A gold surface anticoagulant coating structure and a preparation method and application thereof

Abstract

The present application relates to the technical field of medical noble metal materials and medical devices, and in particular to a gold surface anti-coagulation coating structure, a preparation method and application thereof.The present application uses chloroauric acid to construct a micro-nano morphology surface in situ by wet chemical reduction on the surface of a gold layer, uses fluorothiol to modify the surface of the micro-nano gold layer, and injects a lubricant into the modified micro-nano gold surface to construct a lubricant-injected porous self-lubricating surface (SLIPS).The locking ability of the nano gold layer surface modified by fluorothiol is significantly improved, so that the lubricating layer is not prone to loss, thereby having a long-lasting anti-coagulation function.The present application solves the problem that the injected lubricating liquid is prone to depletion and the anti-coagulation performance has poor durability when a liquid injection surface method is used to perform anti-coagulation treatment on the surface of a material.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical noble metal materials and medical devices, and further relates to a gold surface anticoagulant coating structure, a preparation method and application thereof. BACKGROUND

[0002] Blood-contacting medical devices are widely used in the treatment of cardiovascular diseases, saving countless lives. Blood-contacting medical devices include in-vivo implants (such as central venous catheters and coronary stent), extracorporeal life support system components (such as dialysis circuits and extracorporeal membrane oxygenation (ECMO) circuits), and other blood-contacting materials (such as materials used for blood collection and storage). However, due to the poor blood compatibility and weak surface anticoagulant performance of blood-contacting medical devices, they often easily trigger endogenous coagulation cascade reaction, leading to thrombosis, inflammatory reaction and bacterial infection, resulting in failure of medical devices. More seriously, thrombus may enter important organs such as lungs and brain with blood circulation, leading to vascular and pulmonary embolism, and further causing a series of complications, which not only significantly increases the treatment cost, but also may pose a serious threat to the patient's life.

[0003] Coagulation on the surface of blood-contacting medical devices is initiated by protein adsorption, and the protein layer formed on the material surface further induces platelet adhesion, activation and aggregation, activates the coagulation cascade reaction and forms thrombus. Therefore, modifying the surface of blood-contacting medical device materials through surface modification strategies that minimize non-specific adhesion of proteins and cells is the most effective method to weaken coagulation on the material surface. Surface modification is to resist coagulation and activation of the immune system by changing the blood-substance interface, which is divided into physical-chemical methods and surface biological functionalization. Surface biological functionalization endows the surface with the ability to interfere with thrombin and coagulation factors, such as endothelialized surface, heparinized surface, NO releasing surface. Physical-chemical methods change the material surface morphology, charge and hydrophilicity / hydrophobicity on the nanoscale to affect the interaction between the material surface and proteins, platelets, etc. in blood to inhibit thrombus formation, such as hydrophobic surface, patterned surface, liquid infused surface, hydrogel-based surface, etc.

[0004] Liquid-infused surfaces (LIS) can effectively repel different types of liquids, such as water, hydrocarbons, crude oil, and blood, by infusing a layer of viscous liquid on the surface to form a smooth interface. Meanwhile, the surface can also maintain a low contact angle hysteresis and quickly recover its liquid-repellent properties after physical damage. This technology has a wide application prospect in medical and marine fields in terms of anti-biofouling, reducing frictional resistance, and preventing icing. Inspired by the pitcher plant, Joanna Aizenberg's team designed a liquid-infused porous surface in 2011, which successfully prepared a long-lasting lubricating layer by using a micro-nano structured substrate to fix the infused lubricating liquid. The smooth surface with infused liquid shows a better pressure resistance than the super-hydrophobic surface. However, the infused liquid is prone to loss, so there is still a certain deficiency in durability. SUMMARY

[0005] The technical problem solved by the present application is that when the liquid-infused surface method is used for the anticoagulant treatment of the material surface, the infused lubricating liquid is prone to be depleted, resulting in the failure of the anticoagulant performance; that is, the anticoagulant performance durability is poor.

