A hydrophilic coating on the surface of an interventional guidewire and its preparation process and application

Abstract

The present invention discloses a hydrophilic coating on the surface of an interventional guidewire, and a preparation process and application thereof. The hydrophilic coating on the surface of the interventional guidewire includes an inner layer and an outer layer. In parts by weight, the inner layer includes: 5 to 15 parts of polyacrylate, 1 to 5 parts of coupling agent, and 50 to 60 parts of methyl ethyl ketone solvent; the outer layer includes: 10 to 30 parts of polyurethane, 1 to 5 parts of 1,3-propylene glycol cyclic sulfate, 1 to 3 parts of cross-linking agent, 1 to 3 parts of photoinitiator, and 90 to 100 parts of methyl ethyl ketone solvent; the outer layer material of the interventional guidewire is polyetheramide or perfluoro copolymer. The hydrophilic coating of the present invention has strong adhesion on the surface of the polyetheramide or perfluoro copolymer interventional guidewire, can prevent the coating from falling off or being damaged during operation, ensure the long-term stability of the coating, and the scope of application of the guidewire is wide.

Description

Technical Field

[0001] The invention relates to the technical field of chemical engineering, and in particular to a hydrophilic coating on the surface of an interventional guide wire and a preparation process and application thereof. Background Art

[0002] Interventional guidewires are an important part of interventional medical devices and are widely used in minimally invasive surgeries in the fields of blood vessels, urology, digestion, etc. The main function of the guidewire is to guide other instruments such as catheters into the target position through narrow and curved blood vessels or cavities. During the operation, the guidewire needs to be operated in a narrow and humid environment, so its surface properties have an important impact on the smooth progress of the operation. When the guidewire enters and exits the blood vessel and moves in the blood vessel, the highly lubricating surface can effectively avoid the adhesion of plasma proteins, platelets, etc. in the blood on the surface of the material, reduce damage to blood cells and blood vessel walls, reduce interference with blood laminar flow, and inhibit the occurrence of coagulation reactions. Although both highly hydrophobic and highly hydrophilic surfaces can produce lubrication properties, since interventional instruments are in direct contact with body fluids, body fluids must infiltrate medical instruments. Therefore, if the instrument is to have low friction when in contact with the body, or the instrument needs to be wetted by body fluids but not contaminated, or to prevent the formation of bubbles, a highly hydrophilic surface is more suitable.

[0003] However, most of the outer polymer materials used to make guidewires are hydrophobic, so hydrophilic coatings are often used to improve the lubricity of metal guidewires used in interventional medical treatment. In addition to meeting the high hydrophilic lubrication performance, the coating must also focus on the firmness and stability of the lubrication performance. The coating must not fall off after repeated friction and maintain good comprehensive performance. However, the existing hydrophilic coatings have good hydrophilic lubricity for guidewires with polyurethane outer layers, but for other types of polymer outer layers, the coating has insufficient adhesion and poor durability, and is easily worn or falls off during use. This wear will not only reduce the lubrication effect of the guidewire, but may also cause the coating fragments to fall off, causing inflammation or thrombosis.

[0004] Therefore, there is an urgent need to provide a hydrophilic coating with high adhesion, strong hydrophilicity and smoothness for different outer polymer materials to meet the needs of practical applications. Summary of the invention

[0005] In view of the defects in the prior art, the present invention proposes a hydrophilic coating on the surface of an interventional guidewire, and its preparation process and application. The present invention designs a double-layer hydrophilic coating system, including an inner layer and an outer layer. The polyacrylate and coupling agent in the inner layer ensure the strong adhesion between the coating and the polyetheramide or perfluoro copolymer guidewire, avoiding the peeling of the coating during use. The hydrophilic materials such as polyurethane and 1,3-propylene glycol cyclic sulfate in the outer layer form an extremely lubricated surface, so that the guidewire has low friction and high lubricity when operated in the body. By using polyacrylate with strong adhesion as the inner layer, a solid foundation can be provided for the outer layer of polyurethane to prevent the coating from falling off. The compounding of the two significantly enhances the overall adhesion of the coating.

