Degradable super-hydrophobic covering film as well as preparation method and application thereof

Abstract

The invention discloses a preparation method of a degradable super-hydrophobic coating film, which comprises the following steps: A, carrying out modification treatment on nano-scale zinc oxide to obtain a solution containing nano-scale modified zinc oxide; carrying out centrifugal separation and drying on the solution containing the nano-scale modified zinc oxide to obtain the nano-scale modified zinc oxide; b, carrying out modification treatment on micron-sized polycaprolactone to obtain a solution containing micron-sized modified polycaprolactone; c, adding the nano-scale modified zinc oxide into the solution containing the micron-scale modified polycaprolactone to obtain an electrostatic spinning solution; and D, carrying out electrostatic spinning on the electrostatic spinning solution by utilizing electrostatic spinning equipment, and drying to obtain the degradable super-hydrophobic covering film. According to the preparation method of the degradable super-hydrophobic covering film, the preparation method is simple and high in operability, and it is ensured that when the obtained covering film is applied to preparation of a covered stent, the covered stent can have extremely low risks of restenosis, thrombosis and inflammation.

Description

Technical Field

[0001] The present invention relates to the field of film coating technology, and in particular to a degradable super-hydrophobic film and a preparation method and application thereof. Background Art

[0002] In the medical field, medical stents are important therapeutic tools and are widely used for implantation in human cavities such as blood vessels, bile ducts, and trachea, with the aim of maintaining, opening, or expanding these cavities. Medical stents mainly include the following categories: (1) Bare stents. Bare stents are usually made of metal materials with good biocompatibility with the human body, such as stainless steel, nickel-titanium alloy, and cobalt-chromium alloy. Their surfaces are only polished and have a hollow structure, which makes it easy for external tissues or cells to grow inside the bare stent, resulting in a higher risk of restenosis, thrombosis, and inflammation; (2) Drug-coated stents, which are made by coating the surface of the bare stent with anti-thrombotic or anti-inflammatory drugs such as abciximab, dexamethasone, rapamycin, or paclitaxel. Compared with bare stents, drug-coated stents have higher biocompatibility and better therapeutic effects. However, since their surface is still a hollow structure, it is also easy for external tissues or cells to grow into the inside of the bare stent, making it more likely to have restenosis, thrombosis and inflammation. (3) Covered stents. Covered stents are prepared by attaching a layer of coating to a bare stent. The coating forms a physical barrier on the surface of the bare stent, making the covered stent have a lower risk of restenosis (restenosis refers to the narrowing of the blood vessel lumen diameter after vascular intervention), thrombosis (thrombosis refers to the formation of blood clots in the blood vessel after vascular intervention) and inflammation than bare stents and drug-coated stents. They are widely used in the field of medical stents.

[0003] At present, the coatings used for medical stents are mainly divided into two categories: non-degradable coatings (materials mainly include polytetrafluoroethylene, polyurethane, silicone and high-density polyethylene) and degradable coatings (materials mainly include polylactic acid, polyglycolic acid and polylactic-glycolic acid copolymer). Although the durability of non-degradable coatings is good, their non-degradability can easily cause inflammatory reactions or rejection reactions, resulting in the coated stents prepared using them still having certain risks of restenosis, thrombosis and inflammation. Although the degradable coating has good degradability, it may form a microenvironment suitable for bacterial growth during the degradation process, especially when small holes or cracks are generated on the surface of the coating during the degradation process, which can easily cause plasma proteins and bacteria to adhere to its surface, thereby increasing the risks of restenosis, thrombosis and inflammation of the coated stents prepared using them.

[0004] In order to overcome the above defects, the existing technology increases the hydrophobicity of the surface of the degradable coating to reduce the adsorption of plasma proteins and the adhesion of bacteria on its surface, thereby reducing the risk of restenosis, thrombosis and inflammation of the coated stent. However, due to the limitations of the existing preparation process and raw material selection, the static water contact angle of the degradable coating is only 60-120°, and the hydrophobic effect is limited, so that the risk of restenosis, thrombosis and inflammation of the coated stent prepared by using it is limited, and it is still difficult to meet the use requirements. Summary of the invention

[0005] The first purpose of the present invention is to propose a method for preparing a degradable superhydrophobic coating. The preparation method is simple and easy to operate, and ensures that when the obtained coating is used to prepare a coated stent, the coated stent has an extremely low risk of restenosis, thrombosis and inflammation, so as to solve the technical problems in the prior art that the coated stent has a high risk of thrombosis, the stent is easy to restenosis, and the possibility of inflammation is high.

[0006] The second purpose of the present invention is to propose a degradable super-hydrophobic coating with a degradation rate ≥90% and a static water contact angle >150°, to ensure that when the obtained coating is used to prepare a coated stent, the coated stent has an extremely low risk of restenosis, thrombosis and inflammation, so as to meet actual usage requirements.

[0007] The third purpose of the present invention is to use a degradable super-hydrophobic coating to prepare a coated stent, thereby ensuring that the obtained coated stent has an extremely low risk of restenosis, thrombosis and inflammation.

[0008] To achieve this object, the present invention adopts the following technical solutions:

[0009] A method for preparing a degradable super-hydrophobic coating comprises the following steps:

[0010] A. adding nano-scale zinc oxide to a low surface energy solution for modification to obtain a solution containing nano-scale modified zinc oxide; centrifuging and drying the solution containing nano-scale modified zinc oxide in sequence to obtain nano-scale modified zinc oxide;

[0011] B. adding micron-sized polycaprolactone into a low surface energy solution for modification to obtain a solution containing micron-sized modified polycaprolactone;

[0012] C. adding nano-scale modified zinc oxide into a solution containing micro-scale modified polycaprolactone, and mixing them evenly to obtain an electrospinning solution;

[0013] D. The electrospinning solution is electrospun using an electrospinning device, and a degradable super-hydrophobic coating is obtained after drying.

