An ultra-thin lubricous and anti-coagulation coating for an indwelling needle cannula and a method of making the same

Abstract

The application discloses an ultra-thin lubricating anti-coagulation coating for a remaining needle cannula and a preparation method thereof, and comprises the following steps: immersing the remaining needle cannula into a NaOH aqueous solution for pretreatment to obtain a pretreated remaining needle cannula; and immersing the pretreated remaining needle cannula into a mixed solution containing an epoxy silane coupling agent and an amino phosphoyl choline polymer for ultrasonic forming of an ultra-thin lubricating anti-coagulation coating. In the application, the remaining needle cannula is pretreated by sodium hydroxide to endow the surface of the remaining needle cannula with a large number of hydroxyl groups, and then the chemical reaction is accelerated by means of sonochemistry to shorten the induction period, so that the phosphocholine is covalently grafted on the surface of the instrument rapidly under relatively mild conditions, and a uniform ultra-thin coating is obtained. The application reduces the steps of coating preparation and shortens the process time. More importantly, high-temperature incubation is not needed in the solution, and the mechanical properties of the remaining needle cannula are not obviously affected.

Description

Technical Field

[0001] This invention relates to the field of medical device surface modification technology, specifically to an ultrathin lubricating and anticoagulant coating for indwelling needle cannulas and its preparation method. Background Technology

[0002] An indwelling catheter is an infusion tool that involves leaving a soft cannula in a blood vessel for intravenous infusion. Depending on factors such as vascular conditions, drug properties, and the patient's condition, it needs to be left in the blood vessel for about 3 days to meet the needs of long-term, rapid, and simultaneous infusion of different fluids. It can reduce the pain of multiple punctures for patients, help protect the patient's blood vessels, and reduce the workload of nursing staff. It is currently widely used in clinical practice. Its core components are the soft catheter / cannula placed in the blood vessel and the stainless steel puncture guide needle core.

[0003] An indwelling catheter is a tubing made of materials such as silicone, PVC, or Teflon, inserted into a large vein for intravenous infusion therapy. The most common adverse reaction to indwelling catheters is pain; one of the serious complications resulting from prolonged use is venous thrombosis, with an incidence rate of 5.5%-77.5%. This is mostly due to the slowing of local blood flow caused by fixing the catheter, and the relatively small lumen size (0.6-1.5 mm) makes it easy for platelets to deposit. Therefore, effectively reducing pain and preventing thrombosis caused by indwelling catheters is of significant practical importance.

[0004] Drugs used for the prevention and treatment of venous thrombosis may cause adverse reactions such as coagulation disorders. Therefore, it is essential to research safer anticoagulation and antifouling strategies for indwelling needles. Modification of material surfaces and interfaces is receiving increasing attention and is currently a widely used approach to improve the lubrication, blood compatibility, and tissue compatibility of materials. Among these, coating technology, including bioactive coatings and bioinert coatings, has demonstrated excellent anticoagulation and antifouling properties in medical devices.

[0005] CN117398531A discloses a coating-modified indwelling needle with dual anticoagulant and hemostatic functions, its preparation method, and its application. For the inner surface of the indwelling needle catheter, a polydopamine / polyethyleneimine primer is deposited on the inner surface using the oxidative self-polymerization of dopamine / polyethyleneimine in an alkaline Tris-HCl solution. Then, a heparin solution containing a catalyst is injected into the indwelling needle catheter, and a PDA / PEI-Hep anticoagulant coating is prepared by utilizing the covalent and electrostatic interactions between the carboxyl groups in heparin and the amino groups on the surface of the PDA / PEI primer. For the outer surface of the indwelling needle catheter, a hyperbranched polymer adhesive is spin-coated, followed by a carboxymethyl chitosan / aldehyde-functionalized hyaluronic acid hydrogel with hemostatic properties, resulting in an HBPA@CMCS / HA-CHO hemostatic coating.

