Preparation method of dressing inner membrane under humid high-alkalinity seawater environment
The ZnCo-ZIF-PLA composite nanofiber membrane prepared by electrospinning solves the problem of poor wound healing effect of dressings in humid and highly alkaline seawater environments, achieving efficient antibacterial properties, promoting healing, and safe use.
Patent Information
- Application Number
- CN202511078680.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-01
- Publication Date
- 2025-10-31
AI Technical Summary
Existing dressings are mostly designed based on excellent medical conditions and terrestrial environments. However, in humid and highly alkaline seawater environments, there are complex bacterial colonies such as Vibrio vulnificus and parahaemolytic bacteria. Furthermore, the high humidity and high osmotic pressure of the environment lead to poor wound healing.
Polylactic acid nanofiber membranes were prepared using electrospinning technology, and ZnCo-ZIF nanoparticles were grown in situ on their surface using reverse diffusion technology to form a three-layer membrane structure of hydrophobic-philic-hydrophobic. The outer layer is waterproof and breathable, the middle layer is loaded with ZnCo-ZIF crystals for antibacterial purposes, and the inner layer is PLA nanofibers.
It effectively blocks seawater intrusion, inhibits bacterial infection in seawater, promotes wound healing, accelerates granulation tissue formation, reduces scarring, and improves user comfort and safety.
Smart Images
Figure CN120860282A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of wound dressing technology, and more particularly to a method for preparing the inner membrane of a dressing for use in moist, highly alkaline seawater environments. Background Technology
[0002] Approximately 71% of the Earth's surface is covered by seawater, making the ocean and related areas crucial for human work, leisure, and activities. People who work or play near the ocean for extended periods inevitably develop wounds or abrasions on their skin. Wound healing is a slow and delicate biological process, primarily involving four stages: hemostasis, inflammatory response, cell proliferation, and wound remodeling. During this process, the open, moist, and complex biological environment can lead to wound deterioration, and the unique characteristics of the marine environment exacerbate this problem.
[0003] Seawater contains various microorganisms (such as bacteria, viruses, and fungi), trace elements, and has a hypertonic effect. When a wound comes into contact with seawater, it alters the normal physiological environment for healing, making the wound more susceptible to mixed infections, increasing the risk of inflammatory lesions, slowing the healing process, and prolonging the healing period. In severe cases, the wound may be infected by a large number of microorganisms in seawater, leading to edema and necrosis of the tissues near the wound. For example, Vibrio vulnificus in the ocean can cause infection through wound contact with seawater, leading to various inflammations such as cellulitis and osteomyelitis. In severe cases, it can rapidly lead to bacteremia or sepsis, with a high mortality rate.
[0004] A study published in the *American Journal of Surgery* involving 156 patients injured in marine accidents found that 20% developed secondary infections caused by seawater, and 10% experienced significant tissue necrosis requiring hospitalization. The average healing time for these patients was 2-3 weeks longer than for uninfected patients. A study published in the *Journal of Emergency Medicine* of 120 cases of marine-related infections reported in Queensland, Australia, between 2015 and 2020 showed that approximately 40% of cases involved mixed infections with multiple bacterial species, 25% of patients experienced varying degrees of tissue necrosis requiring debridement, and the mortality rate was 5%, with sepsis and multiple organ failure being the leading causes of death. Therefore, in the early stages of wound healing, appropriate protective measures should be taken to avoid contact with seawater and other irritating liquids to reduce health risks.
[0005] ZnCo-ZIF, as a metal-organic framework material, has a zeolite-like structure, with Zn as the base material. 2+ and Co2 + ZnCo-ZIF is a crystalline porous material composed of metal ions that form a periodic network structure with imidazole ligands. Compared to single-metal ZIF materials, its pore size is more uniform and tunable, reaching the nanoscale, providing a large number of active sites and exhibiting drug sustained-release properties. However, in practical applications, the tendency of nanomaterials to aggregate severely affects the application performance of ZnCo-ZIF materials.
