A solid ultrasonic coupling pad that can be adhered to both sides and its preparation method

Abstract

This invention belongs to the fields of acoustics, medicine, and hydrogel materials, and discloses a double-sided adhesive solid ultrasonic coupling pad and its preparation method. The solid ultrasonic coupling pad comprises a polyol-based humectant, phenols, polyacrylic acid-based adhesive components, and polyacrylamide-based mechanical support components. The double-sided adhesive solid ultrasonic coupling pad is a homogeneous hydrogel sheet formed by covalent and non-covalent interactions of these components; the mass fraction of the polyacrylamide component in the homogeneous hydrogel sheet is 1.93~5.57 wt%. This invention improves the composition and preparation method of the solid ultrasonic coupling pad, including the corresponding reaction materials and reaction process design. The resulting solid ultrasonic coupling pad possesses both excellent acoustic properties and the ability to couple ultrasound, as well as excellent adhesion performance, effectively overcoming the problem of insufficient adhesion in conventional solid ultrasonic coupling pads during use.

Description

Technical Field

[0001] This invention belongs to the fields of acoustics, medicine, and hydrogel materials, and more specifically, relates to a double-sided adhesive solid ultrasound coupling pad and its preparation method. The resulting double-sided adhesive solid ultrasound coupling pad can be used, in particular, as a novel auxiliary material for ultrasound monitoring in clinical applications, enabling long-term stable imaging between the ultrasound probe and the skin surface. Background Technology

[0002] Ultrasound testing is a common medical diagnostic method that utilizes the propagation of ultrasound waves within the human body for high-quality imaging and disease diagnosis. Ultrasound coupling pads, essential components of ultrasound testing, improve the transmission of sound energy between the probe and the human body. By eliminating air gaps between the probe and the body surface, they increase the reciprocating transmission rate of ultrasound waves, allowing them to effectively enter the body.

[0003] However, conventional ultrasound coupling pads are usually made of liquid materials, which presents problems such as inconvenience in use, the need for regular replacement, and difficulty in fixation. Existing solid ultrasound coupling pads have limited research, and their adhesion properties do not meet clinical requirements, making them unsuitable for imaging irregular skin surfaces.

[0004] The research group of the inventors of this invention previously developed a hydrogel ultrasound coupling patch for long-term stable continuous monitoring (see Chinese patent application CN120661701A). Although it also disclosed an adhesive solid ultrasound coupling patch, when the sodium alginate patch is adhered to a fixed position for a long time, sweat will be present on the skin surface. The sodium ions in the sweat will undergo ion exchange with the carboxyl groups of sodium alginate, thereby destroying the hydrogen bonds between sodium alginate and glycerol. This leads to the dissociation or even dissolution of the cross-linked structure of the patch. Therefore, it cannot be used for long-term stable ultrasound detection, especially for postoperative stable detection in people who sweat easily and for long-term high-intensity focused ultrasound treatment. Summary of the Invention

[0005] To address the aforementioned deficiencies or improvement needs of existing technologies, the present invention aims to provide a double-sided adhesive solid ultrasound coupling pad and its preparation method. By improving the composition and preparation method of the solid ultrasound coupling pad, including the corresponding reaction materials and reaction process design, the resulting solid ultrasound coupling pad possesses both excellent acoustic properties and the ability to couple ultrasound waves, as well as excellent adhesive properties. This effectively overcomes the problem of insufficient adhesion in conventional solid ultrasound coupling pads during use, optimizes the contact between the ultrasound probe and the skin, and significantly improves ultrasound transmission efficiency and imaging quality. Furthermore, its excellent tensile and elongation properties make it particularly suitable for instruments requiring large-area imaging, such as breast ultrasound.

[0006] To achieve the above objectives, according to one aspect of the present invention, a double-sided adhesive solid ultrasonic coupling pad is provided, characterized in that it comprises a polyol-based moisturizing agent, phenols, polyacrylic acid-based adhesive components, and polyacrylamide-based mechanical support components, wherein the double-sided adhesive solid ultrasonic coupling pad is a homogeneous hydrogel sheet formed by these components through covalent and non-covalent interactions. The phenols include both polydopamine and tannic acid. The mass fraction of polyacrylamide components in the homogeneous hydrogel sheet is 1.93~5.57 wt%.

[0007] As a further preferred embodiment of the present invention, the polyol moisturizing component includes one of glycerol, propylene glycol, and butylene glycol; Preferably, the polyol-based moisturizing agent is glycerol; the mass fraction of the polyol-based moisturizing agent in the homogeneous hydrogel sheet is 30.45~31.62 wt%. The polyacrylic adhesive component is selected from at least one of polyacrylic acid and polymethacrylic acid; The polyacrylamide-based mechanical support component is selected from at least one of polyacrylamide, polyhydroxymethylacrylamide, and polydimethylaminoacrylamide.

[0008] As a further preferred embodiment of the present invention, the phenolic compound is a mixture of polydopamine and tannic acid, or the phenolic compound is a mixture of polydopamine, tannic acid and other polyphenolic hydroxyl materials; preferably, the other polyphenolic hydroxyl materials are pyrocyanic acid.

[0009] As a further preferred embodiment of the present invention, the tensile stress at break of the solid ultrasonic coupling pad does not exceed 15.11 kPa, and the strain is 200%~900%. Preferably, the thickness of the double-sided adhered solid ultrasonic coupling pad is 1.0~10mm.

[0010] As a further preferred embodiment of the present invention, the polyacrylic acid composition in the homogeneous hydrogel sheet is 13.93~14.46 wt%; The tannic acid in the homogeneous hydrogel sheet has a mass fraction of 2.78~2.89 wt%.

