Arteriovenous fistula external dressing for preventing vascular calcification and preparation method thereof

Abstract

The present invention belongs to the technical field of medical supplies and specifically relates to an arteriovenous fistula external dressing for preventing vascular calcification and a preparation method thereof. The arteriovenous fistula external dressing for preventing vascular calcification comprises the following raw materials, by weight: 15 to 25 parts of polyethylene glycol-grafted polylactic-co-glycolic acid copolymer, 15 to 25 parts of chitosan@plant-peptide composite gel, and 10 to 20 parts of modified microporous polyethylene. The polylactic-co-glycolic acid copolymer (PLGA) is modified with silane and grafted with polyethylene glycol (PEG) to enhance its hydrophilicity and compatibility with the chitosan@PNIPAM vitamin K2-phosphate gel, creating a composite dressing that provides physical protection through a microporous polyethylene outer layer while utilizing a temperature-sensitive gel to stabilize and control the release of plant extracts, vitamin K2, and bisphosphates, optimizing drug release, enhancing biocompatibility, and mechanical stability, making it suitable for dynamic loading environments.

Description

Technical Field

[0001] The invention belongs to the technical field of medical supplies, and in particular relates to an arteriovenous fistula external dressing for preventing vascular calcification and a preparation method thereof. Background Art

[0002] With the continuous advancement of modern medical technology, hemodialysis has become a vital means of maintaining life for many patients with chronic kidney disease. As an essential vascular connection for hemodialysis treatment, maintaining the health and function of arteriovenous fistulas is crucial to patients' treatment outcomes and quality of life. However, over the long term, arteriovenous fistulas often face the threat of various complications, among which vascular calcification is a significant issue.

[0003] Vascular calcification is a common pathological condition in patients with chronic kidney disease and the elderly, characterized by the accumulation of calcium salts in the blood vessel walls. This calcification process leads to reduced vascular elasticity and hardening, which in turn affects blood flow dynamics and may increase the risk of cardiovascular events. Especially for patients undergoing dialysis treatment, arteriovenous fistulas are their main vascular access, and their health status is directly related to the dialysis effect and the patient's quality of life. Arteriovenous fistulas directly connect the patient's arteries and veins to provide efficient blood flow for dialysis, but complications of fistulas such as fistula stenosis and vascular calcification can seriously affect their lifespan and function.

[0004] Currently, the prevention and treatment of vascular calcification primarily relies on medication, lifestyle adjustments, and regular medical monitoring. However, these measures often fail to specifically target calcification at the site of arteriovenous fistulas. Medication can be associated with side effects, and their effectiveness varies significantly between patients. Therefore, developing a topical dressing that prevents infection, prevents vascular calcification, and is comfortable to use is a pressing technical challenge. Summary of the Invention

[0005] In response to the above technical problems, the present invention provides an arteriovenous fistula external dressing for preventing vascular calcification and a preparation method thereof.

[0006] The present invention is achieved through the following technical solutions:

[0007] An arteriovenous fistula external dressing for preventing vascular calcification comprises the following raw materials in parts by weight: 15 to 25 parts of polyethylene glycol-graft-polylactic acid-glycolic acid copolymer, 15 to 25 parts of chitosan@plant-peptide composite gel, 10 to 20 parts of modified microporous polyethylene, and 2 to 5 parts of polyvinyl alcohol binder.

[0008] Furthermore, the preparation of the polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer comprises the following steps:

[0009] A1: Add poly(lactic acid-co-glycolic acid) copolymer to dichloromethane, mix and dissolve uniformly to obtain a 2 wt% poly(lactic acid-co-glycolic acid) copolymer solution; slowly dropwise add trimethylsilane to the poly(lactic acid-co-glycolic acid) copolymer solution, and stir at 500 rpm with a magnetic stirrer for 5-10 minutes. Then, slowly add 98 wt% concentrated sulfuric acid over 10 minutes. Control the temperature at 35°C in a water bath and stir at 100 rpm for 2-4 hours. After the reaction is completed, allow the mixture to cool to room temperature to obtain a mixed solution.

[0010] A2: The mixed solution prepared in step A1 was added to a rotary evaporator, and the pressure was controlled to 2.5-5 kPa, the temperature was 40-60°C, the rotation speed was 100-160 rpm, and the condenser temperature was 5-10°C. After evaporation for 1-2 hours, a concentrated solution was obtained; the concentrated solution was centrifuged at 8000 rpm for 10 minutes, and the precipitate was collected, washed with ethanol three times, and freeze-dried in a vacuum at -20°C for 12 hours to obtain a modified poly(lactic acid-co-glycolic acid) copolymer;

[0011] A3: adding the modified polylactic acid-co-glycolic acid copolymer prepared in step A2 to N,N-dimethylformamide, mixing and dissolving them uniformly to obtain a 10 wt % modified polylactic acid-co-glycolic acid copolymer solution; dissolving polyethylene glycol in N,N-dimethylformamide, mixing and dissolving them uniformly to obtain a 20 wt % polyethylene glycol solution;

[0012] A4: N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added to the modified polylactic acid-co-glycolic acid solution prepared in step A3, and the mixture was stirred at 100-300 rpm for 10 minutes. The polyethylene glycol solution prepared in step A3 was then slowly added over 30 minutes. The mixture was heated in a water bath at 40°C for 12-16 hours, and then 5 volumes of deionized water were added to terminate the reaction. The mixture was filtered through a 10-20 kDa dialysis bag and freeze-dried in a vacuum at -30°C for 18-24 hours to obtain polyethylene glycol-grafted polylactic acid-co-glycolic acid.

[0013] Preferably, in step A1, the ratio of trimethylsilane to polylactic acid-co-glycolic acid is 0.05-0.1 mL:1 g; and the ratio of 98 wt% concentrated sulfuric acid to polylactic acid-co-glycolic acid is 0.02 mL:1 g.

[0014] Preferably, the volume ratio of the modified polylactic acid-glycolic acid copolymer solution to the polyethylene glycol solution in step A4 is 1:0.5; the mass ratio of the N-hydroxysuccinimide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide and the modified polylactic acid-glycolic acid copolymer is 0.05-0.1:0.1:1.

[0015] Furthermore, the chitosan@PNIPAM vitamin K2-phosphate gel includes chitosan, N-isopropylacrylamide, plant extracts, vitamin K2 and bisphosphate.

[0016] Furthermore, the plant extract is formed by mixing green tea extract, grape seed extract, turmeric extract and ginseng extract in a mass ratio of 0.8:1.2:1.5:0.7; the green tea extract is extracted by gentle heating in a water bath using ethanol as a solvent; the grape seed extract is extracted by immersion using ethanol as a solvent; the turmeric extract is extracted by gentle heating in a water bath using ethanol as a solvent; and the ginseng extract is extracted by heating in a water bath using ethanol as a solvent.

