Nano coating for vascular intervention balloon catheter as well as preparation method and application of nano coating

Abstract

The invention belongs to the technical field of medicine, and particularly relates to a nano coating for a vascular intervention balloon catheter and a preparation method and application thereof.The nano coating comprises phenylboronic acid-quercetin prodrugs of crosslinked phenylboronic acid and quercetin, and the phenylboronic acid-quercetin prodrugs are connected through phenylboronic acid ester bonds; and the antioxidant capability of responding to active oxygen is realized. The nano-coating can respond to prodrugs of ROS to be used for efficiently resisting oxidative stress, and quercetin released by the reaction is used for long-acting anti-inflammatory treatment. The traditional Chinese medicine composition has the synergistic effect of relieving vascular mechanical injury, resisting proliferation, resisting inflammation and resisting oxidation treatment, can obviously protect and recover the normal function of endothelial cells, relieves proliferation of smooth muscle cells so as to prevent vascular restenosis, and provides a new way for improving the safety and effectiveness of vascular interventional therapy.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a nano coating for a vascular intervention balloon catheter, and a preparation method and application thereof. Background Art

[0002] Vascular balloon angioplasty is the main technology of clinical vascular interventional treatment at present. It is a treatment method that uses interventional surgery to send a balloon to a predetermined location for expansion, thereby dilating narrowed blood vessels and allowing blood to pass through the blood vessels normally.

[0003] However, current clinical balloon angioplasty causes oxidative stress and inflammation in blood vessels after balloon dilation, which further leads to damage to vascular tissue, affects the normal function of endothelial cells, and ultimately causes restenosis of blood vessels. Summary of the invention

[0004] The purpose of the present invention is to provide a nano coating for a vascular intervention balloon catheter and a preparation method thereof. The nano coating can respond to prodrugs of active oxygen and be used to effectively resist oxidative stress. The quercetin released by the reaction is used for long-term anti-inflammatory treatment to solve the problems raised in the above-mentioned background technology.

[0005] To achieve the above-mentioned purpose, the present invention provides, on the one hand, a nanocoating for a vascular intervention balloon catheter, wherein the nanocoating comprises a phenylboronic acid-quercetin prodrug of cross-linked phenylboronic acid and quercetin, wherein the phenylboronic acid-quercetin prodrug is connected by a phenylboronic acid ester bond and has an antioxidant ability to respond to active oxygen. The phenylboronic acid-quercetin prodrug is combined with a polylactic acid-glycolic acid copolymer to form a core-shell structure, wherein the polylactic acid-glycolic acid copolymer serves as a carrier to encapsulate the phenylboronic acid-quercetin prodrug; and the outer layer of the core-shell structure also comprises sticky polydopamine.

[0006] Another aspect of the present invention provides a method for preparing a nano coating for a vascular intervention balloon catheter, comprising the following steps:

[0007] Phenylboronic acid and quercetin are reacted in a tetrahydrofuran solution to generate a phenylboronic acid-quercetin prodrug; the phenylboronic acid-quercetin prodrug is mixed with a polylactic acid-glycolic acid copolymer by an emulsion method to form nanoparticles of the phenylboronic acid-quercetin prodrug wrapped by the polylactic acid-glycolic acid copolymer; dopamine hydrochloride is added to the nanoparticle solution to polymerize the dopamine hydrochloride on the surface of the nanoparticle to form a sticky polydopamine shell; the working solution containing the nanoparticles of the phenylboronic acid-quercetin prodrug wrapped by the polylactic acid-glycolic acid copolymer is coated on a balloon catheter, and the final nanocoating is obtained by a coprecipitation method.

[0008] Preferably, the step of reacting phenylboronic acid with quercetin in a tetrahydrofuran solution comprises: reacting phenylboronic acid with quercetin under reflux at 100-120° C. for 20-24 hours.

[0009] Preferably, the method of mixing the phenylboronic acid-quercetin prodrug with the polylactic acid-glycolic acid copolymer using an emulsion method comprises: dissolving the polylactic acid-glycolic acid copolymer using dimethyl sulfoxide, and stirring for 10-12 hours under ice bath conditions to form nanoparticles of the polylactic acid-glycolic acid copolymer encapsulating the phenylboronic acid-quercetin prodrug.

