Medical dressing with both tissue adhesion and antifouling properties and method for preparing the same
By combining a hydrophilic hydrogel adhesion layer and a hydrophobic silicone antifouling barrier layer and using inorganic nanoparticles to enhance adhesion, the problem that existing medical dressings cannot effectively isolate digestive fluid and prevent fouling on complex wound surfaces is solved, strong adhesion and multiple barrier functions are achieved, and wound healing is promoted.
Patent Information
- Application Number
- CN202411121453.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-15
- Publication Date
- 2025-10-10
- Estimated Expiration
- 2044-08-15
AI Technical Summary
Existing medical dressings cannot effectively isolate the penetration of digestive juices and gastric acid in complex wounds such as those in the stomach, and adhesives cannot establish long-lasting and effective protection on the wound surface, and cannot provide a reliable repair barrier for the ulcer surface.
By coupling the hydrophilic hydrogel adhesion layer and the hydrophobic silicone antifouling barrier layer, using inorganic nanoparticles to provide more bonding sites, and combining differential wettability and lubrication design, a multi-barrier functional adhesion gel is formed to enhance adhesion, isolate H+ penetration, and prevent microbial attachment.
It achieves strong adhesion on complex wound surfaces, isolates H+ penetration, prevents microbial attachment and has multiple barrier functions of solid lubrication, promoting wound healing.
Smart Images
Figure CN119838040B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of medical dressings, and in particular relates to a medical dressing having both tissue adhesion and antifouling properties and a preparation method thereof. Background Art
[0002] A wound is an injury that causes a loss of continuity in the skin, tissue, and mucous membranes. Because wounds are often directly exposed to a complex environment, they are susceptible to bacterial infection, which in turn causes a persistent inflammatory response at the site of infection, leading to delayed wound healing and, in some cases, even serious complications.
[0003] Medical dressings are commonly used to cover wounds and create a moist environment for wound healing. Among them, traditional dressings such as cotton wool, cotton wool, and gauze have been widely used in clinical practice due to their affordability to ensure wound cleanliness and prevent bacterial infection. However, fibers easily adhere to granulation tissue, causing pain and secondary damage when removing the dressing. The new gel dressing can maintain the ideal temperature and humidity of the wound and stimulate wound healing. In addition, hydrogels have both the high biocompatibility of natural polymers and the elastic mechanical properties of synthetic polymers, making them more suitable for various wounds and therefore widely used.
[0004] Some self-gelling gel powders, such as polyethyleneimine and polyacrylic acid powders, can absorb interfacial water within 2 seconds due to the strong physical interactions between the polymers, forming physically cross-linked hydrogels in situ. Furthermore, the physically cross-linked polymers can diffuse into the substrate polymer network, enhancing wet adhesion.
[0005] However, due to the interference of excessive interfacial water and limited interaction between the adhesive and the tissue, this gel powder still cannot meet the repair requirements of some complex wounds in clinical practice. For example, for patients with gastric cancer treated by endoscopic submucosal dissection, artificial ulcer surfaces will be left after surgery. Although the powder can be delivered to the wound surface under endoscopy, in the special environment of the stomach, the hydrogel cannot isolate the penetration of digestive fluid and gastric acid from causing erosion and irritation to the wound surface, as well as infection by various bacteria and enzymes. The adhesive cannot establish long-lasting and effective protection on the wound surface. Providing a reliable repair barrier for the ulcer surface through this gel strategy remains a challenge and an urgent clinical need.
[0006] Cross-linked polydimethylsiloxane (PDMS) and other polymer materials have been widely used in artificial skin, medical cosmetic surgery, and other fields due to their excellent flexibility, corrosion resistance, and biocompatibility. However, the formation of the three-dimensional cross-linked PDMS network typically relies on the hydrosilylation reaction between PDMS containing two vinyl end groups and a multifunctional cross-linking agent. As a result, PDMS itself lacks dynamic covalent bonds and bioadhesion, making it unsuitable for direct wound protection.
