A modified chitosan surgical suture and preparation method thereof
By using quaternary ammonium carboxymethyl chitosan/silver ion composite antibacterial layer and chitosan layer with growth factor-containing growth factor in chitosan surgical sutures, the problems of short antibacterial time and easy infection in existing sutures are solved, and long-term antibacterial and healing effects are achieved.
Patent Information
- Application Number
- CN202510046608.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-13
- Publication Date
- 2025-04-04
AI Technical Summary
Existing chitosan surgical sutures have short antibacterial time and are prone to infection problems, especially in gynecological surgery.
A quaternary ammonium carboxymethyl chitosan/silver ion composite antibacterial layer and a growth factor-containing chitosan layer were used to combine with an inabsorbable polyester core to form a modified chitosan surgical suture.
It achieves long-term antibacterial properties, promotes wound healing, reduces infection risk, and has good mechanical properties and biocompatibility.
Smart Images
Figure BDA0005238637650000091
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of medical devices, and in particular to a modified chitosan surgical suture and a preparation method thereof. Background Art
[0002] Cervical incompetence refers to the inability of the cervix to bear the increasing weight of the contents of the uterine cavity due to congenital malformations or acquired damage-induced functional defects of the cervix in the absence of clinical uterine contractions and other clear pathological signs and symptoms (such as bleeding, infection, and premature rupture of membranes) in the middle and late stages of pregnancy, leading to late miscarriage or premature birth. The incidence rate has been gradually increasing in recent years. Cervical cerclage is currently one of the most effective methods for treating cervical incompetence. Cervical cerclage includes vaginal cervical cerclage and abdominal cervical cerclage. Abdominal cerclage is the preferred treatment for patients with cervical incompetence and a history of failed vaginal cervical cerclage. Compared with vaginal cervical cerclage, the cerclage of abdominal cervical cerclage is higher in the cervical isthmus, which reduces the slippage of the cerclage band. Because the cerclage band is located in the abdominal cavity, it avoids the risk of infection and premature rupture of membranes caused by leaving the cerclage band in the vagina during vaginal cerclage. In addition, patients can choose to keep the cerclage band after delivery to prepare for the next pregnancy. The current disadvantages of cervical cerclage are: cervical cerclage is an invasive method, which can easily become a predisposing factor for cervical infection or even ascending intrauterine infection; the silk thread used for suture is relatively thin and has a high tension, which can easily cause cutting trauma to cervical tissue, especially when the suture is left in place for a long time, which can more easily damage tissue and cause infection.
[0003] Chitosan is the product of chitin deacetylation in nature. Due to its unique chemical structure, it has excellent properties, such as biodegradability, biocompatibility, antibacterial, non-toxic, anticoagulant properties, etc. It is precisely because chitosan has good biological effects and can be absorbed by organisms that it has very wide applications in many fields such as biomaterials, medical absorbable materials and drug sustained-release materials, as well as other daily chemical industries. In recent years, there has been an increasing number of studies on the application of chitosan in absorbable medical surgical sutures. This is mainly because chitosan can be biodegraded by chitosanase, lysozyme, etc., and the products after degradation have no toxic side effects on the human body, and can also promote epithelial cell growth, platelet aggregation, and wound healing. However, the existing chitosan sutures cannot meet the requirements of cervical cerclage. Based on this, it is urgent to develop a chitosan surgical suture with higher performance. Summary of the invention
[0004] The purpose of the present invention is to provide a modified chitosan surgical suture and a preparation method thereof, to solve the following technical problems:
[0005] Existing chitosan surgical sutures have the problems of short antibacterial time and easy infection in gynecological surgery.
[0006] The purpose of the present invention can be achieved through the following technical solutions:
[0007] A modified chitosan surgical suture, comprising at least:
[0008] The inner core is a non-absorbable polyester suture;
[0009] An antibacterial layer is arranged on the inner core, and the antibacterial layer is a quaternary ammonium salt carboxymethyl chitosan / silver ion composite antibacterial layer;
[0010] The growth-promoting layer is arranged on the antibacterial layer, and the growth-promoting layer at least comprises a chitosan layer encapsulating growth factors.