[0006] In recent years, although a large number of new wound dressings with hemostatic, moisturizing, and antibacterial functions have been developed, these dressings are mostly designed based on excellent medical conditions and terrestrial environments. In marine environments, due to the presence of complex bacterial colonies dominated by Vibrio vulnificus and parahaemolytic bacteria (Gram-negative bacteria), and the high humidity and high osmotic pressure, the wound healing effect is poor.
[0007] Based on this, the present invention proposes a method for preparing the inner membrane of a dressing for use in humid and highly alkaline seawater environments. Summary of the Invention
[0008] The purpose of this invention is to address the problem that existing dressings are mostly designed based on excellent medical conditions and terrestrial environments. In seawater environments, due to the presence of complex bacterial colonies, mainly Vibrio vulnificus and parahaemolytic bacteria (Gram-negative bacteria), and the high humidity and high osmotic pressure, the wound healing effect is poor. This invention proposes a method for preparing the inner membrane of dressings for humid and highly alkaline seawater environments.
[0009] The technical solution of the present invention: a method for preparing the inner membrane of a dressing for use in humid and highly alkaline seawater environments, comprising the following steps:
[0010] S1. Mix N,N dimethylformamide and dichloromethane at a volume ratio of 1:1 to 1:3, and add polylactic acid particles to prepare a polylactic acid spinning solution with a mass fraction of 8wt% to 12wt%.
[0011] S2. Inject polylactic acid spinning solution into an electrospinning device, set the spinning voltage to 15-20kV and the spinning distance to 15-20cm, and use a composite membrane made of polyurethane and pH-responsive material as the receiving electrode to prepare a polylactic acid nanofiber membrane.
[0012] S3. Place the polylactic acid nanofiber membrane in a reverse diffusion container. Add a solution containing zinc nitrate alcohol and imidazoline alcohol to one side of the container, and add a solution containing cobalt nitrate alcohol and imidazoline alcohol to the other side of the container. The molar ratio of zinc nitrate, cobalt nitrate and imidazoline alcohol solution is 6-10:6-10:12-20. React at room temperature for 14-18 hours to grow ZnCo-ZIF nanoparticles in situ on the surface of polylactic acid fibers, and obtain a ZnCo-ZIF-PLA composite nanofiber membrane.
[0013] Optionally, in step S1, the solvent of the polylactic acid spinning solution is composed of N,N dimethylformamide and dichloromethane in a volume ratio of 1:1 to 1:3.
[0014] Optionally, in step S1, the molecular weight of polylactic acid is 80,000-120,000 g / mol.
[0015] Optionally, in step S2, the electrospinning environment temperature is 25±2℃ and the relative humidity is 40%-60%.
[0016] Optionally, in step S3, the alcohol solution in the zinc nitrate alcohol solution and the cobalt nitrate alcohol solution is a methanol solution or an ethanol solution with a concentration of 0.1-0.5 mol / L.
[0017] Optionally, the alcohol solution in the imidazolidin solution in step S3 is a methanol solution or an ethanol solution with a concentration of 0.2-1.0 mol / L.
[0018] Optionally, the water contact angle of the ZnCo-ZIF-PLA composite nanofiber membrane obtained in step S3 is ≥100°.
[0019] Optionally, in step S2, the electrospinning process uses a receiving roller to collect the fibers.
[0020] Optionally, in step S2, the electrospinning device further includes a 23G needle with an inner diameter of 0.33mm ± 0.01mm and an outer diameter of 0.64mm ± 0.02mm.
[0021] Optionally, the diameter of the PLA composite fibers in the ZnCo-ZIF-PLA composite nanofiber membrane is 325nm-611nm.
[0022] Compared with the prior art, this application includes at least one of the following beneficial technical effects:
[0023] 1. By adopting a three-layer membrane structure of hydrophobic-hydrophobic-hydrophobic, the outer waterproof and breathable membrane can block the intrusion of liquids in humid environments such as seawater, avoiding interference with the moisture-wicking effect of wound exudate. This solves the problem that traditional dressings affect wound healing in humid environments due to the water absorption of the outer hydrophilic material, and ensures the effective protection of the wound by the inner membrane.
