A distal access catheter and a method for preparing the same

Abstract

The present invention relates to the field of medical device technology, specifically disclosing a distal access catheter and a method for preparing the same. The method comprises the following steps: the catheter comprises a tube body, a stress tube, a Luer seat, and an introducer sheath; the tube body comprises, from the tapered end of the stress tube, a PTFE lining layer, a coil layer, a braided layer, a developer ring, and a plastic layer, sequentially from the inside out; the outer surface of the plastic layer is coated with a coating, dried, and sterilized with ethylene oxide. The distal access catheter is thus obtained. The catheter prepared by the present invention has excellent antifouling and lubricity, as well as an excellent antibacterial effect, and can effectively reduce the risk of infection.

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 that are directly connected to the human body, play an indispensable role in the medical field. They have a wide range of applications, covering drainage, blood transfer, auxiliary introduction of other medical devices, and the detection of biological conditions with the help of sensing elements. Distal access catheters are designed to penetrate into the body's difficult-to-reach distal areas (such as small blood vessels in the brain) through blood vessels or other cavities. They mainly serve as a "channel bridge" to help other devices (such as microcatheters, coils, stents, etc.) or drugs accurately reach the target area, thereby improving surgical precision. In recent years, with the steady improvement of people's quality of life, clinical performance requirements for 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, medical catheters are mainly made of 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 actual application. Due to the large surface friction resistance of hydrophobic materials, they can easily cause damage to blood vessels and cavity tissues during use, thereby causing inflammation and causing additional pain to patients. Taking the commonly used urinary catheters in clinical practice as an example, in order to improve their lubricity, lubricants such as glycerol and silicone oil are usually coated on the surface of the catheter. However, this method is not ideal for improving the lubricity of the catheter and there are many inconveniences in actual operation.

[0004] CN118406273A discloses a TPU material and its production process for use in medical catheters, belonging to the field of medical materials technology. This material, based on a thermoplastic polyurethane (TPU) matrix, incorporates modified starch and tungsten powder to synergistically optimize ultrasonic imaging performance. The modified starch, due to its high porosity, effectively enhances ultrasonic imaging clarity when used in medical catheters. Furthermore, the material is coated with ε-polylysine, whose molecular structure is rich in primary amine groups that react with residual anhydrides for secure adhesion. This design not only imparts excellent antibacterial properties and solves the problem of ε-polylysine coatings being easily detached, but also improves the inherent hydrophobicity of the TPU material through its excellent hydrophilicity, reducing the risk of tissue damage during insertion of medical catheters.

[0005] CN110343284A focuses on the field of medical devices, and in particular relates to a method for preparing an antibacterial and anticoagulant coating on the surface of a polyurethane interventional catheter. In this invention, propylene sulfonic acid and vinyl acetate undergo a cross-linking reaction on the surface of a polyurethane tube, which significantly improves the bonding strength between the coating and the surface of the tube, and successfully introduces sulfonic acid groups with anticoagulant properties. After the hydroxyl group is introduced by saponification, it further reacts with PEG-PAMAM to introduce a PEG fragment with strong hydrophilicity and anticoagulant function into the coating system. It is worth mentioning that the introduced PAMAM can form a complex with Ag⁺, which has antibacterial efficacy, by virtue of coordination, thereby giving the coating good antibacterial properties. The raw materials used in this preparation method are low in cost, and the coating formed not only has both antibacterial and anticoagulant effects, but also the network structure constructed by the cross-linking reaction is firmly fixed on the surface of the tube, ensuring that the coating has excellent durability.

[0006] Surface modification of medical catheters to ensure lubricity while maintaining physical and mechanical properties has become a current research focus. Studies have found that both highly hydrophilic and highly hydrophobic polymer surfaces exhibit good lubricity in body fluids or tissue fluid environments. However, in clinical practice, highly hydrophilic polymers are more favored. Compared to highly hydrophobic materials, highly hydrophilic polymers have superior surface properties, effectively reducing the adsorption of bacteria and other substances 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 in 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 being hydrophilic and lubricating, biofilm formation on the catheter surface is another major issue that urgently needs to be addressed. Proteins attached to the catheter provide anchor points for bacterial adhesion and biofilm formation, potentially leading to side effects such as thrombosis. Antifouling treatment of the catheter can reduce initial microbial attachment by repelling it, but antifouling surfaces do not kill bacteria. Some bacteria will still adhere to the catheter surface and form biofilms, potentially causing infection.