[0017] Furthermore, the preparation method of the chitosan@PNIPAM vitamin K2-phosphate gel comprises the following steps:

[0018] B1: Grind chitosan and sieve through a 100-mesh sieve to obtain chitosan powder; dissolve the chitosan powder in a 1 wt% acetic acid solution until uniformly dissolved to obtain a 2 wt% chitosan solution; dissolve N-isopropylacrylamide in deionized water, control the temperature at 32°C in a water bath, and stir at 200-500 rpm for 10 minutes until uniformly dissolved to obtain an 8 wt% N-isopropylacrylamide solution; slowly add the N-isopropylacrylamide solution to the chitosan solution, and stir at 300 rpm at room temperature for 30 minutes to obtain a mixed solution;

[0019] B2: Add vitamin K2, bisphosphate and plant extract to the mixed solution in step B1, mix well, add N,N'-methylenebisacrylamide and azobisisobutyronitrile, heat in a water bath, control the temperature at 32-42°C, stir continuously at 500-800 rpm for 5-10 minutes, then reduce the speed to 100-300 rpm and continue stirring for 2-4 hours, cool naturally to room temperature, wash three times with deionized water, and freeze-dry in a vacuum at -30°C for 12 hours to obtain chitosan@PNIPAM vitamin K2-phosphate gel.

[0020] Preferably, the volume ratio of the chitosan solution to the N-isopropylacrylamide solution in step B1 is 1:1.2-2.

[0021] Preferably, in step B2, the ratio of the amount of vitamin K2, bisphosphonate, plant extract and mixed solution is 0.001 g: 0.005-0.01 g: 0.01-0.02 g: 1 mL; the ratio of the amount of N,N'-methylenebisacrylamide, azobisisobutyronitrile and mixed solution is 0.005 g: 0.001-0.002 g: 1 mL.

[0022] Furthermore, the preparation of the modified microporous polyethylene comprises the following steps:

[0023] C1: Polyethylene, sodium chloride, and dioctyl phthalate were uniformly mixed to obtain a mixture; the mixture was formed into a film through an extruder with setting parameters of 160-200°C, an extrusion speed of 0.5-1 m / min, and a thickness of 0.05-0.1 mm. After extrusion, the film was rapidly cooled to room temperature and soaked in warm water at 35-45°C for 24-48 hours, with the warm water being replaced every 6 hours, to obtain microporous polyethylene;

[0024] C2: The microporous polyethylene prepared in step C1 is immersed in 5 times the mass volume of a 1wt% 3-aminopropyltrimethoxysilane solution for 2 to 4 hours, and then dried at 60 to 80°C for 1 to 2 hours to obtain a silane-modified product; the silane-modified product is added to 5 times the mass volume of a 2wt% polyethylene glycol solution, and then 0.5% pentanediol is added. After stirring at 300 rpm at room temperature for 4 to 6 hours, the product is dried at 70 to 90°C for 6 hours to obtain a modified microporous polyethylene.

[0025] The polyethylene in step C1 is low-density polyethylene; the usage ratio of polyethylene, sodium chloride and dioctyl phthalate is 1g:0.3-0.5g:0.05-0.1mL.

[0026] Another aspect of the present invention is to provide a method for preparing an arteriovenous fistula external dressing for preventing vascular calcification, comprising the following steps:

[0027] S1: Add polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer by weight to 4 times the mass volume of chloroform solution, coat on a flat plate to a thickness of 0.1-0.5 mm, control the temperature at 30°C and the humidity at 45% and dry for 6-12 hours to obtain a polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer film;

[0028] S2: Chitosan@PNIPAM vitamin K2-phosphate gel was diluted by 2 times the mass volume of deionized water, and coated onto the polyethylene glycol-graft-polylactic acid-co-glycolic acid film in step S1 to a thickness of 0.2-0.4 mm. The temperature was controlled at 25°C and the humidity was 40%, and the mixture was dried for 12-24 hours to obtain a composite coating.

[0029] S3: bonding the modified microporous polyethylene to the composite coating prepared in step S2 according to parts by weight. Before bonding, a layer of polyvinyl alcohol adhesive needs to be coated on the modified microporous polyethylene. The modified microporous polyethylene is allowed to stand at room temperature for 10 to 14 hours to obtain a dressing.

[0030] The beneficial effects of the present invention are as follows:

[0031] Poly(lactic-co-glycolic acid) (PLGA) has excellent biocompatibility and biodegradability. Silane modification increases its hydrophilicity, effectively improving its water solubility when in contact with active ingredients such as aqueous plant extracts, while also improving the release efficiency of the active ingredients in the entire dressing system. Furthermore, by grafting the modified poly(lactic-co-glycolic acid) with polyethylene glycol (PEG) through covalent bonds between the carboxyl and hydroxyl ends, its elasticity is effectively improved and its degradation cycle is prolonged, making it more suitable for dressings under dynamic load environments. Furthermore, the modified poly(lactic-co-glycolic acid) grafted with polyethylene glycol (PLGA-PEG) effectively improves its compatibility with the chitosan hydrogel matrix, further facilitating the synergistic combination of the two materials.

[0032] Plant extracts, vitamin K2, and bisphosphonates work synergistically. The natural extracts help vitamin K2 and bisphosphonates more effectively prevent vascular sclerosis by controlling inflammatory responses and optimizing calcium metabolism. They also protect blood vessels from free radical damage and inhibit excessive calcium release, helping to prevent calcification of the blood vessel walls. Furthermore, when these active ingredients are loaded into the chitosan@PNIPAM gel in the middle layer, they are released in a controlled manner through the gel's porous structure when needed. N-isopropylacrylamide (PNIPAM), as a temperature-sensitive material, can adjust its gel properties in response to changes in local body temperature, thereby regulating the release rate of the active ingredients. The sustained-release properties of the modified poly(lactic-co-glycolic acid) grafted polyethylene glycol enable the stable and prolonged release of the active ingredients (plant extracts, vitamin K2, and bisphosphonates), maintaining effective local concentrations and effectively preventing calcification. Chitosan, with its high biocompatibility, supports cell growth and possesses antimicrobial properties, helping to reduce the risk of infection at the dressing application site. The enhanced stability and hydrophilicity of modified poly(lactic-co-glycolic acid) grafted polyethylene glycol reduced the inflammatory response induced by exogenous substances, making the dressing more suitable for prolonged contact with skin and blood vessels.

