Dressing with repairing function and preparation method thereof

Abstract

The invention relates to the technical field of medical dressings, in particular to a preparation method of a dressing with a repairing function, which comprises the following steps: mixing citric acid modified fucoidin and chitosan, adding water, heating, performing ultrasonic oscillation, adding a cross-linking agent, and heating while stirring to obtain a stock solution; mixing a calendula extract, a centella asiatica extract, a dandelion extract, a green tea extract and honey, adding the mixture into a high-speed dispersion machine, adding water, dispersing at a high speed, adding the mixture into the stock solution, continuously stirring, filtering, evaporating, standing and defoaming to obtain a precursor solution; soaking the porous skeleton in the precursor solution, enabling the precursor solution to permeate into pores of the porous skeleton through capillary action, and performing irradiation crosslinking curing to obtain the dressing with the repairing function. According to the dressing with the repairing function, specific components are selected for matching, a specific method is adopted for preparation, and the prepared dressing with the repairing function has good moisture retention, antibacterial property and mechanical strength while maintaining the good wound repairing function.

Description

Technical Field

[0001] The present application relates to the technical field of medical dressings, and in particular to a dressing with a repair function and a preparation method thereof. Background Art

[0002] Medical dressings are medical materials used to cover wounds, promote healing and protect wounds from infection, and play a very important role in human health.

[0003] Traditional medical dressings are gauze, which are made of cotton or synthetic fibers. They have good air permeability, but poor moisture retention and are prone to adhesion to wounds. There are many types of modern dressings, including hydrogel dressings, hydrocolloid dressings, foam dressings, alginate dressings, silver ion dressings, and nanofiber dressings, among which hydrogel dressings and nanofiber dressings are more popular. Hydrogel dressings have good moisture retention, relieve pain, and are easy to use, but they are weak and easy to tear; nanofiber dressings are naturally antibacterial and have high strength, but they have poor moisture retention and are more dependent on the fiber's ability to absorb liquid.

[0004] Therefore, there is an urgent need to provide a more comprehensive medical dressing that is not only easy to use but also has multiple functions such as moisturizing, antibacterial, and strength to cope with different types of trauma. Summary of the invention

[0005] The present application aims to overcome at least one of the defects of the prior art and provide a dressing with a repair function and a preparation method thereof. By selecting specific components for combination and adopting a specific preparation method, the prepared dressing with a repair function has the advantages of both a hydrogel dressing and a nanofiber dressing. While maintaining a good wound repair function, it has good moisture retention, antibacterial properties and mechanical strength.

[0006] In a first aspect, the present application provides a method for preparing a dressing with a repair function, which is achieved through the following technical solutions:

[0007] A method for preparing a dressing with a repair function comprises the following steps:

[0008] (1) Mix 20-40 parts of citric acid-modified fucoidan and 6-12 parts of chitosan by weight, add 60-120 parts of deionized water in an ultrasonic oscillator, heat and oscillate ultrasonically, then add 2-3 parts of a crosslinking agent, heat and stir while heating to obtain a fucoidan hydrogel stock solution;

[0009] (2) 1-2 parts of calendula extract, 1-2 parts of Centella asiatica extract, 1-2 parts of dandelion extract, 2-3 parts of green tea extract, and 1-2 parts of honey are mixed and added to a high-speed disperser, and then 25-60 parts of deionized water are added. After high-speed dispersion, the mixture is added to the fucoidan hydrogel stock solution of step (1), and the mixture is continuously stirred and mixed, and then filtered, evaporated, and allowed to stand to remove bubbles, to obtain a fucoidan hydrogel precursor solution;

[0010] (3) Immersing the nanofiber porous skeleton structure in the fucoidan hydrogel precursor solution of step (2), allowing the fucoidan hydrogel precursor solution to penetrate into the pores of the nanofiber porous skeleton structure by capillary action, and cross-linking and curing the structure by electron beam irradiation to obtain a dressing with repair function.

[0011] According to the method for preparing a dressing with a repair function according to an embodiment of the present application, there are at least the following beneficial effects:

[0012] The preparation method of the present application is to fill the fucoidan hydrogel into the porous skeleton structure of the nanofibers. The nanofiber skeleton provides good mechanical strength and structural stability, which makes up for the disadvantage of insufficient mechanical strength of the hydrogel. The composite dressing has both the flexibility of the nanofibers and the elasticity of the hydrogel, and can adapt to changes in wound shape; the high water content of the hydrogel can keep the wound moist, promote cell migration and proliferation, and accelerate wound healing. The lubricating effect of the hydrogel reduces the adhesion between the dressing and the wound, and alleviates the pain during dressing changes; the hydrogel can be used as a drug carrier to achieve sustained and controlled release of drugs, and the nanofiber skeleton provides a channel for drug release, which can load multiple drugs at the same time to achieve multiple functions such as antibacterial, anti-inflammatory, and healing promotion; the high specific surface area of ​​the nanofibers is conducive to cell attachment and growth, and the moist environment of the hydrogel promotes cell migration and proliferation. Both materials have good biocompatibility and reduce immune rejection reactions.

