Ultrasonic imaging catheter and its preparation method and application

Abstract

The present application provides an ultrasound imaging catheter and a preparation method and application thereof. The preparation method comprises the following steps: mixing a transparent thermoplastic resin, methacrylic gelatin (GelMA), a photoinitiator, a coupling agent, and water to obtain a mixture, heating and melting the mixture, extruding the mixture, and reacting the mixture under light conditions to obtain a porous inner tube catheter; mixing a coating thermoplastic resin, a compatibilizer, and a plasticizer, heating and liquefying the mixture to obtain a liquid resin material, and coating the porous inner tube catheter with the liquid resin material to obtain a porous ultrasound imaging catheter with a smooth surface; the melting temperature of the transparent thermoplastic resin is ≥ that of the coating thermoplastic resin; and the ultrasound imaging catheter obtained has good ultrasound imaging effect, good mechanical properties, and little biological loss through the combination of light curing, water vapor heating to generate holes, and surface coating processes.

Description

Technical Field

[0001] The present invention relates to the field of medical materials, and in particular to an ultrasonic imaging catheter and a preparation method and application thereof. Background Art

[0002] The working principle of ultrasound imaging catheter is mainly based on the scattering and reflection principle of ultrasound. When ultrasound encounters media of different densities, scattering and reflection phenomena will occur. Since the polymer fiber filaments inside the ultrasound imaging catheter form ultrasound imaging areas of different densities, these areas will produce obvious scattering and reflection signals under the irradiation of ultrasound, thus forming a clear catheter image on the ultrasound image.

[0003] Since the acoustic impedance of existing medical interventional catheter materials is similar to that of human soft tissue (1.52×10 6 kg / m 2 s) is close, making the ultrasound image of the existing interventional catheter in the human body unclear. Therefore, researchers have adopted different methods to enhance the ultrasound reflection coefficient of the interventional catheter and thus improve the clarity of the ultrasound image of the interventional catheter in the human body. For example, the imaging catheter is perforated to enhance the sound wave scattering and reflection ability of the material surface and improve the ultrasound imaging effect. However, this will cause the mechanical properties of the imaging catheter to decrease, and the pores on the outside of the imaging catheter will destroy the smoothness of the product surface, increase the friction between it and the blood vessels during its movement in the body, and easily damage the blood vessels.

[0004] Therefore, it is necessary to provide an ultrasound imaging catheter with good ultrasound imaging effect, good mechanical properties and small biological loss. Summary of the invention

[0005] In view of the defects in the prior art, the present invention proposes an ultrasound imaging catheter and a preparation method and application thereof to solve the problem of how to improve the ultrasound imaging effect, mechanical properties and safety of the ultrasound imaging catheter.

[0006] In order to solve the above technical problems, this application provides the following technical solutions:

[0007] In a first aspect, the present application provides a method for preparing an ultrasound imaging catheter, comprising the following steps:

[0008] S1. A transparent thermoplastic resin, methacrylic gelatin (GelMA), a photoinitiator, a coupling agent, and water are mixed to obtain a mixture, the mixture is heated to melt, extruded, and then reacted under light conditions to obtain a porous inner tube catheter;

[0009] S2. The coated thermoplastic resin, compatibilizer, and plasticizer are mixed and heated to liquefy to obtain a liquid resin material, and the porous inner tube catheter is coated with the liquid resin material to obtain a porous ultrasound imaging catheter with a smooth surface;

[0010] The melting temperature of the transparent thermoplastic resin is ≥ that of the coating thermoplastic resin.

[0011] Preferably, the transparent thermoplastic resin includes one or more of polypropylene, polymethyl methacrylate, and polystyrene.

[0012] Preferably, the coating type thermoplastic resin comprises polyethylene.

[0013] Preferably, the coupling agent is a silane coupling agent.

[0014] Preferably, the compatibilizer includes one or more of PE-G-MAH, EAA, SPEEK, and PS-G-MAH; and the plasticizer includes one or more of polyvinyl alcohol, acrylate, and sodium alkylbenzene sulfonate.

[0015] Preferably, the coating method is: taking out after coating and / or dipping, and then cooling and curing.

[0016] Preferably, in step S1, the water content of the mixture is 3-7%; the water content of the methacrylated gelatin is less than 0.02%.

[0017] Preferably, the illumination is ultraviolet light and / or blue light.

[0018] In a second aspect, the present application provides an ultrasound imaging catheter.

[0019] In a third aspect, the present application provides an application of an ultrasound imaging catheter in the preparation of medical materials.

