A composite medical dressing and its preparation method

Abstract

This invention relates to a composite medical dressing and its preparation method, belonging to the field of medical dressing technology. The composite medical dressing includes a wound contact layer and a fluid-absorbing layer. The wound contact layer comprises catechol-modified hyaluronic acid, polysulfobetaine methacrylate, alginate-phenylboronic acid, and ferric ions. The alginate-phenylboronic acid and ferric ions can form reversible dynamic bonds with the catechol groups to reduce peeling damage while providing wet adhesion. The fluid-absorbing layer has capillary channels oriented along the thickness direction of the dressing, enabling rapid and directional transport of wound exudate into the dressing interior, preventing liquid accumulation at the interface. The preparation method includes forming the fluid-absorbing layer with oriented capillary channels through directional freezing. This application solves the technical challenges of existing dressings in wet adhesion, exudate management, and low-damage dressing changes through the synergistic design of chemical function and physical structure.

Description

Technical Field

[0001] This application belongs to the technical fields of medical polymer materials, wound care materials and moist healing dressings, and particularly relates to a composite medical dressing and its preparation method. Background Technology

[0002] Medical dressings are crucial consumables for treating various wounds. An ideal dressing should conform to the wound surface, remain fixed in a moist environment, absorb exudate and maintain moisture, block bacteria and provide protection, and be easily and painlessly removed during dressing changes. However, in the moist wound environment, there are often irreconcilable contradictions among these performance requirements.

[0003] To improve the interfacial stability and biocompatibility of medical materials in humid environments, existing technologies have incorporated catechol-based adhesive units and zwitterionic hydrophilic units onto the material surface. For example, Chinese invention patent CN110885665B discloses a method for preparing a highly stable hydrophilic coating for medical device surfaces. This method involves forming an adhesive layer containing catechol components on the surface of a medical device substrate and further preparing a zwitterionic polymer hydrophilic coating containing dopamine groups, thereby imparting hydrophilicity, biocompatibility, and anticoagulant properties to the medical device surface. However, this type of approach primarily focuses on modifying the surface coating of the medical device substrate, typically remaining at the level of homogeneous or near-homogeneous surface functional layers. It does not establish a complete composite structure design for exudate absorption, thickness-directed translocation, and low-damage peeling during dressing changes in wound dressings.

[0004] First, improving wet adhesion solely at the interfacial chemistry level without a controllable dynamic debonding and interfacial hydration mechanism may increase the external force required for dressing removal, raising the risk of secondary damage to newly formed granulation tissue. Second, while continuous, dense surface functional layers improve the hydrophilicity or biocompatibility of the material surface, they do not necessarily possess the structural ability to rapidly absorb and directionally drain wound exudate, easily leading to exudate accumulation between the dressing and the wound. Third, such surface coating solutions typically lack interconnected capillary structures oriented along the dressing thickness direction, making it difficult to achieve directional transport of wound exudate from the wound interface to the dressing interior. Therefore, there is still a need for existing technologies to provide a composite medical dressing that simultaneously achieves wet adhesion, low-damage removal, and directional exudate management. Summary of the Invention

[0005] The purpose of this application is to solve the technical problem that in the pursuit of high wet adhesion in existing composite medical dressings, peeling damage is inevitably aggravated and exudate drainage is obstructed. The application provides a composite medical dressing and its preparation method that can simultaneously achieve reliable adhesion and sealing, efficient directional transport of exudate, and low-damage peeling during dressing changes.

[0006] To achieve the above objectives, this application provides a composite medical dressing, including a wound contact layer and a fluid-absorbing layer disposed on one side of the wound contact layer;

[0007] The wound contact layer comprises catechol-modified hyaluronic acid, polysulfobetaine methacrylate, alginate-phenylboronic acid, gelatin, glycerin, and ferric ions; wherein, the catechol groups in the catechol-modified hyaluronic acid provide wet tissue adhesion, the polysulfobetaine methacrylate forms a hydration layer at the interface between the dressing and the wound tissue, the phenylboronic acid groups in the alginate-phenylboronic acid form dynamic borate ester bonds with the catechol groups, and the ferric ions form metal-catechin coordination bonds with the catechol groups;

[0008] The liquid-absorbing layer comprises polyvinyl alcohol, sodium carboxymethyl cellulose and nanocellulose, and has capillary channels oriented and interconnected along the thickness direction of the dressing. The average pore size of the capillary channels is 50-150 μm and the vertical orientation is 65-85%.

[0009] Furthermore, the catechin-modified hyaluronic acid, alginate-phenylboronic acid, and gelatin form a continuous phase of hydrophilic biocompatible polymer; the wound contact layer also includes one or more auxiliary hydrophilic polymers selected from hyaluronic acid, sodium alginate, and sodium carboxymethyl cellulose, and the total amount of the auxiliary hydrophilic polymers does not exceed 30 wt% of the total amount of solid components in the wound contact layer.

[0010] Furthermore, the polysulfobetaine methacrylate provides zwitterionic hydration units, wherein the zwitterionic hydration units are sulfobetaine groups.

[0011] Furthermore, the molar ratio of the ferric ions to the catechol groups is 0.02 to 0.20:1.

[0012] Furthermore, the degree of substitution of the catechin groups in the catechin-modified hyaluronic acid is 5–15 mol.

[0013] When the degree of substitution of catechol groups is within the above range, the wound contact layer can form a stable adhesion on the surface of moist tissue; at the same time, under the synergistic effect of zwitterionic hydration units and reversible dynamic bonds, it can avoid the significant increase in peeling work and tissue residue rate due to excessive catechol group content.

[0014] Furthermore, the average pore size of the capillary channels in the liquid-guiding and liquid-absorbing layer is 80–120 μm.

[0015] Furthermore, the vertical orientation of the capillary channels in the liquid-conducting and absorbent layer is 70-82%; wherein, the vertical orientation is the percentage of channels in a dry cross-sectional scanning electron microscope image of the liquid-conducting and absorbent layer whose angle between the long axis of the channel and the thickness direction of the dressing is not greater than 30° out of the total number of identifiable channels.