[0006] The present invention provides a hydrophilic coating on the surface of an interventional guidewire, wherein the hydrophilic coating on the surface of the interventional guidewire comprises an inner layer and an outer layer, wherein the inner layer comprises the following components in parts by weight:

[0007] Polyacrylate 5-15 parts;

[0008] 1~5 parts of coupling agent;

[0009] 90-100 parts of methyl ethyl ketone solvent;

[0010] The outer layer comprises the following components:

[0011] 10-30 parts of polyurethane;

[0012] 1-5 parts of 1,3-propylene glycol cyclic sulfate;

[0013] 1~3 parts of cross-linking agent;

[0014] 1~3 parts of photoinitiator;

[0015] 90-100 parts of methyl ethyl ketone solvent;

[0016] The outer layer material of the interventional guide wire is polyetheramide or perfluoro copolymer; the perfluoro copolymer is any one of polytetrafluoroethylene (PTFE), perfluoroethylene propylene (FEP), ethylene-tetrafluoroethylene copolymer (ETFE), perfluoroalkoxy polymer (PFA) and polyvinylidene fluoride (PVDF).

[0017] Polyacrylate has strong polar functional groups, carboxyl and ester groups, which can interact with the surface of polyetheramide or perfluorocopolymer through hydrogen bonding or electrostatic interaction, thereby improving the adhesion of the interface. In addition, polyacrylate has good film-forming properties and can penetrate into the microstructure or surface pores of the polyetheramide or perfluorocopolymer substrate to form a mechanical fit, which enhances the adhesion of the coating.

[0018] The present invention adopts polyurethane as the main hydrophilic substance, compounded with 1,3-propylene glycol cyclic sulfate, and cross-linked by a cross-linking agent and a photoinitiator to form a stable surface coating, which has good compatibility with polyetheramide and perfluoro copolymer, can significantly improve the hydrophilicity and lubricity of the surface of the polyetheramide or perfluoro copolymer guide wire, and prevent the adhesion of blood or other biological substances.

[0019] The present invention selects methyl ethyl ketone as the solvent, which is helpful to evenly disperse the polyacrylate and the coupling agent to form a uniform coating, so that the coating has good surface flatness and adhesion after curing.

[0020] A certain amount of 1,3-propylene glycol cyclic sulfate is added to the hydrophilic coating of the present invention. 1,3-propylene glycol cyclic sulfate has biocompatibility and excellent film-forming properties, and its molecular structure can form a soft and uniform film on the surface of the coating, which not only enhances the hydrophilicity, but also improves the lubrication effect and reduces the friction between the guide wire and the surrounding tissues.

[0021] In some embodiments, the mass ratio of the polyacrylate to the coupling agent is (1-3):1; at a suitable ratio, the coupling agent has a moderate concentration and can form an appropriate amount of chemical bonding on the surface of the substrate, forming a synergistic effect with the mechanical intercalation of the polyacrylate, thereby avoiding the coating from being too fragile or rigid, maintaining good durability, and thus improving the performance of the entire hydrophilic coating.

[0022] In some embodiments, the mass ratio of the polyurethane to 1,3-propylene glycol cyclic sulfate is (2-6):1; the high lubricity of the polyurethane ensures the hydrophilicity and low friction properties of the coating, while the 1,3-propylene glycol cyclic sulfate provides structural support, so that the coating has sufficient mechanical strength and toughness. This balance allows the coating to maintain excellent lubricity without reducing the durability of the coating due to being too soft.

[0023] 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.

[0024] In some embodiments, the cross-linking agent is any one or more of glycerol triacrylate, ethylene glycol diacrylate, hexamethylene glycol diacrylate, polyethylene glycol diacrylate, and 1,6-hexanediol diacrylate.

[0025] In some embodiments, the photoinitiator is any one or more of 2-hydroxy-2-methylpropiophenone, 1-hydroxycyclohexyl phenyl ketone, benzophenone, methylphenylglycine, ethyl (2,4,6-trimethylbenzoyl) phenylphosphonate and diphenyl dimethoxyacetophenone.

[0026] The present invention also provides a method for preparing the hydrophilic coating on the surface of the interventional guidewire, comprising the following steps:

[0027] (i) Preparation of the inner layer: Add polyacrylate to methyl ethyl ketone solvent, stir for 30-60 min until completely dissolved, add coupling agent, continue stirring, and filter;

[0028] (ii) Preparation of outer layer: polyurethane and 1,3-propylene glycol cyclic sulfate are added to methyl ethyl ketone solvent and stirred for 30 to 60 minutes until they are completely dissolved, a crosslinking agent and a photoinitiator are added, stirring is continued, and filtering is performed.

[0029] The present invention also provides a preparation process of an interventional guidewire, including a coating process of the hydrophilic coating on the surface of the interventional guidewire, wherein the coating process includes the following steps:

[0030] (1) Immerse the cleaned interventional guide wire into the inner solution;

[0031] (2) immersing the interventional guide wire obtained in step (1) into the outer layer solution;

[0032] (3) The interventional guide wire that has completed step (2) is rinsed with physiological buffer and then dried.