[0020] In summary, compared with the prior art, the present invention achieves the following technical effects: the present application improves the ultrasonic imaging effect by adding water when heating and melting the transparent thermoplastic resin; the methacrylic gelatin is evenly distributed in the transparent thermoplastic resin through a coupling agent, thereby overcoming the negative impact of ultrasonic imaging caused by the addition of water and improving the mechanical properties of the ultrasonic imaging catheter; and then the coated thermoplastic resin is embedded with the inner tube catheter through a surface coating method to improve the smoothness of the ultrasonic imaging catheter and avoid damage to the body during use. Through the combination of light curing, water vapor heating to produce holes, and surface coating processes, the obtained ultrasonic imaging catheter has good ultrasonic imaging effect, good mechanical properties, and small biological body loss. DETAILED DESCRIPTION

[0021] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are only embodiments of a part of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0022] A method for preparing an ultrasound imaging catheter comprises the following steps:

[0023] S1. A transparent thermoplastic resin, methacrylic gelatin (GelMA), a photoinitiator, a coupling agent, and water are mixed to obtain a mixture, the mixture is heated to melt, extruded, and then reacted under light conditions to obtain a porous inner tube catheter;

[0024] S2. The coated thermoplastic resin, compatibilizer, and plasticizer are mixed and heated to liquefy to obtain a liquid resin material, and the porous inner tube catheter is coated with the liquid resin material to obtain a porous ultrasound imaging catheter with a smooth surface;

[0025] The melting temperature of the transparent thermoplastic resin is ≥ that of the coating thermoplastic resin.

[0026] The present application adds water when heating and melting the transparent thermoplastic resin so that during the melt extrusion, the water evaporates and expands to form water vapor, and then forms pores on the inner and outer surfaces of the inner tube, thereby changing the acoustic resistance and improving the ultrasonic imaging effect; however, as the pore forming extrusion molding process is also completed with a cooling process, the water vapor in the pores will condense into water, resulting in a reduction in the ultrasonic imaging effect. The present application uses a coupling agent to evenly distribute methacrylic gelatin in the transparent thermoplastic resin. On the one hand, methacrylic gelatin can absorb condensed water (methacrylic gelatin can absorb water before and after photocuring) to overcome the disadvantage of reduced ultrasonic imaging effect. On the other hand, methacrylic gelatin is cured under the action of a photoinitiator (under light conditions, the photosensitive groups in GelMA react, resulting in an increase in cross-linking density and rigidification of the molecular chain, thereby enhancing its mechanical properties) to overcome the disadvantage of reduced mechanical strength of the ultrasonic imaging catheter caused by the formation of pores; therefore, the transparent thermoplastic resin, methacrylic gelatin, photoinitiator, coupling agent, and water cooperate with each other to improve the ultrasonic imaging effect.

[0027] Although the operation of step S1 can improve the ultrasonic imaging effect, the inner-bore catheter obtained has holes both inside and outside due to the uncontrollable expansion of water vapor. When it moves in the body, the friction between it and the blood vessels is too large, which may cause blood vessel damage. Therefore, the present application combines the coated thermoplastic resin with the inner tube catheter with holes on the surface and inside through the surface coating method of step S2, so that the obtained ultrasonic imaging catheter has a smooth outer surface, which reduces the friction between the ultrasonic imaging catheter and the blood vessels when it moves in the body, thereby avoiding blood vessel damage; at the same time, since there are certain pores on the outer surface of the porous inner tube catheter, the fluid coated thermoplastic resin can achieve mutual embedding of the transparent thermoplastic resin and the coated thermoplastic resin after coating the porous inner tube catheter, and with the help of the compatibilizer, they are more tightly combined, thereby avoiding the inner and outer layers of the ultrasonic imaging catheter from separating from each other after long-term use, thereby improving the stability of the ultrasonic imaging catheter. Furthermore, in order to improve the bonding strength between the transparent thermoplastic resin and the coated thermoplastic resin, a compatibilizer is added to improve the compatibility; in order to reduce the heating liquefaction temperature of the coated thermoplastic resin, a plasticizer is added. The advantage of reducing the liquefaction temperature is that it prevents the transparent thermoplastic resin from softening or melting when the coated thermoplastic resin is wrapped in the inner tube catheter during coating, thereby preventing the pores from collapsing.

