A hydrocolloid dressing

Abstract

This invention relates to the field of medical dressing technology, and more particularly to a hydrocolloid dressing comprising a sustained-release hydrocolloid layer. The sustained-release hydrocolloid layer, by weight, comprises the following components: 10-35 parts sodium carboxymethyl cellulose; 5-15 parts copper-containing microspheres; and 40-70 parts hot melt adhesive. The copper-containing microspheres include a core and a shell covering the outer surface of the core. The core is a copper-loaded microsphere; the shell comprises a sodium alginate-calcium carbonate composite layer. The hydrocolloid dressing provided by this invention, by introducing copper-containing microspheres with a core-shell structure, enables the release of copper ions to be pH-responsive, thereby achieving gradient sustained release of copper ions and long-lasting antibacterial effects, effectively enhancing the healing-promoting function of the hydrocolloid dressing.

Description

Technical Field

[0001] This invention relates to the field of medical dressing technology, and more particularly to a hydrocolloid dressing. Background Technology

[0002] Hydrocolloid dressings are one of the most widely used types of dressings in modern wound care. They promote autologous debridement and epithelial cell migration by creating a closed, moist environment on the wound surface. However, traditional hydrocolloid dressings lack active antibacterial capabilities and are difficult to use in wounds that are already infected or susceptible to infection.

[0003] To impart antibacterial properties, current technologies typically involve directly incorporating inorganic antibacterial agents such as silver and zinc into the hydrocolloid matrix. This method has several drawbacks: first, it easily leads to a burst release of the antibacterial agent in the initial stages, potentially causing cytotoxicity and insufficient antibacterial efficacy in the later stages; second, some antibacterial agents have poor thermal stability and cannot withstand the high-temperature melting and mixing processes involved in the production of hydrocolloid dressings; and third, the antibacterial function is limited, resulting in a limited effect on promoting wound healing.

[0004] Copper ions, as a broad-spectrum antibacterial agent, have attracted much attention in recent years due to their unique bioactivity in promoting angiogenesis and epithelial regeneration. However, the effective concentration window of copper ions is narrow, and high concentrations are cytotoxic. Directly introducing copper ions into hydrocolloid dressings makes it difficult to achieve controlled release. Summary of the Invention

[0005] To address the problem that existing hydrocolloid dressings struggle to achieve controlled release of copper ions, this invention provides a hydrocolloid dressing that incorporates a slow-release hydrocolloid layer, enabling intelligent pH-responsive copper ion release. This allows the dressing to dynamically adjust its release behavior based on changes in the wound environment, thus resolving the issue of controlled copper ion release in existing hydrocolloid dressings.

[0006] The technical solution adopted by this invention to solve its technical problem is: A hydrocolloid dressing includes a sustained-release hydrocolloid layer; the raw material of the sustained-release hydrocolloid layer comprises the following components in parts by weight: 10-35 parts of sodium carboxymethyl cellulose; 5-15 parts containing copper microspheres; 40-70 parts hot melt adhesive; The copper-containing microspheres include a core and a shell covering the outer side of the core; The core is a copper-loaded microsphere; The shell includes a sodium alginate-calcium carbonate composite layer.

[0007] Optionally, the thickness of the sodium alginate-calcium carbonate composite layer is 15-40 μm.

[0008] Optionally, the shell further includes a controlled-release layer covering the outside of the sodium alginate-calcium carbonate composite layer.

[0009] Optionally, the controlled-release layer is an ethyl cellulose layer.

[0010] Optionally, the thickness of the ethyl cellulose layer is 20-50 μm.

[0011] Optionally, the copper-loaded microspheres are halloysite nanotubes loaded with copper ions.

[0012] Optionally, in the halloysite nanotubes loaded with copper ions, the loading of copper element is 1%-20% of the mass of the halloysite nanotubes.

[0013] Optionally, the diameter of the halloysite nanotubes is 30-100 nanometers.

[0014] Optionally, the halloysite nanotubes have a length of 1-3 μm.

[0015] Optionally, it also includes a backing layer and a release layer respectively disposed on both sides of the slow-release hydrocolloid layer.