[0007] In view of this, the present application provides a medical dressing having both tissue adhesion and anti-fouling properties and a preparation method thereof to solve the above technical problems. Summary of the Invention
[0008] In response to the above-mentioned problems in the prior art, the present application proposes a medical dressing with both tissue adhesion and anti-fouling properties and a preparation method thereof. The method utilizes inorganic nanoparticles to provide more bonding sites, couples the hydrophilic hydrogel adhesion layer and the hydrophobic silicone anti-fouling barrier layer, and develops a multi-barrier functional adhesion gel based on differential wettability and lubrication design, which has application prospects in tissue damage repair in a variety of complex environments.
[0009] A medical dressing with both tissue adhesion and antifouling properties comprises an antifouling barrier layer and a tissue adhesion layer, wherein the antifouling barrier layer and the tissue adhesion layer are coupled via inorganic nanoparticles.
[0010] As a preferred solution, the antifouling barrier layer is a hydrophobic organosilicon antifouling barrier layer, wherein the hydrophobic organosilicon antifouling barrier layer is made by curing a lubricating liquid and a silicone liquid in a one-step process.
[0011] As a preferred solution, the tissue adhesion layer is a hydrophilic hydrogel adhesion layer, and the hydrophilic hydrogel adhesion layer is formed by PEI / PAA-NHS hydrogel powder absorbing water and gelling in situ on the wound surface.
[0012] As a preferred solution, the inorganic nanoparticles are a thin layer of nano-silica powder evenly sprayed on the surface of the bioadhesive material. The nano-silica powder can provide more bonding sites and strengthen the interlayer adhesion.
[0013] A method for preparing a medical dressing having both tissue adhesion and antifouling properties comprises the following steps:
[0014] S1. Synthesis of N-hydroxysuccinimide-grafted polyacrylate. Dissolve polyacrylic acid, N,N-dicyclohexylcarbodiimide, and N-hydroxysuccinimide in a 1:1 mixture of dichloromethane and N,N-dimethylformamide in an ice bath. Add the N,N-dicyclohexylcarbodiimide pre-solution dropwise to the polyacrylic acid solution. Five minutes later, add the N-hydroxysuccinimide pre-solution dropwise to the reaction solution in the same manner. Stir for 1 hour in an ice bath and then continue stirring at 22°C for 12 hours. During the reaction, N,N-dicyclohexylcarbodiimide is converted to N,N-dicyclohexylurea, which is insoluble in organic reagents. Filter the filtrate, and dry it at low temperature. The resulting product is washed with aqueous ammonia and dichloromethane, then dried in a vacuum.
[0015] S2. Preparation of polyethyleneimine / polyacrylate hydrogel powder: 10 wt% polyethyleneimine solution and 10 wt% polyacrylate solution were mixed in a certain ratio while stirring. The resulting polyethyleneimine / polyacrylate hydrogel solution was poured into liquid nitrogen for freezing, grinding, and freeze-drying. The prepared polyethyleneimine / polyacrylate hydrogel powder was stored in a low-temperature, dry environment.
[0016] S3. Formation of an Adhesive Gel Layer: Spray the prepared polyethyleneimine / polyacrylate hydrogel powder onto the wound surface. The dry powder quickly absorbs water and gels in situ, fully adapting to complex wound morphologies.
[0017] S4. Strengthening interlayer adhesion. Evenly spray a thin layer of nano-silica powder on the surface of the bioadhesive material to provide more bonding sites and strengthen interlayer adhesion;
[0018] S5. Preparation of silicone barrier layer prepolymer. At low temperature, mix a certain proportion of silicone liquid, lubricant, and silane coupling agent, and centrifuge at 1500 rpm for 1 minute to degas.
[0019] S6. Formation of a multifunctional barrier: Inject the prepared silicone barrier layer prepolymer onto the hydrogel layer and wait for 10 minutes at room temperature for it to fully solidify, thereby forming a medical dressing with both tissue adhesion and anti-fouling properties.
[0020] As a preferred solution, the degree of polymerization of the polyacrylic acid in step S1 is 200k~800kDa.
[0021] As a preferred solution, in step S1, the molar ratio of N,N-dicyclohexylcarbodiimide as a coupling mediator to N-hydroxysuccinimide is maintained at 1:1; the mass ratio of N-hydroxysuccinimide to polyacrylic acid is between 3:1 and 1:1.
[0022] As a preferred solution, the degree of polymerization of the polyethyleneimine in step S2 is 70 kDa.