[0016] The average pore diameter is the arithmetic mean of the equivalent circular diameters of each identifiable pore, measured by scanning electron microscopy of the dry cross-section of the liquid-conducting and absorbent layer. The vertical orientation is the percentage of pores whose long axis is at an angle of no more than 30° to the dressing thickness direction, as measured by scanning electron microscopy of the dry cross-section of the liquid-conducting and absorbent layer, out of the total number of identifiable pores.

[0017] When the average pore size of the capillary channels is within the above range, the fluid-absorbing layer can take into account both the capillary suction driving force and the fluid flux; when the vertical orientation of the capillary channels is within the above range, the exudate is more likely to migrate along the thickness direction of the dressing, thereby reducing the accumulation and lateral diffusion of fluid at the wound-dressing interface.

[0018] This application also provides a method for preparing the above-mentioned composite medical dressing, comprising the following steps:

[0019] S1. Polyvinyl alcohol, sodium carboxymethyl cellulose and nanocellulose are dispersed in water to form a liquid-conducting and liquid-absorbing layer precursor liquid under heating and stirring conditions; the liquid-conducting and liquid-absorbing layer precursor liquid is placed in a mold with a unidirectional temperature gradient for directional freezing, and then freeze-dried to form a liquid-conducting and liquid-absorbing layer with capillary channels oriented along the thickness direction of the dressing.

[0020] S2. Catechol-modified hyaluronic acid, polysulfobetaine methacrylate, alginate-phenylboronic acid, gelatin, and glycerin are dissolved in water to form a wound contact layer premix. Under stirring conditions, ferric chloride aqueous solution is added to the wound contact layer premix to allow ferric ions to form a reversible coordination reaction with the catechol groups and to allow the phenylboronic acid groups to form a dynamic borate ester reaction with the catechol groups, so as to obtain a wound contact layer precursor solution.

[0021] S3. Apply the wound contact layer precursor solution to one side of the fluid-absorbing layer, so that part of the wound contact layer precursor solution penetrates into the capillary channels on the surface of the fluid-absorbing layer. After low-temperature static gelation and drying treatment, the composite medical dressing is obtained.

[0022] Furthermore, the directional freezing step includes freezing under a unidirectional temperature gradient of 5–30 °C / cm.

[0023] When the unidirectional temperature gradient is below 5℃ / cm, the directionality of ice crystal growth is insufficient, resulting in a decrease in the vertical orientation of the resulting channels. When the unidirectional temperature gradient is above 30℃ / cm, the ice crystal growth rate is too fast, which can easily lead to excessively small pore sizes or decreased local channel connectivity. Therefore, controlling the unidirectional temperature gradient within the range of 5–30℃ / cm can stably form capillary channels with an average pore size of 50–150 μm and a vertical orientation of 65–85%.

[0024] Furthermore, the catechin-modified hyaluronic acid and alginate-phenylboronic acid in step S2 are prepared respectively through the following steps:

[0025] The preparation steps of the catechin-modified hyaluronic acid are as follows: sodium hyaluronate is dissolved in a buffer solution, and N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) are added for activation; after activation, dopamine hydrochloride is added, and the reaction is carried out under protective gas and light-protected conditions; after the reaction is completed, the hyaluronic acid is purified and dried to obtain the catechin-modified hyaluronic acid.

[0026] The preparation steps of the alginate-phenylboronic acid are as follows: sodium alginate is dissolved in water and the pH of the system is adjusted. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide are added for activation. After activation, the pH of the system is adjusted and 3-aminophenylboronic acid is added for reaction. After the reaction is completed, the alginate-phenylboronic acid is obtained by purification and drying.

[0027] Compared with the prior art, this application has the following beneficial effects:

[0028] 1. The wound contact layer of this application provides wet tissue adhesion through catechol-modified hyaluronic acid, forms a hydration layer through polysulfobetaine methacrylate, and forms reversible dynamic bonds with catechol groups through alginate-phenylboronic acid and ferric ions, thereby reducing peeling work and tissue residue rate while maintaining wet adhesion ability.

[0029] 2. In this application, the degree of substitution of catechol groups is controlled at 5-15 mol%, so that the wound contact layer can take into account both wet adhesion strength and low-damage peeling performance.

[0030] 3. The liquid-conducting and absorbent layer of this application forms capillary channels that are oriented and interconnected along the thickness direction of the dressing through directional freezing, and controls the average pore size of the capillary channels to 50-150 μm and the vertical orientation to 65-85%, thereby promoting the transmission of exudate along the thickness direction of the dressing and reducing interfacial liquid accumulation and lateral diffusion.

[0031] 4. This application improves the adhesion and fixation, low-damage peeling, exudate management and long-term service stability of composite medical dressings in moist wound environments by combining the dynamic adhesion / hydration dissolution effect of the wound contact layer with the vertical fluid conduction effect of the fluid-absorbing layer. Attached Figure Description

[0032] Figure 1 These are the NMR spectra of the raw materials and functional intermediates in the embodiments of this application;

[0033] Figure 2 This is a comparison of the Fourier transform infrared spectra of sodium hyaluronate and catechin-modified hyaluronic acid in the embodiments of this application.

[0034] Figure 3 A flowchart illustrating the preparation process of a composite medical dressing provided in this application embodiment;

[0035] Figure 4 This is a force-displacement curve of the composite medical dressing in the embodiments of this application under the 90° peel test condition. Detailed Implementation

[0036] To make the objectives, technical solutions, and advantages of this application clearer, the application will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be noted that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the application.

[0037] Example 1

[0038] In one embodiment of this application, a method for preparing and characterizing key functional polymeric intermediates for composite medical dressings is provided. Specifically, this embodiment aims to prepare and characterize two intermediates: catechol-modified hyaluronic acid and alginate-phenylboronic acid. These two intermediates are intended to provide the core wet adhesion function and dynamic cross-linking function, respectively, for the subsequently constructed wound contact layer.