[0016] The beneficial effects of this invention are: The hydrocolloid dressing provided by this invention introduces copper-containing microspheres with a core-shell structure, enabling the release of copper ions to be pH-responsive, thereby achieving gradient slow release of copper ions and long-lasting antibacterial effect, effectively enhancing the healing-promoting function of the hydrocolloid dressing. Detailed Implementation

[0017] The present invention will now be described in further detail. The embodiments described below are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0018] Copper ions, as a broad-spectrum antibacterial agent, have been proven to have multiple biological effects, including promoting angiogenesis, accelerating wound healing, and regulating inflammatory responses. However, the direct addition of copper ions to hydrocolloid dressings can lead to excessively rapid release, potentially causing local toxicity and affecting their long-term efficacy. Therefore, achieving safe, continuous, and controllable release of copper ions has become a key issue in improving the functionality of hydrocolloid dressings.

[0019] To address the problem of controlled copper ion release in existing hydrocolloid dressings, this invention provides a hydrocolloid dressing comprising a sustained-release hydrocolloid layer. This sustained-release hydrocolloid layer is the core layer of the hydrocolloid dressing and is composed of a hydrocolloid matrix and copper-containing microspheres uniformly dispersed therein. Specifically, by weight, the raw materials of the sustained-release hydrocolloid layer include the following components: 10-35 parts of sodium carboxymethyl cellulose; 5-15 parts containing copper microspheres; 40-70 parts hot melt adhesive; The copper-containing microspheres have a core-shell structure. Specifically, the copper-containing microspheres include a core and a shell covering the outer side of the core. The core is a copper-loaded microsphere used to release copper ions during use. The shell includes a sodium alginate-calcium carbonate composite layer, which is a pH-responsive layer. Preferably, a layer of pH-responsive polymer sodium alginate-calcium carbonate composite layer is coated onto the surface of the core by fluidized bed spraying. This sodium alginate-calcium carbonate composite layer forms a stable three-dimensional network structure through cross-linking of sodium alginate and calcium ions, giving the copper-containing microspheres good mechanical strength and initial barrier function. It also enables dual intelligent response; when the hydrocolloid dressing initially contacts the wound (weakly acidic), the composite layer reacts due to the calcium ions... 2+ Cross-linking with sodium alginate forms a gel, increasing the density of the pH-responsive layer and effectively preventing burst release. As the wound gradually heals and the pH rises back to neutral / slightly alkaline, the cross-linking weakens, the sodium alginate gel becomes looser, and copper ions are released more rapidly, thus achieving controlled release of copper ions and allowing the sleeping dressing to remain antibacterial even in the later stages of use.

[0020] The preferred hot melt adhesive of the present invention is styrene-isoprene-styrene block copolymer (SIS) hot melt adhesive.

[0021] The hydrocolloid dressing provided by this invention introduces copper-containing microspheres with a core-shell structure, enabling the release of copper ions to be pH-responsive, thereby achieving gradient slow release of copper ions and long-lasting antibacterial effect, effectively enhancing the healing-promoting function of the hydrocolloid dressing.

[0022] The preferred thickness of the sodium alginate-calcium carbonate composite layer in this invention is 15-40 μm.

[0023] To further improve the controllability of copper ion release, the present invention preferably includes a controlled-release layer covering the outside of the sodium alginate-calcium carbonate composite layer. This controlled-release layer acts as a second barrier, significantly slowing down the rate of internal copper ion diffusion outward, avoiding early burst release, and ensuring that an effective concentration is maintained throughout the entire wound healing cycle.

[0024] Specifically, the controlled-release layer of the present invention is preferably an ethyl cellulose layer, which is a water-insoluble but permeable film that slowly controls water penetration and drug dissolution through a diffusion mechanism to provide long-lasting release.

[0025] The present invention preferably uses an ethyl cellulose layer with a thickness of 20-50 μm. Within this thickness range, sufficient barrier capacity can be ensured without excessive release delay due to excessive thickness, which would affect the early antibacterial effect.

