An antibacterial wound dressing and a method of making the same

Abstract

The application relates to the technical field of skin damage repair, and discloses an antibacterial wound dressing and a preparation process thereof, wherein the wound dressing comprises a nucleotide / sodium carboxymethyl cellulose compound and an auxiliary material; the nucleotide / sodium carboxymethyl cellulose compound is prepared by addition and dehydration of nucleotides and sodium carboxymethyl cellulose. The five-carbon sugar structure contained in the molecular structure of the nucleotide / sodium carboxymethyl cellulose compound has the effect of enhancing and toughening; the nitrogen base structure connected to the five-carbon sugar has strong positive electricity, and can cause inactivation of bacteria and microorganisms; the existence of the organic base and the hydroxyl group makes the nucleotide / sodium carboxymethyl cellulose compound have good self-assembly film forming property, provides a safe and sterile environment for wound healing, and promotes the healing of the wound; in addition, the alginate oligosaccharide and the nucleotide can synergistically act to help scar-free wound healing.

Description

TECHNICAL FIELD

[0001] The present application relates to a medical dressing, in particular to an antibacterial wound dressing and a preparation method thereof. BACKGROUND

[0002] Medical dressing is a kind of medical material which is used to temporarily cover the surface of various wounds. The most important function of medical dressing is to provide a favorable environment for wound healing: protecting the wound, controlling the exudate of the wound, avoiding bacterial and dust pollution. The ideal medical dressing should have the following functions: 1. Good biocompatibility, which can prevent excessive loss of water and body fluid; 2. Good adhesion to the wound surface, and the dressing will not adhere to the wound when removed, which can avoid secondary damage caused by dressing replacement; 3. Resist the invasion of bacteria and harmful particles, prevent infection; 4. Moisture-permeable, air-permeable, absorb excess exudate while maintaining a certain humidity on the contact surface, reducing wound pain; 5. Good mechanical properties, which can provide support for proliferating cells. At present, there is no dressing that can completely meet the above requirements.

[0003] Hydrogel dressing is a new type of wound dressing developed in recent years. It has wide raw material sources, low cost, good elasticity, softness, moisture permeability and air permeability, and no toxic side effects. Compared with traditional dressings, hydrogel dressing has better hydrophilicity, can absorb wound exudate without adhesion to the wound, so that the newly formed granulation or epithelial tissue will not be damaged during dressing change, and the impact on the wound during dressing change is small, thus promoting better wound healing, improving the microenvironment of the wound, inhibiting bacterial growth and reducing patient pain, and thus is very suitable for common body surface injuries such as abrasions, scratches, and bedsores. After the wound heals, the hydrogel can be easily removed or washed off from the skin without leaving fibers and other impurities, and the transparent nature of the hydrogel also allows the patient and the doctor to observe the healing of the wound at any time. In addition, certain drugs can be added to the preparation of hydrogel dressing, which can achieve local antibacterial function when used. Therefore, hydrogel dressings have been the focus of research and development at home and abroad, and good progress has been made. Seprafilm Bioresorbable Membrane produced by Genzyme Company of the United States can be used for preventing postoperative adhesion in abdominal surgery. DuoDERM Hydroactive Gel produced by Convatec can be used for the treatment of surface skin ulcers, bedsores, etc. The existing hydrogel dressings have achieved good results in clinical application, but there is still room for development in enhancing antibacterial properties.

[0004] The commonly used hydrogel raw materials include chitosan, cellulose, alginic acid, fibrin, collagen, polyvinyl alcohol, etc. Cellulose is the largest organic resource on earth, which can be divided into plant cellulose, animal cellulose and bacterial cellulose. Sodium carboxymethyl cellulose (CMC) is a water-soluble cellulose ether, which can be used as a binder for tablets, an emulsifier for injections and a film-forming agent in the pharmaceutical industry. Studies have shown that CMC has better effect than hyaluronic acid in reducing postoperative peritoneal adhesion. However, the mechanical strength of CMC cannot meet the use requirements in some application scenarios, and its antibacterial property needs to be improved. SUMMARY

[0005] In order to solve the problems of the prior art, the present application provides an antibacterial wound dressing and a preparation process thereof.