[0009] Therefore, the present invention provides a coating that is antibacterial, antifouling, lubricating, and capable of reducing the risk of infection and thrombosis. When a catheter is dipped in the coating and then dried, the resulting coating is formed. Polylysine contains a large number of amino groups and carries a positive charge, strongly binding to water molecules through hydrogen bonds and electrostatic interactions, resulting in excellent hydrophilicity. Its positive charge also allows it to bind to negatively charged phospholipids on the surface of bacteria, disrupting cell membranes, inhibiting metabolic activity, and reducing biofilm formation, thus exhibiting excellent antibacterial properties. Polylysine is covalently bonded to caffeic acid, and the catechol groups in the caffeic acid impart adhesion to the coating in complex environments, ensuring the coating's robustness. Xanthan gum is non-covalently bonded, further imparting excellent lubricity, hydrophilicity, and film-forming properties to the coating. While killing bacteria, it also resists protein adhesion, reducing infection and other risks.

[0010] To achieve the above-mentioned object, the present invention provides a distal access catheter, characterized in that it is composed of a tube body, a stress tube, a Luer seat, and an introducer sheath;

[0011] The tube body is composed of a PTFE lining layer, a coil layer, a braided layer, a developing ring and a plastic layer from the inside to the outside starting from the tapered end of the stress tube;

[0012] The PTFE lining layer covers the stress tube from the tapered end to the end of the tube body in the axial direction; the thickness of the PTFE lining layer on one side is 0.02 mm;

[0013] 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 a round metal wire helical spring; the material of the coil layer is 304 stainless steel wire or nickel-titanium alloy wire; the wall thickness of the helical spring is set to 0.05-0.3mm, and the pitch of the helical spring is set to 0.07-0.35mm;

[0014] The braided layer covers the tapered end of the stress tube axially 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 alternatingly weaving single flat metal wires; the material of the braided layer is 304 stainless steel wire or nickel-titanium alloy wire.

[0015] The material used for the braided layer and the material used for the coil layer have the same thickness.

[0016] Among them, the developing ring axially covers the end of the tube body from a preset distance from the conical end of the stress tube, and the developing ring and the braided layer have overlapping areas; the material of the developing ring is a metal material such as platinum-iridium alloy or tungsten-rhenium alloy.

[0017] The plastic layer extends axially from the tapered end of the stress tube to the end of the tube body; the material of the plastic layer is at least one of nylon, segmented polyetheramide elastomer or polyurethane elastomer.

[0018] The outer surface of the plastic layer is coated with a coating to form a coating layer, specifically, the outer surface of the plastic layer is coated with a coating to form a coating layer, dried, and sterilized with ethylene oxide.

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

[0020] X1. Add caffeic acid to MES buffer, dissolve by ultrasonication, then add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide. Stir for 20-40 minutes, then add polylysine in MES buffer and continue stirring for 10-20 hours.

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

[0022] Furthermore, 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] Furthermore, the concentration of caffeic acid in the MES buffer is 1-5 wt %.

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

[0025] Furthermore, the amount of glycine added is 1 to 3 times that of caffeic acid.

[0026] Preferably, the method for preparing the coating comprises the following steps:

[0027] X1. Add caffeic acid to MES buffer and dissolve it by ultrasonication to obtain a 1-5 wt% solution. Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide. Stir for 20-40 min. Then, add 10-20 wt% polylysine in MES buffer and continue stirring for 10-20 h.

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

[0029] The present invention also provides a distal access catheter and application thereof, wherein 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 antifouling and lubricity, excellent antibacterial effect and good firmness.