[0026] The preferred copper-loaded microspheres of this invention are halloysite nanotubes loaded with copper ions. Halloysite nanotubes are a naturally occurring aluminosilicate mineral nanotubes with a hollow tubular structure, high specific surface area and good biocompatibility. Their inner cavities can efficiently load copper ions through ion exchange or adsorption, and they have the advantages of being non-toxic and having a precise and controllable copper loading amount.

[0027] In this invention, the copper loading in halloysite nanotubes is preferably 1%-20% of the mass of the halloysite nanotubes, and more preferably 5%-15%. This loading range can meet the effective copper ion concentration required for antibacterial activity while avoiding the risk of cytotoxicity caused by excessive loading, thus balancing safety and efficacy.

[0028] The present invention preferably uses halloysite nanotubes with a diameter of 30-100 nanometers and a length of 1-3 μm. This size range is conducive to the uniform dispersion of halloysite nanotubes in the hot melt adhesive matrix, preventing agglomeration, and at the same time, it is easy for macrophages to recognize and participate in the tissue repair process, thereby enhancing the local immune regulation effect.

[0029] The copper-containing microspheres provided by this invention can be prepared according to the following method: S11: Weigh 1-5 parts by weight of sodium alginate, dissolve it in 100 parts of purified water, and stir until completely dissolved to obtain a sodium alginate solution. S12: Add 0.5-3 parts by weight of calcium carbonate powder to sodium alginate solution and stir to form a uniform and stable sodium alginate-calcium carbonate composite suspension; S13: Weigh 5-10 parts by weight of halloysite nanotubes and disperse them in 50 parts of purified water to form a uniform nanotube suspension; while stirring, add the nanotube suspension to 100-150 parts by weight of 0.02-0.2 mol / L copper solution, and after centrifugation, washing and drying, obtain halloysite nanotube powder loaded with copper ions. Preferably, the copper solution in this step is a soluble copper salt solution, and more preferably, the copper solution includes, but is not limited to, copper sulfate solution and copper nitrate solution; Halloysite nanotube powder loaded with copper ions is mixed with 3-6 parts by weight of excipient (such as microcrystalline cellulose) and 1-4 parts by weight of binder (hydroxypropyl methylcellulose), and then extruded, spheroidized, dried and sieved to obtain microspheres with a particle size of 50-300 μm, namely copper-loaded microspheres. Since halloysite nanotubes loaded with copper ions are in powder form, while the next intermediate layer is liquid, direct stirring or spraying will cause the powder to clump and the coating to fail. Therefore, excipients and binders are added to form microspheres to obtain copper-loaded microspheres. Preferably, the particle size of the copper-loaded microspheres is 50-300 μm. S14: The prepared sodium alginate-calcium carbonate composite suspension is uniformly sprayed onto the surface of copper-loaded microspheres to obtain a coating thickness of 15-40 μm, forming primary embedded microspheres. S15: Spray an ethanol solution of ethyl cellulose (EC) onto the surface of the primary embedded microspheres with the intermediate layer. By controlling the spraying amount and time, a coating with a specific thickness of 20-50 μm is obtained to form the final multi-stage embedded microspheres, namely copper-containing microspheres.

[0030] In summary, the copper-containing microspheres provided by this invention are multi-level encapsulated copper-containing microspheres, with the following structure: a core consisting of halloysite nanotubes loaded with copper ions; a middle layer consisting of a pH-responsive polymer coating; and an outermost layer consisting of a controlled-release layer to control the dissolution rate. The overall particle size range of these multi-level encapsulated copper-containing microspheres is 100-500 μm, preferably 150-350 μm.

[0031] This multi-level encapsulated copper-containing microsphere, through a three-layer structure design of copper-loaded microspheres-sodium alginate / calcium carbonate-ethyl cellulose, achieves dual controlled release of copper ions, effectively avoiding burst release and prolonging the duration of action. The released copper ions exhibit broad-spectrum inhibitory effects on both Gram-positive and Gram-negative bacteria, demonstrating potent antibacterial capabilities. Copper ions can participate in the expression regulation of various growth factors (such as VEGF and TGF-β), helping to improve the rate of granulation tissue formation and re-epithelialization efficiency, and promoting wound healing. The copper-containing microspheres are not easily broken during processing and storage, and the hot melt adhesive matrix has good encapsulation and dispersibility, making the prepared hydrocolloid dressing reliable in structure and stable in performance.

