Effectiveness exploration method for inhibiting AM by exciting LIPUS through flexible ultrasonic patch

Abstract

The invention discloses an effectiveness exploration method for inhibiting AM by exciting LIPUS through a flexible ultrasonic patch, and belongs to the field of medical equipment and biomedical engineering. The patch comprises a flexible substrate, an island bridge type metal electrode, an adjustable array type piezoelectric ceramic unit and a flexible packaging layer, can be precisely attached to a focus area, outputs low-intensity pulse ultrasound with the frequency of 1-3 MHz and the sound intensity of 30-120 mW / cm < 2 >, and can inhibit expression of proinflammatory factors, up-regulate E-cadherin, induce apoptosis of ectopic endometrial cells and inhibit activity of pain ion channels, so that the pain of a patient is relieved, and the pain of the patient is relieved. In-vivo and in-vitro experiments show that the patch does not have significant uterus and ovarian toxicity, can reduce the fibrosis area by 40% or more, can increase the apoptosis rate to 45%, supports a continuous or pulse type adjustable treatment mode, integrates a flexible electronic technology and ultrasonic medicine, and has a wide application prospect. A noninvasive, accurate and wearable innovative treatment scheme is provided for adenomyosis, and the clinical transformation value is remarkable.

Description

Technical Field

[0001] The present invention relates to medical devices and biomedical engineering, and particularly to a method for exploring the effectiveness of a flexible ultrasound patch in stimulating LIPUS to inhibit AM. Background Art

[0002] Adenomyosis (AM) is a common gynecological disease in women of childbearing age, characterized by the invasion of endometrial glands and stroma into the myometrium, and the clinical manifestations include dysmenorrhea, menorrhagia, chronic pelvic pain, and infertility, etc. At present, drug treatments (such as hormone therapy, non-steroidal anti-inflammatory drugs) can only relieve symptoms, and surgical treatments (such as hysterectomy, focused ultrasound ablation) have limitations of large trauma or affecting fertility, and there is a lack of safe and effective non-invasive treatment means.

[0003] Low-intensity pulsed ultrasound (LIPUS, sound intensity < 3W / cm 2 ) shows potential in tissue repair, anti-inflammation, and pain relief due to its advantages of non-invasiveness and no significant thermal damage. However, traditional LIPUS devices are large in size, the probe is rigid, and the operation is interfered by human factors, making it difficult to accurately fit the complex anatomical structure of the uterus, which limits its clinical application. The development of flexible electronics provides a new idea for solving the above problems. Through designs such as island-bridge structures and serpentine lines, portable and wearable flexible ultrasound devices can be fabricated to achieve continuous and adjustable ultrasound stimulation of the target area. Summary of the Invention

[0004] Object of the Invention: The object of the present invention is to provide a safe, effective, and wearable flexible ultrasound patch for targeted treatment of adenomyosis by low-intensity pulsed ultrasound, to solve the limitations of traditional devices, and to provide a new solution for non-invasive treatment of AM.

[0005] Technical Solution: A flexible ultrasound patch, comprising:

[0006] A flexible substrate, made of a biocompatible material, having bendability and mechanical stability, with a thickness of 50 - 200μm;

[0007] Island-bridge type metal electrodes, distributed on the surface of the flexible substrate, forming a stretchable conductive network through serpentine lines or corrugated structures;

[0008] Array-type piezoelectric ceramic units, integrated on the flexible substrate, with a single unit size of 1 - 5mm, the material selected from lead zirconate titanate (PZT) or polyvinylidene fluoride (PVDF), and the array scale of 1×1 to 10×10;

[0009] A flexible encapsulation layer, covering the surface of the flexible substrate and the piezoelectric ceramic units, made of a waterproof and breathable biocompatible material, with a thickness of 20 - 50μm.

[0010] Preferably, the material of the island-bridge type metal electrode is selected from gold, silver or copper, the width of the serpentine line is 50 μm, and the spacing is 100 μm.

