Dual-mode response type postoperative infection early-warning intelligent dressing and preparation method thereof

Abstract

The invention discloses a dual-mode response type postoperative infection early-warning intelligent dressing and a preparation method thereof, which are urgent for a novel postoperative dressing with precise infection monitoring, intelligent drug release, excellent material performance, reliable intelligent remote management and low-cost mass production potential. The invention aims at solving the problems of the existing dressing in all directions through an innovative technical scheme. According to the dual-mode response type postoperative infection early-warning intelligent dressing and the preparation method thereof, infection signals are accurately captured, intervention is performed in advance, through cooperative monitoring of the pH sensor (the detection error is + / -0.1) and the temperature sensor (the precision is + / -0.1 DEG C), compared with a traditional single-mode dressing, infection symptoms (for example, the pH is larger than 7.5, and the temperature is larger than 37.5 DEG C) are found 12-48 hours earlier, the infection early-warning accuracy rate is increased to 95% or above, and the application range is wide. The self-calibration technology has the advantages that background interference of double emission silicon points (427nm / 500nm fluorescence peaks) is eliminated through the fluorescence intensity ratio, errors of single-wavelength detection are avoided, and the method is suitable for a complex wound environment.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of surgical prognosis, in particular to a dual-mode response type postoperative infection early warning intelligent dressing and a preparation method thereof. BACKGROUND

[0002] Postoperative infection is a key factor affecting surgical prognosis, seriously threatening the health and rehabilitation process of patients. According to authoritative medical statistics, the incidence of postoperative infection is at a high level worldwide, and the annual additional medical expenditure caused by postoperative infection amounts to tens of billions of dollars. At the same time, the hospitalization time of patients is significantly prolonged, and the pain and death risk of patients are increased.

[0003] Ordinary medical dressings have exposed many difficult-to-overcome technical shortcomings in dealing with postoperative nursing needs. In terms of infection monitoring, at present, most dressings rely on medical staff to regularly uncover the dressing for direct observation. This method not only has a serious time lag, and the infection is often detected when it has developed to a relatively obvious stage, thus delaying the best intervention opportunity. Moreover, the judgment process highly depends on the subjective experience of medical staff, and the judgment standards of different personnel are different, which easily causes misdiagnosis and missed diagnosis.

[0004] In terms of drug release mechanism, the design of traditional dressings has obvious defects. In most cases, the antibacterial drugs are simply loaded in the dressing material and contact the wound by relying on natural diffusion. This passive diffusion process cannot accurately control the release rate and dose of the drugs. At the initial stage of wound infection, when high-concentration drugs are urgently needed to inhibit the reproduction of bacteria, the release amount of the drugs is often insufficient. With the passage of time, when the wound environment is improved, a large amount of drugs may still be continuously released, which not only causes waste of drugs but also increases the risk of drug resistance of bacteria.

[0005] From the perspective of material performance, the material system of the existing dressing is difficult to meet the clinical actual needs. In terms of the balance between air permeability and waterproofness, an ideal solution has always been difficult to find. Some dressings that emphasize air permeability can ensure a certain gas exchange between the wound and the outside world, which is beneficial to cell metabolism, but the waterproof performance is poor, and external pollutants and moisture can easily penetrate into the wound, greatly increasing the risk of infection. Dressings that focus on waterproofness often have poor air permeability, leading to a hot and humid environment in the local wound, which is not conducive to wound healing and may even breed bacteria. In addition, the biocompatibility of the dressing and the wound tissue is also a prominent problem. Some dressing materials can cause allergic reactions, inflammatory stimuli and other adverse reactions during long-term contact with the wound, affecting the normal healing process of the wound. Moreover, when the dressing is replaced, it is easy to adhere to the newly generated granulation tissue, causing secondary damage and additional pain to the patient. SUMMARY

[0006] (1) Technical problems solved

[0007] In view of the deficiencies of the prior art, the present application provides a dual-mode responsive postoperative infection early warning intelligent dressing and a preparation method thereof, and a new type of postoperative dressing with precise infection monitoring, intelligent drug release, excellent material performance, reliable intelligent remote management, and low-cost mass production potential is urgently needed. The present application is based on such a background and is committed to solving the problems existing in the prior art through an innovative technical solution, and providing a more effective means for the prevention and treatment of postoperative infection.

