Modified nano-silver, hydrogel dressing and preparation method and application thereof
Modified nano-silver was prepared by controlling the molar ratio of silver salt, lanthanum salt, and cerium salt, and then reacted with mercaptocarboxylic acid. Combined with gelatin and carboxymethyl chitosan crosslinking, the problem of insufficient antibacterial properties of hydrogel dressings was solved, achieving more efficient antibacterial effect and safety.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- THE GBA NAT INST FOR NANOTECHNOLOGY INNOVATION
- Filing Date
- 2024-12-09
- Publication Date
- 2026-06-09
AI Technical Summary
The antibacterial properties of existing hydrogel dressings need to be improved, as they are difficult to effectively inhibit bacterial growth at the wound site.
Modified silver nanoparticles were prepared by controlling the molar ratio of silver salt, lanthanum salt, and cerium salt, and then reacted with mercaptocarboxylic acid to form modified silver nanoparticles stably linked to the hydrogel dressing framework. The antibacterial properties were improved by utilizing the cross-linking reaction of modified silver nanoparticles with gelatin and carboxymethyl chitosan.
It significantly improves the antibacterial properties of hydrogel dressings, reduces the risk of modified nano-silver entering the body through wounds, and enhances the protective effect on wounds.
Smart Images
Figure BDA0005177569140000061 
Figure BDA0005177569140000071 
Figure BDA0005177569140000111
Abstract
Description
Technical Field
[0001] This invention relates to the field of materials technology, and more specifically, to a modified nano-silver hydrogel dressing, its preparation method, and its application. Background Technology
[0002] Dressings refer to auxiliary materials used in addition to the main material of an item. Traditional dressings mainly consist of dry gauze and oil-soaked gauze, while modern wound dressings include interactive wound dressings, hydrogel dressings, calcium alginate dressings, foam dressings, hydrocolloid dressings, and so on. Among them, hydrogel dressings are a new type of wound care material, mainly composed of hydrogel materials. They have excellent water absorption and moisturizing properties, absorbing exudate from the wound surface and keeping the wound moist, promoting wound healing. At the same time, the moist environment they provide can promote cell regeneration and repair at the wound site, thereby reducing the risk of wound infection. In addition, because hydrogel dressings contain a large amount of water, when they come into contact with the skin, heat exchange occurs due to the temperature difference between the skin and the gel, causing the skin temperature to drop, resulting in a cooling and analgesic effect. Most importantly, hydrogel dressings are non-irritating to the skin, have low immunogenicity, and are highly safe.
[0003] Currently, hydrogel dressings are used for various acute and chronic wounds, chronic non-healing wounds, surgical incisions, and postoperative wounds. Acute and chronic wounds include superficial wounds such as abrasions, cuts, and burns, while chronic non-healing wounds include diabetic foot ulcers, pressure sores, and venous ulcers. If a hydrogel dressing has antibacterial properties, it can inhibit or kill bacteria at the wound site, reducing bacterial growth and further lowering the risk of wound infection. It can also reduce the use of antibiotics and help control the development of drug resistance. Existing technology incorporates nano-silver as an antibacterial agent into hydrogel dressings to impart antibacterial properties; however, the antibacterial performance of this hydrogel dressing still needs improvement.
[0004] Therefore, developing a modified silver nanoparticle that can improve the antibacterial properties of hydrogel dressings is of great significance. Summary of the Invention
[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a modified nano-silver, hydrogel dressing, preparation method and application for improving the antibacterial properties of hydrogel dressings.
[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0007] In a first aspect, the present invention provides a modified silver nanoparticle, the preparation method of which includes the following steps:
[0008] S1. Add silver salt, lanthanum salt, cerium salt, stabilizer and borohydride to water and react to obtain lanthanum-cerium nano-silver;
[0009] S2. Mix lanthanum- and cerium-containing nano-silver and mercaptocarboxylic acid to react and obtain modified nano-silver;
[0010] In step S1, the molar ratio of silver in the silver salt, lanthanum in the lanthanum salt, and cerium in the cerium salt is Ag:La:Ce = 1:(0.005-0.030):(0.10-0.30).
[0011] In this invention, the content of lanthanum and cerium in modified nano-silver is adjustable by controlling the molar ratio of silver in silver salt, lanthanum in lanthanum salt, and cerium in cerium salt, so that lanthanum and cerium are evenly distributed in the modified nano-silver, thereby effectively promoting the antibacterial effect of nano-silver and improving the antibacterial performance of hydrogel dressings prepared using modified nano-silver.
