Developing catheter as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of developing catheters, and particularly relates to a developing catheter as well as a preparation method and application thereof. The developing catheter is prepared from the following raw materials in parts by weight: 30 to 60 parts of nano barium sulfate, 40 to 70 parts of thermoplastic elastomer, 1 to 2 parts of dispersing agent and 0.1 to 1 part of coupling agent, and the sum of the parts by weight of the nano barium sulfate and the thermoplastic elastomer is 100; the coupling agent comprises an amino silane coupling agent and an aluminate coupling agent, and the mass ratio of the amino silane coupling agent to the aluminate coupling agent is 1: 1-1: 3.

Description

Technical Field

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

[0002] Barium sulfate, as an inorganic material with a high atomic number and high electron density, occupies a crucial position in the field of medical imaging, especially in X-ray angiography, due to its remarkable X-ray absorption characteristics. This strong X-ray attenuation ability stems from the effective interaction between the inner-layer electrons of its atoms and X-ray photons, converting the photon energy into heat or other forms, thereby reducing the penetration of X-rays and forming an obvious contrast in the image, effectively enhancing the visual presentation of tissue structures. Therefore, barium sulfate is widely used in gastrointestinal imaging, angiography, and other interventional diagnoses and treatments, providing crucial imaging information for clinicians.

[0003] However, despite the excellent X-ray blocking performance of barium sulfate, its application as an inorganic filler in polymer matrices still faces many technical challenges. In the manufacture of imaging catheters, to achieve an ideal X-ray imaging effect, a high proportion of barium sulfate is usually added to polymers such as TPU or Pebax. However, high concentrations of inorganic particle fillers often lead to a series of negative effects, including: Dispersibility problems: Barium sulfate particles, especially nano-sized particles, are prone to agglomeration due to their extremely large specific surface area and high surface energy. This agglomeration phenomenon not only reduces the uniform dispersion of barium sulfate in the polymer matrix but also forms stress concentration points at the micro level, thus significantly reducing the overall mechanical properties of the composite material, such as toughness and fracture strength. Interface compatibility challenges: Polymer matrices usually have a low surface energy, resulting in poor interfacial wettability and insufficient adhesion between them and inorganic barium sulfate particles. This incompatibility forms an obvious phase separation interface between the two, which not only affects the mechanical properties of the material but also hinders the effective stress transfer of the composite material, reducing the overall performance of the composite material. In addition, such interfacial defects can also lead to an uneven microstructure, burrs in the final product, and even precipitation during the use of the product. Processability problems: At high filling levels, the addition of barium sulfate powder significantly increases the viscosity of the polymer melt, leading to increased processing difficulty and affecting the stability of processes such as extrusion molding. At the same time, the particle size and distribution of the powder also directly affect the surface quality and performance of the final product. Reduction of material properties: The introduction of a high concentration of barium sulfate dilutes the continuous phase of the polymer matrix, resulting in a significant decline in the mechanical properties of the polymer itself, such as tensile strength and elongation at break. At the same time, it also affects other properties of the product such as density and toughness, thus limiting the performance and lifespan of the product in practical applications.

[0004] In order to overcome the above challenges, technicians in this field have proposed a variety of surface modification methods to improve the interfacial compatibility between barium sulfate particles and polymer matrices and to improve the dispersibility of barium sulfate particles. Common modification methods include dry modification, coupling agent modification, surfactant modification, precipitation reaction modification, and in-situ modification. Among them, coupling agent modification is a common and effective method, such as silane, aluminate and titanate coupling agents. However, these methods still have some shortcomings. For example: although silane coupling agents are widely used, their binding force with the surface of barium sulfate is limited; and although titanate coupling agents can form chemical bonds with barium sulfate, they are expensive and some of their components are potentially harmful to human health, which limits their large-scale application.

[0005] Therefore, developing an efficient, economical and environmentally friendly method for surface modification of barium sulfate to improve its dispersibility in polymer matrices, enhance interfacial compatibility, and ultimately improve the mechanical properties and development effects of composite materials has become a key issue to be urgently addressed in this field. Summary of the invention

[0006] The purpose of the present invention is to solve the above-mentioned deficiencies and provide a development catheter and a preparation method and application thereof.

[0007] In a first aspect, a developing catheter adopts the following technical solution:

[0008] A developing catheter, wherein the raw materials of the developing catheter include, by weight: 30-60 parts of nano-barium sulfate, 40-70 parts of thermoplastic elastomer, 1-2 parts of dispersant and 0.1-1 parts of coupling agent, wherein the total weight of the nano-barium sulfate and the thermoplastic elastomer is 100 parts;

[0009] The coupling agent comprises an amino silane coupling agent and an aluminate coupling agent, wherein the mass ratio of the amino silane coupling agent to the aluminate coupling agent is 1:1 to 1:3.

[0010] Furthermore, the thermoplastic elastomer includes one or more of a block polyetheramide elastomer and a polyurethane elastomer.

[0011] Furthermore, the dispersant includes one or more of PEG-200, PEG-400, PEG-600 and PEG-800.

[0012] Furthermore, the amino silane coupling agent includes one or more of the brands KH-550, KH-792, and KH-602.

[0013] Furthermore, the aluminate coupling agent includes one or more of the brands SG-Al821, DL-411, DL-411AF, DL-411D, and DL-411DF.

[0014] In a second aspect, a method for preparing a developing catheter adopts the following technical solution:

[0015] A method for preparing a developing catheter comprises the following steps:

[0016] The dispersant and the coupling agent are sequentially added to the heated amide solvent, fully stirred and dispersed, and the nano-barium sulfate is slowly added. After fully dispersed, the thermoplastic elastomer is added, and the mixture is heated and stirred to react to obtain a blending system;

[0017] The blending system is allowed to stand at room temperature, free water is removed, and then the solvent is removed by rotary evaporation, washed, and dried to obtain amino-modified elastomer slices, which are mixed and extruded to obtain the developing catheter.