[0033] The modified microporous polyethylene in the outer layer provides a physical barrier, protecting the inner and middle layers from direct influences of the external environment while allowing oxygen and moisture to pass through, maintaining the dressing's breathability and preventing excessive wetting or drying. This microporous structure also helps maintain the dressing's overall structural stability and prevent damage caused by mechanical stress. Furthermore, the regulatory function of microporous polyethylene also includes helping to maintain a stable temperature under the dressing, a property that benefits the temperature-sensitive gel in the middle layer. The drug release characteristics of N-isopropylacrylamide are related to temperature changes, and the microporous structure can mitigate the effects of external temperature fluctuations, making drug release more stable. The polyethylene material is chemically stable and does not react with drugs or other chemicals in the dressing, ensuring the dressing's safety and long-term effectiveness. Through the design of this composite material, the dressing can be optimized in terms of release control, biocompatibility, and mechanical properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0035] Figure 1 FTIR spectrum of the polyethylene glycol-grafted polylactic acid-glycolic acid copolymer prepared in Example 3;

[0036] Figure 2 This is the FTIR infrared spectrum of the chitosan@PNIPAM vitamin K2-phosphate gel prepared in Example 3;

[0037] Figure 3 is a SEM scanning electron micrograph of the chitosan@PNIPAM vitamin K2-phosphate gel prepared in Example 3;

[0038] Figure 4 This is a cytotoxicity test chart of the arteriovenous fistula external dressing for preventing vascular calcification prepared in Examples 1 to 4;

[0039] Figure 5 This is a dissolution and release diagram of the arteriovenous fistula external dressing for preventing vascular calcification prepared in Examples 1 to 4 and Comparative Examples 1 to 2;

[0040] Figure 6 This is a test chart of the water vapor transmission rate of the arteriovenous fistula external dressing for preventing vascular calcification prepared in Examples 1 to 4 and Comparative Examples 1 to 2;

[0041] Figure 7 This is a test chart of the antibacterial rate of the arteriovenous fistula external dressing for preventing vascular calcification prepared in Examples 1 to 4. DETAILED DESCRIPTION

[0042] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0043] It should be noted that, unless otherwise specified, the raw materials involved in the present invention were purchased through conventional commercial channels.

[0044] Example 1: An arteriovenous fistula external dressing for preventing vascular calcification comprises the following raw materials in parts by weight: 15 parts of polyethylene glycol-graft-polylactic acid-glycolic acid copolymer, 15 parts of chitosan@plant-peptide composite gel, 10 parts of modified microporous polyethylene, and 2 parts of polyvinyl alcohol binder.

[0045] 1. Preparation of polyethylene glycol-grafted polylactic acid-glycolic acid copolymer:

[0046] A1: 20 g of poly(lactic acid-co-glycolic acid) was added to 1000 mL of dichloromethane and mixed and dissolved uniformly to obtain a 2 wt% poly(lactic acid-co-glycolic acid) solution; 1 mL of trimethylsilane was slowly and dropwise added to the 1000 mL poly(lactic acid-co-glycolic acid) solution and stirred at 500 rpm for 5 minutes using a magnetic stirrer. 0.4 mL of 98 wt% concentrated sulfuric acid was then slowly added over 10 minutes. The temperature was controlled at 35°C in a water bath and stirred at 100 rpm for 2 hours. After the reaction was completed, the mixture was allowed to cool to room temperature to obtain a mixed solution.

[0047] A2: The mixed solution prepared in step A1 was added to a rotary evaporator, and the pressure, temperature, and rotation speed were controlled to 2.5 kPa, 40°C, 100 rpm, and 10°C, respectively. After evaporation for 1 hour, a concentrated solution was obtained. The concentrated solution was centrifuged at 8000 rpm for 10 minutes, and the precipitate was collected, washed three times with ethanol, and freeze-dried at -20°C in a vacuum vacuum for 12 hours to obtain a modified poly(lactic acid-co-glycolic acid) copolymer.

[0048] A3: 20 g of the modified poly(lactic acid-co-glycolic acid) prepared in step A2 was added to 2000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 10 wt % modified poly(lactic acid-co-glycolic acid) solution, and 200 g of polyethylene glycol was dissolved in 1000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 20 wt % polyethylene glycol solution;

[0049] A4: 1 g of N-hydroxysuccinimide and 2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added to 2000 mL of the modified polylactic acid-co-glycolic acid solution prepared in step A3, and stirred at 100 rpm for 10 min. Then, 1000 mL of the polyethylene glycol solution prepared in step A3 was slowly added over 30 min. The mixture was heated in a water bath at 40 ° C. for 12 h, and then 15 L of deionized water was added to terminate the reaction. The mixture was filtered through a 10 KDa dialysis bag and freeze-dried in a vacuum at -30 ° C. for 18 h to obtain polyethylene glycol-grafted-polylactic acid-co-glycolic acid.

[0050] 2. Preparation of Chitosan@PNIPAM Vitamin K2-Phosphate Gel:

[0051] B1: Grind chitosan and sieve through a 100-mesh sieve to obtain chitosan powder; dissolve 20 g of chitosan powder in 1000 mL of 1 wt% acetic acid solution until uniformly dissolved to obtain a 2 wt% chitosan solution; dissolve 80 g of N-isopropylacrylamide in 1000 mL of deionized water, control the temperature at 32°C in a water bath, and stir at 200 rpm for 10 min until uniformly dissolved to obtain an 8 wt% N-isopropylacrylamide solution; then slowly add 600 mL of the N-isopropylacrylamide solution to 500 mL of the chitosan solution and stir at 300 rpm at room temperature for 30 min to obtain a mixed solution;

[0052] B2: Add 1.1 g vitamin K2, 5.5 g bisphosphate and 11 g plant extract to 1100 mL of the mixed solution in step B1. After mixing evenly, add 5.5 g N,N'-methylenebisacrylamide and 1.1 g azobisisobutyronitrile. Heat in a water bath and control the temperature to 42°C. Stir continuously at 500 rpm for 5 min, then reduce the speed to 100 rpm and continue stirring for 2 h. Cool naturally to room temperature, wash three times with deionized water, and freeze-dry in a vacuum at -30°C for 12 h to obtain chitosan@PNIPAM vitamin K2-phosphate gel.

[0053] 3. Preparation of modified microporous polyethylene:

[0054] C1: 100 g of low-density polyethylene, 30 g of sodium chloride, and 5 mL of dioctyl phthalate were mixed to obtain a mixture; the mixture was extruded into a film at 160°C, an extrusion speed of 1 m / min, and a thickness of 0.1 mm. After extrusion, the film was rapidly cooled to room temperature and soaked in 35°C warm water for 24 h, with the warm water replaced every 6 h, to obtain microporous polyethylene;

[0055] C2: Soak 100 g of the microporous polyethylene prepared in step C1 in 500 mL of a 1 wt% 3-aminopropyltrimethoxysilane solution for 2 h, and then dry at 60 ° C for 1 h to obtain a silane-modified product; add 100 g of the silane-modified product to 500 mL of a 2 wt% polyethylene glycol solution, and then add 2.5 mL of pentanediol. After stirring at 300 rpm at room temperature for 4 h, dry at 70 ° C for 6 h to obtain a modified microporous polyethylene.