[0006] The present application utilizes the in-situ wet chemical reduction of chloroauric acid on the surface of the gold layer to construct a micro-nano morphology, modifies the surface of the micro-nano gold layer with fluorosulfhydryl, and infuses lubricant into the modified micro-nano gold surface to construct a porous self-lubricating surface (SLIPS). The locking ability of the micro-nano gold layer surface modified by fluorosulfhydryl to the lubricant is significantly improved, so that the lubricant is not prone to loss, thereby having a long-lasting anticoagulant function.

[0007] One of the purposes of the present application is to provide a gold surface anticoagulant coating structure.

[0008] The gold surface anticoagulant coating structure comprises, from bottom to top, a micro-nano gold surface, a grafting modification layer, and an anticoagulant layer.

[0009] The grafting modification layer contains fluorosulfhydryl, which is grafted on the micro-nano gold surface. The fluorosulfhydryl has a mercapto functional group, which can react with the gold surface to form a gold-sulfur covalent bond; the fluorosulfhydryl is grafted on the micro-nano gold surface through gold-sulfur interaction to form a fluorine-containing film on the micro-nano gold surface.

[0010] The fluorosulfhydryl is selected from one or more of 1H, 1H, 2H, 2H-perfluorodecanethiol, 3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 8-tridecafluoro-1-octanethiol, and 3, 3, 4, 4, 5, 5, 6, 5, 6-n-fluoro-1-hexanethiol; preferably 1H, 1H, 2H, 2H-perfluorodecanethiol.

[0011] The anti-coagulation layer contains a lubricant. Specifically, the anti-coagulation layer is formed by the lubricant. The lubricant can be selected from one or more of perfluoropolyether, silicone oil, fluorinated lubricating oil, ionic liquid, and polyethylene glycol.

[0012] The grafting modification layer is a fluorine-containing film grafted on the surface of the micro-nano gold through gold-sulfur covalent bond. Compared with the three-dimensional network structure of the polymer, the storage capacity of the fluorine-containing film is limited, but the fluorine-containing film and the lubricant can be strongly adsorbed to each other through low surface energy, so that the lubricant is adsorbed on the surface of the micro-nano gold, and the lubricant is less lost or even not lost during use. As can be seen, the fluorine-containing thiol grafting modification layer is firmly grafted on the surface of the micro-nano gold through gold-sulfur interaction, and the lubricant is strongly adsorbed to the surface of the micro-nano gold through low surface energy, so that the lubricant is firmly attached to the surface of the micro-nano gold, solving the problem of easy loss of the lubricant and poor durability of the anti-coagulation effect.

[0013] When the lubricant contains fluorine, the fluorine-containing thiol in the grafting modification layer and the fluorine-containing lubricant can also maintain the adhesion of the lubricant through fluorine-fluorine interaction, thereby further improving the adhesion of the lubricant to the surface of the micro-nano gold. Therefore, as a preferred solution, the lubricant is a fluorine-containing lubricant, and more preferably a perfluoropolyether.

[0014] The present application constructs a micro-nano morphology on the surface of the gold plating layer through in-situ wet chemical reduction reaction of chloroauric acid, grafts fluorine-containing thiol on the surface of the micro-nano gold layer through gold-sulfur interaction, and injects the lubricant into the modified surface of the micro-nano gold, thereby constructing a porous self-lubricating surface (SLIPS), which can greatly reduce the resistance of blood flow and resist the adhesion of blood. By preparing the micro-nano gold surface, using the affinity of fluorine-containing thiol to the lubricant and the strong interaction between gold and sulfur, the locking capacity of the gold surface to the lubricant is greatly increased, and the anti-coagulation performance is durable. Compared with the current anti-coagulation measures, the present application improves the locking capacity of the lubricating layer by using the capillary action of the micro-nano structure surface and the affinity of the fluorine-containing thiol to the lubricant.

[0015] The second object of the present application is to provide a preparation method of the gold surface anti-coagulation coating structure according to the first object of the present application.

[0016] The preparation method of the gold surface anti-coagulation coating structure comprises:

[0017] (1) coating a chloroauric acid solution on the gold surface to obtain a micro-nano gold surface;

[0018] (2) coating a fluorine-containing thiol solution on the micro-nano gold surface, standing and drying to form a grafting modification layer;

[0019] (3) placing the micro-nano gold surface containing the grafted modification layer in a lubricant, soaking, taking out and then vertically placing to form an anti-coagulation layer.