[0033] In some embodiments, the outer layer material of the interventional guide wire is polyetheramide or perfluoro copolymer.

[0034] The present invention also provides application of the hydrophilic coating on the surface of the interventional guidewire in preparing the interventional guidewire.

[0035] In summary, compared with the prior art, the present invention achieves the following technical effects:

[0036] 1. The hydrophilic coating of the present invention has strong adhesion to the surface of the polyetheramide or perfluoro copolymer interventional guidewire, which can prevent the coating from falling off or being damaged during operation, thereby ensuring the long-term stability of the coating.

[0037] 2. The hydrophilic coating of the present invention has extremely strong hydrophilicity, can absorb water and form a lubricating water layer on the surface, reduce the friction coefficient, thereby reducing tissue damage, improving the smoothness of operation, having good lubricity and strong self-cleaning ability.

[0038] 3. The coating surface of the present invention can form a stable water film, which effectively prevents the adhesion of blood or other biological substances on the surface of the guide wire, reduces the formation of thrombus, and improves the safety of the guide wire in clinical use. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0040] Figure 1 Schematic diagram of coating an interventional guidewire with the hydrophilic coating of the present invention. DETAILED DESCRIPTION

[0041] In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only embodiments of a part of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work should fall within the scope of protection of the present invention.

[0042] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials and reagents used are all commercially available unless otherwise specified.

[0043] Main raw material sources:

[0044] Polyacrylate: 24938-16-7, Wuhan Kangqiong Biopharmaceutical Technology Co., Ltd.;

[0045] Polyacrylic acid acrylamide: T24543, Shanghai Yuanye Biotechnology Co., Ltd.;

[0046] Coupling agent: γ-glycidyloxypropyltrimethoxysilane, G107576, Aladdin;

[0047] Methyl ethyl ketone solvent: Xiamen Minghuiyang Chemical Co., Ltd.;

[0048] Polyurethane: Tengyuan Chemical;

[0049] 1,3-Propanediol cyclic sulfate: Huaxiang Kejie;

[0050] Polyvinylpyrrolidone: UPS43, Huzhou Shenhua;

[0051] Cross-linking agent: glyceryl triacrylate, G00320, Shanghai Xingui Biotechnology Co., Ltd.;

[0052] Photoinitiator: 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)butanone, Huada Chemical.

[0053] The hydrophilic coating ratios of the embodiments and comparative examples are shown in Table 1:

[0054] Table 1 Proportions of hydrophilic coatings in Examples and Comparative Examples (parts by weight)

[0055]

[0056] Preparation process

[0057] The preparation method of the hydrophilic coating of the interventional guide wire comprises the following steps:

[0058] (1) Preparation of the inner layer solution: Add polyacrylate to methyl ethyl ketone solvent, stir at room temperature (20-25°C) for 60 min until completely dissolved, add coupling agent and continue stirring, filter through a 0.45 μm filter to ensure the purity of the solution and prevent particulate impurities;

[0059] (2) Preparation of outer layer solution: Add polyurethane and 1,3-propylene glycol cyclic sulfate into methyl ethyl ketone solvent, stir at 40-50 °C for 60 min until completely dissolved, add cross-linking agent and photoinitiator and continue stirring for 30 min, filter through a 0.45 μm filter to prevent impurities from affecting the coating quality.

[0060] (3) Preparation of an ultra-smooth hydrophilic coating for an interventional guidewire: The inner layer solution obtained in step (1) is applied to the surface of the guidewire, and then dried in an oven at 60°C to form a bottom film. The outer layer solution obtained in step (2) is applied to the bottom film, and then cured using 365nm UV for 2 min.

[0061] Test methods and results

[0062] (1) Adhesion performance test:

[0063] Adhesion test is carried out by cross-cut method. The specific steps are as follows:

[0064] Referring to the ratios of each embodiment and comparative example, the inner layer solution and the outer layer solution are sequentially cured on a TPU (thermoplastic polyurethane) plate, a polyetheramide plate and a polytetrafluoroethylene plate to form a coating, and a 6×6 cross grid is drawn on the surface of the guide wire coating with a grid spacing of 1 mm. Use 3M tape to stick to the drawn grid surface to ensure that the tape is completely covered. Quickly tear off the tape and observe the coating falling off from the substrate. According to the number of grids that fall off, they are graded as 0, 1, 2, 3, 4, and 5, respectively. Grade 0 means that there is no coating falling off, and grade 5 means a large amount of falling off.

