Gel dressing for treating diabetic foot and preparation method thereof

Abstract

The invention relates to the technical field of gel dressings, in particular to a gel dressing for treating diabetic foot and a preparation method thereof. The gel dressing is prepared from the following raw materials in parts by weight: 10 to 15 parts of modified polyvinyl alcohol, 1 to 1.5 parts of modified nano-silver liposome, 1.5 to 2 parts of traditional Chinese medicine extract, 0.8 to 1.2 parts of ellagic acid, 0.6 to 0.8 part of hesperidin and 4 to 6 parts of chitosan. The dressing prepared by the invention has a three-dimensional network structure, can effectively resist bacteria and oxidation and promote wound healing, and is relatively good in stability.

Description

Technical Field

[0001] The invention relates to the technical field of gel dressings, and in particular to a gel dressing for treating diabetic foot and a preparation method thereof. Background Art

[0002] Diabetic foot is one of the common complications of diabetic patients, manifested as foot infection, ulcers, gangrene, etc., which can lead to amputation in severe cases. The occurrence of diabetic foot is related to many factors, including neuropathy, vascular disease, immunodeficiency, infection and trauma caused by diabetes. Dressings can maintain a moist environment at the ulcer site and release bioactive substances, thereby reducing ulcer infection and accelerating wound healing. They play an important role in the treatment of diabetic foot ulcers. Gel dressings are commonly used wound dressings. They are three-dimensional network materials constructed by natural polymers or synthetic polymers through covalent bonds or non-covalent bonds. They have the advantages of good biocompatibility and adjustable structure and function. When diabetic foot patients are in mild or early stages of the disease, the soles of their feet are affected by pressure or shear force during their activities, resulting in insufficient blood supply and susceptibility to bacterial infection, which may lead to worsening of the disease and wound deterioration. In addition, diabetic foot ulcers heal slowly due to bacterial infection and inflammatory response. Summary of the invention

[0003] In view of the deficiencies in the prior art, the present invention provides a gel dressing for treating diabetic foot and a preparation method thereof.

[0004] The present invention is achieved through the following technical solutions: A gel dressing for treating diabetic foot. The preparation raw materials include the following components in parts by weight: 10-15 parts of modified polyvinyl alcohol, 1-1.5 parts of modified nanosilver liposomes, 1.5-2 parts of traditional Chinese medicine extracts, 0.8-1.2 parts of ellagic acid, 0.6-0.8 parts of hesperidin, and 4-6 parts of chitosan.

[0005] Furthermore, the raw materials for preparing the modified polyvinyl alcohol include the following components in parts by weight: 20-30 parts of vinyl acetate (VAC) and 2-3 parts of resveratrol.

[0006] Furthermore, the preparation method of the modified polyvinyl alcohol comprises the following steps: A1: Take VAC, resveratrol and azobisisobutyronitrile and add them to methanol solvent, mix well, heat to 60-70℃, react for 3-4 hours, remove the solvent under reduced pressure, wash with methanol, and dry under vacuum to obtain VAC-resveratrol; A2: Add VAC-resveratrol obtained in step A1 to methanol, add 0.03-0.05 g / mL of sodium hydroxide methanol solution and mix well, heat in a 40°C water bath for 2-3 h, filter, wash the filter cake with methanol, and vacuum dry to obtain modified polyvinyl alcohol.

[0007] Furthermore, in step A1, the usage ratio of VAC to methanol solvent is 1 g:2 mL.

[0008] Furthermore, in step A1, the amount of azobisisobutyronitrile used is 1-1.5 wt % of VAC.

[0009] Furthermore, in step A2, the ratio of VAC-resveratrol to methanol is 1 g: 20-30 mL.

[0010] Furthermore, in step A2, the mass ratio of sodium hydroxide to VAC-resveratrol is 0.15-0.2:10.

[0011] Furthermore, the composition of the Chinese medicine extract includes the following components by weight: 1-2 parts of Salvia miltiorrhiza extract, 1.5-3 parts of Carthamus tinctorius extract, 2-3 parts of Lithospermum officinale extract, 1.5-2.5 parts of Scutellaria baicalensis extract and 2-4 parts of Centella asiatica extract.

[0012] Furthermore, the salvia miltiorrhiza extract, safflower extract, lithospermum officinale extract, scutellaria baicalensis extract and centella asiatica extract are all obtained by extraction and preparation through conventional technical means.

