Ultrasonic phantom material as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biomimetic materials, and discloses an ultrasonic phantom material as well as a preparation method and application thereof. The ultrasonic phantom material comprises the following raw material components: a macromonomer, a micromolecule monomer, a micromolecule cross-linking agent, a macromolecular cross-linking agent, a photoinitiator and water, the macromonomer comprises a hydrophilic substance of which the side chain contains double bonds and the main chain contains hydrogen bonds; the small molecular monomer comprises an amide compound; the macromolecular cross-linking agent comprises nano clay; the micromolecule crosslinking agent is an organic matter crosslinking agent. The ultrasonic phantom material is a hydrogel elastomer with a self-healing function, has good transparency and mechanical properties and good stretchability, the good mechanical properties are matched with the ultrasonic conduction performance, and the sound velocity of the ultrasonic phantom material is close to that of human tissue and is 1540 + / -10 m / s.

Description

Technical Field

[0001] The present invention belongs to the technical field of bionic materials, and particularly relates to an ultrasonic phantom material, a preparation method thereof, and an application thereof. Background Art

[0002] In the medical field, an ultrasonic phantom is an ultrasonic detection tool used to simulate human tissues and organs. The ultrasonic human tissue-like material (TM material) is the core of the ultrasonic phantom. The ultrasonic human tissue-like material is usually made of materials similar to human tissues and has acoustic properties similar to those of human tissues. It plays an important role in ultrasonic detection and imaging technologies. The design of this material aims to simulate the acoustic properties of human tissues, including key parameters such as sound velocity and sound attenuation coefficient, so as to be better applied in the performance testing of ultrasonic devices, medical student training, and clinical skills practice.

[0003] The selection of ultrasonic phantom materials needs to meet several key requirements: ① Sound velocity matching: The sound velocity of the material should be close to that of human tissues, usually within 1540 ± 10 m / s, to ensure that the propagation speed of ultrasonic waves in the phantom is similar to that in the human body. ② Sound attenuation coefficient: The sound attenuation coefficient of the material should also match that of the human body, usually around 0.3 to 0.7 dB per megahertz per centimeter, to ensure the authenticity and accuracy of ultrasonic images. ③ Biocompatibility: For some applications, such as teaching and training, the phantom material also needs to have good biocompatibility to ensure the safety of users. ④ Durability: Phantoms for scientific research and teaching often require more advanced and durable materials to withstand frequent use and disinfection processes.

[0004] In the prior art, although hydrogel materials have been widely used in the preparation of ultrasonic human tissue-like materials, there are still significant technical bottlenecks: First, the mechanical properties of conventional hydrogel materials are poor and are prone to fragmentation. Although the mechanical properties such as elasticity and hardness can be improved through modification, it often leads to the ultrasonic conduction rate exceeding the standard range of 1550 m / s, making the ultrasonic conduction rate of the hydrogel phantom material unable to meet the requirements. This is because hydrogel, as a solid-like material, has viscoelastic characteristics, and its ultrasonic conduction rate is positively correlated with the elastic modulus. While improving the comprehensive mechanical properties, it will inevitably lead to an increase in the ultrasonic conduction rate. This contradictory relationship has become a key problem restricting the improvement of material performance.

[0005] Secondly, in ultrasonic puncture applications, existing hydrogel phantom materials face serious durability issues. When repeated punctures are performed using puncture instruments such as needles, irreversible puncture marks will be formed inside the material. These defects will produce artifacts in ultrasonic imaging, seriously affecting the precise positioning of preset targets in the phantom. In addition, although the hydrogel has good flexibility, when the hydrogel is damaged during use, the microscopic cracks inside the damaged hydrogel are difficult to restore and repair. This results in a significant decrease in the structural integrity and mechanical strength of the material, loss of function, and a significant shortening of the service life. As the number of punctures increases, the internal defects of the material continue to accumulate, eventually leading to complete failure of the phantom. Therefore, how to improve the durability of ultrasonic phantom materials under long-term repeated puncture conditions is another technical problem that needs to be solved urgently.

