Medical polyimide catheter with developing function as well as preparation method and application of medical polyimide catheter

Abstract

The invention discloses a polyimide catheter with an X-ray developing function as well as a preparation method and application of the polyimide catheter. The polyimide catheter at least comprises a multi-layer composite structure of a first base material layer, a metal developing layer and a second base material layer from inside to outside. The first base material layer and the second base material layer are both prepared from a rigid straight type dianhydride monomer and a rigid straight type diamine monomer; the metal developing layer is prepared by sputtering metal to the surface of the first base material layer or the second base material layer by adopting a vacuum magnetron sputtering method. A vacuum magnetron sputtering method is utilized to deposit a compact metal thin layer of tungsten, bismuth, molybdenum, barium and the like on a PI conduit cured at a high temperature, then a layer of polyamide acid is dip-coated on the surface of the metal thin layer, and the multilayer composite PI conduit with a developing layer in the middle is formed after curing. Therefore, the technical problems that the heavy metal is difficult to disperse due to great density difference and surface inertia and the performance of the PI conduit base material layer is degraded due to large doping are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of polyimide materials, and in particular, to the technical field of minimally invasive interventional medical devices. Specifically, it relates to a medical polyimide catheter with a radiopaque function, its preparation method and application. Background Art

[0002] With the increasing aging of the population, the needs for the prevention and treatment of cardiovascular and cerebrovascular diseases, urinary system stone diseases, cancer prevention and treatment, etc. are gradually deepening. At the same time, along with the decline of the physical functions of the elderly population, minimally invasive interventional therapy has been deeply favored by the majority of patients, especially the elderly population, due to its advantages such as small incision, light pain, short hospital stay, less bleeding, fast recovery and reduction of complications. It has developed into one of the three effective contemporary clinical diagnostic and treatment methods alongside internal medicine and surgery. Minimally invasive interventional therapy is to diagnose and treat the affected area through the smallest trauma using minimally invasive interventional medical devices through vascular or non-vascular channels under image guidance, and has been widely used in the fields of cardiovascular intervention, cardiac intervention, neurointervention, aortic and peripheral vascular intervention, gastrointestinal intervention, orthopedic intervention, endoscopy, tumor intervention, etc. At present, the market share of minimally invasive interventional medical devices has accounted for 15-20% of the total medical devices and is still growing rapidly. Many minimally invasive interventional therapies require the use of medical precision catheters to penetrate deep into the body for remote surgical operations. The catheter is the transmission channel for various interventional devices, and at the same time, it also has functions such as wall support, intraoperative pressure monitoring, pipeline drug delivery and stone extraction. It is the basis and key for the success of minimally invasive interventional therapy and is also the most important component in interventional medical devices.

[0003] Polyimide (PI) has become the preferred material for ultra-fine and high-precision medical catheters due to its good biocompatibility that can pass the ISO10993-5, 10 detection standards, excellent chemical resistance, radiation resistance, outstanding stress strength, torque transmission, bending toughness, etc., and can well meet the requirements of minimally invasive interventional treatment operations over long distances in the body. Many medical device companies in the United States, such as ZEUS, Nordson MEDICAL, Microlumen, etc., have formed product systems such as pure PI catheters, PI braided reinforced catheters, PI radiopaque catheters, etc. through long-term technical accumulation and product development, and have monopolized the high-end PI catheters for global minimally invasive interventional treatment.

[0004] PI imaging catheter can help doctors clearly see the specific position of the catheter in the patient's body under X-ray irradiation and guide its movement in the body, which can greatly improve the success rate of surgery and is currently attracting the attention of domestic and foreign enterprises and research institutions. Chinese invention patent CN114874623A discloses a polyimide catheter. By adding metal powders such as tungsten powder, bismuth powder, tungsten trioxide, and bismuth trioxide to a polyamic acid solution and then performing imidization treatment, a PI catheter with imaging effect is obtained. However, in this method, the densities of tungsten powder, bismuth powder, tungsten trioxide, and bismuth trioxide are 19.35 g / cm 3 、9.78 g / cm 3 、7.16 g / cm 3 、8.55 g / cm 3 respectively, and the density of the polyamic acid varnish is 1 g / cm 3 . The density differences are significant, and the surfaces of tungsten powder and bismuth powder have no active groups, resulting in low dispersion modification effect. Rapid sedimentation will occur at a resin viscosity of 10 - 30 Pa·s, and it is difficult to obtain a uniformly dispersed polyamic acid varnish and polyimide catheter. Moreover, tungsten trioxide and bismuth trioxide are somewhat toxic, and long-term contact is likely to cause symptoms such as general weakness, fever, measles-like rash, proteinuria or headache, dizziness, nausea, and vomiting respectively. In addition, introducing inorganic fillers into the polyimide catheter substrate will inevitably greatly reduce the flexibility and anti-twisting performance of the catheter, and there is a risk of fracture during in vivo use, thus posing a safety hazard.

[0005] Based on the problems existing in the prior art, the present invention provides a polyimide catheter with X-ray imaging, improving properties such as column stiffness, circumferential compression resistance, and anti-kinking. Summary of the Invention

[0006] In order to overcome the above deficiencies of the prior art, the purpose of the present invention is to provide a polyimide catheter with X-ray imaging function, its preparation method and application, improving the safety of use.

[0007] To achieve the above purpose, the present invention provides the following technical solutions.

[0008] One aspect of the present invention provides a polyimide catheter with X-ray imaging function, which at least includes a multi-layer composite structure of a first substrate layer - metal imaging layer - second substrate layer from the inside to the outside; both the first substrate layer and the second substrate layer are prepared from rigid dianhydride monomers and rigid diamine monomers; the metal imaging layer is prepared by sputtering a metal onto the surface of the first substrate layer or the second substrate layer using a vacuum magnetron sputtering method.

[0009] Preferably, the metal is selected from one or a combination of tungsten, molybdenum, bismuth, barium, tantalum, etc., but not limited thereto.

[0010] Preferably, the purity of the metal is ≥99.9%; more preferably, the purity of the metal is ≥99.99%.

[0011] Preferably, the thickness of the metal developing layer is 0.1 μm to 10 μm; more preferably, the thickness of the metal developing layer is 5 μm to 5 μm. The metal thin film formed on the first substrate layer by vacuum sputtering has the characteristics of being extremely thin and dense, and can achieve good developing effects.

[0012] Preferably, the rigid dianhydride monomer is selected from one or more combinations of pyromellitic dianhydride, pyrazine tetracarboxylic dianhydride, 1,4,5,8-naphthalenetetracarboxylic dianhydride, 4,4'-biphenyltetracarboxylic dianhydride, 2,3,6,7-anthracenetetracarboxylic dianhydride, dibenzodioxane dianhydride, 4,4'-p-terphenyl dianhydride, 3,4,9,10-pyrenetetracarboxylic dianhydride, p-phenylenebis(trimellitate) dianhydride, etc., but not limited thereto.

[0013] Preferably, the rigid diamine monomer is selected from one or more combinations of p-phenylenediamine, 2,6-diaminopyridine, 1,4-diaminobenzene, 4,4'-diaminodiphenyl ether, 4,4'-diamino-2,2'-dimethylbiphenyl, 4,4'-diamino-2,2'-bis(trifluoromethyl)biphenyl, 2-(4-aminophenyl)-5-aminobenzoxazole, 2-amino-5(4-aminophenyl)-pyrimidine, 2,5-bis(4-aminophenyl)pyridine, 5-amino-2-(3'-aminophenyl)benzimidazole, 3,3'-dihydroxybiphenyldiamine, 3,3'-diaminobenzanilide, etc., but not limited thereto.

[0014] Preferably, the length of the first substrate layer is the same as the length of the second substrate layer.

