Preparation method of intelligent constant-temperature physiotherapy patch

Abstract

This invention discloses a method for preparing an intelligent constant-temperature physiotherapy patch, belonging to the field of physiotherapy patch technology. The method includes substrate pretreatment, preparation of a pH-responsive self-heating core layer, preparation of a biodegradable stem cell exosome carrier layer, composite molding, outer layer lamination, finished product processing, and quality inspection steps. Specifically, the pH-responsive self-heating core layer regulates the heating rate by sensing changes in wound pH; the biodegradable stem cell exosome carrier layer uses a composite biodegradable matrix combined with ultrasonic dispersion to achieve uniform exosome release; and the outer layer lamination uses windproof, waterproof, and breathable materials with edge sealing. This invention, through the synergy of multiple technologies, ensures that the physiotherapy patch maintains a stable constant temperature in high-altitude, low-temperature environments, adaptively adjusts the release of healing-promoting components, and possesses windproof, waterproof, and breathable properties. It can shorten the wound healing cycle and reduce the risk of infection, making it suitable for physiotherapy and healing promotion of difficult-to-heal wounds such as trauma and frostbite in extreme environments such as high altitudes and polar regions.

Description

Technical Field

[0001] This invention relates to the field of physiotherapy patch technology, specifically a method for preparing an intelligent constant temperature physiotherapy patch. Background Technology

[0002] High-altitude, low-temperature environments are characterized by low temperatures (-10℃ to 5℃), large diurnal temperature ranges, frequent winds and rain, and low air pressure. Such environments can slow down local blood circulation and reduce cell metabolism in wounds, resulting in a wound healing period that is more than 30% longer than in plains areas. Furthermore, the windy and rainy environment can cause dressings to become damp and fall off, further increasing the risk of infection, with an infection rate of 20%-30%.

[0003] In existing physiotherapy patches or dressings, self-heating products can only achieve passive heating and cannot adjust heating parameters according to the wound infection status (such as pH changes); protective products struggle to balance windproof and waterproof properties with breathability, easily leading to stuffy skin or failure of the heating core layer. These problems directly restrict the efficient healing of wounds in extreme environments.

[0004] In view of the above, this application is hereby submitted. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing an intelligent constant temperature physiotherapy patch to solve the problems mentioned in the background art.

[0006] To solve the above-mentioned technical problems, the present invention provides a method for preparing an intelligent constant temperature physiotherapy patch, comprising the following steps: S1: Substrate pretreatment, selecting medical-grade flexible substrate for cleaning and drying; S2: Preparation of pH-responsive self-heating core layer: The self-heating material is mixed with a pH-sensitive regulator to form a core layer. The pH-responsive self-heating core layer can regulate the heating rate by sensing changes in the external pH. S3: Preparation of the biodegradable stem cell exosome carrier layer, including the following sub-steps: S31, Selecting polycaprolactone and gelatin, mixing them in a preset ratio, heating and melting them to prepare a biodegradable carrier matrix; S32, Mixing stem cell exosomes with the carrier matrix, and dispersing them uniformly in the carrier matrix by ultrasonic dispersion treatment; S33, Coating the carrier matrix containing exosomes onto a release membrane, cooling and molding it, and then peeling off the release membrane to obtain the biodegradable stem cell exosome carrier layer; S4: Composite molding, in which a pH-responsive self-heating core layer, a biodegradable stem cell exosome carrier layer and a pH-responsive antibacterial membrane are sequentially composited on a pretreated substrate to form a composite layer; S5: Outer layer composite, with a windproof and waterproof membrane laminated on the side of the composite layer away from the substrate; S6. Finished product processing: The composite structure is cut and the edges are sealed to obtain the intelligent constant temperature physiotherapy patch; In step S4, the heating rate of the pH-responsive self-heating core layer and the exosome release rate of the degradable stem cell exosome carrier layer are synchronously regulated by pH response signals. This ensures that the therapeutic patch maintains stable heating within a constant temperature range of 36-37℃, and the exosome release rate is adaptively adjusted according to pH changes. The pH response signal enables synergistic regulation of the self-heating core layer and the exosome carrier layer, ensuring both the constant temperature therapeutic effect of the therapeutic patch and the adaptive adjustment of exosome release based on pH changes at the wound or treatment site. Simultaneously, the polycaprolactone-gelatin composite carrier matrix, combined with ultrasonic dispersion technology, ensures uniform dispersion of exosomes and degradability of the carrier layer, avoiding the problem of uneven release caused by local exosome aggregation. This further enhances the synergistic effect of therapy and healing promotion, solving the problem that existing therapeutic patches cannot simultaneously achieve constant temperature stability, precise release of functional components, and environmental degradability.

[0007] Further, in step S2, the preparation of the pH-responsive self-heating core layer includes the following sub-steps: S21, mixing iron powder, activated carbon, and vermiculite in a preset ratio to obtain a basic self-heating mixture; S22, adding a pH-sensitive regulator to the basic self-heating mixture, wherein the pH-sensitive regulator is a compound of chitosan quaternary ammonium salt and bromocresol purple; S23, placing the mixed material in a molding mold and pressing it under a preset pressure to form a sheet-like core layer blank; S24, subjecting the core layer blank to low-temperature drying treatment to obtain a pH-responsive self-heating core layer; through a specific pH-sensitive regulator compounding scheme and molding process, it is ensured that the self-heating core layer can accurately sense pH changes and regulate the heating rate, avoiding the problem of uncontrollable heating rate of traditional self-heating materials, while improving the structural stability of the core layer and preventing material spillage during use.

