Multi-effect medical wound healing patch and preparation method thereof

Abstract

The present application relates to the technical field of medical wound healing patch, and discloses a multi-effect medical wound healing patch and a preparation method thereof, which comprises a three-layer composite structure, the three-layer composite structure is sequentially arranged from the side of contacting wound surface to the outer side as follows: an inner hydrogel matrix layer, a middle drug-loaded functional layer and an outer high-elasticity supporting layer; the inner hydrogel matrix layer comprises the following components by weight percentage: 5-20% of hydrophilic polymer, 0.5-10% of natural polysaccharide, 3-15% of moisturizing factor, 0.05-2% of natural bacteriostatic component, and the balance of water. The three-layer composite structure of the inner hydrogel matrix layer (thickness 0.5-3mm)-the middle drug-loaded functional layer (thickness 0.1-1mm, drug-loaded microspheres account for 10-60%)-the outer high-elasticity supporting layer (thickness 0.05-0.3mm) is constructed, the spatial partition of function and the time coordination integration are realized, and the fundamental contradiction that the existing dressing has single function and cannot cover the whole cycle demand of wound healing (anti-infection-promoting healing-suppression of scar) is solved.

Description

Technical Field

[0001] This invention patent relates to the field of medical wound healing patch technology, specifically a multi-effect medical wound healing patch and its preparation method. Background Technology

[0002] Repairing full-thickness skin injuries is a complex and ordered biological process, including the hemostasis phase, inflammation phase, proliferation phase, and remodeling phase. Each phase has different functional requirements for dressings: in the early stage, they need to fight infection, manage exudate, and reduce inflammation; in the middle stage, they need to promote cell migration and angiogenesis; and in the later stage, they need to inhibit excessive fibroblast proliferation and abnormal collagen deposition to prevent scar hyperplasia.

[0003] Existing dressings mostly meet only one or some needs:

[0004] Traditional dressings (gauze, cotton pads): mainly serve to cover and absorb, but they are prone to adhering to the wound surface, causing secondary damage, and cannot provide a moist environment, thus delaying healing.

[0005] Modern functional dressings: hydrogel / hydrocolloid dressings: can provide a moist environment and relieve pain, but have poor mechanical properties, lack active anti-infection and anti-scarring capabilities, and the drugs are mostly simple admixtures with uncontrollable release behavior.

[0006] Silver / antibiotic dressings: They can effectively fight infection, but there are risks of antibiotic resistance, silver ion cytotoxicity and drug burst release, and they do not have anti-scarring function.

[0007] Silicone scar patches / gels: They can improve existing hypertrophic scars to some extent, but their mechanism of action is passive (closing hydration), making them unsuitable for acute wounds, and they have no healing-promoting or anti-infective activity.

[0008] Growth factor dressings can promote granulation tissue growth, but the factors have poor stability, short half-life, high cost, and cannot inhibit subsequent scarring.

[0009] Despite the abundance of existing technologies, several significant shortcomings remain in practical applications and effectiveness.

[0010] The contradiction between functional singularity and the need for comprehensive repair: Existing products struggle to meet the diverse needs across the entire repair cycle, from "anti-infection" to "scar suppression," with a single integrated solution. This invention provides synergistic support for each repair stage through a three-layer composite structure (corresponding to claim 1): "inner layer promoting healing - middle layer time-controlled release - outer layer mechanical regulation."

[0011] Drug release behavior is out of sync with the healing process: Simply mixing drugs with different release kinetics (such as fast-acting antibiotics and long-acting anti-scar drugs) cannot achieve precise timing matching of release.

[0012] The physical and chemical properties of dressings are not compatible with the dynamic microenvironment of the wound: Traditional dressings passively respond to the wound and cannot dynamically adjust humidity, oxygen permeability and mechanical environment.

[0013] Poor interface performance includes adhesion, loose fit, and poor comfort. The optimized composition of the inner hydrogel in this invention provides excellent biocompatibility and non-adhesive properties, while the composite structure design ensures overall conformability.

[0014] In view of this, we propose a multi-effect medical wound healing patch and its preparation method.

[0015] Invention Patent Content

[0016] The purpose of this invention is to provide a multi-effect medical wound healing patch and its preparation method to solve the problems existing in the background art.

[0017] To achieve the above objectives, this invention provides the following technical solution:

[0018] A multi-effect medical wound healing patch includes a three-layer composite structure, which, from the side in contact with the wound to the outside, consists of: an inner hydrogel matrix layer, a middle drug-loaded functional layer, and an outer highly elastic support layer.