[0024] 2. ZnCo-ZIF crystals were loaded onto the surface of PLA nanofiber membranes using electrospinning combined with reverse diffusion technology. The Zn2+ released by ZnCo-ZIF... + and Co2 + It exhibits an 18-hour inhibition rate of over 99.9% against Gram-positive bacteria such as Staphylococcus aureus and Gram-negative bacteria such as Escherichia coli, effectively addressing complex bacterial colonies in seawater and reducing the risk of mixed infections.
[0025] 3. Through Zn 2+ Promotes fibroblast proliferation and migration, and accelerates granulation tissue formation; Co 2+ It can regulate cell metabolism and maintain the normal physiological function of the wound; the porous structure of ZnCo-ZIF can also load drugs and release them slowly in the weakly acidic environment in the later stage of wound healing, further accelerating healing and reducing scarring.
[0026] 4. PLA nanofibers exhibit excellent biocompatibility, while ZnCo-ZIF degradation products are essential zinc and cobalt ions and biocompatible imidazole compounds with no significant toxicological reactions. Both materials possess thermal stability, maintaining structural and drug integrity during high-temperature sterilization, ensuring safe and reliable use. The hydrophobic surface of the materials (water contact angle 103.36°) reduces adhesion to granulation tissue during replacement, preventing secondary tearing of the wound and improving user comfort.
[0027] This invention, through a special structural design and material combination, integrates waterproofing, moisture barrier, strong antibacterial properties, healing promotion, high safety, and a good user experience. It can specifically solve the problem of wound healing in humid and highly alkaline seawater environments, and provide an effective solution for wound protection in marine-related scenarios. Attached Figure Description
[0028] Figure 1 The microstructure of the PLAMF layer fibers in the PLA composite film dressing material prepared in Example 1 is shown.
[0029] Figure 2 This is a bar chart showing the diameter distribution of the PLAMF layer fibers in the PLA composite film dressing material prepared in Example 1.
[0030] Figure 3 The microstructure of the PLAMF layer fibers in the PLA composite film dressing material prepared in Example 1 is shown.
[0031] Figure 4 This is a bar chart showing the diameter distribution of the PLAMF layer fibers in the PLA composite film dressing material prepared in Example 1.
[0032] Figure 5 The microstructure of the PLAMF layer fibers in the PLA composite film dressing material prepared in Example 1 is shown.
[0033] Figure 6 This is a bar chart showing the diameter distribution of the PLAMF layer fibers in the PLA composite film dressing material prepared in Example 1.
[0034] Figure 7 The image shows a physical picture of ZnCo-ZIF-PLANFM in the composite film dressing material prepared in Example 2.
[0035] Figure 8 The image shows the microstructure of the ZnCo-ZIF-PLANFM layer fibers in the composite membrane dressing material prepared in Example 2.
[0036] Figure 9 The X-ray diffraction results are for ZnCo-ZIF-PLANFM in the composite film dressing material prepared in Example 2.
[0037] Figure 10The results of the hydrophilicity / hydrophobicity test of the ZnCo-ZIF-PLANFM surface in the composite membrane dressing material prepared in Example 2 are shown.
[0038] Figure 11 The results of the test on Staphylococcus aureus are shown for the composite film dressing prepared in Example 2.
[0039] Figure 12 The test results of the composite film dressing prepared in Example 2 on Escherichia coli are shown. Detailed Implementation
[0040] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that, unless otherwise specified, the following embodiments and features described therein can be combined with each other.
[0041] Example 1
[0042] Step 1: Mix NN dimethylformamide (DMF) and dichloromethane (DCM) in a certain proportion and stir until homogeneous. Add a certain mass of polylactic acid (PLA) particles to the DCM / DMF mixture and stir until homogeneous to obtain PLA spinning solutions of 8wt%, 10wt%, and 12wt%.