[0020] In step (1), after the gold surface is coated with the chloroauric acid solution, the chloroauric acid in the chloroauric acid solution rapidly undergoes a redox reaction with the gold surface, and the chloroauric acid is reduced in situ on the surface of the gold plating layer to construct a micro-nano morphology surface, thereby obtaining a micro-nano gold surface. Specifically, the gold surface is coated with the chloroauric acid solution and left to stand for 10 minutes, thereby obtaining a micro-nano gold surface.

[0021] In step (1), the coating can be performed by using a conventional coating method in the art. Specifically, a certain amount of the chloroauric acid solution can be added dropwise to the gold surface by using a pipette, and then evenly spread to cover the gold surface.

[0022] In step (1), the gold surface can be a surface of metallic gold or a surface of a gold plating layer on a substrate of another material.

[0023] In step (1), the solvent of the chloroauric acid solution is pure water.

[0024] In step (1), the concentration of the chloroauric acid solution can be selected within a wide range, and a skilled person can select a suitable concentration of the chloroauric acid solution according to actual needs. As a preferred solution, the concentration of the chloroauric acid solution is 10 mM to 100 mM, and more preferably 50 mM to 100 mM.

[0025] In step (1), the amount of the chloroauric acid solution can be selected within a wide range, and a skilled person can select a suitable amount of the chloroauric acid solution according to actual needs. As a preferred solution, the amount of the chloroauric acid solution is 20 μL to 100 μL, and preferably 20 μL to 50 μL, per 1×1 cm 2 The amount of the chloroauric acid solution for the gold surface is 20 μL to 100 μL, and preferably 20 μL to 50 μL.

[0026] In step (2), the solvent of the fluorine-containing mercaptan solution can be selected within a wide range, and a skilled person can select a suitable solvent according to actual needs. Preferably, an organic solvent that is easy to evaporate is selected, for example, which can be selected from anhydrous ethanol, acetone or isopropanol.

[0027] In step (2), the concentration of the fluorine-containing mercaptan solution can be selected within a wide range, and a skilled person can select a suitable concentration according to actual needs. Specifically, the concentration of the fluorine-containing mercaptan solution is 1 to 5 M, and preferably 2 to 3 M, for example, 2 M.

[0028] In step (2), the role of standing is to make the fluorine-containing thiol react with gold sufficiently; the role of drying is to make the solvent in the fluorine-containing thiol solution volatilize and remove the free fluorine-containing thiol on the surface. The standing time and drying conditions can be selected within a wide range, and the skilled person can select appropriate standing time and drying conditions according to actual needs. Specifically, the standing time can be 12 h or more, for example, 12 h; the drying condition can be vacuum, room temperature (for example, 25℃), and the drying time can be 1 h or more, for example, 1 h.

[0029] In step (3), the role of soaking is to make the lubricant fill the surface of the grafted and modified micro-nano gold structure sufficiently; "vertically" means that the gold surface is perpendicular to the horizontal plane, and the role of placing the gold surface vertically is to remove the excess lubricant on the surface. The soaking temperature, soaking time and vertical placement time can be selected within a wide range, and the skilled person can select appropriate soaking temperature, soaking time and vertical placement time according to actual needs. Specifically, the soaking temperature can be 60~80℃, for example, 80℃; the soaking time can be 48 h or more, for example, 48 h; and the vertical placement time can be 12 h or more, for example, 12 h.

[0030] The preparation method of the gold surface anticoagulant coating structure can further include, before step (1), surface cleaning of gold. The surface cleaning of gold can be performed by conventional operation. Specifically, it can include: first, ultrasonic treatment of the surface with anhydrous ethanol solution for 10 min to wash off grease, dust and other impurities; then ultrasonic treatment with deionized water for 10 min to further clean the residual ethanol; finally, using a forced air drying oven to set the temperature to 80℃ to dry the surface moisture.

