Preparation method of metal ion modified composite antibacterial hydrogel wound dressing
By combining inulin with gallic acid-carboxymethyl chitosan graft and adding gallium ions, a gallium ion-doped oxide inulin and polyphenol grafted carboxymethyl chitosan hydrogel was prepared, which solved the problem of inconvenience in synthesis and poor antibacterial effect of existing hydrogel wound dressings, and achieved high yield, good biocompatibility and antibacterial properties.
Patent Information
- Application Number
- CN202510091584.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2024-09-13
- Filing Date
- 2025-01-21
- Publication Date
- 2025-04-11
AI Technical Summary
The existing hydrogel wound dressings have problems such as insufficient synthesis method, low yield, non-natural products of the material are harmful to the environment and skin, poor antibacterial effect, and poor water absorption and swelling, adhesion and mechanical properties.
Inulin is used as raw material, and an aldehyde-modified oxidized inulin is obtained through oxidation reaction, and combined with gallium nitrate hydrate solution is added to form gallium ion-doped oxidized inulin and polyphenol grafted carboxymethyl chitosan hydrogel.
It realizes a high yield and simple preparation method of hydrogel wound dressing, has good biocompatibility, adhesion and antibacterial properties, and can promote wound healing.
Abstract
Description
Technical Field
[0001] The invention relates to a method for preparing a metal ion modified composite antibacterial hydrogel wound dressing. Background Art
[0002] Bacterial infection has always been a major problem faced by the world, especially when the skin is broken, the impact on wound healing is particularly serious. In the early stage, the treatment of bacterial infection often took the method of injecting antibiotics. With the emergence of bacterial resistance, people are forced to find new antibacterial methods. There are many wound dressings on the market for bacterial infections. Traditional wound dressings, such as gauze, cotton pads, etc., have poor air permeability and promote slow wound healing. Hydrogel, as a new type of wound dressing, can provide a moist environment for the wound, absorb tissue exudates, and has good biocompatibility and adhesion. It is a new type of wound dressing with practical prospects.
[0003] At present, most hydrogel wound dressings have some common problems, such as the synthesis method is not detailed and simple enough, the yield is not high, the materials used are not natural products, there is a certain amount of pollution to the environment, and there is a certain amount of harm to the skin and body. In addition, some hydrogels made of natural materials may have problems such as poor antibacterial effect, poor water absorption and swelling, poor adhesion, and poor mechanical properties.
[0004] As a natural dietary fiber extracted from plants, inulin has been widely studied in the food field, but the aldehyde-modified oxidized inulin has been less studied in the field of antibacterial hydrogels. Carboxymethyl chitosan has significant antibacterial activity and can prevent wound infection. Gallic acid is a common polyphenol compound with anti-inflammatory and antioxidant functions. The polyphenols were successfully grafted onto the carboxymethyl chitosan skeleton, and the prepared gallic acid-carboxymethyl chitosan graft had significant antibacterial, antioxidant and anti-inflammatory biological functions. The hydrogel formed by the coordination of metal ions with other substances has multiple properties and has broad biological application prospects.
[0005] So far, there are few studies on metal antibacterial hydrogels involving metal gallium ions. The gelation mechanism of gallium ions and various natural products and the antibacterial effect of gallium ion hydrogels have not been deeply explored. Gallium ions, as a non-toxic and environmentally friendly metal ion, have significant antibacterial effects and are particularly important in solving bacterial antibiotic resistance. Due to the lack of active functional groups and weak interactions, single-component main chain hydrogels often have great deficiencies in adjusting the physical and chemical properties of hydrogel materials, such as the reaction pH conditions and gelation time. Summary of the invention
[0006] The present invention aims to provide a novel metal ion-modified natural material antibacterial hydrogel, which has excellent antibacterial properties, a simple preparation method, good cell compatibility and blood compatibility, excellent adhesion and photothermal conversion, and can promote tissue regeneration, re-epithelialization and accelerate wound healing.
[0007] The present invention uses inulin as a raw material, and performs an oxidation reaction on the hydroxyl groups on the inulin to obtain aldehyde-modified oxidized inulin. Then, the carboxyl groups on the gallic acid are activated to make them cross-linked with the amino groups on the carboxymethyl chitosan to obtain a gallic acid-carboxymethyl chitosan graft. The oxidized inulin and the gallic acid-carboxymethyl chitosan graft are configured into a precursor solution, and mixed with a gallium nitrate hydrate solution in a certain proportion to form a two-component interpenetrating polymer network hydrogel in which the metals are dissolved in deionized water, and the gallium ions are doped with oxidized inulin and polyphenol grafted carboxymethyl chitosan. The method is simple in synthesis, environmentally friendly, and has a high yield. The synthesized hydrogel wound dressing has a more practical antibacterial prospect.
