Absorbable gel dressing of polymerized silver ion nanofiber and preparation method of absorbable gel dressing

Abstract

The invention discloses an absorbable gel dressing of polymerized silver ion nanofibers and a preparation method of the absorbable gel dressing. The gel dressing is prepared from the following components in percentage by mass: 1 to 4 percent of methacrylated sodium hyaluronate, 1 to 2.5 percent of carboxymethyl chitosan, 0.1 to 0.4 percent of reduced graphene oxide, 0.1 to 0.5 percent of sodium hyaluronate, 0.05 to 0.6 percent of bioactive glass, 0.0005 to 0.003 percent of titanium dioxide, 0.5 to 2.5 percent of antibacterial nano silver powder, 0.05 to 0.3 percent of chitosan particles and 0.0005 to 0.003 percent of exosome. According to the gel dressing provided by the invention, through the synergistic effect of the organic exosome component, the inorganic bioactive glass component and the titanium dioxide, angiogenesis and cell migration can be promoted, and the titanium dioxide has good adhesion to fibroblasts and endothelial cells and also has an excellent bacteriostatic effect; the gel dressing contains reduced graphene oxide, so that the gel dressing has an antibacterial effect while ensuring the mechanical strength of a carrier. The method is simple in preparation process, mild in reaction condition, free of toxic and harmful reagents and environmentally friendly.

Description

Technical Field

[0001] The invention relates to the technical field of medical dressings, in particular to an absorbable gel dressing of polymerized silver ion nanofibers and a preparation method thereof. Background Art

[0002] In daily life, people are prone to accidentally causing epidermal trauma in a variety of situations. In order to prevent wound infection, dressings are often used to cover the wound to form a protective layer on the wound surface, which acts as a physical barrier to prevent scarring and promote wound healing.

[0003] Currently, the dressings used for wound repair on the market are mainly divided into gel dressings, liquid dressings, non-woven dressings and spray dressings. Non-woven dressings are the most widely used, and they play an anti-infection role by infiltrating antimicrobial agents on the dressings. However, their shape is relatively fixed, which makes them inconvenient to use for wounds in specific parts. They have poor air permeability and are mostly fixed with adhesives, which may cause allergic reactions in some people. Although common liquid, spray and gel dressings are easy to use, they have a short action time, poor film-forming effect and poor clinical effect.

[0004] Therefore, it is necessary to develop a dressing that is suitable for a variety of wounds, is not prone to allergies, and can provide long-term protection and repair effects on the wound. Summary of the invention

[0005] The object of the present invention is to provide an absorbable gel dressing of polymerized silver ion nanofibers and a preparation method thereof, so as to solve the problems raised in the above-mentioned background technology.

[0006] To achieve the above-mentioned purpose, the present invention provides the following technical scheme: an absorbable gel dressing of polymerized silver ion nanofibers, wherein the gel dressing ingredients include, by mass percentage: 1-4% methacrylated sodium hyaluronate, 1-2.5% carboxymethyl chitosan, 0.1-0.4% reduced graphene oxide, 0.1-0.5% sodium hyaluronate, 0.05-0.6% bioactive glass, 0.0005-0.003% titanium dioxide, 0.5-2.5% antibacterial nano-silver powder, 0.05-0.3% chitosan particles and 0.0005-0.003% exosomes.

[0007] Preferably, the gel dressing ingredients include, by mass percentage: 2% sodium methacrylate hyaluronate, 1.5-2% carboxymethyl chitosan, 0.2% reduced graphene oxide, 0.3% sodium hyaluronate, 0.1-0.2% bioactive glass, 0.001-0.002% titanium dioxide, 1% antibacterial nanosilver powder, 0.1-0.2% chitosan particles and 0.001-0.002% exosomes.

[0008] A method for preparing the composite hydrogel dressing according to claim 1 or 2, comprising the following steps:

[0009] S1. preparing methacryloyl sodium hyaluronate;

[0010] S2. dissolving carboxymethyl chitosan in deionized water to obtain carboxymethyl chitosan hydrogel;

[0011] S3. The methacrylated sodium hyaluronate prepared in S1 is added to a phosphate buffer solution containing a photoinitiator under light-proof conditions, and then reduced graphene oxide is added under light-proof conditions, and stirred thoroughly to form a homogeneous viscous solution;

[0012] S4. Using ultraviolet light to irradiate the viscous solution obtained in S3 to cross-link it to form a gel as a gel dressing carrier;

[0013] S5. Sodium hyaluronate, recombinant collagen and polydeoxyribonucleotide are mixed and dissolved in purified water, and sterilized by wet heat to prepare a gel;

[0014] S6. Immersing the product obtained in S5 in a silver salt aqueous solution containing antibacterial nano-silver powder, so that the hydrogel material absorbs the silver ions loaded in the silver salt aqueous solution and adsorbs the antibacterial nano-silver to obtain a silver ion hydrogel dressing;

[0015] S7. Add the mixture obtained in S5 and the exosome-loaded chitosan particles, bioactive glass and titanium dioxide into the carboxymethyl chitosan hydrogel, mix well to obtain a composite hydrogel dressing.