[0013] Furthermore, the raw materials for preparing the modified nanosilver liposomes include the following components in parts by weight: 3-4.5 parts of lecithin, 0.5-0.75 parts of cholesterol, 0.015-0.02 parts of distearoylphosphatidylethanolamine-polyethylene glycol-carboxyl (DSPE-PEG-COOH), 0.03-0.04 parts of oleanolic acid (OA), and 0.01-0.015 parts of nanosilver.

[0014] Furthermore, the preparation method of the modified nanosilver liposome comprises the following steps: B1: Dissolve DSPE-PEG-COOH, DMAP and EDC in CH2Cl2, stir at 0℃ for 1 h, add OA and continue to react for 1 h, react at room temperature for 12-14 h, remove the solvent by rotary evaporation, wash with ether, and dry in vacuum to obtain DSPE-PEG-OA; B2: Dissolve lecithin and cholesterol in a mixed solvent of chloroform and ether (v / v=4:1), remove the solvent by vacuum rotary evaporation at 40-60°C to obtain a lipid film, add 200 μg / mL of nanosilver solution, and hydrate by ultrasound at 250 W and 40 kHz to obtain a liposome suspension; B3: The liposome suspension obtained in step B2 was slowly injected with 2-4 mg / mL DSPE-PEG-OA solution obtained in step B1 while stirring, and the mixture was stirred evenly. The mixture was ultrasonicated in an ice-water bath for 10 min (500 W, with an interval of 3 s), and centrifuged at 3000 r / min for 8-12 min. The supernatant was taken to obtain the modified nanosilver liposomes.

[0015] Furthermore, in step B1, the mass concentration of OA in CH2Cl2 is 6-8 mg / mL.

[0016] Furthermore, in step B1, the mass ratio of OA, EDC and DMAP is 6-8:3-4:1-2.

[0017] Furthermore, in step B2, the mass concentration of cholesterol in the mixed solvent is 2.5-5 mg / mL.

[0018] Furthermore, the present invention also provides a method for preparing the gel dressing for treating diabetic foot, comprising the following steps: S1: Add modified polyvinyl alcohol into deionized water, stir at 80-90°C and 150-200 rpm for 1 h, add modified nanosilver liposomes, stir at 30-40°C and 100-150 rpm for 30 min, and continue stirring at room temperature for 1-2 h to obtain material a; S2: Dissolve chitosan with 1.5-2wt% acetic acid solution, stir at 200-300 rpm for 10-12 h, heat to 100°C and stir for 1-2 h to obtain a 4-5 wt% chitosan solution, add ellagic acid and deionized water, stir at 100°C for 1-1.5 h, add hesperidin, stir at room temperature for 40-60 min, and obtain material b; S3: Add the Chinese herbal medicine extract into deionized water and mix well to obtain a mixed solution, mix the material a obtained in step S1 and the material b obtained in step S2, pour into a mold and freeze at -80°C for 10-12 h, add to the mixed solution and soak at room temperature for 10-12 h, freeze at -20°C for 8-10 h, and thaw at room temperature until melted to obtain a gel dressing for treating diabetic foot.

[0019] Furthermore, in step S1, the mass fraction of the modified polyethylene glycol in deionized water is 2-4wt%.

[0020] Furthermore, in step S2, the mass ratio of ellagic acid to deionized water is 1:2-4.

[0021] Furthermore, in step S3, the ratio of the Chinese herbal extract to deionized water in the mixed solution is 1 g:15-20 mL.