[0008] Further, in step S4, the preparation of the pH-responsive antibacterial membrane includes the following sub-steps: S41, dissolving chitosan in acetic acid solution, adding tea tree oil and stirring evenly to obtain the antibacterial membrane stock solution; S42, adding a pH-sensitive colorimetric agent, bromocresol purple, to the antibacterial membrane stock solution; S43, coating the antibacterial membrane stock solution onto a breathable base membrane, and drying it to form a pH-responsive antibacterial membrane; S44, bonding the pH-responsive antibacterial membrane to the side of the biodegradable stem cell exosome carrier layer away from the pH-responsive self-heating core layer using a medical-grade adhesive; by introducing a pH-sensitive colorimetric agent into the antibacterial membrane, the therapeutic patch combines antibacterial function with pH visualization monitoring capability. Medical personnel or users can intuitively judge the condition of the therapeutic site through the color change of the membrane layer. At the same time, the combination of chitosan and tea tree oil enhances the antibacterial effect and avoids the problem of the single function of traditional antibacterial membranes.

[0009] Further, in step S4, the specific operations of composite molding include: S411, coating a first adhesive layer onto the pretreated substrate surface; S412, attaching the pH-responsive self-heating core layer to the first adhesive layer and applying a preset pressure to ensure a tight bond between the two; S413, coating a second adhesive layer onto the side of the pH-responsive self-heating core layer away from the substrate; S414, attaching the biodegradable stem cell exosome carrier layer to the second adhesive layer and performing hot-pressing treatment at a preset temperature; S415, coating a third adhesive layer onto the side of the biodegradable stem cell exosome carrier layer away from the pH-responsive self-heating core layer, and attaching the pH-responsive antibacterial film onto the third adhesive layer to complete the composite molding; through layered adhesive coating and step-by-step composite process, the bonding between each functional layer is ensured to prevent delamination during use, while the hot-pressing treatment further improves the stability of the composite structure and ensures the structural integrity of the therapeutic patch under bending, stretching, and other usage scenarios.

[0010] Further, in step S5, the specific operation of the outer layer composite includes: S51, selecting polyurethane-coated nylon fabric as the windproof and waterproof membrane substrate; S52, coating one side of the windproof and waterproof membrane substrate with medical-grade pressure-sensitive adhesive; S53, attaching the pressure-sensitive adhesive-coated windproof and waterproof membrane to the side of the pH-responsive antibacterial membrane away from the degradable stem cell exosome carrier layer, and using a roller pressing process to ensure tight composite between the two; S54, sealing the edges of the composite windproof and waterproof membrane to prevent external moisture from penetrating; using polyurethane-coated nylon fabric as the windproof and waterproof membrane not only ensures the windproof and waterproof performance of the physiotherapy patch, avoiding the influence of the external environment on the self-heating core layer and functional layer, but also achieves a stable composite through pressure-sensitive adhesive, and the edge sealing treatment further enhances the protective effect and extends the service life of the physiotherapy patch.

[0011] Furthermore, in step S6, the specific operations for finished product processing include: S61, cutting the composite overall structure according to the preset dimensions to obtain a single physiotherapy patch blank; S62, sealing the edges of the physiotherapy patch blank using a heat-sealing process to form a sealed edge; S63, setting an easy-tear opening on one side of the sealed edge to complete the preparation of the intelligent constant temperature physiotherapy patch; through precise cutting and heat-sealing processes, the dimensional consistency and sealing of a single physiotherapy patch are ensured, preventing the internal functional materials from becoming damp and failing. The easy-tear opening enhances ease of use and solves the problem of difficulty in opening traditional physiotherapy patches.

[0012] Furthermore, it also includes S7: Quality Inspection, which includes the following sub-steps: S71, Selecting a portion of the finished intelligent constant temperature therapy patches and testing their initial heating temperature and constant temperature maintenance time; S72, Simulating different pH environments and testing the changes in the heating rate of the pH-responsive self-heating core layer and the changes in the exosome release rate of the degradable stem cell exosome carrier layer; S73, Testing the waterproof performance of the windproof and waterproof membrane and the bonding strength of each functional layer; S74, Removing unqualified products and retaining qualified products; Through multi-dimensional quality inspection steps, the performance stability and safety of the finished therapy patches are ensured, and unqualified products are prevented from entering the market. Among them, the pH environment simulation test step can verify the effectiveness of the pH response synergistic regulation function, further ensuring the therapeutic effect of the therapy patches.

[0013] Compared with the prior art, the beneficial effects of the present invention are: 1. Through the synergistic application of multiple unique technologies, the core challenges of wound treatment and healing promotion in high-altitude and low-temperature environments have been effectively solved, significantly improving the efficiency and safety of wound healing in extreme conditions. Among these advancements, the pH-responsive self-heating core layer design overcomes the limitations of existing self-heating dressings that are "passive heating with unadjustable parameters." It adaptively regulates the heating rate by sensing changes in the wound's pH value, maintaining a stable and constant temperature when the wound is not infected, providing a suitable temperature environment for healing. When the wound becomes infected, it actively increases the heating rate, promoting local blood circulation and alleviating the slow healing caused by high-altitude and low-temperature conditions from the source.

[0014] 2. The innovative preparation process of the biodegradable stem cell exosome carrier layer achieves a balance between biodegradability and precise release of functional components. The use of a composite biodegradable matrix avoids the secondary damage caused by frequent replacements of traditional non-biodegradable carriers. Combined with ultrasonic dispersion technology, it ensures uniform distribution and stable release of exosomes, significantly enhancing the active healing ability and further shortening the wound healing cycle. Simultaneously, the combination of a windproof, waterproof, and breathable outer layer with a step-by-step low-temperature composite process resolves the contradiction between windproofness / waterproofness and breathability in existing protective dressings. Furthermore, strict temperature control protects the exosome activity and self-heating core layer performance, ensuring the therapeutic patch maintains structural stability and effective function in high-altitude, windy, and rainy environments, significantly reducing the risk of wound infection and providing an integrated solution for wound therapy in extreme environments. Attached Figure Description

[0015] Figure 1 This is a flowchart of a method for preparing an intelligent constant temperature physiotherapy patch. Detailed Implementation

[0016] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0017] Please see Figure 1 This invention provides a technical solution: a method for preparing an intelligent constant-temperature physiotherapy patch, specifically relating to a method for preparing an intelligent constant-temperature physiotherapy patch suitable for high-altitude, low-temperature environments, such as altitudes above 3000 meters and temperatures ranging from -10°C to 5°C. This patch can be used for wound treatment and healing promotion in scenarios such as injuries sustained at high altitudes, frostbite in mountain climbers, and trauma to polar researchers. In high-altitude, low-temperature environments, human wound healing faces three core challenges: First, low temperatures slow local blood circulation, extending the healing period by more than 30% compared to plains areas; second, windy, rainy environments with large diurnal temperature variations easily lead to dressings becoming damp and falling off, increasing the risk of infection, with an infection rate of approximately 20%-30%; third, traditional physiotherapy patches only possess single heating or antibacterial functions, failing to simultaneously address the synergistic needs of constant temperature insulation, infection monitoring, active healing promotion, and environmental protection.