[0016] Preferably, the preparation method of the chitosan particles comprises: dissolving chitosan in an aqueous solution of acetic acid and adjusting the pH value to 4.5-4.6 to obtain a chitosan solution; then dropping a sodium tripolyphosphate solution, mixing evenly, centrifuging, and adding deionized water to the precipitate to obtain a chitosan particle solution; adding exosomes derived from umbilical cord mesenchymal stem cells to the chitosan particle solution and mixing evenly to obtain exosome-loaded chitosan particles.

[0017] Preferably, the average particle size of the titanium dioxide is 10-60 nm.

[0018] Preferably, the chitosan is high viscosity chitosan with a viscosity of 300-700 m.Pas.

[0019] Preferably, the concentration of the chitosan solution is 0.1-0.3%, and the concentration of the sodium tripolyphosphate solution is 0.1-0.15%.

[0020] Preferably, in step S4, the wavelength of ultraviolet rays is 200 to 500 nm, and the irradiation time is 2 to 6 minutes.

[0021] Preferably, in step S5, the moist heat sterilization temperature is 120° C. and the time is 15 minutes.

[0022] Preferably, the method further comprises: packaging the composite hydrogel dressing after sterilization, or freeze-drying the composite hydrogel dressing first, and then adding deionized water to obtain the composite hydrogel dressing when in use.

[0023] The absorbable gel dressing of polymerized silver ion nanofibers and the preparation method thereof proposed by the present invention have the following beneficial effects:

[0024] 1. The gel dressing provided by the present invention can promote angiogenesis and cell migration through the synergistic effect of organic exosome components, inorganic bioactive glass components and titanium dioxide. Titanium dioxide has good adhesion to fibroblasts and endothelial cells and also has excellent antibacterial effect. At the same time, under the synergistic effect of various components, the dosage of the effective ingredient is significantly reduced.

[0025] 2. The gel dressing of the present invention contains reduced graphene oxide, which has antibacterial effect while ensuring the mechanical strength of the carrier. The preparation process of the present invention is simple, the reaction conditions are mild, there are no toxic or harmful reagents, and it is environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The present invention is a schematic diagram of the preparation steps of an absorbable gel dressing of polymerized silver ion nanofibers and a preparation method thereof. DETAILED DESCRIPTION

[0027] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] See also Figure 1 The present invention provides a technical solution: an absorbable gel dressing of polymerized silver ion nanofibers, wherein the gel dressing ingredients include, by mass percentage: 1-4% methacrylated sodium hyaluronate, 1-2.5% carboxymethyl chitosan, 0.1-0.4% reduced graphene oxide, 0.1-0.5% sodium hyaluronate, 0.05-0.6% bioactive glass, 0.0005-0.003% titanium dioxide, 0.5-2.5% antibacterial nano-silver powder, 0.05-0.3% chitosan particles and 0.0005-0.003% exosomes.

[0029] As a preferred embodiment, further, the gel dressing ingredients include, by mass percentage: 2% sodium methacrylate hyaluronate, 1.5-2% carboxymethyl chitosan, 0.2% reduced graphene oxide, 0.3% sodium hyaluronate, 0.1-0.2% bioactive glass, 0.001-0.002% titanium dioxide, 1% antibacterial nanosilver powder, 0.1-0.2% chitosan particles and 0.001-0.002% exosomes.

[0030] Preparation of chitosan nanoparticles: Take 0.25g high viscosity chitosan (400-600m.PS) and dissolve it in 100ml of 1% acetic acid, and stir it with a magnetic stirrer until it is fully dissolved. Use 1N (1mol / L) sodium hydroxide solution to adjust the pH value to 4.6-4.8; then add 0.1% sodium tripolyphosphate dropwise with a pipette while stirring, until the volume ratio is (chitosan solution: sodium tripolyphosphate solution = 3:1), and obtain a turbid solution containing chitosan nanoparticles. Then centrifuge at 2000×g for 10 minutes, remove the supernatant, resuspend the precipitate with 5% of the original volume of deionized water and ultrasonicate to obtain a chitosan particle solution.

