Preparation method and application of polyurethane elastomer containing in-situ nano-silver

Abstract

The invention discloses a preparation method and application of a polyurethane elastomer containing in-situ nano-silver, and belongs to the field of biomaterials.The preparation method comprises the steps that a, polycaprolactone glycol, dibutyltin dilaurate and a solvent are mixed and stirred to be dissolved, HDI is added, a reaction is conducted, and a prepolymer is obtained; b, adding a chain extender into the reaction system, and carrying out polymer end capping; c, under a dark condition, adding a silver ion solution into the reaction system, and reacting; and d, after the reaction is finished, cooling the system, stopping stirring, pouring the reaction liquid into deionized water, precipitating and separating out the polyurethane elastomer, and carrying out vacuum drying treatment. The prepared polyurethane elastomer containing in-situ nano-silver has excellent antibacterial activity and excellent mechanical properties, is prepared into a nanofiber membrane-like dressing through an electrostatic spinning technology, can be used as a wound dressing or a medical implant material, can be independently used, and can also be compounded with other materials for use.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials, specifically relating to a method for preparing an in-situ silver nanoparticle-containing polyurethane elastomer using polycaprolactone diol as a raw material via a prepolymer method combined with silver nitrate crosslinking technology, and its application. Background Technology

[0002] Polyurethane (PU) is a polymer containing a large number of repeating urethane groups on its main chain, typically obtained by stepwise polymerization of polyisocyanates and polyols. It consists of alternating soft segments (soft segments) with glass transition temperatures below room temperature and rigid segments (hard segments) with glass transition temperatures above room temperature, generally exhibiting excellent mechanical properties and ease of molding and processing. Furthermore, its structure is similar to the amide and ester groups found in human proteins, resulting in good biocompatibility and widespread application in medical materials such as catheters, adhesives, and cardiovascular stents. However, medical polyurethane products lack antibacterial properties during use, and their hydrophobic surfaces readily attract bacteria, potentially leading to post-implantation inflammation and infection with prolonged use, causing patient discomfort. Therefore, developing polyurethane materials with excellent antibacterial properties is a crucial research direction for many scientists. Currently, commonly used antibacterial agents mainly include quaternary ammonium salts, guanidine salts, and imidazole heterocyclic quaternary ammonium salts, with quaternary ammonium salts being the most widely researched and applied due to their low cost and rapid bactericidal action. However, with increased safety awareness and advancements in science and technology, it has been discovered that traditional quaternary ammonium salt small-molecule antibacterial agents suffer from drawbacks such as high toxicity, short duration of action, volatility, and poor chemical stability. In recent years, nano-silver has attracted widespread attention due to its broad-spectrum, long-lasting antibacterial properties and low cytotoxicity.

[0003] Furthermore, polyurethane itself possesses excellent mechanical properties, and constructing a cross-linked network structure allows for more autonomous regulation of the mechanical properties and degradation rate of biomaterials. Therefore, modifying polyurethane materials to acquire antibacterial properties and autonomously adjusting the mechanical properties of the polyurethane matrix has become a hot research topic in recent years. This is of great significance for protecting human health and maintaining the mechanical properties of polyurethane materials.

[0004] Currently, research on the preparation of polyurethane elastomers mainly focuses on monomers and polymers derived from natural resources and their derivatives, as well as some biodegradable polymers. Natural resource derivatives are primarily oligosaccharides, cellulose, starch, and lignin. While these substances possess good biocompatibility and biodegradability, the polyurethane prepared from them often produces metabolic products that are harmful to the human body or cannot be absorbed, thus rendering them unsuitable for medical applications. However, if fully biodegradable polymers such as polylactic acid, polycaprolactone, and polyethylene carbonate are used as the polyol components of polyurethane, the resulting polyurethane is suitable for medical use. Among these, the manufacturing processes of polylactic acid and polyethylene carbonate are complex and costly, hindering industrial production. Polycaprolactone, as an FDA-approved biomaterial, possesses excellent biocompatibility, making it an ideal raw material for producing medical-grade polyurethane.