[0039] First, the catechol-modified hyaluronic acid was prepared. The preparation process included the following steps: 1 gram of pharmaceutical-grade sodium hyaluronate powder was accurately weighed and completely dissolved in 100 mL of a 2-(N-morpholine)ethanesulfonic acid buffer solution with a pH of 5.5 to provide a suitable reaction environment. At room temperature (approximately 25°C), N-hydroxysuccinimide, with a molar amount equal to 1.5 times the carboxyl group of the repeating hyaluronic acid unit, and an equimolar amount of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride were added to the resulting hyaluronic acid solution. The mixture was continuously magnetically stirred for 30 minutes to activate the carboxyl groups on the hyaluronic acid molecular chain, forming an active succinimide ester intermediate, thus laying the foundation for the subsequent grafting reaction.

[0040] After the activation step is completed, dopamine hydrochloride, with a molar amount twice that of the carboxyl group of the repeating unit of hyaluronic acid, is added to the reaction system. To prevent the catechol groups in dopamine from being oxidized during the reaction, the entire reaction system is kept under nitrogen protection and light protection (achieved by wrapping the reaction vessel with aluminum foil) and the reaction is carried out at room temperature for 24 hours to ensure that the grafting reaction is fully carried out.

[0041] After the reaction, the resulting viscous reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 3500 Daltons and dialyzed in a large volume of deionized water to remove unreacted small molecule raw materials and reaction byproducts such as N-hydroxysuccinimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, and dopamine hydrochloride. The dialysis process lasted for 3 days, with the deionized water being changed 3 times daily to ensure purification efficiency. After purification, the solution in the dialysis bag was collected and freeze-dried to obtain a white, loose, flocculent solid product, namely the target product, catechol-modified hyaluronic acid.

[0042] As another part of this embodiment, an alginate-phenylboronic acid was prepared using an EDC / NHS coupling strategy. The specific steps are as follows: 1 gram of sodium alginate (molecular weight approximately 100,000-200,000) was accurately weighed and dissolved in 100 mL of deionized water. The pH of the solution was adjusted to 5.0 using dilute hydrochloric acid. EDC and NHS, in molar amounts 1.2 times that of the sodium alginate uronic acid unit, were added sequentially to the system. The mixture was magnetically stirred continuously at room temperature for 1 hour to fully activate the carboxyl groups. Subsequently, the pH of the system was adjusted to 8.0, and 3-aminophenylboronic acid, in molar amounts 1.5 times that of the uronic acid unit, was added. The reaction was continued at room temperature for 24 hours. The reaction product was dialyzed against deionized water (molecular weight cutoff 3500 Da) for 3 days and then freeze-dried to obtain a solid powder of alginate-phenylboronic acid. By comparing the integrated areas of the proton peaks of the phenylboronic acid benzene ring and the proton peaks of the sodium alginate skeleton using 1H NMR spectroscopy, the degree of substitution of the phenylboronic acid group in this embodiment was calculated to be approximately 12 mol%.

[0043] To confirm the successful synthesis of the aforementioned functional intermediate, the product underwent detailed structural characterization, and its NMR spectrum is shown below. Figure 1As shown, sodium hyaluronate, sodium alginate, and the prepared catechol-modified hyaluronic acid and alginate-phenylboronic acid were dissolved in deuterated water and analyzed using nuclear magnetic resonance spectroscopy. Spectral analysis showed that, in addition to the inherent proton characteristic peaks of the sugar ring in hyaluronic acid, a new multiplex signal at a chemical shift of 6.5-7.0 ppm, belonging to the three protons on the benzene ring of the catechol group, was clearly observed. By comparing the integrated area of ​​the proton signal peak of the benzene ring of the catechol group with the integrated area of ​​the characteristic proton peaks on the sugar ring of hyaluronic acid (e.g., the methyl proton peak of the N-acetyl group), the degree of substitution of the catechol group on the hyaluronic acid chain could be quantitatively calculated. Under the reaction conditions of this embodiment, the calculated degree of substitution of the catechol group on the hyaluronic acid chain was approximately 10 mol%. This result clearly confirms that dopamine has been successfully covalently grafted onto the hyaluronic acid molecular chain via an amide bond. Correspondingly, the 1H NMR spectroscopy analysis of alginate-phenylboronic acid also showed characteristic proton peaks on the benzene ring of the phenylboronic acid group, thus confirming the successful grafting of the phenylboronic acid group.

[0044] Furthermore, the structure of the product was further verified using Fourier transform infrared spectroscopy, and the infrared spectral comparison results are as follows: Figure 2 As shown in the figure, the catechin-modified hyaluronic acid sample was mixed with potassium bromide, compressed into tablets, and tested. Its infrared spectrum was then compared with that of the raw sodium hyaluronate. The results showed that, compared to the raw material spectrum, the spectrum of the catechin-modified hyaluronic acid was significantly larger at approximately 1600 cm⁻¹. -1 (Attributable to the C=O stretching vibration of the amide I band and the skeletal vibration of the benzene ring) and 1500 cm -1 The absorption peak at the region (attributed to the NH bending vibration of the amide II band and the benzene ring skeletal vibration) shows a significant enhancement and broadening. Understandably, this change is attributed to the newly formed amide bond and the introduced benzene ring structure, thus confirming the successful introduction of the catechol group from another perspective.

[0045] In summary, this embodiment successfully prepared key functional raw materials with well-defined structures and reliable quality, laying a material foundation for the subsequent construction of composite medical dressings with multiple functions such as wet adhesion and dynamic cross-linking.