[0006] In one aspect, the present application provides an antibacterial wound dressing, which comprises a nucleotide / sodium carboxymethyl cellulose complex, brown algal oligosaccharide and adjuvant.

[0007] In some embodiments of the present application, the preparation method of the nucleotide / sodium carboxymethyl cellulose complex comprises the following steps:

[0008] S1: Dissolve sodium carboxymethyl cellulose in deionized water, and after complete dissolution, add an oxidizing agent dropwise, adjust the pH of the system to be acidic, stir the system under dark conditions, and obtain oxidized sodium carboxymethyl cellulose by precipitation, washing and freeze-drying;

[0009] S2: Dissolve the oxidized sodium carboxymethyl cellulose obtained in S1 and nucleotides in deionized water, adjust the pH of the system to be acidic, and perform reaction under heating reflux condition. After the reaction is completed, freeze-dry the product to obtain the nucleotide / sodium carboxymethyl cellulose complex.

[0010] In some embodiments of the present application, when preparing the nucleotide / sodium carboxymethyl cellulose complex, the degree of substitution of sodium carboxymethyl cellulose in S1 is 0.85-1.20, and the mass concentration of the solution formed by dissolving in deionized water is 0.05-0.1 g / ml; the oxidizing agent is one of periodate, hypochlorite and permanganate, and the use mass concentration of the oxidizing agent is 0.10-0.15 g / ml.

[0011] The degree of substitution of carboxymethyl cellulose refers to the number of hydroxyl groups substituted by carboxymethyl groups on each structural unit, and since there are three hydroxyl groups on each structural unit of the cellulose molecular chain, the degree of substitution is not greater than 3. The degree of substitution has a certain influence on the solubility of carboxymethyl cellulose, and as the degree of substitution increases, the solubility of carboxymethyl cellulose is better, and the temperature resistance of carboxymethyl cellulose with a lower degree of substitution is insufficient, which may affect its use as a wound dressing. In the present application, the inventors found through comparative tests that the greater the degree of substitution of sodium carboxymethyl cellulose, the more difficult the reaction with nucleotides after oxidation. The inventors speculate that this may be related to the steric hindrance effect, since the nucleotide molecule itself has a five-carbon sugar structure and a nitrogen-containing heterocycle, if the degree of substitution of sodium carboxymethyl cellulose is high, the repulsion between the two molecules is greatly increased, resulting in a higher reaction energy for the addition reaction of the carbonyl group and the amino group. However, nucleotides are not stable under high temperature conditions, therefore, in order to obtain a nucleotide / sodium carboxymethyl cellulose complex with more ideal structure and purity, sodium carboxymethyl cellulose with a degree of substitution of 0.85-1.20 is selected as one of the raw materials for preparation, and the specific selection can be: pharmaceutical grade cross-linked sodium carboxymethyl cellulose (CAS number 74811-65-7) from Shanxi Jinyang Pharmaceutical Auxiliary Material Co., Ltd., pharmaceutical grade sodium carboxymethyl cellulose (CAS number 9004-32-4) from Rui Cheng Kang Pharmaceutical Technology (Shaanxi) Co., Ltd., and medical grade cross-linked sodium carboxymethyl cellulose (CAS number 74811-65-7) from Shaanxi Yangyuanshen Biological Technology Co., Ltd.

