Baicalin-Copper Composite Nanocoated Sheath Tube and Its Preparation Method and Use

Abstract

The present invention provides a baicalin - copper composite nano - coated sheath tube, its preparation method and uses. The preparation method includes the following steps: (1) Prepare a baicalin - copper complex; (2) Coat the baicalin - copper complex on the outer wall of the sheath tube by ultrasonic spraying to make a sheath tube with a baicalin - copper composite nano - coating on its outer wall. And through laser drilling or etching, uniformly distributed micropores are formed on the sheath tube. The present invention provides a sheath tube with a baicalin - copper composite nano - coating on its outer wall. The drug - protecting coating on the outer side of the sheath tube of the present invention enables the radial artery sheath tube with the drug coating to be in full contact with the vascular endothelium during the interventional operation. The drugs in the coating are absorbed by endothelial cells, playing functions such as promoting the proliferation and migration of endothelial cells, being able to protect the vascular endothelial function to a greater extent during the interventional operation, reducing the risk of vascular occlusion in the short - term and long - term after the operation, and greatly improving the diagnosis and treatment experience and effect of patients.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and particularly to a baicalin-copper composite nano-coated sheath tube and its preparation method and use. Background Art

[0002] Currently, with the development of cardiovascular interventional medicine, interventional diagnosis and treatment has become an important diagnostic and treatment method in the cardiovascular field. At present, more than one million coronary artery interventional surgeries are completed in China every year. At the same time, it is estimated that at least three million patients receive coronary angiography examinations every year. With the continuous progress of interventional technology, the transradial artery interventional strategy has become the preferred approach for current interventional surgeries, and the proportion of transradial artery approaches in interventional surgeries in China accounts for 96.37%. Compared with the femoral artery interventional surgery, patients with a transradial artery approach do not have to stay in bed for a long time and can get out of bed and move immediately after the surgery, greatly improving the subjective surgical experience. At the same time, it reduces the surgical complications of patients, shortens the hospital stay, reduces the risk of death, and reduces medical costs.

[0003] According to statistics, the incidence of radial artery occlusion after interventional surgery is about 4-5%. Repeated interventional surgeries, female patients, smoking, and the use of thicker sheath tubes are risk factors for radial artery occlusion. In addition to being used as an approach for future cardiovascular interventional treatments, the radial artery can also be used as an arterial graft for coronary artery bypass surgery and an arteriovenous fistula for dialysis in patients with renal failure. Therefore, making every effort to avoid radial artery occlusion has great value for the treatment of patients in future medical processes, see Figure 1 、 2 。

[0004] Currently, the main strategies for protecting the radial artery are: using thinner sheath tubes, injecting anticoagulant drugs (heparin) and antispasmodic drugs (nitrates and calcium channel blockers) into the radial artery sheath tube, and reducing compression, etc. However, too thin a sheath tube cannot accommodate the necessary instruments to complete the surgical operation; the effect of antispasmodic drugs is short-lived and varies from person to person; arterial compression is a necessary step for postoperative hemostasis, which can be appropriately shortened but cannot be avoided. Therefore, there is an urgent clinical need for a better method to protect the radial artery.

[0005] Endothelial cells play a key role in regulating vascular homeostasis. The vascular endothelium protects arteries by providing an anticoagulant and anti-inflammatory environment and regulating permeability. The endothelium regulates vascular tone by modulating smooth muscle cell proliferation, migration, and contractile function, and regulates changes in local hemodynamics by releasing vasodilatory factors such as nitric oxide (NO) and prostaglandin I2 (PGI2) or vasoconstrictive factors such as endothelin A and angiotensin II (AngII). At the same time, it ensures the integrity of the vascular intima to prevent platelet adhesion, aggregation, and thrombus formation. Although the mechanism of radial artery occlusion is not fully understood at present, the above-mentioned vascular homeostasis and thrombosis play important roles in the pathophysiological process of arterial occlusion. Moreover, arterial endothelial cells are very fragile and are extremely vulnerable to mechanical friction and abrasion. Endothelial cell injury may be the key pathophysiological basis for postoperative radial artery occlusion and is also a key therapeutic target for further preventing radial artery occlusion.