[0011] Preferably, the operating parameters of the low-intensity pulsed ultrasound include: frequency 1 - 3 MHz, pulse repetition frequency 500 Hz - 2 kHz, duty cycle 10% - 70%, sound intensity 30 - 120 mW / cm 2 , and the parameters are adjustable through an external controller.

[0012] Preferably, the array number of the piezoelectric ceramic units is dynamically adjusted according to the lesion range, and the number range is 1 - 100 to achieve regional regulation of ultrasonic energy.

[0013] Preferably, the material of the flexible substrate is selected from polyimide or silicone rubber, and the material of the flexible encapsulation layer is selected from parylene.

[0014] An exploration method for the effectiveness of a flexible ultrasound patch in stimulating LIPUS to inhibit AM is achieved through the following mechanisms:

[0015] Inhibit the expression of pro-inflammatory cytokines IL-1β and IL-6, and down-regulate the NF-κB signaling pathway;

[0016] Up-regulate the expression of E-cadherin and inhibit the over-proliferation of α-smooth muscle actin to improve myometrial fibrosis;

[0017] Induce apoptosis of adenomyosis lesion cells, manifested as up-regulation of Caspase-3 expression and down-regulation of Bcl-2 expression;

[0018] Inhibit the activity of pain-related ion channels through mechanical signal transduction to relieve dysmenorrhea and chronic pelvic pain.

[0019] Preferably, the treatment mode includes continuous or pulsed ultrasound output, the single treatment time is 10 - 60 minutes, 1 - 2 times a day, and lasts for 1 - 4 weeks.

[0020] Preferably, the safety and effectiveness of the patch are verified through in vivo experiments, specifically including:

[0021] There is no significant change in the volume of the uterus and ovaries, and the serum estrogen level is stable;

[0022] H&E staining shows a reduction in myometrial damage, TUNEL staining and Western Blot detection confirm an increase in apoptosis; PAS staining shows a reduction in endometriosis lesions, and Masson staining and elastographic imaging show improvement in myometrial fibrosis. The beneficial effects of the present invention:

[0023] 1. Innovation of flexible electronic technology and wearable design

[0024] By combining flexible electronics technology with ultrasonic medicine, the present invention designs a flexible ultrasonic patch that can conform to the human body surface. Traditional low-intensity pulsed ultrasound (LIPUS) devices rely on rigid probes, which are bulky and difficult to adapt to the complex anatomical structure of the uterus. However, the present invention realizes the bendable and stretchable characteristics of the patch through a flexible substrate, island-bridge metal electrodes, and a flexible encapsulation layer, enabling it to accurately conform to the abdominal or uterine surface. This design solves the problems of limited operation of traditional devices and poor patient compliance, providing a technical basis for non-invasive and wearable continuous treatment.

[0025] 2. Precise regulation of adjustable array piezoelectric ceramic units

[0026] The patch uses array piezoelectric ceramic units with a single unit size of 1-5 mm, and the array scale can be dynamically adjusted from 1×1 to 10×10. By adjusting the number and distribution of units, regional precise regulation of ultrasonic energy can be achieved according to the size and location of adenomyosis lesions. This innovation breaks through the limitations of traditional ultrasonic devices with a "one-size-fits-all" approach, significantly improving the individual adaptation ability of treatment, especially suitable for gynecological diseases with complex lesion morphologies.

[0027] 3. Optimized low-intensity pulsed ultrasound parameters and safety guarantee

[0028] The present invention defines the key parameter range of low-intensity pulsed ultrasound (frequency 1-3 MHz, sound intensity 30-120 mW / cm 2 , duty cycle 10%-70%), and verifies its effectiveness in inhibiting inflammation and inducing apoptosis through experiments. Different from traditional high-intensity ultrasound that is prone to cause thermal damage, this parameter range ensures the treatment effect while avoiding tissue thermal effects and the risks of ovarian and uterine toxicity. This optimization solves the pain points of traditional treatment methods with large trauma and many side effects, providing a guarantee for long-term safe treatment.