[0005] Electrospinning is a novel nanofiber membrane preparation technology with advantages such as simple operation and flexible process. The electrospinning apparatus mainly consists of a high-voltage power supply, a push pump, a syringe equipped with a metal needle, and a receiving device. Under the action of high-voltage electrostatics, the spinning solution forms a liquid cone, and a large number of charges accumulate on the surface of the cone. When the electrostatic force generated by the charges exceeds the surface tension of the liquid, a Taylor cone is formed. Subsequently, under the attraction of electrostatic force, the spinning solution splits into jets that fly towards the receiving device. With the rapid evaporation of the solvent, the jet is stretched to the micro-nano scale during its flight, eventually solidifying and depositing on the receiving device to form nanofiber membranes (ENMs). By adjusting the composition of the spinning solution, process parameters, and environmental parameters, ENMs meeting different needs can be prepared. This highly adjustable preparation process can adapt to the various complex requirements of wound dressings. Summary of the Invention

[0006] The primary objective of this invention is to provide a polyurethane elastomer with good biocompatibility, excellent mechanical properties and sustained broad-spectrum antibacterial properties, and secondly, to provide the application of this polyurethane elastomer in the preparation of wound dressings.

[0007] To achieve the above objectives, this application provides the following technical solution: A method for preparing a polyurethane elastomer containing in-situ silver nanoparticles includes the following steps: Step a: Mix polycaprolactone diol, dibutyltin dilaurate, and solvent, and stir until the reactants are completely dissolved; add hexamethylene diisocyanate (HDI) under an inert environment, and react at 60℃~120℃ for 24~36 hours to obtain the prepolymer; Step b: Under inert gas protection, add the chain extender to the reaction system of step a for polymer end-capping, and react at 60℃~120℃ for 24~48 hours; Step c: Under light-protected conditions, add silver ion solution to the reaction system of step b and react at 60℃~120℃ for 24~48 hours; Step d: After the reaction is complete, cool the system to 20℃~30℃, stop stirring, stop the inert gas protection, pour the reaction solution into deionized water, precipitate the polyurethane elastomer, and vacuum dry it.

[0008] In step a, the polycaprolactone diol (PCL) is a biodegradable aliphatic polyester diol, prepared by ring-opening polymerization of ε-caprolactone monomer, with hydroxyl functional groups at both ends of the molecular chain. Its molecular weight (Mn) is 2000~20000.

[0009] In step a), polycaprolactone diol and dibutyltin dilaurate are dissolved in a solvent in a sealed reactor purged with nitrogen three times, and stirred at 50°C to 120°C until the reactants are completely dissolved. Hexamethylene diisocyanate is then added under inert conditions to initiate the reaction. The molar ratio of hexamethylene diisocyanate to polycaprolactone diol is 1:1 to 2:1.

[0010] In step b, the chain extender is selected from [2-[(2-hydroxyphenyl)methylene]amino]-1,3-propanediol (HPA), 3,4-dihydroxybenzoic acid (PCA), and luteolin (LUT).

[0011] In step c, silver nitrate is preferred as the silver ion source. The amount of silver ion source added is controlled based on the molar ratio of silver ions to polycaprolactone diol, which is 1:4 to 1:1, preferably 1:4, 1:2, or 1:1. Alternatively, the amount of silver ion source added can also be controlled based on the molar ratio of silver ions to the chain extender, which is 4:1 to 1:1, preferably 4:1, 2:1, or 1:1.

[0012] In step d, the vacuum drying temperature is 60℃~120℃, and the vacuum drying time is 12~48 hours.

[0013] The reaction ad was carried out in a DMF solvent environment.