[0032] 2. The present invention creates a coating by dipping the catheter into the coating and then drying it. Polylysine binds to negatively charged phospholipids on the bacterial surface, disrupting cell membranes, inhibiting metabolic activity, and reducing biofilm formation, exhibiting excellent antibacterial properties. Polylysine covalently bonds with caffeic acid, and the catechol groups in caffeic acid impart adhesion to the coating in complex environments, ensuring its durability. Xanthan gum, through non-covalent bonding, further imparts excellent lubricity, hydrophilicity, and film-forming properties to the coating. While killing bacteria, it also resists protein adhesion, reducing infection and other risks. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is a structural diagram of the distal access catheter. DETAILED DESCRIPTION

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

[0035] Escherichia coli, CGMCC1.12883, was commercially available and obtained from the China General Microorganism Collection Center.

[0036] Staphylococcus aureus, CGMCC1.1282, was commercially available and was obtained from the China General Microorganism Collection Center.

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

[0038] Example 1

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

[0040] The tube body is composed of a PTFE lining layer, a coil layer, a braided layer, a developing ring and a plastic layer in sequence from the inside to the outside starting from the tapered end of the stress tube;

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

[0042] The coil layer extends axially from the tapered end of the stress tube to the end of the tube body. The coil layer is made of a round metal wire helical spring, fully utilizing the spring structure's tensile and kink resistance. The coil layer is made of 304 stainless steel wire. The helical spring has a wall thickness of 0.05mm and a pitch of 0.07mm.

[0043] The braided layer extends axially from the tapered end of the stress tube to a predetermined distance from the end of the tube body, but does not extend to the end of the tube body. The braided layer is made of alternating single flat metal wires and is made of 304 stainless steel wire. 304 stainless steel wire exhibits excellent ductility and toughness among metals, ensuring 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 developing ring axially covers the end of the tube body from a preset distance from the conical end of the stress tube, and the developing ring and the braided layer have overlapping areas; the developing ring is made of platinum-iridium alloy.

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

[0046] The outer surface of the plastic layer is coated with a coating to form a coating, specifically, the outer surface of the plastic layer is coated with a coating to form a coating, dried, and sterilized with ethylene oxide, wherein the thickness of the coating is 10 μm;

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

[0048] X1. Add 5 parts of caffeic acid to 100 parts of MES buffer, dissolve under ultrasonication, add 2 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1 part of N-hydroxysuccinimide, stir for 30 minutes, then add 50 parts of 20 wt% polylysine in MES buffer solution, and continue stirring for 15 hours;

[0049] X2. Add 7.5 parts of glycine, stir for 10 minutes and then dialyze, then add 20 parts of xanthan gum and continue stirring for 3 hours to obtain a coating.

[0050] Comparative Example 1

[0051] The same as Example 1, the only difference is the coating;

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

[0053] X1. Add 5 parts of caffeic acid to 100 parts of MES buffer, dissolve under ultrasonication, add 2 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1 part of N-hydroxysuccinimide, stir for 30 minutes, then add 50 parts of 20 wt% polylysine in MES buffer solution, and continue stirring for 15 hours;

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

[0055] Comparative Example 2

[0056] The method is basically the same as Example 1, except that the coating is a 20 wt % polylysine aqueous solution.

[0057] Comparative Example 3

[0058] The process is basically the same as Example 1, except that xanthan gum is replaced with gelatin.

[0059] Comparative Example 4

[0060] The process is basically the same as Example 1, except that xanthan gum is replaced by chitosan.

[0061] Test Example 1

[0062] The catheters prepared in the examples and comparative examples were tested for water contact angle, peeling force, and friction coefficient;

[0063] The water contact angle was measured using an optical contact angle meter. Three different smooth locations were randomly selected on each sample surface for measurement, and the average value was finally taken.

[0064] The sample was subjected to a 90° peel test using a texture analyzer. The crosshead speed was set to 0.5 mm / s and the displacement was 50 mm. The test was repeated three times to obtain the peel strength.

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

[0066] Table 1

[0067]

[0068] Most catheter materials have a highly hydrophobic surface and low surface activity. This poor surface lubricity results in high friction when entering the body, which can easily cause damage and increase the risk of infection. However, hydrophilic modification of catheters creates a hydrated layer on the surface. This layer not only reduces surface energy but also acts as a barrier, reducing the adhesion of bacteria and other microorganisms, thereby preventing the formation of biofilms.

