Distal access catheter and preparation method thereof

Abstract

The invention relates to the technical field of medical instruments, and particularly discloses a far-end access catheter and a preparation method thereof. The preparation method of the far-end passage catheter comprises the following steps: the far-end passage catheter consists of a catheter body, a stress tube, a Luer seat and a guide sheath; the tube body sequentially comprises a PTFE lining layer, a coil layer, a braid layer, a developing ring and a plastic layer from inside to outside from the conical end part of the stress tube; coating the outer surface of the plastic layer with paint to form a coating, drying, and sterilizing with ethylene oxide. And obtaining the far-end access catheter. The prepared catheter is good in antifouling property and lubricity and excellent in antibacterial effect, and the infection risk can be effectively reduced.

Description

Technical Field

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

[0002] Medical catheters, as tubular medical devices directly connected to the human body interior, play an indispensable role in the medical field. Their application scope is extensive, covering multiple important aspects such as drainage, blood transmission, assisting in the introduction of other medical instruments, and detecting the biological condition with the help of sensing elements. The distal access catheter is designed to reach the difficult-to-access distal regions (such as small blood vessels in the brain) deep into the body through blood vessels or other body cavities. It mainly serves as a "channel bridge" to help other instruments (such as microcatheters, coils, stents, etc.) or drugs accurately reach the target site, improving the surgical accuracy. In recent years, with the steady improvement of people's quality of life, the clinical requirements for the performance of medical catheters have become increasingly stringent, which has greatly promoted the in-depth development of catheter-related research, and continuous technological innovation is needed to meet the growing clinical needs.

[0003] Currently, the main materials for making medical catheters are hydrophobic materials such as polyvinyl chloride and silicone rubber. Although these materials provide many conveniences for clinical diagnosis and treatment, they also expose many problems in the actual application process. Due to the large surface friction resistance of hydrophobic materials, they are extremely likely to cause damage to blood vessels and cavity tissues during use, thereby triggering inflammation and bringing additional pain to patients. Taking the commonly used urinary catheter in clinical practice as an example, to improve its lubricity, lubricants such as glycerol and silicone oil are usually coated on the catheter surface, but this method has an unsatisfactory effect on improving the catheter lubricity and there are many inconveniences in actual operation.

[0004] CN118406273A discloses a TPU material and its production process applied to medical catheters, belonging to the technical field of medical materials. This material uses thermoplastic polyurethane (TPU) as the matrix, and by adding modified starch and tungsten powder, it synergistically optimizes the ultrasonic imaging performance. Among them, due to the high porosity of the modified starch, after being made into a medical catheter, it can effectively enhance the ultrasonic imaging clarity. In addition, the surface of the material is coated with ε-polylysine, and its molecular structure is rich in primary amine groups, which can react with residual anhydrides to achieve firm adhesion. This design not only endows the material with excellent antibacterial properties, solves the problem of easy peeling of the ε-polylysine coating, but also improves the original hydrophobicity of the TPU material with its good hydrophilicity, reducing the risk of tissue damage when the medical catheter is inserted into the human body.

[0005] CN110343284A focuses on the field of medical devices, and particularly relates to a method for preparing an antibacterial and anticoagulant coating on the surface of a polyurethane interventional catheter. In this invention, cross-linking reaction occurs between allylsulfonic acid and vinyl acetate on the surface of the polyurethane pipe, significantly improving the bonding force between the coating and the pipe surface, and at the same time successfully introducing sulfonic acid groups with anticoagulant properties. After introducing hydroxyl groups through saponification reaction, further reaction with PEG-PAMAM is carried out to introduce PEG segments with strong hydrophilicity and anticoagulant function into the coating system. It is worth mentioning that the introduced PAMAM can form a complex with Ag⁺ with antibacterial efficacy through coordination, thereby endowing the coating with good antibacterial properties. The raw materials used in this preparation method are low-cost, and the formed coating not only has dual functions of antibacterial and anticoagulant, but also is firmly fixed on the pipe surface through the network structure constructed by cross-linking reaction, ensuring that the coating has excellent durability.

