A guide catheter and its preparation method and application

Abstract

The present invention provides a guide catheter, a preparation method, and applications thereof. The guide catheter comprises the following components, measured by weight: 100 parts of a base material; 5-10 parts of tripropyl citrate; 1-5 parts of polycaprolactone diol; 5-10 parts of 1,4-butanediol sulfate; 0.5-3 parts of a coupling agent; and 0.1-0.5 parts of an antioxidant. The guide catheter of the present invention utilizes the synergistic effects of various materials to regulate the flexibility and lubricity of the base material, thereby improving the catheter's rebound recovery rate and significantly enhancing its ability to recover from deformation when navigating narrow or curved blood vessels. This effectively prevents creases or permanent bends, and enhances maneuverability and safety during delivery.

Description

Technical Field

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

[0002] Guide catheters, as an indispensable and important instrument in interventional medical technology, are widely used in clinical procedures such as cardiovascular, cerebrovascular, and peripheral vascular surgeries. They primarily fulfill the critical function of ensuring that interventional devices such as guide wires, balloon dilatation catheters, and stent systems reach the target lesion site. With the continuous development of minimally invasive interventional technology and the increasing demand for complex surgical operations, more stringent performance requirements are being placed on guide catheters. They must not only possess excellent pushability, torsional controllability, and support strength, but also possess high flexibility, biocompatibility, and low friction to accommodate clinical challenges such as complex anatomical structures and difficult-to-reach lesions.

[0003] Currently, most common guide catheters on the market are made from polymer materials such as polyurethane, polyamide, polyether block amide (PEBA), or polytetrafluoroethylene (PTFE). Although these materials possess certain mechanical strength and processability, they still have numerous deficiencies in actual use. First, in terms of flexibility, catheters made from traditional materials often exhibit a certain degree of rigidity. When faced with complex anatomical structures, tortuous blood vessels, or narrow pathways, they are prone to creases, bends, or permanent deformation, which can impede further advancement of the catheter and even lead to guide failure. This deformation can be particularly significant in delicate surgical areas such as the cerebral vasculature or coronary arteries, where intraoperative safety and efficiency can be directly impacted. Second, the catheter's resilience is also a key indicator of its lifespan and clinical performance. Some materials struggle to return to their original shape after being subjected to tortuosity or pressure, creating the risk of retained deformation and reducing its reliability for reuse. In addition, the guide catheter needs to frequently contact and slide with the inner wall of the blood vessel during the delivery process. If its surface lubricity is poor or the friction coefficient is high, it will significantly increase the pushing resistance, which will not only affect the smoothness of the surgical operation, but also increase the risk of blood vessel wall damage, thereby inducing complications such as thrombosis and inflammation, seriously affecting the patient's prognosis. More importantly, if the polymer material used in the catheter lacks good biocompatibility, it is very easy to cause irritation or cytotoxicity of local tissues, especially in long-term or repeated use scenarios. For example, some residual monomers, additives or degradation products may induce cytotoxic or immune inflammatory reactions, and even cause vascular dysfunction. In addition, in order to improve the performance of the catheter, the existing technology has also tried to add modified ingredients such as plasticizers and lubricants, but some additives have poor compatibility with the base material and are prone to precipitation, affecting the overall mechanical properties and stability of the material.

[0004] Therefore, there is room for improvement in the existing guide catheters in terms of structural design, material properties and manufacturing processes. There is an urgent need to develop a guide catheter material system with excellent comprehensive performance that can not only meet the requirements of high flexibility and low friction performance in interventional operations, but also have excellent resilience, biocompatibility and processing adaptability, so as to comprehensively improve the clinical applicability and safety of catheters in complex vascular interventional treatments. Summary of the Invention

[0005] To address the shortcomings of the existing technology, the present invention proposes a guide catheter, its preparation method, and its application. This invention addresses the technical issues of existing guide catheters, such as poor flexibility, insufficient resilience, high friction coefficient, and limited biocompatibility. It provides a novel guide catheter with promising industrial application prospects and clinical promotion value.

[0006] The present invention provides a guide catheter comprising the following components in parts by weight:

[0007] 100 parts of base material;

[0008] 5-10 parts of tripropyl citrate;

[0009] 1-5 parts of polycaprolactone diol;

[0010] 5-10 parts of 1,4-butanediol sulfate;

[0011] 0.5~3 parts of coupling agent;

[0012] Antioxidant 0.1~0.5.