[0032] Furthermore, the preferred hydrocolloid dressing of the present invention further includes a backing layer and a release layer respectively disposed on both sides of the sustained-release hydrocolloid layer. The backing layer is a semi-permeable polyurethane film or non-woven fabric, used to protect the dressing structure, prevent external contamination, and allow water vapor to pass through; the release layer is silicone kraft paper or a release film, peeled off before use to prevent the sustained-release hydrocolloid layer from sticking and being damaged.

[0033] The hydrocolloid dressing provided by this invention can be prepared according to the following method: S1: Preparation of copper-containing microspheres; S2: According to the formula, put the hot melt adhesive into the glue tank to melt for 30-60 minutes. While melting the adhesive, heat the reaction vessel, controlling the temperature range to 90-160℃. After the adhesive is melted, transfer all the hot melt adhesive in the glue tank to the reaction vessel, slowly add sodium carboxymethyl cellulose and stir. After stirring evenly, add the copper-containing microspheres prepared in S1 and continue stirring for 20-40 minutes until all raw materials are evenly mixed. The time from the start of adding materials to the time of even mixing should be controlled to 30-90 minutes to prepare the hydrocolloid slurry. S3: Apply the hydrocolloid slurry onto the base film backing layer, cover it with release paper, and obtain the hydrocolloid dressing.

[0034] The hydrocolloid dressing provided by the invention achieves an organic combination of gradient slow release of copper ions and long-lasting antibacterial and healing-promoting functions by constructing multi-level core-shell structured copper-containing microspheres and uniformly dispersing them in a hydrocolloid layer with a specific composition.

[0035] After the hydrocolloid dressing provided by this invention is applied to the wound surface, the wound exudate first penetrates into the sustained-release hydrocolloid layer, causing sodium carboxymethyl cellulose to rapidly absorb water and swell to form a hydrophilic gel, maintaining a moist healing environment. Simultaneously, moisture gradually invades the copper-containing microsphere structure: the outer ethyl cellulose controlled-release layer initially functions, limiting the rapid entry of moisture into the core area and slowing the release rate of copper ions; over time, moisture slowly penetrates the controlled-release layer and contacts the sodium alginate-calcium carbonate composite layer. When the wound is weakly acidic, the composite layer, due to the Ca... 2+ Cross-linking with sodium alginate forms a gel, increasing the density of the pH-responsive layer and effectively preventing burst release. As the wound gradually heals and the pH rises back to neutral / weakly alkaline, the cross-linking weakens, the sodium alginate gel becomes loose, and the controlled release of copper ions is initiated. Furthermore, water penetrates into the nucleus, causing the copper ions loaded in halloysite nanotubes to gradually desorb and diffuse outward. The released copper ions inhibit the growth of various common pathogenic bacteria such as Staphylococcus aureus and Escherichia coli. At the same time, trace amounts of copper ions activate fibroblasts and endothelial cells, promote collagen deposition and angiogenesis, and accelerate tissue regeneration.

[0036] In the hydrocolloid dressing provided by this invention, the release process of copper ions presents a gradient release trend of "stable in the early stage, continuous in the middle stage, and gradually weakening in the later stage", which meets the dynamic needs of wounds from the inflammatory stage to the proliferative stage and then to the remodeling stage.

[0037] The hydrocolloid dressing provided by this invention can be prepared into sheet dressings by conventional methods such as blending, extrusion, and coating, which is suitable for large-scale production and has good process feasibility. The prepared hydrocolloid dressing has multiple functions such as liquid absorption, moisturizing, antibacterial, healing promotion and self-adhesion, which helps to reduce the frequency of dressing changes and improve patient compliance.

[0038] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below.

[0039] Unless otherwise specified, the hot melt adhesives in the embodiments and comparative examples of this invention are all styrene-isoprene-styrene block copolymer (SIS) hot melt adhesives, the backing layer is all semi-permeable polyurethane film, and the release layer is all release film.