[0014] Furthermore, in step A and step B, the raw materials of the low surface energy solution include a low surface energy solute and a solvent;

[0015] Calculated by mass percentage, the content of the low surface energy solute in the low surface energy solution is 1-5%.

[0016] Further, the low surface energy solute includes any one or more combinations of heptadecafluorodecyltriethoxysilane, tridecafluorooctyltrimethoxysilane, stearic acid and polydimethylsiloxane;

[0017] The solvent includes any one or more combinations of methanol, ethanol, n-propanol, isopropanol, acetone, tetrahydrofuran, N,N-dimethylformamide and xylene.

[0018] Furthermore, in step A, the particle size of the nano-sized zinc oxide is 5 to 50 nm;

[0019] In step B, the particle size of the micron-sized polycaprolactone is 5 to 10 μm.

[0020] Furthermore, in step A, the specific method of centrifugal separation is: placing the solution containing nano-modified zinc oxide into a centrifuge tube, centrifuging at a centrifugal speed of 1000 to 3000 r / min for 0.1 to 0.3 h, removing the supernatant to obtain a white precipitate;

[0021] The specific drying method is: drying the white precipitate at a temperature of 50-120° C., and weighing it once at a preset interval until the weights of two consecutive weighings are consistent, then the drying is completed to obtain nano-grade modified zinc oxide.

[0022] Furthermore, in step A, the mass ratio of the nano-sized zinc oxide to the low surface energy solution is (1-10): (10-20);

[0023] In step B, the mass ratio of the micron-sized polycaprolactone to the low surface energy solution is (3-20): (101-110);

[0024] In step C, the mass ratio of the nano-scale modified zinc oxide to the solution containing the micron-scale modified polycaprolactone is (0.5-4):(104-130).

[0025] Furthermore, in step D, the caliber of the needle of the electrospinning device is 22 to 30G, the spinning voltage is 15 to 30 kV, the liquid output rate is 1.5 to 15 mL / h, the spinning time is 30 to 180 s, and the receiving distance is 5 to 20 cm.

[0026] Furthermore, in step D, the drying temperature is 30 to 60° C., and the drying time is 1 to 6 hours.

[0027] A degradable super-hydrophobic film is prepared using the above-mentioned method for preparing a degradable super-hydrophobic film. The degradation rate of the degradable super-hydrophobic film is ≥90%, and the static water contact angle is >150°.

[0028] A degradable super-hydrophobic coating is used in the preparation of a coated stent. The above-mentioned degradable super-hydrophobic coating is used in an application method of: adhering the degradable super-hydrophobic coating to the surface of a bare stent to obtain a coated stent.

[0029] The technical solution provided by the present invention may include the following beneficial effects:

[0030] 1. Nano zinc oxide has low toxicity to cells and has good biocompatibility, which is conducive to the good biocompatibility of nano-modified zinc oxide; the molecular structure of micron-sized polycaprolactone is similar to natural substances in the human body, and it is not easy to induce immune response in the human body, which reduces its potential toxicity when interacting with the body, ensuring its good biocompatibility, which is also conducive to the good biocompatibility of micron-sized modified polycaprolactone. Therefore, when nano-sized modified zinc oxide and micron-sized modified polycaprolactone are combined in the electrospinning solution, the coating obtained by electrospinning the electrospinning solution also shows good biocompatibility, significantly reducing the risk of restenosis, thrombosis and inflammation caused by rejection reaction of the coated stent prepared by the coating.

[0031] 2. Nano-scale zinc oxide can be decomposed into zinc ions and water in the human body. Zinc ions are essential trace elements for the human body and are easily absorbed, which gives them degradability, making nano-scale modified zinc oxide also degradable; micron-scale polycaprolactone is hydrolyzed by ester bonds and gradually decomposed into small molecules, which are eventually absorbed by the body and converted into water and carbon dioxide for discharge, showing degradability, making micron-scale modified polycaprolactone also degradable. Therefore, when nano-scale modified zinc oxide and micron-scale modified polycaprolactone are combined in an electrospinning solution, the coating obtained by electrospinning the electrospinning solution is also degradable, avoiding inflammatory reactions or rejection reactions caused by long-term foreign body residues in the human body, thereby reducing the risk of restenosis, thrombosis and inflammation of the coated stent prepared by the coating.

[0032] 3. In this technical solution, nano-scale zinc oxide and micron-scale polycaprolactone are modified by using a low surface energy solution, so that the modified nano-scale modified zinc oxide and micron-scale modified polycaprolactone have lower surface energy, so that the coating has lower surface energy, and the reduction of the surface energy of the coating is directly beneficial to enhancing its hydrophobicity, that is, the coating exhibits higher hydrophobicity. At the same time, nano-scale modified zinc oxide can form a nano-scale rough structure, and micron-scale modified polycaprolactone can form a micron-scale rough structure. The above two sizes of rough structures cooperate with each other to form a micro-nano composite rough structure on the surface of the coating, thereby increasing the irregularity of the coating surface, making it difficult for the liquid to form a stable contact surface on the coating surface, thereby increasing the hydrophobicity of the coating. In addition, when the micro-nano composite rough structure of the coating is matched with its low surface energy characteristics, an extremely thin air film will be formed between the coating surface and the liquid. The above air film can greatly hinder the wetting of the liquid on the coating surface, so that the coating has extremely high hydrophobicity. That is, the present technical solution makes the coating surface super-hydrophobic through the above-mentioned multiple effects. The super-hydrophobicity of the coating surface can significantly reduce the adsorption of plasma proteins and the adhesion of bacteria on its surface, thereby reducing the risk of restenosis, thrombosis and inflammation of the coated stent. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is a physical picture of the product of Example 1 of the present invention.

[0034] Figure 2 It is a schematic diagram of adding water drops to the actual product of Example 1 of the present invention.