[0006] Based on the above technical bottlenecks, developing an ultrasonic phantom material that can simultaneously meet the requirements of mechanical properties (including elasticity, hardness and resistance to repeated puncture) and ultrasonic conduction rate has become a technical problem that urgently needs to be solved in this field. Summary of the invention

[0007] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, the present invention proposes an ultrasonic phantom material and its preparation method and application. The ultrasonic phantom material of the present invention is a hydrogel material that can simultaneously meet the requirements of mechanical properties and ultrasonic conduction rate, and further, has good self-healing properties, prolongs the working life of the hydrogel material, and improves the repeated puncture performance when the hydrogel material is used as an ultrasonic puncture phantom.

[0008] The present invention uses specific macromolecular monomers, small molecule monomers, small molecule cross-linking agents, macromolecular cross-linking agents, photoinitiators and water to form an ultrasonic phantom material through photocuring. Specifically, the present invention uses a hydrogel with self-healing function prepared by combining non-covalent bonds with dynamic covalent bonds, and uses a multiple network structure to improve the mechanical strength of the hydrogel, and enables the hydrogel to simultaneously meet the ultrasonic conduction rate requirements similar to those of human tissue. This is a self-healing elastic hydrogel phantom, which will form puncture marks during the puncture process of the puncture device. Since the elastic self-healing hydrogel has self-repairing properties, the puncture marks will slowly disappear after a period of time after the puncture. This self-repairing process is generally completed during a static process of more than 10 hours, and the hydrogel phantom returns to the state before the puncture.

[0009] A first aspect of the present invention provides an ultrasound phantom material.

[0010] Specifically, an ultrasound phantom material, the raw material components include macromolecular monomers, small molecular monomers, small molecular cross-linking agents, macromolecular cross-linking agents, photoinitiators and water;

[0011] The macromonomer includes a hydrophilic substance with a double bond in the side chain and a hydrogen bond in the main chain;

[0012] The small molecule monomer includes an amide compound

[0013] The macromolecular crosslinking agent includes nano-clay;

[0014] The small molecule crosslinking agent is an organic crosslinking agent.

[0015] Preferably, the macromonomer includes at least one of GelMA (gelatin methacrylate), hyaluronic acid methacrylate (HAMA), chitosan methacrylate (CSMA), carrageenan methacrylate (PEG), polyvinyl alcohol methacrylate (PVAMA), and methacrylated polyethylene glycol.

[0016] Preferably, in the raw material components of the ultrasonic phantom material, the mass of the macromonomer accounts for 0.5-5% of the total mass of all raw material components, and more preferably 1-3%.

[0017] Preferably, the small molecule monomer includes at least one of N-(2-hydroxyethyl) acrylamide, N-isopropylacrylamide (NIPAM), and acryloylglycinamide (NAGA).

[0018] Preferably, in the raw material components of the ultrasonic phantom material, the mass of the small molecule monomer accounts for 1-10% of the total mass of all raw material components, and more preferably 3-6%.

[0019] Preferably, the macromolecular crosslinking agent includes at least one of montmorillonite, hectorite, bentonite, and kaolin, and more preferably hectorite.

[0020] Preferably, in the raw material components of the ultrasonic phantom material, the mass of the macromolecular crosslinking agent accounts for 0.5-5% of the total mass of all raw material components, and more preferably 1-3%.

[0021] Preferably, the small molecule crosslinking agent includes at least one of polyethylene glycol diacrylate and BIS(N,N-methylenebisacrylamide).

[0022] Preferably, in the raw material components of the ultrasonic phantom material, the mass of the small molecule crosslinking agent accounts for 0.01-5% of the total mass of all raw material components, and more preferably 1-3%.

[0023] Preferably, the photoinitiator includes at least one of lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), 2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methyl-1-propanone (Irgacure 2959), and 1-hydroxycyclohexyl phenyl ketone (184).