[0006] Phosphocholine is a class of zwitterionic compounds with biomimetic cell membranes. Notably, phosphocholine coatings have been used for joint lubrication (as seen in the Japanese artificial hip joint Aquala), suggesting that phosphocholine coatings can impart lubricating properties to cannulas, reducing friction during vascular puncture and thus alleviating patient pain. However, currently, these coatings are mostly deposited on the substrate surface through free radical polymerization, resulting in thick coatings. Furthermore, the lack of covalent interaction with the substrate surface leads to poor coating stability, making them unsuitable for devices with narrow lumens, indwelling needle cannulas, balloon catheters, and microvessels requiring long-term performance. More importantly, technological and equipment limitations result in complex preparation steps, long processing times, and low coating efficiency, making them unsuitable for engineering applications. Summary of the Invention

[0007] This invention addresses the need for ultra-thin coatings with lubricating, anti-coating, and anti-fouling properties on indwelling needle cannulas. It provides an efficient and rapid method to prepare an ultra-thin lubricating and anti-coating coating on the surface of the indwelling needle cannulas. The method uses a sonochemical approach to covalently fix anti-fouling and anti-coating polymers on the surface of the indwelling needle cannulas, enabling rapid, economical, and mass production on existing indwelling needle cannulas. This method requires simple equipment and has high production efficiency.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] A method for preparing an ultrathin lubricating and anticoagulant coating for indwelling needle cannulas, comprising the following steps:

[0010] Step 1: Immerse the indwelling needle cannula in NaOH aqueous solution for pretreatment, rinse it with deionized water after removal, then immerse it in anhydrous ethanol for ultrasonic cleaning, and dry it to obtain the pretreated indwelling needle cannula.

[0011] Step 2: Immerse the pretreated indwelling needle cannula in a mixed solution containing epoxy silane coupling agent and aminophosphocholine polymer, sonicate for 1-10 minutes, remove it and rinse the inner and outer surfaces with ethanol, then dry and cure it to form an ultra-thin lubricating and anti-coagulation coating on the surface of the indwelling needle cannula.

[0012] The mixed solution contains an epoxy silane coupling agent with a mass-volume concentration of 0.1-0.8% (w / v) and an aminophosphocholine polymer with a mass-volume concentration of 1-5% (w / v).

[0013] In existing technologies, the preparation process of lubricating and anti-coagulation coatings mostly requires a long incubation period. In this invention, the sleeve is pretreated with sodium hydroxide to impart a large number of hydroxyl groups to its surface. Then, a sonochemical method is used to rapidly react the hydroxyl groups on the substrate with the siloxy groups on the epoxy-containing silane coupling agent, the epoxy groups on the epoxy-containing silane coupling agent, and the amino groups of the amino-containing phosphocholine polymer in a single pot. The principle of the reaction process is as follows: Figure 1 As shown.

[0014] By using mechanical waves to accelerate chemical reactions, shorten the induction period, alter the reaction pathway, reduce side reactions, and increase yield, phosphocholine can be covalently grafted onto the instrument surface rapidly under relatively mild conditions. When ultrasound acts on the liquid medium, it generates a strong "cavitation effect," resulting in localized high temperature and pressure and active free radicals. This accelerates the chemical reactions of hydroxyl groups (on the substrate surface) and siloxy groups (silane coupling agents), as well as the reactions of epoxy groups (silane coupling agents containing epoxy groups) and amino groups (phosphocholine polymers containing amino groups). This constructs a uniform ultrathin coating, reducing the number of coating preparation steps and shortening the process time. More importantly, it eliminates the need for high-temperature incubation in the solution, avoiding significant impacts on the mechanical properties of the sleeve.

[0015] The pretreatment temperature in NaOH aqueous solution is 50-70℃, and the treatment time is 0.1-12h. If the alkaline treatment time is too short, there may be too few active groups such as hydroxyl groups on the casing surface, resulting in a small amount of phosphocholine grafted by silane coupling agent, making it difficult to achieve the purpose of anti-coagulation, anti-fouling, and reducing surface friction. If the alkaline treatment time is too long, the casing surface will be oxidized, affecting the performance of the casing.