[0035] Figure 3 These are SEM images of Example 1 of the present invention at 2000 times and 10000 times respectively. DETAILED DESCRIPTION

[0036] The present technical solution provides a method for preparing a degradable super-hydrophobic coating, comprising the following steps:

[0037] A. adding nano-scale zinc oxide to a low surface energy solution for modification to obtain a solution containing nano-scale modified zinc oxide; centrifuging and drying the solution containing nano-scale modified zinc oxide in sequence to obtain nano-scale modified zinc oxide;

[0038] B. adding micron-sized polycaprolactone into a low surface energy solution for modification to obtain a solution containing micron-sized modified polycaprolactone;

[0039] C. adding nano-scale modified zinc oxide into a solution containing micro-scale modified polycaprolactone, and mixing them evenly to obtain an electrospinning solution;

[0040] D. The electrospinning solution is electrospun using an electrospinning device, and a degradable super-hydrophobic coating is obtained after drying.

[0041] In order to solve the technical problems of high risk of thrombosis, easy restenosis of stents, and high possibility of inflammation in the prior art. This technical solution proposes a method for preparing a degradable superhydrophobic coating, including four steps of A (preparing nano-scale modified zinc oxide), B (preparing a solution containing micron-scale modified polycaprolactone), C (preparing an electrospinning solution) and D (electrospinning), so that when the prepared coating is applied to the preparation of a coated stent, the coated stent can have extremely low risks of restenosis, thrombosis and inflammation, so as to solve the technical problems of high risk of thrombosis of the coated stent, easy restenosis of the stent, and high possibility of inflammation in the prior art. At the same time, the preparation method of this technical solution is simple, highly operable, and easy to scale production.

[0042] Specifically, nano zinc oxide has low toxicity to cells and has good biocompatibility, which is conducive to the good biocompatibility of nano-modified zinc oxide; the molecular structure of micron-sized polycaprolactone is similar to natural substances in the human body, and it is not easy to induce an immune response in the human body, which reduces its potential toxicity when interacting with the body, ensuring its good biocompatibility, which is also conducive to the good biocompatibility of micron-sized modified polycaprolactone. Therefore, when nano-sized modified zinc oxide and micron-sized modified polycaprolactone are combined in an electrospinning solution, the coating obtained by electrospinning the electrospinning solution also shows good biocompatibility, significantly reducing the risk of restenosis, thrombosis and inflammation caused by rejection reactions of the coated stent prepared by the coating.

[0043] Furthermore, nano-scale zinc oxide can be decomposed into zinc ions and water in the human body. Zinc ions, as essential trace elements for the human body, are easily absorbed, giving them degradability, making nano-scale modified zinc oxide also degradable; micron-scale polycaprolactone is hydrolyzed by ester bonds, gradually decomposed into small molecules, and finally absorbed by the body and converted into water and carbon dioxide for discharge, showing degradability, making micron-scale modified polycaprolactone also degradable. Therefore, when nano-scale modified zinc oxide and micron-scale modified polycaprolactone are combined in an electrospinning solution, the coating obtained by electrospinning the electrospinning solution is also degradable, avoiding inflammatory reactions or rejection reactions caused by long-term foreign body residues in the human body, thereby reducing the risk of restenosis, thrombosis and inflammation of the coated stent prepared by the coating.

[0044] Secondly, although the biocompatibility and degradability of nano-zinc oxide and micron-sized polycaprolactone are beneficial to reducing the risk of restenosis, thrombosis and inflammation of the coated stent, the improvement effect is limited, and still does not meet the use requirements of the low risk of restenosis, thrombosis and inflammation of the coated stent. Therefore, in the present technical solution, nano-zinc oxide and micron-sized polycaprolactone are modified by using a low surface energy solution, so that the modified nano-sized modified zinc oxide and micron-sized modified polycaprolactone have a lower surface energy, so that the coating has a lower surface energy, and the reduction of the surface energy of the coating is directly beneficial to enhancing its hydrophobicity, that is, the coating exhibits a higher hydrophobic property. At the same time, the nano-sized modified zinc oxide can form a nano-sized rough structure, and the micron-sized modified polycaprolactone can form a micron-sized rough structure. The above two sizes of rough structures cooperate with each other to form a micro-nano composite rough structure on the surface of the coating, thereby increasing the irregularity of the coating surface, making it difficult for the liquid to form a stable contact surface on the coating surface, thereby increasing the hydrophobicity of the coating. In addition, when the micro-nano composite rough structure of the coating is matched with its low surface energy characteristics, an extremely thin air film will be formed between the coating surface and the liquid. The air film can greatly hinder the wetting of the coating surface by the liquid, making the coating have extremely high hydrophobic properties. That is, this technical solution makes the coating surface super hydrophobic through the above-mentioned multiple effects. The super hydrophobicity of the coating surface can significantly reduce the adsorption of plasma proteins and the adhesion of bacteria on its surface, thereby reducing the risk of restenosis, thrombosis and inflammation of the coated stent.

[0045] Furthermore, nano-zinc oxide can generate highly reactive active oxygen species such as superoxide anion free radicals and hydroxyl free radicals in the human body. The above-mentioned reactive oxygen species can use their super strong oxidizing properties to oxidize bacteria and decompose them into harmless substances. At the same time, when nano-zinc oxide comes into contact with bacteria, it can release zinc ions. Zinc ions will not only destroy the internal environment of the bacteria, causing damage to the cell wall of the bacteria, and then destroy the inherent morphology of the cells, but also zinc ions can combine with active proteases in the bacteria to make them inactive, thereby blocking the life activities of bacteria and achieving a bactericidal effect. In addition, the small size effect of nano-zinc oxide also makes it easier to penetrate the cell wall and cell membrane of the bacteria, directly acting on the inside of the bacteria, making it have a better bactericidal effect than ordinary zinc oxide, thereby further improving the bactericidal effect. That is, the above-mentioned properties of nano-zinc oxide are conducive to making nano-zinc oxide have extremely high bactericidal effect, thereby making the coating also have extremely high bactericidal effect, so that even if bacteria and other microorganisms adhere to the surface of the coated stent prepared by using the coating, the coating can kill the above-mentioned microorganisms by virtue of its bactericidal properties, further reducing the risk of inflammation of the coated stent, and the reduction in the risk of inflammation of the coated stent is conducive to reducing the risk of restenosis of the coating, which is conducive to making the coating have extremely low risks of inflammation and restenosis.

