A water-lubricated ultrasonic film with a Janus gradient structure, its preparation method and application

Abstract

A water-lubricated ultrasonic film with a Janus gradient structure, a preparation method and an application thereof. The preparation method of the water-lubricated ultrasonic film includes four steps: preparing a premixed solution, preparing a pre-gel solution, coating and photocuring. The obtained water-lubricated ultrasonic film can simultaneously ensure the adhesion in contact with the ultrasonic probe and the lubricity in contact with the patient's skin, and at the same time has good ultrasonic signal conduction stability and safety.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical material production, and particularly relates to a preparation method of a water-lubricated ultrasonic film with a Janus gradient structure, and also relates to a water-lubricated ultrasonic film with a Janus gradient structure prepared by the preparation method and the application of the water-lubricated ultrasonic film. Background Art

[0002] Ultrasound is an indispensable diagnostic method in modern clinical medicine. Through ultrasound, various cross-sectional images of each organ and surrounding organs can be clearly displayed, and the images are rich in a sense of entity and close to the true anatomical structure. Therefore, ultrasound can be applied to early clear diagnosis. However, when doctors use the probe, in order to obtain clear and accurate biological information and to protect the probe, a large amount of coupling agent is often applied to the patient's skin. This coupling agent has a high viscosity and is easy to dry, and needs to be applied multiple times during the examination. Moreover, after the patient's ultrasound examination, a large amount of water or toilet paper is needed to remove the residual coupling agent, which has a low psychological acceptance and is unhygienic. In addition, when encountering special scenarios such as minimally invasive interventional surgery, obstetrics and gynecology examinations, neonatal examinations, etc., the ultrasound probe must contact the patient and easily infected parts, and the applied coupling agent may cause patient infection, thus endangering the patient's health. In particular, when endocavity ultrasound examination is required, a condom is often used to isolate the ultrasound probe, but its strength is insufficient and it is easy to break, and the condom has lubricating oil, which will corrode the acoustic lens of the ultrasound probe and damage the ultrasound probe.

[0003] In recent years, researchers have continuously developed new types of coupling agents to overcome the above defects of traditional coupling agents. In particular, the emergence of ultrasonic hydrogel films has solved these defects to a certain extent. Specifically: First, since one of the most important functions of ultrasonic hydrogel films is to isolate air, most ultrasonic hydrogel films have adhesiveness to tightly connect the ultrasound probe, but this also causes inconvenience during the examination and is not conducive to the probe moving around. Second, the nanoparticles introduced into most ultrasonic hydrogel films are only dispersed into the gel system and have no chemical interaction with the polymer chains in the gel, which will lead to the instability of the nanoparticles in the system, and are easy to escape and leak during the examination, causing leakage and pollution. More importantly, it will also lead to instabilities such as leakage and attenuation of the ultrasonic hydrogel film number, affecting the image quality and the accuracy of the examination results, and will also cause side effects that endanger the health of patients. Finally, in special application scenarios, such as minimally invasive interventional surgery, obstetrics and gynecology examinations, etc., the ultrasound probe not only works on the body surface, and almost all ultrasonic hydrogel films ignore the possible infection in the area other than the probe.

[0004] In summary, developing an efficient, safe, stable and low-cost ultrasonic coupling material has become an urgent need in the current ultrasound field. Summary of the Invention

[0005] In view of the above problems, the present invention has conducted a large number of experiments and improvements on traditional ultrasonic coupling agents and new ultrasonic coupling materials in recent years, and obtained a water-lubricated ultrasonic film with a Janus gradient structure. This water-lubricated ultrasonic film can simultaneously ensure the adhesion when contacting the ultrasonic probe and the lubricity when contacting the patient's skin, and at the same time has good ultrasonic signal conduction stability and safety.

[0006] According to a first aspect of the present invention, there is provided a method for preparing a water-lubricated ultrasonic film with a Janus gradient structure, which comprises the following steps:

[0007] S1. Prepare a premixed solution: Mix the first polymer monomer, the second polymer, the surface-modified nanoparticles and the solvent uniformly to obtain the premixed solution;

[0008] S2. Prepare a pre-gel solution: Add a photoinitiator to the premixed solution obtained in step S1 and mix uniformly to obtain the pre-gel solution;

[0009] S3. Coat the pre-gel solution: Coat the pre-gel solution;

[0010] S4. Photo-cure to form a film: Photo-cure the coated pre-gel solution under ultraviolet light to form a film, and the water-lubricated ultrasonic film with a Janus gradient structure of the present invention can be obtained.