[0056] 4. Preparation of arteriovenous fistula dressing for preventing vascular calcification:

[0057] S1: Add polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer by weight to 5 times the mass volume of chloroform solution, coat on a flat plate to a thickness of 0.5 mm, control the temperature at 30°C and the humidity at 45% and dry for 6 h to obtain a polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer film;

[0058] S2: Chitosan@PNIPAM vitamin K2-phosphate gel was diluted by weight in 2 times the mass volume of deionized water and coated onto the polyethylene glycol-graft-polylactic acid-co-glycolic acid film in step S1 to a thickness of 0.4 mm. The temperature was controlled at 25°C and the humidity was 40%, and the mixture was dried for 12 h to obtain a composite coating.

[0059] S3: bonding the modified microporous polyethylene to the composite coating prepared in step S2 according to parts by weight. Before bonding, a layer of polyvinyl alcohol adhesive needs to be coated on the modified microporous polyethylene. The modified microporous polyethylene is allowed to stand at room temperature for 10 hours to obtain a dressing.

[0060] Example 2: An arteriovenous fistula external dressing for preventing vascular calcification comprises the following raw materials in parts by weight: 20 parts of polyethylene glycol-graft-polylactic acid-glycolic acid copolymer, 20 parts of chitosan@plant-peptide composite gel, 15 parts of modified microporous polyethylene, and 3 parts of polyvinyl alcohol binder.

[0061] 1. Preparation of polyethylene glycol-grafted polylactic acid-glycolic acid copolymer:

[0062] A1: 20 g of poly(lactic acid-co-glycolic acid) was added to 1000 mL of dichloromethane, mixed and dissolved uniformly to obtain a 2 wt% poly(lactic acid-co-glycolic acid) solution; 1.5 mL of trimethylsilane was slowly and dropwise added to the 1000 mL poly(lactic acid-co-glycolic acid) solution, and stirred at 500 rpm with a magnetic stirrer for 7 minutes. Then, 0.4 mL of 98 wt% concentrated sulfuric acid was slowly added over 10 minutes. The temperature was controlled at 35°C in a water bath and stirred at 100 rpm for 3 hours. After the reaction was completed, the mixture was allowed to cool to room temperature to obtain a mixed solution.

[0063] A2: The mixed solution prepared in step A1 was added to a rotary evaporator, and the pressure, temperature, and rotation speed were controlled to 3.5 kPa, 50°C, 120 rpm, and 8°C, respectively. After evaporation for 1.5 hours, a concentrated solution was obtained. The concentrated solution was centrifuged at 8000 rpm for 10 minutes, and the precipitate was collected, washed three times with ethanol, and freeze-dried at -20°C in a vacuum vacuum for 12 hours to obtain a modified poly(lactic acid-co-glycolic acid) copolymer.

[0064] A3: 20 g of the modified poly(lactic acid-co-glycolic acid) prepared in step A2 was added to 2000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 10 wt % modified poly(lactic acid-co-glycolic acid) solution, and 200 g of polyethylene glycol was dissolved in 1000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 20 wt % polyethylene glycol solution;

[0065] A4: 1.5 g of N-hydroxysuccinimide and 2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added to 2000 mL of the modified polylactic acid-co-glycolic acid solution prepared in step A3, and stirred at 200 rpm for 10 min. Then, 1000 mL of the polyethylene glycol solution prepared in step A3 was slowly added within 30 min. The mixture was heated in a water bath at 40 ° C. for 14 h, and then 15 L of deionized water was added to terminate the reaction. The mixture was filtered through a 15 KDa dialysis bag and freeze-dried in a vacuum at -30 ° C. for 20 h to obtain polyethylene glycol-grafted-polylactic acid-co-glycolic acid.

[0066] 2. Preparation of Chitosan@PNIPAM Vitamin K2-Phosphate Gel:

[0067] B1: Grind chitosan and sieve through a 100-mesh sieve to obtain chitosan powder; dissolve 20 g of chitosan powder in 1000 mL of 1 wt% acetic acid solution until uniformly dissolved to obtain a 2 wt% chitosan solution; dissolve 160 g of N-isopropylacrylamide in 2000 mL of deionized water, control the temperature at 32°C in a water bath, and stir at 300 rpm for 10 min until uniformly dissolved to obtain an 8 wt% N-isopropylacrylamide solution; then slowly add 1500 mL of N-isopropylacrylamide solution to 1000 mL of chitosan solution, and stir at 300 rpm at room temperature for 30 min to obtain a mixed solution;

[0068] B2: Add 2.5 g of vitamin K2, 18 g of bisphosphate and 35 g of plant extract to 2500 mL of the mixed solution in step B1. After mixing evenly, add 12.5 g of N,N'-methylenebisacrylamide and 3.5 g of azobisisobutyronitrile. Heat in a water bath and control the temperature to 38°C. Stir continuously at 600 rpm for 6 minutes, then reduce the speed to 200 rpm and continue stirring for 3 hours. Cool naturally to room temperature, wash three times with deionized water, and freeze-dry at -30°C in a vacuum freeze-drying machine for 12 hours to obtain chitosan@PNIPAM vitamin K2-phosphate gel.

[0069] 3. Preparation of modified microporous polyethylene:

[0070] C1: 100 g of low-density polyethylene, 35 g of sodium chloride, and 7 mL of dioctyl phthalate were mixed to obtain a mixture; the mixture was extruded into a film at 180°C, a speed of 0.8 m / min, and a thickness of 0.08 mm. After extrusion, the film was rapidly cooled to room temperature and soaked in 40°C warm water for 36 hours, with the warm water replaced every 6 hours, to obtain microporous polyethylene.

[0071] C2: Soak 100 g of the microporous polyethylene prepared in step C1 in 500 mL of a 1 wt% 3-aminopropyltrimethoxysilane solution for 3 h, and then dry at 70 ° C for 1.5 h to obtain a silane-modified product; add 100 g of the silane-modified product to 500 mL of a 2 wt% polyethylene glycol solution, and then add 0.5% pentanediol. After stirring at 300 rpm at room temperature for 5 h, dry at 80 ° C for 6 h to obtain a modified microporous polyethylene.

