A drug-eluting capsule, a drug coating, and a method for preparing the same.

Abstract

This application relates to the field of drug-eluting balloon technology, and more particularly to a drug-eluting balloon, a drug coating, and a method for preparing the same. The drug coating comprises a nanomedicine, which, from the inside out, comprises drug-loaded nanoparticles, an elastin layer, and an adhesion layer. The adhesion layer comprises a polydopamine coating and a cationic polymer coating. This invention provides drug particles with excellent adhesion to target blood vessels. A polydopamine and cationic polymer coating is prepared on the surface of the drug particles, maintaining adhesion in a dynamic scouring environment. Simultaneously, elastin, with excellent elastic buffering properties, is used as the intermediate layer of the drug particles, allowing the drug to adapt to the periodic expansion, contraction, and shear force changes of blood vessels. Under vascular pulsation and blood flow impact, the drug maintains close contact with the blood vessel wall, further enhancing the adhesion stability of the drug and significantly improving the drug retention rate in the target blood vessel.

Description

Technical Field

[0001] This invention relates to the field of drug-eluting balloon technology, and more particularly to a drug-eluting balloon, a drug coating, and a method for preparing the same. Background Technology

[0002] Existing drug-eluting balloons consist of a drug-eluting membrane covering the balloon, used in the treatment of coronary and peripheral atherosclerosis, stenosis, and / or restenosis. After dilation of the target vessel, the drug-eluting membrane adheres to the inner wall of the target vessel. However, due to arterial pulsation and blood flow, relatively little drug remains in the target vessel, resulting in insufficient drug concentration at the target site and affecting treatment efficacy. Summary of the Invention

[0003] The purpose of this invention is to provide a drug-eluting balloon, a drug coating, and a method for preparing the same, in order to improve the aforementioned problems. To achieve the above objective, the technical solution adopted by this invention is as follows:

[0004] A drug coating comprising a nanomedicine, wherein the nanomedicine comprises, from the inside out, drug-loaded nanoparticles, an elastin layer, and an adhesive layer, wherein the adhesive layer comprises a polydopamine coating and a cationic polymer coating.

[0005] Optionally, the elastin layer may be composed of at least one of silk fibroin or spider silk.

[0006] Optionally, the cationic polymer coating may include at least one of polyethyleneimine, poly-L-lysine, chitosan, and poly-β-amino ester.

[0007] Optionally, the surface of the nanomedicine may also be modified with at least one of NHS groups, aldehyde groups, isothiocyanate groups, and phenylboronic acid groups.

[0008] This application also provides a drug-eluting balloon, the surface of which is covered with the aforementioned drug coating.

[0009] This application also provides a method for preparing the above-mentioned drug coating, including:

[0010] Drug-loaded nanoparticles were mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution was then slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0011] The PLGA-protein intermediate was added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate was obtained.

[0012] The polydopamine-encapsulated intermediate was added to a cationic polymer solution, and the resulting reaction yielded a nanomedicine.

[0013] The nanomedicine is coated onto the surface of the capsule by ultrasonic atomization spraying or electrostatic self-assembly to obtain a drug coating.

[0014] Optionally, drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture, and a cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate, comprising:

[0015] Elastin was dissolved in water to prepare an elastin solution with a concentration of 1-5%. Drug-loaded nanoparticles were added to the elastin solution and the mixture was stirred at room temperature to obtain a protein mixture.

[0016] The crosslinking agent is dissolved in a water / ethanol mixture to obtain a crosslinking agent solution with a concentration of 0.5-2%.

[0017] The cross-linking agent solution is added dropwise to the protein mixture, and the mixture is stirred at room temperature for 8-15 hours. After the reaction, the mixture is centrifuged, washed, and freeze-dried to obtain the PLGA-protein intermediate. The cross-linking agent includes at least one of genipin or glutaraldehyde.

[0018] Optionally, the PLGA-protein solid is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated solid is obtained, comprising:

[0019] Dopamine was added to Tris buffer to prepare a dopamine solution with a concentration of 0.5-2 mg / mL;

[0020] The PLGA-protein intermediate was added to the dopamine solution and stirred at room temperature for 4-8 hours. After the reaction, the mixture was centrifuged and washed to obtain polydopamine-encapsulated solid.