[0029] 4. Breakthrough in multi-mechanism collaborative treatment and interdisciplinary integration

[0030] The present invention improves the pathological state of adenomyosis through multi-path collaborative effects: inhibiting the expression of pro-inflammatory factors IL-1β and IL-6, downregulating the NF-κB pathway, while upregulating E-cadherin and inhibiting α-smooth muscle actin, reversing myometrial fibrosis, and improving anti-inflammation and fibrosis; inducing apoptosis by activating Caspase-3 and inhibiting Bcl-2 to target and eliminate ectopic endometrial cells; mechanical signal transduction inhibits pain-related ion channels, relieving dysmenorrhea and chronic pain, and thus alleviating pain. This interdisciplinary integration (flexible electronics + biomedicine) not only fills the technical gap in non-invasive treatment of adenomyosis but also provides an expandable technical platform for innovative therapies for other gynecological diseases. Description of the drawings

[0031] Figure 1 This is the flowchart of the operation of the present invention. Detailed implementation manners

[0032] To make the technical solution of the present invention clearer, the present invention will be further described in detail below with reference to specific embodiments.

[0033] As Figure 1 described, the present invention discloses a flexible ultrasonic patch, comprising:

[0034] A flexible substrate, made of a biocompatible material, having flexibility and mechanical stability, with a thickness of 50 - 200 μm;

[0035] Island - bridge - type metal electrodes, distributed on the surface of the flexible substrate, forming a stretchable conductive network through serpentine lines or corrugated structures;

[0036] Array - type piezoelectric ceramic units, integrated on the flexible substrate, with a single - unit size of 1 - 5 mm, the material selected from lead zirconate titanate (PZT) or polyvinylidene fluoride (PVDF), and the array scale being 1×1 to 10×10;

[0037] A flexible encapsulation layer, covering the surface of the flexible substrate and the piezoelectric ceramic units, made of a waterproof and breathable biocompatible material, with a thickness of 20 - 50 μm;

[0038] Among them, through the combination of the flexible substrate, island - bridge - type electrodes, piezoelectric ceramic units and the encapsulation layer, an ultrasonic treatment device that can fit the human body surface is constructed. The flexible substrate (50 - 200 μm thick) provides mechanical stability and flexibility, adapting to the abdominal or uterine surface; the island - bridge - type electrodes (serpentine - line design) ensure the stability of the conductive network during stretching; the piezoelectric ceramic units (1 - 5 mm in size) achieve controllable output of ultrasonic energy; the encapsulation layer (20 - 50 μm thick) provides waterproof and biosecurity.

[0039] As a preferred implementation manner, the material of the island - bridge - type metal electrode is selected from gold, silver or copper, the width of the serpentine line is 50 μm, and the spacing is 100 μm. Further, the electrode performance is optimized through specific materials (gold / silver / copper) and geometric parameters (serpentine - line width 50 μm, spacing 100 μm). The serpentine corrugated structure endows the electrode with high stretchability (>30% deformation), avoiding bending and breaking; the high - conductivity metal ensures stable signal transmission.

[0040] As a preferred implementation manner, the operating parameters of the low - intensity pulsed ultrasound include: frequency 1 - 3 MHz, pulse repetition frequency 500 Hz - 2 kHz, duty cycle 10% - 70%, and sound intensity 30 - 120 mW / cm 2, and the parameters are adjustable through an external controller. Further, key ultrasound parameters (frequency 1 - 3 MHz, sound intensity 30 - 120 mW / cm 2 ) are defined. Combined with the external controller, dynamic adjustment is achieved. By adjusting the duty cycle (10% - 70%) and pulse repetition frequency (500 Hz - 2 kHz) through the controller, the biological response of the lesion is matched. Low-intensity pulses avoid tissue thermal damage, and the adjustable parameters are adapted to different lesion depths (for example, 1 MHz penetrates deeper, and 3 MHz focuses on the shallow layer).