[0014] A polyurethane elastomer nanofiber membrane, using the polyurethane elastomer containing in-situ silver nanoparticles obtained by the above preparation method as the spinning raw material, specifically the preparation method is as follows: The polyurethane elastomer containing in-situ silver nanoparticles obtained by the above preparation method was dissolved in organic solvents such as hexafluoroisopropanol (1,1,1,3,3,3-hexafluoro-2-propanol, HFIP) and tetrahydrofuran to prepare a spinning solution. Electrospinning was then performed with appropriate process parameters: the concentration of the spinning solution was 10%–30% (w / v), the spinning voltage was 10kV–20kV, the needle type was 23G, and the injection speed was 1 mL·h. -1 ~5mL·h -1 The receiving distance is 8cm~20cm, and the spinning temperature is 20℃~40℃. After completion, the fiber membrane is collected and placed in a vacuum drying oven to dry at 25℃~40℃ for 24~48 hours to remove residual organic solvents, finally obtaining a polyurethane nanofiber membrane made from polycaprolactone diol. The thickness of the nanofiber membrane is 50μm~500μm, the fiber diameter is distributed in the range of 300nm~500nm, and the tensile strength ranges from 1MPa~100MPa.

[0015] A composite nanofiber membrane is prepared by blending an in-situ silver nanoparticle-containing polyurethane elastomer obtained by the above-mentioned preparation method with collagen or gelatin. The proportion of collagen or gelatin added is 1.0%~10% (w / v). Electrospinning process parameters: spinning solution concentration is 10%~30% (w / v), spinning voltage is 10kV~20kV, needle type is 23G, and injection speed is 1mL·h. -1 ~5mL·h -1 The receiving distance is 8cm to 20cm, and the spinning temperature is 20℃ to 40℃. The fiber diameter of this composite nanofiber membrane is distributed in the range of 100nm to 900nm, and the membrane thickness is 50μm to 500μm.

[0016] The polyurethane elastomer containing in-situ nano-silver described in this invention has good antibacterial and antimicrobial effects against Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa.

[0017] Therefore, the present invention also provides the use of the polyurethane elastomer containing in-situ silver nanoparticles, or the polyurethane elastomer nanofiber membrane, or the composite nanofiber membrane as a wound dressing or medical implant material. Specific applications include: Use directly as a wound dressing; As medical implant / contact materials and coatings, they can be used specifically for coatings of implants, implantable artificial organs, contact artificial organs, stents, interventional catheters, tissue engineering scaffolds, and organ assist devices; Body material used in implantable artificial organs, contact artificial organs, stents, interventional catheters, tissue engineering scaffolds and organ assist devices.

[0018] The beneficial effects of this invention are: In this invention, polycaprolactone diol is used as the main polyol chain, and a safe, non-toxic, biodegradable, and biocompatible polyurethane elastomer is synthesized via a prepolymer method. By controlling the molecular weight or the proportion of silver ions added, the crosslinking density is adjusted, ultimately yielding a polyurethane elastomer with excellent mechanical properties and superior antibacterial properties. This synthesis method is simple, the reaction is stable, and it is easy to control.

[0019] The polyurethane elastomer containing in-situ silver nanoparticles prepared by this invention has excellent antibacterial activity and mechanical properties. It is prepared into a nanofiber membrane dressing by electrospinning technology. This dressing can be used as a wound dressing or medical implant material. It can be used alone or in combination with other materials. Specifically, it can be used as a coating material for implantable devices, implantable artificial organs, contact artificial organs, stents, interventional catheters, organ assist devices, and tissue engineering scaffolds. Attached Figure Description

[0020] Figure 1 NMR of the HPA chain extender prepared in Example 1 1 H-NMR spectrum; Figure 2 The infrared spectrum of the polyurethane elastomer containing in-situ silver nanoparticles prepared in Example 2; Figure 3 The antibacterial properties of the polyurethane prepared in Example 2 were tested. Figure 4 The image shows the morphology of the wound dressing prepared in Example 2. Figure 5 The mechanical properties of the wound dressing prepared in Example 2 are shown in the figure; where A: stress-strain curve, B: maximum tensile strength, C: elongation at break, and D: Young's modulus. Figure 6 The wound appearance of the wound film prepared in Example 2 as a wound dressing for the care of infected wounds from deep burns; Figure 7 The wound healing rate of the wound film prepared in Example 2 as a wound dressing for the care of infected deep burn wounds; **p<0.01, ****p<0.0001. Detailed Implementation

[0021] The technical solutions of the present invention will be described in detail below through embodiments. The following embodiments are merely exemplary and can only be used to explain and illustrate the technical solutions of the present invention, and should not be construed as limiting the technical solutions of the present invention.