[0006] Patent CN102784418B provides a programmable release biopharmaceutical nanoporous vascular stent and its preparation method, in which a nanoporous stent is combined with a nanodrug to achieve a treatment process that coincides with the restenosis process. Patent CN101224187 provides a bifunctional polymer nanomicelle and its preparation method and application in the preparation of drugs for treating vascular restenosis. The platelet membrane glycoprotein is chemically conjugated on the surface of the micelle, which can truly specifically target the bifunctional drug micelle to the vascular restenosis part, ensuring that the drug acts directly on the lesion site. The article "Redox Modulatory Cu(II)-Baicalein Microflowers Prepared in One Step Effectively Promote Therapeutic Angiogenesis in Diabetic Mice" provides that a redox modulator is generated by a one-step reaction of baicalein as an organic ligand and copper ions, which can act on the blood vessels of diabetic mice. Figure 3The in vitro culture of human endothelial cells shows that baicalein-copper complex can significantly improve the proliferation and migration ability of endothelial cells. "The prevention of restenosis in vivo with a VEGF gene and paclitaxel co-eluting stent" provides a double-layer PLGA nanoparticle-coated stent containing VEGF plasmid and paclitaxel. Baicalin has significant biological activities, including antibacterial, anti-inflammatory, cholesterol-lowering, antithrombotic, fire-purging and detoxifying, hemostatic, anti-allergic and spasmolytic effects. It has a regulatory effect on certain diseases and also has a strong anti-cancer reaction physiological efficacy. Copper itself has certain physiological activities, and the oxygen atoms in the baicalin molecule have strong coordination abilities. Its spatial structure is also conducive to the formation of metal complexes. Strengthening the research on baicalin metal complexes helps to provide a new direction for protecting the radial artery. Summary of the Invention

[0007] The object of the present invention is to provide a preparation method of a sheath coated with a baicalin-copper composite nano-coating. A drug protection coating is formed on the outer side of the sheath tube, which is in full contact with the vascular endothelium during the interventional operation. The drugs in the coating are absorbed by endothelial cells, playing functions such as promoting the proliferation and migration of endothelial cells, and being beneficial to the repair of damaged endothelium after the operation.

[0008] In order to achieve the above object, the present invention provides the following technical solutions:

[0009] The first aspect of the present invention provides a preparation method of a baicalin-copper composite nano-coated sheath tube, including the following steps:

[0010] (1) Prepare a baicalin-copper complex;

[0011] (2) Coat the baicalin-copper complex on the outer wall of the sheath tube by ultrasonic spraying to form a baicalin-copper composite nano-coated sheath tube.

[0012] The present invention attaches the baicalin-copper complex, a small molecule compound with endothelial protection function, to the outer side of the sheath tube through the process of nanoparticle coating. When the sheath tube is implanted, it is in full contact with endothelial cells. During the operation, the baicalin-copper complex is transferred to the vascular endothelium and continuously plays an endothelial protection role for a long time after the operation to reduce the risks of short-term and long-term vascular occlusion.

[0013] Preferably, the step (1) further includes: forming uniformly distributed micropores on the sheath tube by laser drilling or etching.

[0014] Preferably, the specific conditions for the laser drilling are: using ultraviolet laser for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, and a single pulse energy of 60 - 66 J / cm2 , The repetition frequency is 40 - 45 kHz.

[0015] Preferably, the specific conditions for the laser drilling are as follows: Use ultraviolet laser for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, and a single pulse energy of 63 J / cm 2 , The repetition frequency is 42 kHz.

[0016] In the present invention, ultraviolet laser is selected for drilling. Under these conditions, the photochemical effect is obvious by directly breaking the molecular bonds of the sheath tube material, resulting in a small heat affected zone, neat erosion edges, and good hole quality. If the single photon energy is low, the photothermal effect is obvious, and thermal ablation may occur.