[0023] As a preferred solution, the ratio of the 10% polyethyleneimine solution to the 10% polyacrylate solution in step S2 is 1:3.
[0024] As a preferred solution, the particle size of the nano-silicon dioxide powder in step S4 is 20 to 5000 nm.
[0025] As a preferred solution, the silicone liquid in step S5 is preferably Ecoflex TM 00-35AB, polymethylsiloxane, polyethylsiloxane, epoxysiloxane, fluorocarbon polymer.
[0026] As a preferred solution, the lubricating liquid in step S5 is preferably hydrophobic silicone oil or fluorinated oil.
[0027] As a preferred solution, the silane coupling agent in step S5 is preferably vinyltrimethoxysilane.
[0028] As a preferred solution, in step S5, the mass fraction of the silicone liquid is 30% to 50%, the mass fraction of the lubricating fluid is 50% to 70%, and the mass fraction of the silane coupling agent is 0.1 to 0.2%.
[0029] As a preferred solution, the viscosity of the dimethyl silicone oil in step S5 is 1000 to 10000 cst.
[0030] The above technical features can be combined in a suitable manner or replaced by equivalent technical features, as long as the purpose of the present invention can be achieved.
[0031] Compared with the prior art, the present invention has the following beneficial effects:
[0032] Existing adhesive hydrogel dressings are used for complex wound repair. For example, they show limited clinical efficacy in the gastric environment, which is manifested in the following aspects: 1) The adhesion between the hydrogel and tissue interface is low, and the pulling force caused by gastric peristalsis, contraction, and relaxation can easily cause the dressing to detach; 2) The dressing lacks H+ intervention measures. The H+ in the gastric cavity can penetrate the dressing and erode the wound due to the concentration difference, causing the adhesive interface to become unstable and fall off.
[0033] Based on the needs of wound management, the present invention couples functions and develops a multi-barrier adhesive gel dressing by regulating the wettability of the interface. The adhesive gel includes a hydrophilic gel adhesion layer and a hydrophobic silicone barrier layer. First, the hydrogel adhesion layer is prepared by dry powder water-absorbing in-situ gelation, which has excellent wet adhesion ability and can adapt well to the complex morphology of the wound surface in the stomach. Subsequently, the silicone barrier layer prepolymer is injected onto the hydrogel layer. During the in-situ gelation process, the hydrogel and silicone are stably bonded through silicon-oxygen chemical bonds. The dressing can establish strong adhesion with wet tissue, and the interface is transformed from hydrophilic to hydrophobic, realizing multiple barrier functions of isolating H+ penetration, preventing microbial attachment and solid lubrication. The in-situ construction facilitates application in various scenarios. BRIEF DESCRIPTION OF THE DRAWINGS
[0034] The present invention will be described in more detail below based on embodiments and with reference to the accompanying drawings, wherein:
[0035] Figure 1 The results of the adhesion strength test between Examples 1-3 of the present invention and pig skin tissue are shown;
[0036] Figure 2 Shows the FTIR infrared spectrum test charts of Examples 1-3 of the present invention;
[0037] Figure 3 The statistical graph of the number of E. coli colonies on the plates of Examples 1, 4-7 of the present invention after culturing in E. coli suspension for 6 hours and 24 hours is shown;
[0038] Figure 4 Shows the statistical graph of the surface adhesion protein area of Examples 1, 4-7 of the present invention after being cultured in a fluorescently labeled bovine serum albumin PBS solution for 6 hours and 24 hours;
[0039] Figure 5 Shown is a structural diagram of the medical dressing of the present invention. DETAILED DESCRIPTION
[0040] The present invention will be further described below with reference to the accompanying drawings.
[0041] The present invention provides a medical dressing having both tissue adhesion and antifouling properties and a preparation method thereof. Figure 5As shown, a medical dressing with both tissue adhesion and antifouling properties includes a hydrophilic hydrogel adhesion layer and a hydrophobic organosilicon antifouling barrier layer, wherein the barrier layer is formed by curing a lubricating liquid and a silicone liquid in a one-step process. The present invention also provides a method for preparing a medical dressing with both tissue adhesion and antifouling properties, comprising pre-modifying PAA with NHS, mixing the modified PAA-NHS with PEI to produce a highly adhesive PEI / PAA-NHS hydrogel powder, and then coupling the adhesion layer and barrier layer using inorganic nanoparticles. The medical dressing with both tissue adhesion and antifouling properties prepared by the present invention exhibits excellent wet adhesion while also achieving multiple barrier functions: isolating H+ penetration, preventing microbial adhesion, and providing solid lubrication, effectively promoting wound healing in various situations.
