Supported cationic polymer, preparation method and application thereof
Through the polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymers, combined with hydrophilic acrylamide and natural polysaccharides, the problems of insufficient antibacterial activity and low biocompatibility of traditional antibacterial hydrogel dressings are solved, and better Antibacterial effect and biosafety avoid adhesions and drug resistance problems, and are suitable for industrial production.
Patent Information
- Application Number
- CN202411445562.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-16
- Publication Date
- 2025-01-17
AI Technical Summary
The existing antibacterial hydrogel dressings have antibacterial activity dose dependence, low biocompatibility, and long-term use leads to bacterial resistance and cytotoxicity problems. Traditional wound dressings lack the ability to absorb exudate and are prone to wound adhesion. .
Using polysaccharide-based antibacterial hydrogel dressings loaded with cationic polymers, a new antibacterial hydrogel dressing is formed by combining hydrophilic acrylamide, natural polysaccharides and cationic polymers, and is killed by electrostatic adsorption and hydrogen bonding. Bacteria avoids the adhesion problem of traditional dressings and improves antibacterial properties.
It provides better antibacterial effects, biocompatibility and biodegradability, avoids antibiotic resistance and cytotoxicity problems, and is simple in preparation and low in cost, suitable for industrial production.
Smart Images
Figure CN119320476A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of material science and relates to a loaded cationic polymer, a preparation method and application thereof. Background Art
[0002] During the wound healing process, damaged tissues are easily invaded by external bacteria, causing wound infection, which can even be life-threatening in severe cases. Currently, local debridement is often used in clinical practice to remove necrotic tissue, and traditional wound dressings such as gauze, bandages, and cotton are used for wound care. However, these wound care methods still have some limitations. For example, the use of local debridement to remove infected necrotic tissue can easily cause secondary damage to patients, increasing their pain; although traditional wound dressings such as gauze, bandages, and cotton can physically isolate wounds, their low ability to absorb exudate, lack of inherent antibacterial activity, and easy adhesion to wounds limit their further application.
[0003] As a new type of wound repair material, antibacterial hydrogel dressing can make up for the shortcomings of traditional wound care. It is a three-dimensional network polymer obtained by physical and chemical cross-linking of natural macromolecules or synthetic macromolecules. It has high water content, which is conducive to providing a moist environment for the wound surface and can prevent the wound from contacting external bacteria, effectively protecting the wound; it has good swelling performance, can absorb a large amount of wound exudate, and can effectively prevent wound adhesion problems; it can play an effective antibacterial and anti-infection role by loading various antibacterial substances.
[0004] At present, most antibacterial hydrogel dressings usually work by loading antibiotics and metal nanoparticles. However, the antibacterial activity of these two types of antibacterial materials is often dose-dependent when used, and they have shortcomings such as low biocompatibility. In addition, long-term and repeated use of antibiotics can easily lead to bacterial resistance, and long-term retention of metal ions in the body can easily cause cytotoxicity and tissue damage. The above shortcomings prompted researchers to develop an antibacterial hydrogel dressing with an innovative antibacterial mechanism for antibacterial repair of wounds. Summary of the invention
[0005] The purpose of the present invention is to provide a loaded cationic polymer, a preparation method and its application in view of the above-mentioned problems existing in the prior art. The technical problem to be solved by the present invention is to provide a loaded cationic polymer that can be used as an antibacterial hydrogel dressing and a preparation method thereof.
[0006] The purpose of the present invention can be achieved by the following technical solutions:
[0007] A method for preparing a polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer comprises the following steps:
[0008] (1) Prepare respectively an aqueous solution of acrylamide with a mass fraction of 5 wt% to 20 wt%, an aqueous solution of polysaccharide with a mass fraction of ≤5 wt%, and an aqueous solution of a cationic polymer with a mass fraction of 5 wt% to 10 wt%.
[0009] (2) A 5wt%-20wt% acrylamide aqueous solution, a 5wt% ≤5wt% polysaccharide aqueous solution, and a 5wt%-10wt% cationic polymer aqueous solution are fully mixed in a mass ratio of 10:(2-5):(3.5-10).