[0072] 4. Preparation of arteriovenous fistula dressing for preventing vascular calcification:

[0073] S1: Add polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer by weight to 5 times the mass volume of chloroform solution, coat on a flat plate to a thickness of 0.3 mm, control the temperature at 30°C and the humidity at 45% and dry for 8 h to obtain a polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer film;

[0074] S2: Chitosan@PNIPAM vitamin K2-phosphate gel was diluted by weight in 2 times the mass volume of deionized water and coated onto the polyethylene glycol-graft-polylactic acid-co-glycolic acid film in step S1 to a thickness of 0.3 mm. The temperature was controlled at 25°C and the humidity was 40%, and the mixture was dried for 16 hours to obtain a composite coating.

[0075] S3: bonding the modified microporous polyethylene to the composite coating prepared in step S2 according to parts by weight. Before bonding, a layer of polyvinyl alcohol adhesive needs to be coated on the modified microporous polyethylene. The modified microporous polyethylene is allowed to stand at room temperature for 12 hours to obtain a dressing.

[0076] Example 3: An arteriovenous fistula external dressing for preventing vascular calcification, comprising the following raw materials in parts by weight: 22 parts of polyethylene glycol-graft-polylactic acid-glycolic acid copolymer, 23 parts of chitosan@plant-peptide composite gel, 18 parts of modified microporous polyethylene, and 4 parts of polyvinyl alcohol binder.

[0077] 1. Preparation of polyethylene glycol-grafted polylactic acid-glycolic acid copolymer:

[0078] A1: 20 g of poly(lactic acid-co-glycolic acid) was added to 1000 mL of dichloromethane and mixed and dissolved uniformly to obtain a 2 wt % poly(lactic acid-co-glycolic acid) solution; 1.8 mL of trimethylsilane was slowly and dropwise added to the 1000 mL poly(lactic acid-co-glycolic acid) solution, and stirred at 500 rpm with a magnetic stirrer for 9 minutes. Then, 0.4 mL of 98 wt % concentrated sulfuric acid was slowly added over 10 minutes. The temperature was controlled at 35°C in a water bath and stirred at 100 rpm for 3.5 hours. After the reaction was completed, the mixture was allowed to cool to room temperature to obtain a mixed solution.

[0079] A2: The mixed solution prepared in step A1 was added to a rotary evaporator, and the pressure, temperature, and rotation speed were controlled to 4 kPa, 55°C, 140 rpm, and 6°C, respectively. After evaporation for 1.5 hours, a concentrated solution was obtained. The concentrated solution was centrifuged at 8000 rpm for 10 minutes, and the precipitate was collected, washed three times with ethanol, and freeze-dried at -20°C in a vacuum vacuum for 12 hours to obtain a modified poly(lactic acid-co-glycolic acid) copolymer.

[0080] A3: 20 g of the modified poly(lactic acid-co-glycolic acid) prepared in step A2 was added to 2000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 10 wt % modified poly(lactic acid-co-glycolic acid) solution, and 200 g of polyethylene glycol was dissolved in 1000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 20 wt % polyethylene glycol solution;

[0081] A4: 1.8 g of N-hydroxysuccinimide and 2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added to 2000 mL of the modified polylactic acid-co-glycolic acid solution prepared in step A3, and stirred at 260 rpm for 10 min. Then, 1000 mL of the polyethylene glycol solution prepared in step A3 was slowly added within 30 min. The mixture was heated in a water bath at 40 ° C. for 15 h, and then 15 L of deionized water was added to terminate the reaction. The mixture was filtered through an 18 KDa dialysis bag and freeze-dried in a vacuum at -30 ° C. for 22 h to obtain polyethylene glycol-grafted-polylactic acid-co-glycolic acid.

[0082] 2. Preparation of Chitosan@PNIPAM Vitamin K2-Phosphate Gel:

[0083] B1: Grind chitosan and sieve through a 100-mesh sieve to obtain chitosan powder; dissolve 20 g of chitosan powder in 1000 mL of 1 wt% acetic acid solution until uniformly dissolved to obtain a 2 wt% chitosan solution; dissolve 160 g of N-isopropylacrylamide in 2000 mL of deionized water, control the temperature at 32°C in a water bath, and stir at 400 rpm for 10 min until uniformly dissolved to obtain an 8 wt% N-isopropylacrylamide solution; then slowly add 1800 mL of N-isopropylacrylamide solution to 1000 mL of chitosan solution, and stir at 300 rpm at room temperature for 30 min to obtain a mixed solution;

[0084] B2: Add 2.8 g of vitamin K2, 25 g of bisphosphate and 50 g of plant extract to 2800 mL of the mixed solution in step B1. After mixing evenly, add 14 g of N,N'-methylenebisacrylamide and 5 g of azobisisobutyronitrile. Heat in a water bath and control the temperature to 34 ° C. Stir continuously at 700 rpm for 8 minutes, then reduce the speed to 200 rpm and continue stirring for 3 hours. Cool naturally to room temperature, wash three times with deionized water, and freeze-dry at -30 ° C in a vacuum dryer for 12 hours to obtain chitosan@PNIPAM vitamin K2-phosphate gel.

[0085] 3. Preparation of modified microporous polyethylene:

[0086] C1: 100 g of low-density polyethylene, 45 g of sodium chloride, and 8 mL of dioctyl phthalate were mixed to obtain a mixture; the mixture was extruded into a film at 180°C, a speed of 0.6 m / min, and a thickness of 0.05 mm. After extrusion, the film was rapidly cooled to room temperature and soaked in 45°C warm water for 42 h, with the warm water replaced every 6 h, to obtain microporous polyethylene.

[0087] C2: Soak 100 g of the microporous polyethylene prepared in step C1 in 500 mL of a 1 wt% 3-aminopropyltrimethoxysilane solution for 3 h, and then dry at 75 ° C for 2 h to obtain a silane-modified product; add 100 g of the silane-modified product to 500 mL of a 2 wt% polyethylene glycol solution, and then add 0.5% pentanediol. After stirring at 300 rpm at room temperature for 5 h, dry at 85 ° C for 6 h to obtain a modified microporous polyethylene.

[0088] 4. Preparation of arteriovenous fistula dressing for preventing vascular calcification:

[0089] S1: Add polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer by weight to 5 times the mass volume of chloroform solution, coat on a flat plate to a thickness of 0.2 mm, control the temperature at 30°C and the humidity at 45% and dry for 10 h to obtain a polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer film;

[0090] S2: Chitosan@PNIPAM vitamin K2-phosphate gel was diluted by 2 times the mass volume of deionized water, and coated onto the polyethylene glycol-graft-polylactic acid-co-glycolic acid film in step S1 to a thickness of 0.2 mm. The temperature was controlled at 25°C and the humidity was 40%, and the mixture was dried for 20 h to obtain a composite coating.