[0024] Preferably, in the raw material components of the ultrasonic phantom material, the mass of the photoinitiator accounts for 0.01-0.2% of the total mass of all raw material components, and more preferably 0.02-0.1%.

[0025] Preferably, the water is at least one of deionized water and distilled water.

[0026] Preferably, in terms of mass percentage, the raw material components of the ultrasonic phantom material include 0.5-5% of macromonomer, 1-10% of small molecule monomer, 0.01-5% of small molecule crosslinker, 0.5-5% of macromolecule crosslinker, 0.01-0.2% of photoinitiator, and 74.80-97.49% of water.

[0027] Preferably, the raw material components of the ultrasonic phantom material further include spherical targets. Adding spherical targets is beneficial for the obtained ultrasonic phantom material to be used multiple times during teaching and training.

[0028] The second aspect of the present invention provides a preparation method of an ultrasonic phantom material.

[0029] Specifically, a preparation method of an ultrasonic phantom material includes the following steps:

[0030] Mix all raw material components to obtain a mixture, and pour the mixture into a mold for light curing to obtain the ultrasonic phantom material.

[0031] Preferably, the light wavelength for light curing is 300-400 nm, and more preferably 340-380 nm.

[0032] Preferably, the light intensity for light curing is 100-500 mW / cm 2 , and more preferably 200-400 mW / cm 2 .

[0033] Preferably, the light curing time is 30-300 minutes, and more preferably 60-250 minutes.

[0034] Preferably, the material of the mold is at least one of glass and acrylic. Ensure that the surface of the mold is clean and smooth to facilitate observing the transparency of the hydrogel after molding.

[0035] Preferably, after the photocuring is completed, a layer of silicone material is cured on the top of the mold. The formed silicone layer seals the hydrogel inside the mold to prevent water evaporation.

[0036] Preferably, in the preparation method, spherical targets are also added during the mixing of each raw material component.

[0037] Preferably, the preparation method of the ultrasonic phantom material includes the following steps:

[0038] (1) Add the weighed macromolecular crosslinking agent (nano-clay) into water, and stir at room temperature to fully dissolve it. A magnetic stirrer or a mechanical stirrer can be used, and the stirring speed is controlled within an appropriate range. The stirring time depends on the dissolution situation, generally 1 - 5 hours, until a uniform solution is formed;

[0039] (2) Add the small molecule monomer to the above solution, and stir to ensure that all components are fully mixed evenly to form a stable mixed solution;

[0040] (3) Add the macromolecular monomer to the above solution, and continue to stir for 2 - 4 hours to ensure that all components are fully mixed evenly to form a stable mixed solution;

[0041] (4) Add the small molecule crosslinking agent to the above mixed solution in sequence, and continue to stir for 2 - 4 hours to ensure that all components are fully mixed evenly to form a stable mixed solution;

[0042] (5) Finally, add the photoinitiator and stir evenly to obtain a hydrocolloid solution. The stirring time can be controlled within 0.5 - 1 hour to make the photoinitiator evenly dispersed in the solution;

[0043] (6) Pour the prepared hydrocolloid solution into a mold with a pre-designed shape. The mold material can be selected as glass, acrylic, etc., and ensure that the mold surface is clean and smooth for easy observation of the transparency of the hydrogel after molding;

[0044] (7) Place the mold filled with the hydrocolloid solution in a photocuring device, select a suitable light source wavelength and light intensity. Generally, a UV-LED lamp can be used, with a wavelength range between 300 - 400 nm, and the light intensity is adjusted according to the type and content of the photoinitiator, usually between 100 - 500 mW / cm 2 ²;

[0045] (8) Carry out the photocuring reaction. The light irradiation time is determined according to factors such as the thickness of the hydrogel and the activity of the photoinitiator, generally ranging from 30 - 300 minutes until the hydrocolloid solution is completely cured to form a hydrogel, and the ultrasonic phantom material is obtained.