[0006] Surface modification of medical catheters to make them have good lubricity while maintaining physical and mechanical properties has become the focus of current research. It has been found that in the environment of body fluid or tissue fluid, both highly hydrophilic and highly hydrophobic polymer material surfaces have good lubrication performance. However, in clinical practice, highly hydrophilic polymer materials are more favored. Compared with highly hydrophobic materials, highly hydrophilic polymer materials have more excellent surface properties, can effectively reduce the adsorption of bacteria and the like on their surfaces, thereby reducing the risk of infection and improving the safety and effectiveness of medical catheters. Summary of the Invention

[0007] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present invention is to provide a distal access catheter and a preparation method thereof.

[0008] In addition to hydrophilicity and lubrication, the biofilm formed on the surface of the catheter is also a major problem that needs to be solved urgently. Inside the catheter, the attachment of proteins provides an anchor point for bacterial adhesion and biofilm formation, and may cause side effects such as thrombosis. Anti-fouling treatment of the catheter can reduce the initial attachment of microorganisms by repulsion, but the anti-fouling surface does not kill bacteria, and some bacteria will still adhere to the catheter surface and form a biofilm, thereby causing infection.

[0009] Therefore, the present invention provides a coating with antibacterial, antifouling, lubricating properties and the ability to reduce the risks of infection and thrombosis. After the catheter is impregnated in the coating and dried to obtain a coating, polylysine contains a large number of amino groups and is positively charged, and can strongly bind to water molecules through hydrogen bonds and electrostatic interactions. Therefore, it has excellent hydrophilicity. The positive charge can also bind to the negatively charged phospholipids on the surface of bacteria, thereby destroying the cell membrane, inhibiting metabolic activities, reducing biofilm formation, and exhibiting good antibacterial properties. Polylysine is covalently bonded to caffeic acid, and the catechol group in caffeic acid can endow the coating with adhesion in a complex environment and ensure the firmness of the coating. Xanthan gum is combined in a non-covalent manner, which can further endow the coating with good lubricating, hydrophilic and film-forming properties, and can kill bacteria while also resisting the adhesion of proteins, reducing the risks of infection and others.

[0010] To achieve the above object, the present invention provides a distal access catheter, which is characterized by comprising a tube body, a stress tube, a Luer seat and a guiding sheath;

[0011] Wherein, from the tapered end of the stress tube, the tube body sequentially comprises a PTFE inner lining layer, a coil layer, a braided layer, a radiopaque ring and a plastic layer from inside to outside;

[0012] Wherein, the PTFE inner lining layer extends axially from the tapered end of the stress tube to the end of the tube body; the single-sided wall thickness of the PTFE inner lining layer is 0.02 mm;

[0013] Wherein, the coil layer extends axially from the tapered end of the stress tube to the end of the tube body; the coil layer is formed by helically winding a circular metal wire; the material of the coil layer is 304 stainless steel wire or nitinol wire; the wall thickness of the helical winding is set to 0.05 - 0.3 mm, and the pitch of the helical winding is set to 0.07 - 0.35 mm;

[0014] Wherein, the braided layer extends axially from the tapered end of the stress tube to a preset distance from the end of the tube body and does not extend to the end of the tube body; the braided layer is formed by alternately braiding single flat metal wires; the material of the braided layer is 304 stainless steel wire or nitinol wire.

[0015] Wherein, the material used for the braided layer has the same thickness as that used for the coil layer.

[0016] Wherein, the radiopaque ring extends axially from a preset distance from the tapered end of the stress tube to the end of the tube body, and there is an overlapping area between the radiopaque ring and the braided layer; the material of the radiopaque ring is a metal material such as platinum-iridium alloy or tungsten-rhenium alloy.

[0017] Wherein, the plastic layer axially covers from the conical end of the stress tube to the end of the tube body; the material of the plastic layer is at least one of nylon, block polyetheramide elastomer or polyurethane elastomer.

[0018] Wherein, a coating is formed by coating a coating on the outer surface of the plastic layer, specifically, a coating is formed by coating a coating on the outer surface of the plastic layer, drying, and ethylene oxide sterilization.

[0019] The preparation method of the coating includes the following steps:

[0020] X1. Add caffeic acid to MES buffer solution, after ultrasonic dissolution, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide, stir for 20-40 min, then add the MES buffer solution of polylysine, and continue to stir for 10-20 h;

[0021] X2. Add glycine, stir for 10-20 min and then dialyze, then add xanthan gum, and continue to stir for 2-4 h to obtain the coating.