[0011] As a further solution of the present invention: the thickness of the antibacterial layer is 100-300 μm, and the thickness of the growth-promoting layer is 50-200 μm.
[0012] A method for preparing the modified chitosan surgical suture as described in any one of the above, comprising at least the following preparation steps:
[0013] The inner core is immersed in an antibacterial agent, immersed at 35-45° C. for 30 minutes, taken out and dried, immersed again at 35-45° C. for 30 minutes, dried again, and the immersion and drying steps are repeated at least five times to form an antibacterial layer on the inner core;
[0014] The inner core forming the antibacterial layer is immersed in a growth promoter solution, immersed at 35-45°C for 30 minutes, taken out and dried, immersed at 35-45°C for 30 minutes again, dried again, and the immersion and drying steps are repeated at least five times to form a growth promoter layer on the antibacterial layer to obtain a modified chitosan surgical suture.
[0015] As a further embodiment of the present invention: the preparation method of the growth promoter comprises the following steps:
[0016] Prepare chitosan solution, sodium hyaluronate solution, growth factor solution and sodium tripolyphosphate solution respectively, wherein the chitosan solution is prepared with 1% acetic acid solution, and the rest are prepared with deionized water;
[0017] Under stirring, adding sodium tripolyphosphate solution to the sodium hyaluronate solution to obtain a first pre-cross-linking solution;
[0018] Adding the growth factor solution to the chitosan solution and stirring for 30-40 minutes to obtain a second pre-crosslinking solution;
[0019] The first pre-cross-linking solution is added dropwise to the second pre-cross-linking solution within 20 minutes, and the mixture is stirred at room temperature for 10-20 minutes to obtain a growth promoter.
[0020] As a further embodiment of the present invention: the concentration of the chitosan solution is 0.5-1 mg·mL -1 The concentration of the growth factor solution is 1-3 mg·mL -1 The concentration of the sodium hyaluronate solution is 1-1.5 mg·mL -1 The concentration of the sodium tripolyphosphate solution is 0.5-1 mg·mL -1 .
[0021] As a further embodiment of the present invention: the molar ratio of the sodium tripolyphosphate to the free amino group of the chitosan is 0.1-0.3:1, the mass ratio of the sodium hyaluronate to the chitosan is 1-1.5:1, and the mass ratio of the growth factor to the chitosan is 1:1.5-2.
[0022] As a further embodiment of the present invention: the preparation method of the antibacterial agent comprises the following steps:
[0023] Add carboxymethyl chitosan into deionized water, stir until completely dissolved, adjust the pH value to 10 with sodium hydroxide solution, stir and heat to 70-80°C, add 3-chloro-2-hydroxypropyltrimethylammonium chloride, react for 8-10 hours, and dialysis and purification to obtain a quaternary ammonium salt carboxymethyl chitosan solution;
[0024] Dissolve silver nitrate in deionized water, add sodium hydroxide solution dropwise, and stir continuously until the precipitate no longer increases, then add ammonia solution dropwise until the precipitate is completely dissolved, and filter to obtain a silver ammonia solution;
[0025] The quaternary ammonium salt carboxymethyl chitosan solution is placed in a microwave synthesis reactor, the system temperature is raised to 60-90° C., then the silver ammonia solution is quickly injected, stirring is started to mix evenly, and the reaction is carried out for 40-60 minutes. After the reaction is completed, it is cooled to room temperature, and the antibacterial agent is obtained after purification by dialysis.
[0026] As a further embodiment of the present invention: the mass ratio of the 3-chloro-2-hydroxypropyltrimethylammonium chloride to the carboxymethyl chitosan is 1:4-5, and the mass ratio of the silver nitrate to the carboxymethyl chitosan is 1:1-3.