[0008] The specific technical solution of the present invention is: A method for preparing a metal ion modified composite antibacterial hydrogel wound dressing, characterized in that it comprises the following steps: Step 1: 2.4 g of inulin was dissolved in 50 ml of deionized water, and oxidized with sodium periodate (720 mg) at room temperature and in the dark for four hours to obtain oxidized inulin. After the oxidation was complete, the oxidation reaction was quenched with excess ethylene glycol. The oxidized solution was dialyzed in deionized water with a 1000 Da cutoff membrane for a total of 3 days. The dialyzed solution was then freeze-dried with a freeze dryer, and the oxidation rate was 30%-40%.
[0009] Inulin, also known as inulin, is a reserve polysaccharide in plants. It is mainly derived from plants and can be purchased.
[0010] Step 2: Gallic acid (0.170 g, 1 mmol) was dissolved in a 20 mL mixed solution containing N,N-dimethylformamide and deionized water (N,N-dimethylformamide / deionized water: v / v, 1 / 9), and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.192 g, 1 mmol) and N-hydroxysuccinimide (0.115 g, 1 mmol) were added. The reaction lasted for 1 h in an ice bath and dark atmosphere to activate the carboxyl groups; carboxymethyl chitosan (0.460 g, 2 mmol) was dissolved in pH = 7.4 PbS buffer to prepare a 2% (w / v) solution; the carboxyl-activated GA solution was gradually added to the pre-prepared CMCS solution, and the pH value was adjusted to 6.5. After stirring in the dark for 18 h at room temperature (RT), the product was placed in a dialysis bag (MWCO = 5000 Da) and dialyzed for 3 d; the final compound was freeze-dried and stored; Step 3: 0.4g of gallic acid-carboxymethyl chitosan and 0.3g of oxidized inulin (obtained in step 1) were dissolved in 5ml of deionized water, stirred evenly to completely dissolve, and then 10ml of hydrated gallium nitrate solution (3%) was added after stirring and mixing. The obtained mixed solution was poured into the gel film mold and mixed for 2 hours to obtain the metal gallium ion-doped oxidized inulin and polyphenol grafted carboxymethyl chitosan hydrogel.
[0011] The hydrogel wound dressing of the present invention can provide a moist environment for the wound, absorb tissue exudate, and has good biocompatibility and adhesion, and is a new type of wound dressing with practical prospects. The introduction of metal ions into the hydrogel gives it good antibacterial properties, and the unique multifunctional metal ions are ideal materials for preparing functional hydrogels. DETAILED DESCRIPTION
[0012] Example 1
[0013] 2.4 g of inulin was dissolved in 50 ml of deionized water and oxidized with sodium periodate (720 mg) at room temperature and in the dark for four hours to obtain oxidized inulin. After the oxidation was complete, the oxidation reaction was quenched with excess ethylene glycol, and the oxidized solution was dialyzed in deionized water for a total of 3 days using a 1000 Da cut-off membrane. The dialyzed solution was then freeze-dried using a freeze dryer. The theoretical oxidation rate was 30%.
[0014] GA (0.170 g, 1 mmol) was dissolved in 20 mL of a mixed solution containing N,N-dimethylformamide and deionized water (DMF / deionized water: v / v, 1 / 9), and then EDC (0.192 g, 1 mmol) and NHS (0.115 g, 1 mmol) were added. The reaction was continued for 1 h in an ice bath and dark atmosphere to activate the carboxyl groups. CMCS (0.460 g, 2 mmol) was dissolved in pH = 7.4 PbS buffer to prepare a 2% (w / v) solution. The carboxyl-activated GA solution was gradually added to the pre-prepared CMCS solution, and the pH value was adjusted to 6.5. After stirring in the dark at room temperature (RT) for 18 h, the product was placed in a dialysis bag (MWCO = 5000 Da) and dialyzed for 3 d. The final compound was freeze-dried and stored.
[0015] 0.4g gallic acid-carboxymethyl chitosan and 0.3g oxidized inulin were dissolved in 5ml deionized water respectively, stirred evenly to make them completely dissolved, and after stirring and mixing, 10ml hydrated gallium nitrate solution (3%) was poured into the previously obtained precursor solution. The obtained mixed solution was poured into the gel film mold, and after a period of time, the metal gallium ion-doped oxidized inulin and polyphenol grafted carboxymethyl chitosan hydrogel was obtained.
[0016] Example 2
[0017] 4.8 g of inulin was dissolved in 100 ml of deionized water and oxidized with sodium periodate (1.44 g) at room temperature and in the dark for four hours to obtain oxidized inulin. After the oxidation was complete, the oxidation reaction was quenched with excess ethylene glycol, and the oxidized solution was dialyzed in deionized water for 3 days using a 1000 Da cut-off membrane. The dialyzed solution was then freeze-dried using a freeze dryer. The theoretical oxidation rate was 30%.