[0031] Preparation of exosomes: The cell culture medium of mesenchymal stem cells was ultracentrifuged at 300g, 2000g, 16500g, and finally 100000g for 70min. The concentration of the obtained exosomes was detected by BCA method.

[0032] According to the exosome content of the final dressing being 10ug / ml and the chitosan particle content being 0.1%, the exosomes were added to the chitosan nanoparticle solution, and then the mixture of the two was added to 2% carboxymethyl chitosan hydrogel and mixed.

[0033] Adding bioactive glass: weigh 0.1 g of bioactive glass and add it to 100 ml of carboxymethyl chitosan solution to obtain a mixed solution containing bioactive glass with a final concentration of 0.1%.

[0034] Add titanium dioxide nanoparticles. Weigh 0.001 g of titanium dioxide particles with a diameter of about 20 nm and add them to 100 ml of carboxymethyl chitosan composite hydrogel to a final concentration of 0.001%.

[0035] Preparation of sodium methacrylated hyaluronate: Weigh sodium hyaluronate, add it to sodium hydroxide solution to a total weight of 10g, fully mix and stir to dissolve until a homogeneous viscous solution is obtained, mechanically stir at a speed of 20rpm at low temperature, add methacrylic anhydride after the temperature of the viscous solution stabilizes, stir until the reaction is completed, slowly add a sodium bicarbonate solution with a mass concentration of 0.5% to the reaction system while stirring until no bubbles are generated in the system, stop stirring, add excess ethanol to the system, and obtain a white flocculent precipitate. Repeat the precipitation 3 times, collect the precipitate, vacuum dry it at 40°C, dissolve the dried product in purified water, and freeze-dry it to obtain sodium methacrylated hyaluronate.

[0036] Preparation of dressing carrier: Weigh Irgacure 2959, dissolve it in PBS solution to a total weight of 10 g, then weigh the prepared sodium methacrylated hyaluronate and reduced graphene oxide, add them to the Irgacure 2959-PBS solution in a light-proof environment, mix and stir thoroughly to dissolve until a homogeneous viscous solution is obtained, and then irradiate with ultraviolet light to cross-link it into a gel.

[0037] Finally, a composite hydrogel dressing (containing 2% carboxymethyl chitosan, 0.1% chitosan particles, 10ug / ml exosomes, 0.1% bioactive glass, and 0.001% titanium dioxide) was obtained, sterilized, and then packaged (sealed in a sterile container for storage).

[0038] A method for preparing the composite hydrogel dressing according to claim 1 or 2, comprising the following steps:

[0039] S1. preparing methacryloyl sodium hyaluronate;

[0040] S2. dissolving carboxymethyl chitosan in deionized water to obtain carboxymethyl chitosan hydrogel;

[0041] S3. The methacrylated sodium hyaluronate prepared in S1 is added to a phosphate buffer solution containing a photoinitiator under light-proof conditions, and then reduced graphene oxide is added under light-proof conditions, and stirred thoroughly to form a homogeneous viscous solution;

[0042] S4. Using ultraviolet light to irradiate the viscous solution obtained in S3 to crosslink it to form a gel as a gel dressing carrier, the ultraviolet wavelength is 200 to 500 nm, and the irradiation time is 2 to 6 minutes;

[0043] S5. Sodium hyaluronate, recombinant collagen and polydeoxyribonucleotide are mixed and dissolved in purified water, and sterilized by wet heat to form a gel. The wet heat sterilization temperature is 120°C for 15 minutes.

[0044] S6. Immersing the product obtained in S5 in a silver salt aqueous solution containing antibacterial nano-silver powder, so that the hydrogel material absorbs the silver ions loaded in the silver salt aqueous solution and adsorbs the antibacterial nano-silver to obtain a silver ion hydrogel dressing;

[0045] S7. Add the mixture obtained in S5 and the exosome-loaded chitosan particles, bioactive glass and titanium dioxide to the carboxymethyl chitosan hydrogel, wherein the average particle size of the titanium dioxide is 10-60 nm, and mix them evenly to obtain a composite hydrogel dressing;

[0046] S8. The composite hydrogel dressing is sterilized and then packaged, or freeze-dried first, and then deionized water is added to obtain the composite hydrogel dressing when used.

[0047] As a preferred embodiment, further, the preparation method of the chitosan particles includes: dissolving chitosan in an aqueous solution of acetic acid and adjusting the pH value to 4.5-4.6 to obtain a chitosan solution; then adding a sodium tripolyphosphate solution dropwise, mixing evenly, centrifuging, and adding deionized water to the precipitate to obtain a chitosan particle solution; adding exosomes derived from umbilical cord mesenchymal stem cells to the chitosan particle solution and mixing evenly to obtain exosome-loaded chitosan particles, wherein the chitosan is a high-viscosity chitosan with a viscosity of 300-700 m.Pas, the concentration of the chitosan solution is 0.1-0.3%, and the concentration of the sodium tripolyphosphate solution is 0.1-0.15%.