[0031] The preparation method of the gold surface anticoagulant coating structure, wherein one specific scheme includes:

[0032] Step one, surface cleaning of gold: first, ultrasonic treatment of the surface with anhydrous ethanol solution for 10 min to wash off grease, dust and other impurities; then ultrasonic treatment with deionized water for 10 min to further clean the residual ethanol; finally, using a forced air drying oven to set the temperature to 80℃ to dry the surface moisture;

[0033] Step two, preparation of gold surface modifier: preparing a chloroauric acid solution with a concentration of 10 mM~100 mM using pure water as the solvent, and preparing a fluorine-containing thiol solution with a concentration of 2 M using anhydrous ethanol as the solvent, both of which are used as the gold surface modifier.

[0034] Step three, surface treatment: first, use a pipette to drop 20-100 muL of chloroauric acid solution on the cleaned gold surface and evenly spread it to cover the entire gold surface, and then place it at room temperature for 10 minutes, then wash the surface with pure water to prepare a micro-nano gold surface; second, spread a layer of fluorine-containing thiol solution on the prepared micro-nano gold surface to cover the entire gold surface, and then place it at room temperature overnight, and after 12 hours of reaction, the fluorine-containing thiol is grafted on the gold surface; then place it in a vacuum oven for 1 hour to remove the free fluorine-containing thiol on the surface of the material;

[0035] Step four, oil immersion treatment: place the surface-treated sample in a lubricant in an 80°C oven for 48 hours for oil immersion treatment;

[0036] Step five, oil control treatment: place the oil immersion treated sample vertically for 12 hours to remove excess lubricant.

[0037] The third object of the present application is to provide the application of the gold surface anticoagulant coating structure described in one of the application purposes or the gold surface anticoagulant coating structure prepared by the preparation method described in the second application purpose in medical devices. Specifically, in the field of blood contact medical device materials.

[0038] Compared with the prior art, the present application has the following advantages:

[0039] The gold surface anticoagulant coating structure prepared by treating the gold surface can prevent protein and cell adhesion, prevent platelet activation, inhibit the coagulation cascade reaction, and has good anticoagulant effect. It can avoid complications caused by the use of anticoagulants and inhibit vascular embolism caused by coagulation on the surface of medical devices. The noble metal gold has good biocompatibility, the preparation method is simple, and it is suitable for surface treatment of gold-plated medical implant equipment, and can be applied to the surface anticoagulant treatment of all noble metal medical devices in contact with blood; it has good application prospect in the field of anticoagulant medical devices and medical implant equipment.

[0040] The liquid injection surface prepared by modifying the gold surface and then injecting the lubricant can reduce the resistance of blood flow and resist blood adhesion. By preparing a micro-nano gold surface and using the affinity of fluorine-containing thiol for lubricant and the strong interaction between gold and sulfur, the locking ability of the gold surface for the lubricant is greatly increased, and the locking ability of the gold surface for the lubricant is enhanced by the capillary action of the micro-nano structure of the gold surface, which has high and long-lasting anticoagulant ability, long-term anticoagulant effect, and significantly improved anticoagulant stability of the gold surface.

[0041] The present application uses chloroauric acid to reduce in situ on the gold surface to prepare nanoparticles with controllable morphology, simple method, low preparation cost and low equipment requirement. The self-lubricating anticoagulant surface prepared has good durability and stability, and has long-term anticoagulant effect.

[0042] In the present application, the room temperature is 20-30℃. BRIEF DESCRIPTION OF DRAWINGS

[0043] Figure 1a SEM image of the gold plating layer before modification;

[0044] Figure 1b SEM image of the micro-nano gold surface structure obtained by modification of Example 1;

[0045] Figure 1c SEM image of the micro-nano gold surface structure obtained by modification of Example 2;

[0046] Figure 1d SEM image of the micro-nano gold surface structure obtained by modification of Example 3;

[0047] Figure 2a AFM two-dimensional topography image of the gold plating layer before modification;

[0048] Figure 2b AFM two-dimensional topography image of the micro-nano gold surface structure obtained by modification of Example 1;

[0049] Figure 2c AFM two-dimensional topography image of the micro-nano gold surface structure obtained by modification of Example 2;

[0050] Figure 2d AFM two-dimensional topography image of the micro-nano gold surface structure obtained by modification of Example 3;

[0051] Figure 3a AFM three-dimensional topography image of the gold plating layer before modification;

[0052] Figure 3b AFM three-dimensional topography image of the micro-nano gold surface structure obtained by modification of Example 1;