[0027] Beneficial effects of the present invention:
[0028] The suture prepared in this application includes an inner core and two coating materials coated on the inner core. The inner core is a non-absorbable polyester material with good mechanical properties. It can play a good supporting role in cervical cerclage. The coating close to the inner core is an antibacterial layer, and the other coating is a growth-promoting layer. The inner core and the two coatings cooperate with each other to achieve antibacterial, hemostatic and growth-promoting effects. When the surgical suture is just sutured, the outer growth-promoting layer releases chitosan microspheres containing growth factors, which have hemostatic, antibacterial and growth-promoting effects on the wound, have good drug sustained release and mucosal adhesion, are convenient for cell adhesion and growth, and are beneficial to wound healing. The inner antibacterial layer is a quaternary ammonium carboxymethyl chitosan / silver ion composite antibacterial layer. The quaternary ammonium carboxymethyl chitosan and silver ion are combined with antibacterial, and have strong antibacterial properties against Escherichia coli, Staphylococcus aureus and Candida albicans, can effectively remove bacteria, fungi and other pathogens, and show good sustained release performance. Chitosan is present in both the antibacterial layer and the growth-promoting layer, and the antibacterial effect runs through the entire process of wound healing. The surgical suture of the present invention has the advantages of good mechanical properties, long-lasting antibacterial properties, good hemostatic properties, good biocompatibility, and convenient cell adhesion and tissue growth, and can be applied to suturing of other gynecological surgeries such as cervical cerclage.
[0029] In this application, the cross-linking property of chitosan and hyaluronic acid in the presence of sodium tripolyphosphate is utilized to encapsulate growth factors therein, forming chitosan nanoparticles encapsulating growth factors, forming an outer coating growth-promoting layer, and chitosan degradation releases growth factors, which can promote cell adhesion and proliferation. The chitosan layer encapsulating growth factors in this application not only has mild preparation conditions and a simple preparation method, but also encapsulates bioactive molecules in the cross-linked structure of chitosan and sodium tripolyphosphate, thereby improving the stability of the growth-promoting factors. At the same time, combined with the good antibacterial and hemostatic properties of chitosan itself, it provides a hemostatic effect while suturing the operation, and effectively plays a role in preventing postoperative infection and promoting wound healing.
[0030] This application uses silver ammonia solution as a silver source, carboxymethyl chitosan as a carrier and a reducing agent, and uses a microwave method to synthesize carboxymethyl chitosan / silver ion antibacterial agent. Under the action of microwaves, functional groups such as NH, OH, and -COOH in carboxymethyl chitosan can participate in the synthesis and fixation of silver ions through electrostatic or coordination, thereby realizing the silver ion loading in the carboxymethyl chitosan network structure. Since the silver ion particles in the carboxymethyl chitosan / silver ion antibacterial agent are loaded in the carboxymethyl chitosan polymer network structure, the silver ions can be restricted from oxidative dissolution and release of silver ions; at the same time, the rich functional groups on the carboxymethyl chitosan can produce a strong force with the silver ions, restricting the diffusion of silver ions and showing good sustained-release performance. Carboxymethyl chitosan is a water-soluble derivative of chitosan obtained by carboxylation reaction, which can inhibit the growth of various microorganisms. In the field of gynecological vaginitis treatment, it can not only effectively remove pathogenic bacteria, fungi and other pathogens, but also repair the vaginal mucosa and regulate the local innate immune response. The combined antibacterial effect of carboxymethyl chitosan and silver ions can provide long-term and stable antibacterial effects, and the residual trace metal ions do not cause harm to the human body. DETAILED DESCRIPTION
[0031] The following will be described clearly and completely in conjunction with the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0032] The preparation method of the antibacterial agent of embodiment 1 comprises the following steps:
[0033] 0.3 g of carboxymethyl chitosan was added to 100 mL of deionized water, stirred until completely dissolved, the pH value was adjusted to 10 with 1 mol / L sodium hydroxide solution, the temperature was raised to 80°C with stirring, 0.08 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride was added, the reaction was continued for 8 h, and after purification by dialysis, a quaternary ammonium salt carboxymethyl chitosan solution was obtained;
[0034] Dissolve 0.2 g of silver nitrate in 10 mL of deionized water, add 1 mol / L sodium hydroxide solution drop by drop, and stir continuously until the precipitation no longer increases, then add 2% ammonia solution drop by drop until the precipitation is completely dissolved, and filter through a 0.45 μm filter membrane to obtain a silver ammonia solution;
[0035] The quaternary ammonium salt carboxymethyl chitosan solution was placed in a microwave synthesis reactor, the system temperature was raised to 70°C, and then the silver ammonia solution was quickly injected, stirring was started to mix evenly, and the reaction was carried out for 50 minutes. After the reaction was completed, it was cooled to room temperature, and the antibacterial agent was obtained after purification by dialysis.