[0012] Furthermore, the modified silver nanoparticles prepared by modifying lanthanum-cerium nanoparticles with mercaptocarboxylic acid can be cross-linked by reacting the carboxyl groups directly with the raw materials of hydrogel dressings (amino groups of gelatin and amino groups of carboxymethyl chitosan). This allows the modified silver nanoparticles to be stably and uniformly connected to the framework of the hydrogel dressing through chemical bonding. This not only fully exerts the antibacterial effect of the modified silver nanoparticles, but also reduces or prevents the modified silver nanoparticles from entering the body through the wound when the hydrogel dressing is used on the wound surface.
[0013] Preferably, in step S1, the molar ratio of silver in the silver salt, lanthanum in the lanthanum salt, and cerium in the cerium salt is Ag:La:Ce = 1:(0.010-0.020):(0.15-0.25).
[0014] More preferably, in step S1, the molar ratio of silver in the silver salt, lanthanum in the lanthanum salt, and cerium in the cerium salt is Ag:La:Ce = 1:0.015:0.20.
[0015] Preferably, in step S1, the silver salt is silver nitrate.
[0016] Preferably, in step S1, the lanthanum salt is lanthanum nitrate.
[0017] Preferably, in step S1, the cerium salt is cerium nitrate.
[0018] Preferably, in step S1, the mass ratio of the silver salt to the volume of water is 1g:(1-500)mL.
[0019] Preferably, in step S1, the stabilizer is at least one of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP).
[0020] Preferably, in step S1, the mass ratio of the silver salt to the stabilizer is 1:(0.001-10).
[0021] Preferably, in step S1, the borohydride is at least one of sodium borohydride and potassium borohydride.
[0022] Preferably, in step S1, the molar ratio of the silver salt to the borohydride is 1:(0.5-3).
[0023] Preferably, in step S1, the reaction temperature is 0-80°C.
[0024] Preferably, in step S1, the reaction time is 0.5-18 hours.
[0025] Preferably, in step S1, after the reaction, centrifugation, washing, and drying are also included.
[0026] More preferably, the drying temperature is 50-85°C.
[0027] Preferably, the molar ratio of silver element in the silver salt to mercapto group in the mercaptocarboxylic acid is Ag:-SH=1:(1-10).
[0028] In this invention, by controlling the molar ratio of silver element in silver salt and thiol group in thiocarboxylic acid, modified nano-silver can be more stably and uniformly connected to the hydrogel dressing framework through chemical bonding, thereby further improving the antibacterial effect of modified nano-silver, and further improving the antibacterial performance of hydrogel dressing prepared using modified nano-silver.
[0029] More preferably, the molar ratio of silver element in the silver salt to mercapto group in the mercaptocarboxylic acid is Ag:-SH=1:(3-8).
[0030] More preferably, the molar ratio of silver element in the silver salt to thiol group in the thiol carboxylic acid is Ag:-SH=1:5.
[0031] Preferably, in step S2, the thiocarboxylic acid is at least one selected from thiopropionic acid, thiocarboxylic acid, thiobenzoic acid, thiosuccinic acid, and thioacetic acid.
[0032] Preferably, in step S2, the liquid environment of the reaction is at least one of water, alcohol, ether, ketone, nitrile, haloalkane, and benzene homologue.
[0033] More preferably, in step S2, the liquid environment of the reaction is at least one of water, ethanol, methanol, isopropanol, n-butanol, diethyl ether, acetone, acetonitrile, chloroform, and toluene.
[0034] More preferably, the mass ratio of the mercaptocarboxylic acid to the volume of the liquid environment is 1 g:(1-200) mL.
[0035] Preferably, in step S2, the reaction temperature is 15-80°C.
[0036] Preferably, in step S2, the reaction time is 0.2-10 h.
[0037] Preferably, in step S2, after the reaction of the mixed lanthanum-cerium nano-silver and mercaptocarboxylic acid, centrifugation and drying are also included.
[0038] More preferably, the drying temperature is 50-85°C.
[0039] Secondly, the present invention provides an application of modified nano-silver in antibacterial applications.
