A neurovascular micro guide wire and a preparation method and application thereof

Abstract

The application provides a neurovascular micro guide wire and a preparation method and application thereof. The guide wire comprises an inner layer structure, a coating layer structure and a head end structure; the inner layer structure is a core wire composed of stainless steel; the coating layer structure comprises the following raw materials in parts by weight: polydimethylsiloxane 40-60 parts, fluorovinyl ether 5-20 parts, epoxy adhesive 10-20 parts and antibacterial agent 0.5-2 parts; the head end structure comprises the following raw materials in parts by weight: polyether ether ketone 30-60 parts and phosphoric acid acrylate 0.5-2 parts; and the head end structure is uniformly distributed with trapezoidal groove structure formed by laser etching. The application effectively reduces the frictional resistance of the guide wire in blood vessels, improves the passability and stability of the guide wire in a complex blood vessel path; and the guide wire has excellent shaping maintaining capacity and anti-rebound performance on the basis of maintaining good flexibility.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a neurovascular micro guide wire and a preparation method and application thereof. BACKGROUND

[0002] In the field of neurointervention, micro guide wires are important interventional devices for crossing intracranial blood vessels and establishing operation paths. The flexibility, controllability and vascular adaptability of the micro guide wires directly affect the safety and success rate of the operation. In the prior art, in order to balance the pushability and softness, the micro guide wire is often divided into two segments, i.e., the proximal end is made of stainless steel to ensure sufficient pushability and rigidity, and the distal end is made of nickel-titanium alloy to provide good flexibility and shape memory performance, so that the micro guide wire is more easily adapted to the complex curved path of the cerebral blood vessels and reduces the stimulation and damage to the blood vessel wall. However, the nickel-titanium alloy raw material is expensive, the processing technology is complex, and the connection technology of different materials has problems such as unstable structure and insufficient connection reliability, resulting in high overall production cost, which is not conducive to popularization and large-scale production.

[0003] In addition, the existing micro guide wire still has the problems of poor passability and slow response in control when entering the high-curved or narrow blood vessel area. On the one hand, the flexible structure of the distal end is prone to deformation and rebound in a high-curved environment, resulting in inaccurate target positioning. On the other hand, the surface structure and material combination of the micro guide wire are relatively simple, which is prone to "slipping" in the blood vessel or lacks sufficient shape retention, affecting the navigation accuracy of the doctor, and even increasing the risk of penetrating the blood vessel or misentering the branch.

[0004] Therefore, there is still room for improvement in the structural design and material combination of the existing micro guide wire, and it is urgent to develop a neurovascular micro guide wire with lower cost, better flexibility and stronger passability while maintaining stable performance. SUMMARY

[0005] In view of the defects in the prior art, the present application provides a neurovascular micro guide wire and a preparation method and application thereof. The present application optimizes the cladding layer material, laser etches a trapezoidal groove structure, reduces the material cost, and retains good flexibility, rigidity and balance performance.

[0006] The present application provides a neurovascular micro guide wire, which comprises an inner layer structure, a cladding layer structure and a head end structure.

[0007] The inner layer structure is a core wire composed of stainless steel.

[0008] The cladding layer structure comprises the following raw materials in terms of weight parts:

[0009] 40-60 parts of polydimethylsiloxane, 5-20 parts of fluorovinyl ether, 10-20 parts of epoxy adhesive, 0.5-2 parts of antibacterial agent;

[0010] The head end structure comprises the following raw materials in parts by weight:

[0011] Polyether ether ketone 30~60 parts, phosphoric acid acrylate 0.5~2 parts;

[0012] The head end structure is uniformly distributed with trapezoidal groove structures formed by laser etching.

[0013] The present application adopts polydimethylsiloxane (PDMS) and fluorovinyl ether to cooperatively construct a coating layer, the fluorovinyl ether can form a surface enrichment zone in the PDMS, so that the guide wire surface exhibits an ultra-low friction interface, the PDMS provides an elastic substrate, the fluorovinyl ether provides a hydrophobic and anti-adhesion interface, and the two form a double lubrication and flexibility synergy mechanism, which not only guarantees the softness of the distal end, but also improves the surface lubricity; polyether ether ketone and phosphoric acid acrylate are compounded, after dispersing or in-situ blending the phosphoric acid acrylate in the polyether ether ketone matrix, the material can be given controllable flexibility, and the local bending in the navigation operation of the head end is improved.