[0048] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. An absorbable gel dressing of polymerized silver ion nanofibers, characterized in that: The gel dressing ingredients include, by mass percentage, 1-4% methacrylated sodium hyaluronate, 1-2.5% carboxymethyl chitosan, 0.1-0.4% reduced graphene oxide, 0.1-0.5% sodium hyaluronate, 0.05-0.6% bioactive glass, 0.0005-0.003% titanium dioxide, 0.5-2.5% antibacterial nano-silver powder, 0.05-0.3% chitosan particles and 0.0005-0.003% exosomes.

2. The absorbable gel dressing of polymerized silver ion nanofibers according to claim 1, characterized in that: The gel dressing ingredients include, by mass percentage, 2% methacrylated sodium hyaluronate, 1.5-2% carboxymethyl chitosan, 0.2% reduced graphene oxide, 0.3% sodium hyaluronate, 0.1-0.2% bioactive glass, 0.001-0.002% titanium dioxide, 1% antibacterial nano-silver powder, 0.1-0.2% chitosan particles and 0.001-0.002% exosomes.

3. A method for preparing the composite hydrogel dressing according to claim 1 or 2, characterized in that: The steps include: S1. preparing methacryloyl sodium hyaluronate; S2. dissolving carboxymethyl chitosan in deionized water to obtain carboxymethyl chitosan hydrogel; S3. The methacrylated sodium hyaluronate prepared in S1 is added to a phosphate buffer solution containing a photoinitiator under light-proof conditions, and then reduced graphene oxide is added under light-proof conditions, and stirred thoroughly to form a homogeneous viscous solution; S4. Using ultraviolet light to irradiate the viscous solution obtained in S3 to cross-link it to form a gel as a gel dressing carrier; S5. Sodium hyaluronate, recombinant collagen and polydeoxyribonucleotide are mixed and dissolved in purified water, and sterilized by wet heat to prepare a gel; S6. Immersing the product obtained in S5 in a silver salt aqueous solution containing antibacterial nano-silver powder, so that the hydrogel material absorbs the silver ions loaded in the silver salt aqueous solution and adsorbs the antibacterial nano-silver to obtain a silver ion hydrogel dressing; S7. Add the mixture obtained in S5 and the exosome-loaded chitosan particles, bioactive glass and titanium dioxide into the carboxymethyl chitosan hydrogel, mix well to obtain a composite hydrogel dressing.

4. The method for preparing an absorbable gel dressing of polymerized silver ion nanofibers according to claim 3, characterized in that: The preparation method of the chitosan particles comprises: dissolving chitosan in an aqueous solution of acetic acid and adjusting the pH value to 4.5-4.6 to obtain a chitosan solution; then dropping a sodium tripolyphosphate solution, mixing evenly, centrifuging, and adding deionized water to the precipitate to obtain a chitosan particle solution; adding exosomes derived from umbilical cord mesenchymal stem cells to the chitosan particle solution and mixing evenly to obtain exosome-loaded chitosan particles.

5. The method for preparing an absorbable gel dressing of polymerized silver ion nanofibers according to claim 3, characterized in that: The average particle size of the titanium dioxide is 10-60 nm.

6. The method for preparing an absorbable gel dressing of polymerized silver ion nanofibers according to claim 4, characterized in that: The chitosan is high-viscosity chitosan with a viscosity of 300-700 m.Pas.

7. The method for preparing an absorbable gel dressing of polymerized silver ion nanofibers according to claim 4, characterized in that: The concentration of the chitosan solution is 0.1-0.3%, and the concentration of the sodium tripolyphosphate solution is 0.1-0.15%.

8. The method for preparing an absorbable gel dressing of polymerized silver ion nanofibers according to claim 3, characterized in that: In the step S4, the wavelength of the ultraviolet light is 200 to 500 nm, and the irradiation time is 2 to 6 minutes.

9. The method for preparing an absorbable gel dressing of polymerized silver ion nanofibers according to claim 3, characterized in that: In step S5, the moist heat sterilization temperature is 120° C. and the time is 15 minutes.

10. The method for preparing an absorbable gel dressing of polymerized silver ion nanofibers according to claim 3, characterized in that: Also includes: The composite hydrogel dressing is packaged after being sterilized, or is freeze-dried first, and then deionized water is added to obtain the composite hydrogel dressing when used.

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