[0046] Thirdly, due to the extremely small size of the nano-modified zinc oxide, it is easy to agglomerate and precipitate, which affects its subsequent uniformity of dispersion in the electrospinning solution, and thus affects the performance of the coating. In addition, after the modification of the nano-modified zinc oxide, a certain temperature is required to promote the chemical bonding between the modified group and zinc oxide, thereby ensuring the hydrophobic stability of the nano-modified zinc oxide. Therefore, the technical solution obtains nano-modified zinc oxide by centrifuging and drying the solution containing nano-modified zinc oxide in sequence. Large particles and impurities can be removed by centrifugation, and drying can be used to remove the solvent and promote the chemical bonding between the modified group and zinc oxide, so as to obtain pure and stable nano-modified zinc oxide, thereby ensuring the performance of the coated stent.

[0047] Finally, the prior art generally adopts the scraping method or the hot pressing method to prepare the coating, but due to the limitation of the preparation process, the thickness uniformity of the prepared coating is poor and the fibers forming the coating are arranged in a disordered manner, which makes the coating easy to cause structural fragility when degrading, causing it to rupture or fall off from the bare stent. The present technical solution prepares the coating by electrospinning, which not only ensures that the fibers obtained by spinning the electrospinning solution are evenly distributed, so that the coating presents a network structure with evenly distributed fibers, but also makes the fibers obtained by spinning have a thinner diameter and a higher aspect ratio, so that the interaction between the fibers is closer, thereby improving the mechanical strength and flexibility of the coating, avoiding the phenomenon that the coating is easy to cause structural fragility when degrading, causing it to rupture or fall off from the bare stent, and thus ensuring the performance of the coated stent. At the same time, the fibers are crisscrossed in multiple layers, so that the coating can disperse stress more effectively when subjected to external force, further avoiding the phenomenon of rupture of the coating or falling off from the bare stent due to local stress concentration. In addition, since the coating is composed of multiple layers of criss-crossed spun fibers, it has good air permeability, allowing for better gas exchange between blood vessels and blood even through the coated stent, which helps reduce damage to the blood vessels.

[0048] It should be noted that polylactic acid, polyglycolic acid and polylactic-glycolic acid copolymer cannot be used in this technical solution to replace nano-zinc oxide and micron-sized polycaprolactone, because the lactic acid and glycolic acid produced when polylactic acid, polyglycolic acid and polylactic-glycolic acid copolymer degrade will lead to local acid accumulation, which is easy to cause inflammatory response in surrounding tissues. In addition, titanium dioxide or silicon dioxide cannot be used in this technical solution to replace nano-zinc oxide and micron-sized polycaprolactone, because although titanium dioxide and silicon dioxide improve the hydrophobicity of the coating, the above materials cannot be absorbed by the human body and are not degradable.

[0049] It should be further explained that the technical solution cannot directly mix nano-zinc oxide, micron-sized polycaprolactone and low surface energy solution for modification. The reason is that the particle size of nano-zinc oxide is relatively small. When nano-zinc oxide, micron-sized polycaprolactone and low surface energy solution are mixed, the viscosity of the mixed solution is easily increased significantly. In a high viscosity environment, nano-zinc oxide particles tend to aggregate, making it difficult to achieve a sufficient modification effect. The above-mentioned insufficient modification will not only reduce the performance advantages of nano-zinc oxide itself, but also have an adverse effect on the performance of the final prepared coating.

[0050] Further, in step A and step B, the raw materials of the low surface energy solution include a low surface energy solute and a solvent;

[0051] Calculated by mass percentage, the content of the low surface energy solute in the low surface energy solution is 1-5%.

[0052] Since low surface energy solutes are relatively expensive materials, and the acceptable surface modification groups of nano-zinc oxide and micron-sized polycaprolactone are limited. If the content of low surface energy solutes in the low surface energy solution is too high, it will cause unnecessary waste; if the content of low surface energy solutes in the low surface energy solution is too low, it will easily lead to insufficient modification of nano-zinc oxide and micron-sized polycaprolactone. Therefore, the technical solution preferably limits the content of low surface energy solutes in the low surface energy solution to 1-5%, which is beneficial to ensure that nano-zinc oxide and micron-sized polycaprolactone are fully modified while reducing costs, and thus helps to ensure the performance of the coating.

[0053] Further, the low surface energy solute includes any one or more combinations of heptadecafluorodecyltriethoxysilane, tridecafluorooctyltrimethoxysilane, stearic acid and polydimethylsiloxane;

[0054] The solvent includes any one or more combinations of methanol, ethanol, n-propanol, isopropanol, acetone, tetrahydrofuran, N,N-dimethylformamide and xylene.

[0055] Heptafluorodecyl triethoxysilane, tridecafluorooctyl trimethoxysilane, stearic acid and polydimethylsiloxane all have lower surface energy, and the above raw materials all have Si-OH groups, and the Si-OH groups condense with the -OH groups on the surface of nano-scale modified zinc oxide to form Si-O-Zn, thereby completing the modification of nano-scale modified zinc oxide. In addition, the Si-OH groups can also form Si-OC bonds with the -COO- groups or -OH groups on the surface of micron-scale polycaprolactone, thereby completing the modification of micron-scale polycaprolactone. Therefore, the technical solution preferably selects any one or more combinations of the above-mentioned types of low surface energy solutes, which is conducive to ensuring the performance of the coating. In addition, the preferred low surface energy solute has a high cost performance, which is not only conducive to selecting suitable raw materials according to actual needs and improving the flexibility of the scheme, but also conducive to saving production costs under the premise of ensuring the performance of the coating.