[0043] Step 2: Inject the spinning solution prepared in Step 1 into an electrospinning injector, using a 23G needle with an inner diameter of 0.33mm ± 0.01mm and an outer diameter of 0.64mm ± 0.02mm. Connect the injector needle to the positive terminal of a power supply, using a composite membrane made of polyurethane and pH-responsive material as the receiving electrode; with a spinning distance of 15-20cm between the positive and negative electrodes and a voltage of 15-20kV, PLA composite fibers (fibers interwoven into a film) can be obtained on the receiving roller. In this embodiment, a film made of polyurethane (PU) and carboxymethyl chitosan (CMC) at a mass ratio of 3:1 is used, with a thickness of 0.15 ± 0.03mm, and the swelling degree increases by ≥50% when pH ≥ 7.0.
[0044] Step 3: After drying the PLA composite fibers obtained in Step 2 in an oven, PLA composite film dressing material is obtained.
[0045] The morphology of the inner membrane of the prepared PLA composite film dressing was observed using a scanning electron microscope, such as... Figure 1 , Figure 3 and Figure 5 As shown, the distribution of different intima fibers is as follows: Figure 2 , Figure 4and Figure 6 As shown.
[0046] Example 2
[0047] The PLA composite fiber membrane prepared in Example 1 was grown at room temperature for 16 hours in a diffusion vessel to obtain a ZnCo-ZIF-PLA composite nanofiber membrane, as shown in the figure. Figure 7 As shown. A solution containing zinc nitrate and imidazolidinyl nitrate was added to one side of the container, and a solution containing cobalt nitrate and imidazolidinyl nitrate was added to the other side of the container. The molar ratio of zinc nitrate, cobalt nitrate and imidazolidinyl nitrate was 7.5:7.5:15.
[0048] Experimental Design
[0049] Step 1: Perform antibacterial testing using the shaking method. Adjust the pH of the liquid culture medium to 7.0-7.5 and prepare 200 mL of PBS buffer. After sterilizing the PBS buffer, liquid culture medium, and deionized water, transfer them to a clean bench for natural cooling and irradiate with UV light for 30 min. Sterilize, cool, pour out plates, and air dry the prepared solid culture medium.
[0050] Step 2: In the clean bench area, take 5 mL of liquid culture medium and then 500 μL of the original bacterial suspension into a test tube. Shake well and place it in a constant temperature shaker at 37°C and 150 rpm for 12-24 hours. Add 10 mL of PBS buffer and 715 μL of activated bacterial suspension to several Erlenmeyer flasks. Use Erlenmeyer flasks without samples as the control group, and add 0.1 g each of the original membrane sample and the antibacterial membrane sample to the remaining Erlenmeyer flasks. Using a pipette, take 100 μL of the solution from the sample Erlenmeyer flask at 0 o'clock, transfer it to a PBS buffer centrifuge tube, mix well, and dilute sequentially until 10⁻⁵. Then, take 100 μL of the solution and spread it from bottom to top using a spreader. After there is no excess liquid on the surface, invert the plate and incubate it in a constant temperature incubator at 37°C for 12-24 hours for colony counting.
[0051] Step 3: Place the 0-time contact sample conical flask in a constant temperature shaking incubator and shake at 25℃ and 150 rpm for 18 hours. Then, take 100 μL of the solution and transfer it to a PBS buffer centrifuge tube. Mix well and dilute sequentially until the concentration reaches 10⁻⁵. Then, take 100 μL of the solution and spread it in the center of an agar plate. Use a spreader to spread the solution from bottom to top. After there is no excess liquid on the surface, invert the plate and incubate it in a 37℃ constant temperature incubator for 12-24 hours for colony counting.
[0052] Repeat the above steps three times.