[0018] Furthermore, the amide reagent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, N-ethylpyrrolidone, N-propylpyrrolidone, and N-methylpyrimidine.

[0019] Furthermore, the preparation method of the nano barium sulfate comprises the following steps:

[0020] The soluble barium salt solution and the soluble sulfate solution are added to activated carbon respectively, stirred and purified, and then the pH is adjusted to acidic;

[0021] Slowly adding the EDTA chelating agent solution into the purified barium salt solution and stirring to obtain an EDTA-Ba system solution;

[0022] The purified sulfate solution is slowly added dropwise to the EDTA-Ba system solution, while the temperature is raised and stirred, until the reaction system generates a precipitate and turns into a milky white liquid, which is then filtered, washed, and dried to obtain the nano-barium sulfate.

[0023] Furthermore, the soluble barium salt solution and the soluble sulfate solution are added to activated carbon respectively, stirred and purified, and then the pH is adjusted to acidic, which includes the following process:

[0024] Add activated carbon to the soluble barium salt solution, stir, heat to 60℃~70℃, stir for 1h~2h, filter, and adjust the pH to 2~3; add activated carbon to the soluble sulfate solution, stir, heat to 60℃~70℃, stir for 1h~2h, filter, and adjust the pH to 2~3.

[0025] In a third aspect, an application of a developing catheter adopts the following technical solution:

[0026] Application of the above-described developing catheter in X-ray imaging.

[0027] Advantages of the present invention:

[0028] The developing catheter provided by the present invention realizes the synergistic effect between nano-barium sulfate (barium sulfate) and a thermoplastic elastomer (such as Pebax) matrix in the catheter material by precisely regulating the components, thereby significantly improving the balance between the imaging performance and mechanical properties of the catheter. Specifically, by controlling the addition amount of nano-barium sulfate within the range of 30 to 60 parts by weight, both the X-ray blocking effect and the processing performance of the material are taken into account, so that the catheter can maintain good flexibility and mechanical strength while ensuring sufficient imaging contrast, and it can be ensured that during the manufacturing process of the catheter, nano-barium sulfate will not cause agglomeration due to excessive addition, resulting in a sharp decline in the mechanical properties of the material. At the same time, within the range of 40 to 70 parts by weight of the thermoplastic elastomer, it provides structural support and flexibility for the catheter, ensuring the safety and operability of the catheter in a complex human environment.

[0029] The introduction of a dispersant is a key factor in improving the dispersibility of barium sulfate in the polymer matrix. By using non-ionic surfactants such as polyethylene glycol, the surface energy between barium sulfate particles is effectively reduced, thereby reducing the tendency of particle agglomeration, promoting the uniform dispersion of barium sulfate in the elastomer matrix, and finally ensuring the uniformity of the microstructure of the entire catheter material, improving the uniformity of X-ray absorption, and eliminating imaging artifacts caused by uneven distribution of barium sulfate. The use of a coupling agent is an important means to improve the interfacial compatibility between barium sulfate and the polymer matrix at the molecular level, which not only ensures the effectiveness of its modification but also avoids performance degradation caused by excessive coupling agent. The coupling agent is a combination of an amino-silane coupling agent and an aluminate coupling agent, and the mass ratio between the amino-silane coupling agent and the aluminate coupling agent is controlled. Specifically, the amino group in the amino-silane coupling agent can interact with functional groups such as amide groups or hydroxyl groups in the thermoplastic elastomer to form chemical bonds or hydrogen bonds and other forces, thereby bridging between barium sulfate particles and the polymer matrix and effectively enhancing the interfacial adhesion between the two. At the same time, the aluminate coupling agent can react with the hydroxyl groups on the surface of barium sulfate particles to further enhance the binding with the inorganic filler. Under this dual coupling effect, not only the dispersibility of barium sulfate particles in the polymer is improved, but also the interfacial strength of the composite material is enhanced, thereby effectively improving the overall mechanical properties of the catheter, such as tensile strength, elongation at break, and toughness. At the same time, due to the improvement of the interfacial binding force, the stability of the material in a simulated physiological environment is improved, and the precipitation of material components during use is avoided, thereby ensuring the safety and reliability of the product.

[0030] By controlling the ratio of nano barium sulfate, thermoplastic elastomer, dispersant and composite coupling agent, an effective balance between the imaging effect and mechanical properties in the X-ray imaging catheter is achieved. This method of enhancing the properties of the composite material through a synergistic strategy not only solves the problem of difficult coexistence of imaging and properties in the prior art, but also significantly improves the clinical application value of the product while ensuring the safety and reliability of the product. Detailed implementation manners

[0031] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present application will be further described in detail below. The described embodiments should not be regarded as limitations on the present invention. All other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention.

[0032] In the following description, reference is made to "some embodiments", which describe a subset of all possible embodiments. However, it can be understood that "some embodiments" can be the same subset or different subsets of all possible embodiments, and can be combined with each other without conflict. Unless otherwise defined, all technical and scientific terms used in the embodiments of the present invention have the same meaning as commonly understood by those skilled in the technical field to which the embodiments of the present invention belong. The terms used in the embodiments of the present invention are only for the purpose of describing the embodiments of the present invention and are not intended to limit the present invention.

[0033] Those skilled in the art should understand that in the following description of the embodiments of the present invention, the sequence numbers do not mean the order of execution. Some or all of the steps can be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation to the implementation process of the embodiments of the present invention.

[0034] The terms used in the embodiments of the present invention are only for the purpose of describing specific embodiments, and are not intended to limit the present invention. The singular forms "a" and "the" used in the embodiments of the present invention and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise.