[0018] Among the existing publicly available technologies, research on self-heating dressings includes a medical self-heating dressing and its preparation method, which achieves passive heating only through an iron powder-activated carbon system, lacking pH response regulation capabilities and unable to adjust its function according to the wound infection status (pH value changes); research on stem cell exosome dressings includes a stem cell exosome drug-loaded dressing, which uses a non-degradable polyester substrate, easily leading to secondary damage, and the exosomes are unevenly dispersed, with a utilization rate of less than 50%; research on windproof and waterproof dressings includes an outdoor waterproof dressing, which uses a polyethylene film as the outer layer, with an air permeability of less than 100 mm / s, easily causing the skin to feel stuffy and damp.

[0019] To address the aforementioned shortcomings, this invention utilizes a multi-layered structural design that incorporates "pH-responsive self-heating, biodegradable exosomes for healing, and windproof, waterproof, and breathable composite" combined with a step-by-step, precise manufacturing process to achieve a functional closed loop for wound therapy in high-altitude, low-temperature environments. Its core invention lies in overcoming the limitations of existing technologies that rely on "single-function independent design" and solving the long-standing problem of wound healing at high altitudes through the synergistic application of multiple technologies.

[0020] This embodiment targets the application scenario of high-altitude knee frostbite complicated by mild infection, and prepares a smart constant temperature physiotherapy patch with a size of 10cm×15cm. The specific steps are as follows: S1 Substrate Pretreatment: The substrate is the basic load-bearing layer of the therapeutic patch and must meet three major requirements simultaneously: first, biocompatibility to avoid irritating delicate skin after frostbite; second, low-temperature flexibility to prevent cracking in high-altitude environments (-10℃); and third, surface smoothness to ensure uniform lamination of subsequent functional layers. If the substrate treatment is incomplete, such as with residual oil or a rough surface, the adhesion of the functional layers will decrease, leading to delamination during use. Therefore, a three-step pretreatment process—cleaning, drying, and surface modification—is required to ensure the substrate meets medical safety standards and lamination process requirements, laying the foundation for subsequent lamination. Specific technical methods are as follows: Substrate selection: Medical-grade polyurethane film (0.1mm thickness, Shore A50 hardness) is selected. This material maintains flexibility in the range of -20℃ to 50℃ and has an elongation at break of ≥400%, which meets the mechanical requirements of high-altitude and low-temperature environments. Cleaning treatment: Immerse the polyurethane film in a medical ethanol solution (75% concentration) and clean it for 15 minutes using an ultrasonic cleaner (300W power, 40kHz frequency) to remove surface oil and impurities; after cleaning, rinse three times with deionized water for 5 minutes each time to avoid ethanol residue irritating the skin. Drying treatment: Place the cleaned substrate into a vacuum drying oven, set the temperature to 40℃ and the vacuum degree to -0.09MPa, and dry for 2 hours until the substrate moisture content is ≤0.5% (detected by a halogen moisture analyzer). Surface modification: The surface of the substrate is modified by using a plasma treatment instrument (oxygen gas, power 100W, processing time 30 seconds) to reduce the surface contact angle from 75° to 35°, thereby improving the adhesion of subsequent adhesives.

[0021] Example: In this embodiment, the pretreated polyurethane substrate was folded 100 times in a high-altitude simulated environment at -10℃ to simulate knee bending, and no cracks were generated; after surface modification, the adhesion of the subsequent adhesive coating reached 5N / 25mm, which meets the needs of intense activities during high-altitude training.

[0022] In existing technologies, a disclosed method for processing flexible medical substrates uses only a simple process of rinsing with water and air drying, without plasma modification and low-temperature flexibility optimization. This results in a 30% brittleness rate of the substrate at -10℃ and adhesive adhesion of less than 2N / 25mm. The difference in this approach lies in two aspects: first, the addition of a plasma surface modification process, using oxygen plasma to etch the substrate surface, forming a micro-nano-scale rough structure and increasing the adhesive bonding area; second, strict control of the drying moisture content and substrate mechanical parameters, specifically adapted to high-altitude and low-temperature environments. The low-temperature brittleness rate of the substrate is reduced from 30% in existing technologies to below 5%, and the adhesive adhesion is increased from 2N / 25mm to 5N / 25mm, ensuring that the subsequent functional layers do not detach during strenuous activities at high altitudes, laying the foundation for the overall structural stability of the therapeutic patch.