[0015] Preferably, the length of the metal developing layer is less than the lengths of the first substrate layer and the second substrate layer, so that adhesion layers are formed at both ends of the first substrate layer and the second substrate layer, enabling the first substrate layer and the second substrate layer to be directly adhesively bonded.

[0016] Preferably, the length of the adhesion layer is 5 to 20% of the overall length of the first substrate layer and / or the second substrate layer.

[0017] Preferably, the inner diameter of the polyimide catheter is 10 to 1000 μm.

[0018] As a preferred embodiment, an enhancement layer is further included between the metal developing layer and the first substrate layer or the second substrate layer.

[0019] Preferably, the composite structure includes the first substrate layer - the metal developing layer - the enhancement layer - the second substrate layer.

[0020] Preferably, the reinforcing layer is a braided tube woven from a linear material.

[0021] Preferably, the linear material includes stainless steel, nitinol, liquid crystal polymer fiber, synthetic fiber, or a combination of one or more of these, but not limited thereto.

[0022] Preferably, the braided tube includes a braided mesh or coil wire.

[0023] Preferably, the number of intersections per inch (PIC) of the braided mesh is 10 to 200.

[0024] Preferably, the number of windings per inch (WPI) of the coil wire is 20 to 180.

[0025] Preferably, the linear material is a flat or round wire material.

[0026] Preferably, the size of the cross-section thickness * width of the flat wire material is 0.006 mm * 0.032 mm to 0.05 mm * 0.25 mm, and the cross-section diameter of the round wire material is 0.012 mm to 0.1 mm.

[0027] As a preferred embodiment, the outer sides of the first base layer and the second base layer of the polyimide catheter further include a lubricating layer.

[0028] Preferably, the multi-layer composite structure includes: the first lubricating layer - the first base layer - the metal imaging layer - the reinforcing layer - the second base layer.

[0029] Preferably, the multi-layer composite structure includes: the first lubricating layer - the first base layer - the metal imaging layer - the second base layer.

[0030] Preferably, the material of the lubricating layer includes polytetrafluoroethylene (PTFE), fluorinated ethylene propylene copolymer (FEP), soluble polytetrafluoroethylene (PFA), polyphenylsulfone nylon 11 nylon 12 polyurethane polyether amide or a combination of one or more of these, but not limited thereto.

[0031] Preferably, the thickness of the lubricating layer is 0.5 to 20 μm.

[0032] As another object of the invention, the invention also provides a method for preparing the aforementioned polyimide catheter with X-ray imaging function, comprising the following steps:

[0033] S1. Provide a polyamic acid resin precursor solution: Add a rigid dianhydride and a diamine monomer to an aprotic polar solvent to prepare a polyamic acid, and then obtain the polyamic acid resin precursor solution after imidization;

[0034] S2. Prepare the first substrate layer: Dip-coat the polyamic acid precursor solution on the surface of the die, and perform the first pre-drying and shaping to form a uniform film on the surface of the die, which is the first substrate layer;

[0035] S3. Fabricate a metal development layer: Add a covering layer to both ends of the die after S2 treatment, then perform pre-treatment on the first substrate layer, and perform vacuum magnetron sputtering to form a dense metal film on the surface of the first substrate layer; Remove the covering layer;

[0036] S3. Prepare the second substrate layer: Immerse the die after S3 treatment in the polyamic acid precursor solution, perform high-temperature curing treatment, and completely dry it to form the second substrate layer;

[0037] Finally, peel off the die to obtain the polyimide catheter.

[0038] As a preferred embodiment, a reinforcing layer is further included between S2 and S3; The reinforcing layer can further enhance the anti-twisting strength and the lubricating layer can reduce the surface friction coefficient of the catheter.

[0039] Preferably, a braided tube is nested on the surfaces of the substrate layer and the metal development layer to form a reinforcing layer; Then immerse it in a thermoplastic polyamic acid precursor solution, and the thermoplastic polyamic acid precursor solution fills the gaps of the braided tube, and perform the second pre-drying and shaping to form an adhesion layer on the surface of the reinforcing layer.

[0040] Preferably, the thermoplastic polyamic acid precursor solution is prepared by dissolving a thermoplastic polyimide compound in an aprotic polar solvent.

[0041] Preferably, the thermoplastic polyimide compound is prepared by polycondensation reaction of dianhydride monomers and diamine monomers. Among them, the dianhydride monomers include 4,4'-diphenylether dianhydride, 4,4'-benzophenone tetracarboxylic dianhydride, hydroquinone bis(trimellitate), 4,4'-(3,4-dicarboxyphenoxy)benzophenone dianhydride, 4,4'-diphenylsulfide dianhydride, 4,4'-diphenylsulfone dianhydride, 4,4'-p-phenylene dianhydride, 4,4'-bisphenol A diether dianhydride, etc., one or more combinations thereof; the diamine monomers are 4,4'-diaminodiphenyl ether, 1,4-bis(4-aminophenoxy)benzene, 1,3-bis(4-aminophenoxy)benzene, 4,2'-bis[4-(4-aminophenoxy)phenyl]propane, 3,4'-diaminodiphenyl ether, 2,7-bis(4-aminophenoxy)naphthalene, 4,4'-bis(3-aminophenoxy)biphenyl, 4,4'-bis(3-aminophenoxy)benzophenone, etc., one or several of them, but not limited thereto.

[0042] Preferably, the solid content of the thermoplastic polyamic acid precursor solution is 6-50 wt%.

[0043] As a preferred embodiment, after S3, a lubricating layer is further included.

[0044] The specific preparation steps include: immersing the die prepared in S3 into an aqueous solution of lubricant, coating a lubricating layer on the surface of the adhesion layer, after the third pre-drying and shaping, then performing high-temperature drying, and the lubricant softens to form a dense and smooth surface layer structure, thus obtaining the polyimide catheter.

[0045] Preferably, the lubricant includes polytetrafluoroethylene (PTFE), fluorinated ethylene propylene copolymer (FEP), soluble polytetrafluoroethylene (PFA), polyphenylsulfone nylon 11 nylon 12 polyurethane polyether amide one or more combinations thereof, but not limited thereto.

[0046] Preferably, the high-temperature curing treatment includes drying and imidizing the first substrate layer, the second substrate layer and the adhesion layer by using a multi-stage high-temperature heating process.

[0047] Preferably, the process conditions of the high-temperature curing treatment include first gradually increasing the temperature in stages and then annealing.

[0048] Preferably, the range of the stepwise temperature increase is 200-700 °C, and the heat treatment time for each stage is 1-100 min; the temperature range of the annealing is 150-500 °C, and the annealing time is 1-100 min.

[0049] Preferably, the stepwise temperature increase includes heat treatment at 300 °C, 360 °C, 420 °C, and 480 °C for 3 minutes respectively.

[0050] Preferably, the annealing includes annealing at 400 °C, 300 °C, and 200 °C for 3 minutes respectively.

[0051] Preferably, the vacuum magnetron sputtering method includes a vacuum degree lower than 5.0×10 -5 Torr; more preferably lower than 2.0×10 -5 Torr.

[0052] Preferably, the target power during sputtering is 1000 - 5000 W; more preferably 2000 - 4000 W.

[0053] Preferably, the deposition thickness of the metal layer during sputtering is 0.1 μm - 10 μm; more preferably, the deposition thickness of the metal layer is 5 μm - 5 μm.

[0054] And / or, the polar aprotic solvent includes one or a combination of several of formamide compounds, acetamide compounds, sulfoxide pyrrolidone compounds, phenolic solvents, tetrahydrofuran (THF), dioxane, dichloromethane, chloroform, hexamethylphosphoramide, γ-butyrolactone, cyclopentanone, etc., but not limited thereto.