[0021] Optionally, the polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the reaction yields a nanomedicine comprising:

[0022] The cationic polymer was added to Tris buffer to prepare a cationic polymer solution with a concentration of 1-4 mg / mL;

[0023] The polydopamine-encapsulated intermediate was added to the cationic polymer solution, and the mixture was stirred at room temperature for 1-3 hours. After the reaction, the mixture was centrifuged and washed to obtain the polydopamine-encapsulated solid.

[0024] Optionally, the drug-loaded nanoparticles are PLGA drug-loaded nanoparticles, and their preparation method includes:

[0025] Prepare the first aqueous phase solution;

[0026] The PLGA polymer was mixed with a drug solution to obtain an organic phase;

[0027] The first aqueous solution was added to the organic phase and fully emulsified to obtain a reverse emulsion.

[0028] The reverse emulsion was added to the second aqueous phase solution, and the mixture was stirred and emulsified thoroughly. The emulsion was then centrifuged to obtain PLGA drug-loaded nanoparticles.

[0029] The beneficial effects of this invention are as follows:

[0030] This invention provides a drug particle with excellent adhesion to target blood vessels. The drug particle surface is coated with a polydopamine and cationic polymer coating, which allows the drug to maintain adhesion in a dynamic scouring environment. At the same time, elastin with excellent elastic buffering properties is used as the intermediate layer of the drug particle, which enables the drug to adapt to the periodic expansion, contraction and shear force changes of blood vessels. Under vascular pulsation and blood flow impact, the drug can maintain close contact with the blood vessel wall, further enhancing the adhesion stability of the drug and greatly improving the drug retention rate in the target blood vessel.

[0031] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing embodiments of the invention. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments.

[0033] In this application, numerical ranges are referred to as continuous unless otherwise specified, and include the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Furthermore, when the range refers to integers, it includes every integer between the minimum and maximum values ​​of the range. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges may be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are incorporated.

[0034] Although drug-eluting balloons have been used in the treatment of cardiovascular and cerebrovascular diseases, current drug-eluting balloons still have the following problems:

[0035] 1. Water-soluble drugs cannot be used as a coating, as water-soluble drugs usually dissolve quickly in the blood.

[0036] 2. Conventional drug-eluting balloons, once inserted into the bloodstream, are generally required to reach the target lesion and open within 15-30 seconds. Otherwise, the drug will dissolve and be released into the bloodstream, failing to guarantee a local drug concentration.

[0037] 3. The retention rate of existing drug coatings in target blood vessels is very low, only about 10-20%.

[0038] To address the existing technical problems, this application provides a method for preparing a drug coating, comprising:

[0039] S100, Preparation of drug-loaded nanoparticles;

[0040] Drugs are generally classified into hydrophobic drugs and hydrophilic drugs. Different encapsulation materials need to be designed for different drugs to ensure that the drugs can be concentrated in the target blood vessel and released at an appropriate rate.

[0041] This application provides a method for preparing hydrophobic drug-loaded PLGA nanoparticles, the preparation method of which includes:

[0042] PBS solution was prepared as the first aqueous phase solution, and PLGA polymer was mixed with the drug solution as the organic phase.

[0043] The first aqueous solution was added to the organic phase and fully emulsified to obtain a reverse emulsion.

[0044] The reverse emulsion was added to the second aqueous phase solution and emulsified thoroughly until the organic solvent completely evaporated. Large precipitate particles were removed by centrifugation, and the supernatant was centrifuged again to obtain PLGA-loaded nanoparticles. By adjusting the PLGA concentration, the ratio of organic to aqueous phases, and the stirring speed, particles with varying sizes (range 100-1000 nm) can be obtained.

[0045] This application also provides calcium phosphate nanoparticles loaded with hydrophilic drugs, the preparation method of which includes:

[0046] An organic phase was prepared using surfactant Igepal CO-520 and cyclohexane in a mass ratio of 3:7. Two reverse emulsions, A and B, were prepared: reverse emulsion A contained CaCl2 and a hydrophilic drug; reverse emulsion B contained Na2HPO4 (25 mM, pH = 9) and DOPA. Both reverse emulsions A and B were added to the organic phase, mixed, stirred, centrifuged, and quenched with ethanol. The resulting precipitate, along with soybean lecithin and cholesterol, was dissolved in chloroform, evaporated to dryness, and then hydrated to obtain calcium phosphate nanoparticles encapsulating the hydrophilic drug.

