A method for preparing a functional glycidyl ether-based polymer and applications thereof
By independently grafting antioxidant and antibacterial functional molecules onto glycidyl ether-based polymers, the problems of low grafting efficiency and uneven distribution of functional molecules in hydrogel materials are solved, achieving highly efficient antibacterial and antioxidant properties, and improving the water retention and wound healing effects of hydrogel dressings.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- BOHUI (ZHEJIANG) BIOTECHNOLOGY CO LTD
- Filing Date
- 2026-03-23
- Publication Date
- 2026-06-23
AI Technical Summary
Existing hydrogel materials, when endowed with antibacterial and antioxidant functions, suffer from problems such as low grafting efficiency of functional molecules, uneven distribution, and difficulty in controlling the loading amount, resulting in unstable performance and potential cytotoxicity.
By independently grafting antioxidant and antibacterial functional molecules onto glycidyl ether-based polymers, competitive reactions of functional groups and steric hindrance effects are avoided, enabling precise control. The resulting polymers possessing both antibacterial and antioxidant functions are then obtained through subsequent mixing.
It improved the grafting efficiency of antibacterial and antioxidant functions, achieving a high antibacterial rate (99.9%) and antioxidant performance (97% ABTS+ clearance rate within 5 minutes), and enhanced the water retention and wound healing effect of hydrogel dressings.
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Figure CN122255449A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical polymer materials technology, and in particular to a method for preparing a functionalized glycidyl ether-based polymer with both antibacterial and antioxidant functions, and its application. Background Technology
[0002] Hydrogels, with their unique three-dimensional network structure, high water content, and controllable mechanical strength, exhibit excellent skin adhesion and are therefore widely used in the life and health fields. Taking wound dressings as an example, hydrogels not only possess suitable mechanical strength, providing effective support for wounds, but also maintain a moist microenvironment due to their high water content. This characteristic greatly promotes cell migration and proliferation, accelerates epidermal regeneration, and reduces scab formation, creating favorable conditions for wound healing. However, in special application scenarios such as burns and infected wounds, and in environments with high levels of inflammation, the performance of ordinary hydrogels becomes insufficient. Under these complex and demanding conditions, hydrogels need to be endowed with specific antibacterial or antioxidant functions to meet higher therapeutic needs. By introducing components with antibacterial or antioxidant activity, hydrogels can effectively inhibit bacterial growth and oxidative stress while protecting the wound, thereby further enhancing their application value in special medical scenarios.
[0003] However, in existing technologies, to achieve multifunctional hydrogels (such as antibacterial modification and antioxidant modification), it is common practice to pre-prepare the required hydrogel matrix solution, and then directly introduce antibacterial and antioxidant functional molecules into the hydrogel matrix solution, either by blending or through chemical grafting. While this method can endow materials with the desired additional antibacterial and antioxidant functions, it also has the following significant drawbacks: First, when functionalized molecules (such as antibacterial or antioxidant molecules containing active functional groups such as amino and carboxyl groups) undergo chemical grafting with the polymer matrix, the grafting efficiency is easily reduced due to competition between functional groups; second, due to steric hindrance, the distribution of functional molecules in the gel network is difficult to be uniform, making it impossible to precisely control the loading of each functional component; third, if functional molecules fail to graft effectively and remain in the material system, they may cause cytotoxicity and pose a potential hazard to the wound. These problems make it difficult for traditional methods to simultaneously achieve efficient antibacterial, antioxidant, and other multiple functions, and the material performance has poor stability and low controllability. Summary of the Invention
[0004] In view of this, this invention proposes a method for preparing functionalized glycidyl ether-based polymers and their applications. These functionalized polymers can be directly processed into new biomaterials. By subjecting the glycidyl ether-based polymers to antioxidant and antibacterial modifications, precise and efficient grafting of functional molecules is achieved. This strategy implements the grafting process of different functional molecules independently, effectively avoiding functional group competition reactions and steric hindrance effects, thereby enabling precise control of the grafting rate of antibacterial and antioxidant molecules. Furthermore, this method, through targeted functionalization design, significantly improves the antibacterial and antioxidant efficacy of the material simultaneously, fundamentally solving the technical bottlenecks of poor functional synergy and uncontrollable performance in traditional methods.