[0056] In addition, when methanol, ethanol, n-propanol, isopropanol, acetone, tetrahydrofuran solution, N,N-dimethylformamide and xylene are preferably used as solvents, the solvents have good solubility for low surface energy solutes, which is conducive to fully dissolving low surface energy solutes and ensuring the performance of low surface energy solutions. In addition, the volatility of the solvents is relatively good, which can effectively save the drying time of nano-modified zinc oxide and improve production efficiency.

[0057] Further, in step A, the particle size of the nano-sized zinc oxide is 5 to 50 nm;

[0058] In step B, the particle size of the micron-sized polycaprolactone is 5 to 10 μm.

[0059] If the particle size of nano-zinc oxide and micron-sized polycaprolactone is too small, the surface area of ​​the film is too large, which makes it easier to adsorb polar molecules such as water molecules, thereby affecting its hydrophobic properties; if the particle size of nano-zinc oxide and micron-sized polycaprolactone is too large, not only will the micro-nano composite rough structure on the surface of the film become less uniform or less dense, making it difficult for the air film to exist stably, but it will also easily make the energy distribution on the surface of the film uneven, making it easier for certain areas to adsorb polar molecules such as water molecules, thereby reducing the hydrophobicity of the film surface. Therefore, the present technical solution limits the particle size of nano-zinc oxide and micron-sized polycaprolactone, which is conducive to ensuring the hydrophobicity of the film.

[0060] Further, in step A, the specific method of centrifugal separation is: putting the solution containing nano-modified zinc oxide into a centrifuge tube, centrifuging at a centrifugal speed of 1000 to 3000 r / min for 0.1 to 0.3 h, removing the supernatant, and obtaining a white precipitate;

[0061] The specific drying method is: drying the white precipitate at a temperature of 50-120° C., and weighing it once at a preset interval until the weights of two consecutive weighings are consistent, then the drying is completed to obtain nano-grade modified zinc oxide.

[0062] By optimizing the specific methods and parameters of centrifugal separation and drying, it is helpful to ensure the performance of nano-modified zinc oxide, thereby improving the performance of the coating.

[0063] Further, in step A, the mass ratio of the nano-sized zinc oxide to the low surface energy solution is (1-10): (10-20);

[0064] In step B, the mass ratio of the micron-sized polycaprolactone to the low surface energy solution is (3-20): (101-110);

[0065] In step C, the mass ratio of the nano-scale modified zinc oxide to the solution containing the micron-scale modified polycaprolactone is (0.5-4):(104-130).

[0066] This scheme optimizes the mass ratio of nano-zinc oxide added to the low surface energy solution, the mass ratio of micron-sized polycaprolactone to the low surface energy solution, and the mass ratio of nano-sized modified zinc oxide to the solution containing micron-sized modified polycaprolactone. This is not only conducive to adjusting the mass ratio of nano-zinc oxide added to the low surface energy solution, the mass ratio of micron-sized polycaprolactone to the low surface energy solution, and the mass ratio of nano-sized modified zinc oxide to the solution containing micron-sized modified polycaprolactone according to actual needs, thereby improving the flexibility of the scheme, but also conducive to ensuring the performance of the coating at a lower cost.

[0067] Further explanation, in step D, the caliber of the needle of the electrospinning equipment is 22-30G, the spinning voltage is 15-30kV, the liquid output rate is 1.5-15mL / h, the spinning time is 30-180s, and the receiving distance is 5-20cm.

[0068] If the caliber of the needle is too small, although the air permeability of the coating is good, the strength is slightly insufficient; if the caliber of the needle is too large, although the strength of the coating is high, the air permeability is slightly insufficient; if the spinning voltage and the liquid discharge rate are too small, electrospinning is not easy, which affects the efficiency of electrospinning; if the spinning voltage and the liquid discharge rate are too large, the coating obtained by spinning the electrospinning solution is easy to be stained with droplets. If the receiving distance is too small, although the electrospinning speed is fast, the uniformity is poor; in addition, if the receiving distance is too small, the electrostatic effect will be too strong, making the coating obtained by spinning the electrospinning solution easy to be stained with droplets; if the receiving distance is too large, although the electrospinning uniformity is good, the electrospinning speed is slow. In addition, if the receiving distance is too large, the electrostatic effect will be too weak, the spinning guidance is poor, and it is not easy to collect the coating obtained by spinning the electrospinning solution. If the spinning time is too short, the thickness of the obtained coating is too thin, its strength is poor, and it is easy to break or deform; if the spinning time is too long, the thickness of the obtained coating is too thick, the flexibility is poor, and it is easy to affect the implantation and compliance of the coated stent. Therefore, this technical solution limits the caliber, spinning voltage, liquid discharge rate, spinning time and receiving distance of the electrospinning equipment, which is conducive to ensuring the performance of the coating. It should be noted that the receiving distance refers to the distance between the needle of the electrospinning equipment and the receiving container that receives the coating.

[0069] Further, in step D, the drying temperature is 30 to 60° C., and the drying time is 1 to 6 hours.

[0070] If the drying temperature is too low, the bonding strength of the coating obtained after drying is poor; if the drying temperature is too high, the micron-sized modified polycaprolactone is easily degraded. If the drying time is too short, the coating is not completely dried; if the drying time is too short, the drying efficiency is too low, resulting in excessively high production costs and low production efficiency. Therefore, the technical solution limits the drying temperature and drying time of the drying in step D, which is conducive to ensuring the performance and production efficiency of the coating.

[0071] A degradable super-hydrophobic film is prepared using the above-mentioned method for preparing a degradable super-hydrophobic film. The degradation rate of the degradable super-hydrophobic film is ≥90%, and the static water contact angle is >150°.