[0011] In the preparation method of the present invention, coating the pre-gel solution on a substrate and performing ultraviolet light photo-curing can obtain the water-lubricated ultrasonic film with a Janus gradient structure of the present invention ( Figure 11 ), wherein, since the nanoparticles have light-impermeability, when ultraviolet light irradiates the coated gel pre-polymer solution from top to bottom, the light intensity decays in a gradient. The cross-linking degree of the upper-layer pre-polymer solution is high, the double bonds are consumed more, and the reaction degree with the surface-modified nanoparticles is low, resulting in the gel being more hydrophilic and more conducive to the probe moving around; on the contrary, the cross-linking degree of the lower-layer pre-polymer solution is low, the double bonds are consumed less, and the reaction degree with the surface-modified nanoparticles is high, resulting in the gel being more hydrophobic (see Figure 1 ), thereby realizing the gradient structure of the ultrasonic film, and further realizing that the water-lubricated ultrasonic film can simultaneously ensure the adhesion when contacting the ultrasonic probe and the lubricity when contacting the patient's skin ( Figure 5 and 6 ).

[0012] In addition, in the present invention, steps S1 and S2 can be carried out simultaneously, that is, mixing the first polymer monomer, the second polymer, the photoinitiator, the surface-modified nanoparticles and the solvent uniformly, wherein the first polymer monomer, the second polymer and the photoinitiator are dissolved in the solvent. In other words, the method for preparing a water-lubricated ultrasonic film with a Janus gradient structure of the present invention can alternatively comprise the following steps:

[0013] SA. Preparation of the pre-gel solution: Mix the first polymer monomer, the second polymer, a photoinitiator, surface-modified nanoparticles, and a solvent uniformly to obtain the pre-gel solution;

[0014] SB. Coating the pre-gel solution: Coat the pre-gel solution,

[0015] SC. Photo-curing into a film: Photo-cure the coated pre-gel solution under ultraviolet light to form a film, and the water-lubricated ultrasonic film with a Janus gradient structure of the present invention can be obtained.

[0016] The choice between these two alternative schemes is specifically determined by the usage scenario, the type of photoinitiator, or the type of the first polymer monomer. Exemplarily, when the photoinitiator can only dissolve in the solvent at a certain temperature, and the unsaturated bonds in the first polymer monomer are unstable at this temperature, it is necessary to first prepare a pre-mixture, and then add the photoinitiator solution to the pre-mixture and stir evenly to obtain the pre-gel solution. Another exemplarily, when the photoinitiator is easily soluble in the solvent and the unsaturated bonds in the first polymer monomer are relatively stable, the first polymer monomer, the second polymer, and the photoinitiator can be simultaneously dissolved in the solvent and mixed evenly without dissolving step by step. Still another exemplarily, in the case of actual large-scale industrial production, the presence of the photoinitiator may cause the photopolymer of the first polymer monomer in the pre-gel solution. In this case, a large amount of pre-mixture can be prepared in advance, and the photoinitiator is added to the pre-mixture to obtain the pre-gel solution before producing the water-lubricated ultrasonic film.

[0017] Preferably, in the above method, the first polymer monomer is a photopolymerizable monomer, which can be either a monomer containing an ethylenic unsaturated group or selected from conventional photopolymerizable monomers. Specifically, it includes, but is not limited to, any one or more of acrylamide, acrylic acid, methacrylic acid, itaconic acid, and acrylate. As an example, the acrylate can be at least one of 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl methacrylate, 2-hydroxypropyl acrylate, norbornene acrylate, norbornene methacrylate, adamantyl acrylate, and adamantyl methacrylate. Based on the medical application of the water-lubricated ultrasonic film with a Janus gradient structure of the present invention, the selection of the first polymer monomer needs to be harmless to the human body. The above exemplary examples are currently relatively commonly used and meet the safety requirements.

[0018] Preferably, in the above method, the second polymer is a natural polymer, and the natural polymer is selected from, but not limited to, chitosan, chitin, silk fibroin, hyaluronic acid, carboxylated cellulose, inulin, protein, starch, pectin, sesbania gum, alginic acid, sodium alginate, seaweed acid, sodium alginate, lignin, polyglutamic acid, or modified natural polymers, etc. The modified natural polymers can be modified by amination, hydroxylation, amidation, etc. The molecular chains of natural polymers are relatively complex and have a branched structure, and there are also a large number of heteroatom groups between molecules, especially a large number of carboxyl or hydroxyl groups. These groups can form physical bonds such as hydrogen bonds with the polymer formed by the first polymer monomer and the surface-modified nanoparticles and entangle with each other, which can increase the mechanical properties of the obtained water-lubricated ultrasonic film. In addition, the hydrogen bond is a reversible bond. When stretched, some hydrogen bonds break, and new hydrogen bonds form. The same is true when released, which can increase the elasticity of the water-lubricated ultrasonic film while keeping it from breaking.

[0019] Preferably, in the above method, the mass ratio of the first polymer monomer to the second polymer is (1 - 20):1, and most preferably (1 - 10):1. When the first polymer monomer and the second polymer are within this range, the obtained water-lubricated ultrasonic film with a Janus gradient structure has good mechanical properties and imaging properties.

[0020] Preferably, in the above method, the mass fraction of the first polymer monomer in the pre-gel solution is 5 - 25%, preferably 10 - 20%. If the content of the first polymer monomer is too high, the obtained ultrasonic film has poor flexibility and cannot be applied to the ultrasonic probe. If it is too low, a gel-like substance cannot be obtained, and thus the ultrasonic film of the present invention cannot be prepared.