[0013] The fucoidan of the present application is an excellent natural moisturizer with good hygroscopicity and moisturizing properties. It can effectively lock in skin moisture, prevent dryness, maintain a moist environment for the wound, promote cell regeneration and wound healing, and has broad-spectrum antibacterial and antiviral effects. It can stimulate cell regeneration, accelerate the repair of skin cells, and reduce scar formation. Fucoidan also has an immunomodulatory effect, which can stimulate the body to produce a specific immune response and enhance immunity. In dressings, it helps to improve the local immune defense capability of the wound, prevent the spread of infection, and further promote wound healing.

[0014] The fucoidan of the present application contains sulfate groups, which can be complexed with components such as calendula extract, Centella asiatica extract, dandelion extract, and green tea extract to increase the loading capacity of the hydrogel and slow down the release of active ingredients.

[0015] The calendula extract of the present application is a natural ingredient, suitable for sensitive skin, and can be anti-inflammatory, antibacterial, and promote cell regeneration; Centella asiatica extract is a traditional herbal medicine with high safety, and can promote collagen synthesis, accelerate wound healing, and reduce scar formation; Dandelion extract can be anti-inflammatory and detumescent, antibacterial, antiviral, promote wound healing, and soothe the skin; Green tea extract is rich in polyphenol compounds, has antioxidant, anti-inflammatory and antibacterial effects, and helps reduce oxidative stress; Honey is natural and easy to obtain, suitable for a variety of wound types, has antibacterial, anti-inflammatory and moisturizing effects, and can promote wound healing.

[0016] According to some embodiments of the present application, the preparation of the nanofiber porous skeleton structure in step (3) comprises the following steps: dissolving 5-10 parts of polyvinyl alcohol in 100-120 parts of anhydrous ethanol by weight, mixing evenly, adding 20-60 parts of hydrated aluminum silicate and 1-2 parts of zinc chloride, mixing evenly, adding hydrochloric acid to adjust the pH value of the solution, and under light-proof and protective gas atmosphere conditions, adding dropwise 2-4 parts of an ethanol solution of 50% by mass of curcumin while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution; using an electrospinning device to spin the curcumin / hydrated aluminum silicate / polyvinyl alcohol solution into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 10-30 kV, collecting the curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers to form a nanofiber porous skeleton structure.

[0017] The hydrated aluminum silicate nanofibers of the present application have good biocompatibility, small size, high charge, strong hydrophilicity, can stably exist in an aqueous system, and can easily achieve good dispersion in a solution. In addition, the hydrated aluminum silicate nanofibers have a unique cavity structure, have strong adsorption capacity for a variety of molecules, can load curcumin, and at the same time control the release rate of curcumin to achieve a sustained release effect.

[0018] The polyvinyl alcohol of the present application has good hydrophilicity, and the antibacterial, anti-inflammatory and antioxidant properties of curcumin are combined with the hydrophilicity and water retention capacity of polyvinyl alcohol to improve the hydrophilicity, high swelling capacity and high drug absorption of the dressing, and can promote cell survival and proliferation.

[0019] Zn in this application 2+ The formation of a complex with curcumin can enhance the structural strength of curcumin nanoparticles, enhance the stability of curcumin, and improve the bioavailability of curcumin. Zinc ions also have antibacterial and anti-inflammatory effects, promote cell proliferation and collagen synthesis, and promote wound healing. When combined with curcumin, it can further enhance the antibacterial, anti-inflammatory and wound repair functions of the dressing.

[0020] Furthermore, the pH value of the adjustment solution is 5-6.5. Adjusting the pH value of the solution to 5-6.5 can keep the pH value of the reaction solution relatively stable and inhibit the Zn 2+ The hydrolysis of curcumin-Zn 2+ The stability of the complex reduces the decomposition of curcumin and promotes the reaction. If the pH value of the reaction system is too high, curcumin is easily decomposed. 2+ It is easy to hydrolyze, which affects the formation of the complex.

[0021] Furthermore, the parameters of the electrospinning equipment include: a receiving distance of 10-20 cm, and a liquid outlet speed of 5-20 μL / min.

[0022] According to some embodiments of the present application, the method for preparing citric acid-modified fucoidan in step (1) comprises the following steps:

[0023] Add fucoidan to citric acid solution, add EDC, stir, react at 70-90°C for 2h-4h, then cool the solution, adjust the pH to 6.5-7.5, dialyze with tap water for 40h-50h, dialyze with distilled water for 20h-30h, and then freeze-dry to obtain citric acid-modified fucoidan.

[0024] Furthermore, the usage ratio of the fucoidan, the citric acid and the EDC is (5-10) mg:(0.04-0.06) mmol:(0.05-0.1) mmol.

[0025] By using citric acid to modify fucoidan, the citric acid-modified fucoidan has good biocompatibility and will not cause obvious immune response or tissue damage. The solubility of the citric acid-modified fucoidan in water is improved, which is beneficial to its loading in the hydrogel. At the same time, the citric acid-modified fucoidan has better stability and biological activity, such as anti-inflammatory and antioxidant effects, which improves the repair effect of the dressing.