[0041] As a preferred embodiment, the number of arrays of the piezoelectric ceramic units is dynamically adjusted according to the lesion range, and the number range is 1 - 100 to achieve regional regulation of ultrasonic energy. Further, through modular design, the user can increase or decrease the number of piezoelectric units (such as cutting PVDF film into 2 mm units and pasting them). The external controller activates the partitions, and the number of piezoelectric units is adjustable (1 - 100), supporting regional energy output. Specific units are activated for local lesions (such as an 8×8 array) to avoid excessive exposure of healthy tissues; it is adapted to different lesion ranges (for example, only a 1×1 unit is required for small lesions).

[0042] As a preferred embodiment, the material of the flexible substrate is selected from polyimide or silicone rubber, and the material of the flexible encapsulation layer is selected from parylene. Further, material pretreatment (such as plasma cleaning to enhance adhesion), and the edge sealing process of the encapsulation layer ensures no leakage. Specific materials of the flexible substrate (polyimide / silicone rubber) and the encapsulation layer (parylene) are defined. Polyimide is heat-resistant, and silicone rubber is soft and conforms to the skin; parylene is waterproof and breathable, avoiding tissue irritation.

[0043] A method for exploring the effectiveness of a flexible ultrasound patch in stimulating LIPUS to inhibit AM is achieved through the following mechanisms:

[0044] Inhibit the expression of pro-inflammatory cytokines IL-1β and IL-6, and down-regulate the NF-κB signaling pathway;

[0045] Up-regulate the expression of E-cadherin and inhibit the over-proliferation of α-smooth muscle actin, improving myometrial fibrosis;

[0046] Induce apoptosis of adenomyosis lesion cells, manifested as an up-regulation of Caspase-3 expression and a down-regulation of Bcl-2 expression;

[0047] Inhibit the activity of pain-related ion channels through mechanical signal transduction, alleviating dysmenorrhea and chronic pelvic pain;

[0048] Among them, ultrasonic mechanical force regulates cell signaling pathways (such as NF-κB, TGF-β), verifies molecular expression changes through experiments, and achieves treatment through four mechanisms: inhibiting inflammation, inducing apoptosis, improving fibrosis, and relieving pain. It has multi-target intervention (such as downregulating IL-1β / IL-6 and upregulating E-cadherin), comprehensively reversing the pathological process.

[0049] As a preferred implementation mode, the treatment mode includes continuous or pulsed ultrasonic output. The single treatment time is 10 - 60 minutes, 1 - 2 times a day, for 1 - 4 weeks. Further, the controller presets multiple programs (such as 20-minute pulsed treatment once a day), optimizes parameters in combination with clinical feedback, supports continuous or pulsed output modes, defines the single treatment time (10 - 60 minutes) and the treatment course cycle (1 - 4 weeks), and selects the mode according to the patient's tolerance (such as the pulsed mode to reduce discomfort). Long-term treatment can continuously inhibit the lesion.

[0050] As a preferred implementation mode, the safety and effectiveness of the patch are verified through in-vivo experiments, specifically including:

[0051] There are no significant changes in the volume of the uterus and ovaries, and the serum estrogen level is stable;

[0052] H&E staining shows a reduction in myometrial injury, and TUNEL staining and Western Blot detection confirm an increase in apoptosis;

[0053] PAS staining shows a reduction in endometriosis lesions, and Masson staining and elastographic imaging show improvement in myometrial fibrosis. Further, a standardized experimental process (such as H&E staining, TUNEL detection) is used to quantitatively analyze indicators such as inflammatory factors and apoptotic proteins, and the biological effects of the patch are verified through in-vivo and in-vitro experiments (such as rat models, cell models): The data supports non-toxicity (stable uterine volume, normal estrogen), and the curative effect is clear (more than 50% reduction in fibrosis).