[0014] The trapezoidal grooves adopted in the present application have a small “occlusion” or “interlacing” between the structures after being deformed by external force, and when the material elastically returns, micro-friction and interface slip are generated in the material, which increases the friction regulation between the guide wire and the inner wall of the blood vessel, and is beneficial to realize the micro-positioning effect of the navigation position.

[0015] In some embodiments, the mass ratio of the polydimethylsiloxane and the fluorovinyl ether is (3~6):1; the present application finds through a large amount of research that the mass ratio of the polydimethylsiloxane and the fluorovinyl ether can affect the performance of the guide wire, and within the ratio range, the low friction and anti-adhesion properties of the fluorovinyl ether component can be maximized on the premise of ensuring the flexibility and shape adaptability of the guide wire; if the fluorovinyl ether content is too low, the lubricating effect is not obvious; if it is too high, the compatibility may be poor or the mechanical strength may be reduced; the present application realizes the synergy balance of flexible support and surface lubrication in the ratio, which not only maintains the stability of the guide wire during advancement, but also ensures excellent passability and operation responsiveness in complex blood vessel paths.

[0016] In some embodiments, in the trapezoidal groove structure, the upper wide part of the trapezoidal groove is 5~10 μm, and the depth is 5~10 μm; if the groove width and depth are too small, it will be difficult to form an effective stress disturbance zone, and the shape retention ability will be reduced; and if the size is too large, the structural integrity of the head end material will be damaged, and the risk of blood vessel stimulation will be increased.

[0017] In some embodiments, the coverage area of the trapezoidal groove structure is 50-70%; the trapezoidal groove dissipates energy through micro-deformation, so that the guide wire generates more energy dissipation when stressed, avoiding stress concentration caused by elastic recovery. The coverage area of 50-70% can balance the shape retention and fluid dynamics while ensuring the locking effect, thereby avoiding the increase of friction caused by too dense structure.

[0018] In some embodiments, the antibacterial agent is 2-methacryloyloxyethylphosphocholine or a polymer thereof.

[0019] In some embodiments, the polyether ether ketone has a heat distortion temperature greater than 150 DEG C and a tensile strength not less than 90 MPa.

[0020] In some embodiments, the core wire has a diameter of 0.2-0.4 mm, and the head structure has a length of 5-15 mm.

[0021] The application also provides a preparation method of the neurovascular micro guide wire, comprising the following steps:

[0022] (1) The raw materials are weighed by weight parts, and are coated on the outer surface of the core wire by blending extrusion, and the coated structure is heat cured at 120-150 DEG C to form a coating layer structure;

[0023] (2) The head structure is coated on the distal end of the guide wire, and the head structure is formed into a fixed length of the head section by a molding process;

[0024] (3) The trapezoidal groove structure is formed on the head structure by laser etching.

[0025] In some embodiments, the laser etching in step (3) is performed by femtosecond laser, and the laser wavelength is 800-1200 nm and the pulse width is 200-500 fs.

[0026] The application also provides an application of the neurovascular micro guide wire in preparing a vascular interventional instrument or a neural interventional instrument.

[0027] In summary, compared with the prior art, the application achieves the following technical effects:

[0028] (1) The application uses a composite material of polydimethylsiloxane and fluorovinyl ether to construct the coating layer, which effectively reduces the frictional resistance of the guide wire in the blood vessel, and improves the passability and stability of the guide wire in the complex blood vessel path. At the same time, the head structure introduces a high modulus polymer and a functional monomer composite material, and combines with a fine laser etching trapezoidal groove structure design, so that the guide wire has excellent shape retention ability and anti-rebound performance on the basis of good flexibility.

[0029] (2) The present application can achieve a good balance among structural continuity, pushing property and distal responsiveness without relying on nickel-titanium alloy, simplify the preparation process, reduce the cost, and greatly improve the steering performance and clinical applicability of the guide wire, which has significant technical progress and application value. DETAILED DESCRIPTION

[0030] In order for those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor should belong to the scope of protection of the present application.