[0091] S3: bonding the modified microporous polyethylene to the composite coating prepared in step S2 according to parts by weight. Before bonding, a layer of polyvinyl alcohol adhesive needs to be coated on the modified microporous polyethylene. The modified microporous polyethylene is allowed to stand at room temperature for 14 hours to obtain a dressing.

[0092] Example 4: An arteriovenous fistula external dressing for preventing vascular calcification comprises the following raw materials in parts by weight: 25 parts of polyethylene glycol-graft-polylactic acid-glycolic acid copolymer, 25 parts of chitosan@plant-peptide composite gel, 20 parts of modified microporous polyethylene, and 5 parts of polyvinyl alcohol binder.

[0093] 1. Preparation of polyethylene glycol-grafted polylactic acid-glycolic acid copolymer:

[0094] A1: 20 g of poly(lactic acid-co-glycolic acid) was added to 1000 mL of dichloromethane, mixed and dissolved uniformly to obtain a 2 wt% poly(lactic acid-co-glycolic acid) solution; 2 mL of trimethylsilane was slowly and dropwise added to the 1000 mL poly(lactic acid-co-glycolic acid) solution, and stirred at 500 rpm for 10 minutes using a magnetic stirrer. 0.4 mL of 98 wt% concentrated sulfuric acid was then slowly added over 10 minutes. The temperature was controlled at 35°C in a water bath and stirred at 100 rpm for 4 hours. After the reaction was completed, the mixture was allowed to cool to room temperature to obtain a mixed solution.

[0095] A2: The mixed solution prepared in step A1 was added to a rotary evaporator, and the pressure, temperature, and speed were controlled to 5 kPa, 60°C, 160 rpm, and condenser temperature to 5°C. After evaporation for 2 hours, a concentrated solution was obtained. The concentrated solution was centrifuged at 8000 rpm for 10 minutes, and the precipitate was collected, washed three times with ethanol, and freeze-dried at -20°C in a vacuum vacuum for 12 hours to obtain a modified poly(lactic acid-co-glycolic acid) copolymer.

[0096] A3: 20 g of the modified poly(lactic acid-co-glycolic acid) prepared in step A2 was added to 2000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 10 wt % modified poly(lactic acid-co-glycolic acid) solution, and 200 g of polyethylene glycol was dissolved in 1000 mL of N,N-dimethylformamide, mixed and dissolved uniformly to obtain a 20 wt % polyethylene glycol solution;

[0097] A4: 2 g of N-hydroxysuccinimide and 2 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide were added to 2000 mL of the modified polylactic acid-glycolic acid copolymer solution prepared in step A3, and stirred at 300 rpm for 10 min. Then, 1000 mL of the polyethylene glycol solution prepared in step A3 was slowly added within 30 min. The mixture was heated in a water bath at 40 ° C. for 16 h, and then 15 L of deionized water was added to terminate the reaction. The mixture was filtered through a 20 KDa dialysis bag and freeze-dried in a vacuum at -30 ° C. for 24 h to obtain polyethylene glycol-grafted polylactic acid-glycolic acid copolymer.

[0098] 2. Preparation of Chitosan@PNIPAM Vitamin K2-Phosphate Gel:

[0099] B1: Grind chitosan and sieve through a 100-mesh sieve to obtain chitosan powder; dissolve 20 g of chitosan powder in 1000 mL of 1 wt% acetic acid solution until uniformly dissolved to obtain a 2 wt% chitosan solution; dissolve 160 g of N-isopropylacrylamide in 2000 mL of deionized water, control the temperature at 32°C in a water bath, and stir at 500 rpm for 10 min until uniformly dissolved to obtain an 8 wt% N-isopropylacrylamide solution; then slowly add 2000 mL of N-isopropylacrylamide solution to 1000 mL of chitosan solution, and stir at 300 rpm at room temperature for 30 min to obtain a mixed solution;

[0100] B2: Add 3 g of vitamin K2, 30 g of bisphosphate and 60 g of plant extract to 3000 mL of the mixed solution in step B1. After mixing evenly, add 15 g of N,N'-methylenebisacrylamide and 6 g of azobisisobutyronitrile. Heat in a water bath and control the temperature to 32°C. Stir continuously at 800 rpm for 10 min, then reduce the speed to 300 rpm and continue stirring for 4 h. Cool naturally to room temperature, wash three times with deionized water, and freeze-dry at -30°C in a vacuum freeze-drying machine for 12 h to obtain chitosan@PNIPAM vitamin K2-phosphate gel.

[0101] 3. Preparation of modified microporous polyethylene:

[0102] C1: 100 g of polyethylene, 50 g of sodium chloride, and 10 mL of dioctyl phthalate were mixed to obtain a mixture; the mixture was extruded into a film at 200°C, a speed of 0.5 m / min, and a thickness of 0.05 mm. After extrusion, the film was rapidly cooled to room temperature and soaked in 45°C warm water for 48 hours, with the warm water replaced every 6 hours, to obtain microporous polyethylene.

[0103] C2: Soak 100 g of the microporous polyethylene prepared in step C1 in 500 mL of a 1 wt% 3-aminopropyltrimethoxysilane solution for 4 h, and then dry at 80 ° C for 2 h to obtain a silane-modified product; add 100 g of the silane-modified product to 500 mL of a 2 wt% polyethylene glycol solution, and then add 0.5% pentanediol. After stirring at 300 rpm at room temperature for 6 h, dry at 90 ° C for 6 h to obtain a modified microporous polyethylene.

[0104] 4. Preparation of arteriovenous fistula dressing for preventing vascular calcification:

[0105] S1: Add polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer by weight to 5 times the mass volume of chloroform solution, coat on a flat plate to a thickness of 0.1 mm, control the temperature at 30°C and the humidity at 45% and dry for 12 h to obtain a polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer film;

[0106] S2: Chitosan@PNIPAM vitamin K2-phosphate gel was diluted by weight in 2 times the mass volume of deionized water, and coated on the polyethylene glycol-graft-polylactic acid-co-glycolic acid film in step S1 to a thickness of 0.2 mm. The temperature was controlled at 25°C and the humidity was 40%, and the mixture was dried for 24 hours to obtain a composite coating.

[0107] S3: bonding the modified microporous polyethylene to the composite coating prepared in step S2 according to parts by weight. Before bonding, a layer of polyvinyl alcohol adhesive needs to be coated on the modified microporous polyethylene. The modified microporous polyethylene is allowed to stand at room temperature for 14 hours to obtain a dressing.

[0108] Comparative Example 1: Comparative Example 1 is basically the same as Example 2, except that Comparative Example 1 does not use modified polylactic acid-glycolic acid copolymer grafted with polyethylene glycol, but directly uses polylactic acid-glycolic acid copolymer as the inner layer.