[0035] Those skilled in the art should understand that the numerical ranges in the embodiments of the present invention should be understood as specifically disclosing each intermediate value between the upper and lower limits of the range. Each intermediate value between any stated value and the stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0036] Unless otherwise specified, the technical / scientific terms used herein have the same meanings as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the examples or test examples of the present invention. All documents mentioned in this specification are generally incorporated by reference to disclose and describe the methods and / or materials related to the said documents. In case of conflict with any incorporated document, the content of this application shall prevail.

[0037] It should be noted that all raw materials and / or reagents in the embodiments of the present invention are purchased on the market or prepared by conventional methods well-known to those skilled in the art.

[0038] For the barium sulfate nanoparticles prepared in the following examples and some comparative examples, the following intermediate detections need to be carried out. The barium sulfate nanoparticles that pass both the sulfide detection and the soluble barium salt detection are used for the operations of the corresponding examples or comparative examples.

[0039] Detection of sulfide: Take the prepared nanoscale barium sulfate, add dilute hydrochloric acid and deionized water, heat and boil, and its vapor shall not turn the lead acetate test paper black.

[0040] Detection of soluble barium salt: Let the above-mentioned boiled solution stand and cool to room temperature, repeatedly filter the filtrate with filter paper until the filtrate is clear and transparent. Take the filtrate and add it to dilute sulfuric acid. After stirring and standing, the solution shall not become turbid or precipitate.

[0041] Examples

[0042] Example 1

[0043] Example 1 provides a developing catheter, and the raw materials include 30 kg of barium sulfate nanoparticles, 70 kg of block polyether amide elastomer, 1 kg of PEG-200, and 0.1 kg of coupling agent; wherein, the coupling agent is a compound coupling agent of KH-550 and SG-Al821 with a mass ratio of 1:1.

[0044] Example 1 also provides a preparation method of the developing catheter, including the following steps:

[0045] Add 100 L of DMAc solvent to the reaction kettle, heat to 60 °C, sequentially add PEG-200 and the coupling agent to the reaction kettle, stir well for 2.5 h, slowly add the barium sulfate nanoparticles to the reaction kettle, continue to stir for 1.5 h, add the block polyether amide elastomer, and continue to heat and stir for 7 h. After the reaction ends, a blend system is obtained.

[0046] The blend system was allowed to stand at room temperature for 7 days. After removing free water, the mixture was decompressed by a vacuum pump using a rotary evaporator, and the temperature was controlled at 60°C to remove the solvent. The mixture was washed several times with ethanol aqueous solution (volume ratio 70:30). The washed mixture was dried in a vacuum oven and dried at 85°C for 48 hours to obtain amino-modified BaSO 4 / Pebax slices; amino-modified BaSO 4 / Pebax slices were passed through an extruder, and the extrusion process was controlled (screw speed was 100 rpm, extrusion temperature was 200° C.) to obtain a developing catheter.

[0047] Embodiment 1 also provides a method for preparing nano barium sulfate, comprising the following steps:

[0048] Take barium chloride and add 0.5wt% activated carbon, add water and stir, raise the temperature to 70°C, stir for 1h, use a vacuum pump to filter, and adjust the pH value of the filtrate to 2-3 with dilute hydrochloric acid; take sodium sulfate and add 0.5% activated carbon, add water and stir, raise the temperature to 70°C, stir for 1h, use a vacuum pump to filter, and adjust the pH value of the filtrate to 2-3 with dilute sulfuric acid;

[0049] Take EDTA-2Na and add water and stir, raise the temperature to 60°C, stir thoroughly, cool to room temperature and let stand; slowly add the EDTA-2Na aqueous solution to the purified barium chloride aqueous solution, and slowly stir for 2 hours to obtain an EDTA-Ba system solution;

[0050] Gradually add the purified sodium sulfate aqueous solution to the above EDTA-Ba system solution, while adding dropwise while heating and stirring, until the reaction system generates a precipitate and turns into a milky white liquid; filter the product after the reaction, and wash it repeatedly with deionized water and ethanol until the pH value is 5.5-6.0; vacuum dry the washed barium sulfate, and dry it at 80°C for 48 hours to obtain nano barium sulfate.

[0051] Example 2

[0052] Example 2 provides a developing catheter, the raw materials of which include 60 kg of nano barium sulfate, 40 kg of block polyetheramide elastomer, 2 kg of PEG-800, and 1 kg of coupling agent; wherein the coupling agent is a complex coupling agent of KH-792 and DL-411 in a mass ratio of 1:3.

[0053] Embodiment 2 also provides a method for preparing a development catheter, comprising the following steps:

[0054] Add 100 L of N-methylpyrrolidone (NMP) solvent to the reaction kettle, heat it to 60 °C, add PEG-800 and the coupling agent to the reaction kettle in sequence, stir well for 2.5 h, slowly add nano-barium sulfate to the reaction kettle, continue to stir for 1.5 h, add the block polyether amide elastomer, continue to heat and stir for 8 h. After the reaction is completed, a blend system is obtained;

[0055] Let the blend system stand at room temperature for 7 d. After removing the free water, use a rotary evaporator to reduce the pressure through a vacuum pump, and control the temperature at 60 °C to remove the solvent. Wash it repeatedly with an ethanol aqueous solution (volume ratio 70:30). Dry the washed mixture using a vacuum oven. After vacuum drying at 85 °C for 48 h, amino-modified BaSO 4 / Pebax slices can be obtained; 4 Pass the amino-modified BaSO

[0056] Example 2 also provides a preparation method of nano-barium sulfate, which includes the following steps:

[0057] Take barium chloride, add 0.5 wt% of activated carbon, add water and stir, while heating to 70 °C, stir for 1 h, use a vacuum pump for suction filtration, and adjust the pH value of the filtrate to 2-3 with dilute hydrochloric acid; take sodium sulfate, add 0.5% of activated carbon, add water and stir, while heating to 70 °C, stir for 1 h, use a vacuum pump for suction filtration, and adjust the pH value of the filtrate to 2-3 with dilute sulfuric acid;

[0058] Take EDTA-2Na, add water and stir, while heating to 70 °C, stir well, cool to room temperature and let stand; slowly add the EDTA-2Na aqueous solution to the purified barium chloride aqueous solution, while stirring slowly for 2 h to obtain an EDTA-Ba system solution;

[0059] Gradually add the purified sodium sulfate aqueous solution to the above EDTA-Ba system solution, heat and stir while dropping, until the reaction system generates a precipitate and becomes a milky white liquid; filter the product after the reaction is completed, wash it repeatedly with deionized water and ethanol until the pH value is between 5.5 and 6.0; vacuum dry the washed barium sulfate, and dry it at 80 °C for 48 h to obtain nano-barium sulfate.