[0010] Preferably, the working solution containing nanoparticles of polylactic acid-glycolic acid copolymer encapsulating phenylboronic acid-quercetin prodrug is coated on the balloon catheter, and the final nanocoating is prepared by coprecipitation method, which includes: the working solution concentration is 9-10 mg / ml, the balloon catheter is placed in the working solution for coprecipitation for 20-24 hours, and then freeze-dried.

[0011] Preferably, phenylboric acid is 0.3-0.4 g, tetrahydrofuran is 40-60 ml, quercetin is 0.3-0.5 g, polylactic acid-glycolic acid copolymer is 90-110 mg, dimethyl sulfoxide is 0.5-1.5 ml, and dopamine hydrochloride is 90-110 mg.

[0012] Preferably, phenylboric acid is 0.366 g, tetrahydrofuran is 50 ml, quercetin is 0.453 g, polylactic acid-glycolic acid copolymer is 100 mg, dimethyl sulfoxide is 1 ml, and dopamine hydrochloride is 100 mg.

[0013] Another aspect of the present invention provides an application of a nano coating in the preparation of a medical device for alleviating oxidative stress and inflammatory response after vascular balloon dilatation.

[0014] Technical effects and advantages of the present invention: Compared with the prior art, the nano coating for vascular intervention balloon catheter and the preparation method thereof proposed by the present invention have the following advantages:

[0015] The present invention designs and develops a new type of balloon nano coating for reactive oxygen species (ROS) and inflammation generated during balloon dilatation. This nano coating can respond to ROS prodrugs and is used to effectively resist oxidative stress, and the quercetin released in the reaction is used for long-term anti-inflammatory treatment. The synergistic effects of reducing vascular mechanical damage, anti-proliferation, anti-inflammatory and antioxidant treatments can significantly protect and restore the normal function of endothelial cells, reduce the proliferation of smooth muscle cells, and thus prevent vascular restenosis, which provides a new way to improve the safety and effectiveness of vascular interventional treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a characterization diagram of the QHA prodrug of the present invention;

[0017] Figure 2 This is the surface morphology of the nano coating of the present invention;

[0018] Figure 3 It is a characterization diagram of the QHA-PLGA@PDA nanoparticles of the present invention;

[0019] Figure 4 This is a test diagram of the antioxidant function of the balloon coating of the present invention;

[0020] Figure 5 Live / dead cell staining images of QHA-PLGA@PDA balloon coatings with different components of the present invention;

[0021] Figure 6 This is a diagram for verifying the active oxygen scavenging function of the present invention;

[0022] Figure 7 This is a graph evaluating the anti-inflammatory effect of the present invention. DETAILED DESCRIPTION

[0023] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0024] Example 1

[0025] The present invention provides a nano coating for vascular intervention balloon catheters, which is mainly designed and developed for reactive oxygen species (ROS) and inflammation generated during balloon dilation. This nano coating can respond to ROS prodrugs and is used to effectively resist oxidative stress, and the quercetin released in the reaction is used for long-term anti-inflammatory treatment. The synergistic effect of reducing vascular mechanical damage, anti-proliferation, anti-inflammatory and antioxidant treatment can theoretically significantly protect and restore the normal function of endothelial cells, reduce the proliferation of smooth muscle cells, and thus prevent vascular restenosis.

[0026] Quercetin (Que) is a natural flavonoid compound with multiple functions such as anti-inflammatory and cardiovascular protection. In this embodiment, a prodrug QHA of cross-linked phenylboronic acid (HPBA) and Que is designed.