[0010] (3) Adding a cross-linking agent of 0.1% to 1% by weight of acrylamide and an initiator of 0.1% to 0.5% by weight of acrylamide to the mixed solution obtained in step (2), stirring at a low speed to evenly dissolve the cross-linking agent and the initiator.
[0011] (4) Add 0.5% to 1% of the total mass of the catalyst to the mixed solution obtained in step (3), and stir thoroughly until a viscous solution is obtained.
[0012] (5) The viscous material obtained in step (4) is injected into a porous mold, and then transferred to an oven at 60° C. to 80° C. to react for 3 to 6 hours, thereby obtaining a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer.
[0013] Preferably, the acrylamide solution, polysaccharide aqueous solution and cationic polymer aqueous solution in step (1) are prepared at room temperature and magnetically stirred at 500-1000 rpm for 10-20 min to make the solution evenly dispersed.
[0014] Preferably, the polysaccharide aqueous solution in step (1) is a mixture of one or more of a chitosan aqueous solution, a hyaluronic acid aqueous solution, a dextran aqueous solution and a sodium alginate aqueous solution.
[0015] Preferably, the chitosan solution in step (1) is prepared by mixing chitosan powder with a deacetylation degree of 65% to 90% and an acetic acid solution with a mass fraction of 1% to 5%.
[0016] Preferably, the molecular weight (MW) of hyaluronic acid in the hyaluronic acid aqueous solution in step (1) is 200 to 800 KDa.
[0017] Preferably, the molecular weight (MW) of the dextran aqueous solution in step (1) is 50,000 to 70,000 KDa.
[0018] Preferably, the cationic polymer aqueous solution in step (1) is a mixture of one or more of a polyethyleneimine aqueous solution, an ε-polylysine aqueous solution, a polyhexamethyleneguanidine hydrochloride aqueous solution, and polydimethyldiallylammonium hydrochloride.
[0019] Preferably, the mixing and stirring time of the acrylamide aqueous solution, the polysaccharide aqueous solution and the cationic polymer aqueous solution in step (2) is 3 to 5 minutes, and the rotation speed is 300 to 400 rpm.
[0020] Preferably, in step (3), the cross-linking agent is N,N-methylenebisacrylamide, and the initiator is a mixture of one or more of ammonium persulfate, sodium persulfate, and potassium persulfate.
[0021] Preferably, the mixing and stirring time of the polymer aqueous solution in step (3) is 2 to 5 minutes, and the rotation speed is 200 to 300 rpm.
[0022] Preferably, the catalyst in step (4) is tetramethylethylenediamine.
[0023] Preferably, the stirring time of the mixed solution in step (4) is 1 to 3 minutes, and the rotation speed is 300 to 400 rpm.
[0024] In order to overcome the technical problems and defects in the background technology, the present invention designs a novel polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymers. The antibacterial hydrogel dressing is polymerized by hydrophilic acrylamide, natural polysaccharides and cationic polymers. Hydrophilic acrylamide has excellent swelling properties, can absorb a large amount of exudate from the wound, and effectively avoids the problem of wound adhesion caused by gauze, bandages, cotton, etc. Natural polysaccharides, as a kind of polymer material of pure natural origin, have the advantages of wide sources, safety and non-toxicity, and have been widely used in the field of biomaterials to promote wound healing and repair. The use of natural polysaccharides to prepare antibacterial dressings has the advantages of high antibacterial efficiency, fast wound healing speed, simple preparation process, good biodegradability, etc. Although most natural polysaccharide polymers themselves have certain antibacterial properties, their antibacterial properties still need to be improved in actual clinical applications. Cationic antibacterial, as a new type of antibacterial technology, can replace antibiotics for daily antibacterial. Cationic polymers can combine with negatively charged bacteria through electrostatic adsorption and hydrogen bonding, destroying the protein structure on the bacterial cell wall, changing the permeability of the cell membrane, causing protein leakage in the bacteria and killing the bacteria. They have excellent antibacterial activity and less toxic side effects. Based on this, we load cationic polymers in natural polysaccharide-based antibacterial hydrogel dressings to give wound dressings excellent antibacterial properties to meet their actual clinical needs.
[0025] The beneficial effects of the present invention are:
[0026] 1. The antibacterial hydrogel dressing provided by the present invention has better antibacterial effect than traditional wound dressings such as gauze, bandages, and cotton, and can moisten the wound to prevent wound adhesion.