[0055] The solid content of the polyamic acid precursor solution is 6 - 50 wt%.

[0056] And / or, the dip coating includes immersing the die and conveying it in the polyamic acid precursor solution, and the conveying speed is 0.1 - 50 m / min.

[0057] It should be noted that the materials and preparation methods selected for the first substrate layer and the second substrate layer are the same.

[0058] As one of the invention purposes, the present invention also provides the application of the aforementioned polyimide catheter with X-ray imaging function as a medical device in X-ray imaging technology.

[0059] As one of the invention purposes, the present invention also provides an X-ray imaging tube prepared from the aforementioned polyimide catheter with X-ray imaging function.

[0060] The technical effects of the technical solution of the present invention:

[0061] 1. By adopting the technical solution of the present invention, taking advantage of the high deposition efficiency, uniform thin film, low-temperature deposition achievable, and suitability for large-area deposition of vacuum magnetron sputtering, a dense metal thin layer such as tungsten, bismuth, molybdenum, barium, etc. is deposited on the PI catheter after high-temperature curing. Then, a layer of polyamic acid is dip-coated on the surface of the metal thin layer, and after curing, a multi-layer composite PI catheter with a developing layer in the middle is formed, thus solving the technical problems of the difficult dispersion of heavy metals due to the large density difference and surface inertness and the deterioration of the performance of the PI catheter substrate layer caused by a large amount of doping.

[0062] 2. By adopting the technical solution of the present invention, introducing the developing material into the PI catheter structure and using the method of sputtering coating can effectively solve the problems of sedimentation and uneven dispersion caused by the large density difference between heavy metals such as tungsten and molybdenum and the polyamic acid sizing solution. Moreover, the coating is denser and flatter, which can reduce the diffraction penetration of X-rays and other rays, thereby reducing the amount of heavy metals added and the raw material cost. Also, by using upper and lower PI layers and adhering both ends through double-layer pure PI to seal the metal layer in the middle, the migration of metals can be avoided to reduce the safety risk. In particular, the method of sputtering coating can also avoid the risks of various defects and reduced flexibility of the PI substrate caused by the mixing of fillers.

[0063] 3. The present invention has an extremely low CTE characteristic of 4-10 ppm / °C for heavy metals such as tungsten and molybdenum. To avoid the problems of excessive thermal stress and interface delamination caused by the mismatch of CTE values of each layer, combined with the rigid polyimide molecular structure with a low CTE value, such as the combination of 4,4'-biphenyltetracarboxylic dianhydride and p-phenylenediamine, and the combination of pyromellitic dianhydride and 2-(4-aminophenyl)-5-aminobenzoxazole, whose CTE values can be in the range of 4-10 ppm / °C, so as to achieve synchronous contraction and expansion when the layers are subjected to thermal and cold shocks. Moreover, the adopted rigid polyimide molecular structure has an extremely high heat resistance level (≥450 °C), and the tube film does not deform during sputtering deposition, ensuring that the deposited metal layer is uniform and dense.

[0064] 4. The polyimide catheter adopted by the present invention has a two-layer PI structure. The preparation method uses the solution coating molding method to pass the tube core through the polyamic acid sizing tank, the scraping die, and the pre-baking channel, and controls the thickness of the substrate layer by adjusting the viscosity, solid content of the polyamic acid resin, the running speed of the tube core, and the size of the die orifice. BRIEF DESCRIPTION OF THE DRAWINGS

[0065] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments recorded in the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0066] Figure 1 It is a schematic diagram of the principle of magnetron sputtering used in the preparation of the polyimide catheter in Embodiment 1 of the present invention.

[0067] Figure 2 It is a schematic diagram of the structural simulation of the polyimide catheter prepared in Embodiment 1 of the present invention.

[0068] Figure 3 It is an imaging diagram of the polyimide catheter prepared in Embodiment 1 of the present invention in a mouse body. Detailed implementation manners

[0069] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are clearly and completely described. Apparently, the described embodiments are a part rather than all of the embodiments of this application. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the protection scope of the present invention.

[0070] The full texts of all patents and non-patent literatures cited in the present invention are incorporated herein by reference.

[0071] As used in the invention, the terms "comprise", "include", "contain", "cover", "have", "carry" or any other variations thereof are intended to cover non-exclusive inclusion. For example, a process, method, article or device including a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to the process, method, article or device. In addition, unless expressly stated to the contrary, "or" means inclusive "or" rather than exclusive "or". For example, condition A or B is satisfied by any of the following: A is true (or present) and B is false (or absent), A is false (or absent) and B is true (or present), and both A and B are true (or present). The phrase "one or more" is intended to cover non-exclusive inclusion. For example, one or more of A, B and C means any of the following cases: A alone, B alone, C alone, a combination of A and B, a combination of B and C, a combination of A and C, or a combination of A, B and C.

[0072] In addition, "a" or "an" is used to describe the elements and components described herein. This is done merely for convenience and to provide a general sense of the scope of the present invention. This description should be understood to include one or at least one, a kind or at least one kind, and the singular also includes the plural, unless clearly indicated otherwise.

[0073] Taking advantage of the high deposition efficiency, uniform thin films, low-temperature deposition, and suitability for large-area deposition of vacuum magnetron sputtering, a dense metal thin layer of tungsten, bismuth, molybdenum, barium, etc. is deposited on a PI catheter that has been cured at high temperature and is rotating at a constant speed. Then, a layer of polyamic acid is dip-coated on the surface of the metal thin layer, and after curing, a multi-layer composite PI catheter with a developing layer in the middle is formed, thus solving the technical problems of the dispersion difficulty caused by the large density difference and surface inertness of heavy metals and the performance deterioration of the PI catheter substrate layer caused by a large amount of doping. In addition, according to the characteristics of the low linear thermal expansion coefficient (CTE) of these heavy metals, a low-CTE polyimide substrate that matches them is selected to reduce the delamination failure caused by interlayer thermal stress, which can greatly reduce the medical accidents caused by the slippage between layers of the multi-layer catheter.

[0074] The present invention adopts the method of vacuum magnetron sputtering. Refer to Figure 1 As shown in the schematic diagram of magnetron sputtering for the polyimide catheter, taking advantage of its high deposition efficiency, uniform thin films, low-temperature deposition, and suitability for large-area deposition, a dense metal thin layer of tungsten, bismuth, molybdenum, barium, etc. is deposited on a PI catheter that has been cured at high temperature and is rotating at a constant speed. Then, a layer of polyamic acid is dip-coated on the surface of the metal thin layer, and after curing, a multi-layer composite PI catheter with a developing layer in the middle is formed, thus solving the technical problems of the dispersion difficulty caused by the large density difference and surface inertness of heavy metals and the performance deterioration of the PI catheter substrate layer caused by a large amount of doping. In addition, according to the characteristics of the low linear thermal expansion coefficient (CTE) of these heavy metals, such as tungsten and molybdenum being 4.45 and 5.4 ppm / °C respectively, a low-CTE polyimide substrate that matches them is selected to reduce the delamination failure caused by interlayer thermal stress.

[0075] As Figure 2 shown, it is a schematic diagram of a polyimide catheter with a multi-layer composite structure having a developing function. The sputtered metal layer is controlled to only account for 60 - 90% of the middle length, and 5 - 20% of the length is left at both ends for the composite of the two PI substrate layers. Moreover, before sputtering, the PI catheter substrate is subjected to multiple cleaning and corona treatments to improve the surface adhesion and bonding force, avoiding potential safety hazards caused by interlayer slippage.