[0011] According to another aspect of the present invention, the present invention provides a method for preparing the above-mentioned double-sided adhesive solid ultrasonic coupling pad, characterized in that the preparation method involves mixing and dissolving a polyol humectant, a phenolic raw material, an acrylic monomer raw material, an acrylamide monomer raw material, an initiator, and a crosslinking agent in a NaOH solution, stirring uniformly to form a prepolymer solution; placing the prepolymer solution in a sheet mold for sealing and polymerizing it into a sheet hydrogel by ultraviolet light initiation; washing after soaking to obtain the double-sided adhesive solid ultrasonic coupling pad; wherein the free radical initiator includes any one of 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (L2959), ammonium persulfate (APS), α-ketoglutarate, and 2-hydroxy-2-methyl-1-phenyl-1-propanone (1173); The crosslinking agent is any one of N,N-methylenebisacrylamide, gelatin methacrylate, hyaluronic acid methacrylate, oxidized methacrylate, diacrylic acid, polyvinyl alcohol, cycloalkenyl acrylate, amino acrylate, polyethylene glycol diacrylate, and polyethylene glycol dimethacrylate. Preferably, the sheet mold is a hollow acrylic mold with a glass sheet at the bottom, and the upper surface of the mold can be sealed by another glass sheet.

[0012] As a further preferred embodiment of the present invention, the phenolic raw material includes both dopamine hydrochloride and tannic acid, and the preparation method specifically includes the following steps: (1) Dissolve dopamine hydrochloride in NaOH solution, and let dopamine hydrochloride self-polymerize in air atmosphere under stirring, and form polydopamine chains by oxygen and base-induced prepolymerization; (2) Add acrylic monomer raw materials, tannic acid, polyol and acrylamide monomer raw materials to the solution obtained in step (1) and mix evenly; (3) Under light-protected conditions, the crosslinking agent and free radical initiator are added to the solution obtained in step (2) and stirred to dissolve, thus obtaining the overall solution; (4) Pour the total solution obtained in step (3) into a hollow acrylic mold with a glass plate at the bottom, and seal it with another glass plate. (5) Place the sealed mold containing the solution under ultraviolet light for cross-linking and curing. After gelation, a hydrogel sheet with adhesive properties can be obtained. (6) For the hydrogel sheet obtained in step (5), remove the glass sheets on both sides of the mold, clean and remove the residual solution on the surface, and you can get a solid ultrasonic coupling pad with double-sided adhesion.

[0013] As a further preferred embodiment of the present invention, in step (1), the concentration of the NaOH solution is 0.1~0.3 M; dopamine hydrochloride is dissolved in the NaOH solution, and the concentration of the dopamine hydrochloride is 2-5 mg / mL; the self-polymerization time is 40~60 min; In step (2), the acrylic monomer raw material is acrylic acid, with a concentration of 13.93~14.46 wt% in the total solution; the tannic acid has a concentration of 2.78~2.89 wt% in the total solution; the polyol is glycerol, with a concentration of 30.45~31.62 wt% in the total solution; and the acrylamide monomer raw material is acrylamide, with a concentration of 1.93~5.57 wt% in the total solution. In step (3), the crosslinking agent is N,N-methylenebisacrylamide, and its concentration in the total solution is 0.093~0.096 wt%; the free radical initiator is 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (L2959), and its concentration in the total solution is 0.84~0.87 wt%; the stirring is done by magnetic stirring, with a stirring speed of 50~2000 r / min and a stirring time of 1~60 min; In step (4), the depth of the mold is 1~10 mm; In step (5), the ultraviolet wavelength of the ultraviolet light irradiation is 365 nm, and the intensity is 200~500 mJ / cm. 2 The time is 40-60 minutes.

[0014] As a further preferred embodiment of the present invention, in step (6), the cleaning is performed by rinsing with deionized water.

[0015] According to another aspect of the present invention, the present invention provides the application of the above-mentioned double-sided adhesive solid ultrasound coupling pad in the preparation of an in vitro ultrasound coupling patch, wherein the in vitro ultrasound coupling patch is used to adhere between the skin surface and the ultrasound probe, and can form covalent and non-covalent bonds with the skin surface and non-covalent bonds with the probe surface, thereby achieving long-term stable imaging detection. Preferably, the external ultrasound coupling patch is a sweat-resistant external ultrasound coupling patch that can withstand the sweat secreted by the skin.

[0016] Compared with existing technologies, the solid coupling pad obtained by this invention primarily functions as a hydrogel patch (e.g., a circular patch), allowing the ultrasound probe to be tightly adhered to the skin surface via its adhesive surface. When used as a coupling medium for ultrasound imaging, it enables clear observation of the radial artery, kidneys, bladder, and liver. Testing has shown that the ultrasound coupling pad exhibits good ultrasound performance. When used as a coupling medium for ultrasound imaging, and in conjunction with a medical topical ultrasound coupling agent for small areas of the radial artery, it consistently produces good imaging results. Using the ultrasound coupling pad as a coupling medium also enables clear large-area imaging of the breast using ultrasound. Furthermore, the ultrasound coupling pad does not damage the skin when applied to the skin surface, demonstrating good skin-friendliness.

[0017] The double-sided adhesive hydrogel ultrasound coupling pad obtained by this invention is a novel solid coupling patch with excellent adhesion properties, enabling the ultrasound probe to adhere stably to the skin surface for imaging, such as the radial artery and breast. The double-sided adhesive ultrasound coupling pad obtained by this invention possesses excellent mechanical properties, softness, and skin-friendliness, and will not cause discomfort or skin allergies in patients during testing.