[0026] According to some embodiments of the present application, the cross-linking agent in step (1) is at least one of N-hydroxymethyl acrylamide, tetramethyl-1,2-ethylenediamine, hexamethylenetetramine, and aluminum glycolate.

[0027] According to some embodiments of the present application, the temperature of the ultrasonic oscillation in step (1) is 45-55°C.

[0028] According to some embodiments of the present application, the frequency of the ultrasonic oscillation in step (1) is 25-30 kHz.

[0029] According to some embodiments of the present application, the ultrasonic intensity of the ultrasonic oscillation in step (1) is 2-3 W / cm2 .

[0030] According to some embodiments of the present application, the ultrasonic oscillation time in step (1) is 5-10 min.

[0031] According to some embodiments of the present application, the stirring speed in step (1) is 300-400 r / min.

[0032] According to some embodiments of the present application, the stirring time in step (1) is 1-2 hours.

[0033] According to some embodiments of the present application, the heating temperature in step (1) is 55-65°C.

[0034] In a second aspect, an embodiment of the present application provides a dressing with a repair function made by the preparation method of the above-mentioned dressing with a repair function.

[0035] A dressing with a repair function according to an embodiment of the present application has at least the following beneficial effects:

[0036] The dressing with repair function of the present application has good mechanical strength and structural stability, and has both the flexibility of nanofibers and the elasticity of hydrogels, and can adapt to changes in wound shape; it can keep the wound moist, promote cell migration and proliferation, and accelerate wound healing.

[0037] In a third aspect, the embodiments of the present application provide the use of the above-mentioned dressing with repair function in repairing skin wounds. Covering human skin wounds with the dressing with repair function of the present application can accelerate the repair and healing of the wound and reduce wound infection and inflammation. DETAILED DESCRIPTION

[0038] To make the purpose, technical solution and advantages of the present application clearer, the following will be further described in detail in conjunction with specific embodiments. The embodiments described here are only part of the embodiments of the present application and cannot be understood as limiting the scope of protection of the present application.

[0039] Example 1

[0040] Preparation of dressings with repair function:

[0041] (1) Preparation of a porous framework structure of nanofibers: 8 parts of polyvinyl alcohol were dissolved in 110 parts of anhydrous ethanol according to weight parts, and the mixture was uniformly mixed. 40 parts of hydrated aluminum silicate and 1.5 parts of zinc chloride were added, and the mixture was uniformly mixed. Hydrochloric acid was added to adjust the pH value of the solution to 6. Under light-proof and protective gas atmosphere conditions, 3 parts of a 50% by weight ethanol solution of curcumin were added dropwise while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution. An electrospinning device was used with a receiving distance of 15 cm and a liquid discharge rate of 10 μL / min. The curcumin / hydrated aluminum silicate / polyvinyl alcohol solution was spun into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 20 kV voltage. The curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers were collected to form a porous framework structure of nanofibers.

[0042] (2) Preparation of citric acid-modified fucoidan: fucoidan was added to a citric acid solution, EDC was added, stirred, and reacted at 80°C for 3 hours, then the solution was cooled, and the pH was adjusted to 7, dialyzed with tap water for 45 hours, dialyzed with distilled water for 25 hours, and then freeze-dried to obtain citric acid-modified fucoidan, wherein the amount ratio of the fucoidan, the citric acid and the EDC was 8 mg: 0.05 mmol: 0.07 mmol;

[0043] (3) 30 parts of citric acid-modified fucoidan and 9 parts of chitosan were mixed according to weight, and then 90 parts of deionized water were added to an ultrasonic oscillator. After heating, ultrasonic oscillation was performed for 8 minutes. The temperature of the ultrasonic oscillation was 50°C, the frequency of the ultrasonic oscillation was 28kHz, and the ultrasonic intensity of the ultrasonic oscillation was 2.5W / cm 2 , then add 2.5 parts of N-hydroxymethyl acrylamide, and heat to 60°C while stirring at a speed of 350 r / min for 1.5 hours to obtain a fucoidan hydrogel stock solution;

[0044] (4) 1.5 parts of calendula extract, 1.5 parts of Centella asiatica extract, 1.5 parts of dandelion extract, 2.5 parts of green tea extract and 1.5 parts of honey were mixed and added to a high-speed disperser, and then 40 parts of deionized water were added. After high-speed dispersion, the mixture was added to the fucoidan hydrogel stock solution, and the mixture was continuously stirred and mixed, and then filtered and evaporated, and allowed to stand to remove bubbles, to obtain a fucoidan hydrogel precursor solution;

[0045] (5) The nanofiber porous skeleton structure is immersed in a fucoidan hydrogel precursor solution, the fucoidan hydrogel precursor solution is infiltrated into the pores of the nanofiber porous skeleton structure by capillary action, and the nanofiber porous skeleton structure is cross-linked and cured by electron beam irradiation to obtain a dressing with repair function.