[0031] Raw materials:

[0032] Polydimethylsiloxane: 1317318, Dow Corning;

[0033] Fluorinated vinyl ether #1: trifluoromethyl trifluorovinyl ether, 1187-93-5, Debiec;

[0034] Fluorinated vinyl ether #2: perfluoro-n-propyl vinyl ether, P73060-250g, Jiezhisheng Biochemical;

[0035] Epoxy-based adhesive: B5005321073, 3M Scotch-Weld epoxy resin adhesive DP190;

[0036] Antibacterial agent: 2-methacryloyloxyethyl phosphorylcholine, 730114, Merck;

[0037] Polyether ether ketone: LH-66, Wuhan Luhao New Material Co., Ltd.;

[0038] Phosphoric acid acrylate: DO 1100 phosphate acrylate, EVER RAY.

[0039] The preparation methods of the neurovascular micro guide wire in different embodiments and comparative examples are as follows:

[0040] Embodiment 1

[0041] The preparation method of the neurovascular micro guide wire of the present embodiment is as follows:

[0042] (1) Processing of the core wire: using medical-grade stainless steel wire material SUS304 to prepare the core wire, adopting mechanical processing method, using a wire drawing machine to draw step by step, reducing the diameter step by step at each stage, and accurately controlling the final diameter of the core wire to be 0.3 mm.

[0043] (2) Preparation of the coating layer:

[0044] Polydimethylsiloxane 40 parts, fluoro vinyl ether #1 5 parts, epoxy adhesive 10 parts, antibacterial agent 0.5 parts are weighed by weight parts;

[0045] The specific steps are: stirring in a vacuum mixer for 30 minutes (rotation speed 300 rpm, vacuum-0.09 MPa), heating the mixture to 60℃, and then using extrusion coating process to coat it to the surface of the core wire, the extrusion nozzle aperture is 0.5 mm, the linear speed is set to 10 cm / min, and the whole is heated and cured in a continuous heat curing furnace at 140℃ for 10 minutes to form a uniform coating layer, the coating thickness is about 50 μm, and the overall diameter of the coated guide wire is about 0.80 mm.

[0046] (3) Formation of head end structure:

[0047] The head end section is prepared by mold coating process, and the head end raw material composition is as follows (weight parts): polyether ether ketone 30 parts, propylene acrylate phosphate 0.5 parts;

[0048] The process parameters are as follows: after mixing the raw materials, the double screw extruder is used for granulation, heating to 390℃, and then injection molding is carried out by using precision mold to form the head end section, and the mold pressure is 15 MPa, the holding time is 60 seconds, and the head end is shaped after cooling and demolding.

[0049] (4) Laser etching to form trapezoidal groove structure:

[0050] The femtosecond laser equipment (pulse width 300 fs, wavelength 1030 nm) is used to etch the trapezoidal groove on the head end structure: the trapezoidal groove size is 8 μm wide at the top and 4 μm wide at the bottom, the depth is 7 μm; the groove spacing (center distance of the groove) is 20 μm; the groove coverage range is 60% of the head end surface area; the laser scanning speed is 2 mm / s, the repetition frequency is 500 kHz, and the energy density is 1.2 J / cm 2 .

[0051] Example 2

[0052] The difference from example 1 is that in the coating layer raw material, polydimethylsiloxane 45 parts, fluoro vinyl ether #1 15 parts.

[0053] Example 3

[0054] The difference from example 1 is that in the coating layer raw material, polydimethylsiloxane 60 parts, fluoro vinyl ether 20 parts, epoxy adhesive 20 parts, antibacterial agent 2 parts; in the head end structure, polyether ether ketone 60 parts, propylene acrylate phosphate 2 parts.

[0055] Example 4

[0056] The difference from Example 1 is that the fluoro vinyl ether #1 in the cladding material is replaced by fluoro vinyl ether #2.

[0057] Example 5

[0058] The difference from Example 1 is that the femtosecond laser device (pulse width 300 fs, wavelength 1030 nm) is used to perform trapezoidal groove etching on the head-end structure: trapezoidal groove size: upper width 10 μm, lower width 6 μm, depth 10 μm.

[0059] Example 6

[0060] The difference from Example 1 is that the femtosecond laser device (pulse width 300 fs, wavelength 1030 nm) is used to perform trapezoidal groove etching on the head-end structure: trapezoidal groove size: upper width 5 μm, lower width 2 μm, depth 5 μm.

[0061] Comparative Example 1

[0062] The difference from Example 2 is that no cladding material is added.