[0021] Preferably, in the above method, the surface-modified nanoparticles include one or a combination of metal single-nanomaterials such as amino-modified barium titanate nanoparticles, nanoclay sheets, and nanogold, nano-metal oxides such as zinc oxide nanoparticles and iron oxide nanoparticles, and carbon nanomaterials (mainly including fullerenes, carbon nanotubes, graphene, and carbon quantum dots). The amino modification can be the surface modification of nanoparticles by amino siloxane and / or dopamine.

[0022] The method for modifying the nanoparticles in the surface-modified nanoparticles is a commonly used method in the art. The mass ratio of the surface modifier used in the modification process to the nanoparticles is (0.25 - 3):1, and more preferably: (0.5 - 2):1.

[0023] Exemplarily, the surface-modified nanoparticles are dopamine-modified nanoparticles on the surface. The specific process is to disperse the nanoparticles in an alkaline buffer solution (such as Tris-HCl solution with pH = 9), then add dopamine, and stir for a period of time such as 2 hours, 3 hours, 4 hours or more under aerobic atmosphere. Subsequently, solid-liquid separation, washing and drying are carried out to obtain dopamine-modified nanoparticles.

[0024] In the present invention, the surface amino groups of the amino surface-modified nanoparticles can undergo Schiff base reaction with double bonds. And due to the existence of the nanoparticles and relatively weak ultraviolet light transmittance, the reactivity of the double bonds in the upper and lower layers after photocuring into a film is different, which results in different amounts of double bonds that can react with the nanoparticles in the upper and lower layers. The reacted nanoparticles can stably exist in the ultrasonic film. In addition, the chemically crosslinked nanoparticles can be tightly connected with the polymer chains in the ultrasonic film, thereby enhancing the stability of the ultrasonic film. This tight connection makes the nanoparticles more stable in the ultrasonic film and not easily released, so as to better maintain the gradient structure. In contrast, the unreacted nanoparticles are freely dispersed in the ultrasonic film system and have no interaction with the polymers in the ultrasonic film, and are easily lost from the system, which leads to different amounts of nanoparticles varying with the thickness of the ultrasonic film (see Figure 10 ).

[0025] Preferably, in the above method, the particle size of the surface-modified nanoparticles is 200 - 400 nm. The particle size of the nanoparticles will directly affect the ultrasonic imaging effect, so it is necessary to control the particle size of the nanoparticles.

[0026] Preferably, in the above method, the mass fraction of the surface-modified nanoparticles in the pre-gel solution is 0.01 - 10%. The dosage of the nanoparticles needs to consider both cost and imaging effect, so it is necessary to control an appropriate amount of nanoparticles.

[0027] Preferably, in the above method, the solvent is water, PBS buffer solution or physiological saline. These solvents are harmless to the human body and can dissolve the first polymer monomer and the second polymer, and are very suitable for preparing the water-based lubricating ultrasonic film with Janus gradient structure of the present invention.

[0028] In the above method, the types and dosages of the photoinitiator are both conventional types and usages in the field of polymer photopolymerization. Specifically, the photoinitiator includes but is not limited to at least one of 2-methyl-1-(4-methylthiophenyl)-2-morpholin-1-one, 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-ethanone, diethyl oxalate, benzoyl peroxide, benzophenone, camphorquinone, dilauroyl peroxide, N,N-dimethyl-p-toluidine, azobisisobutyronitrile, azobisisoheptonitrile, tert-butyl peroxybenzoate, diphenyl-2,4,6-(trimethylbenzoyl)phosphine oxide, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, ethyl 4-(dimethylamino)benzoate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphate. More specifically, the dosage of the photoinitiator is 0.01% - 5% of the first polymer monomer.

[0029] Preferably, in the above method, the process of coating the pre-gel solution is carried out on a template, and the shape of the template is not strictly limited.

[0030] Preferably, in the above method, the process of coating the pre-gel solution can also be carried out in a model with a certain three-dimensional geometric shape, such as a pear-shaped bulb or a sphere.

[0031] In the present invention, the shape of the coating during the process of coating the pre-gel solution needs to be determined according to the situation. For example, if the user needs a flat shape, it can be carried out on a template such as a square, rectangle, circle, or rhombus template. If the user wants to customize specifically according to the shape of the ultrasonic probe, the coating process can also be carried out in a customized model. In addition, in the above method, the material of the template or model used during the process of coating the pre-gel solution is not strict and can be a glass sheet, polytetrafluoro material, acrylic, etc.

[0032] Preferably, in the above method, the coating amount of the pre-gel solution during the process of coating the pre-gel solution is 0.2 - 0.5 g / cm 2 , the water-lubricated ultrasonic film with a Janus gradient structure of the present invention is a medical consumable and belongs to disposable consumer goods. If the coating amount is too large, the obtained ultrasonic film is too thick, inconvenient to use, with a poor experience and increased cost. If the coating amount is insufficient, the obtained ultrasonic film is too thin, with poor imaging, and is prone to rupture during use, resulting in detection failure.