[0018] GA (0.340 g, 2 mmol) was dissolved in 40 mL of a mixed solution containing N,N-dimethylformamide and deionized water (DMF / deionized water: v / v, 1 / 9), and then EDC (0.384 g, 2 mmol) and NHS (0.230 g, 2 mmol) were added. The reaction was continued for 1 h in an ice bath and dark atmosphere to activate the carboxyl groups. CMCS (0.920 g, 4 mmol) was dissolved in pH = 7.4 PbS buffer to prepare a 2% (w / v) solution. The carboxyl-activated GA solution was gradually added to the pre-prepared CMCS solution, and the pH value was adjusted to 6.5. After stirring in the dark for 18 h at room temperature (RT), the product was placed in a dialysis bag (MWCO = 5000 Da) and dialyzed for 3 d. The final compound was freeze-dried and stored.
[0019] 0.8g of gallic acid-carboxymethyl chitosan and 0.6g of oxidized inulin were dissolved in 10ml of deionized water, stirred evenly to make them completely dissolved, and after stirring and mixing, 20ml of hydrated gallium nitrate solution (3%) was poured into the previously obtained precursor solution. The obtained mixed solution was poured into the gel film mold, and after a period of time, the metal gallium ion-doped oxidized inulin and polyphenol grafted carboxymethyl chitosan hydrogel was obtained.
[0020] Example 3
[0021] 3.6 g of inulin was dissolved in 75 ml of deionized water and oxidized with sodium periodate (1.08 g) at room temperature and in the dark for four hours to obtain oxidized inulin. After the oxidation was complete, the oxidation reaction was quenched with excess ethylene glycol, and the oxidized solution was dialyzed in deionized water for 3 days using a 1000 Da cut-off membrane. The dialyzed solution was then freeze-dried using a freeze dryer. The theoretical oxidation rate was 30%.
[0022] GA (0.255 g, 1.5 mmol) was dissolved in 20 mL of a mixed solution containing N,N-dimethylformamide and deionized water (DMF / deionized water: v / v, 1 / 9), and then EDC (0.288 g, 1.5 mmol) and NHS (0.173 g, 1.5 mmol) were added. The reaction was continued for 1 h in an ice bath and dark atmosphere to activate the carboxyl groups. CMCS (0.690 g, 3 mmol) was dissolved in pH = 7.4 PbS buffer to prepare a 2% (w / v) solution. The carboxyl-activated GA solution was gradually added to the pre-prepared CMCS solution and the pH was adjusted to 6.5. After stirring in the dark for 18 h at room temperature (RT), the product was placed in a dialysis bag (MWCO = 5000 Da) and dialyzed for 3 d. The final compound was freeze-dried and stored.
[0023] 0.6g of gallic acid-carboxymethyl chitosan and 0.45g of oxidized inulin were dissolved in 7.5ml of deionized water, stirred evenly to make them completely dissolved, and after stirring and mixing, 15ml of hydrated gallium nitrate solution (3%) was poured into the previously obtained precursor solution. The obtained mixed solution was poured into the gel film mold, and after a period of time, the metal gallium ion-doped oxidized inulin and polyphenol grafted carboxymethyl chitosan hydrogel was obtained.
Claims
1. A method for preparing a metal ion modified composite antibacterial hydrogel wound dressing, characterized in that: The steps include: Step 1: 2.4 g of inulin was dissolved in 50 ml of deionized water, and oxidized with sodium periodate (720 mg) at room temperature and in the dark for four hours to obtain oxidized inulin. After the oxidation was complete, an excess of ethylene glycol was used to quench the oxidation reaction. The oxidized solution was dialyzed in deionized water with a 1000 Da cutoff membrane for a total of 3 days. The dialyzed solution was then freeze-dried with a freeze dryer, and the theoretical oxidation rate was 30%; Step 2: GA (0.170 g, 1 mmol) was dissolved in a 20 mL mixed solution containing N,N-dimethylformamide and deionized water (DMF / deionized water: v / v, 1 / 9), and then EDC (0.192 g, 1 mmol) and NHS (0.115 g, 1 mmol) were added. The reaction lasted for 1 h in an ice bath and dark atmosphere to activate the carboxyl group; CMCS (0.460 g, 2 mmol) was dissolved in pH = 7.4 PbS buffer to prepare a 2% (w / v) solution; the carboxyl-activated GA solution was gradually added to the pre-prepared CMCS solution, and the pH value was adjusted to 6.
5. After stirring in the dark for 18 h at room temperature (RT), the product was placed in a dialysis bag (MWCO = 5000 Da) for 3 d; the final compound was freeze-dried and stored; Step 3: 0.4g gallic acid-carboxymethyl chitosan and 0.3g oxidized inulin were dissolved in 5ml deionized water respectively, stirred evenly to make them completely dissolved, and after stirring and mixing, 10ml hydrated gallium nitrate solution (3%) was poured into the previously obtained precursor solution. The obtained mixed solution was poured into the gel film mold, and after a period of time, the metal gallium ion-doped oxidized inulin and polyphenol grafted carboxymethyl chitosan hydrogel was obtained.