[0040] Thirdly, the present invention provides a hydrogel dressing, which is prepared by heating and reacting modified nano-silver, gelatin, and carboxymethyl chitosan;
[0041] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:(10-80):(5-50).
[0042] In this invention, cross-linking is achieved through a condensation reaction between the carboxyl groups of modified nano-silver, the carboxyl and amino groups of gelatin, and the amino groups of carboxymethyl chitosan, thereby forming a hydrogel dressing. Furthermore, by controlling the mass ratio of modified nano-silver, gelatin, and carboxymethyl chitosan, the antibacterial modified nano-silver and carboxymethyl chitosan can be uniformly modified between gelatin molecules, which is beneficial for further improving the antibacterial properties of the hydrogel dressing.
[0043] Preferably, the mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:(10-50):(5-25).
[0044] More preferably, the mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:(20-40):(10-20).
[0045] More preferably, the mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15.
[0046] Preferably, the reaction temperature is 50-90°C.
[0047] Preferably, the reaction time is 0.5-20 hours.
[0048] Preferably, the preparation method of the hydrogel dressing is as follows: modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) are added to water, heated to react, and dialyzed to obtain the hydrogel dressing.
[0049] In this invention, the purpose of the dialysis is to remove EDC and NHS.
[0050] More preferably, the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) is 1:(1-5):(0.5-5).
[0051] More preferably, the mass ratio of the gelatin to the volume of the water is (1-75) g: 100 mL.
[0052] Fourthly, the present invention provides an application of a hydrogel dressing in antibacterial applications.
[0053] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0054] In this invention, the content of lanthanum and cerium in modified nano-silver is adjustable by controlling the molar ratio of silver in silver salt, lanthanum in lanthanum salt, and cerium in cerium salt, so that lanthanum and cerium are evenly distributed in the modified nano-silver, thereby effectively promoting the antibacterial effect of nano-silver and improving the antibacterial performance of hydrogel dressings prepared using modified nano-silver.
[0055] In this invention, the modified silver nanoparticles prepared by modifying lanthanum-cerium nanoparticles with mercaptocarboxylic acid can be cross-linked by reacting the carboxyl groups directly with the raw materials of the hydrogel dressing (the amino groups of gelatin and carboxymethyl chitosan). This allows the modified silver nanoparticles to be stably and uniformly connected to the framework of the hydrogel dressing through chemical bonding. This not only fully exerts the antibacterial effect of the modified silver nanoparticles, but also reduces or prevents the modified silver nanoparticles from entering the body through the wound when the hydrogel dressing is used on the wound surface.
[0056] In this invention, by controlling the molar ratio of silver element in silver salt and thiol group in thiocarboxylic acid, modified nano-silver can be more stably and uniformly connected to the hydrogel dressing framework through chemical bonding, thereby further improving the antibacterial effect of modified nano-silver, and further improving the antibacterial performance of hydrogel dressing prepared using modified nano-silver.
[0057] In this invention, cross-linking is achieved through a condensation reaction between the carboxyl groups of modified nano-silver, the carboxyl and amino groups of gelatin, and the amino groups of carboxymethyl chitosan, thereby forming a hydrogel dressing. Furthermore, by controlling the mass ratio of modified nano-silver, gelatin, and carboxymethyl chitosan, the antibacterial modified nano-silver and carboxymethyl chitosan can be uniformly modified between gelatin molecules, which is beneficial for further improving the antibacterial properties of the hydrogel dressing. Detailed Implementation
[0058] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.
[0059] The experimental methods in the following examples, comparative examples, application examples and comparative application examples, unless otherwise specified, are generally performed under conventional conditions in the art or under conditions recommended by the manufacturer; the raw materials and reagents used, unless otherwise specified, are all commercially available from the conventional market.
[0060] The use of reagents in the various embodiments, comparative examples, application examples, and comparative application examples of this invention is as follows:
[0061] Gelatin, G6317, Shanghai McLean;
[0062] Carboxymethyl chitosan, C804727, Shanghai Maclean's.
[0063] Example 1
[0064] This embodiment provides a modified silver nanoparticle, the preparation method of which includes the following steps:
[0065] S1. Add 1 mol silver nitrate, 0.015 mol lanthanum nitrate, 0.20 mol cerium nitrate, polyvinyl alcohol (PVA) and 1 mol sodium borohydride to water, heat to 65℃ and react for 3 h, centrifuge, wash with water, and dry in an oven at 60℃ to obtain lanthanum-cerium nano-silver.
