at 40°C for 20 h, after the reaction was completed, washed, suction filtered, dried to obtain intermediate 4;

[0032] (6) 2.33 g of intermediate 4, 2.04 g of cinnamic acid was added to 20 mL of ethanol solution, stirred uniformly, then 0.3 g of N,N'-dicyclohexyl carbodiimide was added, reacted at 60°C for 3 h, after the reaction was completed, washed and dried to obtain modified sodium alginate;

[0033] (7) 4 parts by weight of modified chitosan, 3 parts by weight of modified sodium alginate, 1 part by weight of carrageenan were dispersed in 8 parts by weight of deionized water, stirred until completely dissolved at 40°C, then 0.5 parts by weight of citric acid, 0.8 parts by weight of glycerol was added, magnetically stirred for 1 h, placed at room temperature for 12 h to obtain a sustained-release dressing with antibacterial and hemostatic functions.

[0034] Example 2

[0035] (1) 30 mL of tetrahydrofuran solvent was added to the reactor, pre-cooled in a cold hydrazine at -12°C for 25 min, then 4.46 g of ethylene glycol diglycidyl ether, 2.62 g of 1,3-propanedithiol, 0.13 g of lithium hydroxide was added, stirred uniformly, stirred at 5°C ice water bath for 8 h, after the reaction was completed, centrifuged, rotary evaporated to remove the solvent, dried to obtain intermediate 1;

[0036] (2) Under the protection of nitrogen gas, 3.88 g of intermediate 1, 0.75 g of thioctic acid, 0.52 g of 4-dimethylaminopyridine, and 0.88 g of N,N-dicyclohexylcarbodiimide were added to 15 mL of N,N-dimethylformamide solvent, stirred and mixed, and then stirred at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, washed, and dried to obtain intermediate 2;

[0037] (3) 3.16 g of chloroacetic acid was added to 15 mL of anhydrous ethanol solvent, cooled to 5°C in an ice bath, and 0.6 g of a 40% mass fraction sodium hydroxide aqueous solution was slowly added dropwise. Then, 2.18 g of intermediate 2 was added thereto, stirred and mixed, and then reacted at 70°C for 12 h under the protection of nitrogen gas. After the reaction was completed, it was filtered, purified, and dried to obtain intermediate 3;

[0038] (4) 1.63 g of chitosan was swelled in 18 mL of a 3% mass fraction acetic acid solution for 2 h, and 2.28 g of intermediate 3, 0.26 g of N,N-methylene bisacrylamide, and 0.8 g of silver nitrate were added thereto. Nitrogen was introduced for 15 min, and then 0.32 g of azobisisobutyronitrile catalyst was added. An oil bath was performed at 75°C for 8 h. After the reaction was completed, the mixture was dialyzed in a dialysis bag with a molecular weight cut-off of 3500 for 48 h, washed, and dried to obtain modified chitosan;

[0039] (5) 4.06 g of sodium alginate was added to 82 mL of deionized water, and stirred by a magnetic stirrer until completely dissolved. Nitrogen was introduced for 15 min, and then 1.98 g of epichlorohydrin and 6.48 mL of N,N-dimethyldecylamine were added and stirred and mixed. The reaction was performed at 45°C for 24 h. After the reaction was completed, it was washed, suction-filtered, and dried to obtain intermediate 4;

[0040] (6) 2.37 g of intermediate 4 and 2.08 g of cinnamic acid were added to 25 mL of an ethanol solution, stirred and mixed, and then 0.4 g of N,N'-dicyclohexylcarbodiimide was added. The reaction was performed at 80°C for 4 h. After the reaction was completed, it was washed and dried to obtain modified sodium alginate;

[0041] (7) 6 parts by weight of modified chitosan, 5 parts by weight of modified sodium alginate, and 2 parts by weight of carrageenan were dispersed in 10 parts by weight of deionized water, and stirred and dissolved at 50°C. Then, 0.6 parts by weight of citric acid and 1 part by weight of glycerol were added thereto, and stirred by a magnetic stirrer for 2 h. After being left to stand at room temperature for 24 h, a sustained-release dressing having an antibacterial hemostatic function was obtained.