[0060] Example 3

[0061] Example 3 provides a developing catheter, and the raw materials include 45 kg of nano-barium sulfate, 55 kg of block polyether amide elastomer, 1.5 kg of PEG-400, and 0.5 kg of coupling agent; among them, the coupling agent is a compound coupling agent of KH-602 and DL-411AF with a mass ratio of 1:2.

[0062] Example 3 also provides a method for preparing a developing catheter, comprising the following steps:

[0063] Add a mixed solvent of N,N-dimethylacetamide (DMAc) and N-ethylpyrrolidone (NEP) with a volume ratio of 1:1 and a total amount of 100 L to a reaction kettle, heat to 65 °C, successively add PEG-400 and a coupling agent to the reaction kettle, stir well for 3 h, slowly add nano-barium sulfate to the reaction kettle, continue to stir for 1.5 h, add a block polyether amide elastomer, continue to heat and stir for 6 h, and after the reaction ends, obtain a blend system;

[0064] Let the blend system stand at room temperature for 5 d, remove free water, then use a rotary evaporator to reduce the pressure through a vacuum pump, control the temperature at 60 °C to remove the solvent, wash with an ethanol aqueous solution (volume ratio 70:30) multiple times, dry the washed mixture using a vacuum oven, and after vacuum drying at 85 °C for 48 h, amino-modified BaSO 4 / Pebax slices can be obtained; Extrude the amino-modified BaSO 4 / Pebax slices through an extruder, control the processing and extrusion process (screw speed is 100 rpm, extrusion temperature is 200 °C) to obtain a developing catheter.

[0065] Example 3 also provides a method for preparing nano-barium sulfate, comprising the following steps:

[0066] Take barium chloride, add 0.5 wt% of activated carbon, add water and stir, while raising the temperature to 65 °C, stir for 1.5 h, use a vacuum pump for suction filtration, and adjust the pH value of the filtrate to 2 - 3 with dilute hydrochloric acid; Take sodium sulfate, add 0.5% of activated carbon, add water and stir, while raising the temperature to 65 °C, stir for 1.5 h, use a vacuum pump for suction filtration, and adjust the pH value of the filtrate to 2 - 3 with dilute sulfuric acid;

[0067] Take EDTA-2Na, add water and stir, while raising the temperature to 65 °C, stir well, and cool to room temperature and let stand; Slowly add the EDTA-2Na aqueous solution to the purified barium chloride aqueous solution while slowly stirring for 2 h to obtain an EDTA-Ba system solution;

[0068] Gradually add the purified sodium sulfate aqueous solution to the above EDTA-Ba system solution, while dropping and raising the temperature and stirring, until the reaction system generates a precipitate and becomes a milky white liquid; Filter the product after the reaction ends, wash repeatedly with deionized water and ethanol until the pH value is between 5.5 and 6.0; Vacuum dry the washed barium sulfate and dry at 80 °C for 48 h to obtain nano-barium sulfate.

[0069] Example 4

[0070] Example 4 provides a developing catheter. The raw materials include 30 kg of nano barium sulfate, 70 kg of block polyether amide elastomer, 1 kg of PEG-600, and 0.8 kg of coupling agent; among them, the coupling agent is a compound coupling agent of KH-550 and SG-Al821 with a mass ratio of 1:1.

[0071] Example 4 also provides a preparation method of the developing catheter, including the following steps:

[0072] Add 100 L of N-propylpyrrolidone (NPP) solvent to the reaction kettle, heat it to 60 °C, sequentially add PEG-600 and the coupling agent to the reaction kettle, stir well for 2.5 h, slowly add nano barium sulfate to the reaction kettle, continue to stir for 1.5 h, add the block polyether amide elastomer, continue to heat and stir for 7 h. After the reaction ends, a blend system is obtained;

[0073] Let the blend system stand at room temperature for 6 d. After removing the free water, use a rotary evaporator to reduce the pressure through a vacuum pump, and control the temperature at 70 °C to remove the solvent. Wash it multiple times with an ethanol aqueous solution (volume ratio 70:30), and dry the washed mixture using a vacuum drying oven. After vacuum drying at 85 °C for 48 h, amino-modified BaSO 4 / Pebax slices can be obtained; Extrude the amino-modified BaSO 4 / Pebax slices through an extruder, control the processing and extrusion process (screw speed is 100 rpm, extrusion temperature is 200 °C) to obtain the developing catheter.

[0074] Example 4 also provides a preparation method of nano barium sulfate, which is the same as that in Example 3.

[0075] Example 5

[0076] Example 5 provides a developing catheter. The raw materials include 50 kg of nano barium sulfate, 50 kg of polyurethane elastomer, 1.8 kg of PEG-200, and 0.2 kg of coupling agent; among them, the coupling agent is a compound coupling agent of KH-792 and DL-411D with a mass ratio of 1:3.