[0012] The degree of substitution of carboxymethyl cellulose refers to the number of hydroxyl groups substituted by carboxymethyl groups on each structural unit, and since there are three hydroxyl groups on each structural unit of the cellulose molecular chain, the degree of substitution is not greater than 3. The degree of substitution has a certain influence on the solubility of carboxymethyl cellulose, and as the degree of substitution increases, the solubility of carboxymethyl cellulose is better, and the temperature resistance of carboxymethyl cellulose with a lower degree of substitution is insufficient, which may affect its use as a wound dressing. In the present application, the inventors found through comparative tests that the greater the degree of substitution of sodium carboxymethyl cellulose, the more difficult the reaction with nucleotides after oxidation. The inventors speculate that this may be related to the steric hindrance effect, since the nucleotide molecule itself has a five-carbon sugar structure and a nitrogen-containing heterocycle, if the degree of substitution of sodium carboxymethyl cellulose is high, the repulsion between the two molecules is greatly increased, resulting in a higher reaction energy for the addition reaction of the carbonyl group and the amino group. However, nucleotides are not stable under high temperature conditions, therefore, in order to obtain a nucleotide / sodium carboxymethyl cellulose complex with more ideal structure and purity, sodium carboxymethyl cellulose with a degree of substitution of 0.85-1.20 is selected as one of the raw materials for preparation, and the specific selection can be: pharmaceutical grade cross-linked sodium carboxymethyl cellulose (CAS number 74811-65-7) from Shanxi Jinyang Pharmaceutical Auxiliary Material Co., Ltd., pharmaceutical grade sodium carboxymethyl cellulose (CAS number 9004-32-4) from Rui Cheng Kang Pharmaceutical Technology (Shaanxi) Co., Ltd., and medical grade cross-linked sodium carboxymethyl cellulose (CAS number 74811-65-7) from Shaanxi Yangyuanshen Biological Technology Co., Ltd.

[0013]

[0014] wherein B is the millimoles of carboxymethyl groups contained in each gram of sample, mmol / g; V1 is the volume value of the sulfuric acid standard titration solution, mL; c1 is the concentration of the sulfuric acid standard titration solution, 0.05055 mol / L; and m is the mass of the purified sample, g.

[0015] In some embodiments of the present application, the volume ratio of the aqueous sodium carboxymethyl cellulose solution to the aqueous oxidizing agent solution is 2:0.8-1 when the sodium carboxymethyl cellulose is oxidized.

[0016] In some embodiments of the present application, the pH of the oxidation system is adjusted to 3-5, the reaction temperature is 35-40℃, and the reaction time is 4-5h.

[0017] In some embodiments of the present application, the nucleotide used is one or more of adenine nucleotide, guanine nucleotide, xanthine nucleotide, cytosine nucleotide, and thymine nucleotide, and derivatives of the aforementioned nucleotides. The nucleotide molecule structure comprises a base, a phosphate, and a five-carbon sugar, and the synthesis of the nucleotide / sodium carboxymethyl cellulose complex is completed by the Schiff base reaction between the base in the molecule and the carbonyl group on the oxidized carboxymethyl cellulose molecule. The type of amino group carried by the base has a very important influence on the dehydration reaction after addition. Primary and secondary amines can ultimately form carbon-nitrogen double bonds with carbonyl groups, but tertiary amines cannot undergo Schiff base reaction with carbonyl groups. Therefore, in the present application, one of adenine nucleotide, guanine nucleotide, xanthine nucleotide, cytosine nucleotide, and thymine nucleotide can be selected as the nucleotide raw material. In addition, derivatives of the aforementioned nucleotides, such as adenosine 5'-2-thiophosphate trihydride, 2'-deoxy-5'-O-acetylguanosine 3'-diphosphate trihydride, xanthosine 3'-diphosphate trihydride, etc., have phosphate groups connected to the carbon atoms of the five-carbon sugar, and the number of phosphate groups is different, and can also be one of the choices of nucleotides.

[0018] In some embodiments of the present application, the mass ratio of the obtained oxidized sodium carboxymethyl cellulose to the nucleotide is 3:5-7. The oxidized sodium carboxymethyl cellulose and the nucleotide undergo Schiff base reaction for grafting, and the obtained complex has more groups that can form hydrogen bonds, such as hydroxyl groups, carboxyl groups, nitrogen-containing carbon rings, etc., and has good self-assembly film-forming property. However, when the preparation conditions are explored, the inventors found that when the nucleotide is added too much, the viscosity of the obtained complex increases, and it cannot be well cast into a film. If the amount of nucleotide added is small, the self-assembly property of the obtained complex is insufficient, and the film-forming is slow. In summary, the mass ratio of the oxidized sodium carboxymethyl cellulose to the nucleotide is 3:5-7.