[0027] The phenyl boronate bond in the prodrug has antioxidant capacity in response to reactive oxygen species (ROS), resisting local oxidative stress in blood vessels after balloon dilation, and the released quercetin has excellent anti-inflammatory effects. The synergistic effect of the two can significantly protect and restore the normal function of endothelial cells, reduce intimal hyperplasia, and prevent vascular restenosis. At the same time, polylactic acid-co-glycolic acid (PLGA) with excellent biocompatibility was selected as a carrier to load the QHA prodrug, and a highly biocompatible viscous polydopamine (PDA) shell was added to the outer layer of PLGA. Preliminary experiments such as in vitro materials science and cytology experiments have verified that this QHA-PLGA@PDA interventional balloon nanocoating has antioxidant and anti-inflammatory functions. The details are as follows:

[0028] In this embodiment, the nanocoating for a vascular intervention balloon catheter comprises a phenylboronic acid-quercetin prodrug (QHA) of cross-linked phenylboronic acid (HPBA) and quercetin (Que), wherein the phenylboronic acid-quercetin prodrug is connected by a phenylboronic acid ester bond and has an antioxidant capacity that responds to reactive oxygen species.

[0029] Furthermore, the phenylboronic acid-quercetin prodrug is combined with poly(lactic acid-co-glycolic acid) to form a core-shell structure, wherein the poly(lactic acid-co-glycolic acid) serves as a carrier to encapsulate the phenylboronic acid-quercetin prodrug. In addition, the outer layer of the core-shell structure also contains sticky polydopamine to improve biocompatibility and enhance the stability of the nanoparticles.

[0030] Example 2

[0031] This embodiment provides a method for preparing a nano coating for a vascular intervention balloon catheter, comprising the following steps:

[0032] (1) reacting phenylboronic acid with quercetin in a tetrahydrofuran solution to generate phenylboronic acid-quercetin prodrug (QHA), specifically:

[0033] 0.3 g of phenylboronic acid (HPBA) dissolved in 40 ml of tetrahydrofuran (THF) was added to 0.3 g of quercetin (Que) dissolved in 40 ml of THF and refluxed at 100 ° C for 20 h. In order to complete the reaction and increase the yield, 0.3 g of quercetin was then added, and finally refluxed at 100 ° C for 24 h. The resulting precipitate was filtered, washed with THF and dried to obtain 0.380 g of brown solid with a yield of 30.31%.

[0034] (2) Using an emulsion method, phenylboronic acid-quercetin prodrug and polylactic acid-glycolic acid copolymer are mixed to form polylactic acid-glycolic acid copolymer-encapsulated phenylboronic acid-quercetin prodrug nanoparticles (QHA-PLGA), and dopamine hydrochloride is added to the nanoparticle solution to polymerize dopamine hydrochloride on the surface of the nanoparticles to form a sticky polydopamine shell, specifically:

[0035] First, PLGA-encapsulated QHA nanoparticles were prepared by the emulsion method. First, 100 mg PLGA was dissolved in 0.5 g of dimethyl sulfoxide (DMSO). After 30 minutes of complete dissolution, 50 mg of prepared QHA was added and stirred at 500 rpm for 30 minutes. After complete dissolution, it was added dropwise to 10 ml of deionized water and stirred at 500 rpm for 10 hours under an ice bath to obtain PLGA-encapsulated QHA nanoparticles. Then 90 mg of dopamine hydrochloride was added and stirred at 100 rpm for 12 hours. After centrifugation at 12,000 rpm, the particles were collected and washed three times with ultrapure water to remove impurities, and then redispersed in 15 ml of ultrapure water and stored at 4°C in the dark to obtain dopamine-shelled PLGA-encapsulated QHA nanoparticles (QHA-PLGA@PDA).

[0036] (3) The working solution containing the nanoparticles of polylactic acid-co-glycolic acid encapsulated phenylboronic acid-quercetin prodrug is applied to the balloon catheter, and the final nanocoating is prepared by a coprecipitation method, specifically:

[0037] The prepared QHA-PLGA@PDA nanoparticles were prepared into a 9 mg / ml working solution, and the interventional balloon catheter was placed in the working solution for co-precipitation. After 20 days, the solution was freeze-dried and collected to obtain an interventional balloon catheter with a QHA-PLGA@PDA nano-coating.