[0046] Preferably, after the photocuring is completed, a layer of silicone material is cured on the top of the mold. The formed silicone layer seals the hydrogel inside the mold to prevent water evaporation.

[0047] The third aspect of the present invention provides an application of an ultrasonic phantom material.

[0048] An ultrasonic phantom includes the above ultrasonic phantom material.

[0049] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0050] 1) The ultrasonic phantom material of the present invention is a hydrogel elastomer with a self-healing function, having good transparency and mechanical properties, good stretchability, and the good mechanical properties match the ultrasonic conduction performance. The sound velocity of the ultrasonic phantom material of the present invention is close to that of human tissues, at 1540 ± 10 m / s. Dynamic cross-linking macromolecular cross-linking agents such as nanoclay can effectively enhance the strength of the hydrogel. However, when the amount of nanoclay increases, the conduction rate of the sound velocity will increase, causing the ultrasonic conduction rate to exceed the required range. At this time, by reducing the total monomer concentration, the ultrasonic transmission rate can be effectively regulated. Reducing the total monomer concentration can effectively reduce the ultrasonic conduction rate, making the mechanical properties improved and the ultrasonic conduction rate matched. The macromolecular monomers of the present invention can combine with nanoclay at a relatively low concentration to obtain a high-strength ultrasonic phantom material.

[0051] 2) The ultrasonic phantom material of the present invention has the structural characteristics of multiple cross-linkings: the present invention adopts a multiple cross-linking structure of combining macromolecular monomers with hydrogen bonds and small molecular monomers with hydrogen bonds, dynamic cross-linking macromolecular cross-linking agents and small molecular cross-linking agents, and physical cross-linking combined with chemical cross-linking; this structure enables the system to obtain a high-strength hydrogel elastomer at a relatively low monomer concentration.

[0052] 3) The ultrasonic phantom material of the present invention has self-healing properties. The marks and defects formed under repeated punctures can generally be automatically repaired within 10 - 10 hours, and the ultrasonic phantom material returns to the state before puncture.

[0053] Based on the above three points, the core competitiveness of the ultrasonic phantom material in the market is greatly improved. Description of the Drawings

[0054] Figure 1 It is a physical diagram of the ultrasonic phantom material prepared in Example 1 of the present invention;

[0055] Figure 2 It is a puncture mark diagram left by puncturing the ultrasonic phantom material prepared in Example 1 with a puncture needle;

[0056] Figure 3The puncture trace diagram of the ultrasound phantom material prepared for Example 1 of the puncture needle after standing for 10 hours. Detailed implementation manners

[0057] In order to make those skilled in the art more clearly understand the technical solutions of the present invention, the following examples are listed for illustration. It should be noted that the following examples do not limit the protection scope required by the present invention.

[0058] The raw materials, reagents or devices used in the following examples can be obtained from conventional commercial channels or can be obtained by existing known methods without special instructions.

[0059] Gelatin methacrylate is a commercial product. For example, the relevant information of this product is recorded in https: / / www.sigmaaldrich.cn / CN / zh / product / aldrich / 900622.

[0060] Hyaluronic acid methacrylate is a commercial product. For example, the relevant information of this product is recorded in https: / / www.sigmaaldrich.cn / CN / zh / substance / hyaluronicacidmethacrylate1234598765.

[0061] Polyvinyl alcohol methacrylate is a commercial product. For example, the relevant information of this product is recorded in https: / / www.otrixell.com / productinfo / 3025481.html.

[0062] Example 1

[0063] An ultrasound phantom material, calculated by mass percentage, the raw material components include 0.5% GelMA (gelatin methacrylate), 1% N-(2-hydroxyethyl) acrylamide, 0.01% polyethylene glycol diacrylate, 0.5% lithium saponite, 0.01% LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphite) and the balance of deionized water.