[0076] In addition, according to the usage requirements, other functional upgrades are carried out on this multi-layer catheter with a developing function. For example, a reinforcing body is woven on the surface of the catheter to further improve the anti-torque and anti-bending performance of the catheter, and a lubricating layer is coated on the surface of the catheter to reduce the surface resistance of the catheter, improve the smoothness and pushability, and relieve the pain of patients.

[0077] Both layers of PI in direct contact with the sputtered layer are thermosetting PI polymers with a low thermal expansion coefficient; a rigid dianhydride and diamine monomer are prepared into a precursor polyamic acid in a polar aprotic solution, then dip-coated into pipes with different inner diameters and wall thicknesses, and finally cured at multiple gradients of high temperature to form a polyimide catheter.

[0078] Preferably, the rigid dianhydride monomers include, but are not limited to, one or more combinations of pyromellitic dianhydride, pyrazine tetracarboxylic dianhydride, 1,4,5,8-naphthalenetetracarboxylic dianhydride, 4,4'-biphenyltetracarboxylic dianhydride, 2,3,6,7-anthracenetetracarboxylic dianhydride, dibenzodioxane dianhydride, 4,4'-p-terphenyl dianhydride, 3,4,9,10-pyrenetetracarboxylic dianhydride, p-phenylenebis(trimellitate) dianhydride, etc.; the rigid diamine monomers include p-phenylenediamine, 2,6-diaminopyridine, 1,4-diaminobenzene, 4,4'-diaminodiphenyl ether, 4,4'-diamino-2,2'-dimethylbiphenyl, 4,4'-diamino-2,2'-bis(trifluoromethyl)biphenyl, 2-(4-aminophenyl)-5-aminobenzoxazole, 2-amino-5(4-aminophenyl)-pyrimidine, 2,5-bis(4-aminophenyl)pyridine, 5-amino-2-(3'-aminophenyl)benzimidazole, 3,3'-dihydroxybiphenyl diamine, 3,3'-diaminobenzanilide, etc.

[0079] In the present invention, the solvents for preparing the polyamic acid precursor are mainly polar aprotic solvents, including N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, tetrahydrofuran, dioxane, methyl ethyl ketone, etc., which are used alone or in combination of two or more according to needs.

[0080] In the present invention, the solid content of the polyamic acid solution is preferably 6-50 wt%, more preferably 8-40 wt%, and further preferably 10-30 wt%; if the solid content is lower than 6 wt%, the polyimide component impregnated on the catheter is less and the single coating amount is low; if the solid content is higher than 50 wt%, it will cause the resin to be too viscous or the molecular weight to be too small, making it impossible to coat and form or the performance to be brittle.

[0081] The viscosity of the polyamic acid precursor solution prepared by the present invention is preferably 3000-30000 cP, more preferably 5000-20000 cP; when the viscosity is less than 3000 cP, the solution is too dilute to adhere to the surface of the tube core, and when the viscosity is higher than 30000 cP, the solution is too thick, the leveling property of the glue liquid is low, the surface of the catheter film is not smooth, and the apparent quality is poor.

[0082] In the present invention, the polyimide catheter substrate layer is prepared by dip coating. The tube core is passed through the glue tank of the thermosetting polyimide precursor, and its conveying speed is preferably 0.1 - 50 m / min, more preferably 0.5 - 30 m / min, and further preferably 1 - 10 m / min. At the same time, a die is used to scrape off the excess glue. The dry film thickness formed in a single pass is preferably 0.5 - 10 μm, more preferably 1 - 7 μm, and even more preferably 2 - 4 μm. In addition, the tube core dipped with the glue is pre-baked in time, and the temperature of the baking channel is preferably 80 - 200 °C, more preferably 100 - 180 °C, and even more preferably 120 - 160 °C. After pre-baking, a multi-stage high-temperature heating process is used for drying and imidization. First, the temperature is raised and then annealed. The high-temperature treatment temperature range is preferably 200 - 700 °C, further preferably 250 - 600 °C, and the treatment time is preferably 1 - 100 min, further preferably 2 - 40 min.

[0083] The metal film developing layer such as tungsten, molybdenum, and bismuth is formed on the surface of the PI catheter by vacuum magnetron sputtering, which has the following main advantages: 1. It is applicable to various materials that can be made into targets, especially for elements with high melting points and low vapor pressures such as tungsten and molybdenum, and has high purity, high density, and strong bonding force with the substrate; 2. The deposition rate can be relatively stable and the film thickness can be regulated by controlling parameters such as air pressure, sputtering power, and gas flow rate, and multi-component coating films can be prepared by co-sputtering of multiple targets; 3. It is applicable to large-area and large-scale industrial applications, and has advantages such as controllability, energy conservation, environmental protection, and stable process. Coating process: 1) First, wrap two turns of PI insulating tape around each 10% length at both ends of the PI catheter with a metal tube core as the non-sputtering part, then place it in acetone, ethanol, and deionized water for cleaning in sequence, blow dry the surface water with compressed air, then place it in a clean vacuum oven at 100 - 120 °C for drying, and finally perform corona treatment to improve the surface tension; 2) Fix the PI catheter on the workpiece rack that can rotate at a constant speed in the furnace cavity, and then install the metal target; 3) First, start the mechanical pump to extract low vacuum, and then start the molecular pump to extract high vacuum. When the required vacuum degree is reached, start deposition. After deposition, take out the sample after the furnace temperature drops to room temperature.

[0084] Preferably, the metals for the developing layer include, but are not limited to, one or several combinations of tungsten, molybdenum, bismuth, barium, tantalum, etc.

[0085] Preferably, the purity of the metals for the developing layer is not less than 99.9%.

[0086] More preferably, the purity of the metals for the developing layer is not less than 99.99%.

[0087] Preferably, the gases for sputtering include, but are not limited to, helium, argon, krypton, xenon, etc.

[0088] Further preferably, the gas used for sputtering is argon gas; its purity is preferably not less than 99.99%, and further preferably not less than 99.999%.

[0089] Preferably, the vacuum degree at the start of sputtering is preferably lower than 5.0*10 -5 Torr, and further preferably lower than 2.0*10 - 5 Torr.

[0090] Preferably, the target power during sputtering is preferably 1000 - 5000 W, and further preferably 2000 - 4000 W.

[0091] Preferably, the deposition thickness of the metal layer during sputtering is preferably 0.1 μm - 10 μm, and further preferably 2 μm - 5 μm, because the sputtered layer is very dense, and an extremely thin layer can achieve a good development effect.

[0092] A polyimide layer is coated again on the sputtered layer of the PI catheter, and its formulation structure and preparation process are the same as those of the above substrate layer method.

[0093] Function optimization is carried out on the PI catheter with a development effect, mainly including preparing a reinforcement layer to further improve the anti-twisting strength and a lubricating layer to reduce the surface friction coefficient of the catheter.

[0094] Preferably, the material of the reinforcement layer is one or more of stainless steel, nitinol alloy, liquid crystal polymer fiber, synthetic fiber; the reinforcing material is preferably flat or circular linear material. For the flat linear material, the size of the cross-section thickness * width is preferably 0.006 mm * 0.032 mm to 0.05 mm * 0.25 mm, and the number of intersections per inch (PIC) of the mesh is preferably 10 - 200; for the circular linear material, the cross-section diameter is preferably 0.012 mm - 0.1 mm, and the number of windings per inch (WPI) of the coil wire is preferably 20 - 180.

[0095] Preferably, the material of the lubricating layer is one or a combination of several of polytetrafluoroethylene (PTFE), fluorinated ethylene propylene copolymer (FEP), soluble polytetrafluoroethylene (PFA), polyphenylsulfone nylon 11 nylon 12 polyurethane polyether amide in one or more combinations.