[0040] Example 1 This embodiment provides a method for preparing a hydrocolloid dressing, including the following steps: S1: Preparation of copper-containing microspheres: S11: Weigh 3 parts by weight of sodium alginate, dissolve it in 100 parts by weight of purified water, and stir until completely dissolved to obtain a sodium alginate solution. S12: Add 1 part by weight of calcium carbonate micro powder to sodium alginate solution and stir to form a uniform and stable sodium alginate-calcium carbonate composite suspension. S13: Weigh 8 parts by weight of halloysite nanotubes with a diameter of 70 nm and a length of 3 μm and disperse them in 50 parts by weight of purified water to form a uniform nanotube suspension; while stirring, add 120 parts by weight of 0.05 mol / L copper sulfate solution to the nanotube suspension, and after centrifugation, washing and drying, obtain halloysite nanotube powder loaded with copper ions; mix the halloysite nanotube powder loaded with copper ions with 5 parts by weight of excipient microcrystalline cellulose and 3 parts by weight of binder hydroxypropyl methylcellulose, and after extrusion, spheroidization, drying and sieving, obtain copper-loaded microspheres with a particle size of 200 μm; S14: The prepared sodium alginate-calcium carbonate composite suspension is uniformly sprayed onto the surface of copper-loaded microspheres to form primary embedded microspheres with a coating thickness of 25μm. S15: Spray the primary embedded microspheres with the intermediate layer onto the ethanol solution of EC. By controlling the spraying amount and time, a coating of a specific thickness of 30μm is obtained to form the final multi-level embedded microspheres, namely copper-containing microspheres. S2: Preparation of hydrocolloid slurry containing multi-stage embedded copper microspheres: Take 53 parts by weight of hot melt adhesive and put it into the glue tank to melt for 45 minutes. While melting the adhesive, heat the reactor at 160°C. After melting, pump all the hot melt adhesive in the glue tank into the reactor and slowly add 35 parts by weight of sodium carboxymethyl cellulose while stirring. After stirring evenly, add 12 parts of the multi-stage embedded copper microspheres prepared by S1 and continue stirring for 30 minutes until all raw materials are evenly mixed to prepare the hydrocolloid slurry. S3: Apply the above hydrocolloid slurry onto the base film, cover it with release paper, and obtain the hydrocolloid dressing.

[0041] Example 2 This embodiment provides a method for preparing a hydrocolloid dressing, including the following steps: S1: Preparation of copper-containing microspheres: S11: Weigh 3 parts by weight of sodium alginate, dissolve it in 100 parts by weight of purified water, and stir until completely dissolved to obtain a sodium alginate solution. S12: Add 1 part by weight of calcium carbonate micro powder to sodium alginate solution and stir to form a uniform and stable sodium alginate-calcium carbonate composite suspension. S13: Weigh 5 parts by weight of halloysite nanotubes with a diameter of 50 nm and a length of 1 μm and disperse them in 50 parts by weight of purified water to form a uniform nanotube suspension; while stirring, add 100 parts by weight of 0.02 mol / L copper sulfate solution to the nanotube suspension, and after centrifugation, washing and drying, obtain halloysite nanotube powder loaded with copper ions; mix the halloysite nanotube powder loaded with copper ions with 5 parts by weight of excipient microcrystalline cellulose and 3 parts by weight of binder hydroxypropyl methylcellulose, and after extrusion, spheroidization, drying and sieving, obtain copper-loaded microspheres with a particle size of 200 μm; S14: The prepared sodium alginate-calcium carbonate composite suspension is uniformly sprayed onto the surface of copper-loaded microspheres to form primary embedded microspheres with a coating thickness of 20μm. S15: Spray the primary embedded microspheres with the intermediate layer onto the ethanol solution of EC. By controlling the spraying amount and time, a coating with a specific thickness of 25μm is obtained to form the final multi-level embedded microspheres, namely copper-containing microspheres. S2: Preparation of hydrocolloid slurry containing multi-stage embedded copper microspheres: Take 60 parts by weight of hot melt adhesive and put it into the glue tank to melt for 45 minutes. While melting the adhesive, heat the reactor at 160℃. After melting, pump all the hot melt adhesive in the glue tank into the reactor and slowly add 30 parts by weight of sodium carboxymethyl cellulose while stirring. After stirring evenly, add 10 parts of the multi-stage embedded copper microspheres prepared by S1 and continue stirring for 30 minutes until all raw materials are evenly mixed to prepare the hydrocolloid slurry. S3: Apply the above hydrocolloid slurry onto the base film, cover it with release paper, and obtain the hydrocolloid dressing.