[0064] A preparation method of an ultrasound phantom material, comprising the following steps:

[0065] (1) Take 0.5% lithium saponite (macromolecular crosslinking agent), add it to deionized water, and stir for 1 hour to form a uniform solution;

[0066] (2) Add 1% N-(2-hydroxyethyl) acrylamide (small molecule monomer) to the solution and continue to stir for 1 hour;

[0067] (3) Continuously add 0.5% GelMA (methacrylated gelatin, macromonomer), and continue stirring for 1 hour;

[0068] (4) Continuously add 0.01% polyethylene glycol diacrylate (small molecule crosslinker), and continue stirring for 1 hour;

[0069] (5) Continuously add 0.01% LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate, photoinitiator), stir evenly, and stir for 0.5 hour;

[0070] (6) Pour the solution obtained in step (5) into a mold, and suspend several black plastic balls (as targets) in the solution with a fine metal needle. Use a UV-LED lamp with a wavelength of 400 nm and a light intensity of 100 mW / cm 2 , and perform photocuring for 30 minutes. After photocuring is completed, withdraw the fine metal needle, and the black plastic balls are left in the phantom;

[0071] (7) Naturally cool and cure a layer of silicone material on the top of the hydrogel (the process of curing a layer of silicone material is a conventional process in the art), to form an ultrasonic phantom material.

[0072] Example 2

[0073] A method for preparing an ultrasonic phantom material, comprising the following steps:

[0074] (1) Take 5% lithium saponite (macromolecule crosslinker), add it to deionized water, and stir for 5 hours to form a uniform solution;

[0075] (2) Add 10% N-isopropylacrylamide (NIPAM, small molecule monomer) to the solution, and continue stirring for 4 hours;

[0076] (3) Continuously add 5% GelMA (methacrylated gelatin, macromonomer), and continue stirring for 4 hours;

[0077] (4) Continuously add 0.1% polyethylene glycol diacrylate (small molecule crosslinker), and continue stirring for 4 hours;

[0078] (5) Continuously add 0.2% 2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methyl-1-propanone (Irgacure 2959) as a photoinitiator, stir evenly, and stir for 1 hour;

[0079] (6) Pour the solution obtained in step (5) into a mold, and suspend several black plastic balls (as targets) in the solution with a fine metal needle. Use a UV-LED lamp with a wavelength of 300 nm and a light intensity of 500 mW / cm 2, perform photocuring with a light irradiation time of 300 minutes. After the photocuring is completed, withdraw the fine metal needle, and the black plastic balls are left in the phantom;

[0080] (7) Naturally cool and cure a layer of silicone material on the top of the hydrogel to form the ultrasonic phantom material.

[0081] Example 3

[0082] A method for preparing an ultrasonic phantom material, comprising the following steps:

[0083] (1) Take 1% lithium saponite (macromolecular crosslinking agent), add it to deionized water, and stir for 2 hours to form a homogeneous solution;

[0084] (2) Add 3% of N-isopropylacrylamide (NIPAM, small molecule monomer) to the solution, and continue stirring for 2 hours;

[0085] (3) Continue to add 1% GelMA (methacrylated gelatin, macromolecular monomer), and continue stirring for 2 hours;

[0086] (4) Continue to add 0.02% polyethylene glycol diacrylate (small molecule crosslinking agent), and continue stirring for 2 hours;

[0087] (5) Continue to add 0.02% of LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) as a photoinitiator, stir evenly, and stir for 0.5 hours;

[0088] (6) Pour the solution obtained in step (5) into a mold, and suspend several black plastic balls (as targets) in the solution with fine metal needles. Use a UV-LED lamp with a wavelength of 365 nm and a light intensity of 200 mW / cm 2 , perform photocuring with a light irradiation time of 60 minutes. After the photocuring is completed, withdraw the fine metal needle, and the black plastic balls are left in the phantom;

[0089] (7) Naturally cool and cure a layer of silicone material on the top of the hydrogel to form the ultrasonic phantom material.