[0016] Preferably, the pretreatment time in NaOH aqueous solution is 0.5-2 hours.

[0017] The molar concentration of the NaOH aqueous solution is 2-3 mol / L; rinse with deionized water 3-5 times; ultrasonic cleaning with anhydrous ethanol for 0.1-1 h;

[0018] The epoxy silane coupling agent is one or more of 3-glycidyl etheroxypropyltrimethoxysilane (KH560), 3-glycidyl etheroxypropyltriethoxysilane, 3-glycidyl etheroxypropylmethyldiethoxysilane (KH-78), and 1-(3-glycidyl etheroxypropyl)-1,1,3,3,3-pentaethoxy-1,3-disilpropane.

[0019] The aminophosphocholine polymer has the following structural formula.

[0020]

[0021] Where m:n = 1:5 - 1:30.

[0022] The preparation of the aminophosphorylcholine polymer includes: using 2-methacryloyloxyethylphosphorylcholine and glycidyl methacrylate as raw materials, polymerizing them via free radical initiation, and reacting them with 2-aminoethanethiol to obtain the aminophosphorylcholine polymer.

[0023] Preferably, the molar ratio of 2-methacryloyloxyethyl phosphorylcholine to glycidyl methacrylate is 3-10:1, more preferably 3-6:1.

[0024] Preferably, the mass-volume concentration of the epoxy silane coupling agent in the mixed solution is 0.3-0.6% (w / v), and the mass-volume concentration of the aminophosphorylcholine polymer is 1.5-3% (w / v), wherein the molar ratio of the epoxy group of the epoxy silane coupling agent to the amino group of the aminophosphorylcholine polymer is 1:5-1:30.

[0025] If the mass-volume concentration of the epoxy silane coupling agent and the aminophosphocholine polymer is too low, it is difficult to obtain a phosphocholine polymer coating on the indwelling needle; if the concentration of both is too high, the thickness of the coating on the indwelling needle will increase sharply, which will have a certain impact on its inner diameter, reduce the liquid flow rate, and increase the liquid flow velocity due to the reduced inner diameter, which will also increase the risk of coating peeling off.

[0026] The solvent of the mixed solution includes one or more of ethanol, water, methanol, dichloromethane, n-hexane, and isopropanol. Preferably, the solvent is a mixed solution of ethanol and water.

[0027] Preferably, the ultrasonic time in step 2 is 3-10 minutes. Obviously, the ultrasonic time affects the degree of reaction. If the ultrasonic time is too short, the reaction degree between silicon oxide and the hydroxyl groups on the surface of the indwelling needle cannula, and between the epoxy groups on the silane and the amino groups on the phosphocholine group is too low, resulting in the failure to successfully prepare a coating on the indwelling needle cannula. If the ultrasonic reaction time is too long, it may lead to an excessively high degree of reaction, resulting in an excessively thick coating on the indwelling needle cannula, which affects the microstructure of the indwelling needle cannula itself and also affects the safety of the coating.

[0028] In step 2, the ultrasonic frequency is 15-30 kHz and the ultrasonic power is 100-1000 W. Preferably, the ultrasonic frequency is 20 kHz and the ultrasonic power is 300-800 W.

[0029] The temperature for blower drying is 40-70℃, and the time is 0.1-6h; preferably, the curing time is 1-3h.