[0019] The inner hydrogel matrix layer, by weight percentage, comprises the following components:

[0020] Hydrophilic polymers 5%-20%;

[0021] Natural polysaccharides 0.5%-10%;

[0022] Moisturizing factor 3%-15%;

[0023] Natural antibacterial ingredients: 0.05%-2%;

[0024] The remainder is water;

[0025] The intermediate drug-loaded functional layer is composed of drug-loaded microspheres dispersed in a second polymer matrix, wherein the mass percentage of the drug-loaded microspheres in the intermediate drug-loaded functional layer is 10%-60%.

[0026] The drug-loaded microspheres include a first type of drug-loaded microspheres and a second type of drug-loaded microspheres. The first type of drug-loaded microspheres are loaded with an antibacterial agent, and the second type of drug-loaded microspheres are loaded with an antiproliferative cytokine inhibitor.

[0027] The outer high-elasticity support layer is an elastomeric film with a breathable microporous structure;

[0028] The inner hydrogel matrix layer has a thickness of 0.5-3 mm, the intermediate drug-carrying functional layer has a thickness of 0.1-1 mm, and the outer high-elasticity support layer has a thickness of 0.05-0.3 mm.

[0029] Preferably, the hydrophilic polymer is selected from at least one of polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate, and polyacrylamide; the natural polysaccharide is selected from at least one of hyaluronic acid, sodium alginate, carboxymethyl chitosan, and sulfonated chitosan; the moisturizing factor is glycerin or sorbitol; and the natural antibacterial ingredient is selected from at least one of tea polyphenols, paeonol, and baicalin.

[0030] Preferably, the first type of drug-loaded microspheres and the second type of drug-loaded microspheres are microspheres with different degradation or swelling properties;

[0031] The first type of drug-loaded microspheres are prepared from a first carrier material that can be rapidly degraded or swollen in the wound microenvironment. The first carrier material is selected from at least one of gelatin, calcium alginate, and low molecular weight polylactic acid-glycolic acid copolymer.

[0032] The second type of drug-loaded microspheres are prepared from a second carrier material that slowly degrades in the wound microenvironment. The second carrier material is selected from at least one of high molecular weight polylactic acid-glycolic acid copolymer, polycaprolactone, and polylactic acid.

[0033] Preferably, the antibacterial agent is selected from at least one of levofloxacin hydrochloride, mupirocin, and silver sulfadiazine; the antiproliferative cytokine inhibitor is selected from at least one of anti-transforming growth factor-β1 antibody, anti-connective tissue growth factor antibody, Decorin, and Halofuginone.

[0034] Preferably, the second polymer matrix is ​​a hydrogel or hydrocolloid, and its composition may be the same as or different from that of the inner hydrogel matrix layer.

[0035] Preferably, the elastomer of the outer high-elasticity support layer is thermoplastic polyurethane, silicone rubber, or styrene-ethylene-butene-styrene block copolymer; the average pore size of the breathable microporous structure is 1-50 micrometers, and the porosity is 30%-70%.

[0036] Preferably, the mass ratio of the first type of drug-loaded microspheres to the second type of drug-loaded microspheres in the intermediate drug-loaded functional layer is 1:5 to 5:1.

[0037] Preferably, the outer surface of the outer high-elasticity support layer is further covered with a medical pressure-sensitive adhesive layer, and the medical pressure-sensitive adhesive layer is covered with release paper.

[0038] A method for creating a multi-effect medical wound healing patch includes the following steps:

[0039] S1. Preparation of the inner hydrogel matrix layer: The hydrophilic polymer, natural polysaccharide, moisturizing factor and natural antibacterial component are dissolved or dispersed in water to form a first homogeneous solution, which is then injected into a mold and cured by physical crosslinking or chemical crosslinking to form the inner hydrogel matrix layer.

[0040] S2. Preparation of intermediate drug-loading functional layer:

[0041] S2.1. Prepare first-type drug-loaded microspheres and second-type drug-loaded microspheres respectively: use emulsification-solvent evaporation method, spray drying method or ion gel method to encapsulate the antibacterial agent in the first carrier material and encapsulate the antiproliferative cytokine inhibitor in the second carrier material respectively;

[0042] S2.2. The first type of drug-loaded microspheres and the second type of drug-loaded microspheres obtained in step S2.1 are uniformly dispersed in the prepolymer solution constituting the second polymer matrix, coated on the surface of the inner hydrogel matrix layer obtained in step S1, and formed an intermediate drug-loaded functional layer composite on the inner hydrogel matrix layer by crosslinking or drying and curing.