[0005] This invention proposes a method for preparing a functionalized glycidyl ether-based polymer, wherein the functionalization is to possess both antioxidant and antibacterial functions. The method involves grafting the glycidyl ether-based polymer with antibacterial and antioxidant functional molecules, respectively. The grafting processes of different functional molecules are carried out independently to avoid competitive reactions and steric hindrance effects between functional groups. In application, the two types of grafted products are mixed to obtain a glycidyl ether-based polymer with both antibacterial and antioxidant functions.
[0006] Furthermore, the glycidyl ether-based polymer is at least one of polypropylene glycidyl ether, polyethylene glycol diglycidyl ether, poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate), and poly(ethylene-co-glycidyl methacrylate).
[0007] Furthermore, the preparation method includes the following steps: 1) Modify the glycidyl ether-based polymer with at least one of ketethiolated thiols or ketethiolated selenyl diamine to obtain antioxidant glycidyl ether-based polymer A; 2) Antibacterial glycidyl ether polymer B was obtained by modifying glycidyl ether polymers with lysine polymers and their derivatives with a number average molecular weight of 2000-10000 Da. 3) The obtained antioxidant glycidyl ether polymer A and antibacterial glycidyl ether polymer B are mixed to obtain a glycidyl ether polymer with both antibacterial and antioxidant functions.
[0008] Furthermore, the method in 1) specifically involves adding ketethiolated thiols or ketethiolated selenyl diamine to an aqueous solution of glycidyl ether polymer, stirring at 40-60 degrees Celsius for 10-12 hours, grafting antioxidant molecules with epoxy bonds to obtain an antioxidant glycidyl ether polymer solution, and then performing dialysis and vacuum freeze-drying to obtain antioxidant glycidyl ether polymer A.
[0009] Furthermore, the method in 2) specifically involves adding the antibacterial functional molecule lysine polymer and its derivatives to an aqueous solution of glycidyl ether polymer, stirring at 40-60 degrees Celsius for 10-12 hours, grafting the antibacterial functional molecule with epoxy bonds to obtain an antibacterial glycidyl ether polymer solution, and then dialyzing and freeze-drying it under vacuum to obtain antibacterial glycidyl ether polymer B.
[0010] Furthermore, the mass ratio of the mixed antioxidant glycidyl ether polymer A and the antibacterial glycidyl ether polymer B is 0.5-2.5:1 (A:B).
[0011] Furthermore, the lysine polymer and its derivatives are at least one of α-polylysine, ε-polylysine, dendritic polylysine, hyperbranched polylysine, and astral polylysine.
[0012] A functionalized glycidyl ether-based polymer is prepared by the method described in any of the preceding methods.
[0013] An antibacterial, antioxidant, and water-retaining hydrogel dressing is prepared by dissolving a glycidyl ether polymer with both antibacterial and antioxidant functions prepared by any of the above methods in a 10% polyvinyl alcohol solution. After centrifuging and defoaming the solution, the solution is poured into a mold. The mold is subjected to freeze-thaw treatment, and the freeze-thaw process is repeated three times to obtain a hydrogel. The hydrogel is then sterilized by irradiation to obtain the dressing.
[0014] Furthermore, the freeze-thaw process involves freezing at -20 degrees Celsius for 3-8 hours, then removing it and allowing it to thaw at room temperature for 6-24 hours.
[0015] The glycidyl ether-based polymer is particularly preferably poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate). The glycidyl ether-based polymer modified with both antibacterial and antioxidant properties has excellent antibacterial properties as well as excellent antioxidant properties.
[0016] The synthesis method of the glycidyl ether-based polymer poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate) is as follows: Polyethylene glycol methyl ether methacrylate monomer (PEGMA), glycidyl methacrylate monomer (GMA), and azobisisobutyronitrile (AIBN) were dissolved in methanol and the mixture was magnetically stirred and refluxed at 50-80°C for 10 hours. After the reaction was completed, the reaction solution was precipitated in ice-cold diethyl ether, the product was collected by centrifugation, and dried to obtain a crude product. The crude product was dissolved in methanol and then precipitated in ice-cold diethyl ether to remove impurities. This process was repeated several times before collecting the product and drying it under vacuum to obtain poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate), i.e., Poly(PEGMA-co-GMA, PPG). The beneficial effects of this invention are as follows: The method of this invention effectively avoids the reaction competition between functional groups of antibacterial and antioxidant functional molecules by using a strategy of single-functional modification and remixing of glycidyl ether-based polymers, thereby improving the grafting efficiency of antibacterial and antioxidant functional molecules while ensuring both antibacterial and antioxidant efficiencies. Verification has shown that the antibacterial rate exceeds 99.9%, and the antioxidant performance against ABTS within 5 minutes... +· With a clearance rate exceeding 97%, the hydrogel dressing prepared by adding functionalized glycidyl ether polymers to a hydrophilic polymer solution not only possesses excellent antibacterial and antioxidant properties, but also exhibits outstanding water retention and long-lasting effects. Attached Figure Description
[0017] Figure 1 NMR and Raman results for antioxidant glycidyl ether polymers; Figure 2 NMR and Raman results for antibacterial glycidyl ether polymers; Figure 3 The antioxidant results are for Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3; Figure 4 The antioxidant stress results are for Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3; Figure 5 The images show the antibacterial effects of Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3. Figure 6 The results show the antibacterial rates of Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3. Figure 7 The appearance of the hydrogel dressing of the antioxidant and antibacterial water-retaining polymer in Example 3;
[0018] Figure 8 This is the water retention effect of Example 3. Detailed Implementation
[0019] The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings. The glycidyl ether-based polymer PPG used in all embodiments of the present invention is poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate).