[0023] Preparation of S2pH-responsive self-heating core layer: In high-altitude, low-temperature environments, when the local wound temperature is below 35℃, the blood circulation rate decreases by 40%, leading to a prolonged healing period. Simultaneously, when the wound becomes infected, such as in cases of frostbite complicated by bacterial infection, bacterial metabolism causes the pH of the exudate to rise from the normal 5.5 to above 7.0. Therefore, the self-heating core layer needs to simultaneously achieve "constant temperature of 36-37℃ (optimal human healing temperature)" and "pH-responsive regulation": when the wound is not infected (pH=5.5-6.5), it maintains the basic heating rate to avoid overheating and burns; when the wound is infected (pH≥7.0), it increases the heating rate, promoting blood circulation and subsequent exosome release, achieving a synergistic effect of "infection warning - temperature increase to promote healing." The specific technical solution is as follows: Preparation of basic self-heating mixture: Weigh reduced iron powder (particle size 50μm, purity 99%) and activated carbon (specific surface area 1000m²) at a mass ratio of 70:15:15. 2 / g), vermiculite (expansion ratio 20 times), are placed in a three-dimensional mixer (speed 300r / min) and mixed for 30 minutes to obtain a homogeneous mixture; vermiculite acts as a heat-insulating agent, which can slow down heat loss and prolong the constant temperature time; Preparation of pH-sensitive regulator: Chitosan quaternary ammonium salt (80% degree of substitution) and bromocresol purple (analytical grade) were weighed at a mass ratio of 9:1, dissolved in deionized water (concentration 5%), and stirred for 30 minutes until completely dissolved to obtain the pH-sensitive regulator; Chitosan quaternary ammonium salt has both antibacterial and pH-responsive properties, and bromocresol purple, as a pH indicator, can help observe the infection status; Core layer molding: Mix the basic self-heating mixture with the pH-sensitive adjuster at a mass ratio of 10:1, stir for 20 minutes, place it into a sheet mold (size 10cm×15cm, thickness 0.5mm), and press it for 10 minutes using a flat vulcanizing machine (pressure 0.5MPa, temperature 50℃) to obtain the core layer blank; Low-temperature drying: Place the core layer blank into a forced-air drying oven, set the temperature to 35℃ and the wind speed to 1m / s, and dry for 4 hours until the moisture content of the core layer is ≤1% to avoid premature oxidation of iron powder (the self-heating principle is the exothermic oxidation of iron powder).

[0024] Example: In this embodiment, the prepared self-heating core layer, under a simulated high-altitude environment of -10℃: when the pH=6.0 (uninfected), the heating rate is 0.5W / g, the temperature is maintained at 36℃, and the constant temperature time reaches 12 hours; when the pH=7.2 (infected), the chitosan quaternary ammonium salt undergoes structural changes due to the increase in pH, releasing more active groups, accelerating the oxidation of iron powder, increasing the heating rate to 0.8W / g, and raising the temperature to 37℃, thus achieving the function of "heating up to promote healing during infection" and meeting the requirement of not needing to change the dressing for 12 hours at night on the plateau.

[0025] In existing technologies, a self-heating medical dressing uses an "iron powder-activated carbon-sodium chloride" system, which can only achieve passive heating without pH-responsive control. This means it cannot adjust the heating rate during infection, leading to a 30% decrease in healing efficiency. Furthermore, its constant temperature time is only 8 hours, which cannot meet the requirements for nighttime dressing changes at high altitudes. The difference in this approach is twofold: first, it introduces a pH-sensitive regulator composed of chitosan quaternary ammonium salt and bromocresol purple, which regulates the iron powder oxidation rate through pH changes, achieving adaptive heating rate; second, it adds vermiculite as a heat-insulating agent, extending the constant temperature time to 12 hours, suitable for long-term use at high altitudes. In infected conditions, a 1°C increase in local wound temperature increases blood circulation rate by 20%; the constant temperature time is extended from 8 hours to 12 hours, reducing dressing change frequency by 50%; simultaneously, the antibacterial properties of chitosan quaternary ammonium salt reduce the infection rate from 20% in existing technologies to below 8%, significantly improving wound healing efficiency at high altitudes.

[0026] Preparation of S3 Degradable Stem Cell Exosome Carrier Layer: The core problem of difficult-to-heal wounds at high altitudes, such as frostbite, is insufficient local angiogenesis and slow cell proliferation. Traditional dressings can only provide basic protection and cannot actively promote healing. Furthermore, medical conditions at high altitudes are limited; if the dressings are non-degradable, frequent replacements are necessary, increasing the risk of secondary damage. Therefore, the carrier layer needs to achieve three major functions: "degradability - precise exosome release - active healing promotion." This involves using degradable materials to avoid secondary damage, loading mesenchymal stem cell exosomes to promote angiogenesis and cell proliferation, and using ultrasound dispersion to ensure uniform exosome release. Determining the material selection and exosome loading of the carrier layer improves healing efficiency. Specific technical methods are as follows: Preparation of biodegradable carrier matrix: Weigh polycaprolactone (number average molecular weight 8×10⁻⁶) at a mass ratio of 6:4. 4 Polycaprolactone (melting point 60℃) and gelatin (medical grade, freeze strength 250 Bloom) were melt-blended in a twin-screw extruder (temperature 120℃, speed 200 r / min) for 20 minutes. After extrusion, the mixture was granulated to obtain composite particles. Polycaprolactone provides long-term degradation stability (degradation cycle 3 months), while gelatin provides biocompatibility and hydrophilicity. The combination of the two can balance degradation rate and mechanical properties. Preparation of exosome loading solution: Take mesenchymal stem cell exosomes (concentration 2×10⁻⁶) 10 The exosome loading solution was prepared by diluting exosomes at a volume ratio of 1:1 with physiological saline. The exosomes were derived from human umbilical cord mesenchymal stem cells and conformed to the "Preparation and Testing Specifications for Human Mesenchymal Stem Cell Exosomes". Exosome dispersion and carrier layer formation: The composite particles were placed in a flat vulcanizing machine (temperature 70℃, pressure 0.3MPa) and pressed into a film with a thickness of 0.2mm. Then, the exosome loading liquid was uniformly sprayed onto the film surface at a spraying rate of 0.5mL / cm². 2Immediately place the exosomes into an ultrasonic disperser (frequency 30kHz, power 150W) and treat for 15 minutes to allow the exosomes to penetrate the membrane surface and disperse evenly in the carrier matrix; Cooling and molding: The dispersed film was placed in a cooling box (temperature 25℃, wind speed 0.5m / s) and cooled for 30 minutes. Then the release film (the release film is made of PET material and is 0.05mm thick) was peeled off to obtain a biodegradable stem cell exosome carrier layer. The exosome dispersion uniformity was observed to be ≥90% by fluorescence microscopy.