[0043] S3. Preparation of outer high-elasticity support layer: Prepare an elastomer film with a breathable microporous structure by using phase separation method, pore-forming agent method or foaming process;

[0044] S4. Composite: The outer high-elasticity support layer obtained in step S3 is composited to the other side of the inner hydrogel matrix layer with the intermediate drug-carrying functional layer obtained in step S2 using an adhesive or hot pressing method, to obtain a three-layer composite structure. Optionally, medical pressure-sensitive adhesive is coated on the outer surface of the outer high-elasticity support layer and covered with release paper to obtain the multi-effect medical wound healing patch.

[0045] Preferably, in step S2.1, when preparing drug-loaded microspheres using the emulsification-solvent evaporation method, the average particle size of the first type of drug-loaded microspheres is 1-10 micrometers, and the average particle size of the second type of drug-loaded microspheres is 10-50 micrometers.

[0046] By employing the above technical solution, this invention patent provides a multi-effect medical wound healing patch and its preparation method. It possesses at least the following beneficial effects:

[0047] This invention patent constructs a three-layer composite structure consisting of an inner hydrogel matrix layer (thickness 0.5-3mm), an intermediate drug-loaded functional layer (thickness 0.1-1mm, with drug-loaded microspheres accounting for 10%-60%), and an outer high-elasticity support layer (thickness 0.05-0.3mm). This achieves spatial partitioning and temporal synergistic integration of functions, solving the fundamental contradiction that existing dressings have limited functions and cannot cover the full-cycle needs of wound healing, including "anti-infection, promoting healing, and inhibiting scarring."

[0048] By designing and preparing a first type of drug-loaded microspheres composed of rapidly degradable materials (such as gelatin and calcium alginate) and a second type of drug-loaded microspheres composed of slowly degradable materials (such as high molecular weight PLGA and PCL), and controlling their mass ratio in the intermediate layer to be 1:5 to 5:1, the time-controlled release of antibacterial agents and anti-proliferation inhibitors was achieved, solving the problems of mismatch between drug release behavior and healing physiological process, drug efficacy conflict or waste in traditional medicated dressings;

[0049] By limiting the inner hydrogel to contain a specific proportion (5%-20%) of hydrophilic polymers and (0.5%-10%) of natural polysaccharides (such as hyaluronic acid and carboxymethyl chitosan), and combining it with a highly elastic support layer with a specific microporous structure (pore size 1-50μm, porosity 30%-70%), dynamic and active regulation of wound humidity, oxygen permeability and mechanical microenvironment is achieved, solving the problem of traditional dressings being passive in response to changes in the microenvironment and having insufficient regulatory capacity.

[0050] By optimizing the composition and cross-linking degree of the inner hydrogel and carefully designing the thickness and composite interface of each layer, excellent dressing-wound interface performance and overall user experience were achieved, solving the problems of dressing adhesion leading to secondary damage, poor adhesion leading to exudate leakage or bacterial invasion, and poor patient comfort.

[0051] By adopting a stepwise preparation method (first preparing the inner layer and microspheres, then coating the composite intermediate layer, and finally composite the outer layer), and controlling key process parameters (such as microsphere particle size: 1-10μm for the first type and 10-50μm for the second type), stable and controllable preparation of complex and functionally integrated three-layer composite dressings has been achieved. This has solved the technical problems of difficult processing of multi-layer functional dressings, weak interlayer bonding, uneven distribution of active ingredients, or easy inactivation. Detailed Implementation

[0052] The technical solutions in the embodiments of this patent will be clearly and completely described below with reference to the present invention. Obviously, the described embodiments are only a part of the embodiments of this patent, and not all of them. Based on the embodiments of this patent, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this patent.

[0053] This invention provides a multi-effect medical wound healing patch, comprising a three-layer composite structure, wherein the three-layer composite structure, from the side in contact with the wound to the outside, consists of: an inner hydrogel matrix layer, a middle drug-loaded functional layer, and an outer highly elastic support layer.

[0054] The inner hydrogel matrix layer, by weight percentage, comprises the following components:

[0055] Hydrophilic polymers 5%-20%;

[0056] Natural polysaccharides 0.5%-10%;

[0057] Moisturizing factor 3%-15%;

[0058] Natural antibacterial ingredients: 0.05%-2%;

[0059] The remainder is water;

[0060] The intermediate drug-loaded functional layer is composed of drug-loaded microspheres dispersed in a second polymer matrix, wherein the mass percentage of the drug-loaded microspheres in the intermediate drug-loaded functional layer is 10%-60%.

[0061] The drug-loaded microspheres include a first type of drug-loaded microspheres and a second type of drug-loaded microspheres. The first type of drug-loaded microspheres are loaded with an antibacterial agent, and the second type of drug-loaded microspheres are loaded with an antiproliferative cytokine inhibitor.