[0022] Further, the mass ratio of caffeic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, N-hydroxysuccinimide, polylysine, and xanthan gum is 1:0.3-0.5:0.1-0.3:1-3:3-5.

[0023] Further, the concentration of caffeic acid in the MES buffer solution is 1-5 wt%.

[0024] Further, the concentration of the MES buffer solution of polylysine is 10-20 wt%.

[0025] Further, the addition amount of glycine is 1-3 times that of caffeic acid.

[0026] Preferably, the preparation method of the coating includes the following steps:

[0027] X1. Add caffeic acid to MES buffer solution, after ultrasonic dissolution, obtain a 1-5 wt% solution, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide, stir for 20-40 min, then add the MES buffer solution of 10-20 wt% polylysine, and continue to stir for 10-20 h;

[0028] X2. Add glycine, stir for 10-20 min and then dialyze, then add xanthan gum, and the mass ratio of caffeic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, N-hydroxysuccinimide, polylysine, xanthan gum, and glycine is 1:0.3-0.5:0.1-0.3:1-3:3-5:1-3, continue to stir for 2-4 h to obtain the coating.

[0029] The present invention also provides a distal access catheter and its application, and the catheter is prepared by the above method.

[0030] Beneficial effects of the present invention:

[0031] 1. Compared with the prior art, the catheter coating prepared by the present invention has good anti-fouling and lubricating properties, excellent antibacterial effect and good firmness.

[0032] 2. In the present invention, the catheter is impregnated in the coating material and then dried to obtain the coating. Polylysine can bind to the negatively charged phospholipids on the surface of bacteria, thereby destroying the cell membrane, inhibiting metabolic activities, reducing the formation of biofilms, and playing a good antibacterial performance. Polylysine and caffeic acid are covalently bonded, and the catechol group in caffeic acid can endow the coating with adhesion in a complex environment and ensure the firmness of the coating. Xanthan gum is combined in a non-covalent manner, which can further endow the coating with good lubricating, hydrophilic and film-forming properties, and can also resist the adhesion of proteins while killing bacteria, reducing the risk of infection and others. Description of the drawings

[0033] Figure 1 It is a structural diagram of the distal access catheter. Detailed implementation manners

[0034] Polylysine, purity: 99%, sourced from Nanjing Qiushi Medical Technology Co., Ltd.

[0035] Escherichia coli, CGMCC1.12883, commercially available, sourced from China General Microbiological Culture Collection Center.

[0036] Staphylococcus aureus, CGMCC1.1282, commercially available, sourced from China General Microbiological Culture Collection Center.

[0037] MES buffer solution, 0.5 mol / L, pH = 6.

[0038] Example 1

[0039] A distal access catheter is composed of a tube body, a stress tube, a Luer seat and a guiding sheath. The specific structural composition is shown in the attached Figure 1 ;

[0040] From the tapered end of the stress tube, the tube body is sequentially composed of a PTFE inner lining layer, a coil layer, a braided layer, a radiopaque ring and a plastic layer from the inside out;

[0041] The PTFE inner lining layer extends axially from the tapered end of the stress tube to the end of the tube body; the single-side wall thickness of the PTFE inner lining layer is 0.02 mm, which is a typical medical material and is non-toxic and harmless to the human body.

[0042] The coil layer axially covers from the tapered end of the stress tube to the end of the tube body; the coil layer is formed by helically winding a circular metal wire, making full use of the tensile resistance and anti-kinking properties of the helical winding structure. The material of the coil layer is 304 stainless steel wire. The wall thickness of the helical winding is set to 0.05 mm, and the pitch of the helical winding is set to 0.07 mm;

[0043] The braided layer axially covers from the tapered end of the stress tube to a preset distance from the end of the tube body and does not extend to the end of the tube body; the braided layer is formed by alternately braiding single flat metal wires; the material of the braided layer is 304 stainless steel wire. Among them, 304 stainless steel wire has good ductility and toughness in metals, which can better ensure that the distal access catheter is not easily deformed. The material used for the braided layer is the same thickness as that used for the coil layer.

[0044] The radiopaque ring axially covers from a preset distance from the tapered end of the stress tube to the end of the tube body, and there is an overlapping area between the radiopaque ring and the braided layer; the material of the radiopaque ring is platinum-iridium alloy.