[0018] Specifically, the present invention can achieve the following beneficial effects: 1. The substrate material of the double-sided adhesive solid coupling pad obtained by the present invention is a hydrogel with adhesive properties. Its excellent adhesive properties enable the ultrasound probe to fit more closely with the skin surface, thereby eliminating the possibility of unclear imaging caused by air and air bubbles between the coupling pad and the skin.

[0019] 2. The double-sided adhesive solid coupling pad obtained by the present invention has long-term moisture retention and stability, does not require constant replenishment of coupling material, and can achieve long-term monitoring without affecting the test subject's small-scale movements.

[0020] 3. The solid coupling pad obtained by the present invention adopts a multi-network structure (i.e., polyacrylamide / polyacrylic acid / polydopamine), which makes it not only have good tensile properties but also less prone to breakage, and can effectively meet the application of breast ultrasound, which requires a large area of ​​ultrasound coupling pad.

[0021] 4. This invention uses polyacrylamide as the mechanical support component, especially polyacrylamide (the corresponding monomer raw material used is acrylamide). During the preparation process, the amount of acrylamide added is controlled to be 1.93~5.57wt% of the total solution. Under free radical reaction, the vinyl group of acrylamide will break to form a long chain structure, which not only ensures the smooth gelation of the coupling pad, but also improves the mechanical properties of the coupling pad through dissipative mechanics (the mass fraction of polyacrylamide in the obtained solid ultrasonic coupling pad is 1.93~5.57wt%).

[0022] 5. Furthermore, unlike previous research findings on hydrogel ultrasonic coupling patches for long-term stable continuous monitoring (see Chinese patent application CN120661701A), the solid ultrasonic coupling pad that can be adhered to both sides of the present invention exhibits better sweat resistance, making it particularly suitable for use as a sweat-resistant external ultrasonic coupling patch. Moreover, the coupling pad prepared by the present invention has a lower attenuation coefficient and better acoustic properties compared to previous research results. Attached Figure Description

[0023] Figure 1 These are physical images and network structure diagrams of a double-sided adhesive solid ultrasonic coupling pad.

[0024] Figure 2 These are the stress-strain curves of the ultrasonic coupling pads obtained in Examples 1-3 and Comparative Example 2. In Example 1, the acrylamide mass was 10 g; in Example 2, it was 20 g; in Example 3, it was 30 g; and in Comparative Example 2, it was 40 g.

[0025] Figure 3 This is the adhesion strength of the double-sided adhesive solid ultrasonic coupling pad obtained in Implementation Case 3 to the probe and pigskin compared to the commercial coupling patch. Additionally, the commercial coupling patch was purchased from Zhengzhou Kangyijian Medical Device Co., Ltd., and is circular with a diameter of 45 mm and a thickness of 3 mm, with an error of + / -10% (Product Registration Number: Yu Zheng Xie Bei 20160052, Production Registration Certificate Number: Yu Zheng Shi Yao Jian Xie Sheng Chan Bei 20150009).

[0026] Figure 4 This is a comparison of the ultrasound performance data of the solid coupling pad obtained in Implementation Case 3 and the alginate patch of Example 1 in the previous research Chinese patent application CN120661701A. It shows the small-area imaging effect of the human radial artery compared to commercial coupling agents (from left to right: ultrasound coupling pad radial artery imaging, ultrasound coupling agent radial artery imaging, ultrasound coupling pad radial artery imaging after 24 hours; where "ultrasound coupling pad radial artery imaging" is the immediate imaging after application; "ultrasound coupling pad radial artery imaging after 24 hours" refers to ultrasound imaging performed after the ultrasound coupling pad was continuously applied to the arm of the subject volunteer for 24 hours; ultrasound imaging with a specific time mentioned in this invention refers to imaging after the corresponding application time; ultrasound imaging without a specific time mentioned refers to immediate imaging after application), and the effect of large-area imaging of the human breast.

[0027] Figure 5 The test results for the water loss rate of the solid coupling pad obtained in Example Case 3 within 48 hours under ambient temperature of 25 ℃ and body temperature simulation environment of 37 ℃.

[0028] Figure 6The toxicity of human immortalized epidermal cells (HaCaT) co-cultured with the solid ultrasonic coupling pad obtained in Case 3 for 24 h and 72 h was evaluated using the CCK-8 assay. The specific procedures for the "solid coupling pad" group were as follows: ① The solid coupling pad obtained in Case 3 was thoroughly soaked in deionized water to remove unreacted residues, and then sterilized with ultraviolet light after soaking; ② A small piece of the coupling pad was placed in cell culture medium to form an extract solution of 0.2 g / mL; ③ HaCaT cells in the logarithmic growth phase were seeded into 96-well plates (5,000 cells / well). After cell attachment, the corresponding extract solution was used to culture the cells in the 96-well plates for 24 h and 72 h, respectively; ④ After culture, the culture medium was removed, each well was washed twice with PBS, 10 μl of CCK-8 working solution was added, and the plates were incubated in a 5% CO2, 37℃ incubator for 4 h. After 4 h of culture, the absorbance at 450 nm was measured using a microplate reader. The "control group" used culture medium without hydrogel sheets to culture cells. Results showed that the solid coupling pad did not affect the growth of HaCaT cells (cell survival rate exceeding the critical requirement of 75%), demonstrating good skin-friendliness.