[0027] Example: In this embodiment, when the prepared carrier layer was applied to frostbite wounds at high altitudes: one month after implantation, the polycaprolactone-gelatin matrix began to degrade, and it was completely degraded without residue after three months; exosomes were slowly released at pH=6.0, with a release rate of 1×10⁻⁶. 9 Cells / mL / day, at pH=7.2 (infection), due to the influence of the pH-sensitive regulator on the carrier matrix (pH signal transduction in step S2), the release rate increases to 2×10⁻⁶. 9 Cells / mL / day promote angiogenesis in frostbite sites (increasing blood vessel density by 50%, as observed in tissue sections), shortening the healing cycle from 28 days to 14 days.

[0028] In existing technologies, a stem cell exosome-loaded dressing uses polyacrylate as a carrier matrix (non-degradable), requiring removal 7 days post-surgery, resulting in a secondary damage rate of 25%. Furthermore, the exosomes are loaded using a simple "soaking" method, achieving only 60% dispersion uniformity and less than 50% utilization. The key differences in this approach are: first, the use of a polycaprolactone-gelatin composite biodegradable matrix, with a degradation cycle matching the wound healing cycle (3 months), avoiding secondary damage; and second, the adoption of a "spraying + ultrasonic dispersion" process, using ultrasonic vibration to allow exosomes to penetrate the matrix surface, improving dispersion uniformity to over 90%. The carrier layer achieves 100% complete degradation, reducing the secondary damage rate from 25% to below 5%; exosome utilization increases from 50% to 90%, angiogenesis rate increases by 50%, and the wound healing cycle is shortened from 28 days to 14 days, solving the problems of difficult dressing changes and low healing efficiency under high-altitude medical conditions.

[0029] S4 Composite Molding: The therapeutic patch consists of four layers: a substrate, a self-heating core layer, an exosome carrier layer, and a pH-responsive antibacterial membrane. Improper lamination processes, such as incorrect adhesive selection or insufficient lamination pressure, can lead to insufficient interlayer bonding strength, causing delamination and detachment during high-altitude activities, thus losing its therapeutic effect. Therefore, a process of "layered adhesive coating + step-by-step hot pressing" is necessary to ensure tight bonding between the layers while avoiding high temperatures that could damage the exosome activity and the performance of the self-heating core layer. The specific technical solution is as follows: Adhesive selection and pretreatment: Three medical adhesives were selected to meet different interlayer requirements: The first adhesive (substrate-self-heating core layer) was a medical acrylic adhesive (50% solids content, 1000 mPa·s viscosity), with strong adhesion; the second adhesive (self-heating core layer-exosome carrier layer) was a medical silicone adhesive (40% solids content, 800 mPa·s viscosity), with good flexibility to avoid damage to the carrier layer; the third adhesive (exosome carrier layer-pH-responsive antibacterial membrane) was a medical polyurethane adhesive (45% solids content, 900 mPa·s viscosity), with excellent biocompatibility. Step-by-step compounding operation: Apply the first adhesive to the pretreated substrate surface (step S1) using a scraper, with a coating thickness of 0.05 mm, and place it in an oven (temperature 50℃) to dry for 5 minutes until the adhesive is surface dry; The pH-responsive self-heating core layer (step S2) is attached to the first adhesive layer and pressed for 10 seconds using a flatbed press (pressure 0.3MPa, temperature 25℃) to ensure a tight bond between the core layer and the substrate. A second adhesive is applied to the side of the self-heating core layer away from the substrate, with a coating thickness of 0.04 mm, and dried in an oven (temperature 50℃) for 4 minutes. The biodegradable stem cell exosome carrier layer (step S3) is attached to the second adhesive layer and hot-pressed for 10 seconds using a flatbed press (pressure 0.2MPa, temperature 60℃). The temperature is controlled below 60℃ to avoid damaging the exosome activity. S415: A third adhesive is coated on the side of the exosome carrier layer away from the self-heating core layer, with a coating thickness of 0.05 mm. The coating is dried in an oven (temperature 50℃) for 5 minutes. Then, a pH-responsive antibacterial membrane (pre-made, thickness 0.03 mm, made of chitosan-tea tree oil-bromocresol purple) is attached to the third adhesive layer and pressed for 10 seconds using a press (pressure 0.2 MPa, temperature 25℃) to complete the composite molding and obtain the composite layer.

[0030] Example: In this embodiment, the composite structure was subjected to a bending test in a high-altitude simulated environment to simulate knee activity. The bending angle was 90° and the number of cycles was 1000. The tensile strength was tested by a tensile testing machine and the interlayer peel strength remained at 3.5N / 25mm with no delamination. At the same time, the exosome activity test showed that the activity retention rate after hot pressing reached 95%, which meets the requirements for promoting healing.

[0031] In existing technologies, a multilayer medical dressing composite process uses a "single-layer adhesive + one-time pressing" process. The adhesive only fits a single interface, resulting in an interlayer peel strength of less than 2N / 25mm and a delamination rate of 40% after 100 bends. Simultaneously, the hot-pressing temperature is 80℃, leading to a 60% loss of exosome activity. The difference in this process lies in two aspects: first, three different types of adhesives are selected based on the performance requirements of different layers to specifically improve the bonding strength; second, a "step-by-step pressing + low-temperature hot pressing (≤60℃)" process is used to ensure bonding strength while preserving exosome activity. The interlayer peel strength is increased from 2N / 25mm to 3.5N / 25mm, and the delamination rate after 1000 bends decreases from 40% to below 5%. The exosome activity retention rate is increased from 40% to 95%, ensuring stable healing effects and solving the problems of dressing delamination and functional component inactivation during strenuous activities at high altitudes.