[0047] The drug-loaded nanoparticles of this application can encapsulate both water-soluble and lipid-soluble drugs (such as colchicine). Water-soluble drugs typically dissolve rapidly in the blood and cannot exert local effects. Lipid-soluble drugs (such as rapamycin and paclitaxel) are insoluble in the blood and are absorbed by the endothelial cells or smooth muscle cells of the coronary arteries after contact with tissues. In the field of drug-eluting balloons, existing drugs are all lipid-soluble, and there are no water-soluble drugs. This application can encapsulate water-soluble drugs, enabling them to successfully reach the target blood vessel and exert a therapeutic effect.

[0048] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate; specifically:

[0049] Elastin was dissolved in water to prepare an elastin solution with a concentration of 1-5%. Drug-loaded nanoparticles were added to the elastin solution and the mixture was stirred at room temperature to obtain a protein mixture.

[0050] The crosslinking agent is dissolved in a water / ethanol mixture to obtain a crosslinking agent solution with a concentration of 0.5-2%.

[0051] The cross-linking agent solution is added dropwise to the protein mixture, and the mixture is stirred at room temperature for 8-15 hours. After the reaction, the mixture is centrifuged, washed, and freeze-dried to obtain the PLGA-protein intermediate. The cross-linking agent includes at least one of genipin or glutaraldehyde.

[0052] By adjusting the mass ratio of elastin to cross-linking agent, PLGA-protein intermediates with different properties can be obtained.

[0053] S300: The PLGA-protein intermediate is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained; specifically:

[0054] Dopamine was added to Tris buffer to prepare a dopamine solution with a concentration of 0.5-2 mg / mL;

[0055] The PLGA-protein intermediate was added to the dopamine solution and stirred at room temperature for 4-8 hours. After the reaction, the mixture was centrifuged and washed to obtain polydopamine-encapsulated solid.

[0056] S400: The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0057] The cationic polymer was added to Tris buffer to prepare a cationic polymer solution with a concentration of 1-4 mg / mL;

[0058] The polydopamine-encapsulated intermediate was added to the cationic polymer solution, and the mixture was stirred at room temperature for 1-3 hours. After the reaction, the mixture was centrifuged and washed to obtain the nanomedicine.

[0059] Under alkaline conditions, dopamine can undergo oxidative self-polymerization to form polydopamine. The catechol structure in the structure can interact with the cell surface through hydrogen bonding, π–π stacking and other forces. The quinone group formed after the oxidation of catechol covalently binds with the amine group, thiol group and other groups on the cell membrane surface, thus exhibiting good adhesion properties.

[0060] However, due to the high blood flow velocity in coronary arteries and the presence of protein adsorption and enzymatic degradation within the blood vessels, polydopamine alone is insufficient to achieve adequate adhesion. This application further modifies dopamine nanoparticles with materials such as polyacetylation, polylysine, chitosan, hyaluronic acid, chondroitin sulfate, and benzoic acid, or with groups such as NHS, aldehydes, phenylboronic acid, and isothiocyanates. These modifications enhance the vascular adhesion of dopamine nanoparticles through multiple interactions, including electrostatic adsorption and covalent bonding, significantly improving drug retention.

[0061] S500: The nanomedicine is coated onto the surface of the balloon by ultrasonic atomization spraying or electrostatic self-assembly to obtain a drug coating.

[0062] The ultrasonic atomization spraying process includes: preparing a nano-drug solution of a certain concentration, degassing it, and then spraying it onto the surface of the balloon using an ultrasonic atomization method. The drug flow rate is 0.02-0.05 mL / min, preferably 0.03 mL / min; the ultrasonic power is 1.0-3.0 W, preferably 1.5 W; and the number of spraying cycles is 4-10. The nano-drug solution is a mixed solution of nano-drug and one or more excipients such as polyacrylic acid and polylysine, wherein the concentration of the nano-drug is 0.5-5 wt%.