[0046] Example 2

[0047] This embodiment details how to utilize the functional intermediate prepared in Example 1, combined with key technologies such as directional cryotherapy, to prepare a composite medical dressing with the unique structure and function described in this application. In one embodiment of this application, the dressing presents a multi-layered composite structure, mainly comprising a wound contact layer that directly contacts the wound surface, and a fluid-absorbing layer located on one side of the wound contact layer. As a preferred implementation, a back protective layer can also be composited on the side of the fluid-absorbing layer opposite to the wound contact layer, thereby constituting a complete composite medical dressing.

[0048] The preparation process of the composite medical dressing is as follows: Figure 3 As shown, the main steps include:

[0049] Preparation of the fluid-absorbing layer. The core function of this layer is to efficiently and directionally manage wound exudate using its special physical structure. First, the precursor solution is prepared: deionized water is added to a reaction vessel, and then 20 parts by weight of polyvinyl alcohol, 12 parts by weight of sodium carboxymethyl cellulose and 5 parts by weight of nanocellulose are dispersed in water in sequence. Under heating (e.g., 80°C) and continuous stirring, all components are completely dissolved, finally forming a homogeneous, particle-free viscous precursor solution.

[0050] Subsequently, a macroscopic structure with oriented channels was constructed using directional freezing technology. Specifically, the aforementioned liquid-conducting and absorbent layer precursor liquid was injected into a custom mold with a bottom made of a highly thermally conductive material and sidewalls made of an insulating material. The mold was placed on a directional freezing device, with its bottom in close contact with a precisely temperature-controlled cold source (e.g., a low-temperature circulating bath set to -45°C), while the top of the mold was exposed to room temperature (approximately 25°C). This established a stable and unidirectional temperature gradient in the vertical direction of the precursor liquid; according to the parameters of this embodiment, this temperature gradient is approximately 15°C / cm. Driven by this temperature gradient, the crystallization of the solvent (water) begins at the bottom cold source and grows directionally in the opposite direction of the temperature gradient (i.e., from bottom to top), thereby forming a large number of parallel columnar ice crystals that penetrate the thickness of the sample. This directional freezing process lasted for 4 hours to ensure complete ice crystal growth. Subsequently, the entire mold was rapidly transferred to an ultra-low temperature freezer at -80°C for quenching and solidification, and then placed in a freeze dryer for 48 hours of freeze-drying. Under vacuum and low-temperature conditions, oriented ice crystals sublimate directly, leaving capillary channels in the polymer substrate that are shaped and oriented along the thickness direction of the dressing. This process produces a porous scaffold with a vertically conductive and absorbent layer.

[0051] Preparation of the wound contact layer. This layer is key to achieving various chemical functions such as dynamic adhesion, hydrolysis, and sacrificial bond energy dissipation. The chemical composition of the wound contact layer includes a continuous phase of hydrophilic biocompatible polymer as the matrix, and catechol adhesion units, zwitterionic hydration units, and dynamic crosslinking units dispersed or grafted therein. The preparation process of its precursor solution is as follows: 25 parts by weight of catechol-modified hyaluronic acid (catechin substitution degree of 10 mol%) prepared in Example 1, 15 parts by weight of polysulfobetaine methacrylate, 8 parts by weight of alginate-phenylboronic acid prepared in Example 1, 10 parts by weight of gelatin, and 5 parts by weight of glycerol are sequentially dissolved in deionized water to form a homogeneous mixed solution with a solid content of 8-20 wt%, and the pH of the system is adjusted to 6.5-8.0. Subsequently, an aqueous solution of ferric chloride is added under gentle stirring to achieve a molar ratio of ferric ions to catechol groups of 0.02–0.20:1, preferably 0.05–0.12:1. Stirring continues for 1–10 minutes after the addition of ferric chloride to form a precursor solution for the wound contact layer containing metal-catechol coordination bonds and dynamic borate ester bonds. It is understood that the ferric ions in ferric chloride can form reversible metal-catechol coordination bonds with the catechol adhesion units on catechol-modified hyaluronic acid, and the phenylboronic acid groups on alginate-phenylboronic acid can form dynamic borate ester bonds with the catechol groups on catechol-modified hyaluronic acid. These two types of reversible dynamic bonds together construct a dynamic cross-linking network. This dynamic cross-linking network can improve the cohesive strength and anti-swelling ability of the wound contact layer, and dissipate external mechanical energy during the peeling process through the breaking and reconstruction of dynamic bonds. Thus, the precursor solution for the wound contact layer is obtained.

[0052] In this embodiment, polysulfonated betaine methacrylate is uniformly dispersed in a three-dimensional dynamic cross-linked network formed by catechol-modified hyaluronic acid, alginate-phenylboronic acid, gelatin, and ferric ions, forming a stable semi-interpenetrating polymer network structure. To prevent macroscopic loss of polysulfonated betaine methacrylate during long-term liquid absorption and swelling, this application specifically selects polysulfonated betaine methacrylate with a high molecular weight (preferably a weight-average molecular weight of 100,000 to 500,000). The high molecular weight polysulfonated betaine methacrylate has extremely long chains, generating significant steric hindrance through strong multi-chain entanglement and dense hydrogen bonding interactions with the dynamic network. This semi-interpenetrating polymer network effect allows polysulfonated betaine methacrylate to be firmly anchored within the contact layer, ensuring that it can continue to provide zwitterionic hydration lubrication even after absorbing a large amount of exudate.

[0053] Freshly prepared wound contact layer precursor solution was uniformly applied to one side of the prepared porous scaffold with a fluid-conducting and absorbent layer. To prevent excessive penetration of the precursor solution and blockage of the fluid-conducting channels, the dynamic viscosity of the precursor solution was controlled within the range of 500–1500 mPa·s, and a scraping process was used to control the initial thickness of the coating. Given the fluidity of the precursor solution, it partially penetrated into the capillary channels on the surface of the fluid-conducting and absorbent layer under gravity and capillary action. Cross-sectional scanning electron microscopy confirmed that the penetration depth of the precursor solution was controlled between 10% and 20% of the total thickness of the fluid-conducting and absorbent layer. After curing, this limited penetration area formed a physically interlocked interpenetrating network, significantly enhancing the bonding force between the two layers without affecting the overall vertical fluid-conducting performance.