[0019] In some embodiments of the present application, the reaction temperature in the preparation of the nucleotide / sodium carboxymethyl cellulose complex is 35-45℃, and the reaction pH is 5-6.

[0020] In some embodiments of the present application, the molecular weight of the fucoidan is not less than 1000; because the molecular weight of all fucoidan on the market varies, to ensure that the antibacterial wound dressing functions more stably and effectively, the fucoidan purchased from the market is purified in the present application: a dialysis bag with a molecular weight of 1000 that can dialysis is soaked in deionized water for 10 min, and the inner membrane is washed with deionized water for 3 times; the dialysis bag is clamped at one end, filled with deionized water, and then the fucoidan is loaded, and the sample loading end is clamped, and then placed in a beaker for 24 h. The fucoidan in the dialysis bag is extracted using a dialysis dehydrating agent to obtain the fucoidan required by the present application.

[0021] In some embodiments of the present application, the adjuvant comprises at least one of an antibacterial peptide, silk fibroin, chitosan, hyaluronic acid, and sodium alginate.

[0022] In another aspect, the present application also provides a preparation method for preparing the antibacterial wound dressing, comprising the following steps: dissolving the nucleotide / carboxymethyl cellulose sodium complex in deionized water to form an aqueous sol A; dissolving the fucoidan and the adjuvant in an organic acid to form a solution B; mixing the solution B in the aqueous sol A at room temperature and stirring and incubating, and then the obtained mixed gel liquid is cast into a film at room temperature, and then dried at a temperature of 30-40℃ to form a film or freeze-dried to form a film, thereby obtaining the antibacterial wound dressing.

[0023] In some embodiments of the present application, in the aqueous sol A, the mass concentration of the nucleotide / carboxymethyl cellulose sodium complex is 1.5-2.8 g / ml, in the solution B, the mass concentration of the fucoidan is 0.001-0.002 mg / ml; the mass concentration of the adjuvant is 0.10-0.15 g / ml; and the mixing volume ratio of the aqueous sol A and the solution B is 10:1-2.

[0024] Beneficial effects: compared with the prior art, the antibacterial wound dressing provided by the present application contains self-prepared nucleotide / carboxymethyl cellulose sodium complex, the nucleotide reacts with the carbonyl group of the oxidized carboxymethyl cellulose sodium through the base in the molecule to form a complex containing oxygen-containing five-membered carbon ring, phosphoric acid and carbon-nitrogen double bond:

[0025] 1. The presence of the oxygen-containing five-membered carbon ring enhances the toughness of the antibacterial wound dressing; the presence of the phosphoric acid provides energy for cell proliferation during wound healing, and also provides an antioxidant environment to accelerate the healing speed; the carbon-nitrogen double bond forms a Schiff base structure to improve the antibacterial property of the antibacterial wound dressing;

[0026] 2, the nucleotide / carboxymethyl cellulose sodium complex also has more hydrogen bond forming groups, mixed with excipients, intermolecular crosslinking to form a network structure, has self-assembly into a film, on the one hand, the nucleotide structure can be protected from the outside environment is destroyed, continuous for cell proliferation to provide energy, on the other hand, the final formation of the dressing good air permeability and hygroscopicity, can provide a good barrier for wound healing;

[0027] 3, the additional addition of alginate oligosaccharide can synergistically act with nucleotide, further provide good anti-inflammatory and antioxidant effect, make the wound heal faster, and not easy to leave scar after healing. DETAILED DESCRIPTION

[0028] The application will be further described in conjunction with examples. It should be noted that the following examples and comparative examples are examples of the present application, only used to illustrate the present application, and not used to limit the present application. Without deviating from the main idea or scope of the present application, other combinations and various modifications within the concept of the present application can be made.