[0022] Unless otherwise specified, all raw materials and reagents used in this invention can be purchased through commercial channels.

[0023] Example 1

[0024] Schiff base ligand 2-((2-hydroxybenzylidene)amino)propane-1,3-diol ([2-[(2-hydroxyphenyl)methylene]amino]-1,3-propanediol) (HPA) was synthesized via a one-step reaction. CAS No.: 353263-66-8, Molecular Formula: C 10 H 13 NO3.

[0025] 10 mmol of 2-amino-1,3-propanediol was added to a 100 mL methanol solution of 10 mmol of salicylaldehyde. Triethylamine (10 mmol) was then added dropwise to the reaction mixture, which was stirred at room temperature for 5 hours to obtain a yellow solution. The reaction was carried out under anhydrous conditions. After the reaction was complete, the solvent was removed by rotary evaporation. The product was then dissolved in 15 mL of ethyl acetate and allowed to crystallize at -20 °C. The crystallized product was collected and dried under vacuum at 30 °C for 24 hours to obtain HPA, which was used as a chain extender.

[0026] Synthesis route:

[0027] Example 2 Using HPA as a linker, a polyurethane elastomer containing in-situ silver nanoparticles was prepared. The operation steps are as follows: First, polycaprolactone diol (Mn=2000) (4 g) and dibutyltin dilaurate (0.034 g) were dissolved in dry DMF (60 mL) in a sealed reactor purged three times with nitrogen, and heated to 60 °C with mechanical stirring. Then, 10 mL of DMF containing HDI (0.67 g) was added to the above solution. The reaction was carried out at 60 °C for 24 hours to obtain a prepolymer solution (OCN-PCL-NCO).

[0028] Subsequently, 7.0 mL of DMF containing HPA (0.392 g) was added to the above prepolymer solution, and the system was heated to 70 °C and continuously stirred for 24 hours to prepare polyurethane PCL-HPA.

[0029] Finally, under light-protected conditions, 7 mL of DMF solution containing silver nitrate (0.1 g, 0.2 g, 0.3 g) was slowly added to the above reaction system using a syringe, at a molar ratio of HPA:Ag. + The ratios were 4:1, 2:1, and 1:1, and stirred at 70°C for 24 hours to promote Ag... + Coordination of Ag. Simultaneously, in the presence of the solvent DMF, Ag... +In-situ reduction to nano-silver AgNPs. After the reaction, the reaction solution was settled in a large amount of deionized water and washed with water until the color no longer changed, in order to remove unreacted HPA and Ag. + The purified material was then vacuum-dried at 70°C for 48 hours to obtain PCL-HPA@AgNPs, specifically, at a mass ratio of HPA:Ag... + When the ratio is 4:1, the product is denoted as PCL-HPA@AgNPs. （4:1） , when HPA:Ag + When the ratio is 2:1, the product is denoted as PCL-HPA@AgNPs. （2:1） , when HPA:Ag + When the ratio is 1:1, the product is denoted as PCL-HPA@AgNPs. （1:1） .

[0030]

[0031] Example 3 Using 3,4-dihydroxybenzoic acid (PCA) as a linker, a polyurethane elastomer containing in-situ silver nanoparticles was prepared. The operation steps are as follows: First, polycaprolactone diol (Mn=2000) (4.0 g) and dibutyltin dilaurate (0.034 g) were dissolved in 60 mL of dry DMF in a sealed reactor purged three times with nitrogen, and heated to 60 °C with mechanical stirring. Then, 10 mL of DMF containing HDI (0.67 g) was added to the above solution. The reaction was carried out at 60 °C for 24 hours to obtain a prepolymer solution (OCN-PCL-NCO).