[0063] The electrostatic self-assembly process is as follows: First, the capsule is immersed in a solution containing polycations, then rinsed with deionized water and dried with nitrogen gas, thereby forming a coating with a positive charge on the polycation surface. Next, the capsule is immersed in a mixed solution containing nanomedicine and polyanions, and the rinsing and drying are repeated to form a nanomedicine coating with a negative charge on the polyanion surface. By alternating these steps 4–6 times, alternating polyanion and polycation drug coatings can be formed on the capsule surface.

[0064] Preferably, the solution containing polycations is 0.5-1.0 mg / mL of polyethyleneimine, polylysine, or chitosan, and more preferably 0.8 mg / mL of polyethyleneimine; the mixed solution of nanomedicine and polyanionic compounds is 2.0-5.0 mg / mL of nanomedicine mixed with one or more of polyacrylic acid, hyaluronic acid, polyaspartic acid, etc., and more preferably 3.5 mg / mL of nanoparticles and polyacrylic acid.

[0065] This application is not limited to this; other suitable methods can also be used to prepare drug coatings.

[0066] Based on the same inventive concept, this application also provides a drug coating comprising a nanomedicine, wherein the nanomedicine comprises, from the inside out, drug-loaded nanoparticles, an elastin layer, and an adhesive layer, wherein the adhesive layer comprises a polydopamine coating and a cationic polymer coating. This drug coating can be prepared by the method for preparing drug coatings of this application.

[0067] In nanomedicines, the elastin layer comprises at least one of silk fibroin or spider silk. Elastin possesses excellent elastic buffering properties, enabling it to adapt to dynamic changes in the blood vessel wall. Therefore, it is incorporated into the structure to construct a three-layer structure consisting of a drug-loaded core, an elastin intermediate layer (elastic buffer), and a dopamine and PEI coating, mimicking physiological elasticity to form a super-adhesive formulation.

[0068] In nanomedicines, the cationic polymer coating comprises at least one of polyethyleneimine, poly-L-lysine, chitosan, and poly-β-amino ester. Positively charged cationic polymers such as polyethyleneimine (PEI) interact with negatively charged cell membranes (phospholipid head groups, glycoproteins) through electrostatic adsorption, and can also form hydrogen bonds with polar groups such as hydroxyl and carboxyl groups in biomolecules, enhancing bioadhesion.

[0069] The surface of the nanomedicine is further modified with at least one of the following: NHS groups, aldehyde groups, isothiocyanate groups, and phenylboronic acid groups. These groups can covalently bind to amino and hydroxyl groups on the surface of blood vessel cell membranes, while phenylboronic acid can form borate bonds with the cis-diol structure of glycoproteins on the cell membrane surface, thereby significantly improving the adhesion of nanoparticles to the blood vessel wall. Additionally, chitosan and chondroitin sulfate can also bind to integrin receptors on the cell membrane surface, enhancing adhesion.

[0070] In the nanomedicine, the thickness ratio of the elastin layer, the polydopamine coating, and the cationic polymer coating is (4-6):3:(1-3); preferably 5:3:2.

[0071] This application also provides a drug-eluting balloon, the surface of which is covered with the drug coating of this application. The drug-eluting balloon is used in the treatment of atherosclerosis, stenosis and / or restenosis of coronary and peripheral blood vessels. In use, the drug coating is coated on the balloon and carried to the target blood vessel by the balloon. After the balloon is inflated, the drug coating adheres to the inner wall of the blood vessel and slowly releases the drug, thereby achieving continuous treatment.

[0072] The drug-eluting balloon of this application can effectively improve the retention rate of drugs in target blood vessels. The principle behind this is mainly based on three aspects:

[0073] (1) The adhesion layer can ensure that the drug adheres to the vascular tissue and has more retention in the target blood vessel;

[0074] (2) Using elastin with buffering properties as the middle layer of drug particles allows the drug to maintain close contact with the irregular inner wall of blood vessels and prevent it from detaching from the blood vessels due to pulsation.

[0075] (3) By encapsulating nanomedicines with elastin and adhesion layers, the timeline of drug release can be controlled, thus prolonging the duration of drug release in the target blood vessels.