[0062] The outer high-elasticity support layer is an elastomeric film with a breathable microporous structure;

[0063] The inner hydrogel matrix layer has a thickness of 0.5-3 mm, the intermediate drug-carrying functional layer has a thickness of 0.1-1 mm, and the outer high-elasticity support layer has a thickness of 0.05-0.3 mm.

[0064] The hydrophilic polymer is selected from at least one of polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate, and polyacrylamide; the natural polysaccharide is selected from at least one of hyaluronic acid, sodium alginate, carboxymethyl chitosan, and sulfonated chitosan; the moisturizing factor is glycerin or sorbitol; and the natural antibacterial ingredient is selected from at least one of tea polyphenols, paeonol, and baicalin.

[0065] It should be noted that at this concentration, the hydrophilic polymer can form a three-dimensional network with suitable mechanical strength and efficient water absorption and retention capacity, which forms the framework of the hydrogel. The addition of natural polysaccharides not only enhances the system's moisturizing properties and biocompatibility, but their inherent bioactivity (such as hyaluronic acid's cell migration-promoting effect and carboxymethyl chitosan's hemostatic and healing-promoting effects) actively participates in wound repair. Moisturizing factors are used to regulate the softness of the hydrogel and prevent excessive water evaporation. Natural antibacterial components provide a gentle antibacterial barrier in the early stages of wound healing, helping to control inflammation and reduce immediate dependence on antibiotics. The remaining water serves as a solvent and is a major component of the final gel.

[0066] The first type of drug-loaded microspheres and the second type of drug-loaded microspheres are microspheres with different degradation or swelling properties;

[0067] The first type of drug-loaded microspheres are prepared from a first carrier material that can be rapidly degraded or swollen in the wound microenvironment. The first carrier material is selected from at least one of gelatin, calcium alginate, and low molecular weight polylactic acid-glycolic acid copolymer.

[0068] The second type of drug-loaded microspheres are prepared from a second carrier material that slowly degrades in the wound microenvironment. The second carrier material is selected from at least one of high molecular weight polylactic acid-glycolic acid copolymer, polycaprolactone, and polylactic acid.

[0069] It should be noted that the first type of drug-loaded microspheres uses materials that can rapidly degrade or swell in the wound microenvironment (such as gelatin and calcium alginate). This aims to respond to the abundant proteases or specific ion concentrations in the inflammatory exudate during the early stages of wound healing, achieving rapid release of antibacterial drugs to control the risk of infection during the golden window period. The second type of drug-loaded microspheres uses materials that degrade slowly (such as high molecular weight PLGA and PCL), with degradation cycles lasting up to several weeks. This allows for synchronization with the wound's proliferation and remodeling phases, achieving long-term sustained release of anti-proliferative drugs and thus continuously inhibiting scar formation. The difference in degradation characteristics between the two types of materials is the physical basis for achieving "time-controlled release."

[0070] The antibacterial agent is selected from at least one of levofloxacin hydrochloride, mupirocin, and silver sulfadiazine; the antiproliferative cytokine inhibitor is selected from at least one of anti-transforming growth factor-β1 antibody, anti-connective tissue growth factor antibody, Decorin, and Halofuginone.

[0071] It should be noted that the antibacterial agents (levofloxacin hydrochloride, mupirocin, and silver sulfadiazine) are all broad-spectrum, highly effective topical anti-infective drugs that can effectively cover common pathogens on skin wounds. The selected anti-proliferative cytokine inhibitors (anti-TGF-β1 antibody, anti-CTGF antibody, Decorin, and Halofuginone) are all proven to specifically block key signaling pathways in scar formation (such as TGF-β / Smad). Encapsulating them separately allows these two classes of drugs, with their distinct mechanisms of action (antibacterial and anti-scarring), to work synergistically and without interference within a single system.

[0072] The second polymer matrix is ​​a hydrogel or hydrocolloid, and its composition may be the same as or different from that of the inner hydrogel matrix layer;

[0073] It should be noted that the second polymer matrix, as the continuous phase of the intermediate drug-loaded functional layer, mainly functions to fix and disperse the drug-loaded microspheres and to act as a medium for bonding with the inner layer. Its composition can be the same as that of the inner layer (such as an integrated crosslinking not explicitly stated in the examples but which can be inferred) to achieve seamless integration; or it can be different, for example, using other hydrogels or hydrocolloids such as sodium alginate or sodium carboxymethyl cellulose to impart specific physicochemical properties to the intermediate layer (such as ionic crosslinking strength and adhesion), thereby assisting drug release or enhancing interlayer stability.

[0074] The elastomer of the outer high-elasticity support layer is thermoplastic polyurethane, silicone rubber, or styrene-ethylene-butene-styrene block copolymer; the average pore size of the breathable microporous structure is 1-50 micrometers, and the porosity is 30%-70%.