[0032] Subsequently, 7 mL of DMF containing PCA (0.3082 g) was added to the above prepolymer solution, and the system was heated to 70 °C and continuously stirred for 24 hours to prepare polyurethane PCL-PCA.

[0033] Finally, under light-protected conditions, 7 mL of DMF solution containing silver nitrate (0.1 g, 0.2 g, 0.3 g) was added at a molar ratio of PCA:Ag. + The ratios of PCA, PCA, and Ag were slowly added to the above reaction system using a syringe at ratios of 4:1, 2:1, and 1:1, and the mixture was stirred at 70°C for 24 hours. After the reaction was complete, the polymer solution was settled in a large volume of deionized water and washed with water until the color no longer changed, in order to remove unreacted PCA and Ag. + The purified material was then vacuum-dried at 70°C for 48 hours to obtain black PCL-PCA@AgNPs. Specifically, the mass ratio was [missing information - likely a specific ratio] when PCA:Ag [missing information - likely a specific ratio]. + When the ratio is 4:1, the product is denoted as PCL-PCA@AgNPs. （4:1） When PCA:Ag + When the ratio is 2:1, the product is denoted as PCL-PCA@AgNPs. （2:1） , when HPA:Ag + When the ratio is 1:1, the product is denoted as PCL-PCA@AgNPs. （1:1） .

[0034]

[0035] Example 4 Using luteolin (LUT) as a linker, a polyurethane elastomer containing in-situ silver nanoparticles was prepared. The operation steps are as follows: First, polycaprolactone diol (Mn=2000) (4.0 g) and dibutyltin dilaurate (0.034 g) were dissolved in 60 mL of dry DMF in a sealed reactor purged three times with nitrogen, and heated to 60 °C with mechanical stirring. Then, 10 mL of DMF containing HDI (0.67 g) was added to the above solution. The reaction was carried out at 60 °C for 24 hours to obtain a prepolymer solution (OCN-PCL-NCO).

[0036] Subsequently, 7 mL of DMF containing LUT (0.572 g) was added to the above prepolymer solution, and the system was heated to 70 °C and continuously stirred for 24 hours to prepare polyurethane PCL-LUT.

[0037] Finally, under light-protected conditions, 7 mL of DMF solution containing silver nitrate (0.1 g, 0.2 g, 0.3 g) was added at a molar ratio of LUT:Ag. + The ratios of LUT to AgNPs were 4:1, 2:1, and 1:1, and were slowly added to the above reaction system using a syringe, and the mixture was stirred at 70°C for 24 hours. After the reaction was complete, the reaction solution was precipitated in a large amount of deionized water and washed with water until the color no longer changed. The purified material was then vacuum-dried at 70°C for 48 hours to obtain PCL-LUT@AgNPs. Specifically, the mass ratio was 4:1, 2:1, and 1:1, when LUT:AgNPs were added to the above reaction system. + When the ratio is 4:1, the product is denoted as PCL-LUT@AgNPs （4:1） When LUT:Ag + When the ratio is 2:1, the product is denoted as PCL-LUT@AgNPs （2:1） When LUT:Ag + When the ratio is 1:1, the product is denoted as PCL-LUT@AgNPs. （1:1） .

[0038]

[0039] Performance testing: The chain extender HPA prepared in Example 1 was characterized by 1H NMR spectroscopy as follows: Figure 1 As shown, the target peak appears at δ=13.3ppm. 1 H-NMR spectrum (deuterated solvent acetone-d6, tetramethylsilane (TMS) as internal standard, frequency 600 MHz).

[0040] The polyurethane material obtained in Example 2 was subjected to infrared spectroscopy, such as... Figure 2 As shown, 2273cm -1 The absorption peak for -NCO is at 1723 cm⁻¹. -1 1729cm -1 These are the absorption peaks of the urethane (C=O stretching vibration) of PU, indicating that the isocyanate has been completely converted into the urethane structure, proving that the polyurethane structure has been formed.