[0017] Preferably, the preparation method of the baicalin - copper complex in the step (1) is as follows: Mix an aqueous solution of baicalin with a concentration of 0.1 - 100 mg / mL and Cu 2+ solution in a molar ratio of 1:0.1 - 10, gradually drop it into a phosphate buffer solution, stir and react to obtain a precipitate, wash the precipitate with distilled water and dry it to obtain the baicalin - copper complex.

[0018] Preferably, the preparation method of the baicalin - copper complex in the step (1) is as follows: Mix an aqueous solution of baicalin with a concentration of 60 mg / mL and Cu 2+ solution in a molar ratio of 1:1, gradually drop it into a phosphate buffer solution, stir and react to obtain a precipitate, wash the precipitate with distilled water and dry it to obtain the baicalin - copper complex.

[0019] Preferably, the pH of the phosphate buffer solution is 7.

[0020] Preferably, the method of ultrasonic spraying in the step (2) is as follows: Dissolve the baicalin - copper complex in a solvent to form a spraying solution, and use ultrasonic atomization spraying to spray the spraying solution onto the sheath tube to form a composite nano - coating; among them, an ultrasonic atomization spraying instrument is used for the ultrasonic atomization spraying step, and the spraying parameters are set as follows: spraying air pressure 0.8 - 1.5 psi; atomization power 0.5 - 1.0 W; liquid feeding rate 0.07 - 0.10 mL / min.

[0021] Preferably, the spraying parameters are set as follows: spraying air pressure 1.0 psi; atomization power 0.7 W; liquid feeding rate 0.08 mL / min.

[0022] Preferably, the Cu 2+ solution is CuSO4·5H2O solution or CuCl2 solution; the solvent is acetone.

[0023] The inventors found that during the spraying process, the setting of spraying parameters can affect the quality of the coating and the release of drugs. The composite nano-coating formed by the parameters of the present invention has a higher quality, and the drug release rate is more ideal. There are micropores in the sheath tube of the present invention, and the micropores change the surface morphology of the sheath tube. The spraying conditions are closely related to the micropores. The spraying parameters of the present invention can enable better coating of baicalin-copper complex in the micropores, resulting in a larger coating surface area. The coating will not affect drug release due to excessive density, nor will it cause sudden release due to excessive looseness. The spraying liquid and the spraying parameters work together to improve the spraying process of the coated drug.

[0024] The second aspect of the present invention provides a baicalin-copper composite nano-coated sheath tube prepared by the described preparation method.

[0025] Preferably, the sheath tube is a radial artery sheath tube, a femoral artery sheath tube or a venous sheath tube.

[0026] As Figure 3 shown, the structure of the radial artery sheath tube: it is composed of an inner sheath core and an outer sheath tube. In clinical use, the sheath core is used to increase hardness and support force to facilitate the insertion of the sheath tube into the blood vessel; when the sheath tube is completely inserted into the blood vessel, the sheath core is withdrawn, and the sheath tube is left in place. The present invention designs to coat the outer part of the sheath tube with the endothelial protective drug baicalin-copper complex so that it can fully contact the blood vessel and play the role of endothelial protection.

[0027] The present invention provides a novel radial artery sheath tube with endothelial protection. The present invention has a completely different design concept from the previous radial artery protection strategies, focusing on the protection of endothelial cells. Baicalin-copper complex can significantly promote the proliferation and migration ability of endothelial cells and has a good endothelial protection effect.

[0028] The third aspect of the present invention provides the application of the described sheath tube in the preparation of a cardiovascular sheath tube for treatment.

[0029] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows:

[0030] The present invention provides a baicalin-copper composite nano-coated sheath tube. The drug protection coating on the outer side of the sheath tube of the present invention enables the radial artery sheath tube with the drug coating to fully contact the vascular endothelium during the interventional operation. The drugs in the coating are absorbed by endothelial cells, playing functions such as promoting the proliferation and migration of endothelial cells, which is beneficial to the repair of damaged endothelium after the operation, greatly reducing the risk of recent and long-term radial artery occlusion, and reserving the possibility of multiple future radial artery interventional operations, transradial arteriovenous fistula dialysis and radial artery-coronary artery bypass surgery for patients, enabling patients to obtain better treatment effects and lower surgical risks in future medical processes.