[0029] Figure 7 The coupling pad of Example 3 and the alginate patch of Example 1 in Chinese patent application CN120661701A were immersed in simulated sweat to verify their ability to resist the effects of sweat. The simulated sweat was prepared by dissolving 0.45 g sodium chloride, 0.3 g potassium chloride, 0.3 g sodium sulfate, 0.2 g ammonium chloride, and 0.2 g lactic acid in deionized water and bringing the volume to 100 mL. Example 3 and the alginate coupling patch were placed in petri dishes containing the same volume of solution, and the structural state of the two coupling media was observed after immersion for 4 h and 8 h, respectively. Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0031] The raw materials used in the following examples and comparative examples, such as dopamine hydrochloride (CAS: 62-31-7), acrylamide (CAS: 79-06-1), acrylic acid (CAS: 79-10-7), and glycerin (CAS: 56-81-5), were all commercially available.

[0032] Implementation Case 1: (1) Add dopamine hydrochloride to a 0.1 M NaOH solution and stir for self-polymerization at room temperature for 40 min. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad described in this invention, the concentration of dopamine is 5 mg / mL.

[0033] (2) Add acrylic acid, tannic acid, acrylamide, and glycerol (without introducing additional water or other solvents) to 200 g of polydopamine solution, and dissolve by magnetic stirring at room temperature, a magnetic stirring rate of 250 r / min, and a stirring time of 30 min. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad of the present invention, the mass ratio of tannic acid to polyacrylic acid is tannic acid:acrylic acid = 3:15 (wherein, the mass fraction of tannic acid is 2.89 wt%, and the mass fraction of acrylic acid is 14.46 wt%; in this embodiment, the amount of tannic acid is 15 g, and the amount of acrylic acid is 75 g); the amount of glycerol is 164 g, and the corresponding mass fraction of glycerol is 31.62 wt%; the amount of acrylamide is 10 g, and the corresponding mass fraction of acrylamide is 1.93 wt% (the mass fractions appearing in this paragraph are the mass fractions of the corresponding components in the total solution obtained in the subsequent step 3; the subsequent embodiments are similar).

[0034] (3) Under light-protected conditions, N,N-methylenebisacrylamide crosslinking agent (in the form of an aqueous crosslinking agent solution with a crosslinking agent concentration of 1 wt%) and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone initiator (in the form of a pure solid initiator) are added to the mixed solution and stirred continuously until completely dissolved to obtain the total solution. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad of the present invention, the amount of the crosslinking agent aqueous solution is 50 g, and the corresponding crosslinking agent is 0.096 wt% (this mass fraction refers to the mass fraction of the crosslinking agent in the total solution obtained in step 3; subsequent embodiments are similar); the amount of the initiator is 4.5 g, and the corresponding initiator is 0.87 wt% (this mass fraction refers to the mass fraction of the initiator in the total solution obtained in step 3; subsequent embodiments are similar), and the total mass of the solution is 518.5 g.

[0035] (4) Pour the completely dissolved solution into a 2 mm thick mold (the molds used in this embodiment are all 2 mm hollow acrylic plates), seal the top and bottom with glass plates (to prevent excessive oxygen from affecting the reaction), and place it at 365 nm 500 mJ / cm 2 The hydrogel sheet is cured and formed in an ultraviolet crosslinker with light intensity, and can be obtained after 40 minutes.

[0036] (5) After the hydrogel sheet is demolded from the glass sheet, the residual solution on the surface is rinsed with deionized water to obtain the ultrasonic coupling pad with double-sided adhesion.

[0037] Implementation Case 2: (1) Add dopamine hydrochloride to a 0.1 M NaOH solution and stir for self-polymerization at room temperature for 40 min. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad described in this invention, the concentration of dopamine is 5 mg / mL.

[0038] (2) Add acrylic acid, tannic acid, acrylamide, and glycerol (without introducing additional water or other solvents) to 200 g of polydopamine solution, and dissolve by magnetic stirring at room temperature, a magnetic stirring rate of 250 r / min, and a stirring time of 30 min. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad of the present invention, the mass ratio of tannic acid to polyacrylic acid is tannic acid:acrylic acid = 3:15 (wherein, the mass fraction of tannic acid is 2.84 wt%, and the mass fraction of acrylic acid is 14.2 wt%; in this embodiment, the amount of tannic acid is 15 g, and the amount of acrylic acid is 75 g); the amount of glycerol is 164 g, and the corresponding mass fraction of glycerol is 31.03 wt%; the amount of acrylamide is 20 g, and the corresponding mass fraction of acrylamide is 3.78 wt% (the mass fractions appearing in this paragraph are the mass fractions of the corresponding components in the total solution obtained in the subsequent step 3; the subsequent embodiments are similar).

[0039] (3) Under light-protected conditions, N,N-methylenebisacrylamide crosslinking agent (in the form of an aqueous crosslinking agent solution with a crosslinking agent concentration of 1 wt%) and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone initiator (in the form of a pure solid initiator) are added to the mixed solution and stirred continuously until completely dissolved to obtain the total solution. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad of the present invention, the amount of the crosslinking agent aqueous solution is 50 g, and the corresponding crosslinking agent is 0.095 wt% (this mass fraction refers to the mass fraction of the crosslinking agent in the total solution obtained in step 3; subsequent embodiments are similar); the amount of the initiator is 4.5 g, and the corresponding initiator is 0.85 wt% (this mass fraction refers to the mass fraction of the initiator in the total solution obtained in step 3; subsequent embodiments are similar), and the total mass of the solution is 528.5 g.

[0040] (4) Pour the completely dissolved solution into a 2 mm thick mold (the molds used in this embodiment are all 2 mm hollow acrylic plates), seal the top and bottom with glass plates (to prevent excessive oxygen from affecting the reaction), and place it at 365 nm 500 mJ / cm 2 The hydrogel sheet is cured and formed in an ultraviolet crosslinker with light intensity, and can be obtained after 40 minutes.