[0020] Example 1
[0021] Glycidyl ether polymer (PPG) was dissolved in deionized water and stirred with a magnetic stirrer to obtain an aqueous solution of glycidyl ether polymer. The antioxidant functional molecule thioketal (TK) was added to the aqueous solution of glycidyl ether polymer and stirred at 50 degrees Celsius for 12 hours. The solution was then dialyzed for three days and freeze-dried under vacuum to obtain the antioxidant glycidyl ether polymer (PPG-TK). The antibacterial functional molecule hyperbranched poly-L-lysine (HBPL) was added to the aqueous solution of glycidyl ether polymer (PPG) and stirred at 50 degrees Celsius for 12 hours. The solution was then dialyzed for three days and freeze-dried under vacuum to obtain the antibacterial glycidyl ether polymer (PPG-HBPL).
[0022] Two mg of antioxidant glycidyl ether polymer (PPG-TK) and four mg of antibacterial glycidyl ether polymer (PPG-HBPL) were dissolved in 1 mL of deionized water and stirred at 40°C for 4 hours. Experimental results confirmed that the mixture exhibited excellent antibacterial and antioxidant effects, with an antibacterial rate of 99% and an antioxidant rate exceeding 97% within five minutes.
[0023] Example 2
[0024] Glycidyl ether polymer (PPG) was dissolved in deionized water and stirred with a magnetic stirrer to obtain an aqueous solution of glycidyl ether polymer. The antioxidant functional molecule thioketal (TK) was added to the aqueous solution of glycidyl ether polymer and stirred at 50 degrees Celsius for 12 hours. The solution was then dialyzed for three days and freeze-dried under vacuum to obtain the antioxidant glycidyl ether polymer (PPG-TK). The antibacterial functional molecule hyperbranched poly-L-lysine (HBPL) was added to the aqueous solution of glycidyl ether polymer (PPG) and stirred at 50 degrees Celsius for 12 hours. The solution was then dialyzed for three days and freeze-dried under vacuum to obtain the antibacterial glycidyl ether polymer (PPG-HBPL).
[0025] 4 mg of antioxidant glycidyl ether polymer (PPG-TK) and 8 mg of antibacterial glycidyl ether polymer (PPG-HBPL) were dissolved in 1 mL of deionized water and stirred at 40°C for 4 hours. Experimental results verified that both the antibacterial and antioxidant effects were excellent, with an antibacterial rate of 99% and an antioxidant rate exceeding 97% within five minutes.
[0026] Example 3
[0027] Glycidyl ether polymer (PPG) was dissolved in deionized water and stirred with a magnetic stirrer to obtain an aqueous solution of glycidyl ether polymer. The antioxidant functional molecule thioketal (TK) was added to the aqueous solution of glycidyl ether polymer and stirred at 50 degrees Celsius for 12 hours. The solution was then dialyzed for three days and freeze-dried under vacuum to obtain the antioxidant glycidyl ether polymer (PPG-TK). The antibacterial functional molecule hyperbranched poly-L-lysine (HBPL) was added to the aqueous solution of glycidyl ether polymer (PPG) and stirred at 50 degrees Celsius for 12 hours. The solution was then dialyzed for three days and freeze-dried under vacuum to obtain the antibacterial glycidyl ether polymer (PPG-HBPL).