[0042] Example 3 This embodiment provides a method for preparing a hydrocolloid dressing, including the following steps: S1: Preparation of copper-containing microspheres: S11: Weigh 3 parts by weight of sodium alginate, dissolve it in 100 parts by weight of purified water, and stir until completely dissolved to obtain a sodium alginate solution. S12: Add 1 part by weight of calcium carbonate micro powder to sodium alginate solution and stir to form a uniform and stable sodium alginate-calcium carbonate composite suspension. S13: Weigh 0 parts by weight of halloysite nanotubes with a diameter of 100 nm and a length of 3 μm and disperse them in 50 parts by weight of purified water to form a uniform nanotube suspension; while stirring, add the nanotube suspension to 150 parts by weight of 0.2 mol / L copper sulfate solution, and after centrifugation, washing, and drying, obtain halloysite nanotube powder loaded with copper ions; mix the halloysite nanotube powder loaded with copper ions with 5 parts by weight of excipient microcrystalline cellulose and 3 parts by weight of binder hydroxypropyl methylcellulose, and after extrusion, spheroidization, drying, and sieving, obtain copper-loaded microspheres with a particle size of 200 μm; S14: The prepared sodium alginate-calcium carbonate composite suspension is uniformly sprayed onto the surface of copper-loaded microspheres to form primary embedded microspheres with a coating thickness of 30μm. S15: Spray the primary embedded microspheres with the intermediate layer onto the ethanol solution of EC. By controlling the spraying amount and time, a coating with a specific thickness of 35μm is obtained to form the final multi-level embedded microspheres, namely copper-containing microspheres. S2: Preparation of hydrocolloid slurry containing multi-stage embedded copper microspheres: Take 60 parts by weight of hot melt adhesive and put it into the glue tank to melt for 45 minutes. While melting the adhesive, heat the reactor at 160℃. After melting, pump all the hot melt adhesive in the glue tank into the reactor and slowly add 25 parts by weight of sodium carboxymethyl cellulose while stirring. After stirring evenly, add 15 parts of the multi-stage embedded copper microspheres prepared by S1 and continue stirring for 30 minutes until all raw materials are evenly mixed to prepare the hydrocolloid slurry. S3: Apply the above hydrocolloid slurry onto the base film, cover it with release paper, and obtain the hydrocolloid dressing.

[0043] In this invention, all comparative examples are compared with Example 1.

[0044] Comparative Example 1 This comparative example provides a method for preparing a hydrocolloid dressing, comprising the following steps: S1: Preparation of hydrocolloid slurry containing copper microspheres without multi-stage encapsulation: Take 53 parts by weight of hot melt adhesive and put it into the glue tank to melt for 45 minutes. While melting the adhesive, heat the reaction vessel and control the temperature at 160℃. After the adhesive is melted, pump all the hot melt adhesive in the glue tank into the reaction vessel, slowly add 35 parts by weight of sodium carboxymethyl cellulose and stir until all raw materials are stirred evenly to prepare a hydrocolloid slurry. S2: Apply the above hydrocolloid slurry onto the base film, cover it with release paper, and obtain the hydrocolloid dressing.

[0045] Comparative Example 2 This comparative example provides a method for preparing a hydrocolloid dressing, comprising the following steps: S1: Preparation of hydrocolloid slurry: Take 53 parts by weight of hot melt adhesive and put it into the glue tank to melt for 45 minutes. While melting the adhesive, heat the reaction vessel at 160℃. After melting, pump all the hot melt adhesive in the glue tank into the reaction vessel, slowly add 35 parts by weight of sodium carboxymethyl cellulose and stir. After stirring evenly, add 12 parts of 0.05 mol / L copper sulfate solution and continue stirring for 30 minutes until all raw materials are evenly mixed to prepare a hydrocolloid slurry. S2: Apply the above hydrocolloid slurry onto the base film, cover it with release paper, and obtain the hydrocolloid dressing.