[0022] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a gel dressing for treating diabetic foot, using modified polyvinyl alcohol and chitosan as substrates, adding modified nano silver liposomes, a variety of Chinese medicine extracts and ellagic acid, hesperidin and other active ingredients, various active ingredients are evenly distributed in the gel, improve the utilization rate and efficacy of the drug, synergistically play advantages, and cross-link to form a network structure. The present invention initiates a reaction by azobisisobutyronitrile, copolymerizes resveratrol and vinyl acetate, and then performs an alcoholysis reaction to obtain modified polyvinyl alcohol, introduces resveratrol on the polyvinyl alcohol chain, enhances hydrophilicity, improves biocompatibility, and improves utilization. The modified polyvinyl alcohol finally obtained not only has the basic characteristics of good film-forming and adhesion of polyvinyl alcohol, but also the anti-oxidation and anti-inflammatory effects of resveratrol help to improve the microenvironment of local tissues, reduce the inflammatory response of diabetic foot, inhibit oxidative stress, and promote wound healing. The present invention encapsulates nanosilver in liposomes. As a highly effective antibacterial agent, nanosilver can effectively inhibit the growth and reproduction of pathogens such as bacteria and fungi on the wound surface of diabetic foot ulcers, reducing the risk of infection. The modified structure of the liposome gives the nanosilver good biocompatibility, avoiding the cytotoxicity problem that may be caused by the direct use of nanosilver, while enhancing its retention time and effect on the wound surface. The liposome structure composed of lecithin and cholesterol can also provide certain protection and moisturizing effects for the wound surface, promoting cell repair and tissue regeneration. The present invention covalently grafts oleanolic acid onto DSPE-PEG-COOH to obtain DSPE-PEG-OA for modifying liposomes, utilizes the hydroxyl group on OA to form an ester bond with the carboxyl group at the end of DSPE-PEG-COOH, carries OA on the PEG chain end to form DSPE-PEG-OA, connects oleanolic acid to the PEG chain, improves its hydrophilicity, and is beneficial to the utilization of oleanolic acid, co-incubates DSPE-PEG-OA and liposome suspension, inserts the hydrophobic end (DSPE) molecule into the lipid membrane, and the hydrophilic part (PEG-OA) extends on the surface of the lipid membrane, forms a hydration protective layer on the surface of the liposome, improves the hydrophilicity of the lipid membrane, and improves the stability of the liposome, and the OA group on the surface contains a carboxyl group, which can generate hydrogen bond interaction with components such as modified polyvinyl alcohol and chitosan, and oleanolic acid and resveratrol can generate hydrogen bonds and π-π stacking effects, thereby enhancing the compatibility of oleanolic acid with the modified polyvinyl alcohol substrate, and effectively cross-linking the liposomes and the oleanolic acid and dispersing them into the gel dressing. The present invention adopts Chinese herbal extracts, wherein the salvia miltiorrhiza extract has the effect of promoting blood circulation and removing blood stasis, and is helpful to improve the blood circulation of the feet of patients with diabetic foot; the safflower extract can promote blood circulation and improve the blood circulation effect; the lithospermum officinale extract has the characteristics of anti-inflammatory and promoting wound healing, and can reduce the damage of inflammation to the wound surface and accelerate the healing of the wound; the scutellaria baicalensis extract has the effect of antibacterial and anti-inflammatory, and can inhibit the growth of bacteria and reduce infection; the Centella asiatica extract can promote cell proliferation and tissue regeneration, and is helpful to repair damaged skin and tissue. The Chinese herbal extracts act synergistically to improve the treatment effect.The addition of ellagic acid and hesperidin of the present invention adds antioxidant and anti-inflammatory activity to the gel dressing, helps to remove local tissue free radicals, alleviates inflammatory reactions, protects wound cells from oxidative damage, promotes wound repair and healing, utilizes the good biocompatibility and antibacterial properties of chitosan, prevents external pathogens from invading, and at the same time, its affinity for the wound surface can promote cell adhesion, proliferation and differentiation, and provide a suitable microenvironment for wound healing. Chitosan can also regulate the immune response of the wound surface, promote the formation of granulation tissue and the growth of epithelial cells, and chitosan is mutually coordinated with ellagic acid and hesperidin, cross-linked by hydrogen bonds, and ellagic acid and hesperidin are loaded in a chitosan substrate to improve compatibility. The dressing of the present invention is a gel with a three-dimensional reticular structure, which can better load active ingredients and promote the continuous and slow release of drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings in the following description are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 The wound healing effects of the gel dressings described in Example 1 and Comparative Examples 1-4 of the present invention; Figure 2 The antibacterial properties of the gel dressings described in Example 2 of the present invention and Comparative Examples 1-4; Figure 3 The antioxidant properties of the gel dressings described in Example 3 of the present invention and Comparative Examples 1-4; Figure 4 This is a scanning electron microscope image of the gel dressing described in Example 1 of the present invention; Figure 5 The stability of the gel dressings described in Example 1 of the present invention and Comparative Examples 1-4. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical scheme and advantages of the present invention more clear, the present invention is further described in detail below in conjunction with specific embodiments, but the present invention is not limited to the following embodiments. It should be noted that, unless otherwise specified, the chemical reagents involved in the present invention are purchased through commercial channels.

[0026] Example 1: A gel dressing for treating diabetic foot, comprising the following raw materials: 15 parts of modified polyvinyl alcohol, 1.5 parts of modified nanosilver liposomes, 2 parts of Chinese herbal medicine extract, 1.2 parts of ellagic acid, 0.8 parts of hesperidin, and 6 parts of chitosan.

[0027] The raw materials for preparing the modified polyvinyl alcohol include the following components in parts by weight: 30 parts of vinyl acetate (VAC) and 3 parts of resveratrol.