[0090] Example 4

[0091] A method for preparing an ultrasonic phantom material, comprising the following steps:

[0092] (1) Take 3% montmorillonite (macromolecular crosslinking agent), add it to deionized water, and stir for 3.5 hours to form a homogeneous solution;

[0093] (2) Add 6% of N-isopropylacrylamide (NIPAM, small molecule monomer) to the solution, and continue stirring for 3.5 hours;

[0094] (3) Continuously add 3% GelMA (methacrylated gelatin, macromonomer), and continue stirring for 3.5 hours;

[0095] (4) Continuously add 0.05% polyethylene glycol diacrylate (small molecule crosslinker), and continue stirring for 3.5 hours;

[0096] (5) Continuously add 0.1% 2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methyl-1-propanone (Irgacure 2959) as a photoinitiator, stir evenly, and stir for 1 hour;

[0097] (6) Pour the solution obtained in step (5) into a mold, and suspend several black plastic balls (as targets) in the solution with a thin metal needle. Use a UV-LED lamp with a wavelength of 350 nm, and the light intensity is 300 mW / cm 2 , and carry out photocuring for 120 minutes. After photocuring is completed, withdraw the thin metal needle, and the black plastic balls are left in the phantom;

[0098] (7) Naturally cool and cure a layer of silicone material on the top of the hydrogel to form an ultrasonic phantom material.

[0099] Example 5

[0100] A method for preparing an ultrasonic phantom material, comprising the following steps:

[0101] (1) Take 2.5% bentonite (macromolecule crosslinker), add it to deionized water, and stir for 2.5 hours to form a uniform solution;

[0102] (2) Add 4% acryloylglycinamide (NAGA, small molecule monomer) to the solution, and continue stirring for 2.5 hours;

[0103] (3) Continuously add 2% methacrylated hyaluronic acid (HAMA, macromolecule monomer), and continue stirring for 2.5 hours;

[0104] (4) Continuously add 0.03% BIS (N,N-methylenebisacrylamide, small molecule crosslinker), and continue stirring for 2.5 hours;

[0105] (5) Continuously add 0.03% 1-hydroxycyclohexyl phenyl ketone (184) as a photoinitiator, stir evenly, and stir for 0.5 hours;

[0106] (6) Pour the solution obtained in step (5) into a mold, and suspend several black plastic balls (as targets) in the solution with a thin metal needle. Use a UV-LED lamp with a wavelength of 375 nm, and the light intensity is 250 mW / cm 2, perform photocuring with a light exposure time of 90 minutes. After photocuring is completed, withdraw the fine metal needle, and leave the black plastic ball in the phantom;

[0107] (7) Naturally cool and cure a layer of silicone material on the top of the hydrogel to form an ultrasonic phantom material.

[0108] Example 6

[0109] A method for preparing an ultrasonic phantom material, comprising the following steps:

[0110] (1) Take 4% kaolin (macromolecular crosslinking agent), add it to deionized water, and stir for 4 hours to form a homogeneous solution;

[0111] (2) Add 8% N-(2-hydroxyethyl) acrylamide (small molecule monomer) to the solution, and continue to stir for 4 hours;

[0112] (3) Continue to add 4% polyvinyl alcohol methacrylate (PVAMA, macromolecular monomer), and continue to stir for 4 hours;

[0113] (4) Continue to add 0.04% BIS (N,N-methylenebisacrylamide, small molecule crosslinking agent), and continue to stir for 4 hours;

[0114] (5) Continue to add 0.04% LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) as a photoinitiator, stir evenly, and stir for 1 hour;

[0115] (6) Pour the solution obtained in step (5) into a mold, and suspend several black plastic balls (as targets) in the solution with a fine metal needle. Use a UV-LED lamp with a wavelength of 330 nm and a light intensity of 400 mW / cm 2 , perform photocuring with a light exposure time of 180 minutes. After photocuring is completed, withdraw the fine metal needle, and leave the black plastic ball in the phantom;

[0116] (7) Naturally cool and cure a layer of silicone material on the top of the hydrogel to form an ultrasonic phantom material.