[0030] This invention also provides an ultrathin lubricating and anticoagulant coating prepared on an indwelling needle cannula by the aforementioned method. The ultrathin lubricating and anticoagulant coating has a thickness of 10-50 nm, and the surface friction coefficient of the cannula after coating is below 0.4. The method of this invention can form an ultrathin hydrophilic coating on the inner and outer surfaces of the cannula, endowing the inner and outer surfaces of the indwelling needle cannula with highly efficient anticoagulant and antifouling properties, reducing the occurrence of thrombotic adverse events; at the same time, it significantly reduces the friction between the cannula and soft tissue, alleviating patient pain; and it does not significantly affect the inner diameter of the cannula, thus not significantly affecting its function. The indwelling needle cannula, through this ultrathin lubricating and anticoagulant coating, can be endowed with anticoagulant, antifouling, and lubricating functions through an easily engineered, economical, and environmentally friendly process, enabling rapid, economical, and mass production on existing indwelling needle cannulas. This method requires simple equipment and has high production efficiency.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] (1) The method for preparing the ultra-thin lubricating and anti-coagulation coating for indwelling needle cannulas in this invention is fast and efficient. A coating with multiple functions can be obtained in tens of minutes or even minutes. Compared with the long incubation method in the prior art, the preparation process is simple and the time is greatly shortened, which is convenient for industrial mass production.

[0033] (2) The ultra-thin lubricating and anti-coagulation coating of the indwelling needle cannula in this invention is thin and uniform in thickness, and has multiple comprehensive effects of anti-coagulation, anti-fouling and lubrication. That is, it gives the indwelling needle cannula the required anti-coagulation, anti-fouling and lubrication effects, without significantly affecting the inner diameter of the cannula, and will not significantly affect its function. Attached Figure Description

[0034] Figure 1 This is a schematic diagram illustrating the principle of forming an ultrathin lubricating and anti-coagulation coating under sonochemical action in this invention.

[0035] Figure 2 The images show the appearance of the indwelling needle cannula with and without coating in Example 1.

[0036] Figure 3 This is a comparison diagram of the anti-fouling properties of the indwelling needle cannula with and without coating in Example 1. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Modifications or equivalent substitutions made by those skilled in the art based on their understanding of the technical solutions of this invention, without departing from the spirit and scope of the invention, should be covered within the protection scope of this invention.

[0038] The raw materials used in the following specific embodiments were all purchased from the market, and the preparation of the aminophosphocholine polymer is as follows:

[0039] Under argon protection, azobisisobutyronitrile (1 wt%), 2-methacryloyloxyethyl phosphorylcholine (MPC), and glycidyl methacrylate (GMA) were added sequentially to a polymerization reaction tube. The molar ratio of MPC to GMA was 4:1. 10 ml of ethanol was added to the reaction tube, and the mixture was stirred to dissolve. The reaction tube was placed at 60°C for 20 h. After the reaction was complete, the temperature was raised to 75°C, and AET (2-aminoethanethiol) (the molar ratio of AET to GMA was 1:1) was added. Propanol was then added, and the reaction continued for another 20 h. After cooling to room temperature, the ethanol solvent was removed by rotary evaporation to obtain the aminophosphorylcholine polymer, in which the amino content was 20%.

[0040] Example 1

[0041] Step 1. Immerse the cannula of the indwelling needle in NaOH aqueous solution (2.7 mol / L) at 60℃ for 0.5 h. After removal, rinse three times with deionized water to remove the surface alkali. After removal, place the cannula in anhydrous ethanol and ultrasonically clean it at room temperature for 0.5 h. Dry it with nitrogen to obtain the pretreated indwelling needle cannula.

[0042] Step 2, weigh KH560 and the amino-containing phosphocholine polymer and add them to the mixed solvent (V 乙醇 V 水 In a mixture of 95:5, the mass-volume concentrations were 0.6% and 3%, respectively. The pretreated cannula was placed in the above mixed solution, and the ultrasonic probe was also placed in the coating solution. The ultrasonic device was started, and the ultrasonic frequency was set to 20 kHz, the ultrasonic power to 400 W, and the ultrasonic time to 10 min. Under the action of ultrasound, the hydroxyl groups on the substrate reacted rapidly with the siloxy groups on the epoxy-containing silane coupling agent, the epoxy groups on the epoxy-containing silane coupling agent, and the amino groups on the amino-containing phosphocholine polymer. Under relatively mild conditions, the phosphocholine polymer was rapidly covalently grafted onto the surface of the instrument. The inner and outer surfaces of the cannula were rinsed with ethanol three times to remove the uncovalently grafted phosphocholine polymer. The cannula was then heated and cured at 50 °C for 0.5 h in a forced-air drying oven, thus obtaining a uniform, ultra-thin, lubricating, and anti-coagulation phosphocholine coating on the inner and outer surfaces of the cannula.