[0036] Example 2 The preparation method of modified silicon dioxide comprises the following steps:
[0037] 0.2 g of carboxymethyl chitosan was added to 100 mL of deionized water, stirred until completely dissolved, the pH value was adjusted to 10 with 1 mol / L sodium hydroxide solution, the temperature was raised to 80°C with stirring, 0.06 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride was added, the reaction was continued for 8 h, and after purification by dialysis, a quaternary ammonium salt carboxymethyl chitosan solution was obtained;
[0038] Dissolve 0.2 g of silver nitrate in 10 mL of deionized water, add 1 mol / L sodium hydroxide solution drop by drop, and stir continuously until the precipitation no longer increases, then add 2% ammonia solution drop by drop until the precipitation is completely dissolved, and filter through a 0.45 μm filter membrane to obtain a silver ammonia solution;
[0039] The quaternary ammonium salt carboxymethyl chitosan solution was placed in a microwave synthesis reactor, the system temperature was raised to 70°C, and then the silver ammonia solution was quickly injected, stirring was started to mix evenly, and the reaction was carried out for 50 minutes. After the reaction was completed, it was cooled to room temperature, and the antibacterial agent was obtained after purification by dialysis.
[0040] The preparation method of the growth promoter of Example 3 comprises the following steps:
[0041] Prepare 0.6 mg mL -1 Chitosan solution, 1.25 mg mL -1 Sodium hyaluronate solution, 2 mg mL -1 of growth factor solution and 0.5 mg mL -1 The sodium tripolyphosphate solution is prepared with 1% acetic acid solution for chitosan solution and the rest is prepared with deionized water.
[0042] Under stirring, add 300 μL of sodium tripolyphosphate solution to 6 mL of sodium hyaluronate solution to obtain a first pre-crosslinking solution;
[0043] Add 2 mL of growth factor solution to 10 mL of chitosan solution and stir for 30-40 min to obtain a second pre-crosslinking solution;
[0044] The first is added dropwise to the second, and stirred for 10-20 minutes to obtain a growth promoter.
[0045] Example 4 Modified chitosan surgical suture and preparation method thereof, prepared by the following method:
[0046] A 35 cm non-absorbable polyester inner core is immersed in the antibacterial agent prepared in Example 1, immersed at 40° C. for 30 minutes, taken out and dried, immersed again at 40° C. for 30 minutes, dried again, and the immersion and drying steps are repeated five times to form an antibacterial layer on the inner core;
[0047] The inner core forming the antibacterial layer is immersed in the growth promoter prepared in Example 3, immersed at 35°C for 30 minutes, taken out and dried, immersed at 35°C for 30 minutes again, dried again, and the immersion and drying steps are repeated five times to form a growth promoter layer on the antibacterial layer to obtain a modified chitosan surgical suture.
[0048] Example 5 Modified chitosan surgical suture and preparation method thereof, prepared by the following method:
[0049] A 35 cm non-absorbable polyester inner core is immersed in the antibacterial agent prepared in Example 2, immersed at 40° C. for 30 minutes, taken out and dried, immersed again at 40° C. for 30 minutes, dried again, and the immersion and drying steps are repeated five times to form an antibacterial layer on the inner core;
[0050] The inner core forming the antibacterial layer is immersed in the growth promoter prepared in Example 3, immersed at 35°C for 30 minutes, taken out and dried, immersed at 35°C for 30 minutes again, dried again, and the immersion and drying steps are repeated five times to form a growth promoter layer on the antibacterial layer to obtain a modified chitosan surgical suture.
[0051] Example 6 Modified chitosan surgical suture and preparation method thereof, prepared by the following method:
[0052] A 35 cm non-absorbable polyester inner core is immersed in the antibacterial agent prepared in Example 1, immersed at 40° C. for 30 minutes, taken out and dried, immersed again at 40° C. for 30 minutes, dried again, and the immersion and drying steps are repeated eight times to form an antibacterial layer on the inner core;
[0053] The inner core forming the antibacterial layer is immersed in the growth promoter prepared in Example 3, immersed at 35°C for 30 minutes, taken out and dried, immersed at 35°C for 30 minutes again, dried again, and the immersion and drying steps are repeated four times to form a growth promoter layer on the antibacterial layer to obtain a modified chitosan surgical suture.