[0042] Example 3

[0043] (1) 28 mL of tetrahydrofuran solvent was added to the reactor, and the reactor was pre-cooled in a cold bath at -10°C for 22 min, then 4.44 g of ethylene glycol diglycidyl ether, 2.6 g of 1,3-propanedithiol, 0.12 g of lithium hydroxide were added, stirred uniformly, and stirred at 2°C in an ice water bath for 6 h. After the reaction was completed, centrifugation was performed, the solvent was removed by rotary evaporation, and drying was performed to obtain intermediate 1;

[0044] (2) Under the protection of nitrogen gas, 3.86 g of intermediate 1, 0.73 g of thioctic acid were added to 12 mL of N,N-dimethylformamide solvent, stirred and mixed, then 0.5 g of 4-dimethylaminopyridine, 0.86 g of N,N-dicyclohexylcarbodiimide were added, stirred at room temperature for 22 h, after the reaction was completed, the solvent was removed by rotary evaporation, washed and dried to obtain intermediate 2;

[0045] (3) 3.14 g of chloroacetic acid was added to 13 mL of anhydrous ethanol solvent, cooled to 2°C in an ice bath, and 0.55 g of a 40% mass fraction sodium hydroxide aqueous solution was slowly added dropwise, then 2.16 g of intermediate 2 was added, stirred and mixed, and then the temperature was increased to 65°C under the protection of nitrogen gas, and the reaction was performed for 9 h. After the reaction was completed, filtration, purification and drying were performed to obtain intermediate 3;

[0046] (4) 1.62 g of chitosan was swelled in 16 mL of a 3% mass fraction acetic acid solution for 1.5 h, 2.26 g of intermediate 3, 0.25 g of N,N-methylene bisacrylamide, 0.7 g of silver nitrate were added, nitrogen was introduced for 12 min, then 0.31 g of azobisisobutyronitrile catalyst was added, and the mixture was subjected to oil bath treatment at 70°C for 7 h. After the reaction was completed, the mixture was dialyzed in a dialysis bag with a molecular weight cut-off of 3400 for 42 h, washed and dried to obtain modified chitosan;

[0047] (5) 4.04 g of sodium alginate was added to 80 mL of deionized water, and magnetic stirring was performed until complete dissolution. Nitrogen was introduced for 12 min, then 1.97 g of epichlorohydrin, 6.46 mL of N,N-dimethyldecylamine were added, stirred and mixed, and the reaction was performed at 42°C for 22 h. After the reaction was completed, washing, suction filtration and drying were performed to obtain intermediate 4;

[0048] (6) 2.35 g of intermediate 4, 2.06 g of cinnamic acid were added to 22 mL of ethanol solution, stirred uniformly, then 0.35 g of N,N'-dicyclohexylcarbodiimide was added, and the reaction was performed at 70°C for 3.5 h. After the reaction was completed, washing and drying were performed to obtain modified sodium alginate;

[0049] (7) 5 parts by weight of modified chitosan, 4 parts by weight of modified sodium alginate, 1.5 parts by weight of carrageenan were dispersed in 9 parts by weight of deionized water, stirred at 45°C until completely dissolved, then 0.5 parts by weight of citric acid, 0.9 parts by weight of glycerol were added, and stirred magnetically for 1.5 h, and placed at room temperature for 18 h, to obtain a sustained-release dressing with antibacterial and hemostatic functions.

[0050] Example 4

[0051] (1) 26 mL of tetrahydrofuran solvent was added to the reactor, pre-cooled in a cold hydrazine at -9°C for 21 min, then 4.43 g of ethylene glycol diglycidyl ether, 2.59 g of 1,3-propanedithiol, 0.11 g of lithium hydroxide were added, stirred uniformly, stirred in an ice water bath at 1°C for 6 h, after the reaction was completed, centrifuged, rotary evaporated to remove the solvent, and dried to obtain intermediate 1;

[0052] (2) Under the protection of nitrogen gas, 3.85 g of intermediate 1, 0.72 g of thioctic acid were added to 11 mL of N,N-dimethylformamide solvent, stirred and mixed, then 0.49 g of 4-dimethylaminopyridine, 0.85 g of N,N-dicyclohexyl carbodiimide were added, stirred at room temperature for 21 h, after the reaction was completed, the solvent was removed by rotary evaporation, washed and dried to obtain intermediate 2;

[0053] (3) 3.13 g of chloroacetic acid was added to 13 mL of anhydrous ethanol solvent, cooled to 1°C in an ice bath, then 0.5 g of 40% mass fraction sodium hydroxide aqueous solution was slowly added dropwise, then 2.15 g of intermediate 2 was added, stirred and mixed, heated to 62°C under the protection of nitrogen gas for 8 h, after the reaction was completed, filtered, purified and dried to obtain intermediate 3;