[0046] Comparative Example 3 This comparative example provides a method for preparing a hydrocolloid dressing, comprising the following steps: S1: Preparation of monolayer-embedded copper-containing microspheres: S11: Weigh 8 parts by weight of halloysite nanotubes with a diameter of 70 nm and a length of 3 μm and disperse them in 50 parts by weight of purified water to form a uniform nanotube suspension; while stirring, add 120 parts by weight of 0.05 mol / L copper sulfate solution to the nanotube suspension, and after centrifugation, washing and drying, obtain halloysite nanotube powder loaded with copper ions; mix the halloysite nanotube powder loaded with copper ions with 5 parts by weight of excipient microcrystalline cellulose and 3 parts by weight of binder hydroxypropyl methylcellulose, and after extrusion, spheroidization, drying and sieving, obtain copper-loaded microspheres with a particle size of 200 μm; S12: Copper-loaded microspheres are sprayed with an ethanol solution of EC. By controlling the spraying amount and time, a coating with a specific thickness of 30 μm is obtained to form a single layer of embedded copper-containing microspheres. S2: Preparation of hydrocolloid slurry: Take 53 parts by weight of hot melt adhesive and put it into the glue tank to melt for 45 minutes. While melting the adhesive, heat the reaction vessel at 160°C. After melting, pump all the hot melt adhesive in the glue tank into the reaction vessel and slowly add 35 parts by weight of sodium carboxymethyl cellulose while stirring. After stirring evenly, add 12 parts of the monolayer embedded copper microspheres prepared in S1 and continue stirring for 30 minutes until all raw materials are evenly mixed to prepare the hydrocolloid slurry. S3: Apply the above hydrocolloid slurry onto the base film, cover it with release paper, and obtain the hydrocolloid dressing.

[0047] The performance of the hydrocolloid dressings prepared in the above embodiments and comparative examples was tested using the following methods: Antibacterial properties: According to GB / T 20944.3-2008 Evaluation of antibacterial properties of textiles - Part 3: Shaking method, the inhibition rate against Escherichia coli (ATCC 8099) and Staphylococcus aureus (ATCC 6538) was tested, and the counts were performed after shaking and incubation for 24 hours.

[0048] Antibacterial durability: The hydrocolloid dressing was placed in a 37°C constant temperature incubator for 7 days, and the above antibacterial test was repeated to compare the antibacterial rate after 7 days. In vitro pH-responsive release validation: To simulate the microenvironment of different stages of wound healing, samples were taken at predetermined time points (1, 24, 48, 72, 96, 120, 144, 168 h) in an acidic environment (acetic acid-sodium acetate buffer, pH 5.8) during the simulated infection period and a neutral / alkaline environment (phosphate buffer, pH 7.4) during the healing period, according to the sodium diethyldithiocarbamate spectrophotometric method for the determination of copper in water quality (HJ 485-2009). The concentration of copper ions in the extract per unit time was measured.

[0049] The test results are shown in Tables 1-3.