[0028] 0.1g of antioxidant glycidyl ether polymer (PPG-TK) and 0.2g of antibacterial glycidyl ether polymer (PPG-HBPL) were dissolved in a 10% polyvinyl alcohol solution and stirred for 4 hours. The mixture was then poured into a mold and frozen at -20°C for 3 hours. After thawing at room temperature for 12 hours, the mixture was cycled 3 times. After irradiation, a hydrogel dressing was obtained. Experimental results showed that the dressing had excellent antibacterial and antioxidant effects, with an antibacterial rate of 99% and an antioxidant rate exceeding 97% within five minutes. The mechanical strength of 25 kPa provided an optimal mechanical environment for wound healing. This dressing has excellent properties and can effectively inhibit scar formation when applied to wounds.
[0029] Comparative Example 1 Glycidyl ether polymer (PPG) was dissolved in deionized water and stirred with a magnetic stirrer to obtain a water-retaining polymer aqueous solution. The antioxidant functional molecule thioketal diamine (TK) was added to the water-retaining polymer aqueous solution and stirred at 50 degrees Celsius for 12 hours. The solution was then dialyzed for three days and freeze-dried under vacuum to obtain the antioxidant glycidyl ether polymer (PPG-TK).
[0030] 1 mg of antioxidant glycidyl ether polymer (PPG-TK) and 4 mg of antibacterial glycidyl ether polymer (PPG-HBPL) were dissolved in 1 mL of deionized water and stirred at 40 degrees Celsius for 4 hours. Experimental results showed that the antioxidant effect reached only 70% within five minutes, and the antibacterial rate was 95%.
[0031] Comparative Example 2 The antibacterial functional molecule hyperbranched poly-L-lysine (HBPL) was added to an aqueous solution of water-retaining polymer (PPG), stirred at 50 degrees Celsius for 12 hours, and then dialyzed for three days. The solution was then freeze-dried under vacuum to obtain the antibacterial water-retaining polymer (PPG-HBPL).
[0032] Two mg of antioxidant glycidyl ether polymer (PPG-TK) and two mg of antibacterial glycidyl ether polymer (PPG-HBPL) were dissolved in 1 mL of deionized water and stirred at 40°C for 4 hours. Experimental results verified that the antioxidant effect was excellent, exceeding 97% within five minutes, while the antibacterial rate was only 85%.
[0033] Comparative Example 3 The antioxidant functional molecule thioketal (TK) and the antibacterial functional molecule hyperbranched poly-L-lysine (HBPL) were simultaneously added to an aqueous solution of a water-retaining polymer. The mixture was stirred at 50°C for 12 hours, followed by dialyzing of the solution for three days. The solution was then freeze-dried under vacuum to obtain an antibacterial and antioxidant water-retaining polymer (PPG-HBPL / TK, i.e., PHT). 6 mg of PHT was dissolved in 1 mL of deionized water and stirred at 40°C for 4 hours. Experimental results showed that the polymer exhibited certain antibacterial and antioxidant properties, but both were relatively weak.
[0034] Figure 1 and Figure 2 The NMR and Raman results of the synthesis process of the antioxidant glycidyl ether polymer and the antibacterial glycidyl ether polymer, and the NMR and Raman results of poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate) showed that the epoxy bonds on the glycidyl ether polymer disappeared, proving the successful synthesis of the product. Figure 3 The results show the antioxidant free radical scavenging effects of Examples 1, 2, 3 and Comparative Examples 1, 2, 3. The free radical scavenging effects of Examples 1, 2, 3 and Comparative Example 2 all reached 97% within five minutes, while the free radical scavenging effects of Comparative Examples 1 and 3 were poor. The results demonstrate that the obtained functionalized glycidyl ether polymer has excellent antioxidant effects at 2 mg PPG-TK per milliliter, while the antioxidant effects at 1 mg PPG-TK per milliliter and the one-step synthesis are slightly worse. Figure 4 The results showed that the antioxidant stress effects of Examples 1, 2, 3 and Comparative Examples 1, 2, 3 were better than those of Comparative Examples 1 and 3. Figure 5 and Figure 6 The antibacterial effects of Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3 are presented. Figure 5 For macroscopic photo comparison, Figure 6 For the calculation of antibacterial rate, the results showed that the functionalized glycidyl ether polymer with more than 4 mg PPG-HBPL per milliliter had excellent antibacterial properties, while the antibacterial properties of 2 mg PPG-HBPL per milliliter and the one-step synthesis were not outstanding. Figure 7The hydrogel dressing prepared in Example 3 is obtained by dissolving antibacterial glycidyl ether polymer and antioxidant glycidyl ether polymer in polyvinyl alcohol and then subjecting it to cyclic freeze-thaw cycles. This hydrogel dressing showed no significant liquid dissolution after being stored in a self-sealing bag at 25 degrees Celsius for 72 hours, and exhibited excellent water retention properties. The hydrogel dressing prepared in Example 3, which combines water retention, antioxidant and antibacterial properties, can accelerate wound healing and inhibit scar formation when applied to wounds.