[0031] By using the radial artery sheath tube coated with baicalin-copper complex of the present invention, the vascular endothelial function can be protected to a greater extent during the interventional operation, the risk of short-term and long-term vascular occlusion after the operation can be reduced, and the diagnosis and treatment experience and effect of patients can be greatly improved. Description of the Drawings

[0032] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0033] Figure 1 is the radial artery sheath tube;

[0034] Figure 2 are the normal radial artery and the occluded radial artery under angiography;

[0035] Figure 3 is the structure of the radial artery sheath tube;

[0036] Figure 4 shows that the baicalin-copper complex can significantly improve the proliferation and migration ability of endothelial cells in the culture of human endothelial cells. Detailed Embodiments

[0037] The following will clearly and completely describe the technical solutions of the present invention with reference to the drawings. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art without creative efforts based on the embodiments of the present invention belong to the scope of protection of the present invention.

[0038] The reagents and instruments used in the following examples are purchased from:

[0039] Baicalin Sigma Aldrich, catalog number 572667

[0040] Radial artery sheath tube Shenzhen Yixinda Medical New Technology Co., Ltd.

[0041] Example 1

[0042] This example provides a preparation method of a sheath tube with a baicalin-copper composite nano-coating on the outer tube wall. The sheath tube is a radial artery sheath tube and includes the following steps:

[0043] (1) Prepare an aqueous solution of baicalin with a concentration of 60 mg / mL. Mix it with a CuSO4·5H2O solution at a molar ratio of 1:1, and gradually add it dropwise to a phosphate buffer solution with a pH of 7. Stir and react for 1 h to obtain a yellowish-brown precipitate. Wash the precipitate with distilled water and dry it at 50 °C to obtain a baicalin-copper complex.

[0044] By means of laser drilling, micropores are formed on the sheath tube. The specific conditions for the laser drilling are as follows: Use ultraviolet laser for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, a single-pulse energy of 63 J / cm 2 and a repetition frequency of 42 kHz.

[0045] (2) Coat the outer wall of the sheath tube with the baicalin-copper complex by ultrasonic spraying. The method of ultrasonic spraying is as follows: Dissolve the baicalin-copper complex in acetone to form a spraying solution, and use ultrasonic atomization spraying to spray the spraying solution onto the sheath tube to form a composite nano-coating; among them, use an ultrasonic atomization spraying instrument for the ultrasonic atomization spraying step, and the spraying parameters are set as follows: spraying air pressure 1.0 psi; atomization power 0.7 W; liquid inlet rate 0.08 mL / min.

[0046] Example 2

[0047] This example provides a method for preparing a sheath tube with a composite nano-coating of baicalin-copper coated on the outer wall. The sheath tube is a radial artery sheath tube, and the method includes the following steps:

[0048] (1) Prepare an aqueous solution of baicalin with a concentration of 70 mg / mL. Mix it with a CuSO4·5H2O solution at a molar ratio of 1:2, and gradually add it dropwise to a phosphate buffer solution with a pH of 7. Stir and react for 1 h to obtain a yellowish-brown precipitate. Wash the precipitate with distilled water and dry it at 50 °C to obtain a baicalin-copper complex.

[0049] By means of laser drilling, micropores are formed on the sheath tube. The specific conditions for the laser drilling are as follows: Use ultraviolet laser for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, a single-pulse energy of 66 J / cm 2 and a repetition frequency of 40 kHz.

[0050] (2) Coat the outer wall of the sheath tube with the baicalin-copper complex by ultrasonic spraying. The method of ultrasonic spraying is as follows: Dissolve the baicalin-copper complex in acetone to form a spraying solution, and use ultrasonic atomization spraying to spray the spraying solution onto the sheath tube to form a composite nano-coating; among them, use an ultrasonic atomization spraying instrument for the ultrasonic atomization spraying step, and the spraying parameters are set as follows: spraying air pressure 0.8 psi; atomization power 0.5 W; liquid inlet rate 0.10 mL / min.