[0077] Example 5 also provides a preparation method of the developing catheter, including the following steps:

[0078] Add 100 L of N-methylpyrimidine (NMPy) solvent to the reaction kettle, heat it to 60 °C, sequentially add PEG-200 and the coupling agent to the reaction kettle, stir well for 2 h, slowly add nano barium sulfate to the reaction kettle, continue to stir for 1.5 h, add the polyurethane elastomer, continue to heat and stir for 7 h. After the reaction ends, a blend system is obtained;

[0079] The blend system was allowed to stand at room temperature for 6 days. After removing the free water, the solvent was removed under reduced pressure using a rotary evaporator with a vacuum pump, and the temperature was controlled at 60 °C. The product was washed repeatedly with an ethanol aqueous solution (volume ratio 70:30), and the washed mixture was dried using a vacuum oven. After vacuum drying at 85 °C for 48 h, amino-modified BaSO4 / TPU slices were obtained. The amino-modified BaSO4 / TPU slices were passed through an extruder, and the processing and extrusion process was controlled (screw speed 100 rpm, extrusion temperature 200 °C) to obtain the imaging catheter.

[0080] Example 5 also provides a method for preparing nano-barium sulfate, which is the same as that in Example 3.

[0081] Example 6

[0082] Example 6 provides an imaging catheter, the raw materials of which include 35 kg of nano-barium sulfate, 65 kg of block polyetheramide elastomer, 1.3 kg of PEG-400, and 0.6 kg of coupling agent; among them, the coupling agent is a compound coupling agent of KH-602 and DL-411DF with a mass ratio of 1:2.

[0083] Example 6 also provides a method for preparing an imaging catheter, which includes the following steps:

[0084] A mixed solvent of N,N-dimethylformamide (DMF) and N-methylpyrrolidone (NMP) with a volume ratio of 2:1 and a total amount of 100 L was added to the reaction kettle, and the temperature was heated to 60 °C. PEG-400 and the coupling agent were successively added to the reaction kettle and stirred thoroughly for 2.5 h. The nano-barium sulfate was slowly added to the reaction kettle, and stirring was continued for 1.5 h. The block polyetheramide elastomer was added, and heating and stirring were continued for 7 h. After the reaction was completed, a blend system was obtained.

[0085] The blend system was allowed to stand at room temperature for 6 days. After removing the free water, the solvent was removed under reduced pressure using a rotary evaporator with a vacuum pump, and the temperature was controlled at 65 °C. The product was washed repeatedly with an ethanol aqueous solution (volume ratio 70:30), and the washed mixture was dried using a vacuum oven. After vacuum drying at 85 °C for 48 h, amino-modified BaSO4 / Pebax slices were obtained. The amino-modified BaSO4 / Pebax slices were passed through an extruder, and the processing and extrusion process was controlled (screw speed 100 rpm, extrusion temperature 200 °C) to obtain the imaging catheter.

[0086] Example 6 also provides a method for preparing nano-barium sulfate, which is the same as that in Example 3.

[0087] Example 7

[0088] Example 7 provides a developing catheter, and the raw materials include 40 kg of nano barium sulfate, 60 kg of polyurethane elastomer, 1.6 kg of PEG-800, and 0.9 kg of coupling agent; wherein, the coupling agent is a compound coupling agent of KH-550 and DL-411 with a mass ratio of 1:1.

[0089] Example 7 also provides a preparation method of the developing catheter, which includes the following steps:

[0090] Add a mixed solvent of N,N-dimethylacetamide (DMAc) and N-propylpyrrolidone (NPP) with a volume ratio of the two solvents of 1:2 and a total amount of 100 L to the reaction kettle, heat to 60 °C, sequentially add PEG-800 and the coupling agent to the reaction kettle, stir well for 2 h, slowly add nano barium sulfate to the reaction kettle, continue to stir for 1.5 h, add the polyurethane elastomer, continue to heat and stir for 7 h, and after the reaction is completed, obtain a blend system;

[0091] Let the blend system stand at room temperature for 6 d, remove the free water, then use a rotary evaporator to reduce the pressure through a vacuum pump, control the temperature at 60 °C to remove the solvent, wash with an ethanol aqueous solution (volume ratio 70:30) multiple times, dry the washed mixture using a vacuum oven, and after vacuum drying at 85 °C for 48 h, amino-modified BaSO4 / TPU slices can be obtained; pass the amino-modified BaSO4 / TPU slices through an extruder, control the processing and extrusion process (screw speed is 100 rpm, extrusion temperature is 200 °C), and obtain the developing catheter.

[0092] Example 7 also provides a preparation method of nano barium sulfate, which is the same as that in Example 3.

[0093] Comparative Example

[0094] The difference between the developing catheter provided by Comparative Example 1 and Example 3 is that the coupling agent is KH-602.

[0095] The preparation method of the developing catheter and the preparation method of nano barium sulfate provided by Comparative Example 1 are the same as those in Example 3.

[0096] Comparative Example 2

[0097] The difference between the developing catheter provided by Comparative Example 2 and Example 3 is that the coupling agent is DL-411AF.

[0098] The preparation method of the developing catheter and the preparation method of nano barium sulfate provided by Comparative Example 2 are the same as those in Example 3.

[0099] Comparative Example 3

[0100] The difference between the developing catheter provided by Comparative Example 3 and Example 3 is that the nano barium sulfate is equivalently replaced with commercially available analytical pure barium sulfate.

[0101] Comparative Example 3 provides a method for preparing a contrast catheter that is the same as that of Example 3. Comparative Example 3 does not provide a method for preparing nano-barium sulfate.

[0102] Comparative Example 4

[0103] Comparative Example 4 provides a contrast catheter that is the same as that of Example 3.