[0027] 2. The antibacterial hydrogel dressing provided by the present invention has excellent swelling performance and can absorb a large amount of wound exudate.
[0028] 3. The antibacterial hydrogel dressing provided by the present invention has excellent biocompatibility and biodegradability, and has better biosafety and is safer to use than traditional antibacterial hydrogels loaded with antibiotics and metal nanoparticles.
[0029] 4. The antibacterial hydrogel dressing provided by the present invention avoids the problems of antibiotic resistance and cytotoxicity caused by long-term use of antibacterial hydrogels loaded with antibiotics and metal nanoparticles.
[0030] 5. The preparation method of the antibacterial hydrogel dressing provided by the present invention is simple and easy, has excellent antibacterial effect, has readily available raw materials, has low production cost, and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS
[0031] Figure 1 This is a physical picture of the novel polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymer prepared in Example 1.
[0032] Figure 2 This is a diagram showing the antibacterial effect of the novel polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymer prepared in Example 2 on Staphylococcus aureus and Escherichia coli (inhibition zone method).
[0033] Figure 3 This is a diagram showing the antibacterial effect of the novel polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymer prepared in Example 3 on Staphylococcus aureus and Escherichia coli (plate count method).
[0034] Figure 4 This is a swelling performance curve of the novel polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymers prepared in Example 4. DETAILED DESCRIPTION
[0035] The following are specific embodiments of the present invention and the accompanying drawings to further describe the technical solution of the present invention, but the present invention is not limited to these embodiments.
[0036] Example 1: A method for preparing a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer, comprising the following steps:
[0037] (1) Prepare 5 wt% acrylamide aqueous solution, 5 wt% chitosan aqueous solution, and 5 wt% polyethyleneimine aqueous solution respectively. Stir magnetically at 500 rpm for 10 min at room temperature to make the solutions uniformly dispersed. The 5 wt% chitosan aqueous solution is prepared from chitosan powder with a deacetylation degree of 65% and 1 wt% acetic acid solution.
[0038] (2) A 5 wt % aqueous solution of acrylamide, a 5 wt % aqueous solution of chitosan, and a 5 wt % aqueous solution of polyethyleneimine were blended in a mass ratio of 10:2:3.5, and stirred for 3 min under a magnetic stirring device at 300 rpm to obtain a mixed solution of the three substances.
[0039] (3) Add 0.1% N,N-methylenebisacrylamide by weight of acrylamide and 0.1% potassium persulfate by weight of acrylamide to the mixed solution obtained in step (2), and stir at a low speed of 200 rpm under magnetic stirring for 2 minutes to evenly dissolve N,N-methylenebisacrylamide and potassium persulfate.
[0040] (4) Add 0.5% of tetramethylethylenediamine by weight of the total system to the mixed solution obtained in step (3), and stir the mixture under magnetic stirring at 300 rpm for 1 min until a viscous solution is obtained.
[0041] (5) The viscous material obtained in step (4) was injected into a porous mold, and then transferred to a 60°C oven for reaction for 3 hours to obtain a novel polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymers.
[0042] Prepared as Figure 1 Hydrogel dressing shown.
[0043] Example 2: A method for preparing a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer, comprising the following steps:
[0044] (1) Prepare 10 wt% acrylamide aqueous solution, 2 wt% hyaluronic acid (MW 200 KDa) aqueous solution, and 10 wt% polyethyleneimine aqueous solution respectively. Stir magnetically at 600 rpm for 10 min at room temperature to make the solutions evenly dispersed.
[0045] (2) A 10 wt % acrylamide aqueous solution, a 2 wt % hyaluronic acid aqueous solution, and a 5 wt % polyethyleneimine aqueous solution were mixed in a mass ratio of 10:5:10, and stirred for 4 min under a magnetic stirrer at 400 rpm to obtain a mixed solution of the three substances.
[0046] (3) Add 0.5% of N,N-methylenebisacrylamide by weight of acrylamide and 0.2% of sodium persulfate by weight of acrylamide to the mixed solution obtained in step (2), and stir at a low speed of 200 rpm under magnetic stirring for 3 minutes to uniformly dissolve N,N-methylenebisacrylamide and sodium persulfate.