[0042] Example 1
[0043] 10 g of a 10 wt% aqueous solution of polyethyleneimine (Mv, ca. 70,000) and 20 g of a 10 wt% aqueous solution of polyacrylic acid (Mv, ca. 240,000) were mixed with stirring, the mixture was poured into liquid nitrogen and frozen, ground, and freeze-dried in a freeze dryer for 48 h to obtain polyacrylic acid / polyethyleneimine hydrogel powder.
[0044] Example 2
[0045] Under ice conditions, 2g of polyacrylic acid, 4.13g of N,N-dicyclohexylcarbodiimide, and 2.30g of N-hydroxysuccinimide were fully dissolved in a 1:1 mixture of dichloromethane and N,N-dimethylformamide. The N,N-dicyclohexylcarbodiimide pre-solution was added dropwise to the polyacrylic acid solution. Five minutes later, the N-hydroxysuccinimide pre-solution was added dropwise to the reaction solution in the same manner. After stirring under ice conditions for 1 hour, stirring was continued at 22°C for 12 hours. During the reaction, N,N-dicyclohexylcarbodiimide was converted to N,N-dicyclohexylurea, which is insoluble in organic reagents. The filtrate was filtered and dried at low temperature. The resulting product was washed with ammonia and dichloromethane and dried under vacuum to obtain a modified polyacrylate powder, which was then dissolved in water to prepare a 20g polyacrylate solution.
[0046] 10 g of a 10 wt% polyethyleneimine solution and 20 g of the polyacrylate solution prepared above were mixed with stirring. The mixture was poured into liquid nitrogen, frozen, ground, and freeze-dried in a freeze dryer for 48 h to obtain a polyethyleneimine / polyacrylate hydrogel powder, which was stored in a low-temperature dry environment.
[0047] Example 3
[0048] Under ice conditions, 2g of polyacrylic acid, 8.26g of N,N-dicyclohexylcarbodiimide, and 4.60g of N-hydroxysuccinimide were fully dissolved in a 1:1 mixture of dichloromethane and N,N-dimethylformamide. The N,N-dicyclohexylcarbodiimide pre-solution was added dropwise to the polyacrylic acid solution. Five minutes later, the N-hydroxysuccinimide pre-solution was added dropwise to the reaction solution in the same manner. After stirring for 1 hour under ice conditions, stirring was continued at 22°C for 12 hours. During the reaction, N,N-dicyclohexylcarbodiimide was converted to N,N-dicyclohexylurea, which is insoluble in organic reagents. The filtrate was filtered and dried at low temperature. The resulting product was washed with ammonia and dichloromethane and dried under vacuum to obtain a modified polyacrylate powder, which was then dissolved in water to prepare a 20g polyacrylate solution.
[0049] 10 g of a 10 wt% polyethyleneimine solution and 20 g of the polyacrylate solution prepared above were mixed with stirring. The mixture was poured into liquid nitrogen, frozen, ground, and freeze-dried in a freeze dryer for 48 h to obtain a polyethyleneimine / polyacrylate hydrogel powder, which was stored in a low-temperature dry environment.
[0050] Example 4
[0051] At low temperature, take 5g of Ecoflex TM 00-35A, 5g Ecoflex TM 00-35B and 0.01 g of vinyltrimethoxysilane were mixed evenly, centrifuged at 1500 rpm for 1 minute to degas, injected between two glass plates, and waited for 10 minutes at room temperature for polymerization.
[0052] Example 5
[0053] At low temperature, take 2g of Ecoflex TM 00-35A, 2g Ecoflex TM 00-35B, 6g of 1000cst dimethyl silicone oil and 0.01g of vinyltrimethoxysilane were mixed evenly, centrifuged at 1500r / min for 1 minute to degas, injected between two glass plates, and waited for 10 minutes at room temperature for polymerization.