[0054] (4) 1.61 g of chitosan was swelled in 16 mL of 3% mass fraction acetic acid solution for 1 h, then 2.26 g of intermediate 3, 0.24 g of N,N-methylene bisacrylamide, 0.6 g of silver nitrate were added, nitrogen was introduced for 11 min, then 0.3 g of azobisisobutyronitrile catalyst was added, and oil bath was carried out at 68°C for 6 h, after the reaction was completed, the mixture was dialyzed in a dialysis bag with a molecular weight cut-off of 3300 for 40 h, washed and dried to obtain modified chitosan;

[0055] (5) 4.03 g of sodium alginate was added to 79 mL of deionized water, stirred magnetically until completely dissolved, then nitrogen was introduced for 11 min, then 1.96 g of epichlorohydrin, 6.45 mL of N,N-dimethyldecylamine were added, stirred and mixed, and reacted at 41°C for 21 h, after the reaction was completed, washed, suction filtered and dried to obtain intermediate 4;

[0056] (6) 2.34 g of intermediate 4, 2.05 g of cinnamic acid, and 0.3 g of N,N'-dicyclohexyl carbodiimide were added to 21 mL of an ethanol solution, stirred uniformly, and then reacted at 65°C for 3 h. After the reaction was completed, washing and drying were performed to obtain modified sodium alginate;

[0057] (7) 4 parts by weight of modified chitosan, 4 parts by weight of modified sodium alginate, and 1 part by weight of carrageenan were dispersed in 9 parts by weight of deionized water, stirred at 42°C until completely dissolved, 0.5 parts by weight of citric acid and 0.9 parts by weight of glycerol were further added thereto, and then stirred by magnetic force for 1 h. After that, the mixture was left to stand at room temperature for 15 h to obtain a sustained-release dressing having an antibacterial hemostatic function.

[0058] Example 5

[0059] (1) 29 mL of a tetrahydrofuran solvent was added to a reactor, pre-cooled in a cold hydrazine at -11°C for 24 min, and then 4.45 g of ethylene glycol diglycidyl ether, 2.61 g of 1,3-propanedithiol, and 0.13 g of lithium hydroxide were added thereto, stirred uniformly, and then stirred in an ice water bath at 4°C for 7 h. After the reaction was completed, centrifugation, removal of the solvent by rotary evaporation, and drying were performed to obtain intermediate 1;

[0060] (2) 3.87 g of intermediate 1 and 0.74 g of lipoic acid were added to 14 mL of an N,N-dimethylformamide solvent under nitrogen gas protection, stirred and mixed, and then 0.51 g of 4-dimethylaminopyridine and 0.87 g of N,N-dicyclohexyl carbodiimide were added thereto, stirred at room temperature for 23 h. After the reaction was completed, the solvent was removed by rotary evaporation, and washing and drying were performed to obtain intermediate 2;

[0061] (3) 3.15 g of chloroacetic acid was added to 14 mL of an anhydrous ethanol solvent, cooled to 4°C in an ice bath, and then 0.6 g of a 40% by mass sodium hydroxide aqueous solution was slowly added dropwise. Then, 2.17 g of intermediate 2 was added thereto, stirred and mixed, and then reacted at 68°C for 10 h under nitrogen gas protection. After the reaction was completed, filtration, purification, and drying were performed to obtain intermediate 3;

[0062] (4) 1.63 g of chitosan was swelled in 17 mL of a 3% by mass acetic acid solution for 2 h, and then 2.27 g of intermediate 3, 0.26 g of N,N-methylene bisacrylamide, 0.8 g of silver nitrate, and 0.32 g of azobisisobutyronitrile catalyst were added thereto. Then, the mixture was subjected to oil bath at 72°C for 8 h. After the reaction was completed, the mixture was dialyzed in a dialysis bag having a molecular weight cut-off of 3500 for 45 h, and then washing and drying were performed to obtain modified chitosan;

[0063] (5) 4.05 g of sodium alginate was added into 81 mL of deionized water, and stirred by magnetic force until completely dissolved, and then 1.98 g of epichlorohydrin, 6.47 mL of N, N-dimethyl decylamine were added, and the mixture was stirred and reacted at 44°C for 23 h. After the reaction was completed, the product was washed, filtered and dried to obtain intermediate 4;

[0064] (6) 2.36 g of intermediate 4, 2.07 g of cinnamic acid were added into 24 mL of ethanol solution, and stirred until uniform, and then 0.4 g of N, N'-dicyclohexyl carbodiimide was added, and the mixture was reacted at 75°C for 4 h. After the reaction was completed, the product was washed and dried to obtain modified sodium alginate;

[0065] (7) 5 parts by weight of modified chitosan, 5 parts by weight of modified sodium alginate, 2 parts by weight of carrageenan were dispersed in 10 parts by weight of deionized water, and stirred until completely dissolved at 48°C, and then 0.6 parts by weight of citric acid, 0.9 parts by weight of glycerol were added, and the mixture was stirred by magnetic force for 2 h, and then placed at room temperature for 20 h to obtain the sustained-release dressing with antibacterial and hemostatic functions.