[0075] It should be noted that the average pore size of the outer membrane is limited to 1-50 micrometers, and the porosity is 30%-70%, based on a balance between antibacterial properties and breathability. This pore size range is sufficient to effectively block most bacteria in the environment (typically >1 micrometer in size) from passing through, while allowing water vapor molecules (much smaller than 1 micrometer in size) to diffuse freely, thus maintaining appropriate moisture permeability while protecting the wound and preventing fluid accumulation. Porosity within this range ensures that the membrane possesses both good flexibility and sufficient mechanical strength.

[0076] The mass ratio of the first type of drug-loaded microspheres to the second type of drug-loaded microspheres in the intermediate drug-loaded functional layer is 1:5 to 5:1;

[0077] It should be noted that limiting the mass ratio of the first to the second type of drug-loaded microspheres to 1:5 to 5:1 provides crucial clinical adjustability for this invention. Physicians can select the optimal ratio within this range based on wound assessments (such as the degree of contamination, infection risk, and the tendency for scar hyperplasia at the site). For example, a ratio leaning towards 5:1 can be used for contaminated wounds to enhance anti-infection efforts; a ratio leaning towards 1:5 can be used for clean surgical incisions to focus on anti-scarring. This parameter is central to achieving individualized, precise treatment.

[0078] The outer surface of the outer high-elasticity support layer is also covered with a medical pressure-sensitive adhesive layer, and the medical pressure-sensitive adhesive layer is covered with release paper;

[0079] It should be noted that placing a medical-grade pressure-sensitive adhesive layer on the outer surface of the high-elasticity support layer and covering it with release paper ensures the product's ease of use and reliable fixation. This pressure-sensitive adhesive must be a medical-grade product with low allergenicity, suitable adhesion, and no residue upon removal to ensure the wound dressing adheres firmly to the surrounding normal skin, preventing dressing displacement that could affect efficacy or cause contamination.

[0080] A method for creating a multi-effect medical wound healing patch includes the following steps:

[0081] S1. Preparation of the inner hydrogel matrix layer: The hydrophilic polymer, natural polysaccharide, moisturizing factor and natural antibacterial component are dissolved or dispersed in water to form a first homogeneous solution, which is then injected into a mold and cured by physical crosslinking or chemical crosslinking to form the inner hydrogel matrix layer.

[0082] It should be noted that solidifying the first homogeneous solution through physical cross-linking (such as freeze-thaw) or chemical cross-linking (such as ionic cross-linking and photocross-linking) is crucial for forming a hydrogel with a stable three-dimensional network structure. The cross-linking method and degree directly determine the swelling properties, mechanical strength, and degradation behavior of the hydrogel. The most suitable method should be selected based on the characteristics of the chosen polymer (e.g., PVA is suitable for freeze-thaw, and sodium alginate is suitable for ionic cross-linking) to ensure that the inner layer possesses the wetting, healing, and non-adhesive properties described in the instructions.

[0083] S2. Preparation of intermediate drug-loading functional layer:

[0084] S2.1. Prepare first-type drug-loaded microspheres and second-type drug-loaded microspheres respectively: use emulsification-solvent evaporation method, spray drying method or ion gel method to encapsulate the antibacterial agent in the first carrier material and encapsulate the antiproliferative cytokine inhibitor in the second carrier material respectively;

[0085] It should be noted that the use of emulsification-solvent evaporation and ionogel methods to prepare drug-loaded microspheres is a core process for controlling microsphere particle size, drug loading, and release kinetics. For example, the emulsification-solvent evaporation method can precisely control the particle size of synthetic polymer microspheres such as PLGA by adjusting the emulsification rate and stabilizer concentration. Ionogel methods can rapidly and gently prepare natural polymer microspheres such as calcium alginate. The choice of method must be matched with the properties of the carrier material and the drug.

[0086] S2.2. The first type of drug-loaded microspheres and the second type of drug-loaded microspheres obtained in step S2.1 are uniformly dispersed in the prepolymer solution constituting the second polymer matrix, coated on the surface of the inner hydrogel matrix layer obtained in step S1, and formed an intermediate drug-loaded functional layer composite on the inner hydrogel matrix layer by crosslinking or drying and curing.

[0087] It should be noted that uniformly dispersing the drug-loaded microspheres in a prepolymer solution of the second polymer matrix, then coating them onto the inner layer surface and curing them, achieves a strong composite between the intermediate and inner layers and ensures the uniform distribution of microspheres within the functional layers. Uniform distribution is crucial for ensuring the uniformity and repeatability of drug release. The coating thickness and curing conditions must be precisely controlled to obtain a uniformly thick and structurally complete intermediate drug-loaded functional layer.