[0046] Example 2

[0047] Preparation of dressings with repair function:

[0048] (1) Preparation of a porous framework structure of nanofibers: Dissolve 10 parts of polyvinyl alcohol in 100 parts of anhydrous ethanol according to weight, mix well, add 60 parts of hydrated aluminum silicate and 1 part of zinc chloride, mix well, add hydrochloric acid to adjust the pH value of the solution to 6.5, and add 2 parts of a 50% by weight ethanol solution of curcumin dropwise under light-proof and protective gas atmosphere conditions while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution; use an electrospinning device with a receiving distance of 20 cm and a liquid outlet speed of 5 μL / min to spin the curcumin / hydrated aluminum silicate / polyvinyl alcohol solution into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 30 kV, collect the curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers, and form a porous framework structure of nanofibers;

[0049] (2) Preparation of citric acid-modified fucoidan: fucoidan was added to a citric acid solution, EDC was added, stirred, and reacted at a temperature of 70°C for 4 hours, then the solution was cooled, and the pH was adjusted to 6.5, dialyzed with tap water for 50 hours, dialyzed with distilled water for 20 hours, and then freeze-dried to obtain citric acid-modified fucoidan, wherein the amount ratio of the fucoidan, the citric acid and the EDC was 10 mg: 0.04 mmol: 0.1 mmol;

[0050] (3) 20 parts of citric acid-modified fucoidan and 12 parts of chitosan were mixed according to weight, and then 60 parts of deionized water were added to an ultrasonic oscillator. After heating, ultrasonic oscillation was performed for 10 minutes. The temperature of the ultrasonic oscillation was 45°C, the frequency of the ultrasonic oscillation was 30kHz, and the ultrasonic intensity of the ultrasonic oscillation was 2W / cm 2 , then add 3 parts of tetramethyl-1,2-ethylenediamine, and heat to 55°C while stirring at a speed of 300 r / min for 2 hours to obtain a fucoidan hydrogel stock solution;

[0051] (4) 2 parts of calendula extract, 1 part of Centella asiatica extract, 2 parts of dandelion extract, 2 parts of green tea extract, and 2 parts of honey are mixed and added to a high-speed disperser, and then 25 parts of deionized water are added. After high-speed dispersion, the mixture is added to the fucoidan hydrogel stock solution, and the mixture is continuously stirred and mixed, filtered, evaporated, and allowed to stand to remove bubbles, thereby obtaining a fucoidan hydrogel precursor solution;

[0052] (5) The nanofiber porous skeleton structure is immersed in a fucoidan hydrogel precursor solution, the fucoidan hydrogel precursor solution is infiltrated into the pores of the nanofiber porous skeleton structure by capillary action, and the nanofiber porous skeleton structure is cross-linked and cured by electron beam irradiation to obtain a dressing with repair function.

[0053] Example 3

[0054] Preparation of dressings with repair function:

[0055] (1) Preparation of a porous framework structure of nanofibers: Dissolve 5 parts of polyvinyl alcohol in 120 parts of anhydrous ethanol according to weight, mix well, add 20 parts of hydrated aluminum silicate and 2 parts of zinc chloride, mix well, add hydrochloric acid to adjust the pH value of the solution to 5, and add 4 parts of a 50% by weight ethanol solution of curcumin dropwise under light-proof and protective gas atmosphere conditions while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution; use an electrospinning device with a receiving distance of 10 cm and a liquid outlet speed of 20 μL / min to spin the curcumin / hydrated aluminum silicate / polyvinyl alcohol solution into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 10 kV, collect the curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers, and form a porous framework structure of nanofibers;

[0056] (2) Preparation of citric acid-modified fucoidan: fucoidan was added to a citric acid solution, EDC was added, stirred, and reacted at 90°C for 2 hours, then the solution was cooled, and the pH was adjusted to 7.5, dialyzed with tap water for 40 hours, dialyzed with distilled water for 30 hours, and then freeze-dried to obtain citric acid-modified fucoidan, wherein the amount ratio of the fucoidan, the citric acid and the EDC was 5 mg: 0.06 mmol: 0.05 mmol;

[0057] (3) 40 parts of citric acid-modified fucoidan and 6 parts of chitosan were mixed according to weight, and then 120 parts of deionized water were added to an ultrasonic oscillator. After heating, ultrasonic oscillation was performed for 5 minutes. The temperature of the ultrasonic oscillation was 55°C, the frequency of the ultrasonic oscillation was 25kHz, and the ultrasonic intensity of the ultrasonic oscillation was 3W / cm 2 , then add 2 parts of hexamethylenetetramine, and heat to 65°C while stirring at a speed of 400 r / min for 1 hour to obtain a fucoidan hydrogel stock solution;

[0058] (4) 1 part of calendula extract, 2 parts of Centella asiatica extract, 1 part of dandelion extract, 3 parts of green tea extract, and 1 part of honey are mixed and added to a high-speed disperser, and then 60 parts of deionized water are added. After high-speed dispersion, the mixture is added to the fucoidan hydrogel stock solution, and the mixture is continuously stirred and mixed, filtered, evaporated, and allowed to stand to remove bubbles, thereby obtaining a fucoidan hydrogel precursor solution;

[0059] (5) The nanofiber porous skeleton structure is immersed in a fucoidan hydrogel precursor solution, the fucoidan hydrogel precursor solution is infiltrated into the pores of the nanofiber porous skeleton structure by capillary action, and the nanofiber porous skeleton structure is cross-linked and cured by electron beam irradiation to obtain a dressing with repair function.