[0008] (ii) Technical solution

[0009] To achieve the above-mentioned object, the present application provides the following technical solution: a dual-mode responsive postoperative infection early warning intelligent dressing, comprising, from bottom to top, a base layer, a sensing layer, a drug release layer and a protective layer; the sensing layer comprises a pH sensor and a temperature sensor, and the drug release layer comprises pH-sensitive drug-loaded microspheres.

[0010] Preferably, the pH sensor is based on a dual-emission fluorescent nanomaterial self-calibration technology, with a detection range of pH 7.0-12.0 and a detection error of ±0.1, and the dual-emission fluorescent nanomaterial has a fluorescence peak of 420-430 nm and 490-510 nm.

[0011] Preferably, the temperature sensor is a thermistor or a two-dimensional nanomaterial, with a detection accuracy of ±0.1℃, and the two-dimensional nanomaterial includes graphene, molybdenum disulfide or hexagonal boron nitride.

[0012] Preferably, the drug-loaded microspheres of the drug release layer are biodegradable polymer microspheres, which are surface-modified with a pH-sensitive polymer coating, and internally encapsulate an antibacterial active ingredient and a pro-coagulation component; when the pH value is >7.5, the drug release rate of the drug-loaded microspheres within 3 minutes is ≥60%.

[0013] Preferably, the biodegradable polymer is poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL), and the pH-sensitive polymer coating is Eudragit-S100 or a chitosan derivative.

[0014] Preferably, the antibacterial active ingredient is a metal ion, an antibiotic or an antibacterial peptide, and the pro-coagulation component is thrombin, fibrinogen or a coagulation factor.

[0015] Preferably, the base layer is a hydrophilic fiber material or a polymer-natural polymer composite material, with a thickness of 0.3-0.8 mm and a liquid absorption capacity of ≥10 g / g, and the hydrophilic fiber material includes non-woven fabric or seaweed fiber, and the composite material includes polyurethane-sodium alginate or polyvinyl alcohol-chitosan.

[0016] Preferably, the protective layer is a breathable waterproof film with a thickness of 0.05-0.2mm and a water vapor transmission rate ≥3000g / m 2 / 24h, and the film material includes polyvinyl alcohol, polyvinylidene fluoride, or polytetrafluoroethylene.

[0017] A preparation method of a dual-mode responsive postoperative infection early warning intelligent dressing, comprising:

[0018] S1, preparing a base layer: hydrophilic fiber material is treated with hydrophilic treatment and sterilization, or a polymer-natural polymer composite film is prepared by a solution mixing-coating method;

[0019] S2, constructing a sensing layer: a pH sensing unit and a temperature sensing unit are formed on the surface of the base layer by a nanomaterial preparation technology;

[0020] S3, preparing a drug release layer: drug-loaded microspheres are prepared by an emulsification-solvent evaporation method, and are coated on the sensing layer after being coated with a pH-sensitive material;

[0021] S4, composite protective layer: a breathable waterproof film is hot-pressed or bonded with the drug release layer.

[0022] Preferably, the nanomaterial of the pH sensing unit in S2 is synthesized by a hydrothermal method or a sol-gel method, the particle size of the drug-loaded microspheres in step (3) is 5-10μm, the encapsulation efficiency is ≥80%, the coating treatment temperature is 25-35℃, and the stirring speed is 200-400r / min.