[0041] (5) After the hydrogel sheet is demolded from the glass sheet, the residual solution on the surface is rinsed with deionized water to obtain the ultrasonic coupling pad with double-sided adhesion.

[0042] Implementation Case 3: (1) Add dopamine hydrochloride to a 0.1 M NaOH solution and stir for self-polymerization at room temperature for 40 min. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad described in this invention, the concentration of dopamine is 5 mg / mL.

[0043] (2) Add acrylic acid, tannic acid, acrylamide, and glycerol (without introducing additional water or other solvents) to 200 g of polydopamine solution, and dissolve by magnetic stirring at room temperature, a magnetic stirring rate of 250 r / min, and a stirring time of 30 min. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad of the present invention, the mass ratio of tannic acid to polyacrylic acid is tannic acid:acrylic acid = 3:15 (wherein, the mass fraction of tannic acid is 2.78 wt%, and the mass fraction of acrylic acid is 13.93 wt%; in this embodiment, the amount of tannic acid used is 15 g, and the amount of acrylic acid used is 75 g); the amount of glycerol used is 164 g, corresponding to a mass fraction of 30.45 wt%; the amount of acrylamide used is 30 g, corresponding to a mass fraction of 5.57 wt%.

[0044] (The mass fractions mentioned in this paragraph refer to the mass fractions of the corresponding components in the total solution obtained in the subsequent step 3; the following examples are similar.)

[0045] (3) Under light-protected conditions, N,N-methylenebisacrylamide crosslinking agent (in the form of an aqueous crosslinking agent solution with a crosslinking agent concentration of 1 wt%) and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone initiator (in the form of a pure solid initiator) are added to the mixed solution and stirred continuously until completely dissolved to obtain the total solution. Further, in the preparation method of the double-sided adhesive ultrasonic coupling pad of the present invention, the amount of the crosslinking agent aqueous solution is 50 g, and the corresponding crosslinking agent is 0.093 wt% (this mass fraction refers to the mass fraction of the crosslinking agent in the total solution obtained in step 3; subsequent embodiments are similar); the amount of the initiator is 4.5 g, and the corresponding initiator is 0.84 wt% (this mass fraction refers to the mass fraction of the initiator in the total solution obtained in step 3; subsequent embodiments are similar), and the total mass of the solution is 538.5 g.

[0046] (4) Pour the completely dissolved solution into a 2 mm thick mold (the molds used in this embodiment are all 2 mm hollow acrylic plates), seal the top and bottom with glass plates (to prevent excessive oxygen from affecting the reaction), and place it at 365 nm 500 mJ / cm 2 The hydrogel sheet is cured and formed in an ultraviolet crosslinker with light intensity, and can be obtained after 40 minutes.

[0047] (5) After the hydrogel sheet is demolded from the glass sheet, the residual solution on the surface is rinsed with deionized water to obtain the ultrasonic coupling pad with double-sided adhesion.

[0048] In addition, a commercially available medical coupling agent was used as a control sample for imaging. This commercially available medical agent was purchased from Haisheng Hainuo Group (product registration number: Luqing Medical Device Registration No. 20210321).

[0049] Comparative Example 1: This comparative example did not include acrylamide; the specific preparation steps are as follows: (1) Add dopamine hydrochloride to a 0.1 M NaOH solution and stir at room temperature for 40 min to self-polymerize. Further, in this comparative example, the concentration of dopamine is 5 mg / mL.

[0050] (2) Add acrylic acid, tannic acid, and glycerol (without introducing additional water or other solvents) to 200g of polydopamine solution, and dissolve by magnetic stirring at room temperature, a magnetic stirring rate of 250 r / min, and a stirring time of 30 min. Further, in this comparative example, the mass ratio of tannic acid to polyacrylic acid is tannic acid:acrylic acid = 3:15 (wherein, the mass fraction of tannic acid is 2.95 wt%, and the mass fraction of acrylic acid is 14.75 wt%; in this example, the amount of tannic acid used is 15g, and the amount of acrylic acid used is 75g); the amount of glycerol used is 164g, and the corresponding mass fraction of glycerol is 32.25 wt% (the mass fractions appearing in this paragraph are all the mass fractions of the corresponding components in the total solution obtained in the subsequent step 3; the subsequent examples are similar).

[0051] (3) Under light-protected conditions, N,N-methylenebisacrylamide crosslinking agent (in the form of an aqueous crosslinking agent solution with a crosslinking agent concentration of 1 wt%) and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone initiator (in the form of a pure solid initiator) were added to the mixed solution and stirred continuously until completely dissolved to obtain the total solution. Further, in this comparative example, the amount of the aqueous crosslinking agent solution was 50 g, and correspondingly, the crosslinking agent was 0.098 wt% (this mass fraction refers to the mass fraction of the crosslinking agent in the total solution obtained in step 3; subsequent examples are similar); the amount of the initiator was 4.5 g, and correspondingly, the initiator was 0.885 wt% (this mass fraction refers to the mass fraction of the initiator in the total solution obtained in step 3; subsequent examples are similar), and the total mass of the solution was 508.5 g.

[0052] (4) Pour the completely dissolved solution into a 2 mm thick mold (the molds used in this embodiment are all 2 mm hollow acrylic plates), seal the top and bottom with glass plates (to prevent excessive oxygen from affecting the reaction), and place it at 365 nm 500 mJ / cm 2 It is cured and molded in an ultraviolet crosslinker with light intensity.

[0053] Acrylamide was not added in this comparative example. Due to the lack of mechanical support, the ultrasonic coupling pad could not be completely polymerized into a gel.