[0072] The present scheme proposes a degradable super-hydrophobic coating prepared by the above-mentioned preparation method, which not only has good biocompatibility, but also has a degradation rate ≥ 90%, a static water contact angle > 150°, and a sterilization rate > 85%. The biocompatibility, degradation rate and static water contact angle are closely related to the risks of restenosis, thrombosis and inflammation of the coated stent prepared by the coating. The higher the biocompatibility, the greater the degradation rate and the greater the static water contact angle, the lower the risk of thrombosis, restenosis and inflammation of the coated stent; at the same time, the sterilization rate is closely related to the possibility of restenosis and inflammation of the coated stent prepared by the coating. The higher the sterilization rate, the lower the possibility of restenosis and inflammation of the coated stent. Therefore, the coated stent prepared by the coating of the present technical scheme has an extremely low risk of restenosis, thrombosis and inflammation, which is conducive to ensuring the safety of the use of the coated stent. It should be noted that the static water contact angle refers to the contact angle between the water droplet and the coating surface. The sterilization rate refers to that the sterilization rate of the coating against Escherichia coli and Staphylococcus aureus is greater than 85%.

[0073] A degradable super-hydrophobic coating is used in the preparation of a coated stent. The above-mentioned degradable super-hydrophobic coating is used in an application method of: adhering the degradable super-hydrophobic coating to the surface of a bare stent to obtain a coated stent.

[0074] This technical solution also proposes the use of a degradable super-hydrophobic coating in the preparation of a coated stent, and the resulting coated stent has an extremely low risk of restenosis, thrombosis and inflammation.

[0075] The technical solution of the present invention is further illustrated below through specific implementation methods.

[0076] Performance Test:

[0077] Biocompatibility: The biocompatibility of the prepared membrane was tested by human vascular smooth muscle cells.

[0078] Degradability: Cut the film into 2cm×2cm film samples, weigh them to get M0, then immerse the film samples in 20ml of simulated human body fluid, place them in a 37℃ constant temperature shaker to simulate degradation, change the simulated body fluid every day, and observe the changes of the film samples in the simulated body fluid. After 15 days, take out the film samples, dry them and weigh them to get M1, and calculate the degradation rate according to the degradation rate = (M0-M1) / M0×100%

[0079] Static water contact angle: At room temperature, 5 μL of water droplets were added to five locations on the surface of the film, and the contact angle between the water droplets and the film surface was measured using a contact angle meter. The average value of the measurement results was taken.

[0080] Bactericidal property: irradiate a 5cm×5cm film under a 1.0mW ultraviolet lamp for 4h, sterilize and set aside, inoculate 5×104cfu of test bacterial solution on the sterilized film surface, stick sterilized plastic wrap, place in a 37℃ constant temperature box, culture for 24h, wash the sample and the plastic wrap bacterial solution to a plate with sterile phosphate buffered saline, dilute 10 times, and then inoculate into a sterile culture dish, place in a 37℃ constant temperature box, culture for 24h, and calculate the bactericidal rate.

[0081] Example 1

[0082] A. Adding nano-scale zinc oxide with a particle size of 10 nm into a low surface energy solution for modification treatment to obtain a solution containing nano-scale modified zinc oxide; placing the solution containing nano-scale modified zinc oxide into a centrifuge tube, centrifuging at a centrifugal speed of 2000 r / min for 0.1 h, removing the supernatant to obtain a white precipitate; drying the white precipitate at a temperature of 70° C., and weighing it once every 30 minutes until the weights of two consecutive weighings are consistent, then drying is completed to obtain nano-scale modified zinc oxide; wherein the mass ratio of nano-scale zinc oxide to the low surface energy solution is 1:10; the raw materials of the low surface energy solution include low heptadecafluorodecyltriethoxysilane and n-propanol; calculated by mass percentage, the content of heptadecafluorodecyltriethoxysilane in the low surface energy solution is 2%;

[0083] B. adding micron-sized polycaprolactone with a particle size of 8 μm into a low surface energy solution for modification to obtain a solution containing micron-sized modified polycaprolactone; wherein the mass ratio of the micron-sized polycaprolactone to the low surface energy solution is 3:101;

[0084] C. adding nano-scale modified zinc oxide to a solution containing micron-scale modified polycaprolactone, and mixing them evenly to obtain an electrospinning solution; wherein the mass ratio of the nano-scale modified zinc oxide to the solution containing micron-scale modified polycaprolactone is 4:105;

[0085] D. The electrospinning solution is electrospun using an electrospinning device, and after drying at 40°C for 2 hours, a degradable super-hydrophobic coating is obtained. The actual product is shown in the figure below. Figure 1 As shown, the schematic diagram of adding water drops to the actual product is as follows Figure 2 As shown, the SEM images of the product at 2000 times and 10000 times are as follows Figure 3 As shown; wherein, the caliber of the needle of the electrospinning equipment is 30G, the spinning voltage is 18kV, the liquid output rate is 8mL / h, the spinning time is 60s, and the receiving distance is 10cm.