[0054] The coated semi-finished product was left to stand at 4°C for 2 hours to allow the wound contact layer to physically gel and initially solidify. Subsequently, on the other side of the absorbent layer (i.e., the side opposite to the wound contact layer), a polyurethane film with good moisture permeability and antibacterial / waterproof properties was laminated using medical-grade pressure-sensitive adhesive to form a protective back layer. Finally, the composite dressing was dried in a 40°C oven to reach equilibrium moisture content and then cut into specific sizes and shapes as needed. The finished product was sterilized with ethylene oxide and aseptically sealed in packaging to obtain the final composite medical dressing. In this embodiment, the total thickness of the prepared dressing was approximately 1.8 mm, with the wound contact layer having a thickness of approximately 150 μm.

[0055] To characterize the microstructure of the prepared dressing, its cross-sectional morphology was observed using scanning electron microscopy. The dressing sample was fractured in liquid nitrogen, and the cross-section was sputter-coated with gold before observation. The scanning electron microscope images clearly revealed that the liquid-absorbing layer contained a large number of long, straight tubular or honeycomb-like pore structures, i.e., capillary channels, arranged along the thickness direction (i.e., perpendicular to the dressing plane), with smooth and continuous pore walls. The cross-sectional images were measured and statistically analyzed using image analysis software: specifically, the cross-sectional area of ​​each identifiable channel was converted into the equivalent circle diameter, and the arithmetic mean was taken as the average pore diameter, which was measured to be approximately 100 μm; simultaneously, by statistically analyzing the angle between the long axis of the channel and the thickness direction of the dressing, the percentage of channels with an angle not greater than 30° was defined as the vertical orientation degree. Calculations showed that the vertical orientation degree of the capillary channels in this embodiment was as high as approximately 78%.

[0056] This structure contrasts sharply with the comparative sample prepared using a conventional random freezing method (whose cross-section exhibits a chaotic, non-uniform pore size, and is mostly a sponge-like structure with closed or semi-closed pores). Scanning electron microscopy observations strongly confirm that this embodiment successfully prepared a composite medical dressing with a unique microstructure, combining a chemically functional contact layer and a liquid-absorbing layer, providing a solid structural foundation for subsequent performance verification.

[0057] Example 3

[0058] This embodiment aims to quantitatively evaluate the performance of the composite medical dressing prepared in Example 2 in terms of wet adhesion and low-damage peeling through a series of in vitro mechanical property tests, and to compare it with comparative examples lacking some key functional units, so as to verify the superiority of the technical solution of this application. The specific settings of each comparative example are as follows:

[0059] Comparative Example 1: The wound contact layer formula does not contain catechin-modified hyaluronic acid, but is replaced with an equal amount of ordinary hyaluronic acid;

[0060] Comparative Example 2: Hyaluronic acid modified with monophenol groups (such as tyrosine) was used instead of catechin-modified hyaluronic acid;

[0061] Comparative Example 3: The wound contact layer formulation contains catechin-modified hyaluronic acid, but its catechin substitution is too high (reaching 25 mol%).

[0062] Comparative Example 4: The wound contact layer formulation contains catechol-modified hyaluronic acid, but lacks zwitterionic hydration units (i.e., it does not contain polysulfobetaine methacrylate).

[0063] Comparative Example 5: The wound contact layer formulation contains polysulfobetaine methacrylate, but does not contain catechol-modified hyaluronic acid.

[0064] Evaluation of wet adhesion strength. This test aims to simulate the fixation ability of dressings in a moist wound environment. Fresh, detached porcine back skin was used as a substrate, as its structure is highly similar to human skin. After the hair on the surface of the porcine skin was scraped off, its surface was moistened with a phosphate buffer solution to simulate the moist state of a wound. The dressing sample prepared in Example 2 (cut into strips of 1 cm × 2 cm) was adhered to the moistened porcine skin with its wound contact layer side facing down, and a slight pressure (e.g., using a 50 g weight) was applied for 1 minute to ensure good contact. Subsequently, the dressing was pulled off the porcine skin using a universal testing machine in lap shear mode at a tensile rate of 10 mm / min. The maximum load was recorded and divided by the adhesion area to calculate the wet adhesion strength.

[0065] Test results showed that the wet adhesion strength of the composite medical dressing prepared in Example 2 reached 38 ± 3.5 kPa. In contrast, to highlight the crucial role of the catechol adhesion unit, several comparative examples were set up: Comparative Example 1 (the wound contact layer formulation did not contain catechol-modified hyaluronic acid, but was replaced with an equal amount of ordinary hyaluronic acid) and Comparative Example 5 (the wound contact layer formulation did not contain catechol-modified hyaluronic acid, but contained polysulfobetaine methacrylate), both of which had a wet adhesion strength of only 9 ± 1.2 kPa, exhibiting almost no effective wet adhesion ability. Furthermore, Comparative Example 2 (using monophenolic groups such as tyrosine-modified hyaluronic acid instead of catechol-modified hyaluronic acid) also had an adhesion strength of only 16 ± 2.1 kPa, significantly lower than that using catechol groups with an ortho-diol structure. These data clearly demonstrate that the catechol adhesion unit is a necessary chemical basis for achieving high wet adhesion performance in dressings.

[0066] To further verify the effect of the degree of substitution of catechol groups on the wet adhesion and low-damage peel performance of dressings, the amount of dopamine hydrochloride added and the reaction time were adjusted according to the method in Example 1 to prepare catechol-modified hyaluronic acid with a degree of substitution of 5 mol%, 10 mol%, and 15 mol%, respectively, and composite medical dressings were prepared according to the method described in Example 2. Except for the different degrees of substitution of catechol groups, the composition and preparation conditions of polysulfobetaine methacrylate, alginate-phenylboronic acid, gelatin, glycerin, ferric chloride, and the liquid-absorbing layer were kept consistent in all groups of samples.