[0063] Comparative Example 2

[0064] The difference from Example 2 is that the proximal end portion of the core wire is selected from medical-grade stainless steel wire SUS304, and the distal end portion is selected from nickel-titanium alloy wire, and a precision laser welding machine (wavelength 1064 nm) is used for spot welding, and a medium-temperature heat treatment (450°C x 5 minutes) is used after welding to eliminate stress; no cladding material is added.

[0065] Comparative Example 3

[0066] The difference from Example 2 is that the polydimethylsiloxane in the cladding material is 60 parts, and no fluoro vinyl ether is added.

[0067] Comparative Example 4

[0068] The difference from Example 2 is that the head-end structure material is the same as the cladding layer.

[0069] Comparative Example 5

[0070] The difference from Example 2 is that no laser etching is performed on the head-end structure.

[0071] <TEST METHODS>

[0072] (1) Guide wire passability test

[0073] In order to evaluate the passability of neurovascular micro guide wires in complex vascular paths, this experiment uses a blood vessel model made of silicone, and tests it in a standardized environment. The specific steps are as follows:

[0074] a. Prepare the guidewire sample: Select a neurovascular guidewire product with a length of 120 cm, ensure that the sample has no obvious damage, and clean the surface before use. Pre-wet in normal saline for 10 minutes to simulate its use in the body environment.

[0075] b. Prepare the vascular model: Use the Biomodels® Neurovascular Phantom model, which contains multiple curvature structures such as 90° turns and S-shaped structures, with an inner diameter of 2.0 mm. Maintain the temperature at 37°C in a constant temperature bath.

[0076] c. Test: Fix the proximal end of the guidewire to the Instron 5943 universal material tester, parallel and linearly connect the model inlet, use the Zwick / Roell Z0.5 material testing machine with clamps to advance, set the guidewire advancement speed to 5 mm / s, advance the guidewire along the vascular path in the model until the guidewire successfully passes through the end of the model, record the maximum pushing force (N) and average pushing force (N), repeat the test 5 times, calculate the average value and standard deviation.

[0077] (2) Steering responsiveness test

[0078] This test item can evaluate whether the distal end of the guidewire responds quickly and accurately after the proximal end is rotated. The specific steps are as follows:

[0079] Select a neurovascular micro-guidewire product with a length of 100 cm, pre-wet in normal saline for 10 minutes, insert into the transparent curved vascular model (Biomodels® Neurovascular Phantom), use the Thorlabs PRM1Z8 rotating clamp to fix the proximal end of the guidewire, and set the clamp rotation angle to 30° and 60°. The Thorlabs DC2100 controller drives the rotating clamp to achieve stable rotation angle setting, while the Photron FASTCAM Mini UX100 high-speed camera system is used to shoot the response process of the distal end. Use ImageJ + TrackMate plugin to analyze the angle of the video. Automatically identify the rotation angle of the distal end through image recognition software, and compare it with the rotation angle of the proximal end to calculate the angle error of the distal end response.

[0080] (3) Springback rate test

[0081] Select a neurovascular micro guidewire product with a length of 100 cm, pre-wet in normal saline for 10 minutes, use Zwick / Roell Z2.5 material testing machine to bend the head end of the guidewire to 60°, put the bent head end of the guidewire into 37℃ normal saline, use Leica M125 microscope with LAS X software for high-definition imaging, record the rebound process of the head end of the guidewire after release. Use ImageJ software to measure the vertical distance change between the bending point of the head end of the guidewire and the original axis, i.e. the rebound displacement (unit: mm).

[0082] (4) Shaping force

[0083] Select a neurovascular micro guidewire product with a length of 100 cm, pre-wet in normal saline for 10 minutes, use Zwick / Roell Z2.5 material testing machine with custom fixtures to fix one end of the guidewire in the fixture, ensure that the guidewire always remains straight and does not slide during the test. Use Shimpo FGJN-10X thrust meter to gradually apply force, apply enough force to the head end of the guidewire to bend the guidewire to a 90° angle. During the force application process, the thrust meter will accurately record the maximum force value applied, and the force change will be displayed through the display interface of the device, each sample is repeated 3 times, and the average value and standard deviation are calculated.