[0033] Preferably, in the above method, the exposure intensity of ultraviolet light during the photo-curing film-forming process is 0.1 - 30 mW·cm -2 , the exposure time is 1 second - 30 minutes, and the exposure dose D (exposure intensity × exposure time) is not less than 0.5 mJ·cm -2If the exposure intensity and exposure time are too small, the obtained ultrasonic film will not react sufficiently, and its mechanical properties will be damaged and it will be easily destroyed; if the exposure intensity and exposure time are too large, the ultrasonic film will be over-crosslinked and lose its elasticity.

[0034] Particularly preferably, the interval time between the two steps of coating the pre-gel solution and photo-curing to form a film does not exceed 10 seconds to prevent the natural sedimentation of the nanoparticles, so that they can be quickly fixed in the hydrogel network, eliminating the influence of the natural sedimentation of the nanoparticles, and making the gradient structure of the water-lubricated ultrasonic film obtained in the present invention controllable.

[0035] Preferably, in the above method, after photo-curing to form a film, the obtained film needs to be immersed or washed in pure water to remove unreacted monomers or nanoparticles, so as to avoid the overflow of unreacted monomers and nanoparticles, which may have an adverse effect on the human body. Moreover, the overflow of unreacted nanoparticles can better reflect the gradient presence of nanoparticles in the obtained water-lubricated ultrasonic film. The cleaning process is very simple, and it can be immersed in pure water for 3 - 20 min, or gently shaken several times in pure water, such as 2 times, 3 times, 4 times or more.

[0036] In the photo-curing film-forming process of the present invention, the nanoparticles are opaque. When ultraviolet light irradiates the gel pre-gel solution, the light intensity attenuates in a gradient. Therefore, the polymerization and crosslinking degree of the pre-gel solution closer to the ultraviolet light source is high, more unsaturated bonds are consumed, and the reaction degree with amino-modified nanoparticles is low, resulting in a more hydrophilic gel, which is more conducive to the probe's movement; on the contrary, the polymerization and crosslinking degree of the pre-gel solution farther from the ultraviolet light source is low, fewer double bonds are consumed, and the reaction degree with amino-modified nanoparticles is high, resulting in a more hydrophobic gel, thereby realizing the gradient structure of the nanoparticle distribution in the ultrasonic film (see Figure 1 ). In addition, the chemical crosslinking of the nanoparticles with the gel system makes the nanoparticles more stable, and they will not transfer to water after being wetted by water, resulting in safety problems, and they will not overflow during use ( Figure 10 ), which is more beneficial to the health of patients. It should also be noted that the Janus gradient structure of the water-lubricated ultrasonic film of the present invention can be precisely controlled by changing the light intensity, nanoparticle concentration, and the amount of photoinitiator in the gel system, with higher stability and better safety.

[0037] According to the second aspect of the present invention, there is also provided a water-lubricated ultrasonic film with a Janus gradient structure prepared by the above preparation method.

[0038] The nanoparticles introduced into the water-lubricated ultrasound film with a Janus gradient structure in the present invention are tightly connected to the gel system through chemical cross-linking, which improves the stability of the ultrasound signal while making it safer. In particular, the two sides of the Janus gradient structure ultrasound film of the present invention have different properties. One side has adhesiveness to isolate air and obtain high-quality ultrasound images, while the other side has the function of water lubrication. It shows adhesiveness in the initial state, which is beneficial for long-term storage. When it comes into contact with water and the patient, it shows a lubricated state, which is beneficial for the probe to move around ( Figure 9 ). In addition, the water-lubricated ultrasound film of the present invention has excellent mechanical properties and is durable. It can adapt to the shape of the ultrasound probe, adhere completely to the ultrasound probe, avoid the leakage and attenuation of the ultrasound signal, and prevent foreign objects and bacteria from entering the body in various scenarios due to the complete adhesion to the ultrasound probe, protecting the patient from infection. Therefore, the water-lubricated ultrasound film of the present invention can be used in special application scenarios, such as minimally invasive interventional surgery, obstetrics and gynecology examinations, etc., avoiding the defects of existing ultrasound coupling agents.

[0039] Preferably, the thickness of the water-lubricated ultrasound film with a Janus gradient structure is 1-2 mm. If it is too thin, the ultrasound film is likely to be damaged during use; if it is too thick, it will affect the quality of the ultrasound image.

[0040] According to the third aspect of the present invention, there is also provided an application of the water-lubricated ultrasound film with a Janus gradient structure prepared by the above preparation method, and the application is ultrasonic detection, that is, the water-lubricated ultrasound film with a Janus gradient structure is applied to ultrasonic detection.