[0117] Comparative Example 1

[0118] Compared with Example 1, the difference in Comparative Example 1 is only that an equal amount of N-isopropylacrylamide is used to replace the methacrylated gelatin in Example 1 of the present invention, and the remaining processes are the same as those in Example 1.

[0119] Comparative Example 2

[0120] Compared with Example 1, the difference in Comparative Example 2 is only that an equal amount of sodium carboxymethyl cellulose is used to replace the lithium soapstone in Example 1 of the present invention, and the remaining processes are the same as those in Example 1.

[0121] Comparative Example 3

[0122] Compared with Example 1, the difference in Comparative Example 3 is only that an equal amount of dolomite is used to replace the saponite in Example 1 of the present invention, and the remaining processes are the same as those in Example 1.

[0123] Product effect test

[0124] The transparency of the ultrasonic phantom materials prepared in the above-mentioned examples and comparative examples containing different nano-clays was tested using an ultraviolet-visible spectrophotometer. The measurement wavelength range was 400 - 800 nm, and the light transmittance at 550 nm is shown in Table 1.

[0125] The ultrasonic phantom materials prepared in the above-mentioned examples and comparative examples were subjected to a tensile test using a universal material testing machine at a tensile rate of 5 mm / min. The elongation at break obtained from the test is shown in Table 1.

[0126] According to the technical requirements of YYT 1521-2017 Ultrasonic Elastic Tissue-Mimicking Phantom and the method in Appendix B, the Young's modulus, sound velocity, and sound attenuation of the ultrasonic phantom materials prepared in the above-mentioned examples and comparative examples were tested, and the results are shown in Table 1.

[0127] Self-healing performance test: The ultrasonic phantom materials prepared in the above-mentioned examples and comparative examples were punctured with a puncture needle, and puncture marks were left on the ultrasonic phantom materials. After 10 hours, the situation of the puncture marks and the recovery of the phantom were observed.

[0128] Table 1

[0129]

[0130] As can be seen from Table 1, the ultrasonic phantom materials prepared in Examples 1-6 of the present invention can simultaneously have good mechanical properties and a sound velocity matching that of human tissues.

[0131] From the results of Example 1 and Comparative Examples 1-3, it can be seen that the mechanical properties and sound velocity matching effect of the ultrasonic phantom materials prepared in the examples of the present invention are significantly better than those of Comparative Examples 1-3. Thus, it can be seen that the technical solution of the present invention has specific selection for the raw material components.

[0132] The ultrasonic phantom material prepared in Example 4 was placed in a water bath at different temperatures (such as 20 °C, 30 °C, 40 °C), and the volume change of the ultrasonic phantom material was observed. The results showed that at 20 °C, at a wavelength of 550 nm, the light transmittance of the ultrasonic phantom material was 95%; when the temperature increased to 30 °C, the light transmittance became 93%; when the temperature increased to 40 °C, the light transmittance was 55%, indicating that the ultrasonic phantom material prepared in Example 4 has temperature-responsive properties due to the introduction of NIPAM. As the temperature increases, the ultrasonic phantom material undergoes a microphase transition behavior.

[0133] The cytotoxicity test method of the hydrogel was carried out according to the national standard GB / T16886.5-2017 "Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test", and was carried out according to the MTT method (a method for detecting cell survival and growth). The results showed that the hydrogel prepared in Example 1 of the present invention had good biocompatibility and could meet the basic requirements of biomedical applications.

[0134] Figure 1 This is a physical diagram of the ultrasonic phantom material prepared in Example 1 of the present invention; Figure 1 In Figure (a), the milky white layer is the silica gel layer, and Figure (b) is the ultrasonic phantom material without the silica gel layer covered; from Figure 1 it can be seen that the ultrasonic phantom material (or called hydrogel) is tightly combined with the silica gel layer, and there is no delamination or cracking phenomenon, indicating that the ultrasonic phantom material has good structural stability and can be used to simulate the long-term performance of biological tissues in a physiological environment.