[0066] Comparative Example 1

[0067] The difference between this comparative example and Example 5 is that chitosan is used instead of modified chitosan.

[0068] Comparative Example 2

[0069] The difference between this comparative example and Example 5 is that sodium alginate is used instead of modified sodium alginate.

[0070] Performance test:

[0071] The sustained-release dressings prepared in Examples 1-5 and Comparative Examples 1-2 were tested for performance.

[0072] (1) The antibacterial performance test method is as follows: according to YY / T 0594 "Test method for antibacterial performance of medical devices", the prepared dressing was placed on an agar plate inoculated with Escherichia coli and Staphylococcus aureus, and the antibacterial performance was evaluated by observing the size of the inhibition zone. The test results are shown in Table 1.

[0073] Table 1 Antibacterial performance test table Item Inhibition rate of E. coli (%) Inhibition rate of S. aureus (%) Example 1 94.6 93.5 Example 2 96.1 95.3 Example 3 95.5 94.8 Example 4 94.8 94.2 Example 5 95.2 95.1 Comparative Example 1 86.9 87.2 Comparative Example 2 89.7 90.0

[0074] As can be seen from Table 1, the sustained-release dressings prepared in Examples 1-5 have higher bacteriostatic rates than the sustained-release dressings prepared in Comparative Examples 1-2, and have good antibacterial performance.

[0075] (2) The hemostatic performance test method is as follows: according to YY / T 1487-2016 "Medical Dressing Hemostatic Performance Evaluation Method", the prepared dressing is covered on the bleeding site of the experimental mouse, and the time from the beginning of the dressing contacting blood to the blood stopping flowing is recorded, and the results are shown in Table 2.

[0076] Table 2 Hemostatic performance test table Item Clotting time (s) Example 1 50 Example 2 45 Example 3 48 Example 4 49 Example 5 46 Comparative Example 1 83 Comparative Example 2 72

[0077] As can be seen from Table 2, the sustained-release dressings prepared in Examples 1-5 have shorter hemostatic time than the sustained-release dressings prepared in Comparative Examples 1-2, and have good hemostatic performance.

[0078] It should be noted that in this article, the terms "including", "containing" or any other variant thereof are intended to cover non-exclusive inclusion, so that the process, method, article or equipment including a series of elements not only includes those elements, but also includes other elements not explicitly listed, or includes elements inherent to such process, method, article or equipment. Without more limitations, the element defined by the statement "including a" does not exclude the presence of other identical elements in the process, method, article or equipment including the element.

[0079] The above examples are only used to illustrate the technical solutions of the present application, but not to limit it; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that they can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacement for part of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

[0080] Those skilled in the art should understand that the above only describes several specific embodiments of the present application, rather than all embodiments. It should be noted that many modifications and improvements can be made by those skilled in the art, and all modifications and improvements that do not exceed the scope of the claims should be considered as the protection scope of the present application.

Claims

1. A sustained-release dressing with antibacterial and hemostatic functions, characterized in that, It includes the following components by weight: 4-6 parts by weight of modified chitosan, 3-5 parts by weight of modified sodium alginate, 1-2 parts by weight of carrageenan, 0.5-0.6 parts by weight of citric acid, 0.8-1 parts by weight of glycerol, and 8-10 parts by weight of deionized water.