[0096] The PI catheter with a development function provided by the present invention can assist doctors in quickly and accurately judging the specific position of the catheter in the body, improving the efficiency and safety of minimally invasive surgery. Based on the above technical solutions, the following analysis is carried out on its structural design and forming process:

[0097] In the present invention, a PI catheter structure is introduced into the developing material, and a plating scheme is adopted, which can effectively avoid the problems of sedimentation and uneven dispersion caused by the large density difference between heavy metals such as tungsten and molybdenum and the polyamic acid solution. Moreover, the plating layer is denser and flatter, which can reduce the diffraction penetration of X-rays and other rays, thereby reducing the addition amount of heavy metals and raw material costs. The upper and lower PI layers are used to seal it in the middle, and the end is made of double-layer pure PI, which can avoid the migration of metals and reduce safety risks. In addition, the plating scheme can avoid the risks of various defects and reduced flexibility of the PI substrate caused by the mixing of fillers.

[0098] In the present invention, heavy metals such as tungsten and molybdenum have extremely low CTE characteristics of 4-10 ppm / °C. To avoid problems such as excessive thermal stress and interface delamination caused by mismatched CTE values of each layer, a rigid polyimide molecular structure with a low CTE value is preferably selected, such as the combination of 4,4'-biphenyltetracarboxylic dianhydride and p-phenylenediamine, and the combination of pyromellitic dianhydride and 2-(4-aminophenyl)-5-aminobenzoxazole. Its CTE value can be 4-10 ppm / °C, so as to achieve synchronous contraction and expansion of the layers when subjected to thermal and cold shocks. In addition, this type of rigid polyimide molecular structure has an extremely high heat resistance level (≥450 °C), and the tube film does not deform during sputter deposition, ensuring that the deposited metal layer is uniform and dense.

[0099] In the present invention, for the synthesis method of the precursor polyamic acid, the effects of reaction concentration, feeding order, reaction temperature and time, stirring method and rate, mass transfer and heat transfer process in the kettle, viscosity control method, etc. on resin polymerization will be fully considered. The molecular weight and its distribution of the resin are detected by mass spectrometry and liquid chromatography, and the relationship between different reaction scales and the molecular weight size, distribution and comprehensive performance is systematically established. The most suitable process conditions are selected to achieve uniform and stable resin performance and batches.

[0100] In the present invention, the external influencing factors for the synthesis of the precursor polyamic acid are strictly controlled. The reaction device is installed in a thousand-level constant temperature and humidity clean room. The powder is fed by a precision automatic feeding system with a weighing deviation of less than ±0.5%. The reaction kettle adopts a jacket heat transfer method, and at the same time, a high-power cooling and heating integrated machine is used for rapid and accurate temperature control. The reaction solvent is transported by a precise metering pump, and the reacted resin solution is filtered through a filter element with a pore size of 1-2 μm and vacuum defoamed to reduce the influence of the external environment.

[0101] In the present invention, the two-layer PI structure of the catheter is prepared by the solution coating molding method. The tube core passes through the polyamic acid glue tank, the scraping die and the pre-baking channel, and the thickness control of the substrate layer is realized by regulating the viscosity, solid content of the polyamic acid resin, the running speed of the tube core and the die aperture size.

[0102] In the present invention, for the drying and curing after the polyamic acid solution is coated, a multi-stage program-controlled temperature heat treatment method is adopted. Because if the solvent volatilizes too slowly, the molecular chains will break severely during the heating process, resulting in poor flexibility; if it is too fast, the plasticizing effect of the residual solvent will be lacking, and the molecular chain movement ability will decline, resulting in insufficient imidization degree and easy generation of film surface bubbling. By optimizing the heat treatment process, the performance and apparent quality of the catheter substrate layer are realized.

[0103] In the present invention, by designing a reinforcing layer, the catheter is made to have high column stiffness, resistance to circumferential compression, resistance to kinking, etc. The metal used, or a braidable organic fiber is selected as the reinforcing material, especially a fiber material suitable for braiding with low density. In terms of shape, a braided mesh or coil wire is selected. At the same time, for the braided mesh, a full-load or half-load braiding pattern is selected and the performance is adjusted by selecting PIC. For example, a higher PIC can improve flexibility, while a lower PIC can increase longitudinal stiffness. For the coil, it is selected to be wound clockwise or counterclockwise and the rigidity-flexibility ratio is adjusted by WPI.

[0104] In the present invention, by designing a lubricating layer, the surface of the catheter is made to meet requirements such as low friction coefficient, good biocompatibility, chemical solvent resistance, low hardness value, good hot melt property and adhesion. The present invention uses a fusible thermoplastic polymer as the lubricating layer material, such as including polytetrafluoroethylene (PTFE), fluorinated ethylene propylene copolymer (FEP), nylon, polyether amide polyurethane, etc. It is formed by coating with a solution or emulsion, and then dried through a hot air drying channel. The target thickness is achieved by controlling the solid content, viscosity and coating times of the solution. Finally, the lubricating layer on the surface is heated to near the melting point for heat treatment to make it dense and smooth.

[0105] In the present invention, the prepared PI catheter with imaging function is first cut to a specific length according to the needs of market users, and then the catheter is separated from the tube core, and finally a multi-layer functional composite catheter is obtained.

[0106] In the following examples and comparative examples, the following methods are used to evaluate the key performance of the multi-layer structure polyimide catheter.

[0107] (1) Evaluation of the biocompatibility of the multi-layer PI catheter

[0108] The composite catheter is strictly carried out for 3 key biocompatibility evaluations including skin irritation test, MTT cytotoxicity test and skin sensitization test in accordance with ISO10993-5, 10 standards.

[0109] (2) Evaluation of the interfacial bonding strength of the multi-layer PI catheter

[0110] Cut the multi-layer PI catheter sample to be tested into multiple small segments and place them in a mold. Then, stir the prepared resin and curing agent (2:1) evenly and slowly pour it into the mold to submerge the catheter. Next, place it in a vacuum oven for heating and curing. After it becomes completely hard, take it out of the mold, and then perform fine grinding, rough polishing, and fine polishing. Finally, clean and dry it to obtain a translucent sample with a cross-section perpendicular to the lens. In addition, bend the catheter 20 times, and cut and prepare the sample at the bent part in the same way. Use a Thermoscientific field emission scanning electron microscope (SEM) to observe and analyze the cross-section of the multi-layer catheter.

[0111] (3) Mechanical property evaluation of multi-layer PI catheter

[0112] Refer to the test standard ASTM D882-2018, use an Instron universal material testing machine, the test span is 100 mm, the test rate is 50 mm / min, and select the key performance indicators of tensile strength and elongation at break for evaluation.

[0113] (4) Development performance evaluation of multi-layer PI catheter

[0114] Refer to the standard YY / T 0586-2016 Test method for X-ray opacity of medical polymer products, use a Mindray DigiEye330 / 350 series digital medical X-ray imaging system (DR) to perform development testing on the PI catheter. The X-ray tube voltage, current, and exposure time are 60 kV, 100 mA, and 0.1 s respectively. Evaluate the development effect according to the gray value. The defined range is from 0 to 255, white is 255, black is 0, and the smaller the number, the better the development effect.

[0115] The technical solution of the present invention will be further described in detail below in conjunction with several preferred embodiments and the accompanying drawings. This embodiment is implemented on the premise of the technical solution of the invention, and the detailed implementation method and specific operation process are given. However, the protection scope of the present invention is not limited to the following embodiments.

[0116] The experimental materials used in the following embodiments can be purchased from conventional biochemical reagent companies without special instructions.

[0117] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosed embodiments of the compositions, the appropriate methods and materials are those described below. All publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference in their entirety unless a specific paragraph is cited. In case of conflict, the present specification and the definitions included therein shall prevail. In addition, the materials, methods, and examples are illustrative only and not restrictive.