[0060] Example 4

[0061] Preparation of dressings with repair function:

[0062] (1) Preparation of a porous framework structure of nanofibers: Dissolve 7 parts of polyvinyl alcohol in 110 parts of anhydrous ethanol according to weight, mix well, add 50 parts of hydrated aluminum silicate and 2 parts of zinc chloride, mix well, add hydrochloric acid to adjust the pH value of the solution to 5.5, and add 3 parts of a 50% by weight ethanol solution of curcumin dropwise under light-proof and protective gas atmosphere conditions while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution; use an electrospinning device with a receiving distance of 15 cm and a liquid discharge rate of 15 μL / min to spin the curcumin / hydrated aluminum silicate / polyvinyl alcohol solution into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 20 kV, collect the curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers, and form a porous framework structure of nanofibers;

[0063] (2) Preparation of citric acid-modified fucoidan: fucoidan was added to a citric acid solution, EDC was added, stirred, and reacted at a temperature of 80°C for 3 hours, then the solution was cooled, and the pH was adjusted to 6, dialyzed with tap water for 45 hours, dialyzed with distilled water for 25 hours, and then freeze-dried to obtain citric acid-modified fucoidan, wherein the amount ratio of the fucoidan, the citric acid and the EDC was 6 mg: 0.05 mmol: 0.08 mmol;

[0064] (3) 30 parts of citric acid-modified fucoidan and 8 parts of chitosan were mixed according to weight, and then 100 parts of deionized water were added to an ultrasonic oscillator. After heating, ultrasonic oscillation was performed for 8 minutes. The temperature of the ultrasonic oscillation was 50°C, the frequency of the ultrasonic oscillation was 28kHz, and the ultrasonic intensity of the ultrasonic oscillation was 2.5W / cm 2 , then add 2.5 parts of aluminum glycolate, and heat to 60°C while stirring at a speed of 350 r / min for 1 hour to obtain a fucoidan hydrogel stock solution;

[0065] (4) 1.5 parts of calendula extract, 1 part of Centella asiatica extract, 2 parts of dandelion extract, 2.5 parts of green tea extract, and 2 parts of honey were mixed and added to a high-speed disperser, and then 35 parts of deionized water were added. After high-speed dispersion, the mixture was added to the fucoidan hydrogel stock solution, and the mixture was continuously stirred and mixed, and then filtered, evaporated, and allowed to stand to remove bubbles, to obtain a fucoidan hydrogel precursor solution;

[0066] (5) The nanofiber porous skeleton structure is immersed in a fucoidan hydrogel precursor solution, the fucoidan hydrogel precursor solution is infiltrated into the pores of the nanofiber porous skeleton structure by capillary action, and the nanofiber porous skeleton structure is cross-linked and cured by electron beam irradiation to obtain a dressing with repair function.

[0067] Comparative Example 1

[0068] Preparation of dressings with repair function:

[0069] (1) Preparation of a porous framework structure of nanofibers: 8 parts of polyvinyl alcohol were dissolved in 110 parts of anhydrous ethanol according to weight parts, and the mixture was uniformly mixed. 40 parts of hydrated aluminum silicate were added, and the mixture was uniformly mixed. Hydrochloric acid was added to adjust the pH value of the solution to 6. Under light-proof and protective gas atmosphere conditions, 3 parts of an ethanol solution of 50% by mass of curcumin were added dropwise while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution. An electrospinning device was used with a receiving distance of 15 cm and a liquid discharge rate of 10 μL / min. The curcumin / hydrated aluminum silicate / polyvinyl alcohol solution was spun into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 20 kV voltage. The curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers were collected to form a porous framework structure of nanofibers.