[0066] S2. Add lanthanum-cerium nano-silver and 5 mol mercaptosuccinic acid to water, stir and mix, heat to 50℃ for 1 hour, centrifuge, and dry in an oven at 60℃ to obtain modified nano-silver.
[0067] In step S1, the molar ratio of silver in the silver salt, lanthanum in the lanthanum salt, and cerium in the cerium salt is Ag:La:Ce = 1:0.015:0.20; the mass ratio of the silver salt (silver nitrate) to the volume of water is 1g:150mL; the mass ratio of the silver salt (silver nitrate) to the stabilizer (PVA) is 1:0.008; and the molar ratio of the silver salt (silver nitrate) to the borohydride (sodium borohydride) is 1:1.
[0068] The molar ratio of silver element in the silver salt (silver nitrate) to mercapto group in the mercaptocarboxylic acid (mercaptosuccinic acid) is Ag:-SH=1:5, and the mass ratio of the mercaptocarboxylic acid (mercaptosuccinic acid) to the volume of the liquid environment (water) is 1g:100mL.
[0069] Examples 2-9 and Comparative Examples 1-4
[0070] Examples 2-9 and Comparative Examples 1-4 provide different modified silver nanoparticles. The difference between them and Example 1 is that the molar ratios of silver in the silver salt, lanthanum in the lanthanum salt, and cerium in the cerium salt are different in step S1. All other aspects are the same as in Example 1, as shown in the table below:
[0071] Table 1. Molar ratios of silver, lanthanum, and cerium in silver salts, lanthanum salts, and cerium salts in Examples 1-9 and Comparative Examples 1-4.
[0072]
[0073] Examples 10-13 and Comparative Example 5
[0074] Examples 10-13 and Comparative Example 5 provide different modified silver nanoparticles. The difference between them and Example 1 is that the molar ratio of silver element in the silver salt and thiol group in the thiol carboxylic acid is different. All other aspects are the same as in Example 1, as shown in the table below:
[0075] Table 2. Molar ratio of silver element in silver salts and thiol groups in thiocarboxylic acids in Examples 1, 10-13 and Comparative Example 5.
[0076]
[0077] Application Example 1
[0078] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0079] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 1 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0080] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0081] Application Example 2
[0082] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0083] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 2 to water, heat to 70°C and react for 2 hours. Then, dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0084] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0085] Application Example 3
[0086] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0087] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 3 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0088] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0089] Application Example 4
[0090] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0091] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 4 to water, heat to 70°C and react for 2h. Then, dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0092] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0093] Application Example 5
[0094] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0095] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 5 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0096] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0097] Application Example 6
[0098] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0099] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 6 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0100] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0101] Application Example 7
[0102] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0103] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 7 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0104] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0105] Application Example 8
[0106] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0107] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 8 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0108] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0109] Application Example 9
[0110] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0111] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 9 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0112] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0113] Application Example 10
[0114] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0115] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 10 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0116] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0117] Application Example 11
[0118] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0119] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 11 to water, heat to 70°C and react for 2h. Then, dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0120] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0121] Application Example 12
[0122] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0123] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 12 to water, heat to 70°C and react for 2 hours. Then, dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0124] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0125] Application Example 13
[0126] This application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0127] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Example 13 to water, heat to 70°C and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0128] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0129] Application Example 14-24
[0130] Application Examples 14-24 provide different hydrogel dressings, which differ from Application Example 1 in that the mass ratio of modified nano-silver, gelatin, and carboxymethyl chitosan prepared in Example 1 is different; otherwise, they are the same as Application Example 1, as shown in the table below:
[0131] Table 3. Mass ratio of modified nano-silver, gelatin, and carboxymethyl chitosan in Application Examples 1, 14-24
[0132]
[0133] Comparative Application Example 1
[0134] This comparative application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0135] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Comparative Example 1 to water, heat to 70℃ and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0136] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0137] Comparative Application Example 2
[0138] This comparative application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0139] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Comparative Example 2 to water, heat to 70℃ and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0140] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0141] Comparative Application Example 3
[0142] This comparative application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0143] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Comparative Example 3 to water, heat to 70℃ and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0144] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0145] Comparative Application Example 4
[0146] This comparative application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0147] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Comparative Example 4 to water, heat to 70℃ and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0148] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0149] Comparative Application Example 5
[0150] This comparative application example provides a hydrogel dressing, the preparation method of which includes the following steps:
[0151] Add 1g of the modified nano-silver, gelatin, carboxymethyl chitosan, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide] and NHS (N-hydroxysuccinimide) prepared in Comparative Example 5 to water, heat to 70℃ and react for 2h, then dialyze to remove EDC and NHS to obtain the hydrogel dressing.