[0041] The water-lubricated ultrasound film prepared by the present invention shows adhesiveness in the initial state (i.e., when it is just prepared), which is beneficial for long-term storage. When it comes into contact with water and the patient, it shows a lubricated state, which is beneficial for the probe to move around. Then the specific use process is that the ultrasound film is stored in a sterile state. When in use, open the package, put it on the surface of the ultrasound probe, pay attention to discharging the air bubbles, and then it can be used after dipping in ultrapure water or pure water or deionized water. Obviously, the water-lubricated ultrasound film prepared by the present invention only needs to be wetted on the surface during use and does not require an ultrasound coupling agent. And through a large number of actual applications, it is proved that the water-lubricated ultrasound film of the present invention has excellent ultrasound imaging effects, and even can present more real images than existing commercial ultrasound coupling agents (see Figure 3 - 7 ), and is very suitable for large-scale applications.

[0042] When the water-lubricated ultrasound film with a Janus gradient structure of the present invention is applied to ultrasonic detection, since the two sides have different properties: one side has adhesiveness and the other side has water lubricity, it can achieve both isolating air to obtain high-quality ultrasonic images and presenting a lubricated state when contacting the patient during ultrasonic detection, which is conducive to the movement of the probe. In addition, the water-lubricated ultrasound film with a Janus gradient structure of the present invention can adapt to the shape of the ultrasonic probe, completely adhere to the ultrasonic probe, avoid the leakage and attenuation of ultrasonic signals, and since it completely adheres to the ultrasonic probe, it can prevent foreign objects and bacteria from entering the body in various scenarios, protecting the patient from infection. Therefore, the water-lubricated ultrasound film of the present invention can be used in special application scenarios such as minimally invasive interventional surgery and obstetrics and gynecology examinations, avoiding the defects of existing ultrasonic coupling agents.

[0043] Compared with the prior art, the present invention has the following advantages.

[0044] First of all, the raw materials of the preparation method of the present invention are rich in sources, simple and easy to operate, and it is very easy to realize large-scale production. Secondly, the water-lubricated ultrasound film with a Janus gradient structure obtained by the preparation method of the present invention is a three-dimensional network structure ( Figure 8 ), which can absorb a large amount of water, and the introduced nanoparticles are tightly connected to the gel system through chemical cross-linking, making its safety higher while improving the stability of ultrasonic signals. Thirdly, the two sides of the Janus gradient structure ultrasound film of the present invention have different properties. One side has adhesiveness to isolate air to obtain high-quality ultrasonic images, while the other side has the function of water lubrication. It shows adhesiveness in the dry state, which is conducive to long-term preservation. When it contacts the patient after encountering water, it presents a lubricated state, which is conducive to the movement of the probe. Finally, the water-lubricated ultrasound film of the present invention has excellent mechanical properties ( Figure 2 ), is durable, can adapt to the shape of the ultrasonic probe, completely adhere to the ultrasonic probe, avoid the leakage and attenuation of ultrasonic signals, and since it completely adheres to the ultrasonic probe, it can prevent foreign objects and bacteria from entering the body in various scenarios, protecting the patient from infection. Therefore, the water-lubricated ultrasound film of the present invention can be used in special application scenarios such as minimally invasive interventional surgery and obstetrics and gynecology examinations, avoiding the defects of existing ultrasonic coupling agents, and escorting the life safety of patients. Description of the Drawings

[0045] Figure 1 It is a schematic diagram of the photocuring film-forming process in the preparation method of the water-lubricated ultrasound film of the present invention.

[0046] Figure 2 It is the tensile stress-strain image of the water-lubricated ultrasound film prepared by using different contents of barium titanate nanoparticles in the preparation method of the present invention.

[0047] Figure 3It is a photo of the water-based lubricating ultrasonic film prepared in Example 1 of the present invention closely attached to the ultrasonic probe.

[0048] Figure 4 It is an ultrasonic image of detecting the radial artery of the human body without using any coupling agent.

[0049] Figure 5 It is an ultrasonic image of detecting the radial artery of the human body in the initial state using the water-based lubricating ultrasonic film prepared in Example 1 of the present invention.

[0050] Figure 6 It is an ultrasonic image of detecting the radial artery of the human body in the water lubrication state (i.e., after dipping in ultrapure water) using the water-based lubricating ultrasonic film prepared in Example 1 of the present invention.

[0051] Figure 7 They are ultrasonic images of detecting the heart of SD rats in different media. Among them, (a) is the ultrasonic probe without using any substance, (b) is the ultrasonic probe using a commercially available liquid ultrasonic coupling agent, and (c) and (d) are the water-based lubricating ultrasonic films prepared using barium titanate nanoparticles with a content of 2 mg / ml and 10 mg / ml in Example 1 and Example 7 of the present invention.

[0052] Figure 8 It is an SEM image showing different crosslinking degrees in the longitudinal section direction of the water-based lubricating ultrasonic film prepared in Example 1 of the present invention.

[0053] Figure 9 It is an image of the water-based lubricating ultrasonic film of Example 1 of the present invention adhering to the bottle cap. Among them, a is the initial state, and b is the water lubrication state (i.e., the state after dipping in ultrapure water).

[0054] Figure 10 It is the particle release curve of the ultrasonic film prepared from nanoparticles and unmodified nanoparticles in the water-based lubricating ultrasonic film prepared in Example 1 of the present invention.