[0028] In some embodiments, transparent thermoplastic resins include polypropylene, polymethyl methacrylate, and polystyrene. Such resins have high transparency, which is conducive to the photocatalytic curing of methacrylic gelatin to enhance the mechanical properties of the ultrasound imaging catheter. At the same time, the cured methacrylic gelatin is hygroscopic and can absorb condensed water to avoid interference of water droplets with ultrasound imaging.

[0029] In some embodiments, the coating thermoplastic resin includes polyethylene; the melting temperature of the transparent thermoplastic resin is 165-200°C (heating and melting temperature of step S1), which will not cause degradation of methacrylated gelatin; the coating thermoplastic resin has a melting and liquefaction temperature of 110-130°C (heating and liquefaction temperature of step S2), which is lower than the melting temperature of the transparent thermoplastic resin.

[0030] In some embodiments, the coupling agent is a silane coupling agent, including one or more of methacryloxypropyltrimethoxysilane (KH-570), γ-aminopropyltriethoxysilane (KH-550), and γ-glycidyloxypropyltrimethoxysilane (KH-560); since methacryloxylated gelatin contains a large number of hydrophilic groups (such as carboxyl groups, hydroxyl groups, etc.), and thermoplastic resin is a hydrophobic material, the two have poor compatibility, so it is necessary to provide a coupling agent to enhance the compatibility of the two, so that the methacryloxylated gelatin is evenly distributed in the transparent thermoplastic resin.

[0031] In some embodiments, the compatibilizer includes one or more of PE-G-MAH, EAA, SPEEK, and PS-G-MAH; the plasticizer includes one or more of polyvinyl alcohol, acrylate, and sodium alkylbenzene sulfonate; the purpose of the compatibilizer is to improve the compatibility of the two thermoplastic resins to achieve better integration, and the role of the plasticizer is to reduce the liquefaction temperature of the coated thermoplastic resin, facilitate processing, and expand the selection range.

[0032] In some embodiments, the coating method is: taking out after coating and / or dipping, and then cooling and curing; so that the coating thermoplastic resin can evenly coat the porous inner layer conduit.

[0033] In some embodiments, in step S1, the water content of the mixture is 3-7%, the methacryloyl gelatin is a hydrogel after drying, and the water content of the methacryloyl gelatin is less than 0.02%; the more water is used, the higher the bubble ratio is, but if the bubble ratio is too high, it will lead to poor transparency and mechanical properties of the tube body, and it will not be conducive to the photocuring of the methacryloyl gelatin; if the bubble ratio is too low, the ultrasonic development effect is not good.

[0034] In some embodiments, the light is ultraviolet light and / or blue light; the photoinitiator includes one or more of Irgacure 295, α-ketoglutaric acid, and benzoin methyl ether. Other process parameters or raw materials not mentioned in this embodiment are all well-known conventional settings.

[0035] The present application provides an ultrasound imaging catheter.

[0036] The present application provides an application of an ultrasound imaging catheter in the preparation of medical materials.

[0037] The present solution is further described below through specific implementation methods.

[0038] Example 1

[0039] A method for preparing an ultrasound imaging catheter comprises the following steps:

[0040] S1. 80 g of polypropylene, 15 g of methacryloyl gelatin (GelMA), 1 g of α-ketoglutaric acid, 1 g of methacryloyloxypropyltrimethoxysilane, and 3 g of water are mixed to obtain a mixture, the mixture is placed in an internal mixer, heated to melt at 200° C., extruded, cooled to 20° C., and then irradiated under ultraviolet light for 5 minutes to react, thereby obtaining a porous inner tube catheter;

[0041] S2.92g of polyethylene, 5g of PE-G-MAH and 3g of polyvinyl alcohol are mixed and heated at 130°C to liquefy to obtain a liquid resin material. The porous inner tube catheter is immersed in the liquid resin material for 2 minutes. After being taken out and cooled and solidified, the immersion (2 minutes) and cooling and solidification treatments are repeated twice to obtain an ultrasound imaging catheter.

[0042] Embodiment 2-5

[0043] A method for preparing an ultrasonic imaging catheter, the other contents are the same as those of Example 1, except that the amounts of water used are 2g, 5g, 7g, and 10g, respectively.

[0044] Comparative Example 1

[0045] A method for preparing an ultrasound imaging catheter, the other contents of which are the same as those of Example 1, except that methacrylated gelatin is replaced by polypropylene.

[0046] Comparative Example 2

[0047] A method for preparing an ultrasound imaging catheter, the other contents of which are the same as those of Example 1, except that water is replaced by polypropylene.