[0028] The preparation method of the modified polyvinyl alcohol comprises the following steps: A1: Take VAC 30 g, resveratrol 3 g and azobisisobutyronitrile 0.45 g, add them into 60 mL methanol solvent and mix well, heat to 70°C, react for 4 h, remove the solvent under reduced pressure, wash with methanol, and dry under vacuum to obtain VAC-resveratrol; A2: Add VAC-resveratrol obtained in step A1 to methanol, the amount ratio of VAC-resveratrol to methanol is 1 g:30 mL, add 0.05 g / mL sodium hydroxide methanol solution and mix well, the mass ratio of sodium hydroxide to VAC-resveratrol is 0.2:10, heat in a water bath at 40°C for 3 h, filter, wash the filter cake with methanol, and vacuum dry to obtain modified polyvinyl alcohol.

[0029] The composition of the Chinese medicine extract includes the following components by weight: 2 parts of salvia miltiorrhiza extract, 3 parts of safflower extract, 3 parts of lithospermum officinale extract, 2.5 parts of scutellaria baicalensis extract and 4 parts of centella asiatica extract.

[0030] The raw materials for preparing the modified nanosilver liposomes include the following components in parts by weight: 4.5 parts of lecithin, 0.75 parts of cholesterol, 0.02 parts of distearoylphosphatidylethanolamine-polyethylene glycol-carboxyl (DSPE-PEG-COOH), 0.04 parts of oleanolic acid (OA), and 0.015 parts of nanosilver.

[0031] The preparation method of the modified nano-silver liposome comprises the following steps: B1: Dissolve 0.02 g of DSPE-PEG-COOH, 0.01 g of DMAP and 0.02 g of EDC in 5 mL of CH2Cl2, stir at 0℃ for 1 h, add 0.04 g of OA and continue to react for 1 h, react at room temperature for 14 h, remove the solvent by rotary evaporation, wash with ether, and dry in vacuum to obtain DSPE-PEG-OA; B2: Dissolve 4.5 g of lecithin and 0.75 g of cholesterol in 150 mL of a mixed solvent of chloroform and ether (v / v=4:1), remove the solvent by vacuum rotary evaporation at 60°C to obtain a lipid film, add 75 mL of a 200 μg / mL nanosilver solution, and hydrate by ultrasound at 250 W and 40 kHz to obtain a liposome suspension; B3: The liposome suspension obtained in step B2 was slowly injected with 4 mg / mL DSPE-PEG-OA solution obtained in step B1 while stirring, and the mixture was stirred evenly. The mixture was ultrasonicated in an ice-water bath for 10 min (500 W, with an interval of 3 s), and centrifuged at 3000 r / min for 12 min. The supernatant was taken to obtain the modified nanosilver liposomes.

[0032] This embodiment also provides a method for preparing the gel dressing for treating diabetic foot, comprising the following steps: S1: Add 15 g of modified polyvinyl alcohol to 350 g of deionized water, stir at 90 °C and 200 rpm for 1 h, add 1.5 g of modified nanosilver liposomes, stir at 40 °C and 150 rpm for 30 min, and continue stirring at room temperature for 2 h to obtain material a; S2: 6 g of chitosan was dissolved in 114 g of 2 wt% acetic acid solution, stirred at 300 rpm for 12 h, heated to 100 °C and stirred for 2 h to obtain a 5 wt% chitosan solution, 1.2 g of ellagic acid and 4.8 g of deionized water were added, stirred at 100 °C for 1.5 h, 0.8 g of hesperidin was added, and stirred at room temperature for 60 min to obtain material b; S3: Add 2 g of the Chinese herbal extract into 40 mL of deionized water and mix well to obtain a mixed solution; mix the material a obtained in step S1 and the material b obtained in step S2, pour into a mold and freeze at -80°C for 12 h; add to the mixed solution and immerse at room temperature for 12 h; freeze at -20°C for 10 h; and thaw at room temperature until melted to obtain a gel dressing for treating diabetic foot.

[0033] Example 2: A gel dressing for treating diabetic foot, comprising the following raw materials: 10 parts of modified polyvinyl alcohol, 1 part of modified nanosilver liposomes, 1.5 parts of Chinese herbal medicine extract, 0.8 parts of ellagic acid, 0.6 parts of hesperidin, and 4 parts of chitosan.

[0034] The raw materials for preparing the modified polyvinyl alcohol include the following components in parts by weight: 20 parts of vinyl acetate (VAC) and 2 parts of resveratrol.