[0055] Figure 11 It is a photo of photocuring film formation in the preparation method of the water-based lubricating ultrasonic film prepared in Example 1 of the present invention.

[0056] Figure 12 It is a linear relationship curve graph of nanoparticle concentration and water contact angle. Detailed implementation manners

[0057] The following further illustrates the detailed implementation manners of the present invention with reference to the accompanying drawings.

[0058] The raw materials used in the following examples are all commercially available. The solvents used are deionized water, physiological saline, and PBS buffer solution. The first polymer monomer is acrylamide (AM), the second polymers are sodium alginate (SA) and chitosan (CTS), the photoinitiators are 2-methyl-1-(4-methylthiophenyl)-2-morpholin-1-propanone (I907), diphenyl-2,4,6-(trimethylbenzoyl)phosphine oxide (TPO), and lithium phenyl(2,4,6-trimethylbenzoyl)phosphate (LAP). The nanoparticles are barium titanate nanoparticles, nanoclay sheets, and nanogold, with a particle size of 200 nm. The reagent used for modifying the nanoparticles is dopamine. The specific modification process is as follows: First, disperse 100 mg of nanoparticles in 50 mL of Tris-HCl solution (10 mM, pH = 9), then add 200 mg of dopamine, expose to air and stir evenly for 6 hours. After that, filter and collect the nanoparticles, wash them 3 times with 50 mL of deionized water, and finally freeze-dry for standby to obtain dopamine-modified nanoparticles. Among them, the dopamine-modified barium titanate nanoparticles, nanoclay sheets, and nanogold are denoted as N1, N2, and N3 respectively.

[0059] Example

[0060] Examples 1 - 10

[0061] According to the amounts and parameter settings of each substance shown in Table 1 below, prepare the water-lubricated ultrasonic film with a Janus gradient structure of the present invention according to the following steps. The products are denoted as: A1, A2, A3, A4, A5, A6, A7, A8, A9, A10.

[0062] S1. Prepare the premixed solution: Mix the first polymer monomer, the second polymer, the surface-modified nanoparticles, and the solvent evenly to obtain the premixed solution.

[0063] S2. Prepare the pre-gel solution: Dissolve the photoinitiator in the premixed solution obtained in step S1 and mix evenly to obtain the pre-gel solution.

[0064] S3. Coat the pre-gel solution: Coat the pre-gel solution on a square glass slide.

[0065] S4. Photo-cure to form a film: Photo-cure the pre-gel solution coated for 2 s under ultraviolet light to form a film, and the water-lubricated ultrasonic film with a Janus gradient structure of the present invention can be obtained.

[0066] Table 1 Amounts (unit: g) of each substance and parameter settings in Examples 1 - 10 of the invention

[0067] Comparative example

[0068] Comparative examples 1 - 20

[0069] Prepare the ultrasonic film according to the amounts and parameter settings of each substance shown in Tables 2 and 3 below in the following steps, and the products are respectively denoted as: B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11, B12, B13, B14, B15, B16, B17, B18, B19, B20.

[0070] S1. Prepare the premixed solution: Mix the first polymer monomer, the second polymer, the surface-modified nanoparticles and the solvent evenly to obtain the premixed solution;

[0071] S2. Prepare the pre-gel solution: Dissolve the photoinitiator in the premixed solution obtained in step S1 and mix evenly to obtain the pre-gel solution;

[0072] S3. Coat the pre-gel solution: Coat the pre-gel solution on a glass slide;

[0073] S4. Photo-cure into a film: Photo-cure the pre-gel solution after coating for 2 s under ultraviolet light to obtain the water-lubricated ultrasonic film with a Janus gradient structure of the present invention.

[0074] Table 2 Amounts of each substance in Comparative Examples 1-20

[0075]

[0076] Table 3 Parameter settings in steps S3 and S4 of Comparative Examples 1-20

[0077]

[0078] Performance test examples

[0079] Performance test example 1 Contact angle test

[0080] Perform contact angle tests on the top and bottom surfaces (i.e., the upper and lower surfaces, where the upper surface is the one close to the ultraviolet light source and the lower surface is the one far from the ultraviolet light source) of the water-lubricated ultrasonic films A1-A10 with a Janus gradient structure prepared in Examples 1-10 and the products B1-B20 prepared in Comparative Examples 1-10. The instrument used is the surface and interface tensiometer DKSH-K100, and the test results are shown in Table 4 below.

[0081] The specific test process of the contact angle is as follows:

[0082] Prepare the sample: Select a flat and uniform solid surface as the test sample, and ensure that the sample surface is clean and pollution-free;

[0083] Drop the liquid droplet: Use a micro syringe to drop a small drop of the test liquid on the sample surface;

[0084] Taking photos: Use a high-definition camera to take photos of the droplet in contact with the solid surface;

[0085] Measuring the contact angle: Measure the contact angle in the photo through image processing software.

