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CN-121987195-A - Integrated patch for wound pH detection and nitric oxide gas treatment and preparation method thereof

CN121987195ACN 121987195 ACN121987195 ACN 121987195ACN-121987195-A

Abstract

An integrated patch for wound pH detection and nitric oxide gas treatment and a preparation method thereof relate to a biomedical engineering device which is used for pH monitoring and Nitric Oxide (NO) treatment at a wound. The system monitors the pH value of the wound in real time by adopting a colorimetric method, and utilizes a micro light-emitting diode (LED) as a switch to control the release of nitric oxide, so that the slow release treatment of low-concentration nitric oxide can be realized, and the sterilization treatment can be performed under the high-concentration condition. The patch specifically comprises a flexible circuit and a PVA film, and wireless gas treatment is realized by fixing an NO donor in the PVA film and light. The invention can collect ultrasonic energy in organisms, convert the ultrasonic energy into electric signals based on piezoelectric effect, and realize wireless energy supply. The invention can realize the slow release and quick release of NO and can realize different requirements in medical scenes.

Inventors

  • Long Zhihe
  • JIANG TIANYOU
  • LI LEI
  • XUE XINYU

Assignees

  • 电子科技大学

Dates

Publication Date
20260508
Application Date
20260319

Claims (8)

  1. 1. An integrated patch for wound pH detection and nitric oxide gas treatment is characterized by comprising a flexible packaging layer (1-1), a polyimide substrate (1-2), a flexible circuit and a PVA film (1-7); The flexible circuit comprises a treatment module (1-3), piezoelectric ceramics (1-4), a monitoring module (1-5) and a Bluetooth module (1-6), wherein all parts of the flexible circuit are electrically connected and integrated on the upper surface of a polyimide substrate (1-2), and a PVA film (1-7) covers the flexible circuit on the upper surface of the polyimide substrate (1-2); The PVA film (1-7) is a variable color hydrogel based on polyvinyl alcohol, and the pH indicator and nitrosoglutathione in the variable color hydrogel are sensitive to weak alkaline environment and release NO through light control; When the piezoelectric ceramic receives ultrasound, the energy of the ultrasound is converted into electric energy to supply power for the whole circuit, when a terminal instruction is sent, the Bluetooth module receives the instruction and controls the monitoring module (1-5) to read the color of the PVA film and convert the color into the pH value, and if the detected pH value is larger than a set value, the treatment module (1-3) is controlled to be opened to promote the PVA film (1-7) to release high-concentration NO.
  2. 2. The integrated patch for wound pH detection and nitric oxide gas therapy according to claim 1, wherein said therapeutic module is an ultraviolet light emitting diode, wherein said variable color hydrogel slowly releases NO under ambient light, and wherein said variable color hydrogel releases high concentrations of NO when said ultraviolet light emitting diode is turned on.
  3. 3. An integrated patch for wound pH detection and nitric oxide gas treatment according to claim 1, wherein the monitoring module (1-5) is a trichromatic sensor for observing the color of the hydrogel and determining the pH value by the color, the data measured by the trichromatic sensor is transmitted to the terminal through the bluetooth module, and is directly converted into the pH value after the terminal is processed, and the inflammation appears in the wound if the measured pH value is more than 7.3.
  4. 4. An integrated patch for wound pH detection and nitric oxide gas treatment according to claim 1, wherein the piezoelectric ceramic (1-4) receives an ultrasonic signal from an external ultrasonic source (3-2), converts the ultrasonic signal into a piezoelectric signal, and the piezoelectric signal is subsequently sent to a rectifier bridge in the flexible circuit, providing an energy source for the flexible circuit.
  5. 5. An integrated patch for wound pH detection and nitric oxide gas treatment according to claim 1, wherein said flexible encapsulation layer (1-1) is polydimethylsiloxane and said pH indicator is phenol red.
  6. 6. An integrated patch for wound pH detection and nitric oxide gas treatment according to claim 2, wherein the concentration of NO is 10-15 μm/min for slow release and 60-70 μm/min for high concentration NO release.
  7. 7. A method of manufacturing an integrated patch for wound pH detection and nitric oxide gas therapy according to any of claims 1-6, comprising the steps of: the method comprises the steps of 1, preparing a flexible substrate, performing structural design by using computer-aided design, and then patterning a polyimide film to prepare the flexible substrate and a wire circuit; Integrating the silver electrodes at the upper end and the lower end of the piezoelectric ceramic, integrating the silver electrode at one side of the piezoelectric ceramic with elements on the flexible substrate by using a reflow soldering technology, and then realizing the electrical connection between the silver electrode of the piezoelectric ceramic and the flexible substrate by flying leads, and welding the monitoring module and the Bluetooth module in place; Step 3, preparing a PVA film, namely adding polyvinyl alcohol and polyvinylpyrrolidone into pure water, stirring in a water bath at 85 ℃, cooling, adding nitrosoglutathione and phenol red, stirring uniformly, adding pentanediol into the water bath, stirring, and putting into a mould for drying and molding; And 4, packaging the whole device, adhering the PVA film and the flexible circuit by using Polydimethylsiloxane (PDMS), manufacturing the PDMS film by adopting a spin coating method, and carrying out a small number of times of packaging treatment on the whole device, wherein the obtained whole device is finally in the shape of a wound plaster.
  8. 8. The method of preparing an integrated patch for wound pH detection and nitric oxide gas therapy according to claim 7, wherein each 1g PVA film contains 0.45mg nitrosoglutathione.