[0035] The preparation method of modified polyvinyl alcohol comprises the following steps: A1: Take VAC 20 g, resveratrol 2 g and azobisisobutyronitrile 0.2 g, add them into 40 mL methanol solvent and mix well, heat to 60°C, react for 3 h, remove the solvent under reduced pressure, wash with methanol, and dry under vacuum to obtain VAC-resveratrol; A2: Add VAC-resveratrol obtained in step A1 to methanol, the amount ratio of VAC-resveratrol to methanol is 1 g:20 mL, add 0.03 g / mL sodium hydroxide methanol solution and mix well, the mass ratio of sodium hydroxide to VAC-resveratrol is 0.15:10, heat in a water bath at 40°C for 2 h, filter, wash the filter cake with methanol, and vacuum dry to obtain modified polyvinyl alcohol.

[0036] The composition of the Chinese medicine extract includes the following components in parts by weight: 1 part of salvia miltiorrhiza extract, 1.5 parts of safflower extract, 2 parts of lithospermum officinale extract, 1.5 parts of scutellaria baicalensis extract and 2 parts of centella asiatica extract.

[0037] The raw materials for preparing the modified nano-silver liposomes include the following components in parts by weight: 3 parts of lecithin, 0.5 parts of cholesterol, 0.015 parts of distearoylphosphatidylethanolamine-polyethylene glycol-carboxyl (DSPE-PEG-COOH), 0.03 parts of oleanolic acid (OA), and 0.01 parts of nano-silver.

[0038] The preparation method of modified nano silver liposomes comprises the following steps: B1: Dissolve 0.015 g of DSPE-PEG-COOH, 0.005 g of DMAP and 0.015 g of EDC in 5 mL of CH2Cl2, stir at 0°C for 1 h, add 0.03 g of OA and continue to react for 1 h, react at room temperature for 12 h, remove the solvent by rotary evaporation, wash with ether, and dry in vacuum to obtain DSPE-PEG-OA; B2: 3 g of lecithin and 0.5 g of cholesterol were dissolved in 200 mL of a mixed solvent of chloroform and ether (v / v=4:1), and the solvent was removed by vacuum rotary evaporation at 40°C to obtain a lipid film, and 50 mL of a 200 μg / mL nanosilver solution was added, and ultrasonic hydration was performed at 250 W and 40 kHz to obtain a liposome suspension; B3: The liposome suspension obtained in step B2 was slowly injected with 2 mg / mL DSPE-PEG-OA solution obtained in step B1 while stirring, and the mixture was stirred evenly. The mixture was ultrasonicated in an ice-water bath for 10 min (500 W, with an interval of 3 s), and centrifuged at 3000 r / min for 8 min. The supernatant was taken to obtain the modified nanosilver liposomes.

[0039] This embodiment also provides a method for preparing the gel dressing for treating diabetic foot, comprising the following steps: S1: Add 10 g of modified polyvinyl alcohol to 490 g of deionized water, stir at 80°C and 150 rpm for 1 h, add 1 g of modified nanosilver liposomes, stir at 30°C and 100 rpm for 30 min, and continue stirring at room temperature for 1 h to obtain material a; S2: Dissolve 4 g of chitosan in 96 g of 1.5 wt% acetic acid solution, stir at 200 rpm for 10 h, heat to 100 °C and stir for 1 h to obtain a 4 wt% chitosan solution, add 0.8 g of ellagic acid and 1.6 g of deionized water, stir at 100 °C for 1 h, add 0.6 g of hesperidin, stir at room temperature for 40 min, and obtain material b; S3: Add 1.5 g of the Chinese herbal extract into 22.5 mL of deionized water and mix well to obtain a mixed solution; mix the material a obtained in step S1 and the material b obtained in step S2, pour into a mold and freeze at -80°C for 10 h; add to the mixed solution and immerse at room temperature for 10 h; freeze at -20°C for 8 h; and thaw at room temperature until melted to obtain a gel dressing for treating diabetic foot.

[0040] Example 3: A gel dressing for treating diabetic foot, the raw materials for preparing the dressing include the following components: 12 parts of modified polyvinyl alcohol, 1.2 parts of modified nanosilver liposomes, 1.8 parts of Chinese herbal medicine extract, 1 part of ellagic acid, 0.7 parts of hesperidin, and 5 parts of chitosan.

[0041] The raw materials for preparing the modified polyvinyl alcohol include the following components in parts by weight: 25 parts of vinyl acetate (VAC) and 2.5 parts of resveratrol.