2. The sustained-release dressing with antibacterial and hemostatic functions according to claim 1, characterized in that, The method for preparing the modified chitosan is as follows: Step 1: Add tetrahydrofuran solvent to the reactor and pre-cool it in cold hydrazine at -8 to -12℃ for 20-25 min. Then add ethylene glycol diglycidyl ether, 1,3-propanedithiol and lithium hydroxide, stir well, and stir the reaction in an ice-water bath at 0-5℃ for 5-8 h. After the reaction is completed, centrifuge, remove the solvent by rotary evaporation, and dry to obtain intermediate 1. Step 2: Under nitrogen protection, add intermediate 1 and lipoic acid to N,N-dimethylformamide solvent, stir and mix, then add 4-dimethylaminopyridine and N,N-dicyclohexylcarbodiimide, stir at room temperature for 20-24 h, after the reaction is completed, remove the solvent by rotary evaporation, wash and dry to obtain intermediate 2; Step 3: Add chloroacetic acid to anhydrous ethanol solvent, cool to 0-5℃ in an ice bath, slowly add 40% sodium hydroxide aqueous solution, then add intermediate 2, stir and mix, and react at 60-70℃ for 6-12 hours under nitrogen protection. After the reaction is completed, filter, purify, and dry to obtain intermediate 3. Step 4: Swell chitosan in a 3% acetic acid solution for 1-2 hours, add intermediate 3, N,N-methylenebisacrylamide and silver nitrate, purge with nitrogen for 10-15 minutes, then add azobisisobutyronitrile catalyst, and incubate in an oil bath at 65-75℃ for 6-8 hours. After the reaction is complete, dialyze the mixture in a dialysis bag with a molecular weight cutoff of 3300-3500 for 36-48 hours, wash and dry to obtain modified chitosan.

3. The sustained-release dressing with antibacterial and hemostatic functions according to claim 2, characterized in that, In step one, the ratio of tetrahydrofuran, ethylene glycol diglycidyl ether, 1,3-propanedithiol, and lithium hydroxide is 25-30 mL: 4.42-4.46 g: 2.58-2.62 g: 0.11-0.13 g.

4. The sustained-release dressing with antibacterial and hemostatic functions according to claim 2, characterized in that, In step two, the ratio of N,N-dimethylformamide, intermediate 1, lipoic acid, 4-dimethylaminopyridine, and N,N-dicyclohexylcarbodiimide is 10-15 mL: 3.84-3.88 g: 0.71-0.75 g: 0.48-0.52 g: 0.84-0.88 g.

5. The sustained-release dressing with antibacterial and hemostatic functions according to claim 2, characterized in that, In step three, the ratio of ethanol, chloroacetic acid, sodium hydroxide, and intermediate 2 is 12-15 mL: 3.12-3.16 g: 0.5-0.6 g: 2.14-2.18 g.

6. The sustained-release dressing with antibacterial and hemostatic functions according to claim 2, characterized in that, In step four, the ratio of chitosan, acetic acid, intermediate 3, N,N-methylenebisacrylamide, silver nitrate, and azobisisobutyronitrile is 1.61-1.63g:15-18mL:2.25-2.28g:0.24-0.26g:0.6-0.8g:0.3-0.32g.

7. The sustained-release dressing with antibacterial and hemostatic functions according to claim 1, characterized in that, The modified sodium alginate is prepared by: S1: Add sodium alginate to deionized water, stir magnetically until completely dissolved, purge with nitrogen for 10-15 min, then add epichlorohydrin and N,N-dimethyldecylamine, stir and mix, and react at 40-45℃ for 20-24 h. After the reaction is complete, wash, filter and dry to obtain intermediate 4. S2: Add intermediate 4 and cinnamic acid to the ethanol solution, stir well, then add N,N'-dicyclohexylcarbodiimide, and react at 60-80℃ for 3-4 hours. After the reaction is complete, wash and dry to obtain modified sodium alginate.

8. The sustained-release dressing with antibacterial and hemostatic functions according to claim 7, characterized in that, The ratio of deionized water, sodium alginate, epichlorohydrin, and N,N-dimethyldecylamine in S1 is 78-82 mL: 4.02-4.06 g: 1.96-1.98 g: 6.44-6.48 mL.

9. The sustained-release dressing with antibacterial and hemostatic functions according to claim 7, characterized in that, The ratio of ethanol, intermediate 4, cinnamic acid, and N,N'-dicyclohexylcarbodiimide in S2 is 20-25 mL: 2.33-2.37 g: 2.04-2.08 g: 0.3-0.4 g.

10. A method for preparing a sustained-release dressing with antibacterial and hemostatic functions according to any one of claims 1-9, characterized in that, Modified chitosan, modified sodium alginate, and carrageenan are dispersed in deionized water and stirred at 40-50℃ until completely dissolved. Citric acid and glycerin are then added, and the mixture is magnetically stirred for 1-2 hours. The mixture is then left at room temperature for 12-24 hours to obtain a sustained-release dressing with antibacterial and hemostatic functions.

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