[0023] (III) Beneficial effects

[0024] Compared with the prior art, the present application provides a dual-mode responsive postoperative infection early warning intelligent dressing and a preparation method thereof, which have the following beneficial effects:

[0025] 1. The dual-mode responsive postoperative infection early warning intelligent dressing and the preparation method thereof can accurately capture infection signals and intervene in advance, and through the cooperative monitoring of a pH sensor (detection error ±0.1) and a temperature sensor (accuracy ±0.1℃), infection signs (such as pH>7.5 and temperature>37.5℃) can be found 12-48 hours earlier than traditional single-mode dressings, the infection early warning accuracy is improved to more than 95%, and the self-calibration technology advantage is that double-emission silicon points (427nm / 500nm fluorescence peaks) eliminate background interference through the fluorescence intensity ratio, avoid the error of single-wavelength detection, and are suitable for complex wound environments.

[0026] 2、The dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method, targeted therapy + reduced side effects, when infection causes pH to rise, Eudragit-S100 modified PLGA microspheres release more than 60% of drugs within 3 minutes, the local drug concentration reaches 5-10 times of that of systemic administration, the antibacterial efficiency is increased by 30%, the amount of antibiotics is reduced by more than 40%, antibacterial drugs (such as silver ions) and coagulation drugs (such as thrombin) are released synchronously, infection is inhibited and hemostasis is accelerated, and the wound healing period is shortened by 15%-20%.

[0027] 3、The dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method, function integration and clinical adaptation, the liquid absorption amount of the non-woven fabric or polyurethane-sodium alginate composite base layer is greater than or equal to 10 g / g, a moist wound environment is maintained, the air permeability is 3200-3500 g / m 2 / 24h, which is increased by 70% compared with traditional dressings, the risk of wound adhesion is reduced, the protective layer is intelligently protected: a water-proof and air-permeable film (such as polyvinylidene fluoride) prevents external pollutants from invading, while allowing oxygen and water vapor to pass through, the dressing replacement frequency is reduced, and the probability of secondary infection is reduced.

[0028] 4、The dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method, biological safety and wearing comfort, the materials such as PLGA and sodium alginate all pass the ISO 10993 cytotoxicity test, and there is no allergic or irritating reaction, so the dressing is suitable for sensitive wounds, the flexible and fitted design: the overall thickness of the dressing is 0.5-1.0 mm, the dressing is soft and fitted to the skin, and the dressing is not easy to shift during movement, the wearing comfort of the patient is improved, and the treatment compliance is improved. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 A dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method total process deployment map are provided for the present application.

[0030] Figure 2 A dressing system internal process of a dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method is provided for the present application.

[0031] Figure 3 A sensing layer working process of a dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method is provided for the present application.

[0032] Figure 4 A drug release layer working process of a dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method is provided for the present application.

[0033] Figure 5 A smart management system working process of a dual-mode responsive postoperative infection early warning intelligent dressing and its preparation method is provided for the present application.

[0034] Figure 6 The application provides a dual-mode response type postoperative infection early warning intelligent dressing and a preparation method thereof and cloud storage and external system interaction process. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the application will be clearly and completely described below with reference to the drawings in the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by a person of ordinary skill in the art without creative work fall within the protection scope of the application.

[0036] Please refer to Figures 1 to 6 The application provides a technical solution: a dual-mode response type postoperative infection early warning intelligent dressing and a preparation method thereof.

[0037] Embodiment 1: Dual-mode response intelligent dressing of polyurethane-sodium alginate base layer

[0038] 1. Base layer preparation

[0039] Polyurethane (PU) with a molecular weight of 80,000 was dissolved in N,N-dimethylformamide (DMF) to prepare a PU solution with a mass-volume ratio of 10%. Sodium alginate (SA) was dissolved in deionized water to prepare a SA solution with a mass-volume ratio of 5%. The PU solution and the SA solution were mixed at a volume ratio of 1:2 and stirred at room temperature for 30 minutes until uniformly dispersed. The mixed solution was coated on a clean glass plate using a film applicator, and the wet film thickness was controlled to be 0.5 mm. Then the glass plate was moved into a constant temperature drying oven at 40℃, and dried for 24 hours until the solvent was completely volatilized. After drying, the solidified film was cut into a size of 10cm x 10cm using a sterile scalpel, and sterilized by ethylene oxide sterilization method (sterilization conditions: temperature 55±5℃, humidity 60±10%, sterilization time 12 hours) to obtain a polyurethane-sodium alginate composite base layer. The base layer has a liquid absorption capacity of 12g / g and good flexibility and air permeability.