[0069] When the catheter is used in the human body, it is always in a liquid environment. After absorbing water, the surface becomes soft and its mechanical properties deteriorate. If the bonding force between the coating and the catheter is weak after long-term use, the coating may easily fall off the catheter surface, enter the body fluids or adhere to the body, which may also cause infection risks.

[0070] As can be seen from Table 1, the conduits prepared by the present invention all have relatively low water contact angles, indicating good hydrophilicity, which results in excellent lubricity. Compared with Reference Example 1, Example 1 has lower water contact angles and lower coefficients of friction, and better robustness. This may be due to the further compounding of xanthan gum in Example 1, which can further enhance hydrophilicity, thereby reducing the coefficient of friction, and can help film formation, thereby enhancing the robustness of the coating. Reference Example 2 only uses polylysine as a coating. Although polylysine has excellent hydrophilicity, it has poor binding to the conduit, resulting in the worst robustness. The catechol group of caffeic acid in the examples has good adhesion, which can also play a role in good adhesion under complex environments.

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

[0072] Test Example 2

[0073] The distal access catheters prepared in the examples and comparative examples were tested for their antibacterial properties. 6 Bacteria with a concentration of 100 cfu / mL were cultured in LB medium for 24 h. After dilution, 100 μL of the diluted sample was applied to the catheter surface and cultured on a plate for 48 h. The number of bacteria on the surfaces of the uncoated catheters 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 not only reduces surface energy but also acts as a barrier, reducing the adhesion of bacteria and other microorganisms, thereby preventing 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 activity, and reducing biofilm formation, thus achieving good antibacterial properties. Polylysine is covalently bonded to caffeic acid, and the catechol groups in caffeic acid can impart adhesion to the coating in complex environments, ensuring the coating's robustness. Xanthan gum is non-covalently bonded, further imparting good lubricity, hydrophilicity, and film-forming properties to the coating. While killing bacteria, it can also resist protein adhesion, reducing infection and other risks.

[0077] Compared to chitosan and xanthan gum, gelatin lacks antibacterial properties and has poorer film-forming properties. Chitosan's poor water solubility may affect the composite effect. Therefore, the catheter in Example 1 has the best antibacterial properties. In contrast, polylysine in Control Example 2 has the worst firmness due to its poor binding to the catheter, which may also be the reason why its antibacterial properties are inferior to those of the Examples.

[0078] The above describes in detail the preferred embodiments of the present invention. It should be understood that those skilled in the art can make numerous modifications and variations based on the concepts of the present invention without inventive effort. Therefore, any technical solutions that can be derived by those skilled in the art through logical analysis, reasoning, or limited experimentation based on the concepts of the present invention and the prior art should be within the scope of protection defined by the claims.

Claims

1. A distal access catheter, characterized in that: The invention is composed of a tube body, a stress tube, a Luer seat, and an introducer sheath; the tube body includes a plastic layer and a coating; wherein the coating is formed by coating the outer surface of the plastic layer; The preparation method of the coating comprises the following steps: X1. Add caffeic acid to MES buffer, dissolve by ultrasonication, then add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide. Stir for 20-40 minutes, then add polylysine in MES buffer and continue stirring for 10-20 hours. X2. Add glycine, stir for 10-20 minutes, and then dialyze. Then add xanthan gum and continue stirring for 2-4 hours to obtain the coating. 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; The concentration of caffeic acid in the MES buffer is 1-5 wt %; The concentration of the polylysine MES buffer is 10-20wt%; The added amount of glycine is 1 to 3 times that of caffeic acid.

2. A method for preparing a distal access catheter according to claim 1, characterized in that: The invention comprises the following steps: the tube body, the stress tube, the Luer seat and the guide sheath are formed; the tube body comprises a plastic layer and a coating; after the outer surface of the plastic layer is coated with paint to form a coating, the catheter is dried and sterilized with ethylene oxide.

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