[0054] Comparative Example 2: (1) Add dopamine hydrochloride to a 0.1 M NaOH solution and stir at room temperature for 40 min to self-polymerize. Further, in this comparative example, the concentration of dopamine is 5 mg / mL.

[0055] (2) Add acrylic acid, tannic acid, acrylamide, and glycerol (without introducing additional water or other solvents) to 200 g of polydopamine solution, and dissolve by magnetic stirring at room temperature, a magnetic stirring rate of 250 r / min, and a stirring time of 30 min. The mass ratio of tannic acid to polyacrylic acid is tannic acid:acrylic acid = 3:15 (wherein, the mass fraction of tannic acid is 2.73%, and the mass fraction of acrylic acid is 13.67 wt%; in this comparative example, the amount of tannic acid used is 15 g, and the amount of acrylic acid used is 75 g); the amount of glycerol used is 164 g, and the corresponding mass fraction of glycerol is 29.89 wt%; the amount of acrylamide used is 40 g, and the corresponding mass fraction of acrylamide is 7.29 wt%.

[0056] (3) Under light-protected conditions, N,N-methylenebisacrylamide crosslinking agent (in the form of an aqueous crosslinking agent solution with a crosslinking agent concentration of 1 wt%) and 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone initiator (in the form of a pure solid initiator) were added to the mixed solution and stirred continuously until completely dissolved to obtain the total solution. Further, in this comparative example, the amount of the aqueous crosslinking agent solution was 50 g, corresponding to 0.0911 wt% of the crosslinking agent; the amount of the initiator was 4.5 g, corresponding to 0.82 wt% of the initiator, and the total mass of the solution was 548.5 g.

[0057] (4) Pour the completely dissolved solution into a 2 mm thick mold (the molds used in this embodiment are all 2 mm hollow acrylic plates), seal the top and bottom with glass plates (to prevent excessive oxygen from affecting the reaction), and place it at 365 nm 500 mJ / cm 2 The hydrogel sheet is cured and formed in an ultraviolet crosslinker with light intensity, and can be obtained after 40 minutes.

[0058] (5) After the hydrogel sheet is demolded from the glass sheet, the residual solution on the surface is rinsed with deionized water to obtain the ultrasonic coupling pad with double-sided adhesion.

[0059] Performance testing: While humectants such as glycerin, which are polyols, have moisturizing effects and can promote the long-term stability of solid ultrasonic coupling pads, their addition can objectively affect gel formation. As illustrated in Comparative Example 1, when acrylamide is not used (i.e., no polyacrylamide is generated), the sample cannot completely polymerize into a gel. However, Examples 1-3 and Comparative Example 2 were able to form a gel.

[0060] The ultrasonic coupling pads obtained in Implementation Cases 1-3 and Comparative Example 2 were subjected to mechanical property tests, and the results are as follows: Figure 2As shown. The stress-strain results of the ultrasonic coupling pad were tested and recorded using a universal testing machine, and the results were obtained using Origin plotting software. Figure 2 The test results showed that with the addition of polyacrylamide, the tensile properties of the ultrasonic coupling pad were improved, and its elongation at break could reach up to about 9 times (from...). Figure 2 As shown by the projection of each curve onto the horizontal axis, Example 1, using 10g of acrylamide, yielded a coupling pad with excellent tensile properties, exhibiting a tensile stress of 3.58 kPa and a strain of 204.92%. Example 2, using 20g of acrylamide, showed even better tensile properties, with a tensile stress of 9.69 kPa and a strain of 388.51%. Example 3, using 30g of acrylamide, exhibited the best tensile properties and the largest tensile length, with a tensile stress of 15.11 kPa and a strain of 892.75%. However, excessive addition of acrylamide can weaken mechanical properties due to excessive crosslinking strength. For example, the ultrasonic coupling pad obtained in Comparative Example 2 showed an increased force required to reach the maximum tensile length and a shorter length (due to...). Figure 2 As shown by the projection of each curve onto the vertical axis, the force required for the longest stretch of the coupling pad in Example 3 is approximately 12N, while the forces required for the longest stretch of the coupling pads in Examples 1 and 2 are lower than those in Example 3. However, the force required for the longest stretch of the sample in Comparative Example 2 is approximately 30N, significantly higher than that in Examples 1, 2, and 3. This indicates that although the sample obtained in Comparative Example 2 can be stretched to a considerable length, it requires a much larger force and is less prone to deformation. Therefore, it cannot better conform to the contours of the skin, often requiring greater force to support deformation and adapt to changes in the skin's surface angle. It is also more likely to return to its original shape, affecting adhesion and hindering practical application. These results demonstrate that the amount of polyacrylamide used needs to be appropriate (the mass fraction of polyacrylamide in a solid ultrasonic coupling pad should be 1.93~5.57 wt%). Otherwise, excessive acrylamide will increase the internal stress of the coupling pad, making it less prone to deformation and negatively impacting adhesion. Coupling pads with an appropriate amount of polyacrylamide can be reused and will not break during tearing. The ultrasonic coupling pad is a multi-network hydrogel composed of three network structures: a polydopamine network structure, a polyacrylic acid network structure, and a polyacrylamide network structure. When the ultrasonic coupling pad is stretched, the three network structures can achieve efficient internal energy dissipation, thus giving the coupling pad higher mechanical strength and toughness, making it less prone to breakage.