[0043] Example 2: Shortened ultrasound time

[0044] The only difference between this embodiment and embodiment 1 is that the conditions for ultrasonic treatment in step 2 are different. The ultrasonic frequency is set to 20KHz, the ultrasonic power to 800W, and the ultrasonic time to 3min.

[0045] Example 3: Increased Alkali Treatment Temperature

[0046] The only difference between this embodiment and Embodiment 1 is that in step 1, the cannula portion of the indwelling needle is immersed in a NaOH aqueous solution (2.7 mol / L) and treated at 70°C for 0.5 h. The cannula is then rinsed three times with deionized water to remove the surface alkali, and then ultrasonically cleaned in deionized water and dried.

[0047] Example 4: Reduced concentration of antifouling polymer

[0048] The only difference between this embodiment and Example 1 is that the mass-volume concentrations of KH560 and the amino-containing phosphocholine polymer in step 2 are 0.3% and 1.5%, respectively.

[0049] Comparative Example 1

[0050] The only difference between this embodiment and embodiment 3 is that ultrasound is not performed in step 2. The pretreated tube is placed in the same mixed solution and incubated at room temperature for 1 hour. Then, the inner and outer surfaces of the tube are rinsed with ethanol three times to remove the uncovalently grafted phosphocholine polymer. The coating is then cured at 50°C for 0.5 hours in a forced-air drying oven.

[0051] Comparative Example 2

[0052] The only difference between this embodiment and embodiment 3 is that the ultrasound is performed for 0.1 min in step 2.

[0053] Comparative Example 3

[0054] The only difference between this embodiment and embodiment 3 is that the ultrasound is performed for 20 minutes in step 2.

[0055] Comparative Example 4

[0056] The only difference between this embodiment and embodiment 2 is that the preprocessing in step 1 is not performed.

[0057] Comparative Example 5

[0058] The only difference between this embodiment and Example 1 is that the mass-volume concentrations of KH560 and the amino-containing phosphocholine polymer in step 2 are 0.01% and 0.5%, respectively.

[0059] Comparative Example 6

[0060] The only difference between this embodiment and Example 1 is that the mass-volume concentrations of KH560 and the amino-containing phosphocholine polymer in step 2 are 2% and 10%, respectively.

[0061] Coating performance analysis

[0062] (1) Lubrication performance test of ultra-thin lubricating and anti-coagulation coating for indwelling needle cannulas

[0063] After coatings were applied to the surface of the indwelling needle cannula in Examples 1-4 and Comparative Examples 1-6, the surface friction was tested using a friction force testing device. One end of the indwelling needle cannula was hung on a tensile test sensor, and the cannula was clamped between two silicone sheets. The clamping force was set to 3N, and the magnitude of the pulling force (N) when the puncture needle was pulled was recorded. Each sample was tested 8 times, and the friction coefficient was calculated by taking the average value. The results are shown in Table 1.

[0064] Table 1. Thickness measurement, lubrication, and antifouling properties of the ultrathin lubricating and anti-coagulation coatings prepared in the examples and comparative examples.