[0048] Comparative Example 3

[0049] A method for preparing an ultrasound imaging catheter, the other contents of which are the same as those of Example 1, except that step S2 is not included.

[0050] Test and Evaluation

[0051] The ultrasonic imaging catheters obtained in the embodiments and comparative examples were tested for ultrasonic effect, mechanical properties and surface morphology.

[0052] Among them, the test method of ultrasound effect is: taking the grayscale of ultrasound image simulating tissue vascular wall as the benchmark, the ultrasound imaging effects of different samples can be compared by comparing the ratio of the b peak area (Sb, representing the brightness of the sample ultrasound image, that is, the light spot density) to the a peak area (Sa, representing the brightness of the blood vessel wall ultrasound image) of different samples. The larger the ratio, the better the development effect of the spline ultrasound image. The results are shown in Table 1.

[0053] The test standard for mechanical properties is: the tensile strength is tested according to GB / T 16421-1996 "Test method for small specimens of plastic tensile properties"; the results are shown in Table 1.

[0054] Table 1 Performance test results of different ultrasound catheters

[0055]

[0056] As can be seen from Table 1, in Examples 1-5, as the amount of water used increases, Sb / Sa shows a trend of first increasing and then decreasing. The reason is that although the porosity increases with the increase in the amount of water used, the amount of water vapor absorbed by the same amount of methacrylic gelatin after condensation is limited, resulting in a decrease in the ultrasonic imaging effect; at the same time, the tensile strength also shows a trend of gradually decreasing with the increase in the amount of water used. Comparative Example 1 does not use methacrylic gelatin, and its ultrasonic imaging effect and mechanical properties are both reduced compared with Example 1; Comparative Example 2 does not use water, and its ultrasonic imaging effect is greatly reduced compared with Example 1, but the mechanical properties do not change much. The surface of the ultrasonic imaging catheter obtained in Comparative Example 3 is not smooth, and its ultrasonic imaging effect does not change much compared with Example 1, but the mechanical properties are reduced, and it is easy to cause damage to the body.

[0057] The present application improves the ultrasonic imaging effect by adding water when heating and melting the transparent thermoplastic resin; by using a coupling agent, methacrylic gelatin is evenly distributed in the transparent thermoplastic resin, thereby overcoming the negative impact of ultrasonic imaging caused by the addition of water and improving the mechanical properties of the ultrasonic imaging catheter; and then by using a surface coating method, the coated thermoplastic resin is embedded with the inner tube catheter to improve the smoothness of the ultrasonic imaging catheter and avoid damage to the body during use. Through the coordination of light curing, water vapor heating to produce holes, and surface coating processes, the obtained ultrasonic imaging catheter has good ultrasonic imaging effect, good mechanical properties, and small biological body loss.

[0058] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing an ultrasound imaging catheter, characterized in that: The following steps are involved: S1. A transparent thermoplastic resin, methacrylated gelatin, a photoinitiator, a coupling agent, and water are mixed to obtain a mixture, the mixture is heated to melt, extruded, and then reacted under light conditions to obtain a porous inner tube catheter; S2. The coated thermoplastic resin, compatibilizer, and plasticizer are mixed and heated to liquefy to obtain a liquid resin material, and the porous inner tube catheter is coated with the liquid resin material to obtain a porous ultrasound imaging catheter with a smooth surface; The melting temperature of the transparent thermoplastic resin is ≥ that of the coated thermoplastic resin; in step S1, the water content of the mixture is 3-7%; the water content of the methacrylated gelatin is less than 0.02%; The transparent thermoplastic resin includes one or more of polypropylene and polymethyl methacrylate; The coated thermoplastic resin includes polyethylene; The coupling agent is a silane coupling agent; The compatibilizer includes one or more of PE-G-MAH, EAA, SPEEK, and PS-G-MAH.

2. The method for preparing an ultrasound imaging catheter according to claim 1, characterized in that: The plasticizer includes one or more of polyvinyl alcohol, acrylate, and sodium alkylbenzene sulfonate.

3. The method for preparing an ultrasound imaging catheter according to claim 1, characterized in that: The coating method is: taking out after coating and / or dipping, and then cooling and curing.

4. The method for preparing an ultrasound imaging catheter according to claim 1, characterized in that: The light is ultraviolet light and / or blue light.

5. An ultrasound imaging catheter obtained by the preparation method according to any one of claims 1 to 4.

6. Use of the ultrasonic imaging catheter as claimed in claim 5 in the preparation of medical materials.

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