[0070] (2) Preparation of citric acid-modified fucoidan: fucoidan was added to a citric acid solution, EDC was added, stirred, and reacted at 80°C for 3 hours, then the solution was cooled, and the pH was adjusted to 7, dialyzed with tap water for 45 hours, dialyzed with distilled water for 25 hours, and then freeze-dried to obtain citric acid-modified fucoidan, wherein the amount ratio of the fucoidan, the citric acid and the EDC was 8 mg: 0.05 mmol: 0.07 mmol;

[0071] (3) 30 parts of citric acid-modified fucoidan and 9 parts of chitosan were mixed according to weight, and then 90 parts of deionized water were added to an ultrasonic oscillator. After heating, ultrasonic oscillation was performed for 8 minutes. The temperature of the ultrasonic oscillation was 50°C, the frequency of the ultrasonic oscillation was 28kHz, and the ultrasonic intensity of the ultrasonic oscillation was 2.5W / cm 2 , then add 2.5 parts of N-hydroxymethyl acrylamide, and heat to 60°C while stirring at a speed of 350 r / min for 1.5 hours to obtain a fucoidan hydrogel stock solution;

[0072] (4) 1.5 parts of calendula extract, 1.5 parts of Centella asiatica extract, 1.5 parts of dandelion extract, 2.5 parts of green tea extract and 1.5 parts of honey were mixed and added to a high-speed disperser, and then 40 parts of deionized water were added. After high-speed dispersion, the mixture was added to the fucoidan hydrogel stock solution, and the mixture was continuously stirred and mixed, and then filtered and evaporated, and allowed to stand to remove bubbles, to obtain a fucoidan hydrogel precursor solution;

[0073] (5) The nanofiber porous skeleton structure is immersed in a fucoidan hydrogel precursor solution, the fucoidan hydrogel precursor solution is infiltrated into the pores of the nanofiber porous skeleton structure by capillary action, and the nanofiber porous skeleton structure is cross-linked and cured by electron beam irradiation to obtain a dressing with repair function.

[0074] Comparative Example 2

[0075] Preparation of dressings with repair function:

[0076] (1) Preparation of a porous nanofiber skeleton structure: 8 parts of polyvinyl alcohol were dissolved in 110 parts of anhydrous ethanol according to weight, and the mixture was uniformly mixed. 40 parts of polylactic acid and 1.5 parts of zinc chloride were added, and the mixture was uniformly mixed. Hydrochloric acid was added to adjust the pH value of the solution to 6. Under light-proof and protective gas atmosphere conditions, 3 parts of a 50% ethanol solution of curcumin were added dropwise while stirring to obtain a curcumin / polylactic acid / polyvinyl alcohol solution. An electrospinning device was used with a receiving distance of 15 cm and a liquid discharge rate of 10 μL / min. The curcumin / polylactic acid / polyvinyl alcohol solution was spun into curcumin / polylactic acid / polyvinyl alcohol nanofibers under an electric field of 20 kV. The curcumin / polylactic acid / polyvinyl alcohol nanofibers were collected to form a porous nanofiber skeleton structure.

[0077] (2) Preparation of citric acid-modified fucoidan: fucoidan was added to a citric acid solution, EDC was added, stirred, and reacted at 80°C for 3 hours, then the solution was cooled, and the pH was adjusted to 7, dialyzed with tap water for 45 hours, dialyzed with distilled water for 25 hours, and then freeze-dried to obtain citric acid-modified fucoidan, wherein the amount ratio of the fucoidan, the citric acid and the EDC was 8 mg: 0.05 mmol: 0.07 mmol;

[0078] (3) 30 parts of citric acid-modified fucoidan and 9 parts of chitosan were mixed according to weight, and then 90 parts of deionized water were added to an ultrasonic oscillator. After heating, ultrasonic oscillation was performed for 8 minutes. The temperature of the ultrasonic oscillation was 50°C, the frequency of the ultrasonic oscillation was 28kHz, and the ultrasonic intensity of the ultrasonic oscillation was 2.5W / cm 2 , then add 2.5 parts of N-hydroxymethyl acrylamide, and heat to 60°C while stirring at a speed of 350 r / min for 1.5 hours to obtain a fucoidan hydrogel stock solution;

[0079] (4) 1.5 parts of calendula extract, 1.5 parts of Centella asiatica extract, 1.5 parts of dandelion extract, 2.5 parts of green tea extract and 1.5 parts of honey were mixed and added to a high-speed disperser, and then 40 parts of deionized water were added. After high-speed dispersion, the mixture was added to the fucoidan hydrogel stock solution, and the mixture was continuously stirred and mixed, and then filtered and evaporated, and allowed to stand to remove bubbles, to obtain a fucoidan hydrogel precursor solution;

[0080] (5) The nanofiber porous skeleton structure is immersed in a fucoidan hydrogel precursor solution, the fucoidan hydrogel precursor solution is infiltrated into the pores of the nanofiber porous skeleton structure by capillary action, and the nanofiber porous skeleton structure is cross-linked and cured by electron beam irradiation to obtain a dressing with repair function.

[0081] Comparative Example 3

[0082] Preparation of dressings with repair function:

[0083] (1) Preparation of a porous framework structure of nanofibers: 8 parts of polyvinyl alcohol were dissolved in 110 parts of anhydrous ethanol according to weight parts, and the mixture was uniformly mixed. 40 parts of hydrated aluminum silicate and 1.5 parts of zinc chloride were added, and the mixture was uniformly mixed. Hydrochloric acid was added to adjust the pH value of the solution to 6. Under light-proof and protective gas atmosphere conditions, 3 parts of a 50% by weight ethanol solution of curcumin were added dropwise while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution. An electrospinning device was used with a receiving distance of 15 cm and a liquid discharge rate of 10 μL / min. The curcumin / hydrated aluminum silicate / polyvinyl alcohol solution was spun into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 20 kV voltage. The curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers were collected to form a porous framework structure of nanofibers.