[0032] S5 Outer Layer Composite: High-altitude environments are characterized by low temperatures, strong winds, heavy rain, and high UV radiation. Without outer layer protection, rainwater and moisture can seep into the self-heating core layer, causing heating failure. Simultaneously, strong winds accelerate heat loss, disrupting the temperature control effect. However, if the outer layer is completely non-breathable, it will cause skin to feel stuffy and damp, increasing the risk of infection. Therefore, the outer layer needs to achieve a synergistic effect of windproof, waterproof, breathable, and heat-insulating properties to provide a stable working environment for the internal functional layers. Specific technical methods are as follows: Selection and pretreatment of windproof and waterproof membrane: Polyurethane-coated nylon fabric was selected, with nylon 66 as the base material and a thickness of 0.1 mm; the polyurethane coating thickness was 0.03 mm, and the coating adopted a microporous structure with a pore size of 0.1 μm. This material has a wind resistance rating of level 6, with no penetration at a wind speed of 10 m / s, a waterproof rating of IPX7, and no water seepage after immersion in 1 m of water for 30 minutes, with an air permeability of 500 mm / s; the nylon fabric was placed in an oven (temperature 60℃) to dry for 30 minutes to remove surface moisture; Pressure-sensitive adhesive coating: Apply medical silicone pressure-sensitive adhesive (50% solid content, 1500 mPa·s viscosity) to one side of the windproof and waterproof membrane (the side that is in contact with the pH-responsive antibacterial membrane) using a comma scraper. The coating thickness is 0.06 mm. Place it in an oven (temperature 70℃) to dry for 10 minutes to allow the pressure-sensitive adhesive to semi-cur. Roller lamination: Align the windproof and waterproof membrane coated with pressure-sensitive adhesive with the composite layer (the composite layer in step S4, with the pH-responsive antibacterial membrane facing outwards), and place it into a roller lamination machine (pressure 0.2MPa, speed 5m / min, temperature 40℃) for roller lamination to ensure that the membrane and the composite layer are tightly bonded. Edge sealing: The edges of the composite structure are heat-sealed using a heat sealing machine (temperature 120℃, pressure 0.1MPa, time 5 seconds) with a heat sealing width of 5mm to form a sealed edge and prevent rainwater from seeping in from the edge; at the same time, a V-shaped easy-tear opening (depth 2mm, angle 60°) is made on one side of the sealed edge (away from the wound contact surface) using laser cutting technology to facilitate opening during use.

[0033] Example: In this embodiment, the outer composite physiotherapy patch was tested in a high-altitude simulated environment (wind speed 10m / s, rainfall 5mm / h, temperature -10℃): After 2 hours, the moisture content of the inner self-heating core layer was only 8% (the moisture content reached 30% when not sealed), and it still maintained a constant temperature of 36℃; at the same time, the humidity on the skin contact side was 45% (the humidity reached 70% when not breathable), without any stuffiness, meeting the usage needs during high-altitude rainy training.

[0034] In existing technology, an outdoor waterproof dressing uses a polyethylene film as the outer layer, with a waterproof rating of only IPX5 (no water penetration in splashes) and a breathability of only 50mm / s. When used in rainy weather, the internal moisture content reaches 30%, causing the heating core layer to fail. Furthermore, it lacks edge sealing, allowing rainwater to easily seep in from the edges. The differences in this approach are: first, the use of a microporous polyurethane-coated nylon fabric, balancing wind and water resistance with high breathability; second, the addition of an edge heat-sealing process to prevent rainwater from seeping in from the edges; and third, the design of a V-shaped easy-tear opening to improve ease of use in high-altitude environments. The waterproof rating is improved from IPX5 to IPX7, the internal moisture content in rainy weather is reduced from 30% to below 8%, and the failure rate of the heating core layer is reduced from 40% to 5%; the breathability is increased from 50mm / s to 500mm / s, and the skin stuffiness rate is reduced from 70% to below 10%; the easy-tear design shortens the opening time from 30 seconds to 3 seconds, making it suitable for one-handed operation in high-altitude environments.

[0035] S6 Finished Product Processing: In high-altitude medical settings, therapeutic patches need to meet the requirements of "size matching the wound, airtight sealing to prevent moisture, and easy opening": improper size will lead to incomplete wound coverage or waste; poor sealing will cause the self-heating core layer to oxidize and fail prematurely; difficulty in opening will delay emergency treatment. Therefore, finished product processing needs to optimize precise cutting, airtight packaging, and easy-tear openings to ensure the reliability and convenience of the product during storage and use. The specific technical solutions are as follows: Precise cutting: The overall structure after the outer layer is composited (step S5) is placed into a CNC cutting machine. The cutting parameters are set according to the target wound size (10cm×15cm in this embodiment), the cutting speed is 10m / min, and the cutting accuracy is ±0.1cm to obtain a single physiotherapy patch blank. After cutting, the edges are treated with a deburring machine (speed 2000r / min) to avoid burrs scratching the skin. Aseptic treatment: Place the cut blanks into an ethylene oxide sterilizer, set the sterilization concentration to 800 mg / L, temperature to 50℃, humidity to 60%, sterilization time to 6 hours, and ventilate for 48 hours after sterilization to ensure that the residual amount of ethylene oxide is ≤10 μg / g. Sealed packaging: Medical-grade aluminum-plastic composite film (inner layer of polyethylene, outer layer of aluminum foil, thickness 0.15mm) is used as the packaging material. The sterile preform is placed in the packaging film and sealed using a three-side sealing packaging machine (temperature 180℃, pressure 0.3MPa, speed 30 packs / min). The sealing width is 8mm and the sealing strength is ≥15N / 15mm. At the same time, product information (including size, expiration date, and instructions for use) is printed on the surface of the packaging film, and an anti-counterfeiting traceability code is affixed. Optimized tear-off opening: A tear line (0.05mm deep) is created on one side of the packaging film (aligned with the tear-off opening of the therapy patch) using a mechanical indentation process, ensuring that users can quickly open the package along the tear line with an opening force ≤5N (tested by a tensile testing machine).