[0054] Experimental Example 6
[0055] At low temperature, take 2g of Ecoflex TM 00-35A, 2g Ecoflex TM00-35B, 6g of 10000cst dimethyl silicone oil and 0.01g of vinyltrimethoxysilane were mixed evenly, centrifuged at 1500r / min for 1 minute to degas, injected between two glass plates, and waited for 10 minutes at room temperature for polymerization.
[0056] Experimental Example 7
[0057] At low temperature, take 2g of Ecoflex TM 00-35A, 2g Ecoflex TM 00-35B, 6 g of 500,000 cst dimethyl silicone oil and 0.01 g of vinyltrimethoxysilane were mixed evenly, centrifuged at 1500 rpm for 1 minute to degas, injected between two glass plates, and waited for 10 minutes at room temperature for polymerization.
[0058] Take the sample prepared in the above experimental example and conduct the following experiment:
[0059] 1. The bioadhesion properties of the hydrogel powders prepared in Experimental Examples 1-3 were tested using a lap shear test. 40 mg of the hydrogel powder was sandwiched between two pieces of pigskin tissue with a bonding area of 1 cm x 1 cm. The sample was then incubated at 37°C for 5 minutes and pressurized (applied pressure of 8 kPa). The maximum tensile stress was then measured using a universal tensile tester.
[0060] Figure 1 The adhesion strength test results of each sample are shown in Figure 2. As can be seen from the figure, the adhesion strength of the hydrogel adhesive powder obtained by N-hydroxysuccinimide modification has been significantly improved, and the adhesion strength increases with the increase of N-hydroxysuccinimide content.
[0061] 2. The hydrogel powders prepared in Experimental Examples 1 to 3 were tested by FTIR infrared spectroscopy. The results are as follows: Figure 2 As shown. Figure 2 It is known that the modification with N-hydroxysuccinimide forms polymerized N-hydroxysuccinimide esters with amide bonds between the original carboxyl groups of polyacrylic acid and the free amino groups, which is also the reason why the adhesion of the modified hydrogel powder is improved.
[0062] 3. In vitro antibacterial testing was performed on the samples prepared in Experimental Examples 1 and 4-7. The samples were cut into 0.5 cm × 0.5 cm sections and incubated in an E. coli suspension (1 × 107 cells ml⁻¹) at 37°C for varying periods of time (6 h and 24 h). After incubation, loosely attached bacteria were washed off the sample surfaces. Surface-attached bacteria were then ultrasonically eluted and collected by centrifugation. The collected bacterial suspension was further diluted and spread onto Luria broth (LB) agar plates, which were then incubated at 37°C for 24 h.
[0063] Figure 3The figures show the antibacterial test results of each sample against Escherichia coli. As can be seen from the figures, the organic silicon barrier layers prepared by the present invention (Experimental Examples 4 to 7) have good antibacterial effects.
[0064] 4. In vitro protein adhesion tests were performed on the samples prepared in Experiments 1 and 4-7. The selected samples were incubated in a suspension of fluorescently labeled bovine serum albumin (BSA-FITC) (10 μl of BSA-FITC was added to 20 ml of PBS buffer) at 37°C for different times (6 h and 24 h). Loosely attached proteins were washed off the sample surfaces, and surface fluorescence was then observed using confocal microscopy to calculate the percentage of adherent protein area.
[0065] Figure 4 2 are the results of the anti-protein adhesion test of each sample. As can be seen from the figure, the organic silicon barrier layer prepared by the present invention (Examples 4 to 7) has a good anti-protein adhesion effect.
[0066] 5. Animal Experimentation. The pig's digestive system is similar to that of humans, and its unique environment is ideal for experimental research on complex wound repair. Therefore, the inventors created two ulcers with a diameter of 0.8 cm in the stomach of living pigs. The wounds were treated with either no treatment or a medical dressing that has both tissue adhesion and anti-fouling properties.
[0067] Experiments have shown that the medical dressing of the present invention having both tissue adhesion and anti-fouling properties has a significant effect on promoting the repair of tissue damage in complex situations.
[0068] Although the present invention is described herein with reference to specific embodiments, it should be understood that these embodiments are merely illustrative of the principles and applications of the invention. It should be understood that many modifications may be made to the illustrative embodiments, and that other arrangements may be devised, without departing from the spirit and scope of the invention as defined by the appended claims. It should be understood that the various dependent claims and features described herein may be combined in ways other than those described in the original claims. It should also be understood that features described in conjunction with individual embodiments may be employed in conjunction with other described embodiments.