[0053] The microstructure of the PLA composite film dressing material obtained above was characterized based on the PLA fiber structure. The results are shown in [Figure number missing]. Figures 1-6 ;
[0054] pass Figure 1 and Figure 2 It can be seen that the diameter of the nanofibers prepared in Example 1 of this invention is mainly distributed within 500 nm; through Figure 3 and Figure 4 It can be seen that the diameter of the nanofibers prepared in Example 1 of this invention is mainly distributed at 325 nm; through Figure 5 and Figure 6 It can be seen that the diameter of the nanofibers prepared in Example 1 of the present invention is mainly distributed at 611 nm; and the nanofibers in all examples are interwoven and uniformly distributed.
[0055] pass Figure 8 and Figure 9 It can be seen that the ZnCo-ZIF-PLANFM prepared in Example 2 of the present invention has nanoparticles on its surface and the particle structure is ZnCo-ZIFNPs.
[0056] pass Figure 10 As can be seen, the ZnCo-ZIF-PLANFM prepared in Example 2 of this invention has a water contact angle of 103.36°, and its surface has good hydrophobicity, which can reduce the adhesion of dressings to granulation tissue during dressing changes and prevent secondary tearing of the wound.
[0057] pass Figure 11 and Figure 12 It can be seen that the ZnCo-ZIF-PLANFM prepared in Example 2 of the present invention has an inhibition rate of more than 99.9% against Gram-positive bacteria, mainly Staphylococcus aureus, and Gram-negative bacteria, mainly Escherichia coli, within 18 hours, and has a good antibacterial effect.
[0058] The dressing of this invention adopts a three-layer "sandwich" membrane structure of hydrophobic-hydrophobic-hydrophobic layers. The outer layer is a waterproof and breathable membrane, which can effectively block the intrusion of liquids in humid environments such as seawater, avoid interference of environmental liquids with the normal moisture conduction of wound exudate, and protect the inner membrane for effective transmission of wound exudate. The middle hydrophobic layer, as the functional core layer, can fully exert its antibacterial and healing-promoting effects, solving the problem that traditional dressings affect wound recovery in humid and hypertonic environments due to the water absorption of the outer hydrophobic material.
[0059] It is worth noting that by combining electrospinning technology with reverse diffusion technology, ZnCo-ZIF crystals were loaded onto the surface of PLA nanofiber membranes. The ZnCo-ZIF contained Zn... 2+ and Co 2+ It can be gradually released and has a significant inhibitory effect on Gram-positive bacteria such as Staphylococcus aureus and Gram-negative bacteria such as Escherichia coli, with an inhibition rate exceeding 99.9% within 18 hours. It can effectively combat complex bacterial colonies in seawater, primarily composed of Vibrio vulnificus and parahaemolyticus, reducing the risk of mixed wound infections. Its effect on promoting wound healing is particularly outstanding. Zn2+ Appropriate release of Co can promote fibroblast proliferation and migration, and accelerate granulation tissue formation; 2+ It can regulate cell growth and metabolism and maintain the normal physiological function of the wound. At the same time, the porous structure of ZnCo-ZIF can load drugs and achieve sustained release. Especially in the weakly acidic environment in the later stage of wound healing, the drugs can be completely released, further accelerating wound recovery, reducing scar formation, and shortening the healing cycle.
[0060] Furthermore, the dressing of this invention exhibits high biocompatibility and safety. The PLA nanofiber substrate possesses excellent biocompatibility, and ZnCo-ZIF can degrade into zinc ions, cobalt ions, and imidazole substances under human physiological conditions. Zinc and cobalt are essential trace elements for the human body and are harmless at normal concentrations. Imidazole substances also possess biocompatibility and do not produce significant toxicological reactions, ensuring the safety of the dressing. It should be noted that the PLA nanofiber does not decompose at 250°C, and ZnCo-ZIF also exhibits good thermal stability, allowing the dressing to maintain structural integrity and drug-loaded integrity under high-temperature environments such as sterilization. Simultaneously, the material surface is hydrophobic (water contact angle 103.36°), reducing adhesion to granulation tissue during dressing changes, preventing secondary wound tearing, and improving user comfort.