[0065] Serial Number Average coating thickness (nm) coefficient of friction Thrombosis status score Example 1 39.3±2.0 0.36 0 Example 2 18.5±1.6 0.37 1 Example 3 43.2±2.3 0.34 0 Example 4 21.0±2.3 0.40 1 Comparative Example 1 - 0.96 3 Comparative Example 2 - 0.89 4 Comparative Example 3 326.6±25.0 0.33 0 Comparative Example 4 - 0.95 4 Comparative Example 5 - 0.96 4 Comparative Example 6 288.0±15.3 0.29 0 control group - 1 4

[0066] The lubricating coating prepared on the surface of the indwelling needle cannula by this invention can significantly reduce surface friction (Examples 1-4), making its coefficient of friction <0.4, thereby reducing the pain caused by the indwelling needle puncture into the blood vessel. Compared with Example 1, Example 2 appropriately shortened the ultrasound time, Example 3 increased the alkaline treatment temperature, and Example 4 appropriately reduced the concentration of silane coupling agent and aminophosphocholine polymer in the mixed coating solution. The coefficient of friction of the indwelling needle cannula surface after coating was reduced by up to 60%, and the coating has obvious lubricating properties.

[0067] In Comparative Example 3, the ultrasonic sonochemical reaction time was too long, yet the coating still exhibited significant lubricating properties. Comparative Example 6, by increasing the concentrations of silane coupling agent and aminophosphocholine polymer in the mixed coating solution, showed a significant improvement in the coating's lubricating properties. However, the thickness also increased significantly, which is detrimental to its practical application with indwelling needles.

[0068] When the indwelling needle cannula is not ultrasonically treated in the coating solution, is incubated at room temperature (Comparative Example 1), or has a short ultrasonic time (Comparative Example 2), the silane coupling agent, phosphocholine polymer, and active groups on the substrate surface do not react or the reaction efficiency is extremely low, resulting in no grafting of phosphocholine polymer on the cannula surface, thus making the improvement of the lubrication performance of the cannula surface extremely limited.

[0069] The lack of pretreatment with alkaline solution (Comparative Example 4) may have resulted in insufficient active groups such as hydroxyl groups on the surface of the indwelling needle cannula, further affecting the effectiveness of phosphocholine grafting via covalent reaction, ultimately leading to an uneven coating and no significant lubrication effect. Similarly, excessively low concentrations of silane coupling agent and phosphocholine in the coating solution (Comparative Example 5) may have resulted in insufficient phosphocholine grafted onto the instrument surface, also failing to obtain a uniform coating and thus affecting its lubrication performance. Therefore, the activation of the indwelling needle cannula through pretreatment, the concentration of the mixed coating solution, and the duration of the ultrasonic reaction all affect the coating preparation, thereby further influencing its lubrication performance.

[0070] (2) Determination of the thickness of the ultra-thin lubricating and anti-coagulation coating for indwelling needle cannulas

[0071] The thickness of the coatings prepared on the surface of the indwelling needle cannula in Examples 1-4 was measured using an ellipsometry. Three measurements were taken three times at three random locations for each sample, and the results are shown in Table 1. The thickness indicates that the lubricating coating for the puncture needle prepared in this invention has a thickness of 10-50 nm, which is ultra-thin. The coating thickness varies with the concentration of silane coupling agent and aminophosphocholine in the coating solution. Compared to Example 1 (coating thickness 39.3 nm), Example 2 appropriately shortened the ultrasonic time, resulting in a thinner coating (18.5 nm); Example 4 appropriately reduced the concentration of silane coupling agent and aminophosphocholine polymer in the mixed coating solution, resulting in a thinner coating (21.0 nm). In Example 3, increasing the alkaline treatment temperature activated the cannula surface but had little effect on the coating thickness (43.2 nm).

[0072] In Comparative Example 1, the indwelling needle cannula was incubated at room temperature in the coating solution. In Comparative Example 2, the sonication time of the needle cannula in the coating solution was too short. In Comparative Example 5, the concentrations of silane coupling agent and phosphocholine in the coating solution were too low. In these cases, the conditions for covalent reaction between amino and epoxy groups, and between siloxy and hydroxyl groups, were not met, resulting in either insufficient grafting of phosphocholine onto the surface or an excessively low amount of covalently grafted phosphocholine. Consequently, no coating was obtained on the cannula surface, and the coating thickness could not be measured. In Comparative Example 4, the outer cannula of the indwelling needle was not pretreated, resulting in a lack of active groups on the surface, making it difficult to covalently graft phosphocholine, which also led to unsuccessful coating preparation.