[0047] (4) Add 1% of tetramethylethylenediamine by weight of the total mass of the system to the mixed solution obtained in step (3), and stir the mixture under magnetic stirring at 400 rpm for 3 min until a viscous solution is obtained.
[0048] (5) The viscous material obtained in step (4) is injected into a porous mold, and then transferred to an oven at 80° C. to react for 6 hours, thereby obtaining a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer.
[0049] Example 3: A method for preparing a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer, comprising the following steps:
[0050] (1) Prepare 15 wt% acrylamide aqueous solution, 3 wt% sodium alginate aqueous solution, and 5 wt% polyhexamethylene guanidine hydrochloride aqueous solution respectively, and stir magnetically at 600 rpm for 10 min at room temperature to make the solutions evenly dispersed.
[0051] (2) A 15 wt % acrylamide aqueous solution, a 3 wt % hyaluronic acid aqueous solution, and a 5 wt % polyhexamethylene guanidine hydrochloride aqueous solution were mixed in a mass ratio of 10:5:5, and stirred for 3 min under a magnetic stirring device at 350 rpm to obtain a mixed solution of the three substances.
[0052] (3) Add 0.1% of N,N-methylenebisacrylamide by weight of acrylamide and 0.5% of ammonium persulfate by weight of acrylamide to the mixed solution obtained in step (2), and stir at a low speed of 200 rpm under magnetic stirring for 3 minutes to uniformly dissolve N,N-methylenebisacrylamide and ammonium persulfate.
[0053] (4) Add 0.8% of tetramethylethylenediamine by weight of the total system to the mixed solution obtained in step (3), and stir the mixture under magnetic stirring at 300 rpm for 4 min until a viscous solution is obtained.
[0054] (5) The viscous material obtained in step (4) is injected into a porous mold, and then transferred to an oven at 80° C. to react for 4 hours, thereby obtaining a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer.
[0055] Example 4: A method for preparing a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer, comprising the following steps:
[0056] (1) Prepare 10 wt% acrylamide aqueous solution, 1 wt% dextran aqueous solution (MW 50000), and 5 wt% polydimethyldiallylammonium hydrochloride aqueous solution respectively. Stir magnetically at 1000 rpm for 20 min at room temperature to make the solution evenly dispersed.
[0057] (2) A 10 wt % acrylamide aqueous solution, a 1 wt % dextran aqueous solution, and a 5 wt % polyhexamethylene guanidine hydrochloride aqueous solution were mixed in a mass ratio of 10:3:6, and stirred for 4.5 min under a magnetic stirring machine at 400 rpm to obtain a mixed solution of the three substances.
[0058] (3) Add 0.15% of N,N-methylenebisacrylamide by weight of acrylamide and 0.3% of sodium persulfate by weight of acrylamide to the mixed solution obtained in step (2), and stir at a low speed of 300 rpm under magnetic stirring for 4.5 min to evenly dissolve N,N-methylenebisacrylamide and sodium persulfate.
[0059] (4) Add 1% of tetramethylethylenediamine by weight of the total mass of the system to the mixed solution obtained in step (3), and stir the mixture at 350 rpm for 1.5 min until a viscous solution is obtained.
[0060] (5) The viscous material obtained in step (4) is injected into a porous mold, and then transferred to a 70° C. oven for reaction for 4.5 hours to obtain a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer.
[0061] Figure 2 This is the antibacterial effect diagram of the new polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymers on Staphylococcus aureus and Escherichia coli (inhibition zone method). It can be seen from the figure that the antibacterial activity of the existing antibacterial dressing is not as good as the antibacterial dressing of this scheme.
[0062] Figure 3 This is a diagram showing the antibacterial effect of a novel polysaccharide-based antibacterial hydrogel dressing loaded with cationic polymers on Staphylococcus aureus and Escherichia coli (plate count method). It can be seen from the figure that the antibacterial activity of the existing antibacterial dressing is not as good as that of the antibacterial dressing of this scheme.