[0152] The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:30:15; the mass ratio of the modified nano-silver, EDC [1-ethyl-(3-dimethylaminopropyl)carbodiimide], and NHS (N-hydroxysuccinimide) is 1:1:2; and the mass ratio of the gelatin to the volume of water is 30g:100mL.
[0153] Performance testing
[0154] The performance of the hydrogel dressings in each application example and the comparative application example was tested, as follows:
[0155] 1. Antibacterial performance test:
[0156] (1) Take 1cm×1cm×1cm of each application example or comparative application example of hydrogel dressing in a glass test tube (15mm×150mm) as the experimental group, and the experiment without adding any hydrogel dressing as the blank control group.
[0157] (2) Add 10 mL of LB liquid culture medium to the glass test tube treated in step (1), and then add 1 mL of 4×10⁻⁶ medium. 8 A CFU / mL Staphylococcus aureus suspension was incubated at 37°C for 6 hours. Then, 100 μL was diluted 1000 times with LB liquid medium. Using the dilution plating method, 100 μL was spread on Luria-Bertani (LB) agar medium and incubated at 37°C for 24 hours. The colony count was then calculated.
[0158] (3) The antibacterial rate of the hydrogel dressings in each application example and the comparative application example was calculated using the following formula:
[0159] The inhibition rate (%) of hydrogel dressing against Staphylococcus aureus = (number of colonies in the blank control group - number of colonies in the experimental group) / number of colonies in the blank control group × 100%;
[0160] 2. Compression strength test:
[0161] The hydrogel dressings of each application example or comparative application example were made into cylinders with a diameter of 40 mm and a height of 20 mm. The compressive strength of the hydrogel dressings was tested using a universal testing machine at a compression rate of 50 mm / min.
[0162] The greater the compressive strength, the better the mechanical properties of the hydrogel dressing;
[0163] The experimental results are shown in the table below:
[0164] Table 4. Performance test results of tiles in various application examples and comparative application examples.
[0165]
[0166]
[0167] As shown in Table 4, in this invention, by controlling the molar ratio of silver in silver salt, lanthanum in lanthanum salt, and cerium in cerium salt, the content of lanthanum and cerium in modified nano-silver can be adjusted, so that lanthanum and cerium are evenly distributed in the modified nano-silver, thereby effectively promoting the antibacterial effect of nano-silver and improving the antibacterial performance of hydrogel dressings prepared using modified nano-silver.
[0168] In this invention, the modified silver nanoparticles prepared by modifying lanthanum-cerium nanoparticles with mercaptocarboxylic acid can be cross-linked by reacting the carboxyl groups directly with the raw materials of the hydrogel dressing (the amino groups of gelatin and carboxymethyl chitosan). This allows the modified silver nanoparticles to be stably and uniformly connected to the framework of the hydrogel dressing through chemical bonding. This not only fully exerts the antibacterial effect of the modified silver nanoparticles, but also reduces or prevents the modified silver nanoparticles from entering the body through the wound when the hydrogel dressing is used on the wound surface.
[0169] Furthermore, as can be seen from Application Examples 1, 10-13 and Comparative Application Example 5, by controlling the molar ratio of silver element in silver salt and mercapto group in mercaptocarboxylic acid, modified nano-silver can be more stably and uniformly connected to the hydrogel dressing framework through chemical bonding, thereby further improving the antibacterial effect of modified nano-silver, and further improving the antibacterial performance of hydrogel dressings prepared using modified nano-silver.
[0170] As shown in Application Examples 1 and 14-24, cross-linking is achieved through a condensation reaction between the carboxyl groups of modified nano-silver, the carboxyl and amino groups of gelatin, and the amino groups of carboxymethyl chitosan, thereby forming a hydrogel dressing. Furthermore, by controlling the mass ratio of modified nano-silver, gelatin, and carboxymethyl chitosan, the antibacterial modified nano-silver and carboxymethyl chitosan can be uniformly modified between gelatin molecules, which is beneficial for further improving the antibacterial properties of the hydrogel dressing.