[0042] The preparation method of modified polyvinyl alcohol comprises the following steps: A1: Take VAC 25 g, resveratrol 2.5 g and azobisisobutyronitrile 0.3 g, add them into 50 mL methanol solvent and mix well. Heat to 65°C, react for 3.5 h, remove the solvent under reduced pressure, wash with methanol, and dry under vacuum to obtain VAC-resveratrol. A2: Add VAC-resveratrol obtained in step A1 to methanol, the dosage ratio of VAC-resveratrol to methanol is 1 g:25 mL, add 0.04 g / mL of sodium hydroxide methanol solution and mix well, the mass ratio of sodium hydroxide to VAC-resveratrol is 0.18:10, heat in a 40°C water bath for 2.5 h, filter, wash the filter cake with methanol, and vacuum dry to obtain modified polyvinyl alcohol.

[0043] The composition of the Chinese medicine extract includes the following components in parts by weight: 1.5 parts of Salvia miltiorrhiza extract, 2 parts of Carthamus tinctorius extract, 2.5 parts of Lithospermum officinale extract, 2 parts of Scutellaria baicalensis extract and 3 parts of Centella asiatica extract.

[0044] The raw materials for preparing the modified nano-silver liposomes include the following components in parts by weight: 4 parts of lecithin, 0.6 parts of cholesterol, 0.018 parts of distearoylphosphatidylethanolamine-polyethylene glycol-carboxyl (DSPE-PEG-COOH), 0.035 parts of oleanolic acid (OA), and 0.012 parts of nano-silver.

[0045] The preparation method of modified nano silver liposomes comprises the following steps: B1: Dissolve 0.018 g of DSPE-PEG-COOH, 0.008 g of DMAP and 0.018 g of EDC in 5 mL of CH2Cl2, stir at 0℃ for 1 h, add 0.035 g of OA and continue to react for 1 h, react at room temperature for 13 h, remove the solvent by rotary evaporation, wash with ether, and dry in vacuum to obtain DSPE-PEG-OA; B2: 4 g of lecithin and 0.6 g of cholesterol were dissolved in 150 mL of a mixed solvent of chloroform and ether (v / v=4:1), and the solvent was removed by vacuum rotary evaporation at 50°C to obtain a lipid film, and 60 mL of a 200 μg / mL nanosilver solution was added, and ultrasonic hydration was performed at 250 W and 40 kHz to obtain a liposome suspension; B3: The liposome suspension obtained in step B2 was slowly injected with 3 mg / mL DSPE-PEG-OA solution obtained in step B1 while stirring, and the mixture was stirred evenly. The mixture was ultrasonicated in an ice-water bath for 10 min (500 W, with an interval of 3 s), and centrifuged at 3000 r / min for 10 min. The supernatant was taken to obtain the modified nanosilver liposomes.

[0046] This embodiment also provides a method for preparing the gel dressing for treating diabetic foot, comprising the following steps: S1: Add 12 g of modified polyvinyl alcohol to 388 mL of deionized water, stir at 85°C and 180 rpm for 1 h, add 1.2 g of modified nanosilver liposomes, stir at 35°C and 120 rpm for 30 min, and continue stirring at room temperature for 1.5 h to obtain material a; S2: Dissolve 5 g of chitosan in 100 g of 1.8 wt% acetic acid solution, stir at 250 rpm for 11 h, heat to 100 °C and stir for 1.5 h to obtain a chitosan solution, add 1 g of ellagic acid and 3 g of deionized water, stir at 100 °C for 1.2 h, add 0.7 g of hesperidin, stir at room temperature for 50 min, and obtain material b; S3: Add 1.8 g of the Chinese herbal extract into 32 mL of deionized water and mix well to obtain a mixed solution; mix the material a obtained in step S1 and the material b obtained in step S2, pour into a mold and freeze at -80°C for 11 h; add to the mixed solution and immerse at room temperature for 11 h; freeze at -20°C for 9 h; and thaw at room temperature until melted to obtain a gel dressing for treating diabetic foot.

[0047] The only difference between Comparative Example 1 and Example 1 is that polyvinyl alcohol is used instead of modified polyvinyl alcohol.

[0048] The only difference between Comparative Example 2 and Example 1 is that DSPE-PEG-OA is not added.

[0049] The only difference between Comparative Example 3 and Example 1 is that ellagic acid and hesperidin are not added.

[0050] The only difference between Comparative Example 4 and Example 1 is that no Chinese herbal medicine extract is added.