[0065] Water resistance test:

[0066] Referring to the proportions of the embodiments and comparative examples, the inner layer solution was cured into coatings on TPU plates, polyetheramide plates and polytetrafluoroethylene plates, respectively. The samples were placed in distilled water at 25±1°C and taken out after 48 hours to observe the surface phenomena of the samples (whether there were bubbles, wrinkles or whitening).

[0067] The results are shown in Tables 2 and 3:

[0068] Table 2 Adhesion test results (grade)

[0069]

[0070] Table 3 Water resistance test results of different coatings

[0071]

[0072] From the results in Tables 2 and 3, it can be seen that the hydrophilic coating prepared in the embodiment can reach the adhesion of 0~1 level to polyetheramide and polytetrafluoroethylene sheets. After long-term immersion in water, there is no blistering, wrinkling, or whitening. The coating has good water resistance, and the adhesion to TPU sheets reaches 2~3 levels, with a small amount of wrinkling and whitening. In Comparative Example 1, polyacrylic acid acrylamide is used in the inner layer of the coating, and polyurethane is not added in Comparative Example 2. The adhesion of the coating is reduced to 4~5 levels, and the water resistance is poor. In Comparative Example 3, the effect of excessive addition of polyurethane on adhesion is low. In Comparative Example 4, polyvinyl pyrrolidone is used to replace polyurethane in the outer layer, which has little effect on the adhesion of the TPU sheet, but the adhesion of polyetheramide and polytetrafluoroethylene sheets is significantly reduced, and blistering, wrinkling, and whitening occur at the same time. In Comparative Example 5, 1,3-propylene glycol cyclic sulfate is not added, and the adhesion and water resistance of the coating are poor. It is shown that the hydrophilic coating of the present invention has strong adhesion to the guide wire with polyetheramide and polytetrafluoroethylene as the outer layer material and good water resistance.

[0073] (2) Contact angle test:

[0074] Referring to the ratios of each embodiment and comparative example, a hydrophilic coating is cured on a TPU guidewire, a polyetheramide guidewire and a polytetrafluoroethylene guidewire, respectively. Use a microsyringe to drip a drop of water on the surface of the guidewire coating, about 2 μL. After the droplet contacts the surface of the guidewire, immediately use a video optical contact angle tension meter (LAUDA Scientific, LSA100) to take a side image of the droplet, use the contact angle measurement software to analyze the droplet profile, and calculate the contact angle. The smaller the contact angle, the stronger the surface hydrophilicity. Among them, the contact angle less than 15° is recorded as Class A, the contact angle of 15°~25° is recorded as Class B, the contact angle of 25°~45° is recorded as Class C, and the contact angle greater than 45° is recorded as Class D.

[0075] The results are shown in Table 4:

[0076] Table 4 Contact angle test results (level)

[0077]

[0078] The smaller the contact angle of the hydrophilic coating, the stronger the wettability of the liquid on its surface, and the better the hydrophilic performance. As shown in Table 4, the contact angle of the hydrophilic coating prepared in the embodiment on polyetheramide and polytetrafluoroethylene sheets is less than 15°, and the contact angle of the TPU sheet is less than 25°. In Comparative Example 1, polyacrylic acid acrylamide is used in the inner layer of the coating, which has no effect on the contact angle of the coating. In Comparative Example 2, polyurethane is not added, and the contact angle of the coating is reduced to Class C. In Comparative Example 3, excessive addition of polyurethane has a low effect on the hydrophilic performance. In Comparative Example 4, polyvinyl pyrrolidone is used to replace polyurethane in the outer layer. In Comparative Example 5, 1,3-propylene glycol cyclic sulfate is not added, and the hydrophilic performance of the coating is significantly reduced. It shows that the hydrophilic coating of the present invention has excellent hydrophilic performance for guide wires with polyetheramide and polytetrafluoroethylene as the outer layer material, has a high surface energy, is suitable for use in high wettability and low friction environments, and improves the sliding performance in blood vessels or cavities. In addition, the good hydrophilicity of the guide wire shows excellent self-cleaning performance.