[0088] S3. Preparation of outer high-elasticity support layer: Prepare an elastomer film with a breathable microporous structure by using phase separation method, pore-forming agent method or foaming process;

[0089] It is worth noting that the preparation of microporous elastomer films using phase separation, pore-forming agent methods, or foaming processes is a core step in endowing the outer highly elastic support layer with air permeability. These methods can create an interconnected microporous network within the elastomer matrix. For example, phase separation utilizes the exchange of solvent and non-solvent to form pores; pore-forming agent methods involve adding soluble microparticles followed by elution to form pores. The choice of process directly affects the pore size, porosity, mechanical properties, and air and moisture permeability of the film.

[0090] S4. Composite: The outer high-elasticity support layer obtained in step S3 is composited to the other side of the inner hydrogel matrix layer with intermediate drug-carrying function layer obtained in step S2 by adhesive or hot pressing to obtain a three-layer composite structure. Optionally, medical pressure-sensitive adhesive is coated on the outer surface of the outer high-elasticity support layer and covered with release paper to obtain the multi-effect medical wound healing patch.

[0091] It is worth noting that when bonding the outer film to the inner-intermediate composite using adhesives or hot pressing, sufficient interlayer bonding strength must be ensured to prevent delamination during product use. Hot pressing is suitable for thermoplastic elastomers (such as TPU), while medical adhesives have broader applicability. The choice of lamination process must balance bonding strength, production efficiency, and the impact on the original properties of each functional layer (especially the water content of the hydrogel and the activity of the microspheres).

[0092] In step S2.1, when preparing drug-loaded microspheres using the emulsification-solvent evaporation method, the average particle size of the first type of drug-loaded microspheres is 1-10 micrometers, and the average particle size of the second type of drug-loaded microspheres is 10-50 micrometers.

[0093] It is worth noting that controlling the average particle size of the first type of drug-loaded microspheres to 1-10 micrometers and that of the second type to 10-50 micrometers demonstrates a clear functional orientation. Smaller particle sizes (1-10 micrometers) mean a larger specific surface area, which is beneficial for the rapid response, degradation, and release of drugs by the first type of microspheres in the wound microenvironment, achieving rapid efficacy. Larger particle sizes (10-50 micrometers) can accommodate more drug and, through a longer diffusion path and a slower overall degradation rate, achieve long-lasting sustained release from the second type of microspheres. Particle size is one of the key parameters for regulating drug release rates.

[0094] Example 1

[0095] A multi-effect medical wound healing patch, wherein the inner hydrogel matrix layer comprises, by weight percentage, the following components:

[0096] Take 10 parts of polyvinyl alcohol (PVA-1788), 2 parts of sodium hyaluronate (low molecular weight), 1 part of carboxymethyl chitosan, 8 parts of glycerol, 0.3 parts of tea polyphenols, and 78.7 parts of deionized water.

[0097] The preparation method is as follows:

[0098] S1, polyvinyl alcohol (PVA-1788), sodium hyaluronate (low molecular weight), carboxymethyl chitosan, glycerol, and tea polyphenols are added to deionized water, stirred and dissolved at 90°C, and then poured into a mold. After three freeze-thaw cycles at -20°C and 25°C, a hydrogel film with a thickness of about 1.5 mm is obtained.

[0099] S2, intermediate drug-carrying functional layer:

[0100] S2.1, Class I drug-loaded microspheres (rapid release): An emulsification-cooling method was used. 2g of gelatin and 0.2g of levofloxacin hydrochloride were dissolved in 20ml of 60℃ hot water as the aqueous phase, and then emulsified dropwise into liquid paraffin containing 2% Span-80. The mixture was cooled in an ice bath and dehydrated with acetone to obtain microspheres with an average particle size of approximately 5μm.

[0101] The second type of drug-loaded microspheres (sustained release): An emulsification-solvent evaporation method was used. 1 g of PLGA (75:25, Mw=50kDa) and 30 mg of Halofuginone were dissolved in 10 ml of dichloromethane as the oil phase, and then emulsified by adding dropwise to a 1% PVA aqueous solution. The solvent was evaporated, the mixture was collected by centrifugation, and freeze-dried to obtain microspheres with an average particle size of approximately 30 μm.

[0102] S2.2. Mix the two types of microspheres at a dry weight ratio of 1:1, with a total weight of 0.3g (approximately 30% of the dry weight of the intermediate layer), and disperse them in 5g of 2% sodium alginate solution. Coat the mixture onto the surface of the inner hydrogel layer and crosslink it with 5% CaCl2 solution to form an intermediate layer with a thickness of approximately 0.3mm.