[0109] Comparative Example 2: Comparative Example 2 is substantially the same as Example 3, except that Comparative Example 2 does not use modified microporous polyethylene and does not have an outer layer structure.

[0110] Performance testing:

[0111] Spectrum measurement: The polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer sample prepared in Example 3 was placed on a potassium bromide substrate, and the spectrum was measured using an FTIR spectrometer; the chitosan@PNIPAM dimension K2-phosphate gel sample prepared in Example 3 was placed on a potassium bromide substrate, and the spectrum was measured using an FTIR spectrometer; the chitosan@PNIPAM dimension K2-phosphate gel sample prepared in Example 3 was placed on a SEM sample tray, fixed with an adhesive carbon tape, covered with a layer of carbon by spraying, the parameters were adjusted to set the voltage to 10 kV, and the sample surface was scanned with an electron beam; the FTIR spectrum of the polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer is shown in FIG. Figure 1 As shown; the FTIR spectrum of chitosan@PNIPAM K2-phosphate gel is shown Figure 2 As shown; the SEM scanning electron microscopy spectrum of chitosan@PNIPAM K2-phosphate gel is shown Figure 3 shown.

[0112] Figure 1 The results show that the polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer prepared in Example 3 has a C=O stretching peak (3400-3500 cm -1 ) has an increased intensity range and a distinct peak; Figure 2 The results show that the chitosan@PNIPAM vitamin K2-phosphate gel prepared in Example 3 has an obvious peak; Figure 3The results show that the chitosan@PNIPAM vitamin K2-phosphate gel prepared in Example 3 has a large surface area and a continuous and porous network structure, which is conducive to adsorption and transport.

[0113] Cytotoxicity test: The external dressings prepared in Examples 1 to 4 were cut into 3×3 cm pieces and immersed in DMEM medium at 37°C for 48 h to obtain an extract. The extracts of the dressing samples of Examples 1 to 4 and the control group (DMEM medium) were evenly distributed in a 96-well plate with 16 wells per group of samples. Fibroblasts were then diluted to 1×10 5 After 50 μL of the culture medium was inoculated into a 96-well plate, the temperature was set at 37°C and the concentration of CO2 was 5%. After incubation for 48 h, 50 μL of 5 mg / mL MTT solution was added and incubation was continued for 4 h. The culture medium in the wells was aspirated and 200 μL of dimethyl sulfoxide was added to the wells. The absorbance (OD value) was measured at 570 nm using a microplate reader, and the activity percentage was measured [cell survival rate (%) = (OD value of the example / OD value of the control group) × 100%]. The results are shown in FIG. Figure 4 shown.

[0114] Figure 4 The results show that the external dressings prepared in Examples 1 to 4 have no toxic effects on cells, but have a certain degree of promoting effect on cells and are highly safe for the skin.

[0115] Dissolution release test: The external dressings prepared in Examples 1 to 4 of the present invention and Comparative Examples 1 to 2 were cut into 3×3 cm pieces and immersed in 200 mL of pH 6.8 phosphate buffer solution at 37°C. Samples were taken at 0.5 h, 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h, with 10 mL of sample taken at each sampling point. After that, 10 mL of solution was added to the solution and the release amount (Xn'=Xn+(X1+X2+X n-1 )V2 / V1; where X n is the relative percentage dissolution measured after correction for the nth time, X n’ is the relative percentage dissolution actually measured for the nth time, V1 is the volume of the dissolution medium, and V2 is the volume added after each sampling). The results are as follows Figure 5 shown.

[0116] Figure 5 The results show that the external dressings prepared in Examples 1 to 4 can achieve stable and sustained release. The results of Comparative Example 1 show that the modified polylactic acid-glycolic acid copolymer grafted with polyethylene glycol can effectively improve its dissolution efficiency. The results of Comparative Example 2 show that the lack of the outer layer of modified microporous polyethylene affects its stability and dissolution performance.

[0117] Water vapor transmission rate test: According to the "YY / T0471.2-2004 Test Method for Contact Wound Dressing Part 2", the water vapor transmission rate of the external dressings prepared in Examples 1 to 4 and Comparative Examples 1 to 2 was tested. Before the test, the samples were cut into 3×3 cm sizes. The results are as follows: Figure 6 shown.

[0118] Figure 6 The results show that the external dressings prepared in Examples 1 to 4 are significantly better than those in Comparative Examples 1 to 2. The modified polylactic acid-glycolic acid copolymer grafted with polyethylene glycol can effectively increase the water vapor permeability of the dressing compared to the polylactic acid-glycolic acid copolymer. The results of Comparative Example 2 show that microporous polyethylene can significantly enhance the water vapor permeability of the dressing.

[0119] Bacterial inhibition test: fresh bacterial suspensions of Staphylococcus aureus, Escherichia coli and Candida albicans were prepared at a concentration of 1×10 8 CFU / mL, the external dressing samples (1×1 cm in size) prepared in Examples 1 to 4 of the present invention were added respectively, and the mixed bacterial solution was placed in a constant temperature oscillator at 37°C for 24 h. The total number of colonies in the bacterial solution was recorded by the plate colony counting method. The test was repeated 3 times, and the average value was taken. The bacterial solution without sample was used as a control (the strains used in this experiment were all purchased from the market), and the inhibition rate was calculated (inhibition rate (%) = (1-the number of bacteria in the control sample / the number of bacteria in the experimental sample) × 100%). The results are as follows Figure 7 shown.

[0120] Figure 7 The results show that the external dressings prepared in Examples 1 to 4 have excellent antibacterial effects and can effectively prevent bacterial infection during use.