[0040] 2. Sensor layer preparation

[0041] 2.1. Preparation of pH sensor:

[0042] The dual-emission silicon dots were prepared by hydrothermal synthesis. Tetraethyl orthosilicate (TEOS), ethanol, and ammonia were mixed in a volume ratio of 1:10:2 and poured into a reaction kettle lined with polytetrafluoroethylene. The hydrothermal reaction was carried out at 80°C for 12 hours. After the reaction was completed, the mixture was transferred to a centrifuge tube and centrifuged at 8000 rpm for 10 minutes. The silicon dot precipitate was collected and washed with ethanol three times, and finally dissolved in ethanol to prepare a silicon dot solution with a concentration of 10 mg / mL. The silicon dot solution was mixed with polyvinylpyrrolidone (PVP, molecular weight 36,000) at a mass ratio of 1:0.5, and ultrasonic dispersion was performed for 30 minutes to obtain a uniform mixture. The mixture was coated on the surface of the base layer using a doctor blade method to form a coating layer with a thickness of about 50 μm. The pH sensing film was dried at 60°C for 2 hours, and the detection range was pH 7.0-12.0 with a detection error of ±0.1.

[0043] 2.2, Temperature sensor preparation:

[0044] A graphene film was prepared on a copper foil substrate by chemical vapor deposition (CVD) method. The copper foil was placed in a quartz tube in a mixed atmosphere of hydrogen and argon (hydrogen flow rate 50 sccm, argon flow rate 500 sccm), heated to 1000°C, and methane (flow rate 50 sccm) was introduced for 30 minutes to prepare a single-layer graphene film. A wet transfer technique was used to transfer the graphene film from the copper foil to the surface of the base layer. An electron beam evaporation device was used to deposit a 5 nm thick titanium layer and a 50 nm thick gold layer on the surface of the graphene film as electrodes. The electrodes were connected by wire bonding technology, and finally the sensor was packaged with polyimide glue to prepare a temperature sensor with a temperature detection accuracy of ±0.1°C.

[0045] 3. Preparation of drug release layer

[0046] 3.1, Preparation of PLGA drug-loaded microspheres:

[0047] 0.5 g of polylactic acid-glycolic acid copolymer (PLGA, molar ratio of lactic acid to glycolic acid 75:25, molecular weight 100,000) was weighed, 100 mg of silver nitrate and 50 mg of thrombin were added, and dissolved in 5 mL of dichloromethane to form an organic phase. The organic phase was slowly added to 50 mL of an aqueous solution containing 1% (mass / volume) polyvinyl alcohol (PVA) and emulsified at a speed of 3000 rpm for 30 minutes to form a stable O / W emulsion. The emulsion was stirred at room temperature for 24 hours to allow the dichloromethane to fully evaporate. After evaporation was complete, the emulsion was transferred to a centrifuge tube and centrifuged at 10,000 rpm for 15 minutes to collect the precipitated microspheres. The microspheres were washed with deionized water three times, and finally dried in a freeze dryer for 48 hours to prepare PLGA drug-loaded microspheres with a particle size of 5-8 μm and a drug encapsulation efficiency of ≥85%.