[0118] The technical solutions, implementation processes, principles, etc. of the present invention will be further explained and illustrated through specific examples below. It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present invention. The described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention. Unless otherwise specified, the reagents and raw materials used in the following examples are commercially available, and the test methods without specific conditions are usually carried out under conventional conditions or according to the conditions recommended by each manufacturer. Additionally, unless otherwise specified, the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt the conventional techniques in the technical field. These techniques are well described in the existing literature.

[0119] The technical solutions of the present invention will be described in detail through specific examples below.

[0120] Example 1

[0121] In this example, the method of vacuum magnetron sputtering is adopted. For the specific method, refer to Figure 1 , first, a thin layer of metals such as tungsten and molybdenum is deposited on a PI catheter rotating at a constant speed, and then a layer of polyamic acid is dip-coated. After curing, a three-layer composite PI catheter with a developing function in the middle is formed, as Figure 2 shown.

[0122] The preparation method of the polyimide catheter with X-ray developing function provided in this example specifically includes the following preparation steps:

[0123] (1) Preparation of polyamic acid: In a thousand-class clean manufacturing workshop with a constant temperature of 25°C and a constant humidity of 50RH%, DMAc (147.7 kg) was pumped into a 200L reactor equipped with mechanical stirring, cold and hot medium jackets, and nitrogen gas through a precision metering pump. The para-phenylenediamine monomer (PDA, 24 mol, 2.595 kg) was added by an automatic powder feeder. The reaction temperature was controlled at 25°C, and after stirring for 2 h, 4,4'-biphenyl dianhydride (4,4'-BPDA, 30 mol, 8.827 kg) was added. After uniform stirring for 4 h, a polyamic acid oligomer with dianhydride as the end group was formed. Then, 2-(4-aminophenyl)-5-aminobenzoxazole (APBOA, 36 mol, 8.109 kg) was added to the solution and stirred for 2 h to dissolve and fully react. Finally, pyromellitic dianhydride (PMDA, 30 mol, 6.544 kg) was slowly added in multiple batches to make the resin viscosity reach about 5000 cP. Finally, after stirring for 4 h, a polyamic acid resin precursor solution with a solid component concentration of 15 wt% was obtained. Then, the polyamic acid resin was defoamed under vacuum (<1 Pa) and left standing for 24 h to remove residual bubbles in the solution, and the impurities were removed through a 2-μm filter element. Finally, a polyamic acid resin precursor solution for the preparation of polyimide catheter was prepared, and the solid content was: 15 wt%.

[0124] (2) Preparation of the catheter substrate layer: A 0.50-mm silver-plated copper wire was selected as the tube core. First, a 0.05-mm PTFE lubricating layer was coated on it, and then the tube core was passed through the above-mentioned polyamic acid precursor glue tank with a conveying speed of 2 m / min. Then, it was baked in pre-ovens at 130°C and 150°C for 3 min to pre-dry and pre-shape the solvent. Finally, high-temperature heat treatment was carried out through a high-temperature hot air channel. First, it was heat-treated at 300°C, 360°C, 420°C, and 480°C for 3 min each, and then annealed at 400°C, 300°C, and 200°C for 3 min each to completely dry and imidize it. Through process adjustment and optimization, the single-pass glue application thickness was 3 μm, and it was dip-coated 10 times. Finally, a PI substrate layer with a thickness of 30 μm was obtained.

[0125] (3) Preparation of the metal developing layer: Five 100-cm-long PI catheters cured in step (2) were selected. At both ends, 10 cm were reserved and wrapped with PI insulating tape twice to make non-sputtering parts. Then, they were successively placed in acetone, ethanol, and deionized water for ultrasonic cleaning for 10 min, and the surface water was blown dry with compressed air. Then, they were placed in a clean vacuum oven at 120°C and baked for 30 min. Finally, corona treatment was carried out at a power of 60 W for 30 s to improve the surface tension; A large closed-field unbalanced magnetron sputtering ion plating machine was selected as the processing equipment, and the furnace cavity size was 300*120*50 cm 3, fix the PI catheter on the workpiece rack in the furnace cavity and rotate it at a constant speed of 5 revolutions per minute. Install a tungsten target with a purity of 99.999%, with a size of diameter 10 cm * height 8 cm; first turn on the mechanical pump to extract low vacuum, and then turn on the molecular pump to extract high vacuum. When the vacuum reaches 2 * 10- 5 Torr, adjust the target power to 3000 W, use 99.999% high-purity argon gas as the sputtering gas, and maintain the vacuum at 1 * 10 -3 Torr during deposition. After depositing for 20 minutes, turn off the target power. Wait for the temperature to drop to 40 - 50 °C, open the cavity door to take out the sample, and measure that the deposition thickness of tungsten metal is 4.02 μm.

[0126] (4) Preparation of the PI layer on the surface of the tungsten metal deposition layer: For the PI catheter with the tungsten metal layer deposited above, first untie the PI films at both ends that shield the sputtering effect, and pass it through the above-mentioned polyamic acid precursor glue tank again. Adopt the same dip coating and curing process as the preparation of the PI substrate, dip coat 4 times to obtain a 12-μm PI surface layer.

[0127] Finally, strip the die to obtain a multi-layer PI catheter with a developing function, and conduct performance evaluation. The test results are shown in Table 1 below.

[0128] Example 2

[0129] Adjust the deposition time in step (3) of Example 1 from 20 minutes to 30 minutes, and keep other conditions exactly the same as in Experiment 1. Evaluate the key performance of the catheter, and the test results are shown in Table 1 below.

[0130] Example 3

[0131] Adjust the deposition time in step (3) of Example 1 from 20 minutes to 10 minutes, and keep other conditions exactly the same as in Experiment 1. Evaluate the key performance of the catheter, and the test results are shown in Table 1 below.

[0132] Example 4

[0133] Replace the target material in step 3 of Example 1 from tungsten metal with molybdenum metal, and keep other conditions exactly the same as in Experiment 1. Evaluate the key performance of the catheter, and the test results are shown in Table 1 below.

[0134] Example 5

[0135] Replace the target material in step 3 of Example 1 from tungsten metal with barium metal, and keep other conditions exactly the same as in Experiment 1. Evaluate the key performance of the catheter, and the test results are shown in Table 1 below.

[0136] Example 6

[0137] An enhanced layer is added to the PI catheter with a developing function developed in Example 1. The 304V stainless steel flat wire is directly woven onto the PI catheter prepared in Example 1, where the size of the flat cross-section in terms of thickness * width is 0.02 mm * 0.08 mm, and the number of crossings per inch (PIC) is 100. Then, it is passed through the polyamic acid precursor glue tank prepared in Step 1 of Example 1 again. Using the same dip coating and curing process as for the PI substrate preparation, dip coating is carried out 10 times to obtain a PI surface layer with a thickness of 30 μm. The 20-μm-thick reinforcing filaments are embedded in the PI surface layer. Finally, the mandrel is peeled off to obtain a multi-layer PI braided catheter with a developing function, and its performance is evaluated. The test results are shown in Table 1 below.

[0138] Example 7

[0139] Using water-soluble polytetrafluoroethylene (PTFE) with a concentration of 10 wt% as the raw material for the lubricating layer, the PI catheter with a developing function developed in Example 1 is passed through the PTFE aqueous solution glue tank at a speed of 1 m / min, and then through a pre-baking oven at 120 °C for drying. The thickness of the PTFE coated each time is about 1 μm, and it is cycled 4 times to prepare a 4-μm lubricating layer. Then, the catheter is heated to 320 °C to soften the PTFE to form a dense and smooth surface structure, thus achieving a good lubricating effect.