[0050] Table 1. Results of antibacterial properties and antibacterial durability of hydrocolloid dressings Example 1 Escherichia coli >99%, Staphylococcus aureus >99% Escherichia coli >99%, Staphylococcus aureus >99% Example 2 Escherichia coli >99%, Staphylococcus aureus >99% Escherichia coli >98%, Staphylococcus aureus >98% Example 3 Escherichia coli >99%, Staphylococcus aureus >99% Escherichia coli >97%, Staphylococcus aureus >98% Comparative Example 1 No antibacterial properties No antibacterial properties Comparative Example 2 Escherichia coli >99%, Staphylococcus aureus >99% Escherichia coli 65%, Staphylococcus aureus 78% Comparative Example 3 Escherichia coli >99%, Staphylococcus aureus >99% Escherichia coli 85%, Staphylococcus aureus 91% Table 2. Release validation at pH 5.8 for 168 hours in vitro (μg / mL) Example 1 12.1 22.3 30.6 36.7 33.1 31.8 26.9 24.5 Example 2 9.8 16.5 23.8 29.4 25.4 19.7 14.8 12.9 Example 3 13.2 20.1 28.3 34.8 27.9 24.4 20.6 17.7 Comparative Example 1 / / / / / / / / Comparative Example 2 34.8 40.2 49.1 28.9 25.3 16.1 11.8 6.9 Comparative Example 3 10.3 23.4 27.1 32.6 30.9 27.3 23.9 20.1 Table 3. Release validation at pH 7.4 for 168 hours in vitro (μg / mL) Example 1 26.3 41.0 54.7 63.2 52.2 47.6 42.1 36.8 Example 2 19.3 34.1 45.2 53.7 46.2 40.4 33.8 27.2 Example 3 23.4 38.2 49.4 57.1 49.8 44.6 37.3 30.7 Comparative Example 1 / / / / / / / / Comparative Example 2 35.3 38.6 47.2 26.0 22.5 14.3 10.7 7.4 Comparative Example 3 9.8 25.3 29.6 34.7 29.5 25.6 24.7 22.9 As can be seen from the data in the table above, the hydrocolloid dressings prepared in each embodiment of the present invention all have excellent antibacterial properties and in vitro pH-responsive release properties.

[0051] The difference between Comparative Example 1 and Example 1 is that no copper-containing functional components were added; it was only a traditional hydrocolloid matrix, and therefore did not have antibacterial properties or release copper ions.

[0052] The difference between Comparative Example 2 and Example 1 is that no sustained-release structure was used; the copper salt solution was directly added to the hydrocolloid matrix. The results showed that this dressing suffered from a severe copper ion burst release problem, leading to a high initial risk of cytotoxicity and a lack of sustained antibacterial efficacy.

[0053] The difference between Comparative Example 3 and Example 1 is that the sodium alginate-calcium carbonate pH-responsive intermediate layer was omitted, and only a single-layer encapsulation structure consisting of a halloysite copper-loaded core and an ethyl cellulose outer layer was used. The results show that although this hydrocolloid dressing has a certain sustained-release capacity, it does not possess intelligent pH-responsive characteristics and cannot dynamically adjust its release behavior according to changes in the wound environment.

[0054] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A hydrocolloid dressing, characterized in that, It includes a slow-release hydrocolloid layer; the raw materials of the slow-release hydrocolloid layer, by weight, include the following components: 10-35 parts of sodium carboxymethyl cellulose; 5-15 parts containing copper microspheres; 40-70 parts hot melt adhesive; The copper-containing microspheres include a core and a shell covering the outer side of the core; The core is a copper-loaded microsphere; The shell includes a sodium alginate-calcium carbonate composite layer; The shell also includes a controlled-release layer covering the outside of the sodium alginate-calcium carbonate composite layer; The controlled-release layer is an ethyl cellulose layer.

2. The hydrocolloid dressing as described in claim 1, characterized in that, The thickness of the sodium alginate-calcium carbonate composite layer is 15-40 μm.

3. The hydrocolloid dressing as described in claim 1, characterized in that, The thickness of the ethyl cellulose layer is 20-50 μm.

4. The hydrocolloid dressing according to any one of claims 1-3, characterized in that, The copper-loaded microspheres are halloysite nanotubes loaded with copper ions.

5. The hydrocolloid dressing as described in claim 4, characterized in that, In the halloysite nanotubes loaded with copper ions, the loading amount of copper element is 1%-20% of the mass of the halloysite nanotubes.

6. The hydrocolloid dressing as described in claim 4, characterized in that, The halloysite nanotubes have a diameter of 30-100 nanometers.

7. The hydrocolloid dressing as described in claim 4, characterized in that, The halloysite nanotubes have a length of 1-3 μm.

8. The hydrocolloid dressing as described in claim 4, characterized in that, It also includes a backing layer and a release layer respectively disposed on both sides of the slow-release hydrocolloid layer.