[0013] In the guide catheter material formula of the present invention, tripropyl citrate, polycaprolactone diol and 1,4-butanediol sulfate serve as key auxiliary agents, which synergistically optimize the flexibility, resilience, processing performance and biocompatibility of the catheter.

[0014] Tripropyl citrate has good polarity and can form strong intermolecular forces with various polymer matrices, significantly lowering the system's glass transition temperature (Tg), thereby improving the material's softness and deformability at room temperature. Polycaprolactone diol is a linear oligoester polyol with a soft molecular chain and low crystallinity. It can be embedded in the matrix polymer, improving the overall material's flexibility and elasticity while also regulating the catheter's resilience and crease resistance. 1,4-Butanediol sulfate, whose polar groups can form hydrogen bonds or electrostatic forces with amide, ether, or ester bonds in the matrix polymer, improves the interfacial compatibility between the components, making the system more uniformly distributed and its performance more stable. The present invention constructs a synergistically enhanced composite polymer system by rationally introducing tripropyl citrate, polycaprolactone diol, 1,4-Butanediol sulfate, a coupling agent, and an antioxidant into the matrix material. The resulting catheter significantly improves its flexibility, resilience, and surface lubricity while maintaining the necessary mechanical strength and support, effectively reducing frictional resistance against the blood vessel wall.

[0015] In some embodiments, the mass ratio of tripropyl citrate to 1,4-butanediol sulfate is (1-2):1. Within this ratio range, tripropyl citrate's dominant role in plasticization is maintained, while the segment support effect of 1,4-butanediol sulfate achieves mechanical reinforcement and balanced control of the material. When tripropyl citrate is added in a moderate ratio, the catheter's flexibility and low-temperature resilience are significantly improved. The introduction of an appropriate amount of 1,4-butanediol sulfate inhibits the migration of tripropyl citrate, improving the system's thermal stability and deformation recovery. Within this ratio range, the synergistic effect of the two ensures that the guide catheter maintains excellent flexibility and resilience while maintaining a low coefficient of friction and good processing properties, ultimately optimizing the material's overall performance.

[0016] In some embodiments, the matrix material is one or more of polyether-amide block copolymer (PEBA), polyurethane resin, and polyamide resin; it is used to impart basic mechanical support, flexibility, and good biocompatibility to the guide catheter. Preferably, a single or combined formulation can be used to achieve balanced performance, depending on the clinical application.

[0017] In some embodiments, the coupling agent is any one or more of a silane coupling agent, an epoxy coupling agent, and a carboxylic acid coupling agent.

[0018] In some embodiments, the antioxidant is a hindered phenol antioxidant or a phosphite antioxidant.

[0019] In some embodiments, the hindered phenol antioxidant includes octyl β-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate, pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl) propionate, 2,2′-methylenebis(6-(1-methylethyl)-4-methylphenyl)-4-methanol and bis(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid acetamide;

[0020] The phosphite antioxidants include tris(2,4-di-tert-butylphenyl)phosphite, tris(nonylphenyl)phosphite, triphenylphosphite and bis(2,4-di-tert-butylphenyl)diphenyl phosphate.

[0021] In some embodiments, the surface of the guide catheter is further provided with an antimicrobial coating; the antimicrobial coating can be constructed using a variety of methods, such as silver nanoparticles, quaternary ammonium polymers, chitosan, antimicrobial peptides, or a drug-loaded sustained-release structure. It exhibits broad-spectrum antimicrobial properties, low toxicity, and excellent adhesion. It can form an antimicrobial barrier at the interface between the catheter and the inner wall of the blood vessel or body fluids, effectively inhibiting the attachment and reproduction of common nosocomial pathogens such as Staphylococcus aureus, Escherichia coli, and Staphylococcus epidermidis, thereby reducing the risk of infection. This allows the guide catheter of the present invention to meet mechanical performance and biosafety requirements while further enhancing its clinical stability and long-term implant safety, making it more suitable for vascular interventional procedures in high-risk infection environments.