[0061] The adhesion performance of the double-sided adhesive solid ultrasonic coupling pad obtained in Case 3 to the probe and skin was tested. The results are as follows: Figure 3As shown. A universal testing machine was used to test and record the maximum peel force data between the ultrasonic coupling pad and RTV rubber (the surface material of the ultrasonic probe) and pigskin, respectively. The peel rate was tested at 50 mm / min. Then, the peel strength of each group was calculated and compared (calculation formula: adhesion strength = 2·peel force / width). The results were obtained using Origin plotting software. Figure 3 The adhesion test results are as follows. Figure 3 As shown, traditional commercial coupling pads lack adhesive properties and cannot help the probe form a tight connection with the skin. However, the adhesive performance of the coupling pads has gradually improved. The ultrasonic coupling pad obtained in Example 3 exhibits good adhesion to both the probe and the skin, with adhesion strengths of 60.75±2.11 N / m and 74.97±2.32 N / m, respectively. Tannic acid and dopamine contain numerous binding sites that can form hydrogen bonds with the probe and skin surfaces, thus possessing excellent adhesive properties. This allows the probe to adhere tightly to the skin surface, preventing air intrusion from affecting imaging.

[0062] The ultrasonic coupling pad obtained in Case 3 was subjected to acoustic performance testing and compared with commercially available coupling agents using imaging. The results are as follows: Figure 4 As shown. First, acoustic characteristics were tested according to the requirements of GB / T YY / T 0299-2022. Second, the ultrasound coupling pad was attached to the skin surface for small-area radial artery imaging (including immediate imaging after attachment and re-imaging after 24 hours) and large-area breast imaging (immediate imaging after attachment). Figure 4 As shown in the figure, it is easy to see that the ultrasound coupling pad has good acoustic performance. The solid coupling pad, like medical ultrasound coupling agents, can achieve good ultrasound imaging for irregular large areas such as the radial artery and breast, and it also has good imaging effect after 24 hours, enabling long-term monitoring.

[0063] The ultrasonic coupling pad obtained in Case Study 3 was subjected to a water loss test. The water loss of the hydrogel ultrasonic coupling patch was quantitatively characterized using a gravimetric method from 0 to 48 hours. The coupling pad was cut into cylindrical shapes with a diameter of 10 mm and a height of 2 mm and placed in vacuum ovens at 25℃ and 37℃. The mass of the hydrogel ultrasonic coupling patch was recorded at different time points. After the experiment, the water loss rate was calculated and plotted using Origin software. Figure 5 The water loss rate versus time curve is shown in the graph. Analysis of the results indicates that the coupling pad prepared in this invention exhibits good water retention due to the presence of glycerol. The highest water loss rates were observed at 48 h, at 8.69% and 10.9%, respectively. Therefore, it can be concluded that the solid coupling pad prepared in this invention can maintain stable physicochemical properties such as shape, size, water content, and flexibility for at least 48 h, enabling this invention to achieve long-term, stable, and continuous ultrasonic monitoring.

[0064] The ultrasonic coupling pad obtained in Case 3 was subjected to a skin-friendliness test, and the results are as follows: Figure 6 As shown, it is easy to see that hydrogel-based solid ultrasonic coupling pads are very friendly to human immortalized epidermal cells, and therefore will not cause allergies, damage, inflammation or other symptoms to our skin during use.

[0065] The ultrasonic coupling pad obtained in Implementation Case 3 and the alginate coupling patch obtained in Example 1 of Chinese Patent Application CN120661701A were analyzed for their resistance to sweat effects. The results are as follows: Figure 7 As shown, after soaking in simulated sweat for 4 hours, the surface of the alginate patch began to turn white. This indicates that sodium ions in the sweat underwent ion exchange with the carboxyl groups of sodium alginate, disrupting the gel network structure formed by hydrogen bonds between sodium alginate and glycerin. In contrast, the surface structure of the patch in Example 3 remained almost unchanged. When soaked in simulated sweat for 8 hours, compared to the coupling pad in Example 3, the solution of the alginate patch became whiter, indicating that the patch had dissolved, while the coupling pad in Example 3 maintained structural stability. Furthermore, from Figure 4 As shown, compared with the previous result CN120661701A, the solid ultrasonic coupling pad obtained by this invention has a lower acoustic attenuation coefficient and better acoustic characteristics of the patch (this is mainly due to the lower proportion of glycerol used in the solid ultrasonic coupling pad of this invention).

[0066] The above embodiments are merely examples. For instance, the above embodiments use dopamine and tannic acid as two polyphenolic hydroxyl materials as phenols. In addition to these two necessary components, other polyphenolic hydroxyl materials can also be introduced as phenols. As another example, besides using acrylic acid as a monomer raw material to form a polyacrylic acid component in the ultrasonic coupling pad, other acrylic acid monomer raw materials can also be used to form a polyacrylic acid component (e.g., polymethacrylic acid). Furthermore, besides using acrylamide as a monomer raw material to form a polyacrylamide component in the ultrasonic coupling pad, other acrylamide monomer raw materials can also be used to form a polyacrylamide component (e.g., polyhydroxymethylacrylamide, polydimethylaminoacrylamide).

[0067] In addition, the double-sided adhesive solid ultrasonic coupling pad of the present invention can be stored under sealed conditions at room temperature and can be taken out for use when needed.

[0068] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A solid ultrasonic coupling pad that can be adhered to both sides, characterized in that, Containing polyol-based moisturizing ingredients, phenols, polyacrylic acid-based adhesive ingredients, and polyacrylamide-based mechanical support ingredients, this double-sided adhesive solid ultrasonic coupling pad is a homogeneous hydrogel sheet formed by these ingredients through covalent and non-covalent interactions. The phenols include both polydopamine and tannic acid. The mass fraction of polyacrylamide components in the homogeneous hydrogel sheet is 1.93~5.57 wt%.