[0086] Example 2

[0087] A. Adding nano-scale zinc oxide with a particle size of 20 nm into a low surface energy solution for modification treatment to obtain a solution containing nano-scale modified zinc oxide; placing the solution containing nano-scale modified zinc oxide into a centrifuge tube, centrifuging at a centrifugal speed of 1000 r / min for 0.3 h, removing the supernatant to obtain a white precipitate; drying the white precipitate at a temperature of 80° C., and weighing it once every 30 minutes until the weights of two consecutive weighings are consistent, then drying is completed to obtain nano-scale modified zinc oxide; wherein the mass ratio of nano-scale zinc oxide to the low surface energy solution is 1:6; the raw materials of the low surface energy solution include tridecafluorooctyltrimethoxysilane and isopropanol; calculated by mass percentage, the content of tridecafluorooctyltrimethoxysilane in the low surface energy solution is 3%;

[0088] B. adding micron-sized polycaprolactone with a particle size of 8 μm into a low surface energy solution for modification to obtain a solution containing micron-sized modified polycaprolactone; wherein the mass ratio of the micron-sized polycaprolactone to the low surface energy solution is 5:36;

[0089] C. adding nano-scale modified zinc oxide to a solution containing micron-scale modified polycaprolactone, and mixing them evenly to obtain an electrospinning solution; wherein the mass ratio of the nano-scale modified zinc oxide to the solution containing micron-scale modified polycaprolactone is 1:52;

[0090] D. The electrospinning solution was electrospun using an electrospinning device, and a degradable superhydrophobic coating was obtained after drying at 60°C for 1 hour; wherein, the needle of the electrospinning device had a caliber of 22G, a spinning voltage of 24kV, a liquid output rate of 10mL / h, a spinning time of 60s, and a receiving distance of 8cm.

[0091] Example 3

[0092] A. Adding nano-scale zinc oxide with a particle size of 18 nm into a low surface energy solution for modification treatment to obtain a solution containing nano-scale modified zinc oxide; placing the solution containing nano-scale modified zinc oxide into a centrifuge tube, centrifuging at a centrifugal speed of 3000 r / min for 0.1 h, removing the supernatant to obtain a white precipitate; drying the white precipitate at a temperature of 100° C., and weighing it once every 30 minutes until the weights of two consecutive weighings are consistent, then drying is completed to obtain nano-scale modified zinc oxide; wherein the mass ratio of nano-scale zinc oxide to the low surface energy solution is 1:3; the raw materials of the low surface energy solution include polydimethylsiloxane and acetone; calculated by mass percentage, the content of polydimethylsiloxane in the low surface energy solution is 4%;

[0093] B. adding micron-sized polycaprolactone with a particle size of 7 μm into a low surface energy solution for modification to obtain a solution containing micron-sized modified polycaprolactone; wherein the mass ratio of the micron-sized polycaprolactone to the low surface energy solution is 4:53;

[0094] C. adding nano-scale modified zinc oxide to a solution containing micron-scale modified polycaprolactone, and mixing them evenly to obtain an electrospinning solution; wherein the mass ratio of the nano-scale modified zinc oxide to the solution containing micron-scale modified polycaprolactone is 3:115;

[0095] D. The electrospinning solution was electrospun using an electrospinning device, and a degradable superhydrophobic coating was obtained after drying at 50°C for 2h; wherein, the needle of the electrospinning device had a caliber of 25G, a spinning voltage of 28kV, a liquid output rate of 13mL / h, a spinning time of 150s, and a receiving distance of 18cm.

[0096] Comparative Example 1

[0097] The preparation method and raw materials of Comparative Example 1 are the same as those of Example 1, except that the electrospinning solution in Comparative Example 1 does not contain nano-modified zinc oxide. That is, in Comparative Example 1, the specific preparation method is:

[0098] A. adding micron-sized polycaprolactone with a particle size of 8 μm into a low surface energy solution for modification treatment to obtain a solution containing micron-sized modified polycaprolactone; wherein the mass ratio of micron-sized polycaprolactone to the low surface energy solution is 3:101; the raw materials of the low surface energy solution include low heptadecafluorodecyltriethoxysilane and n-propanol; calculated by mass percentage, the content of heptadecafluorodecyltriethoxysilane in the low surface energy solution is 2%;

[0099] B. Take a solution containing micron-sized modified polycaprolactone as an electrospinning solution; use an electrospinning device to electrospin the electrospinning solution, and obtain a degradable superhydrophobic coating after drying at 40°C for 2 hours; wherein, the caliber of the needle of the electrospinning device is 30G, the spinning voltage is 18kV, the liquid output rate is 8mL / h, the spinning time is 60s, and the receiving distance is 10cm.

[0100] Comparative Example 2

[0101] The preparation method and raw materials of Comparative Example 2 are the same as those of Example 1, except that the electrospinning solution in Comparative Example 2 does not contain a solution containing micron-sized modified polycaprolactone. That is, in Comparative Example 2, the specific preparation method is:

[0102] A. Adding nano-scale zinc oxide with a particle size of 10 nm into a low surface energy solution for modification treatment to obtain a solution containing nano-scale modified zinc oxide; placing the solution containing nano-scale modified zinc oxide into a centrifuge tube, centrifuging at a centrifugal speed of 2000 r / min for 0.1 h, removing the supernatant to obtain a white precipitate; drying the white precipitate at a temperature of 70° C., and weighing it once every 30 minutes until the weights of two consecutive weighings are consistent, then drying is completed to obtain nano-scale modified zinc oxide; wherein the mass ratio of nano-scale zinc oxide to the low surface energy solution is 1:10; the raw materials of the low surface energy solution include low heptadecafluorodecyltriethoxysilane and n-propanol; calculated by mass percentage, the content of heptadecafluorodecyltriethoxysilane in the low surface energy solution is 2%;

[0103] B. adding nano-scale modified zinc oxide into n-propanol and mixing evenly to obtain an electrospinning solution;

[0104] C. The electrospinning solution was electrospun using an electrospinning device, and a degradable superhydrophobic coating was obtained after drying at 40°C for 2 hours; wherein, the needle of the electrospinning device had a caliber of 30G, a spinning voltage of 18kV, a liquid output rate of 8mL / h, a spinning time of 60s, and a receiving distance of 10cm.

[0105] The coatings were prepared by the preparation methods in the above-mentioned embodiment and comparative example respectively, and the performance of the coatings was tested. The results are shown in Table 1 below.