[0086] Table 4 Contact angle test results

[0087]

[0088] It can be seen from the test results that the surface contact angle of the Janus gradient structure water-lubricated ultrasonic film prepared in Examples 1-10 of the present invention is small, while the bottom contact angle is large, indicating that there is a large difference in the hydrophilicity and hydrophobicity of the upper and lower surfaces of the ultrasonic film. The preparation method of the present invention realizes different distributions of nanoparticles in the upper and lower layers of the ultrasonic film, and further enables the upper and lower surfaces of the ultrasonic film to have different hydrophilicities. The specific analysis is that the surface of the nanoparticles is amino-modified, so it can react with the double bonds in the gel system. Since the upper layer of the gel is directly irradiated with ultraviolet light, more double bonds in the system are consumed, so the reaction with the nanoparticles is less, and finally fewer nanoparticles remain. Since the nanoparticles are hydrophobic, the water contact angle of this layer is also small, and the opposite effect occurs in the lower layer, which also shows that the distribution of nanoparticles in the ultrasonic film has a gradient structure. However, the contact angles of the upper and lower layers of the materials prepared in Comparative Examples 1-20 are not much different. It can be seen that the preparation method of the present invention needs to strictly control the use of raw materials and also needs to control various parameters in the process to achieve the desired Janus structure.

[0089] Performance test Example 2 Gradient structure characterization test

[0090] In order to verify that the distribution of nanoparticles affects the surface hydrophilicity of the water-lubricated ultrasonic film of the present invention, six different materials with a non-gradient structure of nanoparticles were specifically prepared. In order to obtain an ultrasonic film with a non-gradient structure, when ultraviolet light cross-linking the prepolymer solution, the upper and lower surfaces were irradiated simultaneously, and the other steps were the same as those in Example 1. The prepared ultrasonic films with a non-gradient structure were respectively denoted as C1, C2, C3, C4, C5, and C6. The raw materials and parameters involved in this preparation process are shown in Table 5 below. Finally, the contact angle test was carried out on the obtained materials, and the instrument used was the surface and interface tension meter DKSH-K100. The test results are shown in Table 6 below.

[0091] Table 5 The amount of substances (unit: g) and parameters used in the preparation process of the non-gradient structure materials

[0092]

[0093] Table 6 Contact angle test results of the non-gradient structure materials

[0094]

[0095] Processing was carried out on the data in Table 6, and the results are shown in Figure 12 , obviously, the contact angle is positively correlated with the concentration of nanoparticles and has a linear relationship. The formula is: y = 2.60x + 4.94, where x is the concentration of nanoparticles (unit: mg / mL) and y is the water contact angle (unit: degree). The results confirmed that the amino-modified ultrasound-responsive nanoparticles can undergo Schiff base reaction with the double bonds in the ultrasound membrane system, and the water contact angles of the ultrasound membranes with different contents of nanoparticles are different. However, this formula does not represent the relationship between the surface contact angle of the water-lubricated ultrasound membrane of the present invention and the nanoparticles, because the surface contact angle of the water-lubricated ultrasound membrane of the present invention is also affected by other factors such as the first polymer monomer, the second polymer and many other factors.

[0096] Performance Test Example 3 Mechanical Property Test

[0097] The water-lubricated ultrasound membranes A1 - A10 with Janus gradient structure prepared in Examples 1 - 10 and the products B1 - B20 prepared in Comparative Examples 1 - 20 were subjected to mechanical property tests. The instrument used was INSTRON-3400, and the test results are shown in Table 7 below.

[0098] In this performance test example, the elastic modulus of the ultrasound membrane was calculated using the compression test results. The maximum compression of the compression test was set to 80%, the strain rate was 10 mm / min, and the preloading was 0.04 N to obtain the stress-strain curve, and then the elastic modulus was calculated according to the test results. The formula is: E = σ / ε, where E represents the elastic modulus, σ represents the stress, and ε represents the strain.

[0099] Table 7 Mechanical Property Test Results

[0100]

[0101] As can be seen from the above table, the elastic modulus of the obtained ultrasound membrane material is positively correlated with the amount of the first polymer monomer, the amount of photoinitiator, the amount of nanoparticles, etc. used in the preparation process. In Examples 1 - 10 of the present invention, the amounts of the first polymer monomer, photoinitiator, and nanoparticles are appropriate. Therefore, the water-lubricated ultrasound membrane with Janus gradient structure obtained has good elasticity. In addition, the content of the photoinitiator in Comparative Example B6 is small and the exposure intensity is low, resulting in the obtained material being shapeless and having an extremely low elastic modulus; while in Comparative Example B16, the amount of the photoinitiator is high, the exposure intensity is high, and the amount of the first polymer monomer is also relatively large. Therefore, the obtained material has a very high elastic modulus, the material is hard and non-elastic. However, if the elastic modulus is too small, the ultrasound membrane is prone to breakage, and if it is too large, it will lose elasticity. Therefore, a moderate elastic modulus should be selected for actual ultrasonic detection.