[0029] The following exemplary preparation of nucleotide / carboxymethyl cellulose sodium complex used in the examples is described:

[0030] Complex-1

[0031] S1: 1g of carboxymethyl cellulose sodium with a degree of substitution of 0.87 was dissolved in 20ml of deionized water, and after complete dissolution, a carboxymethyl cellulose aqueous solution with a mass concentration of 0.05g / ml was obtained, 10ml of 0.12g / ml sodium periodate solution was added, and the pH of the system was adjusted to 3 with concentrated sulfuric acid, and after stirring at 35℃ in the dark for 5h, the product was precipitated, washed, and freeze-dried to obtain oxidized carboxymethyl cellulose sodium;

[0032] S2: 0.3g of the oxidized carboxymethyl cellulose sodium obtained in S1 was dissolved in deionized water with 0.5g of adenosine nucleotide, the pH of the system was adjusted to 5, and the reaction was carried out under the condition of heating and refluxing to remove water for 12h, and after the reaction was completed, the product was freeze-dried to obtain the nucleotide / carboxymethyl cellulose sodium complex-1.

[0033] Complex-2

[0034] S1: 1g of carboxymethyl cellulose sodium with a degree of substitution of 1.12 was dissolved in 20ml of deionized water, and after complete dissolution, a carboxymethyl cellulose aqueous solution with a mass concentration of 0.05g / ml was obtained, 10ml of 0.12g / ml sodium periodate solution was added, and the pH of the system was adjusted to 3 with concentrated sulfuric acid, and after stirring at 35℃ in the dark for 5h, the product was precipitated, washed, and freeze-dried to obtain oxidized carboxymethyl cellulose sodium;

[0035] S2: 0.3 g of the oxidized carboxymethylcellulose sodium obtained in S1 was dissolved in deionized water together with 0.6 g of xanthine nucleotide, the pH of the system was adjusted to 5, and the reaction was carried out under the condition of heating and refluxing to remove water for 12 h. After the reaction was completed, the product was freeze-dried to obtain the nucleotide / carboxymethylcellulose sodium complex-2.

[0036] Complex-3

[0037] S1: 1 g of carboxymethylcellulose sodium with a degree of substitution of 1.19 was dissolved in 20 ml of deionized water to obtain a carboxymethylcellulose aqueous solution with a mass concentration of 0.05 g / ml. Then, 10 ml of 0.12 g / ml sodium periodate solution was added, and the pH of the system was adjusted to 3 with concentrated sulfuric acid. After stirring at 35 °C in the dark for 5 h, the product was precipitated, washed, and freeze-dried to obtain oxidized carboxymethylcellulose sodium.

[0038] S2: 0.3 g of the oxidized carboxymethylcellulose sodium obtained in S1 was dissolved in deionized water together with 0.7 g of thymine nucleotide, the pH of the system was adjusted to 6, and the reaction was carried out under the condition of heating and refluxing to remove water for 12 h. After the reaction was completed, the product was freeze-dried to obtain the nucleotide / carboxymethylcellulose sodium complex-3.

[0039] Complex-4

[0040] The preparation process was similar to that of complex-1, except that the mass of adenine nucleotide used was 0.45 g.

[0041] Complex-5

[0042] The preparation process was similar to that of complex-3, except that the mass of thymine nucleotide used was 0.75 g.

[0043] Complex-6

[0044] The preparation process was similar to that of complex-3, except that the degree of substitution of carboxymethylcellulose sodium used was 1.30.

[0045] Complex-7

[0046] The preparation process was similar to that of complex-3, except that the degree of substitution of carboxymethylcellulose sodium used was 1.40.

[0047] Example 1

[0048] The nucleotide / sodium carboxymethyl cellulose complex-1 is dissolved in deionized water to form an aqueous sol A with a mass concentration of 1.5 g / ml; the fucoidan and the antimicrobial peptide are sequentially dissolved in acetic acid to form a solution B with a fucoidan mass concentration of 0.001 mg / ml and an antimicrobial peptide mass concentration of 0.15 g / ml; 1 ml of the solution B is mixed with 10 ml of the aqueous sol A at room temperature, and stirred and incubated, and the obtained mixed sol is cast into a film at room temperature, and freeze-dried to form a film, thereby obtaining the antibacterial wound dressing.