[0041] Example 5

[0042] Testing the antibacterial properties of polyurethane materials: The polyurethane materials (PCL-HPA, PCL-HPA@AgNPs) prepared in Example 2 were dissolved together with collagen (COL) in HFIP and then electrospun to obtain COL / PCL-HPA and COL / PCL-HPA@AgNPs (4:1 / 2:1 / 1:1) (molar ratio, HPA:Ag). + The antibacterial effects of nanofiber membranes with ratios of 4:1, 2:1, and 1:1 were confirmed using the shake-flask method and bacterial growth curves. First, 40 mg of each sample was weighed and irradiated with ultraviolet light on both sides for 2 hours each. Next, the suspension of the bacterial solution (4 mL) was adjusted to 10... 6 CFU / mL. The nanofiber membrane was immersed in the bacterial solution and stirred at 150 rpm for 3 days at 37°C. A control group of the bacterial solution was also prepared without any treatment. All samples were repeated three times. During the culture, the turbid liquid of the bacterial solution was collected and fresh LB medium was added. The optical density (OD) was measured at different time points using a microplate reader. 600 Calculate these values ​​and plot them as a growth curve. For example... Figure 3 The growth curves of *Escherichia coli* and *Pseudomonas aeruginosa* are shown. The bacterial activity in bacterial suspensions treated with antibacterial polyurethane is significantly lower than that in untreated polyurethane material (i.e., polyurethane PCL-HPA before the addition of silver nitrate). From... Figure 3 It can be seen that in the control group, *E. coli* grew well, showing normal proliferation; the PCL-HPA group and the COL / PCL-HPA group showed some inhibition of *E. coli* growth, but proliferation still occurred; while the COL / PCL-HPA@AgNPs group showed...（4:1 / 2:1 / 1:1） All groups significantly inhibited the growth of Escherichia coli, OD 600 The level remained almost at 0, and the bacteria hardly multiplied.

[0043] As can be seen, the PCL-HPA@AgNPs prepared in Example 2 of this invention have good antibacterial and antimicrobial effects against Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa. Therefore, this antimicrobial nano-silver polyurethane material can be used as an antibacterial and antimicrobial material.

[0044] Example 6

[0045] Polyurethane elastomer nanofiber membrane dressings were prepared using polyurethane PCL-HPA obtained by the preparation method in Example 2 or polyurethane elastomer PCL-HPA@AgNPs containing in-situ silver nanoparticles as spinning raw materials.

[0046] A spinning solution was prepared by dissolving PCL-HPA or PCL-HPA@AgNPs in HFIP, followed by electrospinning. Electrospinning process parameters: spinning solution concentration 20% w / v, spinning voltage 10kV, needle type 23G, and injection speed 1mL·h. -1 The receiving distance was 15cm, and the spinning temperature was 20℃~30℃. After the process was completed, the fiber membrane was collected and placed in a vacuum drying oven to dry at a temperature of 25℃~30℃ for 24 hours to remove residual organic solvents, thus obtaining a polyurethane nanofiber membrane made from polycaprolactone diol.

[0047] The polyurethane elastomer prepared in Example 2 was used to fabricate wound dressings via electrospinning. Its nanofiber network structure was confirmed by scanning electron microscopy (SEM). First, the dressing samples were adhered to the sample stage with conductive adhesive. Field emission scanning electron microscopy was used to collect surface morphology images of each dressing sample at an accelerating voltage of 3 kV. The average diameter of 100 fibers was measured using ImageJ software, and the diameter distribution was statistically analyzed. Figure 4 As shown in the photos, each dressing sample has a nanofiber mesh structure with a fiber diameter distribution of 300nm~400nm.