[0102] Application Examples

[0103] The water-lubricated ultrasonic films A1 - A110 with Janus gradient structure prepared in Examples 1 - 10 and the products B1 - B20 prepared in Comparative Examples 1 - 20 were subjected to ultrasonic application detection. The specific process was as follows: First, SD rats were anesthetized with isoflurane, and after removing the chest hair of the rats, they were fixed in the supine position. An ultrasonic film was wrapped around the ultrasonic probe, and after dipping in sterile deionized water, it was placed on the left side of the rat's chest. The parasternal long-axis view was positioned at the papillary muscle level using 2D-guided M-mode through the chest, and then images were collected and relevant data were output. The contrast-to-noise ratio was calculated from the output data, and the calculation formula was: CNR = (S1 - S2) / σn, where S1 and S2 were the signal intensities of the two regions being compared, and σn was the standard deviation of the noise. A CNR less than 21 was considered to have poor image quality, less than 11 was considered to have very poor image quality, greater than 20 was considered to have good image quality, and greater than 30 was considered to have very good image quality. The results are shown in Table 8 below.

[0104] Table 8 Ultrasonic Application Detection Results

[0105]

[0106] In addition, in Figure 7 , for comparison with not using any medium and using a commercial ultrasonic coupling agent, the images of the water-lubricated ultrasonic films prepared in Examples A1 and A7 of the present invention for detecting the heart ultrasound of SD rats are shown in Figure 7 . It can be seen that as the content of nanoparticles increases, the clarity of the images also increases, and the CNRs are 30 and 39 respectively, indicating that the quality of the obtained ultrasonic images is closely related to the content of nanoparticles.

[0107] Furthermore, the water-lubricated ultrasonic films A1 - A10 with Janus gradient structure prepared in Examples 1 - 10 were made into a set combination for in-vivo ultrasonic application detection, that is, the ultrasonic probe and the connecting wire were wrapped simultaneously for in-vivo ultrasonic detection of rats, which was helpful for anti-pollution in special application scenarios. The in-vivo ultrasonic detection results of rats are shown in Table 9 below.

[0108] Table 9 In-vivo Ultrasonic Detection Results of Rats

[0109]

[0110] Obviously, as can be seen from the above table, when the water-lubricated ultrasonic film with Janus gradient structure of the present invention is used for in-vivo ultrasonic detection, the detection effect is good and it will not pollute the body. It can be seen that the water-lubricated ultrasonic film with Janus gradient structure of the present invention can not only be applied to in-vitro ultrasonic detection, but also to in-vivo ultrasonic detection, and can be well applied to actual ultrasonic detection.

[0111] Based on the disclosure and teachings of the above specification, those skilled in the art to which the present invention pertains can also make changes and modifications to the above embodiments. Therefore, the present invention is not limited to the specific embodiments disclosed and described above, and some modifications and changes to the invention should also fall within the scope of protection of the claims of the present invention. In addition, although some specific terms are used in this specification, these terms are only for convenience of description and do not constitute any limitation to the present invention.

Claims

1. A method for preparing a water-lubricated ultrasonic film with a Janus gradient structure, characterized in that, It includes the following steps: S1. Prepare a premixed solution: Mix the first polymer monomer, the second polymer, the surface-modified nanoparticles and a solvent uniformly to obtain the premixed solution; S2. Prepare a pre-gel solution: Add a photoinitiator to the premixed solution obtained in step S1 and mix uniformly to obtain the pre-gel solution; S3. Coat the pre-gel solution: Coat the pre-gel solution; S4. Photo-cure to form a film: Photo-cure the coated pre-gel solution under ultraviolet light to form a film, and a water-lubricated ultrasonic film with a Janus gradient structure can be obtained. Among them, the first polymer monomer is any one or more of acrylamide, acrylic acid, methacrylic acid, itaconic acid, and acrylate; the second polymer is any one or more of chitosan, chitin, silk fibroin, hyaluronic acid, carboxylated cellulose, inulin, protein, starch, pectin, sesbania gum, alginic acid, sodium alginate, seaweed acid, sodium alginate, lignin, and polyglutamic acid. The mass ratio of the first polymer monomer to the second polymer is (1-10):

1. The surface-modified nanoparticles are amino surface-modified nanoparticles, and the mass fraction of the surface-modified nanoparticles in the pre-gel solution is 0.01-10%. During the photo-curing film formation process, the exposure intensity of the ultraviolet light is 0.1 - 30 mW·cm -2 , the exposure time is 1 second - 30 minutes, and the exposure dose D is not less than 0.5 mJ·cm -2 .

2. The method according to claim 1, wherein The mass fraction of the first polymer monomer in the pre-gel solution is 5-30%.

3. The method according to claim 1, characterized in that, The solvent is water, PBS buffer solution or physiological saline.

4. The method according to claim 1, characterized in that During the process of coating the pre-gel solution, the coating amount of the pre-gel solution is 0.2 - 0.5 g / cm 2 .

5. A water-lubricated ultrasonic film with a Janus gradient structure, characterized in that, The water-lubricated ultrasonic film is prepared by the method described in any one of claims 1-4.

Images