[0048] 3.2, pH sensitive coating treatment:

[0049] The PLGA drug-loaded microspheres were mixed with an ethanol solution of Eudragit-S100 (mass / volume ratio of 8%) at a mass ratio of 1:2, and added to a three-necked flask. The mixture was stirred at 30°C and 300 r / min for 4 hours. After the coating was completed, the microspheres were dried, and then mixed with a 2% (mass / volume ratio) chitosan solution. The mixed solution was sprayed onto the surface of the sensing layer to form a drug release layer with a thickness of about 100 μm. The drug release layer was cured at room temperature for 12 hours. When the environmental pH value is > 7.5, the drug release layer can release more than 60% of the drug within 3 minutes.

[0050] 4. Protective layer preparation

[0051] A polyvinylidene fluoride (PVDF) solution with a mass / volume ratio of 15% was prepared by dissolving PVDF in N,N-dimethylacetamide (DMAc). The PVDF solution was coated onto the surface of the drug release layer using a doctor blade method to form a wet film with a thickness of about 0.1 mm. The wet film was transferred to a vacuum drying oven at 80°C and dried for 24 hours to obtain a PVDF film. The PVDF film was hot-pressed with the lower layer structure under the following conditions: temperature 80°C, pressure 0.5 MPa, and time 5 minutes. After the hot-pressing was completed, the finished dressing was sterilized by γ-ray sterilization (sterilization dose 25 kGy). The protective layer has a water vapor transmission rate of 3500 g / m 2 / 24h, and has good air permeability and water resistance.

[0052] Example 2: Thermistor-type intelligent dressing based on non-woven fabric base layer

[0053] 1. Base layer preparation

[0054] A polyester non-woven fabric with a grammage of 80 g / m 2 was selected and immersed in a 0.1 mol / L NaOH solution at room temperature for 10 minutes to improve the hydrophilicity of the non-woven fabric. After the treatment was completed, the non-woven fabric was washed to neutral with deionized water, and then placed in a high-pressure steam sterilization pot and sterilized at 121°C and 0.1 MPa for 20 minutes to obtain the non-woven fabric base layer. The liquid absorption capacity of the base layer is 10 g / g, which is increased by 25% compared with the untreated non-woven fabric.

[0055] 2. Sensing layer preparation

[0056] 2.1, Preparation of pH sensor:

[0057] The same method as in Example 1 was used to prepare a dual-emission silicon dot solution, which was mixed with PVP in the same ratio. The mixed solution was coated on the surface of the base layer using a doctor blade method to form a pH sensing thin film with a thickness of about 30 μm, and the drying conditions were the same as in Example 1, thereby preparing a sensor with a pH detection error of ±0.1.

[0058] 2.2, Temperature sensor preparation:

[0059] Preparation of thermistor paste: Barium titanate (BaTiO3) nanoparticles were mixed with an organic binder at a mass ratio of 7:3, and an appropriate amount of solvent was added and ultrasonically dispersed for 1 hour to prepare a uniform paste. The paste was printed on the surface of the base layer using a screen printing technique to form a thermistor pattern with a line width of about 0.5 mm. The printed base layer was placed in a muffle furnace and sintered at 500°C for 2 hours to prepare a negative temperature coefficient (NTC) thermistor. Electrodes were made on both ends of the thermistor by silver paste printing technology, and leads were connected. Finally, the sensor was packaged with epoxy resin to prepare a temperature sensor with a temperature detection accuracy of ±0.1°C.

[0060] 3. Preparation of drug release layer and protective layer

[0061] 3.1, Preparation of drug release layer:

[0062] PLGA drug-loaded microspheres were prepared by the same method as in Example 1, and the emulsification process parameters were adjusted to prepare microspheres with a particle size of 8-10 μm. The microspheres were mixed with Eudragit-S100 ethanol solution at a mass ratio of 1:2.2, stirred at 30°C and 300 r / min for 4 hours, and then mixed with chitosan solution after drying. The mixture was coated on the surface of the sensing layer to form a drug release layer with a thickness of about 80 μm.