[0048] The polyurethane elastomer nanofiber membrane dressings prepared in Example 2 were subjected to mechanical property analysis using a CT-3 / 4500 texture analyzer. First, the thickness of each nanofiber membrane (ENMs) was measured and recorded using a micrometer, ranging from 50 μm to 200 μm. Then, the ENMs (1.0 cm × 2.0 cm) were fixed at both ends to clamps with a clamp spacing of 1.0 cm. A 4500 g load cell was used for measurement, with a tensile speed set at 0.2 mm / s, until the ENMs were completely broken. Each sample was measured in triplicate, stress-strain curves were plotted, and the maximum tensile strength, elongation at break, and Young's modulus were calculated. The results are shown below. Figure 5 As shown, the tensile strength of the dressing film ranges from 1.74 MPa to 8.09 MPa, and the elongation ranges from 92% to 266%, exhibiting excellent mechanical properties.

[0049] Example 7

[0050] The polyurethane elastomer nanofiber membrane dressing prepared in Example 2 was used to establish and treat an infectious animal model of bacterial burns in mice.

[0051] The experimental animals were male C57BL / 6 mice (6-8 weeks old, 20g-22g), purchased from Liaoning Changsheng Biotechnology Co., Ltd. All animal experiments were approved by the Ethics Committee of Shenyang Pharmaceutical University. After anesthesia with sodium pentobarbital via intraperitoneal injection, the mice were shaved, and the hair on their backs was removed with depilatory cream. A YLS-5Q desktop temperature-controlled burn model was used for scalding, with the burn temperature set at 80℃. A 1.0cm diameter arc-shaped metal burner head was selected, and the burn pressure was 3kPa. The preheated metal burner head was placed on the mouse's back, and the burn time was set to 5 seconds. One hour later, necrotic skin was removed with scissors, and then 60μL of a 10% sodium chloride solution was applied to the wound. 7 CFU / mL E. coli suspension, using 3M Tegaderm TM An animal model of post-scald wound infection was obtained by covering the wound with a membrane and keeping it at room temperature for three days.

[0052] After modeling, the mice were randomly divided into five groups (n=20 per group). The first group was the blank control group (Control group) without any wound treatment; the second group was the PCL-HPA ENs group; the third group was the COL / PCL-HPA ENs group; and the fourth group was the COL / PCL-HPA@AgNPs group. (1:1) In the ENs group, the fifth group selected AQUAg for listing. ® As a positive control group, the above dressing was applied to the wound, and 3M Tegaderm was used. TMA dressing was used to immobilize the wound and prevent it from falling off. Mice were housed individually in cages, with ample food and a clean environment. Wounds were photographed on days 0, 3, 7, 10, and 14 to observe changes in wound appearance and to calculate wound healing rates. The changes in skin wound appearance on days 0, 3, 7, 10, and 14 post-surgery are shown below. Figure 6 As shown, in the early stages of wound healing (0-3 days), COL / PCL-HPA@AgNPs (1:1) ENs and AQUAg ® Compared with other groups, this group effectively reduced wound exudate production. During the mid-stage of wound healing (3-7 days), the wound area in each group significantly decreased. By day 14, compared with the blank control group, the PCL-HPA ENs group, COL / PCL-HPA ENs group, and COL / PCL-HPA@AgNPs group showed significantly better results. (1:1) ENs group and AQUAg ® The wounds in the group were nearing closure, and the scabs had fallen off. Changes in wound area were measured (…). Figure 7 It was found that on days 3, 7, 10, and 14, compared with other groups, COL / PCL-HPA@AgNPs (1:1) ENs and AQUAg ® The group showed a significant effect in promoting wound closure.

[0053] The above description is merely a few embodiments of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any changes or modifications made by those skilled in the art without departing from the scope of the technical solution of the present invention using the disclosed technical content are equivalent to equivalent implementation cases and all fall within the scope of the technical solution of the present invention.