[0051] Example 3

[0052] This embodiment provides a method for preparing a sheath tube with a baicalin-copper composite nano-coating on its outer wall. The sheath tube is a radial artery sheath tube and includes the following steps:

[0053] (1) Prepare an aqueous solution of baicalin with a concentration of 30 mg / mL. Mix it with a CuSO4·5H2O solution at a molar ratio of 1:0.5, and gradually drop it into a phosphate buffer solution with a pH of 7. Stir and react for 1 h to obtain a yellowish-brown precipitate. Wash the precipitate with distilled water and dry it at 50 °C to obtain a baicalin-copper complex.

[0054] By means of laser drilling, micropores are formed on the sheath tube. The specific conditions for the laser drilling are as follows: Use ultraviolet laser for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, a single-pulse energy of 63 J / cm 2 and a repetition frequency of 42 kHz.

[0055] (2) Coat the baicalin-copper complex on the outer wall of the sheath tube by ultrasonic spraying. The method of ultrasonic spraying is as follows: Dissolve the baicalin-copper complex in acetone to form a spraying solution, and use ultrasonic atomization spraying to spray the spraying solution on the sheath tube to form a composite nano-coating; among them, use an ultrasonic atomization spraying instrument for the ultrasonic atomization spraying step, and the spraying parameters are set as follows: spraying air pressure 1.0 psi; atomization power 0.7 W; liquid inlet rate 0.08 mL / min.

[0056] Example 4

[0057] This embodiment provides a method for preparing a sheath tube with a baicalin-copper composite nano-coating on its outer wall. The sheath tube is a radial artery sheath tube and includes the following steps:

[0058] (1) Prepare an aqueous solution of baicalin with a concentration of 60 mg / mL. Mix it with a CuSO4·5H2O solution at a molar ratio of 1:1, and gradually drop it into a phosphate buffer solution with a pH of 7. Stir and react for 1 h to obtain a yellowish-brown precipitate. Wash the precipitate with distilled water and dry it at 50 °C to obtain a baicalin-copper complex.

[0059] By means of laser drilling, micropores are formed on the sheath tube. The specific conditions for the laser drilling are as follows: Use ultraviolet laser for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, a single-pulse energy of 50 J / cm 2 and a repetition frequency of 30 kHz.

[0060] (2) Coat the outer wall of the sheath tube with baicalin-copper complex by ultrasonic spraying. The method of ultrasonic spraying is as follows: Dissolve the baicalin-copper complex in acetone to form a spraying solution, and use ultrasonic atomization spraying to spray the spraying solution onto the sheath tube to form a composite nano-coating. Among them, an ultrasonic atomization spraying instrument is used for the ultrasonic atomization spraying step, and the spraying parameters are set as follows: spraying air pressure 1.0 psi; atomization power 0.7 W; liquid inlet rate 0.08 mL / min.

[0061] Example 5

[0062] This example provides a method for preparing a sheath tube with a baicalin-copper composite nano-coating on its outer wall. The sheath tube is a radial artery sheath tube and includes the following steps:

[0063] (1) Prepare an aqueous solution of baicalin with a concentration of 60 mg / mL. Mix it with a CuSO4·5H2O solution at a molar ratio of 1:1, and gradually drop it into a phosphate buffer solution with a pH of 7. Stir and react for 1 h to obtain a yellowish-brown precipitate. Wash the precipitate with distilled water and dry it at 50 °C to obtain the baicalin-copper complex.

[0064] Form micropores on the sheath tube by laser drilling. The specific conditions for the laser drilling are as follows: Use ultraviolet laser for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, a single pulse energy of 63 J / cm 2 , and a repetition frequency of 42 kHz.