[0038] Example 3

[0039] This embodiment provides a method for preparing a nano coating for a vascular intervention balloon catheter, comprising the following steps:

[0040] (1) reacting phenylboronic acid with quercetin in a tetrahydrofuran solution to generate phenylboronic acid-quercetin prodrug (QHA), specifically:

[0041] 0.366 g of phenylboronic acid (HPBA) dissolved in 50 ml of tetrahydrofuran (THF) was added to 0.453 g of quercetin (Que) dissolved in 50 ml of THF and refluxed at 110°C for 24 h. In order to complete the reaction and increase the yield, 0.453 g of quercetin was then added, and finally refluxed at 110°C for 24 h. The resulting precipitate was filtered, washed with THF and dried to obtain 0.386 g of a brown solid with a yield of 30.35%.

[0042] (2) Using an emulsion method, phenylboronic acid-quercetin prodrug and polylactic acid-glycolic acid copolymer are mixed to form polylactic acid-glycolic acid copolymer-encapsulated phenylboronic acid-quercetin prodrug nanoparticles (QHA-PLGA), and dopamine hydrochloride is added to the nanoparticle solution to polymerize dopamine hydrochloride on the surface of the nanoparticles to form a sticky polydopamine shell, specifically:

[0043] First, PLGA-encapsulated QHA nanoparticles were prepared by the emulsion method. First, 100 mg PLGA was dissolved in 1 ml of dimethyl sulfoxide (DMSO). After 30 minutes of complete dissolution, 50 mg of prepared QHA was added and stirred at 500 rpm for 30 minutes. After complete dissolution, it was added dropwise to 10 ml of deionized water and stirred at 500 rpm for 12 hours under an ice bath to obtain PLGA-encapsulated QHA nanoparticles. Then 100 mg of dopamine hydrochloride was added and stirred at 100 rpm for 12 hours. After centrifugation at 12,000 rpm, the particles were collected and washed three times with ultrapure water to remove impurities, and then redispersed in 15 ml of ultrapure water and stored at 4°C in the dark to obtain dopamine-shelled PLGA-encapsulated QHA nanoparticles (QHA-PLGA@PDA).

[0044] (3) The working solution containing the nanoparticles of polylactic acid-co-glycolic acid encapsulated phenylboronic acid-quercetin prodrug is applied to the balloon catheter, and the final nanocoating is prepared by a coprecipitation method, specifically:

[0045] The prepared QHA-PLGA@PDA nanoparticles were prepared into a 10 mg / ml working solution, and the interventional balloon catheter was placed in the working solution for co-precipitation. After 24 hours, the solution was freeze-dried and collected to obtain an interventional balloon catheter with a QHA-PLGA@PDA nano-coating.

[0046] Example 4

[0047] This embodiment provides a method for preparing a nano coating for a vascular intervention balloon catheter, comprising the following steps:

[0048] (1) reacting phenylboronic acid with quercetin in a tetrahydrofuran solution to generate phenylboronic acid-quercetin prodrug (QHA), specifically:

[0049] 0.4 g of phenylboronic acid (HPBA) dissolved in 60 ml of tetrahydrofuran (THF) was added to 0.5 g of quercetin (Que) dissolved in 60 ml of THF and refluxed at 120°C for 24 h. In order to complete the reaction and increase the yield, 0.5 g of quercetin was then added, and finally refluxed at 120°C for 24 h. The resulting precipitate was filtered, washed with THF and dried to obtain 0.383 g of a brown solid with a yield of 30.34%.

[0050] (2) Using an emulsion method, phenylboronic acid-quercetin prodrug and polylactic acid-glycolic acid copolymer are mixed to form polylactic acid-glycolic acid copolymer-encapsulated phenylboronic acid-quercetin prodrug nanoparticles (QHA-PLGA@PDA), and dopamine hydrochloride is added to the nanoparticle solution to polymerize dopamine hydrochloride on the surface of the nanoparticles to form a sticky polydopamine shell, specifically:

[0051] First, PLGA-encapsulated QHA nanoparticles were prepared by the emulsion method. First, 100 mg PLGA was dissolved in 1.5 ml of dimethyl sulfoxide (DMSO). After 30 minutes of complete dissolution, 50 mg of prepared QHA was added and stirred at 500 rpm for 30 minutes. After complete dissolution, it was added dropwise to 10 ml of deionized water and stirred at 500 rpm for 12 hours under an ice bath to obtain PLGA-encapsulated QHA nanoparticles. Then 110 mg of dopamine hydrochloride was added and stirred at 100 rpm for 12 hours. After centrifugation at 12,000 rpm, the particles were collected and washed three times with ultrapure water to remove impurities, and then redispersed in 15 ml of ultrapure water and stored at 4°C in the dark to obtain dopamine-shelled PLGA-encapsulated QHA nanoparticles (QHA-PLGA@PDA).

[0052] (3) The working solution containing the nanoparticles of polylactic acid-co-glycolic acid encapsulated phenylboronic acid-quercetin prodrug is applied to the balloon catheter, and the final nanocoating is prepared by a coprecipitation method, specifically:

[0053] The prepared QHA-PLGA@PDA nanoparticles were prepared into a 10 mg / ml working solution, and the interventional balloon catheter was placed in the working solution for co-precipitation. After 24 hours, the solution was freeze-dried and collected to obtain an interventional balloon catheter with a QHA-PLGA@PDA nano-coating.

[0054] In order to verify the characteristics of the nano coating in this example, the nano coating prepared in Example 3 was used as a sample for experiment, and the experimental results are as follows:

[0055] 1. Characterization of QHA prodrug:

[0056] like Figure 1 As shown, Figure 1 Middle: a UV-visible spectrum test; b Fourier transform infrared spectrum test; c H NMR spectrum.

[0057] QHA prodrug is prepared by one-step cross-linking of phenylboronic acid (HPBA) and quercetin (Que). The phenylboronic acid ester bond in the synthesized QHA prodrug has antioxidant capacity in response to ROS and can be used to resist local oxidative stress in blood vessels after balloon dilation.

[0058] Then, UV-visible and Fourier transform infrared spectroscopy were used to evaluate the coupling effect of HPBA and Que. It can be seen that two characteristic absorption peaks of phenyl borate ester appear in the UV-visible spectrum of QHA ( Figure 1 In the Fourier transform infrared spectrum, the 1130 cm -1 The BOH bond at 1105 cm -1BOC bond at ( Figure 1 b), and the results of H NMR also support the chemical structure of QHA. These indicate the successful synthesis of QHA prodrug.

[0059] 2. Nano coating morphology:

[0060] like Figure 2 As shown in the figure, the QHA-PLGA@PDA interventional balloon nanocoating was prepared by coprecipitation. Scanning electron microscopy showed that the surface of the balloon was covered with uniform spherical shapes ( Figure 2 a, b), and its core-shell structure can be clearly seen through a transmission electron microscope, with QHA-PLGA inside and PDA outside ( Figure 2 (c).

[0061] 3. Characterization of QHA-PLGA@PDA nanoparticles:

[0062] The particle size analysis of QHA-PLGA@PDA nanoparticles revealed that ( Figure 3 In figure a), the particle size of the nanoparticles is mostly concentrated between 200-300 nm, and it can be seen that after the addition of PDA, the surface Zeta potential of the nanoparticles decreased ( Figure 3 b), while the addition of QHA had no significant effect on the Zeta potential. And by comparing the UV absorption method at different QHA concentrations ( Figure 3 In Figure c), the drug loading capacity of nanoparticles under different PLGA:QHA ratios can be roughly calculated ( Figure 3 (d) It can be seen that the drug loading effect of this nanoparticle is best at the ratio of PLGA:QHA=7.5. Figure 3 Middle: P is PLGA; PQ is PLGA-QHA; PQP is PLGA-QHA@PDA.

[0063] 4. In vitro anti-reactive oxygen function verification:

[0064] like Figure 4 As shown, Figure 4 Antioxidant function test of balloon coating at different concentrations. (a) ABTS method; (b) DPPH method; (c) CAT method.