[0106] Table 1 Test results of relevant performance of coating

[0107]

[0108] Biocompatibility, degradation rate and static water contact angle are closely related to the risk of thrombosis, restenosis and inflammation of the coated stent prepared by the coating. The higher the biocompatibility, the greater the degradation rate and the greater the static water contact angle, the lower the risk of thrombosis, restenosis and inflammation of the coated stent; at the same time, the sterilization rate is closely related to the possibility of restenosis and inflammation of the coated stent prepared by the coating, and the higher the sterilization rate, the lower the risk of restenosis and inflammation of the coated stent. From the test results in Table 1, it can be seen that the degradable superhydrophobic coating obtained by the preparation method of the present technical solution not only has good biocompatibility, but also has a degradation rate of ≥90%, a static water contact angle of >150°, and a sterilization rate of >85%. Therefore, the coated stent prepared by the coating of the present technical solution has an extremely low risk of restenosis, thrombosis and inflammation, which is conducive to ensuring the safety of the use of the coated stent.

[0109] In Comparative Example 1, since the electrospinning solution did not add nano-modified zinc oxide, the surface of the coating obtained in Comparative Example 1 could not form a micro-nano composite rough structure, its static water contact angle became smaller, and its hydrophobicity was poor, so that the risk of restenosis, thrombosis and inflammation of the coated stent prepared by the coating of Comparative Example 1 was high. At the same time, in Comparative Example 1, since the electrospinning solution did not add nano-modified zinc oxide, the bactericidal effect of nano-modified zinc oxide could not be utilized, and the coating had basically no bactericidal effect, which further increased the risk of restenosis and inflammation of the coated stent prepared by the coating of Comparative Example 1.

[0110] In Comparative Example 2, since the electrospinning solution did not add a solution containing micron-scale modified polycaprolactone, the surface of the coating obtained in Comparative Example 2 could not form a micro-nano composite rough structure, its static water contact angle became smaller, and its hydrophobicity was poor, resulting in a higher risk of restenosis, thrombosis and inflammation in the coated stent prepared using the coating of Comparative Example 2.

[0111] The technical principle of the present invention is described above in conjunction with specific embodiments. These descriptions are only for explaining the principle of the present invention and cannot be interpreted as limiting the scope of protection of the present invention in any way. Based on the explanations herein, those skilled in the art can associate other specific implementations of the present invention without paying creative labor, and these methods will fall within the scope of protection of the present invention.

Claims

1. A method for preparing a degradable super-hydrophobic film, characterized in that: The following steps are involved: A. adding nano-scale zinc oxide to a low surface energy solution for modification to obtain a solution containing nano-scale modified zinc oxide; centrifuging and drying the solution containing nano-scale modified zinc oxide in sequence to obtain nano-scale modified zinc oxide; B. adding micron-sized polycaprolactone into a low surface energy solution for modification to obtain a solution containing micron-sized modified polycaprolactone; C. adding nano-scale modified zinc oxide into a solution containing micro-scale modified polycaprolactone, and mixing them evenly to obtain an electrospinning solution; D. The electrospinning solution is electrospun using an electrospinning device, and a degradable super-hydrophobic coating is obtained after drying.

2. The method for preparing a degradable super-hydrophobic coating according to claim 1, wherein: In step A and step B, the raw materials of the low surface energy solution include a low surface energy solute and a solvent; Calculated by mass percentage, the content of the low surface energy solute in the low surface energy solution is 1-5%.

3. A method for preparing a degradable super-hydrophobic coating according to claim 2, characterized in that, The low surface energy solute includes any one or more of heptadecafluorodecyltriethoxysilane, tridecafluorooctyltrimethoxysilane, stearic acid and polydimethylsiloxane; The solvent includes any one or more combinations of methanol, ethanol, n-propanol, isopropanol, acetone, tetrahydrofuran, N,N-dimethylformamide and xylene.

4. The method for preparing a degradable super-hydrophobic coating according to claim 1, wherein: In step A, the particle size of the nano-sized zinc oxide is 5 to 50 nm; In step B, the particle size of the micron-sized polycaprolactone is 5 to 10 μm.

5. The method for preparing a degradable super-hydrophobic coating according to claim 1, characterized in that: In step A, the specific method of centrifugal separation is: putting the solution containing nano-modified zinc oxide into a centrifuge tube, centrifuging at a centrifugal speed of 1000 to 3000 r / min for 0.1 to 0.3 h, removing the supernatant to obtain a white precipitate; The specific drying method is: drying the white precipitate at a temperature of 50-120° C., and weighing it once at a preset interval until the weights of two consecutive weighings are consistent, then the drying is completed to obtain nano-grade modified zinc oxide.

6. The method for preparing a degradable super-hydrophobic film according to claim 1, characterized in that: In step A, the mass ratio of the nano-sized zinc oxide to the low surface energy solution is (1-10): (10-20); In step B, the mass ratio of the micron-sized polycaprolactone to the low surface energy solution is (3-20): (101-110); In step C, the mass ratio of the nano-scale modified zinc oxide to the solution containing the micron-scale modified polycaprolactone is (0.5-4):(104-130).

7. The method for preparing a degradable super-hydrophobic film according to claim 1, characterized in that: In step D, the caliber of the needle of the electrospinning equipment is 22 to 30G, the spinning voltage is 15 to 30 kV, the liquid output rate is 1.5 to 15 mL / h, the spinning time is 30 to 180 s, and the receiving distance is 5 to 20 cm.

8. The method for preparing a degradable super-hydrophobic film according to claim 1, characterized in that: In step D, the drying temperature is 30 to 60° C. and the drying time is 1 to 6 hours.

9. A degradable super-hydrophobic film, characterized in that , prepared using the preparation method of a degradable super-hydrophobic coating according to any one of claims 1 to 8, the degradation rate of the degradable super-hydrophobic coating is ≥ 90%, and the static water contact angle is > 150°.

10. Application of a degradable super-hydrophobic film in preparing a coated stent, characterized in that: The degradable super-hydrophobic coating as described in claim 9 is used in an application method as follows: the degradable super-hydrophobic coating is adhered to the surface of a bare stent to obtain a coated stent.

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