2. The double-sided adhered solid ultrasonic coupling pad as described in claim 1, characterized in that, The polyol moisturizing ingredients include one of glycerol, propylene glycol, and butylene glycol; Preferably, the polyol-based moisturizing agent is glycerol; the mass fraction of the polyol-based moisturizing agent in the homogeneous hydrogel sheet is 30.45~31.62 wt%. The polyacrylic adhesive component is selected from at least one of polyacrylic acid and polymethacrylic acid; The polyacrylamide-based mechanical support component is selected from at least one of polyacrylamide, polyhydroxymethylacrylamide, and polydimethylaminoacrylamide.

3. The double-sided adhered solid ultrasonic coupling pad as described in claim 1, characterized in that, The phenolic compound is a mixture of polydopamine and tannic acid, or the phenolic compound is a mixture of polydopamine, tannic acid and other polyphenolic hydroxyl materials; preferably, the other polyphenolic hydroxyl materials are pyrocyanic acid.

4. The double-sided adhered solid ultrasonic coupling pad as described in claim 1, characterized in that, The tensile stress at break of the solid ultrasonic coupling pad does not exceed 15.11 kPa, and the strain is 200%~900%. Preferably, the thickness of the double-sided adhered solid ultrasonic coupling pad is 1.0~10mm.

5. The double-sided adhered solid ultrasonic coupling pad as described in claim 1, characterized in that, The mass fraction of the polyacrylic acid in the homogeneous hydrogel sheet is 13.93~14.46 wt%. The tannic acid in the homogeneous hydrogel sheet has a mass fraction of 2.78~2.89 wt%.

6. The method for preparing the double-sided adhered solid ultrasonic coupling pad as described in any one of claims 1-5, characterized in that, The preparation method involves mixing and dissolving polyol moisturizers, phenolic raw materials, acrylic monomer raw materials, acrylamide monomer raw materials, initiators, and crosslinking agents in NaOH solution, and stirring evenly to form a prepolymer solution; the prepolymer solution is placed in a sheet mold for sealing and polymerized by ultraviolet light to form a sheet hydrogel; after soaking, it is washed to obtain a double-sided adhered solid ultrasonic coupling pad; wherein, the free radical initiator includes any one of 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (L2959), ammonium persulfate (APS), α-ketoglutarate, and 2-hydroxy-2-methyl-1-phenyl-1-propanone (1173); The crosslinking agent is any one of N,N-methylenebisacrylamide, gelatin methacrylate, hyaluronic acid methacrylate, oxidized methacrylate, diacrylic acid, polyvinyl alcohol, cycloalkenyl acrylate, amino acrylate, polyethylene glycol diacrylate, and polyethylene glycol dimethacrylate. Preferably, the sheet mold is a hollow acrylic mold with a glass sheet at the bottom, and the upper surface of the mold can be sealed by another glass sheet.

7. The preparation method according to claim 6, characterized in that, The phenolic raw material includes both dopamine hydrochloride and tannic acid, and the preparation method specifically includes the following steps: (1) Dissolve dopamine hydrochloride in NaOH solution, and let dopamine hydrochloride self-polymerize in air atmosphere under stirring, and form polydopamine chains by oxygen and base-induced prepolymerization; (2) Add acrylic monomer raw materials, tannic acid, polyol and acrylamide monomer raw materials to the solution obtained in step (1) and mix evenly; (3) Under light-protected conditions, the crosslinking agent and free radical initiator are added to the solution obtained in step (2) and stirred to dissolve, thus obtaining the overall solution; (4) Pour the total solution obtained in step (3) into a hollow acrylic mold with a glass plate at the bottom, and seal it with another glass plate. (5) Place the sealed mold containing the solution under ultraviolet light for cross-linking and curing. After gelation, a hydrogel sheet with adhesive properties can be obtained. (6) For the hydrogel sheet obtained in step (5), remove the glass sheets on both sides of the mold, clean and remove the residual solution on the surface, and you can get a solid ultrasonic coupling pad with double-sided adhesion.

8. The preparation method according to claim 7, characterized in that, In step (1), the concentration of the NaOH solution is 0.1~0.3 M; Dopamine hydrochloride was dissolved in NaOH solution, and the concentration of dopamine hydrochloride was 2-5 mg / mL; the self-polymerization time was 40-60 min. In step (2), the acrylic monomer raw material is acrylic acid, with a concentration of 13.93~14.46 wt% in the total solution; the tannic acid has a concentration of 2.78~2.89 wt% in the total solution; the polyol is glycerol, with a concentration of 30.45~31.62 wt% in the total solution; and the acrylamide monomer raw material is acrylamide, with a concentration of 1.93~5.57 wt% in the total solution. In step (3), the crosslinking agent is N,N-methylenebisacrylamide, and its concentration in the total solution is 0.093~0.096 wt%; the free radical initiator is 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (L2959), and its concentration in the total solution is 0.84~0.87 wt%; the stirring is done by magnetic stirring, with a stirring speed of 50~2000 r / min and a stirring time of 1~60 min; In step (4), the depth of the mold is 1~10 mm; In step (5), the UV wavelength of the UV light is 365 nm, the intensity is 200-500 mJ / cm 2 , and the time is 40-60 min.

9. The preparation method according to claim 7, characterized in that, In step (6), the cleaning is performed by rinsing with deionized water.

10. The application of the double-sided adhesive solid ultrasound coupling pad as described in any one of claims 1-5 in the preparation of an in vitro ultrasound coupling patch, wherein the in vitro ultrasound coupling patch is used to adhere between the skin surface and the ultrasound probe, and can form covalent and non-covalent bonds with the skin surface and non-covalent bonds with the probe surface, thereby achieving long-term stable imaging detection; Preferably, the external ultrasound coupling patch is a sweat-resistant external ultrasound coupling patch that can withstand the sweat secreted by the skin.

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