Claims
1. A method for preparing a functionalized glycidyl ether-based polymer, characterized in that, The functionalization is to have both antibacterial and antioxidant functions. The method is to graft and modify the glycidyl ether-based polymer with antibacterial and antioxidant functional molecules respectively. The grafting process of different functional molecules is carried out independently to avoid competitive reactions and steric hindrance effects between functional groups. In application, the two types of grafted products are mixed to obtain the glycidyl ether-based polymer with both antibacterial and antioxidant functions.
2. The method for preparing the functionalized glycidyl ether-based polymer according to claim 1, characterized in that, The glycidyl ether-based polymer is at least one of polypropylene glycidyl ether, polyethylene glycol diglycidyl ether, poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate), and poly(ethylene-co-glycidyl methacrylate).
3. The method for preparing the functionalized glycidyl ether-based polymer according to claim 1, characterized in that, The preparation method includes the following steps: 1) Modify the glycidyl ether-based polymer with at least one of ketethiolated thiols or ketethiolated selenyl diamine to obtain antioxidant glycidyl ether-based polymer A; 2) Antibacterial glycidyl ether polymer B was obtained by modifying glycidyl ether polymers with lysine polymers and their derivatives with a number average molecular weight of 2000-10000 Da. 3) The obtained antioxidant glycidyl ether polymer A and antibacterial glycidyl ether polymer B are mixed to obtain a glycidyl ether polymer with both antibacterial and antioxidant functions.
4. The method for preparing the functionalized glycidyl ether-based polymer according to claim 3, characterized in that, The method described in 1) specifically involves adding ketethiolated thiols or ketethiolated selenyl diamine to an aqueous solution of glycidyl ether polymer, stirring at 40-60 degrees Celsius for 10-12 hours, grafting antioxidant molecules with epoxy bonds to obtain an antioxidant glycidyl ether polymer solution, and then performing dialysis and vacuum freeze-drying to obtain antioxidant glycidyl ether polymer A.
5. The method for preparing the functionalized glycidyl ether-based polymer according to claim 3, characterized in that, The method described in 2) specifically involves adding the antibacterial functional molecule lysine polymer and its derivatives to an aqueous solution of glycidyl ether polymer, stirring at 40-60 degrees Celsius for 10-12 hours, grafting the antibacterial functional molecule with epoxy bonds to obtain an antibacterial glycidyl ether polymer solution, and then dialyzing and freeze-drying it under vacuum to obtain antibacterial glycidyl ether polymer B.
6. The method for preparing the functionalized glycidyl ether-based polymer according to claim 3, characterized in that, The mass ratio of the mixed antioxidant glycidyl ether polymer A and the antibacterial glycidyl ether polymer B is 0.5-2.5:
1.
7. The method for preparing the functionalized glycidyl ether-based polymer according to claim 3, characterized in that, The lysine polymer and its derivatives are at least one of α-polylysine, ε-polylysine, dendritic polylysine, hyperbranched polylysine, and astral polylysine.
8. A functionalized glycidyl ether-based polymer, characterized in that, It is prepared by the method described in any one of claims 1-7.
9. An antibacterial, antioxidant, and water-retaining hydrogel dressing, characterized in that, The preparation method involves dissolving the glycidyl ether polymer with both antibacterial and antioxidant functions prepared by any one of claims 1-7 in a 10% polyvinyl alcohol solution. After centrifuging and defoaming the solution, the solution is poured into a mold. The mold is subjected to freeze-thaw treatment, and the freeze-thaw process is repeated for 3 cycles to obtain a hydrogel. The hydrogel is then sterilized by irradiation to obtain the dressing. One freeze-thaw cycle consists of freezing at -20°C for 3-8 hours and then thawing at room temperature for 6-24 hours.
10. The application of the antibacterial, antioxidant, and water-retaining hydrogel dressing according to claim 9 in the preparation of anti-scarring dressings.