[0140] Comparative Example 1

[0141] The target power in Example 1 is adjusted to 0 W, and no metal sputtering is carried out. Other conditions are exactly the same as those in Example 1, and the key performance of the catheter is evaluated. The test results are shown in Table 1 below.

[0142] Comparative Example 2

[0143] In step (1) of Example 1, the rigid diamine monomers PDA and APBOA in the polyimide structure are replaced with the flexible monomer ODA, and the rigid dianhydride monomers 4,4'-BPDA and PMDA are replaced with the flexible monomer ODPA. The molecular structure is shown in the following figure. Other conditions are exactly the same as those in Example 1, and the key performance of the catheter is evaluated. The test results are shown in Table 1 below.

[0144] Comparative Example 3

[0145] In step (3) of Example 1, the target material, replacing tungsten metal with bismuth trioxide, other conditions are exactly the same as those in Example 1, and the key performance of the catheter is evaluated. The test results are shown in Table 1 below.

[0146] Comparative Example 4

[0147] In this comparative example, a method of doping tungsten metal into the polyamic acid glue solution to prepare a polyimide catheter with a developing function is adopted. Specifically, the preparation steps include:

[0148] In a Class 1000 clean manufacturing workshop maintained at a constant temperature of 25°C and a constant humidity of 50% RH, DMAc (147.7 kg) was pumped into a 2L reaction kettle equipped with mechanical stirring, a cold and heat medium jacket, and nitrogen gas through a precision metering pump. p-Phenylenediamine monomer (PDA, 24 mol, 2.595 kg) was added using an automatic powder feeder. The reaction temperature was controlled at 25°C, and after stirring for 2 hours, 4,4'-Biphenyl dianhydride (4,4'-BPDA, 30 mol, 8.827 kg) was added. The mixture was stirred evenly for 4 hours to form a polyamic acid oligomer with dianhydride at the end groups. Then, 2-(4-Aminophenyl)-5-aminobenzoxazole (APBOA, 36 mol, 8.109 kg) was added to the solution and stirred for 2 hours to dissolve and fully react. Finally, pyromellitic dianhydride (PMDA, 30 mol, 6.544 kg) was added slowly in multiple batches until the resin viscosity reached about 100,000 cP. Finally, after stirring for 4 hours, a polyamic acid resin precursor solution with a solid component concentration of 15 wt% was obtained. In a 500 mL beaker, 137 g of tungsten metal powder with an average particle size of 1 μm and 778 g of DMAc were added. The mixture was dispersed at a speed of 3000 rpm for 1 hour using a high-speed disperser, and then quickly added to the prepared polyamic acid. Then, the two were mixed and dispersed at 1500 rpm using a high-speed dispersant for 30 minutes to obtain a viscosity of 30,000 cP. Then, the polyamic acid resin was filtered through a 2 μm filter element to remove impurities, and then vacuum degassed (<1 Pa) and left standing for 24 hours to remove residual bubbles in the solution. During the filtration and defoaming process, a large amount of tungsten metal began to settle and clog the filter element. The solid content of the prepared polyamic acid colloidal solution was about 15 wt%.

[0149] (2) Conduit preparation: A silver-plated copper wire with a diameter of 0.50 mm was selected as the tube core. First, it was coated with a 0.05 mm PTFE lubricating layer, and then the tube core was passed through the above-mentioned polyamic acid precursor colloid tank at a conveying speed of 2 m / min. It was then baked in pre-ovens at 130°C and 150°C for 3 minutes to pre-dry and pre-shape the solvent. Finally, high-temperature heat treatment was carried out through a high-temperature hot air duct. It was heat-treated at 300°C, 360°C, 420°C, and 480°C for 3 minutes each, and then annealed at 400°C, 300°C, and 200°C for 3 minutes each to completely dry and imidize it. Through process adjustment and optimization, the single-pass coating thickness was 3 μm, and the dip coating was carried out 14 times. Finally, a PI substrate layer with a thickness of 42 μm was obtained.

[0150] Finally, the tube core was peeled off to obtain a multi-layer PI conduit with a developing function, and its performance was evaluated. The test results are shown in Table 1 below.

[0151] Table 1 Performance evaluation results of the polyimide conduits prepared in each example and comparative example

[0152]

[0153] As shown in Table 1, after the tungsten metal is deposited by sputtering in Example 1-Example 3, a good development effect can be shown, and the longer the time, the thicker the deposition and the deeper the blackness; see Figure 3 This is a development picture of the polyimide catheter prepared in Example 1 in a mouse under X-ray irradiation. As can be seen from the figure, the polyimide catheter was developed in the mouse, and the catheter was clearly observed in the mouse under X-ray irradiation.

[0154] In Example 4 and Example 5, metal molybdenum and barium also have developing functions, but their developing effects are lower than metal tungsten; in Example 6, a metal braided layer is introduced, and its mechanical properties are mainly determined by the intrinsic properties of the metal, which is significantly improved; in Example 7, adding a lubricating layer will still maintain good developing effects and mechanical properties; in Example 1 and Comparative Example 1, there is no metal tungsten layer, and it will not have developing ability; in Example 1 and Comparative Example 2, the rigidity of the polyimide substrate is low, which will lead to increased thermal stress in the substrate layer and the metal layer, and will cause interlayer separation after bending, which is easy to cause medical accidents; in Comparative Example 3, some metal oxides have certain toxicity and cannot pass the cell toxicity test, so they are not suitable for medical catheters. In Comparative Example 4, the metal tungsten mixed addition scheme is adopted, and the pipe is prone to brittle cracking in the end, and the black distribution is uneven.

[0155] The above are only preferred embodiments of the present invention, which do not limit the protection scope of the present invention. For those skilled in the art, the present invention may have various modifications and changes. Within the spirit and principle of the present invention, changes, modifications, replacements, integrations and parameter changes to these embodiments by conventional substitutions or by being able to achieve the same functions without departing from the principles and spirit of the present invention all fall within the protection scope of the present invention.

Claims

1. A polyimide catheter with X-ray development function, comprising from inside to outside a multilayer composite structure of at least a first substrate layer-a metal development layer-a second substrate layer; The first substrate layer and the second substrate layer are both prepared from a rigid dianhydride monomer and a rigid diamine monomer; The metal developing layer is prepared by sputtering metal onto the surface of the first substrate layer or the second substrate layer using a vacuum magnetron sputtering method.

2. The polyimide catheter with X-ray development function according to claim 1, characterized in that: The metal is one or a combination of tungsten, molybdenum, bismuth, barium, and tantalum; The purity of the metal is ≥99.9%; and / or, the purity of the metal is ≥99.99%; The thickness of the metal developing layer is 0.1 μm to 10 μm; and / or the thickness of the metal developing layer is 5 μm to 5 μm; And / or, the rigid dianhydride monomer is selected from one or more combinations of phthalic anhydride, pyrazinetetracarboxylic anhydride, 1,4,5,8-naphthalenetetracarboxylic anhydride, 4,4′-biphenyltetracarboxylic anhydride, 2,3,6,7-anthracenetetracarboxylic anhydride, dibenzodioxane dianhydride, 4,4′-terphenyl dianhydride, 3,4,9,10-pyrenetetracarboxylic anhydride, p-phenylenedi(trimellitic acid ester) dianhydride, etc.; And / or, the rigid diamine monomer is preferably one or more combinations of p-phenylenediamine, 2,6-diaminopyridine, 1,4-benzidine, 4,4′-diaminodiphenyl ether, 4,4′-diamino-2,2′-dimethylbiphenyl, 4,4′-diamino-2,2′-bis(trifluoromethyl)biphenyl, 2-(4-aminophenyl)-5-aminobenzoxazole, 2-amino-5(4-aminophenyl)-pyrimidine, 2,5-di(4-aminophenyl)pyridine, 5-amino-2-(3′-aminophenyl)benzimidazole, 3,3′-dihydroxybiphenyl diamine, and 3,3′-diaminobenzanilide.