[0022] In some embodiments, the antimicrobial coating is applied to the surface of the guide catheter by solution dipping, spraying, or evaporation deposition.

[0023] The present invention also provides a method for preparing the guide catheter, comprising the following steps: melt-blending the base material with tripropyl citrate, polycaprolactone diol, 1,4-butanediol sulfate, a coupling agent, and an antioxidant at 100-150° C., and extruding the mixture after cooling to obtain the guide catheter.

[0024] The present invention also provides the use of the guide catheter in the preparation of vascular interventional devices, cardiac interventional devices, and neurointerventional devices.

[0025] In summary, compared with the prior art, the present invention achieves the following technical effects:

[0026] (1) The guide catheter of the present invention introduces materials such as tripropyl citrate, polycaprolactone diol and 1,4-butanediol sulfate to synergistically regulate the flexibility and lubricity of the matrix, so that the catheter exhibits an excellent rebound recovery rate in the three-point bending rebound test, greatly improving the deformation recovery ability of the catheter when passing through stenotic or curved parts of the blood vessels, effectively avoiding the occurrence of creases or permanent bends, and improving the controllability and safety during the pushing process.

[0027] (2) The friction coefficient of the guide catheter of the present invention in the sliding test in a physiological saline environment can be as low as 0.15, which is significantly better than the performance of the comparative sample.

[0028] (3) The results of the cytotoxicity test of the guide catheter of the present invention showed that the cell viability was greater than 94%, which met the biocompatibility requirements of the GB / T16886.5-2017 standard. This shows that the catheter has excellent biosafety while ensuring mechanical properties, meeting the needs of long-term clinical implantation or repeated use. DETAILED DESCRIPTION

[0029] In order to help those skilled in the art better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention are clearly and completely described below. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making any creative efforts should fall within the scope of protection of the present invention.

[0030] The present invention provides a guide catheter with excellent flexibility, low friction and good biocompatibility. By synergistically compounding materials such as polyether-amide block copolymer, tripropyl citrate, polycaprolactone diol, 1,4-butanediol sulfate in a reasonable proportion and adopting a melt blending extrusion molding process, the catheter has extremely high flexibility and resilience while maintaining sufficient support force. The test results of the embodiment show that the rebound recovery rate of the guide catheter of the present invention can reach more than 89%, and the friction coefficient is as low as less than 0.15; the L929 cell viability in the cytotoxicity evaluation is greater than 94%, which meets the biosafety requirements of the GB / T 16886.5-2017 standard. The material of the present invention can effectively avoid the generation of creases, deformation or blockages in the catheter during the pushing process, and reduce the friction resistance with the inner wall of the blood vessel, thereby improving the smoothness and safety of clinical operations, and is suitable for the clinical needs of long-term or repeated use of catheters in stenotic blood vessels or complex pathways.

[0031] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. The materials and reagents used are all commercially available unless otherwise specified.

[0032] Main raw material sources:

[0033] Polyamide resin: S14142, Shanghai Yuanye Biotechnology Co., Ltd.;

[0034] Tripropyl citrate: CAS: 1587-21-9, Shandong Shouhua Chemical Co., Ltd.

[0035] Polycaprolactone diol: CAS: 36890-68-3, Jinshengtai;

[0036] 1,4-Butanediol sulfate: Wuhan Linsheng Technology Co., Ltd.;

[0037] Coupling agent: γ-glycidyloxypropyltrimethoxysilane, G107576, Aladdin;

[0038] Antioxidant: Irganox 1076. Parallel experiments used the same substance.

[0039] The guide catheter configurations of the embodiment and the comparative example are shown in Table 1:

[0040] Table 1 Proportions of guide catheters in Examples and Comparative Examples (parts by weight)

[0041]

[0042] Preparation process

[0043] The preparation method of the guide catheter comprises the following steps:

[0044] (1) Weigh each component according to the ratio in Table 1, place in a vacuum drying oven, and pre-dry at 60°C for 6 to 12 hours to remove moisture and avoid hydrolysis during processing.

[0045] (2) Add all components into a twin-screw extruder or internal mixer and melt blend at 100 °C. Set the speed to 100 rpm and blend for 8 to 12 minutes to ensure that the components of each phase are fully dispersed and evenly blended.