[0054] The working process of the present invention:

[0055] 1. Preparation of the flexible ultrasonic patch

[0056] (1) Flexible substrate treatment

[0057] Material selection: Polyimide (PI) or polydimethylsiloxane (PDMS) is selected as the substrate material. Polyimide is heat-resistant (can withstand lithography process) and has high mechanical strength, while polydimethylsiloxane is soft (elastic modulus 0.1 - 1 MPa) and has good conformability.

[0058] Cutting and Pretreatment: Cut the material into 5 cm × 5 cm squares with a thickness controlled at 50 - 200 μm (too thin is prone to tearing, and too thick affects flexibility). Enhance surface hydrophilicity through oxygen plasma cleaning (power 50 W, time 2 minutes) to improve electrode adhesion.

[0059] (2) Preparation of Island - Bridge - Type Metal Electrodes

[0060] Patterning Process: Use lithography technology (ultraviolet exposure wavelength 365 nm, photoresist AZ 5214) to form a serpentine line pattern on the substrate surface.

[0061] Metal Deposition: Deposit a gold (Au) or silver (Ag) layer (thickness 200 - 500 nm) through magnetron sputtering or electron beam evaporation. The width of the serpentine line is 50 μm, the spacing is 100 μm, and the corrugated structure can be stretched to 30% deformation without breaking.

[0062] Post - treatment: Strip the excess photoresist and ultrasonically clean with ethanol to remove residual particles.

[0063] (3) Integration of Piezoelectric Ceramic Units

[0064] Material Processing: Cut polyvinylidene fluoride (PVDF) film or lead zirconate titanate (PZT) ceramic into 1 - 5 mm square units (laser cutting accuracy ±0.1 mm). PVDF has high flexibility, and PZT has a high piezoelectric coefficient (d33≈500 pC / N).

[0065] Conductive Connection: Use conductive silver paste (containing 80 wt% silver particles) to paste the piezoelectric unit to the electrode node. The curing condition is baking at 80°C for 30 minutes to ensure the resistance < 1 Ω.

[0066] Array Configuration: Dynamically adjust the number of units according to the lesion range (e.g., use a 4×4 array for local lesions and expand to an 8×8 array for extensive lesions).

[0067] (4) Covering with a Flexible Encapsulation Layer

[0068] Material Selection: Parylene C is used as the encapsulation material, which has biocompatibility (ISO 10993 certification), waterproofness (water vapor transmission rate < 0.1 g / m 2 / day), and flexibility.

[0069] Vapor Deposition: Heat the Parylene monomer to 150°C for cracking in a vacuum chamber and deposit it on the substrate surface with a thickness of 20 - 50 μm.

[0070] Edge Sealing: Coat and cure the edge of the patch with medical - grade epoxy resin (such as Sylgard 184) to prevent body fluid infiltration.

[0071] 2. Patch Application and Parameter Setting

[0072] (1) Patch Attachment

[0073] Body Surface Attachment: After cleaning the patient's abdominal skin, fix the patch using medical tape or hydrogel dressing to ensure tight contact with the skin (contact impedance < 10 kΩ).

[0074] In-Vivo Implantation (Optional): Implant the patch on the surface of the uterus through minimally invasive surgery and fix it with biodegradable anchoring microneedles.

[0075] (2) Controller Parameter Configuration

[0076] Frequency Selection: 1 MHz is used for deep lesions (penetration depth of about 5 cm), and 3 MHz is used to focus on superficial tissues (penetration depth of about 1.5 cm).

[0077] Sound Intensity Adjustment: Initially set to 30 mW / cm 2 , and gradually increased to 120 mW / cm according to the patient's pain feedback 2 (within the safety threshold).

[0078] Pulse Mode: Duty cycle from 10% (short pulses reduce tissue fatigue) to 70% (continuous stimulation enhances efficacy), and pulse repetition frequency from 500 Hz (soothing mode) to 2 kHz (intensive stimulation).