[0036] Example: In this embodiment, after the finished therapeutic patch was stored in a high-altitude military warehouse (temperature -5℃ to 25℃, humidity 30%-60%) for 6 months, the opening test showed that the self-heating core layer could still generate heat normally (constant temperature 36℃, lasting for 12 hours), and the exosome activity retention rate reached 90%; at the same time, when the user was in the field, it took only 2 seconds to open the patch with one hand along the tear line, and the size completely covered the 10cm×15cm frostbite wound on the knee, without any waste or incomplete coverage.

[0037] In existing technologies, a method for processing finished medical dressings involves manual cutting, resulting in a dimensional deviation of ±0.5cm and an incomplete wound coverage rate of 30%. Simultaneously, the packaging uses a heat-sealed width of 5mm, with a sealing strength of only 10N / 15mm, leading to a 25% failure rate of the heating core layer after 6 months of storage. Furthermore, the packaging lacks an easy-tear opening, requiring 30 seconds to open. The key differences in this approach are: firstly, the use of CNC cutting improves dimensional accuracy to ±0.1cm; secondly, the addition of a tear line optimizes opening convenience; and thirdly, the increased sealing width and strength extend shelf life. The dimensional deviation is reduced from ±0.5cm to ±0.1cm, and the incomplete wound coverage rate is reduced from 30% to below 5%. The sealing strength is increased from 10N / 15mm to 15N / 15mm, and the failure rate of the heating core layer after 6 months of storage is reduced from 25% to 5%. The packaging opening time is shortened from 30 seconds to 2 seconds, meeting the time requirements of high-altitude emergency rescue scenarios.

[0038] S7 Quality Inspection: In high-altitude environments, the performance and reliability of therapeutic patches directly affect wound healing. Issues such as abnormal heating temperature, pH response failure, and substandard waterproofing can lead to treatment failure or even worsen wound damage. Therefore, multi-dimensional quality inspection simulating high-altitude environments is necessary to eliminate substandard products and ensure that each batch meets usage requirements. Specific technical methods are as follows: Sampling plan: 30 samples are randomly selected from each batch of finished products (sampling ratio 1%), of which 15 are used for performance testing and 15 are used for stability testing; Heating performance test: Ten samples were placed in a high and low temperature test chamber to simulate a high-altitude low temperature environment (temperature -10℃, air pressure 60kPa). Thermocouple temperature sensors (accuracy ±0.1℃) were used to monitor the surface temperature of the samples. The constant temperature and constant temperature time were recorded. The constant temperature was required to be 36-37℃ and the constant temperature time was ≥12 hours. pH response performance test: Take 3 samples and immerse them in phosphate buffer solutions with pH=5.5 (normal wound), pH=7.0 (mild infection), and pH=7.5 (severe infection), respectively. Use a UV spectrophotometer to detect the change in heating rate (the heating rate should increase by 0.2-0.3 W / g for every 0.5 increase in pH). At the same time, observe the color change of the antibacterial film in response to pH (it should change from yellow to purple when pH≥7.0). Waterproof and breathable performance test: Take 2 samples and conduct IPX7 waterproof test (immersion in water depth of 1m for 30 minutes) to test the internal moisture content (requirement ≤10%); use a breathability meter to test the air permeability (requirement ≥300mm / s). Stability testing: Fifteen samples were placed in an accelerated aging test chamber (temperature 40℃, humidity 75%) and stored for 3 months. The above test was then repeated, and the performance degradation rate was required to be ≤10%. Handling of non-conforming products: If any test item of a single sample fails to meet the standard, the batch is deemed unconforming. The process parameters (such as the iron powder ratio of the self-heating core layer and the pressure of the composite process) must be readjusted, and the batch must be re-produced and tested again until it passes the test.

[0039] Example: In this embodiment, sampling inspection of a batch of finished products showed that: the constant temperature of all 15 samples was 36.5℃, and the constant temperature time was 12.5 hours; the heating rate increased from 0.5W / g to 0.7W / g at pH=7.0, and the antibacterial film turned purple; after IPX7 testing, the internal moisture content was 8%, and the air permeability was 500mm / s; after 3 months of accelerated aging, the performance degradation rate was only 5%, and the batch was judged to be qualified and could be distributed for use in high-altitude scenarios.

[0040] In existing technologies, a quality testing method for medical dressings only measures heating temperature and size, without simulating high-altitude environments (low temperature, low air pressure) or testing pH response and stability. This results in a 30% failure rate when used at high altitudes. Furthermore, the lack of accelerated aging testing makes it impossible to determine the shelf life. The differences in this approach are: first, it simulates high-altitude, low-temperature, and low-pressure environments for testing, ensuring product suitability for target scenarios; second, it adds pH response performance and accelerated aging testing, covering functional reliability and storage stability; and third, it establishes a strict process for handling non-conforming products to prevent them from entering the market. The failure rate for high-altitude use is reduced from 30% to below 3%; accelerated aging testing extends the shelf life from 6 months to 12 months; and pH response performance testing reduces the false infection rate from 20% to 2%, ensuring the safety and effectiveness of the therapeutic patch in high-altitude environments.

[0041] In summary, the core technical point of this invention lies in breaking through the limitations of existing technologies' "single-function independent design" and solving the four core challenges of wound treatment in high-altitude and low-temperature environments through multi-technology synergy and process innovation: pH-responsive self-heating technology: Unlike existing passive heating dressings, this technology uses a chitosan quaternary ammonium salt-bromocresol purple compound system to achieve adaptive adjustment of the heating rate according to the pH value of the wound. It raises the temperature to promote healing when infected and provides constant temperature protection when not infected, improving the heating efficiency by 40%. Biodegradable exosome carrier technology: Unlike non-biodegradable carriers, it uses a polycaprolactone-gelatin composite matrix and ultrasonic dispersion process to achieve uniform release and complete degradation of exosomes, improving healing efficiency by 50% and reducing secondary damage rate to below 5%. Windproof, waterproof and breathable composite technology: Unlike non-breathable and waterproof outer layers, it uses microporous polyurethane coated nylon fabric with edge heat sealing to achieve "windproof-waterproof-breathable" synergy, reducing the heat loss rate in rainy weather to 5% and the skin stuffiness rate to below 10%; High-altitude adaptation process: Through plasma substrate modification, step-by-step low-temperature composite, CNC cutting and accelerated aging testing, the product is ensured to work stably in high-altitude environments with temperatures ranging from -10℃ to 5℃ and frequent winds and rain, and the overall healing cycle is shortened from 28 days to 14 days.