[0084] The test results are shown in Tables 1-2:

[0085] Table 1 Test results of examples

[0086]

[0087] Table 2 Test results of comparative examples

[0088]

[0089] From the test results of Table 1 and Table 2, the passing force of Comparative Examples 1 and 3 is less than that of Example 2, indicating that the coating layer constructed by the fluorinated vinyl ether and the polydimethylsiloxane used in the application significantly reduces the frictional resistance of the guide wire to the blood vessel wall and improves the passing efficiency in the complex blood vessel environment. Comparative Example 2 uses a traditional structure, i.e., a near-end stainless steel and a far-end nickel-titanium alloy, and is connected by laser welding. Compared with other comparative examples, it has obvious advantages in performance, showing good passing and steering performance, but has disadvantages such as complex structure connection, stress concentration at the welding interface, high preparation cost, etc. The application can achieve similar or even better results without using nickel-titanium alloy, with the advantages of economy and process simplification. Comparative Example 4 cancels the independent head structure and only continues the coating layer material to the far end, and its flexibility and shaping ability decrease significantly, the head end cannot form an effective support structure, and the far end navigation force is insufficient. Comparative Example 5 does not introduce laser etching microstructure, resulting in a decrease in anti-rebound performance, indicating that the guide wire head end is difficult to maintain the preset shaped state, and the navigation stability decreases. The trapezoidal groove structure formed by laser etching can form damping and support effects at the micro level, and is one of the core processes to improve the steering precision and shaping stability of the guide wire.

[0090] The guide wire made by Examples 1-6 of the application can smoothly pass through the 90° and S-shaped high-curvature simulated blood vessel models, the pushing resistance is reduced to 0.30 N at the lowest, the response error is controlled within 3.6°-4.2°, the head end adopts a high-modulus polyether ether ketone (PEEK) and a phosphoric acid acrylate functional monomer composite material, combined with a micro-groove structure design, the guide wire head end has good shape retention after shaping, the rebound displacement is reduced to 0.6 mm at the lowest, and the force required for the guide wire shaping is maintained within the range of 0.8-0.9 N·cm.

[0091] The above only describes the preferred embodiments of the application and is not intended to limit the application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the application shall be included in the protection scope of the application.

Claims

1. A neurovascular microguide wire, comprising: The inner layer structure, the cladding layer structure and the head end structure are included; The inner layer structure is a core wire composed of stainless steel; The cladding layer structure includes the following raw materials in parts by weight: Polydimethylsiloxane 40-60 parts, fluorovinyl ether 5-20 parts, epoxy adhesive 10-20 parts, antibacterial agent 0.5-2 parts; The head end structure includes the following raw materials in parts by weight: Polyether ether ketone 30-60 parts, phosphoric acid acrylate 0.5-2 parts; The head end structure is uniformly distributed with trapezoidal groove structure formed by laser etching; The mass ratio of polydimethylsiloxane to fluorovinyl ether is (3-6):1; The fluorovinyl ether is any one of trifluoromethyl trifluorovinyl ether or perfluoro-n-propyl vinyl ether.

2. The neurovascular microguide wire of claim 1, wherein, In the trapezoidal groove structure, the upper wide part of the trapezoidal groove is 5-10 μm, and the depth is 5-10 μm.

3. The neurovascular microguide wire of claim 1, wherein, The coverage area of the trapezoidal groove structure is 50-70%.

4. The neurovascular microguide wire of claim 1, wherein, The antibacterial agent is 2-methacryloyloxyethylphosphocholine or its polymer.

5. The neurovascular microguide wire of claim 1, wherein, The polyether ether ketone has a heat distortion temperature greater than 150℃ and a tensile strength not less than 90 MPa.

6. The neurovascular microguide wire of claim 1, wherein, The core wire has a diameter of 0.2-0.4 mm, and the head end structure has a length of 5-15 mm.

7. The method of manufacturing a neurovascular microguide wire according to any one of claims 1 to 6, wherein, The method includes the following steps: (1) The raw materials of the cladding layer structure are weighed in parts by weight, and are coated on the outer surface of the core wire by blending extrusion, and the coated structure is heat cured at 120-150℃ to form the cladding layer structure; (2) The head end structure is coated on the distal end of the guide wire, and is formed into a head end section with a fixed length by a molding process; (3) The trapezoidal groove structure is formed on the head end structure by laser etching.

8. The preparation method according to claim 7, characterized in that, In step (3), the laser etching is performed by femtosecond laser, and the laser wavelength is 800-1200 nm, and the pulse width is 200-500 fs.

9. Use of the neurovascular micro guide wire of any one of claims 1-6 in the preparation of a vascular interventional instrument or a neural interventional instrument.

Images