Claims
1. A medical dressing having both tissue adhesion and antifouling properties, characterized in that: The invention comprises an antifouling barrier layer and a tissue adhesion layer, which are coupled via inorganic nanoparticles; the antifouling barrier layer is a hydrophobic organosilicon antifouling barrier layer, wherein the hydrophobic organosilicon antifouling barrier layer is formed by curing a lubricating liquid and a silicone liquid in one step; the tissue adhesion layer is a hydrophilic hydrogel adhesion layer, which is formed by PEI / PAA-NHS hydrogel powder absorbing water and forming an in-situ gel on the wound surface.
2. The medical dressing having both tissue adhesion and antifouling properties according to claim 1, characterized in that: The inorganic nanoparticles are a thin layer of nano-silica powder evenly sprayed on the surface of the bioadhesive material. The nano-silica powder can provide more bonding sites and strengthen the interlayer adhesion.
3. A method for preparing a medical dressing having both tissue adhesion and antifouling properties, characterized in that: The preparation method comprises the following steps: S1. Dissolve polyacrylic acid, N,N-dicyclohexylcarbodiimide, and N-hydroxysuccinimide in a mixed solution of dichloromethane and N,N-dimethylformamide, respectively, under ice bath conditions; add a pre-solution of N,N-dicyclohexylcarbodiimide to the polyacrylic acid solution, and later add the pre-solution of N-hydroxysuccinimide dropwise to the reaction solution in the same manner; during the reaction, N,N-dicyclohexylcarbodiimide is converted into N,N-dicyclohexylurea, which is insoluble in organic reagents, which is filtered and dried; wash the obtained product with aqueous ammonia and dichloromethane, and then dry; S2. Mixing a 10 wt % polyethyleneimine solution and a 10 wt % polyacrylate solution while stirring, pouring the resulting polyethyleneimine / polyacrylate hydrogel solution into liquid nitrogen for freezing, grinding, and freeze-drying. The prepared polyethyleneimine / polyacrylate hydrogel powder is stored in a low-temperature, dry environment; S3. Spray the prepared polyethyleneimine / polyacrylate hydrogel powder onto the wound surface. The dry powder quickly absorbs water to form a hydrogel, which is fully adaptable to complex wound morphologies. S4. Evenly spray a thin layer of nano-silica powder on the surface of the tissue adhesion layer to provide more bonding sites and strengthen the interlayer adhesion; S5, mixing the siloxane liquid, lubricating liquid and silane coupling agent uniformly and degassing to obtain a prepolymer liquid for the organosilicon barrier layer; S6. Inject the silicone barrier layer prepolymer liquid onto the hydrogel layer and wait at room temperature for it to completely solidify, thereby forming a medical dressing with both tissue adhesion and anti-fouling properties.
4. The method for preparing a medical dressing having both tissue adhesion and antifouling properties according to claim 3, wherein: The degree of polymerization of the polyacrylic acid is 200 kDa to 800 kDa.
5. The method for preparing a medical dressing having both tissue adhesion and antifouling properties according to claim 3, characterized in that: The molar ratio of N,N-dicyclohexylcarbodiimide as a coupling mediator to N-hydroxysuccinimide is maintained at 1:1; the mass ratio of N-hydroxysuccinimide to polyacrylic acid is between 3:1 and 1:
1.
6. The method for preparing a medical dressing having both tissue adhesion and antifouling properties according to claim 3, characterized in that: The mass ratio of the 10% polyethyleneimine solution to the 10% polyacrylate solution is between 1:3 and 1:
1.
7. The method for preparing a medical dressing having both tissue adhesion and antifouling properties according to claim 3, wherein: The silicone liquid is EcoflexTM00-35AB, polymethylsiloxane, polyethylsiloxane, and epoxysiloxane.
8. The method for preparing a medical dressing having both tissue adhesion and antifouling properties according to claim 3, characterized in that: The mass fraction of the silicone liquid is 30% to 50%, the mass fraction of the lubricating fluid is 50% to 70%, and the mass fraction of the silane coupling agent is 0.1% to 0.2%.