[0065] (2) Coat the outer wall of the sheath tube with baicalin-copper complex by ultrasonic spraying. The method of ultrasonic spraying is as follows: Dissolve the baicalin-copper complex in acetone to form a spraying solution, and use ultrasonic atomization spraying to spray the spraying solution onto the sheath tube to form a composite nano-coating. Among them, an ultrasonic atomization spraying instrument is used for the ultrasonic atomization spraying step, and the spraying parameters are set as follows: spraying air pressure 1.8 psi; atomization power 0.5 W; liquid inlet rate 0.05 mL / min.

[0066] Example 6

[0067] This example provides a method for preparing a sheath tube with a baicalin-copper composite nano-coating on its outer wall. The sheath tube is a radial artery sheath tube and includes the following steps:

[0068] (1) Prepare an aqueous solution of baicalin with a concentration of 60 mg / mL. Mix it with a CuSO4·5H2O solution at a molar ratio of 1:1, and gradually drop it into a phosphate buffer solution with a pH of 7. Stir and react for 1 h to obtain a yellowish-brown precipitate. Wash the precipitate with distilled water and dry it at 50 °C to obtain the baicalin-copper complex.

[0069] By means of laser drilling, micropores are formed on the sheath. The specific conditions for the laser drilling are as follows: ultraviolet laser is used for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, a single-pulse energy of 63 J / cm 2 , and a repetition frequency of 42 kHz.

[0070] (2) Baicalin-copper complex is coated on the outer wall of the sheath tube by ultrasonic spraying. The method of ultrasonic spraying is as follows: the baicalin-copper complex is dissolved in ethyl acetate to form a spraying solution, and the spraying solution is sprayed on the sheath tube by ultrasonic atomization spraying to form a composite nano-coating; among them, the ultrasonic atomization spraying step is carried out by using an ultrasonic atomization spraying instrument, and the spraying parameters are set as follows: spraying air pressure 1.0 psi; atomization power 0.7 W; liquid feeding rate 0.08 mL / min.

[0071] Example 7

[0072] This example provides a preparation method of a sheath tube with a baicalin-copper composite nano-coating on the outer wall. The sheath tube is a radial artery sheath tube, and the method includes the following steps:

[0073] (1) Prepare an aqueous solution of baicalin with a concentration of 60 mg / mL, mix it with a CuSO4·5H2O solution in a molar ratio of 1:1, gradually drop it into a phosphate buffer solution with a pH of 7, stir and react for 1 h to obtain a yellowish-brown precipitate. The precipitate is washed with distilled water and dried at 50 °C to obtain the baicalin-copper complex.

[0074] (2) Baicalin-copper complex is coated on the outer wall of the sheath tube by ultrasonic spraying. The method of ultrasonic spraying is as follows: the baicalin-copper complex is dissolved in acetone to form a spraying solution, and the spraying solution is sprayed on the sheath tube by ultrasonic atomization spraying to form a composite nano-coating; among them, the ultrasonic atomization spraying step is carried out by using an ultrasonic atomization spraying instrument, and the spraying parameters are set as follows: spraying air pressure 1.0 psi; atomization power 0.7 W; liquid feeding rate 0.08 mL / min.