[0065] The ROS scavenging ability under different concentration gradients was verified by ABTS, DPPH and CAT. Figure 4 In a, b, and c), it was found that at a concentration of 55ug / ml, the three verification methods could all achieve a response clearance capacity of about 80%, and in the subsequent biocompatibility experiments, it was found that this concentration was safe for organisms.

[0066] 5. Biosafety Experiment:

[0067] The QHA-PLGA@PDA nano-interventional balloon coating system needs to have excellent biosafety and non-toxicity for clinical treatment. The nano-interventional balloon coating was applied to HUVECs cells and the biosafety was verified by live / dead cell staining ( Figure 5 ). From the staining results, it can be found that any component in the coating system is safe for human umbilical vein endothelial cells (HUVECs), and the cell mortality rate is less than 3%.

[0068] 6. Verification of active oxygen removal function:

[0069] like Figure 6 As shown, Figure 6 Middle: a is the ROS response scavenging ability of the balloon coating (labeled with ROS probe); b is the quantification result of the scavenging ability; c is the mitochondrial membrane potential of HUVECs detected by JC-1 under high oxidative stress environment.

[0070] When injury occurs, the ROS-rich microenvironment exerts oxidative stress on endothelial cells, leading to functional loss of human umbilical vein endothelial cells (HUVECs). If not regulated in time, vascular homeostasis may be impaired. In vitro, H2O2 was used to simulate the oxidative stress environment. In order to detect the ROS elimination ability of the balloon coating, a ROS fluorescent probe was used to visualize the intracellular ROS level ( Figure 6 The results showed that the balloon coating exhibited excellent ROS scavenging ability, with a scavenging rate of about 80% ( Figure 6 (b) The fluorescence in the cells was significantly dimmed after treatment. These results indicate that QHA-PLGA@PDA is an ideal antioxidant coating.

[0071] In order to further study the protective mechanism of the balloon coating on HUVECs, the mitochondrial membrane of the cells was tested, because the decrease of mitochondrial membrane potential is highly correlated with cell apoptosis. The JC-1 assay was used to obtain the mitochondrial membrane potential. The red fluorescence from JC-1 indicates normal mitochondrial membrane potential and mitochondrial activity, while the green fluorescence indicates the opposite ( Figure 6 (c) From the fluorescence results, it can be seen that the balloon coating is crucial for maintaining the normal mitochondrial membrane potential, which indicates that the protection of HUVECs by the balloon coating under high oxidative stress is related to the protection of mitochondrial membrane potential.

[0072] 7. Evaluation of anti-inflammatory effects

[0073] First, LPS was used to induce RAW cells to simulate local vascular inflammation, and then QHA-PLGA@PDA was added to the balloon nanocoating. After waiting for 12 h, the cells were double-labeled with CD68 and CD206 ( Figure 7). Through fluorescent excitation dyes, it can be observed that under the action of the balloon coating, RAW cells polarize to the M2 type and the inflammatory response is inhibited.

[0074] In summary, quercetin (Que) is a natural flavonoid compound with multiple functions such as anti-inflammatory and cardiovascular protection. A prodrug QHA of cross-linked phenylboronic acid (HPBA) and Que was designed. The phenylboronic acid ester bond in the prodrug has an antioxidant capacity that responds to reactive oxygen species (ROS) and resists local oxidative stress in blood vessels after balloon dilation. The released quercetin has an excellent anti-inflammatory effect. The synergistic effect of the two can significantly protect and restore the normal function of endothelial cells, reduce intimal hyperplasia, and prevent vascular restenosis.

[0075] At the same time, polylactic acid-co-glycolic acid (PLGA) with excellent biocompatibility was selected as a carrier to load the QHA prodrug, and a highly biocompatible adhesive polydopamine (PDA) shell was added to the outer layer of PLGA. Preliminary experiments such as in vitro material science and cytology experiments verified that this QHA-PLGA@PDA interventional balloon nanocoating has antioxidant and anti-inflammatory functions.

[0076] Example 5

[0077] In this embodiment, a nano-coating is used in the preparation of a medical device for reducing oxidative stress and inflammatory response after vascular balloon dilatation.