Claims

1. A method for preparing an intelligent constant temperature physiotherapy patch, characterized in that: Includes the following steps: S1: Substrate pretreatment, selecting medical-grade flexible substrate for cleaning and drying; S2: Preparation of pH-responsive self-heating core layer: The self-heating material is mixed with a pH-sensitive regulator to form a core layer. The pH-responsive self-heating core layer can regulate the heating rate by sensing changes in the external pH. S3: Preparation of the biodegradable stem cell exosome carrier layer, including the following sub-steps: S31, Selecting polycaprolactone and gelatin, mixing them in a preset ratio, heating and melting them to prepare a biodegradable carrier matrix; S32, Mixing stem cell exosomes with the carrier matrix, and dispersing them uniformly in the carrier matrix by ultrasonic dispersion treatment; S33, Coating the carrier matrix containing exosomes onto a release membrane, cooling and molding it, and then peeling off the release membrane to obtain the biodegradable stem cell exosome carrier layer; S4: Composite molding, in which a pH-responsive self-heating core layer, a biodegradable stem cell exosome carrier layer and a pH-responsive antibacterial membrane are sequentially composited on a pretreated substrate to form a composite layer; S5: Outer layer composite, with a windproof and waterproof membrane laminated on the side of the composite layer away from the substrate; S6. Finished product processing: The composite structure is cut and the edges are sealed to obtain the intelligent constant temperature physiotherapy patch; In step S4, the heating rate of the pH-responsive self-heating core layer and the exosome release rate of the degradable stem cell exosome carrier layer are synchronously regulated by the pH response signal, so that the physiotherapy patch maintains stable heating within the constant temperature range of 36-37℃, and the exosome release rate is adaptively adjusted with pH changes.

2. The method for preparing an intelligent constant temperature physiotherapy patch as described in claim 1, characterized in that: In step S2, the preparation of the pH-responsive self-heating core layer includes the following sub-steps: S21, mixing iron powder, activated carbon, and vermiculite in a preset ratio to obtain a basic self-heating mixture; S22, adding a pH-sensitive regulator to the basic self-heating mixture, wherein the pH-sensitive regulator is a compound of chitosan quaternary ammonium salt and bromocresol purple; S23, placing the mixed material in a molding mold and pressing it under a preset pressure to form a sheet-like core layer blank; S24, subjecting the core layer blank to low-temperature drying treatment to obtain the pH-responsive self-heating core layer.

3. The method for preparing an intelligent constant temperature physiotherapy patch as described in claim 1, characterized in that: In step S4, the preparation of the pH-responsive antibacterial membrane includes the following sub-steps: S41, dissolving chitosan in acetic acid solution, adding tea tree oil and stirring evenly to obtain the antibacterial membrane stock solution; S42, adding a pH-sensitive colorimetric agent, bromocresol purple, to the antibacterial membrane stock solution; S43, coating the antibacterial membrane stock solution onto a breathable base membrane, and drying it to form a pH-responsive antibacterial membrane; S44, attaching the pH-responsive antibacterial membrane to the side of the biodegradable stem cell exosome carrier layer away from the pH-responsive self-heating core layer using a medical-grade adhesive.

4. The method for preparing an intelligent constant temperature physiotherapy patch as described in claim 1, characterized in that: In step S4, the specific operations of composite molding include: S411, coating a first adhesive layer onto the pretreated substrate surface; S412, attaching a pH-responsive self-heating core layer to the first adhesive layer and applying a preset pressure to ensure a tight bond between the two; S413, coating a second adhesive layer onto the side of the pH-responsive self-heating core layer away from the substrate; S414, attaching a biodegradable stem cell exosome carrier layer to the second adhesive layer and performing hot-pressing treatment at a preset temperature; S415, coating a third adhesive layer onto the side of the biodegradable stem cell exosome carrier layer away from the pH-responsive self-heating core layer, and attaching a pH-responsive antibacterial film to the third adhesive layer to complete the composite molding.

5. The method for preparing an intelligent constant temperature physiotherapy patch as described in claim 1, characterized in that: In step S5, the specific operations of the outer layer composite include: S51, selecting polyurethane-coated nylon cloth as the substrate for the windproof and waterproof membrane; S52, coating one side of the windproof and waterproof membrane substrate with medical-grade pressure-sensitive adhesive; S53, attaching the windproof and waterproof membrane coated with pressure-sensitive adhesive to the side of the pH-responsive antibacterial membrane away from the degradable stem cell exosome carrier layer, and using a roller pressing process to make the two tightly composite; S54, sealing the edges of the composite windproof and waterproof membrane to prevent external moisture from penetrating.

6. The method for preparing an intelligent constant temperature physiotherapy patch as described in claim 1, characterized in that: In step S6, the specific operations for finished product processing include: S61, cutting the composite overall structure according to the preset size to obtain a single physiotherapy patch blank; S62, sealing the edge of the physiotherapy patch blank using a heat sealing process to form a sealed edge; S63, setting an easy-tear opening on one side of the sealed edge to complete the preparation of the intelligent constant temperature physiotherapy patch.

7. The method for preparing an intelligent constant temperature physiotherapy patch as described in claim 1, characterized in that: It also includes S7: Quality Inspection, which includes the following sub-steps: S71, Select a portion of the finished smart constant temperature therapy patches and test their initial heating temperature and constant temperature maintenance time; S72. Simulate different pH environments and detect the changes in the heating rate of the pH-responsive self-heating core layer and the changes in the exosome release rate of the degradable stem cell exosome carrier layer; S73. Detect the waterproof performance of the windproof and waterproof membrane and the bonding strength of each functional layer; S74. Discard unqualified products and retain qualified products.

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