[0103] S3. Outer high-elasticity support layer: Phase separation method is adopted. 12g of thermoplastic polyurethane (TPU) is dissolved in 88g of DMF, 40g of NaCl particles with a particle size of about 20μm are added, the mixture is cast into a film, immersed in water to displace the solvent and dissolve the NaCl, and dried to obtain a microporous film with a thickness of about 0.1mm, an average pore size of about 20μm, and a porosity of about 50%.

[0104] S4. Composite: Apply medical-grade silicone adhesive to the back of the hydrogel with the intermediate layer, attach the outer film, and cure under pressure. Cover the outer layer with acrylic pressure-sensitive adhesive and release paper, cut and sterilize to obtain the final product.

[0105] Example 2

[0106] A multi-functional medical wound healing patch,

[0107] Inner layer: composed of 8 parts PVP K30, 3 parts sodium alginate, 0.5 parts paeonol, 10 parts sorbitol, and 78.5 parts water. Crosslinked with CaCl2 solution, thickness 2 mm;

[0108] Intermediate layer:

[0109] Category 1 microspheres: calcium alginate-loaded mupirocin microspheres (ionogel method), particle size ~8μm;

[0110] The second type of microspheres: PCL (Mw=80kDa) microspheres loaded with anti-CTGF antibody fragments, with a particle size of ~40μm;

[0111] The two types of microspheres were mixed at a mass ratio of 3:1, with the total weight accounting for 40% of the intermediate layer. They were then dispersed in a sodium carboxymethyl cellulose solution, coated, and dried to a thickness of 0.2 mm.

[0112] Outer layer: porous silicone rubber film (foaming method), 0.15mm thick.

[0113] Example 3

[0114] A multi-effect medical wound healing patch,

[0115] Inner layer: Sodium polyacrylate and sulfonated chitosan composite hydrogel (UV crosslinking), containing baicalin, 1 mm thick;

[0116] Intermediate layer:

[0117] Type 1 microspheres: Low molecular weight PLGA (50:50, Mw=10kDa) loaded with silver sulfadiazine, particle size ~3μm;

[0118] The second type of microspheres: PLA (Mw=100kDa) loaded with recombinant human Decorin, with a particle size of ~25μm;

[0119] The two types of microspheres were mixed at a mass ratio of 1:4, with the total weight accounting for 20% of the intermediate layer, and then coated in a thermosensitive Pluronic F127 gel with a thickness of 0.15 mm.

[0120] Outer layer: Laser-drilled SEBS film, 0.08mm thick.

[0121] In summary, Example 1 demonstrates a classic formulation using PVA freeze-thaw gel / gelatin & PLGA microspheres / phase-separated TPU membrane; Example 2, by adjusting the microsphere ratio (3:1) and total proportion (40%), demonstrates an enhanced variant for wounds at high infection risk; and Example 3, by selecting different drugs and ratios (1:4), demonstrates a variant focused on anti-scarring. These variations collectively demonstrate the core advantages of this invention: functional integration through a "three-layer composite structure," precise drug delivery through "two types of time-controlled release microspheres," and the ability to customize the product to meet the needs of different types and stages of skin wound management by adjusting key components, ratios, and process parameters, thereby providing an integrated solution to the challenges of healing and scar prevention.

[0122] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0123] Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A multi-effect medical wound healing patch, comprising a three-layer composite structure, characterized in that, The three-layer composite structure, from the side in contact with the wound to the outside, consists of: an inner hydrogel matrix layer, a middle drug-carrying functional layer, and an outer highly elastic support layer. The inner hydrogel matrix layer, by weight percentage, comprises the following components: Hydrophilic polymers 5%-20%; Natural polysaccharides 0.5%-10%; Moisturizing factor 3%-15%; Natural antibacterial ingredients: 0.05%-2%; The remainder is water; The intermediate drug-loaded functional layer is composed of drug-loaded microspheres dispersed in a second polymer matrix, wherein the mass percentage of the drug-loaded microspheres in the intermediate drug-loaded functional layer is 10%-60%. The drug-loaded microspheres include a first type of drug-loaded microspheres and a second type of drug-loaded microspheres. The first type of drug-loaded microspheres are loaded with an antibacterial agent, and the second type of drug-loaded microspheres are loaded with an antiproliferative cytokine inhibitor. The outer high-elasticity support layer is an elastomeric film with a breathable microporous structure; The inner hydrogel matrix layer has a thickness of 0.5-3 mm, the intermediate drug-carrying functional layer has a thickness of 0.1-1 mm, and the outer high-elasticity support layer has a thickness of 0.05-0.3 mm.