[0078] A new type of balloon nanocoating has been designed and developed to target reactive oxygen species (ROS) and inflammation generated during balloon dilatation. This nanocoating can respond to ROS prodrugs and is used to effectively resist oxidative stress. The quercetin released in the reaction is used for long-term anti-inflammatory treatment. The synergistic effects of reducing vascular mechanical damage, anti-proliferation, anti-inflammatory and antioxidant treatments can theoretically significantly protect and restore the normal function of endothelial cells, reduce smooth muscle cell proliferation, and thus prevent vascular restenosis. This is precisely developed to target the key mechanism of vascular restenosis after balloon dilatation.

[0079] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A nano coating for a vascular intervention balloon catheter, characterized in that: The nanocoating comprises a phenylboronic acid-quercetin prodrug cross-linking phenylboronic acid and quercetin, wherein the phenylboronic acid-quercetin prodrug is linked via a phenylboronic acid ester bond, The phenylboronic acid-quercetin prodrug is combined with the polylactic acid-glycolic acid copolymer to form a core-shell structure, wherein the polylactic acid-glycolic acid copolymer is used as a carrier to encapsulate the phenylboronic acid-quercetin prodrug. The outer layer of the core-shell structure also contains sticky polydopamine.

2. A method for preparing the nano coating according to claim 1, characterized in that: The following steps are involved: Phenylboronic acid is reacted with quercetin in a tetrahydrofuran solution to generate a phenylboronic acid-quercetin prodrug; Phenylboronic acid-quercetin prodrug is mixed with poly(lactic acid-co-glycolic acid) copolymer by an emulsion method to form poly(lactic acid-co-glycolic acid) copolymer-encapsulated phenylboronic acid-quercetin prodrug nanoparticles; adding dopamine hydrochloride to the nanoparticle solution to polymerize the dopamine hydrochloride on the surface of the nanoparticle to form a sticky polydopamine shell; The working solution containing polylactic acid-co-glycolic acid nanoparticles encapsulating phenylboronic acid-quercetin prodrug is coated on the balloon catheter, and the final nanocoating is prepared by a coprecipitation method.

3. The method according to claim 2, characterized in that: The step of reacting phenylboronic acid with quercetin in a tetrahydrofuran solution comprises: Phenylboronic acid and quercetin are reacted under reflux at 100-120° C. for 20-24 hours.

4. The method according to claim 3, characterized in that: The method of mixing phenylboronic acid-quercetin prodrug with polylactic acid-glycolic acid copolymer by using an emulsion method comprises: The poly(lactic-co-glycolic acid) was dissolved in dimethyl sulfoxide and stirred for 10-12 hours under ice bath conditions to form poly(lactic-co-glycolic acid) nanoparticles encapsulating phenylboronic acid-quercetin prodrug.

5. The method according to claim 4, characterized in that: The method of coating the working solution containing nanoparticles of polylactic acid-co-glycolic acid copolymer encapsulating phenylboronic acid-quercetin prodrug on the balloon catheter and preparing the final nanocoating by coprecipitation method comprises: The concentration of the working solution is 9-10 mg / ml. The balloon catheter is placed in the working solution for co-precipitation for 20-24 hours and then freeze-dried.

6. The method according to claim 5, characterized in that: Phenylboric acid is 0.3-0.4g, tetrahydrofuran is 40-60ml, quercetin is 0.3-0.5g, polylactic acid-glycolic acid copolymer is 90-110mg, dimethyl sulfoxide is 0.5-1.5ml, and dopamine hydrochloride is 90-110mg.

7. The method according to claim 6, characterized in that: Phenylboric acid is 0.366 g, tetrahydrofuran is 50 ml, quercetin is 0.453 g, polylactic acid-glycolic acid copolymer is 100 mg, dimethyl sulfoxide is 1 ml, and dopamine hydrochloride is 100 mg.

8. Use of the nano coating as claimed in claim 1 in the preparation of a medical device for reducing oxidative stress and inflammatory response after vascular balloon dilatation.

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