[0076] The following specific examples illustrate the implementation of the present invention.

[0077] Example 1

[0078] A method for preparing a drug coating, comprising:

[0079] S100, Preparation of drug-loaded nanoparticles:

[0080] Prepare a PBS solution (10 mg / mL, pH 7.4) as the first aqueous phase solution;

[0081] A 5 mL PLGA polymer solution (lactic acid:glycolic acid = 50:50, molecular weight 10000 kDa, 10 mg / mL) was mixed with a 2.5 mg colchicine solution in dichloromethane to form the organic phase.

[0082] The first aqueous solution was added to the organic phase, and the mixture was treated with a probe ultrasonic emulsifier (80% power, 0.5s sonication, 0.5s interval) for 15 seconds under ice bath to fully emulsify it, thus obtaining a reverse emulsion.

[0083] The reverse emulsion was added to 50 mL of the second aqueous phase solution (1 wt% PVA aqueous solution), and the mixture was stirred thoroughly at 800 rpm until the organic solvent was completely evaporated. Large particles were removed by centrifugation at 2000 g for 5 min. The supernatant was then centrifuged at 12000 g for 30 min to obtain nanoparticles. These nanoparticles were washed three times with ultrapure water to remove excess PVA, and then resuspended in 2 mL of ultrapure water to obtain drug-loaded nanoparticles.

[0084] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0085] Dissolve an appropriate amount of silk fibroin in 10 mL of deionized water to prepare a 2 wt% elastin solution.

[0086] 2 mL of drug-loaded nanoparticles (2 mg / mL) were added to the elastin solution and stirred at room temperature for 1 h to mix thoroughly, thus obtaining a protein mixture.

[0087] The crosslinking agent (genipin) was dissolved in a water / ethanol mixture to obtain a 1% crosslinking agent solution;

[0088] The cross-linking agent solution was slowly added dropwise to the protein mixture, stirred at room temperature for 12 hours, centrifuged at 12000g for 30 minutes, the precipitate was washed three times with ultrapure water and freeze-dried to obtain the PLGA-protein intermediate.

[0089] S300. The PLGA-protein intermediate is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained.

[0090] Dopamine was added to Tris buffer (50 mM, pH = 8.5) to obtain a dopamine solution with a dopamine concentration of 1 mg / mL.

[0091] 10 mg of PLGA-protein intermediate was added to 10 mL of dopamine solution and stirred openly at room temperature for 6 hours, during which the solution gradually turned dark brown. Then, the solution was centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain the polydopamine-encapsulated intermediate.

[0092] S400. The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0093] PEI (25 kDa) was added to Tris buffer (50 mM, pH = 8.5), where the PEI concentration was 2 mg / mL, to obtain a cationic polymer solution;

[0094] 1 mL of polydopamine-encapsulated intermediate (5 mg / mL) was added to 10 mL of cationic polymer solution, stirred at room temperature for 2 h, centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain nanomedicine.

[0095] S500. The nano-drug is coated onto the surface of the balloon by ultrasonic atomization spraying to obtain a drug coating:

[0096] A 2 wt% nanoparticle solution was prepared using polyacrylic acid, degassed, and then sprayed onto the surface of the balloon using ultrasonic atomization. The drug flow rate was 0.02 mL / min; the ultrasonic power was 1.0 W; and the spraying cycle was 6 times to obtain the drug coating.

[0097] Example 2

[0098] S100, Preparation of drug-loaded nanoparticles:

[0099] An organic phase was prepared by using surfactant lgepalCO-520 and cyclohexane in a 3:7 ratio;

[0100] Prepare 25 mL each of two reverse emulsions, A and B. Emulsion A contains 500 μL CaCl2 (2.5 M) and 1 mg of hydrophilic drug; Emulsion B contains 500 μL Na2HPO4 (25 mM, pH 9) and 3 mg DOPA.

[0101] Two reverse emulsions, A and B, were added to the organic phase, mixed, and stirred for 30 min. The mixture was then centrifuged at 12000 g for 20 min and washed three times with ethanol. The resulting precipitate was dissolved in 2 mL of chloroform along with 3 mg of soybean lecithin and 0.3 mg of cholesterol. After drying, the mixture was hydrated to obtain calcium phosphate nanoparticles (drug-loaded nanoparticles) loaded with hydrophilic drugs.