[0045] The plastic layer axially covers from the tapered end of the stress tube to the end of the tube body; the material of the plastic layer is nylon; the thickness is 0.1 mm;

[0046] A coating is formed by coating the outer surface of the plastic layer, specifically, the outer surface of the plastic layer is coated with a coating, dried, and sterilized with ethylene oxide, where the thickness of the coating is 10 µm;

[0047] The preparation method of the coating includes the following steps, in parts by weight:

[0048] X1. Add 5 parts of caffeic acid to 100 parts of MES buffer solution, ultrasonically dissolve it, then add 2 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1 part of N-hydroxysuccinimide, stir for 30 min, and then add 50 parts of MES buffer solution containing 20 wt% polylysine, and continue to stir for 15 h;

[0049] X2. Add 7.5 parts of glycine, stir for 10 min, then dialyze, and then add 20 parts of xanthan gum, and continue to stir for 3 h to obtain the coating.

[0050] Control Example 1

[0051] It is basically the same as Example 1, except only for the difference in the coating;

[0052] The preparation method of the coating includes the following steps, in parts by weight:

[0053] X1. Add 5 parts of caffeic acid to 100 parts of MES buffer solution. After ultrasonic dissolution, add 2 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1 part of N-hydroxysuccinimide. After stirring for 30 min, add 50 parts of MES buffer solution containing 20 wt% polylysine, and continue stirring for 15 h;

[0054] X2. Add 7.5 parts of glycine, stir for 10 min and then dialyze to obtain the coating.

[0055] Control Example 2

[0056] It is basically the same as Example 1, and the only difference lies in the coating; the coating is an aqueous solution of 20 wt% polylysine.

[0057] Control Example 3

[0058] It is basically the same as Example 1, and the only difference is that gelatin is replaced by gelatin.

[0059] Control Example 4

[0060] It is basically the same as Example 1, and the only difference is that gelatin is replaced by chitosan.

[0061] Test Example 1

[0062] Test the water contact angle, peel strength and friction coefficient of the catheters prepared in the examples and control examples;

[0063] The water contact angle is measured by an optical contact angle measuring instrument. Three different smooth positions are randomly selected on the surface of each sample for measurement, and the average value is finally taken;

[0064] Use a texture analyzer to perform a 90° peel test on the sample. Set the speed of the crosshead to 0.5 mm / s and the displacement to 50 mm. The test is repeated 3 times to obtain the peel strength;

[0065] The friction coefficient is measured by a friction and wear tester. Under the conditions of an applied load and a sliding rate of 1 N and 1 Hz respectively, perform linear reciprocating friction on the sample and analyze the friction coefficient.

[0066] Table 1

[0067]

[0068] The surface of most catheter materials has high hydrophobicity and low surface activity. When in use, due to poor surface lubricity, the friction force when entering the human body is large, which is likely to cause damage and increase the risk of infection. After hydrophilic modification of the catheter, a hydration layer can be formed on the surface. The hydration layer can not only reduce the surface energy, but also play a barrier role to reduce the attachment of bacteria and other microorganisms, thus avoiding the formation of biofilms.

[0069] During the use of the catheter in the human body, since it is always in a liquid environment, its surface becomes soft after absorbing water and its mechanical properties decrease. If the bonding strength between the coating and the catheter is weak after a long period of use, the coating is likely to peel off from the catheter surface, enter the body fluid or adhere to the body, which may also lead to infection risks.

[0070] As can be seen from Table 1, the catheters prepared by the present invention all have a low water contact angle, indicating good hydrophilicity, and thus resulting in excellent lubricity. Compared with Control Example 1, Example 1 has a lower water contact angle and friction coefficient, and better firmness. This may be because xanthan gum is further compounded in Example 1, which can further improve hydrophilicity, thereby reducing the friction coefficient, and can help form a film, thus enhancing the firmness of the coating. In Control Example 2, only polylysine is used as the coating. Although polylysine has excellent hydrophilicity, its binding property with the catheter is poor, so the firmness is the worst. And the catechol group of caffeic acid in the examples has good adhesion and can also play a good adhesion role in a complex environment.