3. The polyimide catheter with X-ray development function according to claim 1, characterized in that: The length of the first substrate layer is the same as the length of the second substrate layer; The length of the metal developing layer is shorter than the length of the first substrate layer and the second substrate layer, so that the first substrate layer and the second substrate layer form respective adhesion layers at both ends, so that the first substrate layer and the second substrate layer can be directly adhered and bonded; and / or, the length of the adhesive layer is 5 to 20% of the overall length of the first substrate layer and / or the second substrate layer; And / or, the inner diameter of the polyimide catheter is 10 to 1000 μm.

4. The polyimide catheter with X-ray development function according to any one of claims 1 to 3, characterized in that: A reinforcing layer is further included between the metal developing layer and the first substrate layer or the second substrate layer; The composite structure includes the first substrate layer-the metal developing layer-the reinforcing layer-the second substrate layer; The reinforcing layer is a braided tube braided from linear materials; The linear material is stainless steel, nickel titanium alloy, Liquid crystal polymer fibers, One or a combination of synthetic fibers; and / or, the braided tube comprises a braided mesh or a coiled wire; and / or, the woven mesh has a cross-intersection number per inch (PIC) of 10 to 200; and / or, the number of windings per inch (WPI) of the coil wire is 20 to 180; And / or, the linear material is a flat or round linear material; And / or, the cross-sectional thickness*width of the flat linear material is 0.006mm*0.032mm~0.05mm*0.25mm, and the cross-sectional diameter of the circular linear material is 0.012mm~0.1mm.

5. The polyimide catheter with X-ray development function according to any one of claims 1 to 3, characterized in that: The outer sides of the first substrate layer and the second substrate layer of the polyimide catheter further include a lubricating layer; The multi-layer composite structure includes: the first lubricating layer-the first substrate layer-the metal developing layer-the reinforcing layer-the second substrate layer, or, the multi-layer composite structure includes: the first lubricating layer-the first substrate layer-the metal developing layer-the second substrate layer; And / or, the material of the lubricating layer is tetrafluoroethylene (PTFE), fluorinated ethylene propylene copolymer (FEP), soluble polytetrafluoroethylene (PFA), polyphenylene sulfone Nylon 11 Nylon 12 Polyurethane Polyetheramide One or more combinations of; And / or, the lubricating layer has a thickness of 0.5 to 20 μm.

6. A method for preparing a polyimide catheter with X-ray development function as claimed in any one of claims 1 to 5, characterized in that: The following steps are involved: S1. Providing a polyamic acid resin precursor solution: adding a rigid dianhydride and a diamine monomer to a non-protonic polar solvent to prepare a polyamic acid, and then imidizing to obtain the polyamic acid resin precursor solution; S2. Preparing a first substrate layer: dip-coating the polyamic acid precursor solution on the surface of the tube core, and performing a first pre-drying qualitative step to form a uniform film on the surface of the tube core, which is the first substrate layer; S3. Making a metal developing layer: adding a covering layer to both ends of the tube core after S2 treatment, and then performing vacuum magnetron sputtering on the first substrate layer after pre-treatment to form a dense metal film on the surface of the first substrate layer; Remove the covering layer; S3. Preparing a second substrate layer: immersing the tube core treated by S3 in the polyamic acid precursor solution, performing high temperature curing treatment, and completely drying to form the second substrate layer; Finally, the tube core is peeled off to obtain the polyimide tube.

7. The preparation method according to claim 6, characterized in that: The step between S2 and S3 also includes preparing a reinforcement layer; The braided tube is embedded on the surface of the substrate layer and the metal developing layer to form a reinforcing layer; then immersed in a thermoplastic polyamic acid precursor solution, the thermoplastic polyamic acid precursor solution is filled into the gap of the braided tube, and a second pre-drying is performed to form an adhesion layer on the surface of the reinforcing layer; The thermoplastic polyamic acid precursor solution is prepared by dissolving a thermoplastic polyimide compound in a polar aprotic solvent; The thermoplastic polyimide compound is prepared by polycondensation of dianhydride monomers and diamine monomers, wherein the dianhydride monomers are one or more of 4,4′-diphenyl ether dianhydride, 4,4′-benzophenone tetracarboxylic dianhydride, trimellitic anhydride hydroquinone ester, 4,4′-(3,4-dicarboxyphenoxy)benzophenone dianhydride, 4,4(-diphenyl sulfide dianhydride, 4,4′-diphenyl sulfone dianhydride, 4,4′-phenylene ether dianhydride and 4,4′-bisphenol A diether dianhydride. The diamine monomer is one or more of 4,4′-diaminodiphenyl ether, 1,4-bis(4-aminophenoxy)benzene, 1,3-bis(4-aminophenoxy)benzene, 4,2′-bis[4-(4-aminophenoxy)phenyl]propane, 3,4′-diaminodiphenyl ether, 2,7-bis(4-aminophenoxy)naphthalene, 4,4′-bis(3-aminophenoxy)biphenyl and 4,4′-bis(3-aminophenoxy)benzophenone; The solid content of the thermoplastic polyamic acid precursor solution is 6-50 wt %.

8. The preparation method according to claim 6, characterized in that: After S3, it also includes applying a lubricating layer; The specific steps include: immersing the tube core prepared in S3 into a lubricant aqueous solution, coating a lubricant layer on the surface of the adhesive layer, and after a third pre-drying and characterization, high-temperature drying is performed to soften the lubricant to form a dense and smooth surface structure, thereby obtaining the polyimide catheter; The lubricant is tetrafluoroethylene (PTFE), fluorinated ethylene propylene copolymer (FEP), soluble polytetrafluoroethylene (PFA), polyphenylene sulfone Nylon 11 Nylon 12 Polyurethane Polyetheramide One or more combinations of .

9. The preparation method according to any one of claims 6 to 8, characterized in that: The high temperature curing treatment includes drying and imidizing the first substrate layer, the second substrate layer and the adhesive layer using a multi-stage high temperature heating process; The process conditions of the high temperature curing treatment include first heating up in stages and then annealing; The range of the staged heating is 200-700°C, and the heat treatment time of each stage is 1-100 minutes; the temperature range of the annealing is 150-500°C, and the annealing time is 1-100 minutes; And / or, the staged heating includes heat treatment at 300°C, 360°C, 420°C and 480°C for 3 min respectively; the annealing includes annealing at 400°C, 300°C and 200°C for 3 min respectively; And / or, the vacuum magnetron sputtering method includes a vacuum degree lower than 5.0*10-5Torr; The target power during sputtering is 1000~5000W; The deposition thickness of the metal layer during sputtering is 0.1 μm to 10 μm; or, the deposition thickness of the metal layer is 5 μm to 5 μm; And / or, the polar aprotic solvent is any one or a combination of formamide compounds, acetamide compounds, sulfoxide pyrrolidone compounds, phenolic solvents, tetrahydrofuran (THF), dioxane, dichloromethane, chloroform, hexamethylphosphorus triamide, γ-butyrolactone, and cyclopentanone; The solid content of the polyamic acid precursor solution is 6 to 50 wt %; And / or, the dip coating includes immersing the tube core and conveying it in the polyamic acid precursor solution at a conveying speed of 0.1 to 50 m / min.

10. Use of the polyimide catheter with X-ray imaging function as claimed in any one of claims 1 to 5 as a medical device in X-ray imaging technology.

11. An X-ray developing tube, prepared from the polyimide catheter with X-ray developing function as claimed in any one of claims 1 to 6.

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