[0102] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0103] Dissolve an appropriate amount of silk fibroin in 10 mL of deionized water to prepare a 1.5 wt% elastin solution.

[0104] 2 mL of drug-loaded nanoparticles (3 mg / mL) were added to the elastin solution and stirred at room temperature for 1 h to mix thoroughly, thus obtaining a protein mixture.

[0105] The cross-linking agent (glutaraldehyde) was dissolved in a water / ethanol mixture to obtain a 2% cross-linking agent solution;

[0106] The cross-linking agent solution was slowly added dropwise to the protein mixture, stirred at room temperature for 10 hours, centrifuged at 12000g for 30 minutes, the precipitate was washed three times with ultrapure water and freeze-dried to obtain the PLGA-protein intermediate.

[0107] S300. The PLGA-protein intermediate is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained.

[0108] Dopamine was added to Tris buffer (50 mM, pH = 8.5) to obtain a dopamine solution with a dopamine concentration of 2 mg / mL.

[0109] 10 mg of PLGA-protein intermediate was added to 10 mL of dopamine solution and stirred openly at room temperature for 8 hours, during which the solution gradually turned dark brown. Then, the mixture was centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain the polydopamine-encapsulated intermediate.

[0110] S400. The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0111] PEI was added to Tris buffer (50 mM, pH = 8.5) at a concentration of 3 mg / mL to obtain a cationic polymer solution.

[0112] 1 mL of polydopamine-encapsulated intermediate (4 mg / mL) was added to 10 mL of cationic polymer solution, stirred at room temperature for 3 h, centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain nanomedicine.

[0113] S500. The nano-drug is coated onto the surface of the balloon by ultrasonic atomization spraying to obtain a drug coating:

[0114] A 5 wt% nanoparticle solution was prepared using polyacrylic acid and polylysine, and after degassing, it was sprayed onto the surface of a balloon using ultrasonic atomization. The drug flow rate was 0.03 mL / min; the ultrasonic power was 1.5 W; and the spraying cycle was 8 times to obtain the drug coating.

[0115] Example 3

[0116] A method for preparing a drug coating, comprising:

[0117] S100, Preparation of drug-loaded nanoparticles:

[0118] Prepare a PBS solution (10 mg / mL, pH 7.4) as the first aqueous phase solution;

[0119] The organic phase was prepared by mixing 5 mL of PLGA polymer solution (8 mg / mL) with a dichloromethane solution of 2.0 mg paclitaxel.

[0120] The first aqueous solution was added to the organic phase, and the mixture was treated with a probe ultrasonic emulsifier (80% power, 0.5s sonication, 0.5s interval) for 15 seconds under ice bath to fully emulsify it, thus obtaining a reverse emulsion.

[0121] The reverse emulsion was added to 40 mL of the second aqueous phase solution (1 wt% PVA aqueous solution), and the mixture was stirred thoroughly at 800 rpm until the organic solvent was completely evaporated. Large particles were removed by centrifugation at 2000 g for 5 min. The supernatant was then centrifuged at 12000 g for 30 min to obtain nanoparticles. These nanoparticles were washed three times with ultrapure water to remove excess PVA, and then resuspended in 2 mL of ultrapure water to obtain drug-loaded nanoparticles.

[0122] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0123] Dissolve an appropriate amount of silk fibroin in 10 mL of deionized water to prepare a 4 wt% elastin solution.

[0124] 2 mL of drug-loaded nanoparticles (1.5 mg / mL) were added to the elastin solution and stirred at room temperature for 1 h to mix thoroughly, thus obtaining a protein mixture.

[0125] The crosslinking agent (genipin) was dissolved in a water / ethanol mixture to obtain a 0.5% crosslinking agent solution;

[0126] The cross-linking agent solution was slowly added dropwise to the protein mixture, stirred at room temperature for 15 hours, centrifuged at 12000g for 30 minutes, the precipitate was washed three times with ultrapure water and freeze-dried to obtain the PLGA-protein intermediate.