[0079] (3) Friction coefficient test:

[0080] Referring to the ratios of the embodiments and comparative examples, a hydrophilic coating is cured on the polyetheramide guide wire. Referring to the ASTMD1984 standard, the guide wire is soaked in a matrix of physiological saline and physiological saline containing plasma, the holding force is 4N, the number of friction tests is 25 times, the test sample length is 20cm, the pulling speed is 300mm / min, the test temperature is room temperature (25°C), and the friction coefficient COF in physiological saline and physiological saline containing plasma is tested on a friction force tester; wherein, the friction coefficient COF is less than 0.01 and is recorded as A, the friction coefficient COF is 0.01~0.015 and is recorded as B, the friction coefficient COF is 0.015~0.02 and is recorded as C, the friction coefficient COF is 0.02~0.03 and is recorded as D, the friction coefficient COF is greater than 0.03 and is recorded as E, the smaller the friction coefficient, the better the lubricity, and vice versa.

[0081] The results are shown in Table 5:

[0082] Table 5 Test results of smoothness of hydrophilic coating guide wire

[0083]

[0084] As shown in Table 5, in Comparative Example 1, polyacrylic acid acrylamide is used in the inner layer of the coating, polyurethane is not added in Comparative Example 2, polyurethane is added too much in Comparative Example 3, polyvinyl pyrrolidone is used to replace polyurethane in the outer layer in Comparative Example 4, and 1,3-propylene glycol cyclic sulfate is not added in Comparative Example 5, all of which show poor sliding properties and durability, and the guide wire will generate more resistance during use, resulting in difficulty in smoothly passing through complex or narrow channels during in vivo operation. The hydrophilic coating prepared in the embodiment of the present application has good slipperiness, exhibits low friction resistance, and can reduce the interaction between blood and the guide wire.

[0085] 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 principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A hydrophilic coating on the surface of an interventional guide wire, characterized in that: The hydrophilic coating on the surface of the interventional guidewire comprises an inner layer and an outer layer, and the inner layer comprises the following components in parts by weight: Polyacrylate 5-15 parts; 1~5 parts of coupling agent; 50-60 parts of methyl ethyl ketone solvent; The outer layer comprises the following components: 10-30 parts of polyurethane; 1-5 parts of 1,3-propylene glycol cyclic sulfate; 1~3 parts of cross-linking agent; 1~3 parts of photoinitiator; 90-100 parts of methyl ethyl ketone solvent; The outer layer material of the interventional guidewire is polyetheramide or perfluoro copolymer; The mass ratio of the polyacrylate to the coupling agent is (1-3):1; The mass ratio of the polyurethane to 1,3-propylene glycol cyclic sulfate is (2-6):

1.

2. The hydrophilic coating on the surface of the interventional guidewire according to claim 1, characterized in that: The coupling agent is any one or more of a silane coupling agent, an epoxy coupling agent and a carboxylic acid coupling agent.

3. The hydrophilic coating on the surface of the interventional guidewire according to claim 1, characterized in that: The cross-linking agent is any one or more of glycerol triacrylate, ethylene glycol diacrylate, hexamethylene glycol diacrylate, polyethylene glycol diacrylate and 1,6-hexanediol diacrylate.

4. The hydrophilic coating on the surface of the interventional guidewire according to claim 1, characterized in that: The photoinitiator is any one or more of 2-hydroxy-2-methylpropiophenone, 1-hydroxycyclohexyl phenyl ketone, benzophenone, methylphenylglycine, ethyl (2,4,6-trimethylbenzoyl) phenylphosphonate and diphenyl dimethoxyacetophenone.

5. The method for preparing a hydrophilic coating on the surface of an interventional guidewire according to any one of claims 1 to 4, characterized in that: The steps include: (i) Preparation of inner layer: Add polyacrylate into methyl ethyl ketone solvent, stir until completely dissolved, add coupling agent, continue stirring, and filter; (ii) Preparation of the outer layer: polyurethane and 1,3-propylene glycol cyclic sulfate are added to methyl ethyl ketone solvent, stirred until completely dissolved, a crosslinking agent and a photoinitiator are added, stirring is continued, and filtering is performed.

6. A process for preparing an interventional guide wire, characterized in that: A coating process comprising using the hydrophilic coating on the surface of the interventional guidewire according to any one of claims 1 to 4, wherein the coating process comprises the following steps: (1) Immerse the cleaned interventional guide wire into the inner solution; (2) immersing the interventional guide wire obtained in step (1) into the outer layer solution; (3) The interventional guide wire that has completed step (2) is rinsed with physiological buffer and then dried.

7. The preparation process according to claim 6, characterized in that: The outer layer material of the interventional guide wire is polyetheramide or perfluoro copolymer.

8. Use of the hydrophilic coating on the surface of an interventional guidewire according to any one of claims 1 to 4 in the preparation of an interventional guidewire.

Images