[0067] Test results showed that when the degree of substitution of catechol groups was 5 mol%, the wet adhesion strength of the dressing on the moist pigskin surface was 31 ± 2.8 kPa, and the 90° peel energy was 29 ± 3.6 J·m. -2 The tissue residue rate was 3.8 ± 0.7%; when the degree of substitution of catechol groups was 10 mol%, the wet adhesion strength of the dressing was 38 ± 3.5 kPa, and the 90° peel energy was 34 ± 4.1 J·m. -2 The tissue residue rate was 4.5 ± 0.8%; when the degree of substitution of catechol groups was 15 mol%, the wet adhesion strength of the dressing was 42 ± 4.0 kPa, and the 90° peel energy was 46 ± 5.2 J·m. -2 The tissue residue rate was 6.2 ± 1.0%.

[0068] The above results indicate that when the degree of substitution of catechol groups is in the range of 5–15 mol%, the wound contact layer can provide stable wet adhesion, while maintaining low peeling energy and tissue residue rate under the combined action of the polysulfobetaine methacrylate hydration layer and the dynamic cross-linking network. When the degree of substitution is about 10 mol%, the dressing exhibits a better balance between wet adhesion strength and low-damage peeling performance.

[0069] Understandably, an ideal dressing should not only adhere well but also be easy to remove without causing secondary damage. This experiment quantifies the ease of dressing removal and its damage to the underlying tissue through a 90-degree peel test. A dressing sample (2 cm × 5 cm) was adhered to pigskin and incubated at 37°C and 95% humidity for 4 hours to simulate its actual use in vivo. Subsequently, the dressing was peeled from the pigskin using a universal testing machine at a 90-degree angle and a speed of 50 mm / min, and the force-displacement curve was recorded. The resulting force-displacement curve is shown below. Figure 4 As shown in the figure, the area under the curve represents the peeling work, which is the energy required to peel off a unit area of ​​dressing and is a direct indicator of the ease of peeling. Immediately after peeling, the surface of the pigskin was photographed with a digital camera, and image processing software was used to analyze the residual area of ​​the dressing on the pigskin and calculate the tissue residue rate. This indicator intuitively reflects the degree of tearing of the tissue caused by peeling.

[0070] Test results show that the peeling process of the dressing in Example 2 is stable, and its peeling energy is 34 ± 4.1 J·m. -2 The peeled pigskin surface was smooth with only a very small amount of dressing residue, and the calculated tissue residue rate was only 4.5 ± 0.8%. In stark contrast, Comparative Example 4, while containing catechol-modified hyaluronic acid in its wound contact layer formulation, lacked zwitterionic hydration units (i.e., it did not contain polysulfobetaine methacrylate). Although Comparative Example 4 also exhibited strong wet adhesion, its peeling energy was as high as 110 ± 9.5 J·m. -2 This is more than three times that of Example 2. Not only does it require immense external force during peeling, but the peeled pigskin surface exhibits significant redness and damage, with the tissue residue rate soaring to 20.0 ± 2.5%. Furthermore, Comparative Example 3 (where the catechin substitution in the catechin-modified hyaluronic acid is excessively high, for example reaching 25 mol%) shows even more severe peeling damage, with a peeling energy reaching 120 J·m. -2 The tissue residue rate was 22.0%.

[0071] A comprehensive analysis of the above experimental data clearly reveals the working mechanism of the dressing described in this application. During use, when the dressing is applied to wound tissue, the catechol adhesion units in the wound contact layer provide a solid foundation for the dressing to adhere firmly. During peeling, the zwitterionic hydration units, with their excellent hydrophilicity, strongly adsorb water molecules at the dressing-tissue interface, forming a stable hydration layer. This hydration layer acts as a physical shield, similar to a lubricant, effectively preventing direct and firm bonding between tissue cells and the dressing substrate, thus significantly reducing peeling force. Simultaneously, the numerous reversible dynamic bonds formed within the wound contact layer by dynamic cross-linking units (such as phenylboronic acid groups and iron ions) and catechol adhesion units preferentially break and remodel under peeling forces. This process converts macroscopic mechanical energy into chemical energy at the molecular level and dissipates it. It acts like countless miniature shock absorbers, dissipating external stress within the dressing material rather than directly transmitting it and concentrating it on the adhesion interface between the fragile new tissue and the dressing. This plays a crucial protective role in sacrificial bond energy dissipation.

[0072] The experimental data in this embodiment proves that the composite medical dressing designed in this application has successfully overcome the long-standing technical contradiction between high adhesion and low damage through the synergistic effect of the catechol adhesion unit, the zwitterionic hydration unit and the dynamic cross-linking unit, and has achieved a balance between high wet adhesion and low peel damage.

[0073] Example 4

[0074] This embodiment aims to evaluate the performance of the composite medical dressing prepared in Example 2 in terms of exudate management capability and long-term service stability, in order to further confirm the comprehensive advantages of the technical solution of this application.

[0075] This test aimed to verify whether capillary channels oriented along the thickness direction in the absorbent layer could effectively achieve rapid and directional transport of wound exudate, thereby preventing fluid accumulation at the wound-dressing interface and lateral leakage to the peri-wound skin. The experimental setup was as follows: A 3 cm diameter circular dressing sample was fixed to a support with a central opening, with the wound contact layer facing downwards. A stained artificial exudate (a buffer solution containing salts and proteins) was dripped onto the dressing from below the center using a peristaltic pump at a constant low flow rate (to simulate a wound with moderate exudate). The fluid transport process within the dressing was recorded from the side and bottom using a high-speed camera. Finally, by analyzing the video and weighing data, the absorbance rate along the thickness direction of the dressing was calculated, and the diameter of the fluid spot at the bottom of the dressing after 20 minutes was measured to assess its lateral diffusion.