[0171] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.
Claims
1. A modified nanosilver characterized in that, Its preparation method includes the following steps: S1. Add silver salt, lanthanum salt, cerium salt, stabilizer and borohydride to water and react to obtain lanthanum-cerium nano-silver; S2. Mix lanthanum- and cerium-containing nano-silver and mercaptocarboxylic acid to react and obtain modified nano-silver; In step S1, the molar ratio of silver in the silver salt, lanthanum in the lanthanum salt, and cerium in the cerium salt is Ag:La:Ce = 1:(0.005-0.030):(0.10-0.30).
2. The modified nano-silver of claim 1, wherein the silver nanoparticles are coated with the at least one organic compound. Includes at least one of the following (1)-(2): (1) In step S1, the molar ratio of silver in the silver salt, lanthanum in the lanthanum salt, and cerium in the cerium salt is Ag:La:Ce=1:(0.010-0.020):(0.15-0.25); (2) The molar ratio of silver element in the silver salt and mercapto group in the mercaptocarboxylic acid is Ag:-SH=1:(1-10).
3. The modified nano-silver as described in claim 2, characterized in that, The molar ratio of silver in the silver salt to thiol in the thiol carboxylic acid is Ag:-SH=1:(3-8).
4. The modified nano-silver as described in claim 1, characterized in that, Includes at least one of the following (1)-(7): (1) In step S1, the mass ratio of the silver salt to the volume of water is 1g:(1-500)mL; (2) In step S1, the mass ratio of the silver salt to the stabilizer is 1:(0.001-10); (3) In step S1, the molar ratio of the silver salt to the borohydride is 1:(0.5-3); (4) In step S1, the temperature of the reaction is 0-80℃; (5) In step S1, the reaction time is 0.5-18h; (6) In step S2, the temperature of the reaction is 15-80℃; (7) In step S2, the reaction time is 0.2-10h.
5. The modified nano-silver as described in claim 1, characterized in that, Includes at least one of the following (1)-(7): (1) In step S1, the silver salt is silver nitrate; (2) In step S1, the lanthanum salt is lanthanum nitrate; (3) In step S1, the cerium salt is cerium nitrate; (4) In step S1, the stabilizer is at least one of polyvinyl alcohol and polyvinylpyrrolidone; (5) In step S1, the borohydride is at least one of sodium borohydride and potassium borohydride; (6) In step S2, the thiocarboxylic acid is at least one of thiopropionic acid, thiocarboxylic acid, thiobenzoic acid, thiosuccinic acid, and thioacetic acid; (7) In step S2, the liquid environment of the reaction is at least one of water, alcohol, ether, ketone, nitrile, haloalkanes, and benzene homologues.
6. The application of the modified nano-silver according to any one of claims 1-5 in antibacterial activity.
7. A hydrogel dressing, characterized in that, It is prepared by heating and reacting the modified nano-silver, gelatin, and carboxymethyl chitosan described in any one of claims 1-5. The mass ratio of the modified nano-silver, gelatin, and carboxymethyl chitosan is 1:(10-80):(5-50).
8. The hydrogel dressing as described in claim 7, characterized in that, Includes at least one of the following (1)-(4): (1) The mass ratio of the modified nano-silver, gelatin and carboxymethyl chitosan is 1:(10-50):(5-25); (2) The reaction temperature is 50-90℃; (3) The reaction time is 0.5-20 h; (4) The preparation method of the hydrogel dressing is as follows: add modified nano silver, gelatin, carboxymethyl chitosan, EDC and NHS to water, heat to react, and dialyze to obtain the hydrogel dressing.
9. The hydrogel dressing as described in claim 8, characterized in that, Includes at least one of the following (1)-(3): (1) The mass ratio of the modified nano-silver, gelatin and carboxymethyl chitosan is 1:(20-40):(10-20); (2) The mass ratio of the modified nano-silver, EDC and NHS is 1:(1-5):(0.5-5); (3) The mass ratio of the gelatin to the volume of water is (1-75) g: 100 mL.
10. The use of the hydrogel dressing according to any one of claims 7-9 in antibacterial applications.