[0104] The difference between the method for preparing a contrast catheter provided by Comparative Example 4 and that of Example 3 is that the raw materials of the contrast catheter are not added to the solvent in batches; specifically as follows:

[0105] Comparative Example 4 provides a method for preparing a contrast catheter, including the following steps:

[0106] A mixed solvent of N,N-dimethylacetamide (DMAc) and N-ethylpyrrolidone (NEP) with a volume ratio of 1:1 and a total amount of 100 L was added to the reaction kettle, heated to 65 °C, and PEG-400, a coupling agent, nano-barium sulfate, and block polyether amide elastomer were added in sequence, and heated and stirred for 6 h to obtain a blend system after the reaction ended;

[0107] The blend system was allowed to stand at room temperature for 5 d. After removing free water, it was depressurized by a vacuum pump using a rotary evaporator, and the solvent was removed while controlling the temperature at 60 °C. It was washed repeatedly with an ethanol aqueous solution (volume ratio 70:30), and the washed mixture was dried using a vacuum oven and vacuum-dried at 85 °C for 48 h to obtain amino-modified BaSO 4 / Pebax slices; the amino-modified BaSO 4 / Pebax slices were passed through an extruder, and the processing and extrusion process was controlled (screw speed 100 rpm, extrusion temperature 200 °C) to obtain a contrast catheter.

[0108] The method for preparing a nano-barium sulfate provided by Comparative Example 4 is the same as that of Example 3.

[0109] Comparative Example 5

[0110] Comparative Example 5 provides a contrast catheter that is the same as that of Example 3.

[0111] Comparative Example 5 provides a contrast catheter that is the same as that of Example 3.

[0112] The difference between the method for preparing a nano-barium sulfate provided by Comparative Example 5 and that of Example 3 is that barium chloride and sodium sulfate are not purified with activated carbon, specifically as follows:

[0113] Comparative Example 5 provides a method for preparing a nano-barium sulfate, including the following steps:

[0114] Take EDTA-2Na, add water and stir, while heating to 65°C, stir thoroughly, and cool to room temperature and let stand; slowly add the EDTA-2Na aqueous solution to the barium chloride aqueous solution, while slowly stirring for 2 h to obtain an EDTA-Ba system solution;

[0115] Gradually add the sodium sulfate aqueous solution to the above EDTA-Ba system solution, while dropping and heating and stirring until the reaction system generates a precipitate and turns into a milky white liquid; filter the product after the reaction ends, and wash it repeatedly with deionized water and ethanol until the pH value is between 5.5 and 6.0; vacuum-dry the washed barium sulfate and dry it at 80°C for 48 h to obtain nano-barium sulfate.

[0116] Comparative Example 6

[0117] Comparative Example 6 provides a developing catheter that is the same as that in Example 3.

[0118] Comparative Example 6 provides a method for preparing a developing catheter that is the same as that in Example 3.

[0119] The preparation method of nano-barium sulfate provided by Comparative Example 6 is different from that in Example 3 in that the EDTA-2Na complexation reaction is not carried out, and the specific steps are as follows:

[0120] The preparation method of nano-barium sulfate provided by Comparative Example 6 includes the following steps:

[0121] Take barium chloride, add 0.5 wt% of activated carbon, add water and stir, while heating to 65°C, stir for 1.5 h, carry out suction filtration using a vacuum pump, and adjust the pH value of the filtrate to 2 - 3 with dilute hydrochloric acid; take sodium sulfate, add 0.5% of activated carbon, add water and stir, while heating to 65°C, stir for 1.5 h, carry out suction filtration using a vacuum pump, and adjust the pH value of the filtrate to 2 - 3 with dilute sulfuric acid;

[0122] Gradually add the purified sodium sulfate aqueous solution to the purified sodium sulfate solution, while dropping and heating and stirring until the reaction system generates a precipitate and turns into a milky white liquid; filter the product after the reaction ends, and wash it repeatedly with deionized water and ethanol until the pH value is between 5.5 and 6.0; vacuum-dry the washed barium sulfate and dry it at 80°C for 48 h to obtain nano-barium sulfate.

[0123] Performance Test

[0124] (1) Detection of Tensile Strength and Elongation

[0125] Method: Cut a certain length of specimen axially from the PEBAX tube, usually in dumbbell shape or straight bar shape. The dimensions of the specimen should meet the requirements of relevant standards such as ISO 527 or ASTM D638. Use a vernier caliper with an accuracy of 0.01 mm to measure the width and thickness of the specimen, and measure multiple times at different positions and take the average value to accurately calculate the cross-sectional area of the specimen.

[0126] (2), X-ray imaging evaluation

[0127] 1. Evaluation preparation

[0128] Sample preparation: Place the developed catheter containing barium sulfate properly on the sample stage of the imaging device, ensure the sample position is fixed, and avoid movement during imaging which may affect the imaging quality. Pay attention to the uniformity of the distribution of barium sulfate in the tube to make the sample as representative as possible.

[0129] Equipment parameter setting: According to the type of the imaging instrument (such as X-ray imager), set appropriate tube voltage (generally between 30 - 150 kV), tube current (such as 10 - 100 mA) and exposure time (ranging from a few milliseconds to several seconds).

[0130] 2. Test indicators

[0131] Image contrast: Image contrast refers to the brightness difference between different regions in the image. For the imaging of the developed catheter with barium sulfate, the higher the contrast between the barium sulfate region and the surrounding region, the clearer the imaging, which is more conducive to observing the morphology and distribution of barium sulfate. Quantification method: It can be quantified by calculating the contrast-to-noise ratio (CNR). CNR = (S - B) / SD, where S is the average signal intensity of the target region (barium sulfate), B is the average signal intensity of the background region, and SD is the standard deviation of the signal intensity of the background region. Generally speaking, the higher the CNR value, the better the clarity.

[0132] Edge sharpness: It mainly refers to the clarity of the barium sulfate particles or the boundary of their distribution in the developed catheter. Clear edges can accurately reflect the shape and size of barium sulfate and its contact with the inner wall of the tube or other components. Edge sharpness measurement methods can be used. For example, by calculating the edge gradient, that is, the change rate of pixel gray values along the edge direction. If the edge gradient value is high, it indicates that the edge is clear; qualitative evaluation can also be carried out by observing whether there are phenomena such as edge blurring and ghosting.