[0046] (3) The blended material is melted and extruded through an extruder (equipped with a small-diameter die) with the temperature zones set as follows:

[0047] First heating zone: 120°C; second heating zone: 135°C; die zone: 140°C; extrusion speed: 1.5-3.0 m / min.

[0048] (4) The extruded pipe enters the water cooling tank for rapid cooling and molding. The water temperature is controlled at 25°C and the cooling time is 30 seconds.

[0049] (5) The cooled catheter is pulled and stably rolled up by a traction device, or cut and formed into a desired length to obtain the guide catheter.

[0050] Test methods and results

[0051] (1) Flexibility test

[0052] Three-point bending rebound test:

[0053] The test apparatus includes: a bending fixture with fixed ends and a vertical force applied in the middle; a rebound distance measuring instrument (laser displacement meter); and an optional temperature-controlled platform set to a 37°C body temperature simulated environment.

[0054] Test steps:

[0055] a. Take a 10cm standard length catheter sample and place it horizontally between two supporting points with a distance of 5cm;

[0056] b. Apply a vertical force of 50g at the midpoint and maintain for 30 seconds;

[0057] c. Remove the load, record the time required to rebound to the initial state, and measure the residual bending displacement (the distance not rebounded);

[0058] d. Calculate the "rebound recovery rate" according to the formula:

[0059] .

[0060] (2) Lubricity test

[0061] The lubricity test was conducted in accordance with the standard "YY / T 0506.3-2016". The catheter was placed in a 37°C constant temperature water bath and inserted into a medical-grade silicone simulated blood vessel model with an inner diameter of 2.0 mm. A vertical pressure of 200 g was applied. The catheter was pulled and slid 100 mm at a speed of 20 mm / s using a Mark-10 electronic tensiometer. The maximum friction force F during the pulling process was recorded. f , and combined with the load weight to convert the positive pressure F n , calculate the coefficient of friction (COF):

[0062] .

[0063] The test results are shown in Table 1:

[0064] Table 2 Test results of flexibility and lubricity of guide catheters prepared in Examples and Comparative Examples

[0065]

[0066] The test results are shown in Table 2. The guide catheter prepared in the embodiment has a rebound recovery rate of over 89%, demonstrating excellent flexibility and crease resistance. Furthermore, in a lubricity test conducted in 37°C saline, the catheter friction coefficient was as low as below 0.15, significantly superior to the existing comparative catheter. This demonstrates that the catheter of the present invention can maintain good push performance and smooth operation in complex vascular pathways, reducing resistance generated when the catheter passes through narrow vessels or sharp bends. Its overall performance meets the safety and comfort requirements for long-term implantation and clinical use.

[0067] In Comparative Example 1, no tripropyl citrate is added, and the catheter material has too high rigidity, is prone to creases and is difficult to recover, resulting in a significant decrease in the rebound recovery rate; in Comparative Example 2, no polycaprolactone diol is added, and the catheter cannot effectively store and release strain energy after being subjected to force, which manifests as insufficient rebound performance; in Comparative Example 3, no 1,4-butanediol sulfate is added, and the lubricity between the catheter and body fluids or blood vessel walls is weakened, resulting in a significant increase in friction resistance; in Comparative Example 4, excessive tripropyl citrate will cause excessive plasticization of the base material, reduce the mechanical strength and shape retention of the catheter, and make it easy for it to produce permanent deformation during the bending process, resulting in a decrease in the rebound recovery rate; in Comparative Example 5, excessive flexible polycaprolactone diol will significantly reduce the modulus of the catheter, making it easy for it to bend significantly or even collapse when subjected to force, losing the necessary support force, affecting both the handling performance and reducing the rebound; in Comparative Example 6, excessive 1,4-butanediol sulfate will make the surface polarity too high, triggering protein adsorption in body fluids, resulting in an abnormally high friction coefficient in the biological environment. The above results show that the synergistic effect of each component in a reasonable ratio is the key to obtaining excellent rebound and low friction performance. The absence or excess of any core component will destroy the molecular chain structure balance of the catheter material, resulting in a significant decrease in physical properties and clinical adaptability.

[0068] (3) Biocompatibility testing

[0069] The biocompatibility of the guide catheter of the present invention is evaluated by performing a cytotoxicity test using the extract method according to GB / T 16886.5-2017.