[0054] Comparative Example 1: A modified chitosan surgical suture and a preparation method thereof, which is prepared by the following method:
[0055] A 35 cm non-absorbable polyester inner core was immersed in the antibacterial agent prepared in Example 1, immersed at 40°C for 30 minutes, taken out and dried, immersed at 40°C for 30 minutes again, dried again, and the immersion and drying steps were repeated five times to form an antibacterial layer on the inner core to obtain a modified chitosan surgical suture.
[0056] Comparative Example 2: Modified chitosan surgical suture and preparation method thereof, prepared by the following method:
[0057] A 35-cm non-absorbable polyester inner core was immersed in the growth promoter prepared in Example 3, immersed at 35°C for 30 minutes, taken out and dried, immersed at 35°C for 30 minutes again, dried again, and the immersion and drying steps were repeated five times to form a growth promoting layer on the inner core to obtain a modified chitosan surgical suture.
[0058] The preparation method of the antibacterial agent of Comparative Example 3 comprises the following steps:
[0059] 0.3 g of carboxymethyl chitosan was added to 100 mL of deionized water and stirred until completely dissolved. The pH value was adjusted to 10 with 1 mol / L sodium hydroxide solution. The temperature was raised to 80°C with stirring. 0.08 g of 3-chloro-2-hydroxypropyltrimethylammonium chloride was added and reacted for 8 h. After purification by dialysis, a quaternary ammonium salt carboxymethyl chitosan solution was obtained to obtain an antibacterial agent.
[0060] Modified chitosan surgical suture and preparation method thereof, which are prepared by the following method:
[0061] A 35 cm non-absorbable polyester inner core is immersed in the antibacterial agent prepared in this comparative example, and after being immersed at 40° C. for 30 minutes, it is taken out and dried, and then immersed at 40° C. for 30 minutes again, and dried again, and the immersion and drying steps are repeated five times to form an antibacterial layer on the inner core;
[0062] The inner core forming the antibacterial layer is immersed in the growth promoter prepared in Example 3, immersed at 35°C for 30 minutes, taken out and dried, immersed at 35°C for 30 minutes again, dried again, and the immersion and drying steps are repeated four times to form a growth promoter layer on the antibacterial layer to obtain a modified chitosan surgical suture.
[0063] Comparative Example 4: Modified chitosan surgical suture and preparation method thereof, prepared by the following method:
[0064] A 35-cm nonabsorbable polyester core was soaked in 0.6 mg mL -1 The chitosan solution was immersed at 35°C for 30 minutes, then taken out and dried, immersed at 35°C for 30 minutes again, and dried again. The immersion and drying steps were repeated ten times to form a chitosan antibacterial layer on the inner core to obtain a chitosan surgical suture.
[0065] Performance Testing
[0066] The antibacterial zone width and antibacterial persistence of Examples 4-6 and Comparative Examples 1-4 were investigated respectively, and the test results are shown in the following table;
[0067]
[0068] As can be seen from the above table, the modified chitosan surgical sutures prepared in Examples 4-6 of the present application have good long-term antibacterial properties and can meet the needs of gynecological surgery. In Comparative Example 1, only an antibacterial layer is formed on the inner core, and the antibacterial durability of the obtained suture is reduced. In Comparative Example 2, only a growth-promoting layer is formed on the inner core, and the diameter of the obtained suture antibacterial circle is small, the antibacterial effect on Candida albicans is poor, and the antibacterial durability is reduced. The antibacterial layer formed in Comparative Example 3 does not contain silver ions, and the antibacterial circle diameter and antibacterial durability of the obtained suture are also reduced, and the antibacterial durability is reduced more. Comparative Example 4 is a blank control, and only a chitosan layer is formed on the inner core. The obtained suture has the worst antibacterial effect, and pure chitosan has a poor antibacterial effect on Candida albicans.
[0069] The above is a detailed description of an embodiment of the present invention, but the content is only a preferred embodiment of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the patent coverage of the present invention.