[0049] Example 2

[0050] The nucleotide / sodium carboxymethyl cellulose complex-2 is dissolved in deionized water to form an aqueous sol A with a mass concentration of 2.0 g / ml; the fucoidan and the silk fibroin are sequentially dissolved in acetic acid to form a solution B with a fucoidan mass concentration of 0.001 mg / ml and a silk fibroin mass concentration of 0.12 g / ml; 2 ml of the solution B is mixed with 10 ml of the aqueous sol A at room temperature, and stirred and incubated, and the obtained mixed sol is cast into a film at room temperature, and freeze-dried to form a film, thereby obtaining the antibacterial wound dressing.

[0051] Example 3

[0052] The nucleotide / sodium carboxymethyl cellulose complex-3 is dissolved in deionized water to form an aqueous sol A with a mass concentration of 2.8 g / ml; the fucoidan and the chitosan are sequentially dissolved in acetic acid to form a solution B with a fucoidan mass concentration of 0.002 mg / ml and a chitosan mass concentration of 0.15 g / ml; 3 ml of the solution B is mixed with 15 ml of the aqueous sol A at room temperature, and stirred and incubated, and the obtained mixed sol is cast into a film at room temperature, and freeze-dried to form a film, thereby obtaining the antibacterial wound dressing.

[0053] Example 4

[0054] The operation steps are the same as those in Example 3, except that the complex-4 is used instead of the complex-3.

[0055] Example 5

[0056] The operation steps are the same as those in Example 3, except that the complex-5 is used instead of the complex-3.

[0057] Example 6

[0058] The operation steps are the same as those in Example 3, except that the complex-6 is used instead of the complex-3.

[0059] Example 7

[0060] The operation steps are the same as those in Example 3, except that the complex-7 is used instead of the complex-3.

[0061] Comparative Example 1

[0062] The operation steps are the same as in Example 3, except that carboxymethyl cellulose is used instead of complex-3.

[0063] The antibacterial wound dressings obtained in Examples 1-7 and Comparative Example 1 were subjected to the following performance tests:

[0064] Antibacterial properties: The obtained antibacterial wound dressing was cut into circular gel samples with a diameter of 10 mm and a thickness of 2 mm. 0.1 ml of Staphylococcus aureus was placed in beef broth and incubated at 37°C for 24 h. The mixture was then diluted 10... -6 Prepare a bacterial suspension by dilution, transfer 0.1 ml of the suspension to the surface of the gel sample, and incubate for 12 hours. Wash the dressing sample with sterile water, take 0.1 ml of the washing solution, and continue incubating on a petri dish for 24 hours. Record the number of colonies on the petri dish and perform a blank control test using the formula. Calculate the antibacterial rate of the sample, where S0 is the number of colonies in the blank control experimental group, S1 is the number of colonies in each sample, and P is the antibacterial rate.

[0065] Wound healing: The antibacterial wound dressing prepared according to this invention was used to clinically observe and treat wounds in 27 mice. The average age of the mice was 24 months. The artificial wound area was 20mm × 20mm, and the wound site was the back of the mouse. All wounds were anesthetized and disinfected. The 27 mice were divided into 9 groups, each corresponding to the wound covered with the antibacterial wound dressing obtained in Examples 1-7 and Comparative Example 1, and a blank control group without dressing treatment. The wound dressing was changed at 09:00 every day for the first 3 days after injury. After 3 days of injury, the wound dressing was changed every 2 days at 09:00 until the wound healed. The wound was observed throughout the dressing change period.

[0066] The test results of the antibacterial wound dressings obtained in Examples 1-7 and Comparative Example 1, as well as the blank group, are shown in Table 1:

[0067]