[0133] Detail Resolution: Detail resolution refers to the ability to distinguish the fine internal structure of barium sulfate or its arrangement within the EBAX tube. This is very important for studying the agglomeration of barium sulfate, particle size distribution, etc. It is evaluated by observing the smallest barium sulfate particle size or the smallest interval that can be distinguished in the imaging. For example, in high-resolution imaging, if barium sulfate particles with a diameter of 10 μm can be clearly distinguished, the detail resolution is relatively high. At the same time, the modulation transfer function (MTF) can also be used to quantitatively describe the transfer ability of the imaging system for details with different spatial frequencies. The higher the MTF value, the better the detail resolution.

[0134] 3. Evaluation Criteria

[0135] High Score Criteria: If the image has high contrast (CNR > 10), clear edges (edge gradient greater than a certain set threshold, such as 100), and good detail resolution (able to distinguish details smaller than 20 μm or the MTF has a high value in the high-frequency band), a higher clarity score can be given, such as 8 - 10 points.

[0136] Medium Score Criteria: When one or two of the image contrast, edge sharpness, and detail resolution are at a medium level (e.g., CNR between 5 - 10, edge gradient between 50 - 100, able to distinguish details between 20 - 50 μm or the MTF performs moderately in the mid-frequency band), a score of 4 - 7 points is given.

[0137] Low Score Criteria: If the image has low contrast (CNR < 5), severely blurred edges (edge gradient less than 50), and poor detail resolution (can only distinguish details larger than 50 μm or the MTF has a significant attenuation in the low-frequency band), a score of 0 - 3 points is given.

[0138] (3). Stability Test

[0139] Configuration of Simulated Body Fluid: Composition and Concentration: NaCl (142.0 mM), NaHCO 3 (4.2 mM), KCl (3.0 mM), K 2 HPO 4 ·3H 2 O (1.0 mM), MgCl 2 ·6H 2 O (1.0 mM), CaCl 2 (2.5 mM), Na 2 SO 4 (0.5 mM). pH Adjustment: The pH value of the solution is adjusted to about 7.4 using tris-hydroxymethyl aminomethane and hydrochloric acid (HCl).

[0140] Preparation of test samples: Cut the contrast agent catheter into specimens of a certain size. The surface area and volume of the specimens should be determined according to the test requirements. Generally, the larger the surface area, the more it can reflect the stability of the material in the simulated body fluid. Clean and dry the specimens with absolute ethanol and distilled water to remove surface impurities and oil, and then weigh the specimens and record the initial mass.

[0141] Immersion test: Immerse the prepared contrast agent catheter specimens completely in the simulated body fluid to ensure full contact between the specimen surface and the simulated body fluid. Place the immersion container in a constant temperature water bath or incubator and maintain the temperature at about 37 °C to simulate the human physiological environment. Set the immersion time according to the test requirements, and choose to immerse for 14 days.

[0142] Result analysis: After the immersion test is completed, take out the contrast agent catheter specimens, rinse them thoroughly with distilled water to remove the residual simulated body fluid on the surface, and then dry the specimens to a constant weight, weigh them again and record the mass change. Evaluate the stability of the contrast agent catheter in the simulated body fluid by calculating the mass change rate, as follows:

[0143] Mass change rate: Mass change rate = (mass after immersion - mass before immersion) / mass before immersion × 100%. If the mass change rate is within ±5%, it can be considered that the stability of the material in the simulated body fluid is good.

[0144] Perform the above performance tests on the contrast agent catheters provided in Examples 1-7 and Comparative Examples 1-6, and the test results are shown in Table 1.

[0145] Table 1 Performance tests of the contrast agent catheters provided in Examples 1-7 and Comparative Examples 1-6

[0146]

[0147]

[0148] As can be seen from Table 1, it is a strong evidence for the core technical effect of the application of amino-modified barium sulfate (barium sulfate) in the thermoplastic elastomer contrast agent catheter proposed by the present invention. By comparing and analyzing the various performance indicators of Examples 1-7 and Comparative Examples 1-6, it can be clearly observed that the composite coupling system constructed by the present invention shows obvious advantages in significantly improving the mechanical properties, imaging effect and long-term stability of the catheter material.

[0149] Specifically, Examples 1-7 all exhibited tensile strengths far higher than those of Comparative Examples 1-6, indicating that the composite coupling agent strategy adopted in the present invention can effectively enhance the interfacial bonding strength between nano-barium sulfate and the thermoplastic elastomer matrix. For example, the tensile strength of Example 3 reached 38 MPa, which may be related to the higher interfacial interaction ability of the specific coupling agent combination (KH-602 and DL-411AF) used therein. In sharp contrast, that of Comparative Example 1 was only 25 MPa, indicating that in the absence of the composite coupling agent, the dispersion of nano-barium sulfate in the matrix was poor and the interfacial bonding was insufficient, resulting in a significant decrease in the overall mechanical properties of the material. Similarly, although Comparative Examples 2 and 4 used aluminate coupling agents, they still could not achieve performance comparable to that of the examples, suggesting that it is difficult to exert a synergistic effect by using a single coupling agent alone, while the amino-silane and aluminate composite coupling agent adopted in the examples showed better performance in terms of interfacial bonding force.

[0150] The data in Table 1 show that the elongation at break of Examples 1-7 was generally higher than that of Comparative Examples 1-6, indicating that the composite coupling system adopted in the present invention not only enhanced the strength of the material, but also significantly improved the toughness of the material, enabling the catheter material to have better anti-deformation and anti-destruction capabilities in a complex in-vivo environment. Among them, the elongation at break of Example 1 reached 400%, which may be attributed to its relatively low nano-barium sulfate content and appropriate coupling agent ratio, enabling the polymer matrix to better exert its extensibility performance, thus achieving a higher elongation at break. It is worth noting that the elongation at break of Comparative Example 1 was only 300%, which once again proved the enhancing effect of the composite coupling agent on the material properties.