[0063] 3.2, Preparation of protective layer:

[0064] A PVA solution with a mass-volume ratio of 10% was prepared by dissolving polyvinyl alcohol (PVA, molecular weight 70,000) in deionized water. The PVA solution was coated on the surface of the drug release layer using a doctor blade method to form a wet film with a thickness of about 0.05 mm. After drying, the protective layer was hydrophobically treated with methyltrimethoxysilane to make the contact angle of the protective layer ≥90°, while maintaining a water vapor transmission rate of 3200 g / m 2 / 24h. Finally, the dressing was sterilized using ultraviolet sterilization for 30 minutes.

[0065] Example 3: Single-drug release dressing of polycaprolactone (PCL) microspheres

[0066] 1. Preparation of base layer and sensing layer

[0067] 1.1, Preparation of base layer:

[0068] The polyurethane-sodium alginate composite base layer was prepared by the same method as in Example 1, and the parameters were kept consistent.

[0069] 1.2, Sensing layer preparation:

[0070] The pH sensor and temperature sensor were prepared by the same method as in Example 1, and the parameters were kept consistent.

[0071] 2. Drug release layer preparation

[0072] 2.1, Preparation of PCL drug-loaded microspheres:

[0073] 0.5 g of polycaprolactone (PCL, molecular weight 50,000) was weighed and added to 150 mg of silver nitrate, and dissolved in 5 mL of dichloromethane to form an organic phase. The organic phase was added to a 50 mL aqueous solution containing 1% (mass / volume) PVA, and emulsified at a speed of 3000 rpm for 30 minutes to form an O / W emulsion. The dichloromethane was volatilized at room temperature for 24 hours, and the microspheres were collected by centrifugation (10000 rpm, 15 minutes), washed with deionized water for 3 times, and freeze-dried for 48 hours to obtain PCL drug-loaded microspheres with a particle size of about 10 μm, a drug loading of 15% (mass ratio), and an encapsulation efficiency of ≥80%.

[0074] 2.2, pH-sensitive coating treatment:

[0075] The PCL drug-loaded microspheres were mixed with an ethanol solution of N-succinyl chitosan (mass / volume ratio of 10%) at a mass ratio of 1:2.5, and added to a three-necked flask, and stirred at 40°C and 200 r / min for 6 hours. After the coating was completed, the microspheres were dried, mixed with the chitosan solution, and coated on the surface of the sensing layer to form a drug release layer with a thickness of about 100 μm. When the environmental pH value is >7.5, the drug release layer can release more than 60% of silver ions within 3 minutes.

[0076] 3. Protective layer preparation

[0077] A polytetrafluoroethylene (PTFE) film was prepared by extrusion molding process, and the thickness of the film was controlled to be 0.2 mm. The PTFE film was hot-pressed with the drug release layer under the following conditions: temperature 100°C, pressure 0.8 MPa, and time 8 minutes. After the hot-pressing was completed, the finished product was sterilized by ethylene oxide sterilization method to obtain the finished product. The water vapor transmission rate of the protective layer was 3500 g / m 2 / 24h, and the waterproof level reached IPX5 level.

[0078] Comparative Example 1: ordinary non-woven fabric dressing

[0079] An ordinary non-woven fabric with a grammage of 80 g / m 2The unmodified polyester non-woven fabric of Example 1 was directly placed in a high-pressure steam sterilization pot and sterilized at 121°C and 0.1 MPa for 20 minutes to obtain a common non-woven fabric dressing. The liquid absorption capacity of the dressing was 8 g / g, and the air permeability was 2000 g / m 2 / 24h, without sensing and drug release functions, and only basic water absorption and isolation functions.

[0080] Comparative Example 2: Single pH sensing dressing

[0081] 1. Base layer preparation

[0082] The common non-woven fabric base layer was prepared by the same method as in Comparative Example 1.