[0061] This invention, through a special structural design and material combination, has multiple advantages such as blocking interference from the external humid environment, strong antibacterial effect, promoting wound healing, biosafety and stable performance. It can effectively solve the problems of high infection risk and slow healing speed faced by wounds in humid and highly alkaline seawater environments, and provide a reliable solution for wound protection in marine-related scenarios.
[0062] The above specific embodiments are merely several optional embodiments of the present invention. Based on the technical solutions of the present invention and the relevant teachings of the above embodiments, those skilled in the art can make various alternative improvements and combinations to the above specific embodiments.
Claims
1. A method for preparing the inner membrane of a dressing for use in humid, highly alkaline seawater environments, characterized in that, Includes the following steps: S1. Mix N,N dimethylformamide and dichloromethane at a volume ratio of 1:1 to 1:3, and add polylactic acid particles to prepare a polylactic acid spinning solution with a mass fraction of 8wt% to 12wt%. S2. Inject polylactic acid spinning solution into an electrospinning device, set the spinning voltage to 15-20kV and the spinning distance to 15-20cm, and use a composite membrane made of polyurethane and pH-responsive material as the receiving electrode to prepare a polylactic acid nanofiber membrane. S3. Place the polylactic acid nanofiber membrane in a reverse diffusion container. Add a solution containing zinc nitrate alcohol and imidazoline alcohol to one side of the container, and add a solution containing cobalt nitrate alcohol and imidazoline alcohol to the other side of the container. The molar ratio of zinc nitrate, cobalt nitrate and imidazoline alcohol solution is 6-10:6-10:12-20. React at room temperature for 14-18 hours to grow ZnCo-ZIF nanoparticles in situ on the surface of polylactic acid fibers, and obtain a ZnCo-ZIF-PLA composite nanofiber membrane.
2. The method for preparing the inner membrane of a dressing for use in a humid, highly alkaline seawater environment according to claim 1, characterized in that, In step S1, the solvent of the polylactic acid spinning solution is composed of N,N dimethylformamide and dichloromethane in a volume ratio of 1:1 to 1:
3.
3. The method for preparing the inner membrane of a dressing for use in a humid, highly alkaline seawater environment according to claim 1, characterized in that, In step S1, the molecular weight of polylactic acid is 80,000-120,000 g / mol.
4. The method for preparing the inner membrane of a dressing in a humid, highly alkaline seawater environment according to claim 1, characterized in that, In step S2, the electrospinning environment temperature is 25±2℃ and the relative humidity is 40%-60%.
5. The method for preparing the inner membrane of a dressing for use in a humid, highly alkaline seawater environment according to claim 1, characterized in that, In step S2, the fibers are collected by receiving rollers during electrospinning.
6. The method for preparing the inner membrane of a dressing for use in a humid, highly alkaline seawater environment according to claim 1, characterized in that, In step S2, the electrospinning device also includes a 23G needle with an inner diameter of 0.33mm ± 0.01mm and an outer diameter of 0.64mm ± 0.02mm.
7. The method for preparing the inner membrane of a dressing for use in a humid, highly alkaline seawater environment according to claim 1, characterized in that, In step S3, the alcohol solution in the zinc nitrate alcohol solution and the cobalt nitrate alcohol solution is a methanol solution or an ethanol solution with a concentration of 0.1-0.5 mol / L.
8. The method for preparing the inner membrane of a dressing for use in a humid, highly alkaline seawater environment according to claim 1, characterized in that, The alcohol solution in the imidazolidinedion solution mentioned in step S3 is a methanol solution or an ethanol solution with a concentration of 0.2-1.0 mol / L.
9. A method for preparing an inner lining of a dressing in a humid, highly alkaline seawater environment according to claim 1, characterized in that, The water contact angle of the ZnCo-ZIF-PLA composite nanofiber membrane obtained in step S3 is ≥100°.
10. The method for preparing a dressing inner membrane for a humid and highly alkaline seawater environment according to claim 1, wherein the diameter of the PLA composite fibers in the ZnCo-ZIF-PLA composite nanofiber membrane is 325nm-611nm.