Claims

1. A method for preparing a polyurethane elastomer containing in-situ silver nanoparticles, characterized in that, Includes the following steps: Step a: Mix polycaprolactone diol, dibutyltin dilaurate, and solvent, and stir until the reactants are completely dissolved; Hexamethylene diisocyanate was added under an inert environment, and the reaction was carried out at 60℃~120℃ to obtain a prepolymer; Step b: Under inert gas protection, the chain extender is added to the reaction system of step a, and the reaction is carried out at 60℃~120℃ to perform polymer end capping; Step c: Under light-protected conditions, add silver nitrate solution to the reaction system of step b and react at 60℃~120℃; Step d: After the reaction is complete, cool the system to room temperature, stop stirring, stop the inert gas protection, pour the reaction solution into deionized water, precipitate the polyurethane elastomer, and vacuum dry it.

2. The method for preparing polyurethane elastomer containing in-situ silver nanoparticles according to claim 1, characterized in that, In step a, the molar ratio of hexamethylene diisocyanate to polycaprolactone diol is 1:1 to 2:

1.

3. The method for preparing polyurethane elastomer containing in-situ silver nanoparticles according to claim 1, characterized in that, In step b, the chain extender is selected from any one of [2-[(2-hydroxyphenyl)methylene]amino]-1,3-propanediol, 3,4-dihydroxybenzoic acid, and luteolin.

4. The method for preparing polyurethane elastomer containing in-situ silver nanoparticles according to claim 1, characterized in that, In step c, the amount of silver nitrate added is controlled according to its molar ratio with polycaprolactone diol, which is 1:4 to 1:1; or, the amount of silver nitrate added is controlled according to its molar ratio with the chain extender, which is 4:1 to 1:

1.

5. A polyurethane elastomer nanofiber membrane, characterized in that, The polyurethane elastomer containing in-situ silver nanoparticles obtained by the preparation method according to any one of claims 1-4 is used as a spinning raw material. The preparation method is as follows: the polyurethane elastomer containing in-situ silver nanoparticles is dissolved in an organic solvent to prepare a spinning solution, and electrospinning is performed with the following process parameters: the concentration of the spinning solution is 10%~30% (w / v), the spinning voltage is 10kV~20kV, and the injection speed is 1mL·h. -1 ~5mL·h -1 The receiving distance is 8cm~20cm, and the spinning temperature is 20℃~40℃. After the process is completed, the fiber membrane is collected and vacuum dried to obtain a polyurethane nanofiber membrane made from polycaprolactone diol.

6. The polyurethane elastomer nanofiber membrane according to claim 5, characterized in that, The thickness of the nanofiber membrane is 50μm~500μm, the fiber diameter is distributed in the range of 300nm~500nm, and the tensile strength ranges from 1MPa to 100MPa.

7. A composite nanofiber membrane, characterized in that, The polyurethane elastomer containing in-situ silver nanoparticles obtained by any one of the preparation methods described in claims 1-4 is blended with collagen or gelatin to prepare a composite nanofiber membrane; the fiber diameter of the composite nanofiber membrane is distributed in the range of 100 nm to 900 nm, and the membrane thickness is 50 μm to 500 μm.

8. The composite nanofiber membrane according to claim 7, characterized in that, The addition ratio of collagen or gelatin is 1.0%~10% (w / v). Electrospinning process parameters: spinning solution concentration is 10%~30% (w / v), spinning voltage is 10kV~20kV, and injection speed is 1mL·h. -1 ~5mL·h -1 The receiving distance is 8cm~20cm, and the spinning temperature is 20℃~40℃.

9. The application of the polyurethane elastomer containing in-situ silver nanoparticles prepared by the preparation method according to any one of claims 1-4, or the polyurethane elastomer nanofiber membrane according to claim 5 or 6, or the composite nanofiber membrane according to claim 7 or 8, as a wound dressing or medical implant material.

10. The application according to claim 9, characterized in that, Applications include: direct use as wound dressings; coatings for implantable devices, implantable artificial organs, contact artificial organs, stents, interventional catheters, tissue-engineered scaffolds, and organ assist devices; and body materials for implantable artificial organs, contact artificial organs, stents, interventional catheters, tissue-engineered scaffolds, and organ assist devices.

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