[0135] Figure 2 This is a puncture trace diagram left by puncturing the ultrasonic phantom material prepared in Example 1 with a puncture needle; from Figure 2 it can be seen that puncture marks will be left in the ultrasonic phantom material after puncture.

[0136] Figure 3 This is a puncture trace diagram of the ultrasonic phantom material prepared in Example 1 after being punctured with a puncture needle and standing for 10 hours. From Figure 3 it can be seen that after standing for 10 hours, the puncture marks are hardly visible, indicating that the ultrasonic phantom material prepared by the present invention has good self-healing performance.

Claims

1. An ultrasonic phantom material, characterized in that: The raw material components include macromolecular monomers, small molecular monomers, small molecular cross-linking agents, macromolecular cross-linking agents, photoinitiators and water; The macromonomer includes a hydrophilic substance having a double bond in the side chain and a hydrogen bond in the main chain; The small molecule monomers include amide compounds; The macromolecular cross-linking agent includes nanoclay; The small molecule cross-linking agent is an organic cross-linking agent.

2. The ultrasonic phantom material according to claim 1, characterized in that: The macromonomer comprises at least one of methacrylated gelatin, methacrylated hyaluronic acid, methacrylated chitosan, methacrylated carrageenan, methacrylated polyvinyl alcohol, and methacrylated polyethylene glycol; and / or, among the raw material components of the ultrasonic phantom material, the mass of the macromonomer accounts for 0.5-5% of the total mass of all raw material components.

3. The ultrasonic phantom material according to claim 1, characterized in that: The small molecule monomer includes at least one of N-(2-hydroxyethyl) acrylamide, N-isopropyl acrylamide, and acrylyl glycinamide; and / or, among the raw material components of the ultrasonic phantom material, the mass of the small molecule monomer accounts for 1-10% of the total mass of all raw material components, and more preferably 3-6%.

4. The ultrasonic phantom material according to claim 1, characterized in that: The macromolecular cross-linking agent comprises at least one of montmorillonite, laponite, bentonite and kaolin; and / or, in the raw material components of the ultrasonic phantom material, the mass of the macromolecular cross-linking agent accounts for 0.5-5% of the total mass of all raw material components.

5. The ultrasonic phantom material according to claim 1, characterized in that: The small molecule cross-linking agent includes at least one of polyethylene glycol diacrylate and N,N-methylenebisacrylamide; and / or, in the raw material components of the ultrasonic phantom material, the mass of the small molecule cross-linking agent accounts for 0.01-5% of the total mass of all raw material components.

6. The ultrasonic phantom material according to claim 1, characterized in that: The photoinitiator includes at least one of phenyl-2,4,6-trimethylbenzoyl lithium phosphite, 2-hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methyl-1-propanone, and 1-hydroxycyclohexylphenyl ketone; and / or, among the raw material components of the ultrasonic phantom material, the mass of the photoinitiator accounts for 0.01-0.2% of the total mass of all raw material components.

7. The ultrasonic phantom material according to any one of claims 1 to 6, characterized in that: The ultrasonic phantom material comprises raw material components, calculated by mass percentage, including 0.5-5% macromolecular monomer, 1-10% small molecular monomer, 0.01-5% small molecular crosslinking agent, 0.5-5% macromolecular crosslinking agent, 0.01-0.2% photoinitiator and 74.80-97.49% water.

8. The method for preparing the ultrasonic phantom material according to any one of claims 1 to 7, characterized in that: The following steps are involved: The raw material components are mixed to obtain a mixture, and the mixture is poured into a mold for light curing to obtain the ultrasonic phantom material.

9. The preparation method according to claim 8, characterized in that: The wavelength of the light for photocuring is 300-400nm; and / or the light intensity of the light for photocuring is 100-500mW / cm 2 ; and / or, the light curing time is 30-300 minutes; and / or, the material of the mold is at least one of glass and acrylic; and / or, after the light curing is completed, a layer of silicone material is cured on the top of the mold.

10. An ultrasound phantom, characterized in that: The ultrasonic phantom material comprises any one of claims 1 to 7.

Images