[0053] Figure 3c AFM three-dimensional topography image of the micro-nano gold surface structure obtained by modification of Example 2;

[0054] Figure 3d AFM three-dimensional topography image of the micro-nano gold surface structure obtained by modification of Example 3;

[0055] Figure 4a Platelet adhesion scanning electron microscope image of the gold plating layer before and after modification;

[0056] Figure 4b Platelet adhesion scanning electron microscope image of the self-lubricating gold surface anticoagulant coating structure NP-SLIPS obtained by modification of Example 1; 50 Platelet adhesion scanning electron microscope image of the self-lubricating gold surface anticoagulant coating structure NP-SLIPS obtained by modification of Example 1;

[0057] Figure 4c NP for the self-lubricating gold surface anticoagulant coating structure obtained after modification of Example 2 100-20 SEM images of platelet adhesion of SLIPS;

[0058] Figure 4d NP for the self-lubricating gold surface anticoagulant coating structure obtained after modification of Example 3 100-50 SEM images of platelet adhesion of SLIPS;

[0059] Figures 4a-4d In the middle, the scanning electron microscope magnification is 10WX;

[0060] Figure 5 Quantitative analysis results of platelet adhesion before and after modification of the gold plating layer; the ordinate is the adhesion rate; control is the metal plating layer before modification, NP 50 SLIPS for the self-lubricating gold surface anticoagulant coating structure obtained after modification of Example 1 50 SLIPS, NP 100-20 SLIPS for the self-lubricating gold surface anticoagulant coating structure obtained after modification of Example 2 100-50 SLIPS for the self-lubricating gold surface anticoagulant coating structure obtained after modification of Example 3 100-50 SLIPS;

[0061] Figure 6 The contact angle stability diagram of the self-lubricating gold surface anticoagulant coating structure surface after modification of Examples 1-3 and Comparative Example 1 for different ultrasonic times, the abscissa is the ultrasonic time, and the ordinate is the static water contact angle. DETAILED DESCRIPTION

[0062] The following embodiments and examples are described in detail below, and it is necessary to point out that the following examples are only used to further illustrate the present application, and cannot be understood as limiting the protection scope of the present application. Some non-essential improvements and adjustments of the present application made by those skilled in the art according to the content of the present application still fall within the protection scope of the present application.

[0063] In the following examples and comparative examples, if not specifically stated, the raw materials and reagents used are commercially available products.

[0064] Tetrachloroauric acid (III) trihydrate (Aladdin, HAuCl4·3H2O, 99.9%) and 1H, 1H, 2H, 2H-perfluorodecanethiol (Aladdi, CF3(CF2)7CH2CH2SH, Mn=480.18) were obtained from Aladdin Reagent Co., Ltd. and used as received.

[0065] Perfluoropolyether (Macklin, Mn=4500), PBS buffer (PH=7.2-7.4) were purchased from Macklin.

[0066] Sodium citrate (98%, BR) was purchased from Beijing Solabio Technology Co., Ltd.

[0067] Solvent anhydrous ethanol was purchased from Shanghai Mailei Biochemical Technology Co., Ltd. and used as received.

[0068] Example 1

[0069] (1) Surface cleaning work was performed on the gold-plated surface. First, the gold-plated surface was ultrasonically treated with anhydrous ethanol solution for 10 min to remove grease, dust and other impurities; then ultrasonic deionized water for 10 min to further clean the residual ethanol; finally, the surface moisture was dried using a drying oven with a temperature setting of 80℃. The morphology of the cleaned gold-plated layer (SEM, two-dimensional AFM, three-dimensional AFM) is shown in Figure 1a , Figure 2a , Figure 3a Figure 1a , Figure 2a , Figure 3a respectively, showing that the surface roughness of the unmodified gold-plated layer is low, with an arithmetic average roughness (Arithmetic Average Roughness, abbreviated as Ra) Ra=22.2nm.

[0070] (2) Gold surface modifier was configured. A 50mM, 100mM chloroauric acid solution was prepared with pure water as the solvent; a 2M fluorine-containing mercaptan solution was prepared with anhydrous ethanol as the solvent; both were used as gold surface modifiers.