[0051] Experimental Example 1: 40 SPF-grade 4-week-old healthy male C57BL / 6J mice were adaptively raised for 2 weeks before modeling. They were fasted but not watered for 12 h after 9 pm every night. After weighing on an empty stomach, STZ solution was intraperitoneally injected at a volume of 50 mg / kg, and then the diet was resumed. After repeating the above operation for 5 days, the fasting blood glucose of the mice was measured by tail-cutting blood sampling. When the fasting blood glucose was ≥16.7 mmol / L, the diabetic mouse model was considered to be successfully established, and the diabetic mice were randomly divided into 5 groups, with 8 mice in each group. All 5 groups of mice were treated with wound modeling. After the mice were anesthetized with flurane gas, the backs of the mice were depilated, the back skin of the mice was disinfected with 75% alcohol, and a 6 mm circular wound was made on the back of the mice with a skin circular incision device. The wound was covered with a gel dressing of appropriate size, and the dressing was changed every 2 days. After 7 days, the wound was observed and the wound healing rate was calculated. The wound healing rate (%) = [(initial wound area-wound area after treatment) / initial wound area] × 100%. The results are shown in Figure 1 shown.

[0052] Figure 1 The results showed that the wound healing rate of Example 1 was better than that of Comparative Examples 1-4. Comparative Example 1 used polyvinyl alcohol instead of modified polyvinyl alcohol, and did not introduce resveratrol. It lacked the anti-inflammatory and antioxidant effects of resveratrol, and the wound healing effect was reduced. Comparative Example 2 did not add DSPE-PEG-OA, the active ingredient content decreased, and the liposome dispersibility and stability decreased. Comparative Example 3 did not add ellagic acid and hesperidin, the active ingredient content decreased, and the wound healing effect decreased. Comparative Example 4 did not add traditional Chinese medicine extracts, and the wound healing effect decreased.

[0053] Experimental Example 2: Configuration 10 6 CFU / mL of Staphylococcus aureus liquid was taken, 500 μL of the liquid was evenly coated on the agar solid medium, and cylindrical gel samples with a diameter of 9 mm and a thickness of 3 mm of Example 2 and Comparative Examples 1-4 were placed on the surface of the medium, respectively, and placed in a constant temperature incubator at 37°C for 12 h, and the diameter of the inhibition zone was measured. The results are as follows Figure 2 shown.

[0054] Figure 2The results showed that the diameter of the antibacterial zone of Example 2 was larger than that of Comparative Examples 1-4. Comparative Example 1 used polyvinyl alcohol instead of modified polyvinyl alcohol, and did not introduce resveratrol, so the antibacterial activity decreased. Comparative Example 2 did not add DSPE-PEG-OA, so the antibacterial activity decreased. Comparative Example 3 did not add ellagic acid and hesperidin, so the antibacterial activity decreased. Comparative Example 4 did not add traditional Chinese medicine extracts, so the antibacterial activity decreased.

[0055] Experimental Example 3: 100 mg of the gel dressing prepared in Example 3 and Comparative Examples 1-4 was placed in 5 mL of 0.1 mM DPPH solution, and reacted at room temperature for 30 min under light-proof conditions. The absorbance of the solution at 517 nm was measured using an ultraviolet spectrophotometer, and the DPPH free radical scavenging rate was calculated: DPPH scavenging rate (%) = (A1-A2) / A1×100%, where A1 is the absorbance before the DPPH solution reacts with the hydrogel, and A2 is the absorbance after the DPPH solution and the hydrogel are mixed and reacted for 30 min. The results are as follows: Figure 3 shown.

[0056] Figure 3 The results showed that the DPPH radical scavenging rate of Example 3 was higher than that of Comparative Examples 1-4. Comparative Example 1 used polyvinyl alcohol instead of modified polyvinyl alcohol, and did not introduce resveratrol, so the antioxidant activity was reduced. Comparative Example 1 did not add DSPE-PEG-OA, and the free radical scavenging rate decreased. Comparative Example 3 did not add ellagic acid and hesperidin, and the free radical scavenging rate decreased, and the antioxidant activity decreased. Comparative Example 4 did not add traditional Chinese medicine extracts, and the antioxidant activity was reduced.

[0057] Experimental Example 4: The microstructure of the gel dressing sample prepared in Example 1 of the present invention was observed using a scanning electron microscope to obtain a SEM scanning electron microscope image. The results are as follows: Figure 4 shown.

[0058] Figure 4 The results showed that the gel dressing had a large number of pores and an obvious porous network structure, which was conducive to the adsorption and storage, storage and release of active ingredients. It could better load active ingredients and promote the sustained and slow release of drugs.