[0083] 2. Sensing layer preparation

[0084] Bromothymol blue was dissolved in ethanol to prepare a solution with a concentration of 5 mg / mL. Polyacrylamide monomer, crosslinking agent N,N-methylenebisacrylamide, and initiator ammonium persulfate were mixed in a mass ratio of 10:0.1:0.05. The bromothymol blue solution and deionized water were added and stirred uniformly, then poured into a mold and polymerized at room temperature for 2 hours to form a polyacrylamide gel loaded with bromothymol blue. The gel was cut into the same size as the base layer and pasted onto the surface of the base layer to prepare a pH sensing layer. The detection error of the sensor was ±0.5, and it did not have temperature detection function.

[0085] 3. Drug release layer preparation

[0086] PLGA drug-loaded microspheres were prepared by the same method as in Example 1, but without pH-sensitive coating treatment. The uncoated PLGA microspheres were mixed with a chitosan solution and coated on the surface of the sensing layer to form a drug release layer. The drug release amount of the drug release layer within 30 minutes at pH>7.5 was only 50% of that of Example 1, and the infection warning delay was more than 24 hours.

[0087] Technical effect of the embodiment

[0088] 1. Material performance optimization:

[0089] 1.1. The polyurethane-sodium alginate composite base layer improves the flexibility and mechanical strength of the dressing through the intermolecular interaction between PU and SA. After 1000 bends, the base layer still has no cracking phenomenon, and is suitable for wound care in active parts such as joints.

[0090] 1.2. The degradation period of polycaprolactone (PCL) microspheres is 14-21 days, which matches the normal healing period of a wound, and can avoid long-term retention of microspheres in the body and reduce the risk of adverse reactions.

[0091] 2. Process feasibility analysis:

[0092] 2.1, The reaction temperature for hydrothermal synthesis of dual-emission silicon dots is controlled at 80℃, which can reduce energy consumption by 40% compared with traditional high-temperature synthesis process, and the reaction conditions are mild, which is easy to scale up.

[0093] 2.2, The process cycle for screen printing thermistors is short, and the preparation time of a single batch can be controlled within 4 hours, which is suitable for mass production, and the equipment investment cost is low.

[0094] 3, Function adjustability:

[0095] 3.1, By adjusting the molar ratio of lactic acid to glycolic acid in PLGA (such as from 75:25 to 50:50), the degradation rate of PLGA and the drug release rate can be changed. Experiments show that when the molar ratio of lactic acid to glycolic acid is 50:50, the drug release rate under the condition of pH>7.5 can be increased to 80% / 5min, which can be flexibly adjusted according to the severity of wound infection.

[0096] 3.2, The waterproof and breathable performance of the protective layer can be optimized by adjusting the concentration of the film-forming material and the process parameters. For example, increasing the concentration of the PVDF solution can improve the waterproof performance of the film, but the drying temperature and time need to be adjusted simultaneously to ensure the breathability.

[0097] 4, Sterilization compatibility verification:

[0098] The dressings of Examples 1-3 were sterilized by ethylene oxide, gamma rays and high-pressure steam sterilization, respectively. The results show that after sterilization, the pH sensor accuracy error fluctuation of the dressing is less than 5%, the temperature detection accuracy error fluctuation is less than 3%, and the drug release rate error fluctuation is less than 8%. The sterilization process does not have a significant impact on the core functions of the dressing, and meets the sterilization requirements of medical devices.

[0099] It should be noted that in this paper, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between the entities or operations. Moreover, the terms "include", "contain" or any other variants thereof are intended to cover non-exclusive inclusion, so that the process, method, article or equipment including a series of elements not only includes those elements, but also includes other elements not explicitly listed or inherent to such process, method, article or equipment. Without more limitations, the element defined by the statement "including one" does not exclude the presence of another identical element in the process, method, article or equipment including the element.

[0100] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are merely exemplary of the principles and application of the present application. Numerous modifications and adaptions can be effected without departing from the spirit and scope of the present application, which is not limited to the exact construction and arrangement described. It is intended, therefore, to cover all modifications and adaptions that fall within the scope of the claims and their equivalents.