[0071] (3) 20μL of 50mM chloroauric acid solution was applied to the surface of the cleaned gold-plated layer with a size of 1×1cm 2 , so that the 1×1cm 2 gold-plated surface was completely covered, and placed at room temperature for 10 minutes to fully reduce the chloroauric acid in situ to form a micro-nano gold surface. The morphology of the micro-nano gold surface (SEM, two-dimensional AFM, three-dimensional AFM) is shown in Figure 1b , Figure 2b , Figure 3b . Figure 1b , Figure 2b , Figure 3b showing that the surface roughness of the gold-plated layer after modification in this step is increased, with an arithmetic average roughness Ra=54.2nm. After modification in this step, the gold-plated layer forms a saline-alkali soil-like surface coating, forming a uniform and dense gold nanoparticle coating at the micro-nano level.

[0072] (4) 20μL of 2M fluorine-containing mercaptan solution was applied to the surface of the gold-plated layer with a size of 1×1cm 2 ​The saline-alkali soil-like micro-nano gold surface is smeared with 20 μL of fluorine-containing thiol solution to form a fluorine-containing thiol modified layer.

[0073] (5) The perfluoropolyether is injected into the 1 × 1 cm 2 The saline-alkali soil-like micro-nano gold surface of the fluorine-containing thiol modified layer is placed for 48 h, and then the gold surface is placed vertically to the horizontal plane for 12 h to remove the excess perfluoropolyether, to obtain the self-lubricating gold surface anticoagulant coating structure NP 50 -SLIPS.

[0074] Example 2

[0075] (1) 20 μL of the 100 mM chloroauric acid solution prepared in Example 1 is smeared on the 1 × 1 cm 2 The gold-plated layer surface after cleaning in Example 1 is placed with the 1 × 1 cm 2 The gold-plated surface is completely covered, and is placed at room temperature for 10 minutes to sufficiently perform in-situ reduction of the chloroauric acid to form a micro-nano gold surface. The morphology diagrams (SEM, two-dimensional AFM, and three-dimensional AFM) of the micro-nano gold surface are shown in Figure 1c , Figure 2c , Figure 3c . Figure 1c , Figure 2c , Figure 3c It is shown that the surface roughness of the gold-plated layer is improved after the modification treatment in this step, and the arithmetic average roughness Ra = 41.9 nm. After the modification treatment of the gold-plated layer in this step, a micro-convex dendritic surface coating is formed, and a uniform and dense gold nano-particle coating in the micro-nano level is formed.

[0076] (2) 20 μL of the fluorine-containing thiol solution prepared in Example 1 is smeared on the micro-convex dendritic micro-nano gold surface of the 1 × 1 cm 2 The saline-alkali soil-like micro-nano gold surface is smeared with 20 μL of fluorine-containing thiol solution to form a fluorine-containing thiol modified layer.

[0077] (3) The perfluoropolyether is injected into the 1 × 1 cm 2 The saline-alkali soil-like micro-nano gold surface of the fluorine-containing thiol modified layer is placed for 48 h, and then the gold surface is placed vertically to the horizontal plane for 12 h to remove the excess perfluoropolyether, to obtain the self-lubricating gold surface anticoagulant coating structure NP 100-20 -SLIPS.

[0078] Example 3

[0079] (1) 50 μL of the 100 mM chloroauric acid solution prepared in Example 1 is smeared on the 1 × 1 cm 2 The gold-plated layer surface after cleaning in Example 1 is placed with the 1 × 1 cm 2The gold-plated surface is fully covered and placed at room temperature for 10 minutes to fully perform in-situ reduction of chloroauric acid to form a micro-nano gold surface. The morphology of the micro-nano gold surface (SEM, two-dimensional AFM, three-dimensional AFM) is shown in Figure 1d 、 Figure 2d 、 Figure 3d . Figure 1d 、 Figure 2d 、 Figure 3d It is shown that the surface roughness of the gold-plated layer is improved after modification treatment in this step, and the arithmetic average roughness Ra = 57.9 nm. After modification treatment of the gold-plated layer in this step, a dendritic surface coating is formed, and a uniform and dense gold nanoparticle coating of micro-nano level is formed.