[0059] Experimental Example 5: The gel dressing samples prepared in Example 1 of the present invention and Comparative Examples 1-4 were sealed in commercial packaging and placed at 35°C for 90 days. Samples were taken on the 30th, 60th and 90th days of the test period to test the antibacterial properties. Figure 5 shown.

[0060] Depend on Figure 5The results show that the gel dressing prepared by the present invention can be effectively preserved for a long time, and its active ingredients are effectively loaded and encapsulated, showing excellent stability. From the results of Comparative Examples 1-4, it can be seen that when polyvinyl alcohol is used instead of modified polyvinyl alcohol, without adding DSPE-PEG-OA or ellagic acid and hesperidin, the mechanical properties of the gel itself will be affected, and it is easy to disintegrate in long-term tests, and its compatibility with liposomes is reduced, thereby reducing stability.

[0061] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention is limited to these examples. Under the concept of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.

Claims

1. A gel dressing for treating diabetic foot, characterized in that: The preparation raw materials include the following components in parts by weight: 10-15 parts of modified polyvinyl alcohol, 1-1.5 parts of modified nanosilver liposomes, 1.5-2 parts of Chinese herbal medicine extract, 0.8-1.2 parts of ellagic acid, 0.6-0.8 parts of hesperidin, and 4-6 parts of chitosan; The preparation method of the modified polyvinyl alcohol, The following steps are involved: A1: VAC, resveratrol and azobisisobutyronitrile are added to methanol solvent and mixed evenly, the temperature is raised to react, the solvent is removed, washed, and vacuum dried to obtain VAC-resveratrol; A2: Add VAC-resveratrol obtained in step A1 to methanol, add sodium hydroxide methanol solution to mix, heat in a water bath, filter, wash the filter cake with methanol, and vacuum dry to obtain modified polyvinyl alcohol; The preparation method of the modified nano-silver liposome comprises the following steps: B1: Dissolve DSPE-PEG-COOH, DMAP and EDC in CH2Cl2, stir at 0℃, add OA to continue the reaction, react at room temperature for 12-14 h, remove the solvent by rotary evaporation, wash with ether, and dry in vacuum to obtain DSPE-PEG-OA; B2: dissolving lecithin and cholesterol in a mixed solvent of chloroform and ether, removing the solvent by vacuum rotary evaporation to obtain a lipid film, adding a nanosilver solution, and ultrasonically hydrating to obtain a liposome suspension; B3: The liposome suspension obtained in step B2 was slowly injected with 2-4 mg / mL DSPE-PEG-OA solution obtained in step B1 while stirring, stirred evenly, ultrasonicated in an ice-water bath, centrifuged, and the supernatant was collected to obtain the modified nanosilver liposomes.

2. The gel dressing for treating diabetic foot according to claim 1, characterized in that: In step A1, the dosage ratio of VAC to methanol solvent is 1 g:2 mL; the dosage of azobisisobutyronitrile is 1-1.5wt% of VAC; in step A2, the dosage ratio of VAC-resveratrol to methanol is 1 g:20-30 mL, and the mass ratio of sodium hydroxide to VAC-resveratrol is 0.15-0.2:

10.

3. The gel dressing for treating diabetic foot according to claim 2, characterized in that: The composition of the traditional Chinese medicine extract includes the following components by weight: 1-2 parts of salvia miltiorrhiza extract, 1.5-3 parts of safflower extract, 2-3 parts of lithospermum officinale extract, 1.5-2.5 parts of scutellaria baicalensis extract and 2-4 parts of centella asiatica extract.

4. The gel dressing for treating diabetic foot according to claim 3, characterized in that: In step B1, the mass concentration of OA in CH2Cl2 is 6-8 mg / mL; the mass ratio of OA, EDC and DMAP is 6-8:3-4:1-2; in step B2, the mass concentration of cholesterol in the mixed solvent is 2.5-5 mg / mL.

5. A method for preparing a gel dressing for treating diabetic foot according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1: adding modified polyvinyl alcohol to deionized water, stirring, adding modified nanosilver liposomes, stirring, and obtaining material a; S2: dissolving chitosan with acetic acid solution, stirring, heating and stirring to obtain 4-5 wt% chitosan solution, adding ellagic acid and deionized water, stirring, adding hesperidin, stirring at room temperature, and obtaining material b; S3: Add the Chinese herbal medicine extract to deionized water and mix well to obtain a mixed solution, mix the material a obtained in step S1 and the material b obtained in step S2, freeze them, add them to the mixed solution for immersion, freeze them, and thaw them at room temperature until they melt, to obtain a gel dressing for treating diabetic foot.

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