[0073] In Comparative Example 3, the ultrasonic reaction time was too long, and in Comparative Example 6, the concentrations of silane coupling agent and phosphocholine in the coating solution were too high, resulting in an excessive amount of phosphocholine covalently grafted via the sonochemical reaction. This led to an excessively thick phosphocholine coating, exceeding 250 nm in both cases. Therefore, to obtain an ultrathin phosphocholine coating with significant lubricating properties, it is necessary to pretreat the indwelling needle cannula to obtain active groups, and control the concentrations of silane coupling agent and phosphocholine polymer in the coating solution and the sonochemical reaction time within appropriate ranges. Otherwise, it will be difficult to obtain a coating on the cannula surface, or the prepared coating will be too thick.

[0074] (3) Test of anticoagulation performance of ultrathin lubricating and anticoagulation coating for indwelling needle cannulas

[0075] In Examples 1-4 and Comparative Examples 1-6, after coatings were applied to the surface of indwelling needle cannulas, a Chandler ring model was used to simulate physiological blood flow. These cannulas were fixed in the same position on medical silicone tubes. Freshly recalcified rabbit blood was loaded into the silicone tubes. Subsequently, multiple test rings containing different samples were rotated in a 37°C water bath. After the experiment, each sample was gently washed in PBS. The thrombosis status on the surface of the cannulas was scored according to the scoring scheme in YY / T 1770.1-2021 Medical Device Thrombosis Test. The scoring criteria are shown in Table 2, and the scoring results are shown in Table 1.

[0076] Table 2 Thrombosis Evaluation Scheme for Chandler's Ring Test

[0077]

[0078]

[0079] As shown in Table 1, the inner and outer surfaces of the indwelling needle cannulas in Examples 1-4, Comparative Examples 3 and 6 were almost free of thrombi, while the inner and outer surfaces of the indwelling needle cannulas in Comparative Examples 1-2 and 4-5 showed obvious thrombi. The results indicate that covalently grafting phosphocholine onto the surface of the indwelling needle cannulas can significantly inhibit thrombus formation, giving the cannulas a better anticoagulant effect. Furthermore, the thickness of the phosphocholine coating has little effect on its anticoagulant performance. Therefore, the indwelling needle cannulas in Comparative Examples 3 and 6 also exhibited good anticoagulant performance. However, in Comparative Example 1, the indwelling needle cannulas were incubated at room temperature in the coating solution; in Comparative Example 2, the cannulas were sonicated in the coating solution for too short a time; in Comparative Example 4, the outer cannula of the indwelling needle was not pretreated, resulting in a lack of active groups on the surface; and in Comparative Example 5, the concentrations of silane coupling agent and phosphocholine in the coating solution were too low. All these factors resulted in an uneven coating on the outer cannula surface (as evidenced by coating thickness testing), leading to poor or almost no anticoagulant performance.

[0080] In summary, by pretreating the indwelling needle cannula to obtain active groups and controlling the concentrations of silane coupling agent and phosphocholine polymer and the sonochemical reaction time in the coating solution within an appropriate range, an ultrathin coating can be obtained by covalently grafting phosphocholine onto the surface of the indwelling needle cannula, thus imparting it with lubricating and anticoagulation properties.

[0081] (4) Dyeing observation and antifouling performance test of ultrathin anticoagulant coating for indwelling needle cannulas

[0082] The tube with the ultrathin phosphotcholine coating prepared according to Example 1 was observed by staining with Congo red. The results are shown below. Figure 2 The results show that the coating is complete and uniform. The antifouling performance of the sleeve with the ultrathin coating prepared according to Example 1 was investigated by an anti-nonspecific protein adsorption experiment. The uncoated sleeve and the coated sleeve were incubated with FITC-labeled albumin solution, washed three times, dried, and photographed using a fluorescence microscope. The results are shown below. Figure 3 Covalently grafted phosphoric acid choline polymer indwelling needle cannulas have excellent antifouling properties, reducing the chance of bacteria and biomolecules adhering to the inner and outer surfaces of the cannulas placed in blood vessels, thus reducing the risk of inflammation and thrombosis.