[0151] The imaging clarity scores of Examples 1-7 were all above 8 points, far higher than those of Comparative Examples 1-6. This fully demonstrated the effectiveness of amino-modified nano-barium sulfate and the composite coupling agent in improving the imaging effect. Specifically, the composite coupling agent improved the dispersion of nano-barium sulfate in the polymer, enabling the barium sulfate particles to be more evenly distributed in the catheter material, thus avoiding uneven X-ray absorption caused by particle agglomeration and enhancing the contrast and clarity of the imaging. In particular, the imaging clarity scores of Examples 3 and 6 reached 9 points, which may be related to the synergistic effect of the solvents, dispersants or specific coupling agents selected therein. In contrast, due to insufficient dispersion and poor interfacial compatibility, Comparative Examples 1-6 showed poor imaging effects and could not meet the requirements of clinical applications.

[0152] From the data in Table 1, the mass loss rates of Examples 1-7 are all less than 2.2%, which indicates that the developed catheter prepared by the present invention has good stability in simulated body fluid, can effectively prevent the dissolution of the catheter material components, and ensures its safety and reliability in the in-vivo environment. On the contrary, the mass loss rate of Comparative Example 1 is as high as 5%, indicating that without using the composite coupling agent, the stability of the catheter material is poor and component dissolution is likely to occur, thus affecting its long-term use performance. The mass loss rate of Comparative Example 6 is the highest, at 6%, further corroborating the advantage of the present technical solution in improving the material stability. Comparative Examples 2, 3, and 4 also show significantly higher mass losses than the examples, demonstrating the role of the composite coupling agent.

[0153] In summary, the data in Table 1 fully illustrate that the preparation method of the amino-modified barium sulfate proposed by the present invention and its application in the developed catheter effectively solve the problem in the prior art that it is difficult to balance the imaging effect and mechanical properties. By precisely controlling the component ratio and adopting the composite coupling agent system, the uniform dispersion of nano-barium sulfate in the polymer is achieved, and the interfacial bonding strength and material stability are significantly improved. Finally, the prepared developed catheter has excellent imaging effect and mechanical properties while meeting the safety requirements for long-term use. The improvement of these properties is not the result of the independent action of a single component, but the comprehensive manifestation of the synergistic effect of multiple factors.

[0154] As described above, the above are only specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claimed rights.

Claims

1. A developing catheter, characterized in that: The raw material of the developing catheter comprises, by weight, 30 to 60 parts of nano-barium sulfate, 40 to 70 parts of thermoplastic elastomer, 1 to 2 parts of dispersant and 0.1 to 1 part of coupling agent, wherein the total weight of the nano-barium sulfate and the thermoplastic elastomer is 100 parts; The coupling agent comprises an amino silane coupling agent and an aluminate coupling agent, wherein the mass ratio of the amino silane coupling agent to the aluminate coupling agent is 1:1 to 1:

3.

2. The imaging catheter according to claim 1, characterized in that: The thermoplastic elastomer includes one or more of a block polyether amide elastomer and a polyurethane elastomer.

3. The imaging catheter according to claim 1, characterized in that: The dispersant includes one or more of PEG-200, PEG-400, PEG-600 and PEG-800.

4. The imaging catheter according to claim 1, characterized in that: The amino silane coupling agent includes one or more of the brands KH-550, KH-792 and KH-602.

5. The imaging catheter according to claim 1, characterized in that: The aluminate coupling agent includes one or more of the brands SG-Al821, DL-411, DL-411AF, DL-411D, and DL-411DF.

6. A method for preparing a developing catheter as claimed in any one of claims 1 to 5, characterized in that: The process includes: The dispersant and the coupling agent are sequentially added to the heated amide solvent, fully stirred and dispersed, and the nano-barium sulfate is slowly added. After fully dispersed, the thermoplastic elastomer is added, and the mixture is heated and stirred to react to obtain a blending system; The blending system is allowed to stand at room temperature, free water is removed, and then the solvent is removed by rotary evaporation, washed, and dried to obtain amino-modified elastomer slices, which are mixed and extruded to obtain the developing catheter.

7. The method for preparing a developing catheter according to claim 6, characterized in that: The amide reagent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, N-ethylpyrrolidone, N-propylpyrrolidone and N-methylpyrimidine.

8. The method for preparing a developing catheter according to claim 6, characterized in that: The preparation method of the nano barium sulfate, The process includes: The soluble barium salt solution and the soluble sulfate solution are added to activated carbon respectively, stirred and purified, and then the pH is adjusted to acidic; Slowly adding the EDTA chelating agent solution into the purified barium salt solution and stirring to obtain an EDTA-Ba system solution; The purified sulfate solution is slowly added dropwise to the EDTA-Ba system solution, while the temperature is raised and stirred, until the reaction system generates a precipitate and turns into a milky white liquid, which is then filtered, washed, and dried to obtain the nano-barium sulfate.

9. The method for preparing a developing catheter according to claim 8, characterized in that: The soluble barium salt solution and the soluble sulfate solution are added to activated carbon respectively, stirred and purified, and then the pH is adjusted to acidic. The process includes: Add activated carbon to the soluble barium salt solution, stir, heat to 60℃~70℃, stir for 1h~2h, filter, and adjust the pH to 2~3; add activated carbon to the soluble sulfate solution, stir, heat to 60℃~70℃, stir for 1h~2h, filter, and adjust the pH to 2~3.

10. Use of the imaging catheter according to any one of claims 1 to 5 in X-ray imaging.

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