[0070] The catheter samples sterilized by high-pressure steam sterilization (121°C, 20 minutes) were added to MEM culture medium containing 10% fetal bovine serum at a mass volume ratio of 0.2 g / mL and extracted in a 37°C constant temperature incubator for 24 hours. The obtained extract was sterilized by 0.22 μm filter and the pH value was tested to be stable at 7.3 ± 0.1. L929 mouse fibroblasts were cultured at 2×10 4 Cells were seeded at a density of cells / well in a 96-well plate, with five replicate wells per group. After 24 hours of incubation at 37°C, 5% CO2, and 95% humidity, 100 μL of each of the experimental group (guide catheter extract prepared in Examples 1-5), the negative control group (pure culture medium), and the positive control group (culture medium containing 0.64% phenol) were added, and incubation continued for 24 hours. 20 μL of MTS reagent was then added to each well and incubated for 2 hours. The absorbance was measured at 490 nm using a microplate reader. A blank well (no cells) was used for baseline correction, and relative cell viability was calculated according to the standard formula.

[0071] The test results are shown in Table 3:

[0072] Table 3 Cell viability test results

[0073]

[0074] The results in Table 3 show that the L929 cell survival rate in each example was above 95%, which is significantly higher than the non-toxicity standard of 70% in GB / T16886.5-2017, indicating that each guide catheter formulation of the present invention has good in vitro biocompatibility and meets the biological safety requirements of medical devices.

[0075] In summary, it can be seen from the above examples that the guide catheter material formula and its preparation process provided by the present invention can effectively improve the flexibility, resilience and push smoothness of the catheter. Specifically, by synergistically introducing functional additives such as tripropyl citrate, polycaprolactone diol and 1,4-butanediol sulfate, not only the molecular chain flexibility and interface compatibility of the polymer matrix are improved, but also the friction coefficient of the catheter is significantly reduced while maintaining the structural strength. The performance test results show that the rebound recovery rate of the guide catheter reaches more than 89%, the friction coefficient is lower than 0.15, and the cell survival rate is higher than 94% in the L929 cell viability assessment, which fully verifies its excellent mechanical properties and biosafety. Therefore, the catheter material system of the present invention is suitable for long-term or repeated use of catheters in complex clinical interventional pathways, and has significant practical value and application promotion prospects.

[0076] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A guide catheter, characterized in that: In parts by weight, it is composed of the following components: 100 parts of base material; 5-10 parts of tripropyl citrate; 1-5 parts of polycaprolactone diol; 5-10 parts of 1,4-butanediol sulfate; 0.5~3 parts of coupling agent; Antioxidant 0.1~0.5; The mass ratio of tripropyl citrate and 1,4-butanediol sulfate is (1-2):1; The matrix material is one or more of polyether-amide block copolymer, polyurethane resin and polyamide resin; The coupling agent is any one or more of a silane coupling agent, an epoxy coupling agent and a carboxylic acid coupling agent; The antioxidant is a hindered phenol antioxidant or a phosphite antioxidant; The preparation method of the guide catheter comprises the following steps: melt-blending the base material with tripropyl citrate, polycaprolactone diol, 1,4-butanediol sulfate, a coupling agent and an antioxidant at 100-150° C., and extruding after cooling to obtain the guide catheter.

2. The guide catheter according to claim 1, characterized in that The hindered phenol antioxidants include octyl β-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate, pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl) propionate, 2,2′-methylenebis(6-(1-methylethyl)-4-methylphenyl)-4-methanol and bis(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid acetamide; The phosphite antioxidants include tris(2,4-di-tert-butylphenyl)phosphite, tris(nonylphenyl)phosphite, triphenylphosphite and bis(2,4-di-tert-butylphenyl)diphenyl phosphate.

3. The guide catheter according to claim 1, characterized in that The surface of the guide catheter is also provided with an antibacterial coating.

4. The guide catheter according to claim 3, characterized in that: The antibacterial coating is applied to the surface of the guide catheter by solution dipping, spraying or evaporation deposition.

5. Use of the guide catheter according to any one of claims 1 to 4 in the preparation of vascular interventional devices, cardiac interventional devices, and neurointerventional devices.

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