[0076] Test results showed that the dressing of Example 2 exhibited superior directional fluid-guiding performance. When the artificial exudate came into contact with the wound contact layer, it hardly lingered at the interface but was rapidly absorbed into the dressing. Lateral observation revealed that the stained fluid clearly migrated rapidly upwards along the vertical channels in the fluid-absorbing layer. The calculated thickness-direction absorption rate was as high as 0.85 ± 0.07 g·cm⁻¹. -2 ·min -1 After continuous dripping for 20 minutes, the liquid was mainly confined to the central absorbent area of ​​the dressing, with the liquid spot at the bottom of the dressing (i.e., the lateral diffusion radius) being only 9 ± 1.0 mm.

[0077] In contrast, Comparative Example 6 used the exact same chemical composition as Example 2, but the dressing was prepared using a conventional random freezing method (i.e., the precursor solution was directly frozen in a -80°C freezer) when preparing the liquid-absorbing layer. Its internal structure exhibited a random and irregular pore structure. Under the same testing conditions, the thickness-direction liquid absorption rate of Comparative Example 6 was only 0.32 ± 0.04 g·cm⁻¹. -2 ·min -1 This is significantly lower than in Example 2. More importantly, after entering the dressing, the liquid, lacking directional guidance, tends to diffuse along the path of least resistance in the dressing plane, resulting in a lateral diffusion radius of 25 ± 2.2 mm after 20 minutes, almost three times that of Example 2.

[0078] This process can be understood as follows: when the dressing is applied to the wound tissue, the exudate generated by the wound is captured by numerous capillary channels oriented along the thickness direction in the absorbent layer. These channels, like tens of thousands of micro-channels, utilize powerful capillary forces to rapidly absorb the exudate from the wound-dressing interface and transport it upwards along the thickness direction of the dressing (i.e., perpendicular to the wound) to the deeper absorbent layer away from the wound. Finally, moisture evaporates through the dorsal protective layer. This vertical pumping mechanism effectively avoids wound maceration caused by exudate accumulation at the interface and damage to the peri-wound skin caused by the diffusion of liquid along a planar direction.

[0079] This test aims to evaluate whether a dressing can maintain sufficient adhesion after absorbing a large amount of exudate, ensuring that it does not slip or fall off the wound throughout its entire service life (typically 1-3 days). The experimental method is as follows: A dressing sample is adhered to pigskin, and then the entire pigskin-dressing composite is completely immersed in artificial exudate at 37°C to simulate the long-term working condition of the dressing in an exudate-rich wound environment. After 24 hours of immersion, the sample is removed, excess liquid is gently wiped off, and its remaining wet adhesion strength is tested according to the method in Example 3. This value is compared with the initial adhesion strength before immersion to calculate the adhesion retention rate.

[0080] Test results showed that after soaking in artificial exudate for 24 hours, the dressing of Example 2 maintained its network structure intact, with only slight swelling, and its wet adhesion strength remained at 78 ± 5.5% of its initial value. This high adhesion retention rate is mainly attributed to the dynamic cross-linking network constructed by dynamic cross-linking units in the wound contact layer. These reversible dynamic bonds (such as metal-catechol coordination bonds and dynamic borate ester bonds) enhance the network cohesive strength, effectively improving the anti-swelling ability of the hydrogel network, thereby maintaining the structural integrity of the dressing after absorbing liquid and swelling, and ensuring the durability of adhesion.

[0081] In contrast, Comparative Example 7 (whose formulation was similar to Example 2, but lacked ferric chloride and alginate-phenylboronic acid in the preparation of the wound contact layer precursor solution, i.e., it lacked dynamic cross-linking units) showed that after 24 hours of soaking, its hydrogel network structure became extremely soft and even partially dissolved due to excessive swelling, resulting in a sharp drop in its adhesion retention rate to only 38 ± 4.2%. This comparative result indicates that, in the absence of dynamic cross-linking network protection, physical hydrogels relying solely on polymer chain entanglement exhibit significant instability in humid environments.

[0082] The experimental data in this embodiment fully demonstrate that the composite medical dressing of this application can not only efficiently and directionally manage wound exudate, but also maintain stable adhesion performance in a long-term moist service environment, ensuring its high reliability and effectiveness in clinical applications.

[0083] Example 5

[0084] This embodiment aims to further verify the influence of the degree of substitution of catechol groups, the average pore size of capillary channels, and the vertical orientation of capillary channels on the core performance of composite medical dressings, so as to illustrate the rationality of the parameter range defined in this application.

[0085] First, the effect of the degree of substitution of catechol groups on wet adhesion and low-damage peeling performance was investigated. Following the method of Example 1, catechol-modified hyaluronic acid with catechol group substitution degrees of 5 mol%, 10 mol%, and 15 mol% was prepared, and composite medical dressings were prepared according to the method of Example 2. The test results showed that the sample with a substitution degree of 5 mol% provided stable wet adhesion; although the sample with a substitution degree of 15 mol% showed further improved adhesion strength, the peeling power and tissue residue rate remained within acceptable ranges; the sample with a substitution degree of 10 mol% exhibited a better balance between wet adhesion strength and low-damage peeling.

[0086] Secondly, the effect of the average pore size of the capillary channels on the exudate transport capacity was investigated. By adjusting the liquid-solid content of the precursor layer, the cold source temperature, and the unidirectional temperature gradient, liquid-absorbing layers with average pore sizes of approximately 50 μm, 100 μm, and 150 μm were prepared, respectively. Scanning electron microscopy observations showed that all three groups of samples possessed interconnected capillary channels extending along the dressing thickness direction. Directional fluid transport tests indicated that all three groups of samples were able to transport artificial exudate along the dressing thickness direction, with the sample having an average pore size of approximately 100 μm exhibiting a better balance between capillary suction driving force and fluid flux.