[0121] While 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 these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing an arteriovenous fistula external dressing for preventing vascular calcification, characterized in that: The arteriovenous fistula external dressing comprises the following raw materials in parts by weight: 15 to 25 parts of polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer, 15 to 25 parts of chitosan@PNIPAM vitamin K2-phosphate gel, 10 to 20 parts of modified microporous polyethylene, and 2 to 5 parts of polyvinyl alcohol binder; The preparation of the polyethylene glycol-grafted polylactic acid-glycolic acid copolymer comprises the following steps: A1: Add poly(lactic acid-co-glycolic acid) copolymer to dichloromethane, mix and dissolve uniformly to obtain a 2 wt% poly(lactic acid-co-glycolic acid) copolymer solution; slowly dropwise add trimethylsilane to the poly(lactic acid-co-glycolic acid) copolymer solution, and stir at 500 rpm with a magnetic stirrer for 5-10 minutes. Then, slowly add concentrated sulfuric acid over 10 minutes. Control the temperature at 35°C in a water bath and stir at 100 rpm for 2-4 hours. After the reaction is completed, allow the mixture to cool to room temperature to obtain a mixed solution. A2: The mixed solution prepared in step A1 was added to a rotary evaporator, and the pressure was controlled to 2.5-5 kPa, the temperature was 40-60°C, the rotation speed was 100-160 rpm, and the condenser temperature was 5-10°C. After evaporation for 1-2 hours, a concentrated solution was obtained; the concentrated solution was centrifuged at 8000 rpm for 10 minutes, and the precipitate was collected, washed with ethanol three times, and freeze-dried in a vacuum at -20°C for 12 hours to obtain a modified poly(lactic acid-co-glycolic acid) copolymer; A3: adding the modified polylactic acid-co-glycolic acid copolymer prepared in step A2 to N,N-dimethylformamide, mixing and dissolving them uniformly to obtain a 10 wt % modified polylactic acid-co-glycolic acid copolymer solution; dissolving polyethylene glycol in N,N-dimethylformamide, mixing and dissolving them uniformly to obtain a 20 wt % polyethylene glycol solution; A4: Add N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide to the modified poly(lactic acid-co-glycolic acid) copolymer solution prepared in step A3, stir at 100-300 rpm for 10 minutes, then slowly add the polyethylene glycol solution prepared in step A3 over 30 minutes. Heat in a water bath at 40°C for 12-16 hours, then add 5 volumes of deionized water to terminate the reaction. Filter through a 10-20 kDa dialysis bag, and freeze-dry at -30°C under vacuum for 18-24 hours to obtain polyethylene glycol-grafted poly(lactic acid-co-glycolic acid) copolymer. In step A1, the ratio of trimethylsilane to polylactic acid-co-glycolic acid is 0.05-0.1 mL:1 g; the ratio of concentrated sulfuric acid to polylactic acid-co-glycolic acid is 0.02 mL:1 g; The volume ratio of the modified polylactic acid-co-glycolic acid solution to the polyethylene glycol solution in step A4 is 1:0.5; the mass ratio of the N-hydroxysuccinimide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and the modified polylactic acid-co-glycolic acid is 0.05-0.1:0.1:1; The chitosan@PNIPAM vitamin K2-phosphate gel comprises chitosan, N-isopropylacrylamide, plant extracts, vitamin K2 and bisphosphate; the plant extracts are prepared by mixing green tea extract, grape seed extract, turmeric extract and ginseng extract in a mass ratio of 0.8:1.2:1.5:0.7; the green tea extract is extracted by gentle heating in a water bath using ethanol as a solvent; the grape seed extract is extracted by soaking in ethanol as a solvent; the turmeric extract is extracted by gentle heating in a water bath using ethanol as a solvent; and the ginseng extract is extracted by heating in a water bath using ethanol as a solvent. The preparation method of the chitosan@PNIPAM vitamin K2-phosphate gel comprises the following steps: B1: Grind chitosan and sieve through a 100-mesh sieve to obtain chitosan powder; dissolve the chitosan powder in a 1 wt% acetic acid solution until uniformly dissolved to obtain a 2 wt% chitosan solution; dissolve N-isopropylacrylamide in deionized water, control the temperature at 32°C in a water bath, and stir at 200-500 rpm for 10 minutes until uniformly dissolved to obtain an 8 wt% N-isopropylacrylamide solution; slowly add the N-isopropylacrylamide solution to the chitosan solution, and stir at 300 rpm at room temperature for 30 minutes to obtain a mixed solution; B2: Vitamin K2, bisphosphate, and plant extract were added to the mixed solution in step B1. After mixing evenly, N,N'-methylenebisacrylamide and azobisisobutyronitrile were added. The mixture was heated in a water bath at 32-42°C. Stirring was continued at 500-800 rpm for 5-10 minutes. The stirring speed was then reduced to 100-300 rpm and stirring was continued for 2-4 hours. The mixture was naturally cooled to room temperature, washed three times with deionized water, and freeze-dried at -30°C in a vacuum freeze-drying process for 12 hours to obtain chitosan@PNIPAM vitamin K2-phosphate gel. The volume ratio of the chitosan solution to the N-isopropylacrylamide solution in step B1 is 1:1.2-2; the amount ratio of vitamin K2, bisphosphonate, plant extract and mixed solution in step B2 is 0.001g:0.005-0.01g:0.01-0.02g:1mL; the amount ratio of N,N'-methylenebisacrylamide, azobisisobutyronitrile and mixed solution is 0.005g:0.001-0.002g:1mL; The preparation of the modified microporous polyethylene comprises the following steps: C1: Polyethylene, sodium chloride, and dioctyl phthalate were uniformly mixed to obtain a mixture; the mixture was formed into a film through an extruder with setting parameters of 160-200°C, an extrusion speed of 0.5-1 m / min, and a thickness of 0.05-0.1 mm. After extrusion, the film was rapidly cooled to room temperature and soaked in warm water at 35-45°C for 24-48 hours, with the warm water being replaced every 6 hours, to obtain microporous polyethylene; C2: Immerse the microporous polyethylene prepared in step C1 in 5 times the mass volume of a 1 wt% 3-aminopropyltrimethoxysilane solution for 2 to 4 hours, and then dry at 60 to 80°C for 1 to 2 hours to obtain a silane-modified product; add the silane-modified product to 5 times the mass volume of a 2 wt% polyethylene glycol solution, and then add 0.5% pentanediol, stir at 300 rpm at room temperature for 4 to 6 hours, and then dry at 70 to 90°C for 6 hours to obtain a modified microporous polyethylene; The polyethylene in step C1 is low-density polyethylene; the ratio of polyethylene, sodium chloride and dioctyl phthalate is 1g:0.3-0.5g:0.05-0.1mL; The preparation method of the arteriovenous fistula external dressing comprises the following steps: S1: Add polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer by weight to 4 times the mass volume of chloroform solution, coat on a flat plate to a thickness of 0.1-0.5 mm, control the temperature at 30°C and the humidity at 45% and dry for 6-12 hours to obtain a polyethylene glycol-grafted-polylactic acid-glycolic acid copolymer film; S2: Chitosan@PNIPAM vitamin K2-phosphate gel was diluted by 2 times the mass volume of deionized water, and coated onto the polyethylene glycol-graft-polylactic acid-co-glycolic acid film in step S1 to a thickness of 0.2-0.4 mm. The temperature was controlled at 25°C and the humidity was 40%, and the mixture was dried for 12-24 hours to obtain a composite coating. S3: bonding the modified microporous polyethylene to the composite coating prepared in step S2 according to parts by weight. Before bonding, a layer of polyvinyl alcohol adhesive needs to be coated on the modified microporous polyethylene. The modified microporous polyethylene is allowed to stand at room temperature for 10 to 14 hours to obtain a dressing.

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