[0079] Treatment Plan: Preset 1 - 2 times a day, 10 - 60 minutes each time (extended to 60 minutes in the acute phase), and the treatment course is 1 - 4 weeks (extended treatment course for chronic cases).

[0080] 3. Ultrasound Therapy Execution and Biological Mechanisms

[0081] (1) Ultrasound Generation and Propagation

[0082] Piezoelectric Effect: The controller applies an alternating voltage (±10 V) to the electrode, and the piezoelectric unit undergoes the inverse piezoelectric effect, generating mechanical vibrations (amplitude 1 - 10 μm) and emitting ultrasonic waves with a frequency of 1 - 3 MHz.

[0083] Tissue Penetration: The ultrasonic waves propagate through the skin / uterine wall to the lesion, with a sound pressure amplitude of 0.1 - 0.5 MPa, and the mechanical stress acts on the cell membrane and intracellular structures.

[0084] (2) Multi-Mechanism Synergistic Therapy

[0085] Anti-Inflammatory and Fibrosis Reversal:

[0086] NF-κB Pathway Inhibition: The ultrasonic mechanical force interferes with IκBα phosphorylation, reduces NF-κB nuclear translocation, and downregulates the expression of IL-1β and IL-6 (ELISA detection shows a 50% decrease).

[0087] Upregulation of E-cadherin: Ultrasound promotes the transcription of the E-cadherin gene (RT-qPCR shows a 2-fold increase in expression), enhances cell-cell junctions, and inhibits myometrial fibrosis.

[0088] Induction of apoptosis:

[0089] Activation of Caspase-3: Ultrasound triggers a decrease in mitochondrial membrane potential, releases cytochrome C, and activates Caspase-3 (Western Blot shows a 3-fold increase in activity).

[0090] Downregulation of Bcl-2: Ultrasound inhibits the phosphorylation of Bcl-2 and blocks its anti-apoptotic function (immunofluorescence shows a 60% decrease in Bcl-2 expression).

[0091] Pain relief:

[0092] Inhibition of TRPV1 channels: Ultrasound reduces the opening probability of TRPV1 channels (patch clamp recording shows a 70% decrease in current), reducing the transmission of pain signals.

[0093] 4. Verification of safety and efficacy

[0094] (1) In vivo experiment (rat model)

[0095] Model establishment: An AM model was established by uterine myometrium-endometrium suture, and the formation of lesions was confirmed by ultrasound 1 week after the operation (lesion area > 5 mm 2 ).

[0096] Treatment group: Patch parameters 1 MHz, 60 mW / cm 2 , 20 minutes per day for 4 weeks.

[0097] Detection indicators:

[0098] Safety: Uterine volume was measured by ultrasound (change < 5%), and serum estrogen was detected by ELISA (E2 level maintained at 50 - 100 pg / mL).

[0099] Efficacy: Masson staining showed a 40% reduction in collagen deposition, and elastographic ultrasound imaging showed a 30% decrease in myometrial stiffness.

[0100] Molecular mechanism: TUNEL staining showed that the proportion of apoptotic cells increased from 10% to 45%, and Western Blot verified an increase in Caspase-3 activity.

[0101] (2) In vitro experiment (hEM-15A cell model)

[0102] Model establishment: Cells were stimulated with TGF-β1 (10 ng / mL) for 48 hours to induce cell proliferation, migration, and high expression of IL-6.

[0103] Ultrasonic intervention: A micro patch (4 piezoelectric units) was applied with 30 mW / cm 2 ultrasound for 30 minutes.

[0104] Test results:

[0105] Cell migration: The Transwell experiment showed that the number of cells passing through the membrane decreased by 60% (200 in the control group and 80 in the treatment group).

[0106] Inflammatory factors: ELISA detected that the secretion level of IL-6 decreased from 500 pg / mL to 150 pg / mL.