[0063] Figure 4 This is a swelling performance curve of a novel polysaccharide-based antibacterial hydrogel dressing loaded with a cationic polymer. It can be seen from the figure that the swelling performance of the existing antibacterial dressing is not as good as that of the antibacterial dressing of this solution.
[0064] The specific embodiments described herein are merely examples of the spirit of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in similar ways, but they will not deviate from the spirit of the present invention or exceed the scope defined by the appended claims.
Claims
1. A loaded cationic polymer, characterized in that: It includes an acrylamide aqueous solution with a mass fraction of 5wt% to 20wt%, a polysaccharide aqueous solution with a mass fraction of ≤5wt%, and a cationic polymer aqueous solution with a mass fraction of 5wt% to 10wt%, wherein the mass ratio of the acrylamide aqueous solution, the polysaccharide aqueous solution and the cationic polymer aqueous solution is 10:(2-5):(3.5-10).
2. The loaded cationic polymer according to claim 1, characterized in that The polysaccharide aqueous solution is a mixture of one or more of a chitosan aqueous solution, a hyaluronic acid aqueous solution, a dextran aqueous solution and a sodium alginate aqueous solution.
3. The loaded cationic polymer according to claim 1, characterized in that The chitosan solution is prepared by mixing chitosan powder with a deacetylation degree of 65% to 90% and acetic acid solution with a mass fraction of 1% to 5%. The molecular weight of hyaluronic acid in the hyaluronic acid aqueous solution is 200 to 800 KDa. The molecular weight of the dextran aqueous solution is 50,000 to 70,000 KDa.
4. The loaded cationic polymer according to claim 1, characterized in that The cationic polymer aqueous solution is a mixture of one or more of a polyethyleneimine aqueous solution, an ε-polylysine aqueous solution, a polyhexamethyleneguanidine hydrochloride aqueous solution, and polydimethyldiallylammonium hydrochloride.
5. A method for preparing the loaded cationic polymer according to any one of claims 1 to 4, characterized in that: The following steps are involved: (1) fully mixing the acrylamide aqueous solution, the polysaccharide aqueous solution and the cationic polymer aqueous solution according to a certain proportion; (2) adding a cross-linking agent of 0.1% to 1% by weight of acrylamide and an initiator of 0.1% to 0.5% by weight of acrylamide to the mixed solution obtained in step (1), and stirring at a low speed to uniformly dissolve the cross-linking agent and the initiator; (3) adding 0.5% to 1% of the total mass of the catalyst to the mixed solution obtained in step (2), and stirring thoroughly until a viscous solution is obtained; (4) The viscous solution obtained in step (3) is injected into a porous mold, and then transferred to an oven at 60° C. to 80° C. to react for 3 to 6 hours to obtain the loaded cationic polymer.
6. The method for preparing a loaded cationic polymer according to claim 5, characterized in that: The acrylamide solution, the polysaccharide aqueous solution and the cationic polymer aqueous solution are prepared at room temperature. During preparation, the acrylamide aqueous solution, the polysaccharide aqueous solution and the cationic polymer aqueous solution are magnetically stirred at 500-1000 rpm for 10-20 minutes to make each solution uniformly dispersed. In the step (1), the mixing and stirring time of the acrylamide aqueous solution, the polysaccharide aqueous solution and the cationic polymer aqueous solution is 3-5 minutes, and the rotation speed is 300-400 rpm. In the step (2), the stirring time of the mixed solution is 2-5 minutes, and the rotation speed is 200-300 rpm. In the step (3), the stirring time of the mixed solution is 1-3 minutes, and the rotation speed is 300-400 rpm.
7. The method for preparing a loaded cationic polymer according to claim 5, characterized in that: The cross-linking agent in step (2) is N,N-methylenebisacrylamide, and the initiator is a mixture of one or more of ammonium persulfate, sodium persulfate, and potassium persulfate.
8. The method for preparing a loaded cationic polymer according to claim 5, characterized in that: The catalyst is tetramethylethylenediamine.
9. An application of a loaded cationic polymer, characterized in that: The cationic polymer loaded as claimed in any one of claims 1 to 8 is applied in the field of biological antibacterial, as a polysaccharide-based antibacterial hydrogel dressing to replace the antibiotic-loaded antibacterial hydrogel and the metal nanoparticle-loaded antibacterial hydrogel.