[0084] (2) 30 parts of fucoidan and 9 parts of chitosan were mixed according to weight, and then 90 parts of deionized water were added to an ultrasonic oscillator. After heating, ultrasonic oscillation was performed for 8 minutes. The temperature of the ultrasonic oscillation was 50°C, the frequency of the ultrasonic oscillation was 28kHz, and the ultrasonic intensity of the ultrasonic oscillation was 2.5W / cm 2 , then add 2.5 parts of N-hydroxymethyl acrylamide, and heat to 60°C while stirring at a speed of 350 r / min for 1.5 hours to obtain a fucoidan hydrogel stock solution;

[0085] (3) 1.5 parts of calendula extract, 1.5 parts of Centella asiatica extract, 1.5 parts of dandelion extract, 2.5 parts of green tea extract and 1.5 parts of honey were mixed and added to a high-speed disperser, and then 40 parts of deionized water were added. After high-speed dispersion, the mixture was added to the fucoidan hydrogel stock solution, and the mixture was continuously stirred and mixed, and then filtered, evaporated and allowed to stand to remove bubbles, to obtain a fucoidan hydrogel precursor solution;

[0086] (4) The nanofiber porous skeleton structure is immersed in a fucoidan hydrogel precursor solution, the fucoidan hydrogel precursor solution is infiltrated into the pores of the nanofiber porous skeleton structure by capillary action, and cross-linked and cured by electron beam irradiation to obtain a dressing with repair function.

[0087] Experimental example

[0088] The dressings with repair function prepared in Examples 1-4 and Comparative Examples 1-3 were tested for tensile strength, compressive strength, flame retardancy and corrosion resistance, respectively, and the test methods are as follows:

[0089] The elongation at break is tested according to the standard of GB / T 2421803-2010.

[0090] Cytotoxicity was tested according to the standard of GB / T 14233.2-2005.

[0091] Test method for antibacterial activity: The antibacterial activity of the skin wound repair membrane against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was tested by the agar diffusion method. The dressing with repair function was cut into discs with a diameter of 10 mm. After sterilization under ultraviolet light for 30 minutes, it was placed on a solidified agar culture dish evenly coated with 200 μL bacterial culture solution (3×108 CFU / mL). After incubation at 37°C for 24 hours, the diameter of the inhibition zone around the dressing with repair function was recorded.

[0092] Wound repair performance test method: The dressings with repair function prepared in Examples 1-4 and Comparative Examples 1-3 were applied to the wounds of mice to repair the wounds and observe the wound healing of the mice. The test method is as follows: 70 mice (in good health and weighing 30-40 g) were taken and divided into 7 groups, each with 10 mice. The dressings with repair function of Examples 1-4 and Comparative Examples 1-3 were applied respectively. A 3 cm × 3 cm area was reserved on the back of the mice to remove the back hair. After disinfection, a 1 cm × 1 cm wound was made on the back with a scalpel. The above dressings were cut into a size of 3 cm × 3 cm and applied to the wound surface. The hemostasis of the wound was observed. The dressings were changed once a day until the wounds of the mice were completely healed. The healing time of the wounds of the mice was counted.

[0093] The test data is shown in Table 1 below:

[0094] Table 1

[0095]

[0096]

[0097] It can be seen from Table 1 that the dressings with repair function prepared in Examples 1-4 of the present application have good wound healing properties, are non-cytotoxic, and have good tensile strength and antibacterial properties.

[0098] The raw materials for preparing the nanofiber porous skeleton structure in Comparative Example 1 do not contain zinc chloride, and the rest are the same as those in Example 1. The antibacterial performance and wound healing performance of the dressing with repair function prepared in Comparative Example 1 are significantly poor, indicating that the Zn 2+ The formation of a complex with curcumin can enhance the structural strength of curcumin nanoparticles, enhance the stability of curcumin, and improve the bioavailability of curcumin. Zinc ions also have antibacterial and anti-inflammatory effects, promote cell proliferation and collagen synthesis, and promote wound healing. When combined with curcumin, it can further enhance the antibacterial, anti-inflammatory and wound repair functions of the dressing.

[0099] The hydrated aluminum silicate in the raw material for preparing the nanofiber porous skeleton structure of Comparative Example 2 was replaced with polylactic acid, and the rest was the same as Example 1. The tensile strength, antibacterial performance and wound healing performance of the dressing with repair function prepared in Comparative Example 2 were significantly poor, indicating that the hydrated aluminum silicate nanofibers of the present application have good biocompatibility, small size, high charge, strong hydrophilicity, can exist stably in an aqueous system, and can easily achieve good dispersion in a solution. In addition, the hydrated aluminum silicate nanofibers have a unique cavity structure, strong adsorption capacity for a variety of molecules, can load curcumin, and control the release rate of curcumin to achieve a sustained release effect. Replacing hydrated aluminum silicate with polylactic acid will affect the comprehensive performance of the dressing.