[0080] (2) 20 μL of the fluorine-containing thiol solution prepared in Example 1 is applied to the dendritic micro-nano gold surface of 1 × 1 cm 2 to form a fluorine-containing thiol modified layer.

[0081] (3) The perfluoropolyether is injected into the dendritic micro-nano gold surface of 1 × 1 cm 2 containing fluorine-containing thiol modified layer at 80°C, and after 48 h, the gold surface is placed vertically to the horizontal plane for 12 h to remove excess perfluoropolyether to obtain a self-lubricating gold surface anti-coagulation coating structure NP 100-50 -SLIPS.

[0082] In Examples 1-3, the arithmetic average roughness (Arithmetic Average Roughness) represents the average value of the absolute value of the height deviation of all measured points on the sample surface relative to the reference plane, and Ra can help to quantitatively describe the smoothness or roughness of the surface. High Ra value: represents high surface roughness, and the surface has large ups and downs. Low Ra value: represents a smooth surface, and the surface has small ups and downs.

[0083] Comparative Example 1

[0084] (1) The gold-plated surface is subjected to surface cleaning work. First, the gold-plated surface is subjected to ultrasonic treatment for 10 min with anhydrous ethanol solution to wash off grease, dust and other impurities; then, the residual ethanol is further cleaned by ultrasonic treatment for 10 min with deionized water; finally, the surface moisture is dried by using a drying oven with a temperature setting of 80°C.

[0085] (2) The perfluoropolyether is injected into the surface of the cleaned gold-plated layer of 1 × 1 cm 2 at 80°C, and after 48 h, the gold surface is placed vertically to the horizontal plane for 12 h to remove excess perfluoropolyether to obtain a self-lubricating anti-coagulation gold surface Au-SLIPS.

[0086] Platelet adhesion test

[0087] Platelet adhesion test before and after gold plating layer modification, the specific experimental operation process is as follows:

[0088] 1、 The blood used in this experiment is fresh rabbit blood. Fresh rabbit blood is mixed with 3.8wt% sodium citrate solution according to 10:1, centrifuged at 3000rmp for 15min on centrifuge, and the supernatant is platelet-rich plasma (PRP).

[0089] 2、 The gold plating layer before modification, the self-lubricating gold surface anticoagulant coating structure obtained in example 1-3 is used as sample; the sample is respectively put into twelve-hole plate, 100ul PRP is added on the surface of each sample, and the sample is incubated in 37℃ constant temperature box for 1h.

[0090] 3、 The incubated sample is taken out and washed with PBS for three times, and fixed with 2.5% glutaraldehyde at 4℃ for 4h.

[0091] 4、 Wash (wash with PBS for three times to remove glutaraldehyde solution), dehydrate (dehydrate with gradient alcohol 50%, 70%, 90%, 100% for 10min / time).

[0092] 5、 The dehydrated sample is treated by gold spraying, and observed by scanning electron microscope, as shown in Figure 4a 、 Figure 4b 、 Figure 4c 、 Figure 4d

[0093] Figure 4a It is shown that a large number of platelets adhere to the surface of the unmodified gold plating layer; Figure 4b 、 Figure 4c 、 Figure 4d It is shown that the self-lubricating gold surface anticoagulant coating structure obtained in example 1, 2 and 3 has smooth and flat surface, and almost no platelets adhere to it. It is shown that the self-lubricating gold surface anticoagulant coating structure obtained after modification in example 1, 2 and 3 has good anticoagulant ability.

[0094] 6、 The platelet adhesion area ratio (adhesion rate) of each sample is statistically analyzed by image processing software ImageJ to obtain the quantitative analysis results of platelet adhesion before and after gold plating layer modification; as shown in Figure 5 . Specifically, each sample is repeated for 5 times, and the average value and standard deviation (the error bar shown in the figure is the standard deviation) are calculated; the statistical analysis and final chart are made by using GraphPad Prism 8 software. Figure 5 It is shown that the adhesion rate of the unmodified gold plating layer surface is as high as 40%, while the adhesion rate of the self-lubricating gold surface anticoagulant coating structure obtained in example 1, 2 and 3 is only 2% or less; it is shown that the self-lubricating gold surface anticoagulant coating structure obtained after modification in example 1, 2 and 3 has good anticoagulant ability.​