[0075] Example 8 Application

[0076] Using the radial artery sheaths prepared in Examples 1-7 and commercially available radial artery sheaths, 35-kg healthy ordinary white pigs (male) were selected for the experiment. Before the operation, intramuscular induction anesthesia was performed. After successful anesthesia induction, inhalation anesthesia was carried out, and then endotracheal intubation was performed to establish a respiratory pathway and ear marginal vein puncture was performed to establish a venous pathway. After the animal was moved to the operating table, the areas near the puncture sites of both radial arteries were disinfected. The radial artery was punctured and a radial artery sheath was inserted to establish an arterial pathway. After intravenous injection of low molecular weight heparin to heparinize the experimental animals, a contrast catheter was inserted for angiography and a stent was implanted. Two weeks after normal feeding of the animals after the operation, the changes in the radial artery under angiography were measured again and compared with the previous results. It was found that there was no obvious occlusion in the radial artery of Example 1, there were slight changes in Examples 2 and 3, and the occlusion in Example 2 was less than that in Example 3. There were obvious occlusion phenomena in the radial arteries of Examples 4-7, but the occlusion was milder than that of the commercially available radial artery sheath. The occlusion phenomenon in Example 7 was more serious than that in Examples 4-6. From the above conclusions, it can be seen that compared with the traditional radial artery sheath, the present invention has the same function of the interventional pathway; at the same time, due to the presence of the endothelium-protecting drug baicalin-copper complex on the outer wall of the sheath, during the interventional operation, the radial artery sheath with the drug coating is in full contact with the vascular endothelium, and the drug in the coating is absorbed by the endothelial cells, playing functions such as promoting the proliferation and migration of endothelial cells, which is beneficial to the repair of the damaged endothelium after the operation and greatly reduces the risk of recent and long-term radial artery occlusion.

[0077] Figure 4 The culture of human endothelial cells shows that the baicalin-copper complex can significantly improve the proliferation and migration ability of endothelial cells. Among them, A uses human umbilical vein endothelial cells (HUVEC) or B. human aortic endothelial cells (HAEC) to detect cell viability. Different concentrations of baicalin-Cu (0-200 μg / ml) are added to the two types of endothelial cells, and CCK-8 is used to detect cell viability. It is found that the number of endothelial cells at 48 and 72 hours after adding baicalin-Cu is significantly higher than that of the blank control group. This shows that baicalin-Cu promotes the proliferation of endothelial cells. C. The scratch test of endothelial cells is used to detect the migration ability of endothelial cells. Through the healing of the scratch of human umbilical vein endothelial cells (HUVEC), it is observed that the migration ability of endothelial cells in the experimental group with baicalin-Cu added at 12 and 24 hours after the scratch is significantly better than that of the control group, and is also better than that of the baicalin group and the CuCl2 group. Figure D is the statistical analysis of the total number of migrating cells in Figure C. This shows that baicalin-Cu promotes the migration of endothelial cells. E. The tube formation experiment reflects the angiogenesis function of human umbilical vein endothelial cells (HUVEC). The results include the statistical analysis of the number of nodes (F), the number of intersection points (G), and the length of tube branches (H) formed by HUVEC. It shows that the tube formation ability of HUVEC in the experimental group with baicalin-Cu is significantly better than that of the control group, and is also better than that of the baicalin group and the CuCl2 group. This shows that baicalin-Cu promotes the tube formation of endothelial cells.

[0078] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the various embodiments of the present invention.

Claims

1. Preparation method of baicalin-copper composite nano-coated sheath tube, characterized in that, It includes the following steps: (1) Prepare an aqueous solution of baicalin with a concentration of 60 mg / mL. Mix it with a CuSO4·5H2O solution at a molar ratio of 1:1, and gradually drop it into a phosphate buffer solution with a pH of 7. Stir and react for 1 h to obtain a yellowish-brown precipitate. Wash the precipitate with distilled water and dry it at 50 °C to obtain a baicalin-copper complex; By means of laser drilling, micropores are formed on the tube sheath; the specific conditions for the laser drilling are as follows: ultraviolet laser is used for drilling, with a wavelength of 355 nm, a pulse width of 130 ns, a single pulse energy of 63 J / cm 2 , and a repetition frequency of 42 kHz; (2) Coat the outer wall of the sheath tube with the baicalin-copper complex by ultrasonic spraying. The method of ultrasonic spraying is as follows: Dissolve the baicalin-copper complex in acetone to form a spraying solution, and use ultrasonic atomization spraying to spray the spraying solution onto the sheath tube to form a composite nano-coating. Among them, the ultrasonic atomization spraying step is carried out using an ultrasonic atomization spraying instrument, and the spraying parameters are set as follows: spraying air pressure 1.0 psi; atomization power 0.7 W; liquid inlet rate 0.08 mL / min; The sheath tube is a radial artery sheath tube.

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