[0100] The fucoidan in the preparation raw materials of Comparative Example 3 was not modified by citric acid, and the rest was the same as Example 1. The antibacterial performance and wound healing performance of the dressing with repair function prepared in Comparative Example 3 were significantly poorer, and the tensile strength was also reduced, indicating that by using citric acid to modify the fucoidan, the citric acid-modified fucoidan has good biocompatibility and will not cause obvious immune response or tissue damage. The solubility of the citric acid-modified fucoidan in water is improved, which is beneficial to its loading in the hydrogel. At the same time, the citric acid-modified fucoidan has better stability and biological activity, such as anti-inflammatory and antioxidant effects, which improves the repair effect of the dressing.

[0101] Although the embodiments of the present application have been shown and described, those skilled in the art will appreciate that various changes, modifications, substitutions or variations may be made to the embodiments without departing from the principles and purpose of the present application, and that the technical solutions after these changes, modifications, substitutions or variations will fall within the scope of protection of the present application.

Claims

1. A method for preparing a dressing with a repair function, characterized in that: The following steps are involved: (1) Mix 20-40 parts of citric acid-modified fucoidan and 6-12 parts of chitosan according to weight, add 60-120 parts of deionized water in an ultrasonic oscillator, heat and oscillate ultrasonically, then add 2-3 parts of a cross-linking agent, heat and stir while heating to obtain a fucoidan hydrogel stock solution; (2) 1-2 parts of calendula extract, 1-2 parts of Centella asiatica extract, 1-2 parts of dandelion extract, 2-3 parts of green tea extract and 1-2 parts of honey are mixed and added to a high-speed disperser, and then 25-60 parts of deionized water are added. After high-speed dispersion, the mixture is added to the fucoidan hydrogel stock solution in step (1), and the mixture is continuously stirred and mixed, and then filtered, evaporated and allowed to stand to remove bubbles, to obtain a fucoidan hydrogel precursor solution; (3) Immersing the nanofiber porous skeleton structure in the fucoidan hydrogel precursor solution prepared in step (2), allowing the fucoidan hydrogel precursor solution to penetrate into the pores of the nanofiber porous skeleton structure by capillary action, and cross-linking and curing the structure by electron beam irradiation to obtain a dressing with repair function.

2. The method for preparing a dressing with a repair function according to claim 1, characterized in that: The preparation of the nanofiber porous skeleton structure in step (3) comprises the following steps: dissolving 5-10 parts of polyvinyl alcohol in 100-120 parts of anhydrous ethanol by weight, mixing evenly, adding 20-60 parts of hydrated aluminum silicate and 1-2 parts of zinc chloride, mixing evenly, adding hydrochloric acid to adjust the pH value of the solution, and adding 2-4 parts of a 50% by mass ethanol solution of curcumin dropwise under light-proof and protective gas atmosphere conditions while stirring to obtain a curcumin / hydrated aluminum silicate / polyvinyl alcohol solution; using an electrospinning device to spin the curcumin / hydrated aluminum silicate / polyvinyl alcohol solution into curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers under an electric field of 10-30 kV, and collecting the curcumin / hydrated aluminum silicate / polyvinyl alcohol nanofibers to form a nanofiber porous skeleton structure.

3. The method for preparing a dressing with a repair function according to claim 2, characterized in that: The pH value of the adjustment solution is 5-6.

5.

4. The method for preparing a dressing with a repair function according to claim 2, characterized in that: The parameters of the electrospinning device include: a receiving distance of 10-20 cm and a liquid outlet speed of 5-20 μL / min.

5. The method for preparing a dressing with a repair function according to claim 1, characterized in that: The preparation method of citric acid-modified fucoidan in step (1) comprises the following steps: Add fucoidan to citric acid solution, add EDC, stir, react at 70-90°C for 2h-4h, then cool the solution, adjust the pH to 6.5-7.5, dialyze with tap water for 40h-50h, dialyze with distilled water for 20h-30h, and then freeze-dry to obtain citric acid-modified fucoidan.

6. The method for preparing a dressing with repair function according to claim 5, characterized in that: The usage ratio of the fucoidan, the citric acid and the EDC is (5-10) mg:(0.04-0.06) mmol:(0.05-0.1) mmol.

7. The method for preparing a dressing with repair function according to claim 1, characterized in that: The cross-linking agent in step (1) is at least one of N-hydroxymethyl acrylamide, tetramethyl-1,2-ethylenediamine, hexamethylenetetramine, and aluminum glycolate.

8. The method for preparing a dressing with repair function according to claim 1, characterized in that: The temperature of the ultrasonic oscillation in step (1) is 45-55°C.

9. A dressing with a repair function prepared by the method for preparing a dressing with a repair function according to any one of claims 1 to 8.

10. Use of the dressing with repair function as claimed in claim 9 in repairing skin wounds.

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