[0095] Anti-coagulation durability test

[0096] The self-lubricating gold surface anti-coagulation coating structures obtained from Examples 1-3 and Comparative Example 1 were prepared into 1 cm x 1 cm samples. The water contact angle of the sample surface was measured. Then the prepared samples were treated in PBS (PH = 7.2-7.4) for different times (ultrasonic frequency 40 kHz, ultrasonic power 100 W), and the water contact angle of the sample surface was measured. The test results are shown in Table 1. Figure 6

[0097] Figure 6 It is shown that the surface contact angle of Comparative Example 1 decreased significantly after ultrasonic treatment for 30 minutes, and the oil layer was lost. The surface contact angles of Examples 1, 2 and 3 decreased slowly to different degrees as the ultrasonic time was prolonged, but all maintained at a high level. It is shown that the self-lubricating gold surface anti-coagulation coating structure obtained by modifying the gold layer according to Examples 1-3 has very good stability, the lubricating oil layer is not lost, and has a durable anti-coagulation effect. Among them, the contact angle of Example 3 after ultrasonic treatment for 30 minutes is higher than that of other examples, and has the best stability effect.​

Claims

1. A gold surface anti-coagulation coating structure comprising, from bottom to top, a micro-nano gold surface, a grafting modification layer and an anti-coagulation layer. The grafting modification layer contains fluorine-containing mercaptan, and the fluorine-containing mercaptan is grafted on the micro-nano gold surface. The anti-coagulation layer contains a lubricant.

2. The gold surface anticoagulant coating structure of claim 1, wherein, The fluorine-containing mercaptan is selected from one or more of 1H, 1H, 2H, 2H- perfluorodecanethiol, 3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 8-tridecafluoro-1-octanethiol and 3, 3, 4, 4, 5, 5, 6, 5, 6-n-fluoro-1-hexanethiol. 3.The gold surface anti-coagulation coating structure of claim 1, wherein the lubricant is selected from one or more of perfluoropolyether, silicone oil, fluorinated lubricating oil, ionic liquid and polyethylene glycol. The lubricant is perfluoropolyether or / and fluorinated lubricating oil.

4. The gold surface anticoagulant coating structure of claim 1, wherein, 5.A method for preparing the gold surface anti-coagulation coating structure of any one of claims 1-4, comprising: (1) coating a gold surface with a chloroauric acid solution to obtain a micro-nano gold surface; (2) coating a fluorine-containing mercaptan solution on the micro-nano gold surface, standing, and drying to form a grafting modification layer; (3) placing the micro-nano gold surface with the grafting modification layer in a lubricant, soaking, taking out and vertically placing to form an anti-coagulation layer. In step (1), the gold surface is a gold plating layer surface.

6. The production method according to claim 5, wherein In step (1), 7. The production method according to claim 5, wherein The solvent of the chloroauric acid solution is pure water; or / and, The concentration of the chloroauric acid solution is 10 mM-100 mM; or / and, In step (1), Per 1 x 1 cm 2 The amount of the chloroauric acid solution used on the gold surface is 20 μL to 100 μL.

8. The production method according to claim 5, wherein The concentration of the chloroauric acid solution is 50 mM-100 mM; or / and, In step (2), Per 1 x 1 cm 2 The amount of the chloroauric acid solution used on the gold surface is 20 μL-50 μL.

9. The production method according to claim 5, wherein The solvent of the fluorine-containing mercaptan solution is selected from anhydrous ethanol, acetone or isopropanol; or / and, The concentration of the fluorine-containing mercaptan solution is 1-5 M. In step (2), the concentration of the fluorine-containing mercaptan solution is 2-3 M.

10. The production method according to claim 5, wherein In step (2), 11. The production method according to claim 5, wherein The standing time is 12 h or more; or / and, The drying condition is vacuum and room temperature, and the drying time is 1 h or more. In step (3), 12. The production method according to claim 5, wherein The soaking temperature is 60-80 ℃, the soaking time is 48 h or more, and the vertically placing time is 12 h or more. 13.Use of the gold surface anti-coagulation coating structure of any one of claims 1-3 or the gold surface anti-coagulation coating structure prepared by the method of any one of claims 4-9 in the preparation of a medical device. ​

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