2. The multi-effect medical wound healing patch according to claim 1, characterized in that, The hydrophilic polymer is selected from at least one of polyvinyl alcohol, polyvinylpyrrolidone, sodium polyacrylate, and polyacrylamide; the natural polysaccharide is selected from at least one of hyaluronic acid, sodium alginate, carboxymethyl chitosan, and sulfonated chitosan; the moisturizing factor is glycerin or sorbitol; and the natural antibacterial ingredient is selected from at least one of tea polyphenols, paeonol, and baicalin.

3. The multi-effect medical wound healing patch according to claim 1, characterized in that, The first type of drug-loaded microspheres and the second type of drug-loaded microspheres are microspheres with different degradation or swelling properties; The first type of drug-loaded microspheres are prepared from a first carrier material that can be rapidly degraded or swollen in the wound microenvironment. The first carrier material is selected from at least one of gelatin, calcium alginate, and low molecular weight polylactic acid-glycolic acid copolymer. The second type of drug-loaded microspheres are prepared from a second carrier material that slowly degrades in the wound microenvironment. The second carrier material is selected from at least one of high molecular weight polylactic acid-glycolic acid copolymer, polycaprolactone, and polylactic acid.

4. The multi-effect medical wound healing patch according to claim 1, characterized in that, The antibacterial agent is selected from at least one of levofloxacin hydrochloride, mupirocin, and silver sulfadiazine; the antiproliferative cytokine inhibitor is selected from at least one of anti-transforming growth factor-β1 antibody, anti-connective tissue growth factor antibody, Decorin, and Halofuginone.

5. The multi-effect medical wound healing patch according to claim 1, characterized in that, The second polymer matrix is ​​a hydrogel or hydrocolloid, and its composition may be the same as or different from that of the inner hydrogel matrix layer.

6. The multi-effect medical wound healing patch according to claim 1, characterized in that, The elastomer of the outer high-elasticity support layer is thermoplastic polyurethane, silicone rubber, or styrene-ethylene-butene-styrene block copolymer; the average pore size of the breathable microporous structure is 1-50 micrometers, and the porosity is 30%-70%.

7. The multi-effect medical wound healing patch according to claim 1, characterized in that, The mass ratio of the first type of drug-loaded microspheres to the second type of drug-loaded microspheres in the intermediate drug-loaded functional layer is 1:5 to 5:

1.

8. The multi-effect medical wound healing patch according to claim 1, characterized in that, The outer surface of the outer high-elasticity support layer is also covered with a medical pressure-sensitive adhesive layer, and the medical pressure-sensitive adhesive layer is covered with release paper.

9. A method for preparing a multi-effect medical wound healing patch as described in any one of claims 1-9, characterized in that, Includes the following steps: S1. Preparation of the inner hydrogel matrix layer: The hydrophilic polymer, natural polysaccharide, moisturizing factor and natural antibacterial component are dissolved or dispersed in water to form a first homogeneous solution, which is then injected into a mold and cured by physical crosslinking or chemical crosslinking to form the inner hydrogel matrix layer. S2. Preparation of intermediate drug-loading functional layer: S2.

1. Prepare first-type drug-loaded microspheres and second-type drug-loaded microspheres respectively: use emulsification-solvent evaporation method, spray drying method or ion gel method to encapsulate the antibacterial agent in the first carrier material and encapsulate the antiproliferative cytokine inhibitor in the second carrier material respectively; S2.

2. The first type of drug-loaded microspheres and the second type of drug-loaded microspheres obtained in step S2.1 are uniformly dispersed in the prepolymer solution constituting the second polymer matrix, coated on the surface of the inner hydrogel matrix layer obtained in step S1, and formed an intermediate drug-loaded functional layer composite on the inner hydrogel matrix layer by crosslinking or drying and curing. S3. Preparation of outer high-elasticity support layer: Prepare an elastomer film with a breathable microporous structure by using phase separation method, pore-forming agent method or foaming process; S4. Composite: The outer high-elasticity support layer obtained in step S3 is composited to the other side of the inner hydrogel matrix layer with the intermediate drug-carrying functional layer obtained in step S2 by means of adhesive or hot pressing, to obtain a three-layer composite structure. Optionally, medical pressure-sensitive adhesive is coated on the outer surface of the outer high-elasticity support layer and covered with release paper to obtain the multi-effect medical wound healing patch.

10. A method for preparing a multi-effect medical wound healing patch according to claim 9, characterized in that, In step S2.1, when preparing drug-loaded microspheres using the emulsification-solvent evaporation method, the average particle size of the first type of drug-loaded microspheres is 1-10 micrometers, and the average particle size of the second type of drug-loaded microspheres is 10-50 micrometers.