Claims
1. A modified chitosan surgical suture, characterized in that: At least: The inner core is a non-absorbable polyester suture; An antibacterial layer is arranged on the inner core, and the antibacterial layer is a quaternary ammonium salt carboxymethyl chitosan / silver ion composite antibacterial layer; The growth-promoting layer is arranged on the antibacterial layer, and the growth-promoting layer at least comprises a chitosan layer encapsulating growth factors.
2. The modified chitosan surgical suture according to claim 1, characterized in that: The thickness of the antibacterial layer is 100-300 μm, and the thickness of the growth-promoting layer is 50-200 μm.
3. A method for preparing the modified chitosan surgical suture according to any one of claims 1 to 2, characterized in that: The method comprises at least the following preparation steps: The inner core is immersed in an antibacterial agent, immersed at 35-45° C. for 30 minutes, taken out and dried, immersed again at 35-45° C. for 30 minutes, dried again, and the immersion and drying steps are repeated at least five times to form an antibacterial layer on the inner core; The inner core forming the antibacterial layer is immersed in a growth promoter, immersed at 35-45°C for 30 minutes, taken out and dried, immersed again at 35-45°C for 30 minutes, dried again, and the immersion and drying steps are repeated at least five times to form a growth promoter layer on the antibacterial layer to obtain a modified chitosan surgical suture.
4. The method for preparing a modified chitosan surgical suture according to claim 3, characterized in that: The preparation method of the growth promoter comprises the following steps: Prepare chitosan solution, sodium hyaluronate solution, growth factor solution and sodium tripolyphosphate solution respectively, wherein the chitosan solution is prepared with 1% acetic acid solution, and the rest are prepared with deionized water; Under stirring, adding sodium tripolyphosphate solution to the sodium hyaluronate solution to obtain a first pre-cross-linking solution; Adding the growth factor solution to the chitosan solution and stirring for 30-40 minutes to obtain a second pre-crosslinking solution; The first pre-cross-linking solution is added dropwise to the second pre-cross-linking solution within 20 minutes, and the mixture is stirred at room temperature for 10-20 minutes to obtain a growth promoter.
5. The method for preparing a modified chitosan surgical suture according to claim 4, characterized in that: The concentration of the chitosan solution is 0.5-1 mg·mL -1 The concentration of the growth factor solution is 1-3 mg·mL -1 The concentration of the sodium hyaluronate solution is 1-1.5 mg·mL -1 The concentration of the sodium tripolyphosphate solution is 0.5-1 mg·mL -1 .
6. The method for preparing a modified chitosan surgical suture according to claim 4, characterized in that: The molar ratio of the sodium tripolyphosphate to the free amino group of the chitosan is 0.1-0.3:1, the mass ratio of the sodium hyaluronate to the chitosan is 1-1.5:1, and the mass ratio of the growth factor to the chitosan is 1:1.5-2.
7. The method for preparing a modified chitosan surgical suture according to claim 3, characterized in that: The preparation method of the antibacterial agent comprises the following steps: Add carboxymethyl chitosan into deionized water, stir until completely dissolved, adjust the pH value to 10 with sodium hydroxide solution, stir and heat to 70-80°C, add 3-chloro-2-hydroxypropyltrimethylammonium chloride, react for 8-10 hours, and dialysis and purification to obtain a quaternary ammonium salt carboxymethyl chitosan solution; Dissolve silver nitrate in deionized water, add sodium hydroxide solution dropwise, and stir continuously until the precipitate no longer increases, then add ammonia solution dropwise until the precipitate is completely dissolved, and filter to obtain a silver ammonia solution; The quaternary ammonium salt carboxymethyl chitosan solution is placed in a microwave synthesis reactor, the system temperature is raised to 60-90° C., then the silver ammonia solution is quickly injected, stirring is started to mix evenly, and the reaction is carried out for 40-60 minutes. After the reaction is completed, it is cooled to room temperature, and the antibacterial agent is obtained after purification by dialysis.
8. The method for preparing a modified chitosan surgical suture according to claim 7, characterized in that: The mass ratio of the 3-chloro-2-hydroxypropyltrimethylammonium chloride to the carboxymethyl chitosan is 1:4-5, and the mass ratio of the silver nitrate to the carboxymethyl chitosan is 1:1-3.