[0071] Compared with Control Examples 3-4, Example 1 has better hydrophilicity and film-forming property of xanthan gum, which can better reduce the friction of the catheter. Gelatin has weak hydrophilicity and poor film-forming property, and the solubility of chitosan is affected by its structure. Therefore, the sample in Example 1 shows the best hydrophilicity, firmness and lubricity.

[0072] Test Example 2

[0073] The distal access catheters prepared in the examples and control examples were tested for antibacterial properties. Bacteria with a concentration of 10 6 cfu / mL were cultured in LB medium for 24 h. After dilution, 100 μL of the diluted sample solution was spread on the catheter surface and cultured on the plate for 48 h. The number of bacteria on the surface of the catheter without coating and the catheters prepared in the examples and control examples was measured to obtain the antibacterial rate.

[0074] Table 2

[0075]

[0076] As can be seen from Table 2, the catheters prepared by the present invention all have good antibacterial properties. This is because the hydrophilic coating can form a hydration layer on the surface. The hydration layer can not only reduce the surface energy, but also act as a barrier to reduce the attachment of bacteria and other microorganisms, thus avoiding the formation of biofilms. In addition, polylysine contains a large number of amino groups and is positively charged. It can strongly bind to water molecules through hydrogen bonds and electrostatic interactions. The positive charge can also bind to the negatively charged phospholipids on the bacterial surface, thereby destroying the cell membrane, inhibiting metabolic activities, reducing biofilm formation, and exhibiting good antibacterial properties. Polylysine and caffeic acid are covalently bonded, and the catechol group in caffeic acid can endow the coating with adhesion in complex environments and ensure the firmness of the coating. Xanthan gum is combined in a non-covalent manner, which can further endow the coating with good lubricating, hydrophilic and film-forming properties, kill bacteria while also resisting the adhesion of proteins, and reduce the risk of infection and others.

[0077] Compared with chitosan and xanthan gum, gelatin does not have antibacterial properties and has poor film-forming properties. Chitosan may affect the composite effect due to its poor water solubility. Therefore, the catheter in Example 1 has the best antibacterial property. In Comparative Example 2, the polylysine has the worst firmness due to its poor binding property to the catheter, which may also be the reason for its inferior antibacterial property compared to the examples.

[0078] The preferred specific embodiments of the present invention have been described in detail above. It should be understood that those of ordinary skill in the art can make many modifications and variations based on the concept of the present invention without creative labor. Therefore, all technical solutions that can be obtained by those skilled in the art in the technical field of the present invention based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the protection scope determined by the claims.

Claims

1. A distal access catheter, characterized in that, It consists of a tube body, a stress tube, a Luer seat, and a guiding sheath; the tube body includes a plastic layer and a coating; wherein a coating is formed by coating a coating material on the outer surface of the plastic layer; The preparation method of the coating material includes the following steps: X1. Add caffeic acid to MES buffer solution, ultrasonically dissolve it, then add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide, stir for 20 - 40 min, and then add the MES buffer solution of polylysine, and continue to stir for 10 - 20 h; X2. Add glycine, stir for 10 - 20 min and then dialyze, then add xanthan gum, and continue to stir for 2 - 4 h to obtain the coating material.

2. The distal access catheter according to claim 1, wherein The mass ratio of caffeic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, N-hydroxysuccinimide, polylysine, and xanthan gum is 1:0.3 - 0.5:0.1 - 0.3:1 - 3:3 - 5.

3. The distal access catheter according to claim 1, wherein The concentration of caffeic acid in the MES buffer solution is 1 - 5 wt%.

4. The distal access catheter according to claim 1, wherein The concentration of the MES buffer solution of polylysine is 10 - 20 wt%.

5. The distal access catheter according to claim 1, wherein The addition amount of glycine is 1 - 3 times that of caffeic acid.

6. The distal access catheter according to claim 1, wherein The concentration of caffeic acid in the MES buffer solution is 1 - 5 wt%.

7. A method for preparing a distal access catheter according to any one of claims 1-6, characterized in that, It includes the following steps: It consists of a tube body, a stress tube, a Luer seat, and a guiding sheath; the tube body includes a plastic layer and a coating; wherein a coating is formed by coating a coating material on the outer surface of the plastic layer, dried, and sterilized with ethylene oxide.

8. The application of the distal access catheter according to any one of claims 1 - 6 in the medical field.

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