Claims

1. A method for preparing an ultrathin lubricating and anti-coagulation coating for indwelling needle cannulas, characterized in that, Including the following steps: Step 1: Immerse the indwelling needle cannula in NaOH aqueous solution for pretreatment, rinse it with deionized water after removal, then immerse it in anhydrous ethanol for ultrasonic cleaning, and dry it to obtain the pretreated indwelling needle cannula. Step 2: Immerse the pretreated indwelling needle cannula in a mixed solution containing epoxy silane coupling agent and aminophosphocholine polymer, sonicate for 1-10 min, remove it and rinse the inner and outer surfaces with ethanol, and then dry and cure it with a forced air to form an ultra-thin lubricating and anti-coagulation coating on the surface of the indwelling needle cannula. The mass-volume concentration of the epoxy silane coupling agent in the mixed solution is 0.3-0.6% w / v, and the mass-volume concentration of the aminophosphocholine polymer is 1.5-3% w / v. The molar ratio of the epoxy group of the epoxy silane coupling agent to the amino group of the aminophosphorylcholine polymer in the mixed solution is 1:5-1:

30. The thickness of the ultra-thin lubricating and anti-coagulation coating is 10-50 nm, and the friction coefficient of the sleeve surface after coating is below 0.4; In step 2, the ultrasonic frequency is 15-30 kHz and the ultrasonic power is 100-1000W.

2. The method for preparing the ultrathin lubricating and anticoagulant coating for indwelling needle cannulas according to claim 1, characterized in that, The pretreatment temperature in NaOH aqueous solution is 50-70℃, and the treatment time is 0.1-2 h; The molar concentration of the NaOH aqueous solution is 2-3 mol / L; rinse with deionized water 3-5 times; the ultrasonic cleaning time of anhydrous ethanol in step 1 is 0.1-1 h.

3. The method for preparing the ultrathin lubricating and anti-coagulation coating for indwelling needle cannulas according to claim 1, characterized in that, The epoxy silane coupling agent is one or more of 3-glycidyl etheroxypropyltrimethoxysilane, 3-glycidyl etheroxypropyltriethoxysilane, 3-glycidyl etheroxypropylmethyldiethoxysilane, and 1-(3-glycidyl etheroxypropyl)-1,1,3,3,3-pentaethoxy-1,3-disilpropane.

4. The method for preparing the ultrathin lubricating and anti-coagulation coating for indwelling needle cannulas according to claim 1, characterized in that, The amino-phosphorylcholine polymer has the following structural formula: Where m:n = 1:5 - 1:

30.

5. The method for preparing the ultrathin lubricating and anticoagulant coating for indwelling needle cannulas according to claim 4, characterized in that, The preparation of the aminophosphorylcholine polymer includes: using 2-methacryloyloxyethylphosphorylcholine and glycidyl methacrylate as raw materials, and obtaining the aminophosphorylcholine polymer by free radical initiation polymerization.

6. The method for preparing the ultrathin lubricating and anti-coagulation coating for indwelling needle cannulas according to claim 1, characterized in that, The solvent of the mixed solution includes one or more of ethanol, water, methanol, dichloromethane, n-hexane, and isopropanol.

7. The method for preparing the ultrathin lubricating and anti-coagulation coating for indwelling needle cannulas according to claim 1, characterized in that, The temperature for blower drying is 40-70℃, and the time is 0.1-6 h.

8. The ultrathin lubricating and anti-coagulation coating prepared on an indwelling needle cannula by the method according to any one of claims 1-7, characterized in that, The thickness of the ultra-thin lubricating and anti-coating coating is 10-50 nm, and the friction coefficient of the sleeve surface after coating is below 0.4.

Images