Claims

1. A dual-mode responsive postoperative infection warning smart compress, characterized in that: The invention comprises a base layer, a sensing layer, a drug releasing layer and a protective layer arranged in sequence from bottom to top; the sensing layer comprises a pH sensor and a temperature sensor, and the drug releasing layer comprises pH-sensitive drug-loaded microspheres.

2. The dual-mode responsive postoperative infection warning intelligent dressing according to claim 1, characterized in that: The pH sensor is based on dual-emission fluorescent nanomaterial self-calibration technology, with a detection range of pH 7.0-12.0 and a detection error of ±0.

1. The fluorescence peaks of the dual-emission fluorescent nanomaterial are 420-430nm and 490-510nm.

3. The dual-mode responsive postoperative infection warning intelligent dressing according to claim 1, characterized in that: The temperature sensor is a thermistor or a two-dimensional nanomaterial with a detection accuracy of ±0.1°C. The two-dimensional nanomaterial includes graphene, molybdenum disulfide or hexagonal boron nitride.

4. The dual-mode responsive postoperative infection warning intelligent dressing according to claim 1, characterized in that: The drug-loaded microspheres in the drug-releasing layer are biodegradable polymer microspheres, the surface of which is modified with a pH-sensitive polymer coating and the interior of which contains antibacterial active ingredients and procoagulant ingredients; when the pH value is greater than 7.5, the drug release rate of the drug-loaded microspheres within 3 minutes is greater than or equal to 60%.

5. The dual-mode responsive postoperative infection warning intelligent dressing according to claim 1, characterized in that: The biodegradable polymer is polylactic acid-glycolic acid copolymer (PLGA) or polycaprolactone (PCL), and the pH-sensitive polymer coating is Eudragit-S100 or a chitosan derivative.

6. The dual-mode responsive postoperative infection warning intelligent dressing according to claim 1, characterized in that: The antimicrobial active component is a metal ion, an antibiotic or an antimicrobial peptide, and the procoagulant component is thrombin, fibrinogen or a coagulation factor.

7. The dual-mode responsive postoperative infection warning intelligent dressing according to claim 1, characterized in that: The base layer is a hydrophilic fiber material or a polymer-natural high polymer composite material with a thickness of 0.3-0.8 mm and a liquid absorption capacity of ≥10 g / g. The hydrophilic fiber material includes non-woven fabric or seaweed fiber, and the composite material includes polyurethane-sodium alginate or polyvinyl alcohol-chitosan.

8. The dual-mode responsive postoperative infection warning smart compress according to claim 1, characterized in that: The protective layer is a breathable waterproof film with a thickness of 0.05-0.2mm and a water vapor transmission rate of ≥3000g / m 2 / 24h, the film material includes polyvinyl alcohol, polyvinylidene fluoride or polytetrafluoroethylene.

9. A method for preparing a dual-mode responsive postoperative infection warning intelligent dressing according to any one of claims 1 to 8, characterized in that: include: S1. Preparing a base layer: treating a hydrophilic fiber material and sterilizing it, or preparing a polymer-natural polymer composite membrane by a solution mixing-coating method; S2. Constructing the sensing layer: forming pH sensing units and temperature sensing units on the surface of the base layer through nanomaterial preparation technology; S3. Preparation of drug release layer: drug-loaded microspheres are prepared by emulsification-solvent evaporation method, coated with pH sensitive material and then applied to the sensing layer; S4. Composite protective layer: The breathable and waterproof film is composited with the drug-releasing layer by heat pressing or adhesive.

10. The method for preparing a dual-mode responsive postoperative infection warning intelligent dressing according to claim 1, characterized in that: The nanomaterials of the pH sensing unit in S2 are synthesized by a hydrothermal method or a sol-gel method. The particle size of the drug-loaded microspheres in step (3) is 5-10 μm, the encapsulation efficiency is ≥80%, the coating treatment temperature is 25-35° C., and the stirring speed is 200-400 r / min.

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