Description

Integrated patch for wound pH detection and nitric oxide gas treatment and preparation method thereof Technical Field The invention relates to a biomedical engineering device for pH monitoring and Nitric Oxide (NO) treatment at a wound. The system monitors the pH value of the wound in real time by adopting a colorimetric method, and utilizes a micro light-emitting diode (LED) as a switch to control the release of nitric oxide, so that the slow release treatment of low-concentration nitric oxide can be realized, and the sterilization treatment can be performed under the high-concentration condition. Background Wound healing itself is a highly coordinated, dynamically evolving biological process that includes four overlapping and consecutive stages of hemostasis, inflammation, proliferation and remodeling. The process is regulated by a fine molecular signaling network and involves the synergistic effects of various cells, growth factors and extracellular matrix components. However, this complex process is highly susceptible to interference from a variety of internal and external factors, with bacterial biofilm formation and oxidative stress being the most common negative factors. The former inhibits re-epithelialization and granulation tissue growth by physical barriers and sustained inflammatory stimuli, while the latter destroys cell membranes, proteins and DNA by excess Reactive Oxygen Species (ROS), thereby causing cell senescence or apoptosis. In clinical practice, real-time, accurate assessment of wound status is a precondition for achieving accurate therapy. In recent years, studies have shown that biochemical parameters of the wound microenvironment can be used as effective indicators reflecting the healing process. Among them, the pH value is of great interest because of its convenience in detection and high correlation with healing. Normal skin surfaces are weakly acidic (pH 4-6), whereas acute and chronic wounds often present alkaline environments (pH 7-7.5) due to bacterial metabolism, tissue ischemia and inflammatory cell activity. With the promotion of healing, the pH value of the wound surface is gradually reduced, so that continuous monitoring of the dynamic change of the pH value is not only helpful for judging whether infection exists, but also can be used for evaluating treatment response, and visual healing state feedback is provided for non-professional medical staff and patients. At the same time, the role of gas signaling molecules, in particular Nitric Oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H 2 S), in wound healing regulation is also becoming increasingly important. These endogenous gas transmitters are free to penetrate biological membranes and exert diverse biological effects in deep tissues. NO is produced by Nitric Oxide Synthase (NOS) catalysis, has bidirectional regulation and control effects, namely, the NO promotes angiogenesis, collagen deposition and epithelial proliferation at low concentration, and shows strong antibacterial activity at high concentration, and can directly damage the membrane structure and DNA of pathogens. CO and H 2 S also play an important role in inhibiting inflammation, alleviating oxidative stress, and promoting tissue repair. In particular, NO is clinically used for treating cardiovascular and cerebrovascular diseases (such as pulmonary hypertension and atherosclerosis), and the safety of NO has more evidence-based basis, which lays a foundation for the transformation of NO into the field of wound treatment. Currently, researchers have developed a variety of NO donor molecules (e.g., SNP, GSNO, NONOates) that can release NO in vitro by chemical or photocatalytic mechanisms, and can further be supported in hydrogels, nanoparticles, or polymer matrices to achieve targeted delivery and controlled release. Despite the significant clinical significance of early identification and accurate intervention of wound infection, many challenges remain in the current practice of diagnosis and treatment, resulting in failure of timely and effective treatment by many patients. First, signs of infection (e.g., redness, burning pain, suppuration) tend to be insignificant at an early stage, and clinical manifestations may be very occult especially in elderly, diabetic or immunosuppressed patients. If no continuous and objective monitoring means exists, the intervention window is very easy to miss until severe complications such as bacteremia or tissue necrosis occur. Second, even with suspected infections, current judgment standards are highly dependent on the subjective experience of medical personnel and laboratory microbiological culture results, which typically take 24-72 hours, delaying the precise use of antibiotics and exacerbating the development of drug resistance. In addition, for non-infectious wounds (e.g., ischemic ulcers, venous ulcers), how to avoid overuse of antibacterial drugs, rationally regulate inflammatory reactions, and promote re