[0087] Next, the effect of capillary vertical orientation on the lateral diffusion suppression effect was investigated. Liquid-absorbing layers with vertical orientations of approximately 65%, 78%, and 85% were prepared by adjusting the insulation degree of the mold sidewall, the temperature stability of the cold source, and the unidirectional temperature gradient. Test results showed that all three groups of samples could reduce liquid diffusion in the dressing plane and promote the migration of artificial exudate along the dressing thickness direction. Among them, the sample with a vertical orientation of approximately 78% exhibited a higher liquid absorption rate in the thickness direction and a lower lateral diffusion radius.

[0088] Therefore, it can be seen that when the degree of substitution of catechol groups in catechol-modified hyaluronic acid is 5–15 mol%, the average pore size of the capillary channels in the liquid-absorbing layer is 50–150 μm, and the vertical orientation of the capillary channels is 65–85%, the resulting composite medical dressings can simultaneously achieve wet adhesion, low-damage peeling, and thickness-direction liquid-guiding performance. The above results further demonstrate that the parameter range defined in this application can stably achieve the technical effects of this application.

[0089] The above description is merely a few preferred embodiments of this application and is not intended to limit the scope of this application. For those skilled in the art, various modifications and variations can be made within the spirit and principles of this application. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A composite medical dressing, characterized in that, It includes a wound contact layer and a fluid-conducting and absorbent layer disposed on one side of the wound contact layer; The wound contact layer comprises catechol-modified hyaluronic acid, polysulfobetaine methacrylate, alginate-phenylboronic acid, gelatin, glycerin, and ferric ions; wherein, the catechol groups in the catechol-modified hyaluronic acid provide wet tissue adhesion, the polysulfobetaine methacrylate forms a hydration layer at the interface between the dressing and the wound tissue, the phenylboronic acid groups in the alginate-phenylboronic acid form dynamic borate ester bonds with the catechol groups, and the ferric ions form metal-catechin coordination bonds with the catechol groups; The liquid-absorbing layer comprises polyvinyl alcohol, sodium carboxymethyl cellulose and nanocellulose, and has capillary channels oriented and interconnected along the thickness direction of the dressing. The average pore size of the capillary channels is 50-150 μm and the vertical orientation is 65-85%.

2. The composite medical dressing according to claim 1, characterized in that, The catechin-modified hyaluronic acid, alginate-phenylboronic acid, and gelatin form a continuous phase of hydrophilic biocompatible polymer; the wound contact layer also includes one or more auxiliary hydrophilic polymers selected from hyaluronic acid, sodium alginate, and sodium carboxymethyl cellulose, and the total amount of the auxiliary hydrophilic polymers does not exceed 30 wt% of the total amount of solid components in the wound contact layer.

3. The composite medical dressing according to claim 1, characterized in that, The polysulfobetaine methacrylate provides zwitterionic hydration units, wherein the zwitterionic hydration units are sulfobetaine groups.

4. The composite medical dressing according to claim 1, characterized in that, The molar ratio of the ferric ions to the catechol groups is 0.02 to 0.20:

1.

5. The composite medical dressing according to claim 1, characterized in that, The degree of substitution of catechin groups in the catechin-modified hyaluronic acid is 5–15 mol.

6. The composite medical dressing according to claim 1, characterized in that, The average pore size of the capillary channels in the liquid-conducting and absorbing layer is 80–120 μm.

7. The composite medical dressing according to claim 6, characterized in that, The vertical orientation of the capillary channels in the liquid-conducting and absorbent layer is 70-82%; wherein, the vertical orientation is the percentage of channels with an angle of no more than 30° between the long axis of the channel and the thickness direction of the dressing in a dry cross-section scanning electron microscope image of the liquid-conducting and absorbent layer out of the total number of identifiable channels.

8. A method for preparing the composite medical dressing according to any one of claims 1 to 7, characterized in that, Includes the following steps: S1. Polyvinyl alcohol, sodium carboxymethyl cellulose and nanocellulose are dispersed in water to form a liquid-conducting and liquid-absorbing layer precursor liquid under heating and stirring conditions; the liquid-conducting and liquid-absorbing layer precursor liquid is placed in a mold with a unidirectional temperature gradient for directional freezing, and then freeze-dried to form a liquid-conducting and liquid-absorbing layer with capillary channels oriented along the thickness direction of the dressing. S2. Catechol-modified hyaluronic acid, polysulfobetaine methacrylate, alginate-phenylboronic acid, gelatin, and glycerin are dissolved in water to form a wound contact layer premix. Under stirring conditions, ferric chloride aqueous solution is added to the wound contact layer premix to allow ferric ions to form a reversible coordination reaction with the catechol groups and to allow the phenylboronic acid groups to form a dynamic borate ester reaction with the catechol groups, so as to obtain a wound contact layer precursor solution. S3. Apply the wound contact layer precursor solution to one side of the fluid-absorbing layer, so that part of the wound contact layer precursor solution penetrates into the capillary channels on the surface of the fluid-absorbing layer. After low-temperature static gelation and drying treatment, the composite medical dressing is obtained.

9. The method according to claim 8, characterized in that, The directional freezing step includes freezing under a unidirectional temperature gradient of 5–30 °C / cm.

10. The method according to claim 8, characterized in that, The catechin-modified hyaluronic acid and alginate-phenylboronic acid in step S2 are prepared through the following steps: The preparation steps of the catechin-modified hyaluronic acid are as follows: sodium hyaluronate is dissolved in a buffer solution, and N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride are added for activation; after activation, dopamine hydrochloride is added, and the reaction is carried out under protective gas and light-protected conditions; after the reaction is completed, the catechin-modified hyaluronic acid is obtained by purification and drying. The preparation steps of the alginate-phenylboronic acid are as follows: sodium alginate is dissolved in water and the pH of the system is adjusted. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide are added for activation. After activation, the pH of the system is adjusted and 3-aminophenylboronic acid is added for reaction. After the reaction is completed, the alginate-phenylboronic acid is obtained by purification and drying.

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