[0107] (3) In-depth verification of molecular mechanism

[0108] Transcriptome sequencing: By comparing the normal group, the AM model group and the treatment group, differential genes (such as COX-2, MMP-9) were screened out. KEGG enrichment analysis showed that the NF-κB and TGF-β / Smad pathways were significantly downregulated.

[0109] Functional verification: After knocking down COX-2 with siRNA, the inflammatory factors in the ultrasonic treatment group were further reduced by 20%, confirming that COX-2 is a key regulatory target.

[0110] The above embodiments only represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention should be subject to the appended claims.

Claims

1. A flexible ultrasonic patch, characterized in that, Comprising: A flexible substrate, made of a biocompatible material, having flexibility and mechanical stability, with a thickness of 50 - 200 μm; Island-bridge type metal electrodes, distributed on the surface of the flexible substrate, forming a stretchable conductive network through serpentine lines or corrugated structures; Array-type piezoelectric ceramic units, integrated on the flexible substrate, with a single unit size of 1 - 5 mm, the material selected from lead zirconate titanate (PZT) or polyvinylidene fluoride (PVDF), and the array scale being 1×1 to 10×10; A flexible encapsulation layer, covering the surface of the flexible substrate and the piezoelectric ceramic units, made of a waterproof and breathable biocompatible material, with a thickness of 20 - 50 μm.

2. The flexible ultrasonic patch according to claim 1, wherein The material of the island-bridge type metal electrodes is selected from gold, silver or copper, the width of the serpentine lines is 50 μm, and the spacing is 100 μm.

3. The flexible ultrasonic patch according to claim 1, characterized in that The working parameters of the low-intensity pulsed ultrasound include: frequency 1 - 3 MHz, pulse repetition frequency 500 Hz - 2 kHz, duty cycle 10% - 70%, sound intensity 30 - 120 mW / cm 2 , and the parameters are adjustable through an external controller.

4. The flexible ultrasonic patch according to claim 1, wherein The number of arrays of the piezoelectric ceramic units is dynamically adjusted according to the lesion range, and the number range is 1 - 100 to achieve regional regulation of ultrasonic energy.

5. The flexible ultrasound patch according to claim 1, characterized in that, The material of the flexible substrate is selected from polyimide or silicone rubber, and the material of the flexible encapsulation layer is selected from parylene.

6. An exploration method for the effectiveness of a flexible ultrasonic patch in stimulating LIPUS to inhibit AM according to any one of claims 1-5, characterized in that, It is achieved through the following mechanisms: Inhibiting the expression of pro-inflammatory cytokines IL-1β and IL-6, and downregulating the NF-κB signaling pathway; Upregulating the expression of E-cadherin and inhibiting the over-proliferation of α-smooth muscle actin, improving myometrial fibrosis; Inducing apoptosis of adenomyosis lesion cells, manifested as upregulation of Caspase-3 expression and downregulation of Bcl-2 expression; Inhibiting the activity of pain-related ion channels through mechanical signal transduction, relieving dysmenorrhea and chronic pelvic pain.

7. An exploration method for the effectiveness of a flexible ultrasonic patch in stimulating LIPUS to inhibit AM according to claim 6, characterized in that The treatment mode includes continuous or pulsed ultrasonic output, with a single treatment time of 10 - 60 minutes, 1 - 2 times a day, for 1 - 4 weeks.

8. A method for exploring the effectiveness of a flexible ultrasonic patch in stimulating LIPUS to inhibit AM according to claim 6, characterized in that The safety and effectiveness of the patch are verified through in-vivo experiments, specifically including: No significant changes in the volume of the uterus and ovaries, and stable serum estrogen levels; H&E staining shows reduced myometrial damage, and TUNEL staining and Western Blot detection confirm increased apoptosis; PAS staining shows reduced endometriosis lesions, and Masson staining and elastographic ultrasound imaging show improved myometrial fibrosis.

Images