[0068] As shown in the above table, the antibacterial wound dressings prepared in Examples 1-5 can all make the wound of the mouse heal in about 7 days, and the wound is completely healed in about 13 days without obvious scar. The wound dressings prepared in Examples 4-5 have slight redness in about 3 days, which may be caused by the change of the amount of nucleotide, affecting the air permeability of the wound dressing. The antibacterial wound dressings prepared in Examples 6-7 have a high degree of substitution of sodium carboxymethyl cellulose, affecting the healing speed of the wound, although there is no obvious infection, the wound is completely healed in about 13 days. The antibacterial wound dressing prepared in Comparative Example 1 has slight infection in about 3 days, and the wound is completely healed in about 15 days with a scar, which shows that the presence of carboxymethyl cellulose and alginate oligosaccharide cannot achieve ideal healing without scar; the wound of the blank group has obvious infection in about 3 days, and the wound is completely healed in about 17 days. The above differences are caused by the presence of nucleotide, which provides energy for cell proliferation, effectively accelerates the healing speed of the wound, and also serves as a raw material for protein synthesis, assisting cells to produce collagen, which is beneficial to the wound without scar. Therefore, the antibacterial wound dressing prepared in the application can effectively block the invasion of bacteria, accelerate the healing speed of the wound, and will not leave obvious scar after the wound is healed, which has good application prospect in the medical field.

Claims

1. An antibacterial wound dressing, characterized in that, It contains a nucleotide / sodium carboxymethyl cellulose complex, fucoidan oligosaccharides, and excipients; The preparation method of the nucleotide / sodium carboxymethyl cellulose complex includes the following steps: S1: Dissolve sodium carboxymethyl cellulose in deionized water. After complete dissolution, add an oxidant and adjust the pH of the system to acidic. Stir the reaction under dark conditions. The product is precipitated, washed, and freeze-dried to obtain oxidized sodium carboxymethyl cellulose. S2: Dissolve the sodium oxidized carboxymethyl cellulose obtained in S1 and the nucleotide in deionized water, adjust the pH of the system to acidic, and carry out the reaction under reflux conditions. After the reaction is completed, freeze-dry the product to obtain the nucleotide / sodium carboxymethyl cellulose complex. The degree of substitution of sodium carboxymethyl cellulose in S1 is 0.85-1.20; The mass ratio of sodium oxidized carboxymethyl cellulose to nucleotides obtained in S1 is 3:5-7.

2. The antibacterial wound dressing according to claim 1, characterized in that, The mass concentration of the solution formed by dissolving in deionized water is 0.05-0.1 g / ml; the oxidant is one of periodate, hypochlorite, and permanganate, and the mass concentration of the oxidant used is 0.10-0.15 g / ml.

3. The antibacterial wound dressing according to claim 1, characterized in that, The volume ratio of the sodium carboxymethyl cellulose aqueous solution to the oxidant aqueous solution in S1 is 2:0.8-1.

4. The antibacterial wound dressing according to claim 1, characterized in that, The pH of the system described in S1 is adjusted to 3-5, the reaction temperature is 35-40℃, and the reaction time is 4-5h.

5. The antibacterial wound dressing according to claim 1, characterized in that, The nucleotides mentioned in S2 are one or more of adenonucleotides, guanosine, cytonucleotides, and the aforementioned nucleotide derivatives.

6. The antibacterial wound dressing according to claim 1, characterized in that, The reaction temperature described in S2 is 35-45℃, and the reaction pH is 5-6.

7. The antibacterial wound dressing according to claim 1, characterized in that, The molecular weight of the brown algae oligosaccharide is not less than 1000; the excipients include at least one of antimicrobial peptides, silk fibroin, chitosan, hyaluronic acid, and sodium alginate.

8. The method for preparing the antibacterial wound dressing according to any one of claims 1-7, characterized in that, The process includes the following steps: dissolving the nucleotide / sodium carboxymethyl cellulose complex in deionized water to form hydrosol A; dissolving the alginate oligosaccharide and excipients in an organic acid to form solution B; mixing solution B with hydrosol A at room temperature and stirring and incubating; casting the resulting mixed solution into a film at room temperature; and drying it at 30-40°C or using freeze-drying to form a film, thereby obtaining the antibacterial wound dressing.

9. The preparation method according to claim 8, characterized in that, In the hydrosol A, the mass concentration of the nucleotide / sodium carboxymethyl cellulose complex is 1.5-2.8 g / ml; in the solution B, the mass concentration of the fucoidan oligosaccharide is 0.001-0.002 mg / ml, and the mass concentration of the excipient is 0.10-0.15 g / ml; the mixing volume ratio of hydrosol A to solution B is 10:1-2.

Images