[0127] S300. The PLGA-protein intermediate is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained.

[0128] Dopamine was added to Tris buffer (50 mM, pH = 8.5) to obtain a dopamine solution with a dopamine concentration of 2 mg / mL.

[0129] 10 mg of PLGA-protein intermediate was added to 10 mL of dopamine solution and stirred openly at room temperature for 4 hours, during which the solution gradually turned dark brown. Then, the solution was centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain the polydopamine-encapsulated intermediate.

[0130] S400. The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0131] PEI was added to Tris buffer (50 mM, pH = 8.5) at a concentration of 2 mg / mL to obtain a cationic polymer solution.

[0132] 1 mL of polydopamine-encapsulated intermediate (5 mg / mL) was added to 10 mL of cationic polymer solution, stirred at room temperature for 1.5 h, centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain nanomedicine.

[0133] S500. The nanomedicine is coated onto the surface of the capsule via electrostatic self-assembly to obtain a drug coating:

[0134] The balloon was immersed in a solution of 0.8 mg / mL polyethyleneimine, then rinsed with deionized water and dried with nitrogen to form a coating with a positively charged polycation on the balloon surface. The balloon was then immersed in a mixed solution containing nanoparticles and polyanionic polymers, specifically a mixture of 3.0 mg / mL nanoparticles and polyacrylic acid.

[0135] Repeated washing and drying create a nanoparticle coating with a polyanionic negative charge on the balloon surface. By alternating these steps four times, alternating polyanionic and polycationic drug coatings can be formed on the balloon surface.

[0136] Example 4

[0137] A method for preparing a drug coating, comprising:

[0138] S100, Preparation of drug-loaded nanoparticles:

[0139] Prepare a PBS solution (10 mg / mL, pH 7.4) as the first aqueous phase solution;

[0140] The organic phase was prepared by mixing 5 mL of PLGA polymer solution (8 mg / mL) with a dichloromethane solution of 5.0 mg paclitaxel.

[0141] The first aqueous solution was added to the organic phase, and the mixture was treated with a probe ultrasonic emulsifier (80% power, 0.5s sonication, 0.5s interval) for 15 seconds under ice bath to fully emulsify it, thus obtaining a reverse emulsion.

[0142] The reverse emulsion was added to 60 mL of the second aqueous phase solution (1 wt% PVA aqueous solution), and the mixture was stirred thoroughly at 800 rpm until the organic solvent was completely evaporated. Large particles were removed by centrifugation at 2000 g for 5 min. The supernatant was then centrifuged at 12000 g for 30 min to obtain nanoparticles. These nanoparticles were washed three times with ultrapure water to remove excess PVA, and then resuspended in 2 mL of ultrapure water to obtain drug-loaded nanoparticles.

[0143] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0144] Dissolve an appropriate amount of silk fibroin in 10 mL of deionized water to prepare a 4 wt% elastin solution.

[0145] 2 mL of drug-loaded nanoparticles (3 mg / mL) were added to the elastin solution and stirred at room temperature for 1 h to mix thoroughly, thus obtaining a protein mixture.

[0146] The crosslinking agent (genipin) was dissolved in a water / ethanol mixture to obtain a 2% crosslinking agent solution;

[0147] The cross-linking agent solution was slowly added dropwise to the protein mixture, stirred at room temperature for 8 hours, centrifuged at 12000g for 30 minutes, the precipitate was washed three times with ultrapure water and freeze-dried to obtain the PLGA-protein intermediate.

[0148] S300. The PLGA-protein intermediate is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained.

[0149] Dopamine was added to Tris buffer (50 mM, pH = 8.5) to obtain a dopamine solution with a dopamine concentration of 2 mg / mL.

[0150] 10 mg of PLGA-protein intermediate was added to 10 mL of dopamine solution and stirred openly at room temperature for 7 hours, during which the solution gradually turned dark brown. Then, the solution was centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain the polydopamine-encapsulated intermediate.

[0151] S400. The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0152] PEI was added to Tris buffer (50 mM, pH = 8.5) at a concentration of 2 mg / mL to obtain a cationic polymer solution.

[0153] 1 mL of polydopamine-encapsulated intermediate (3 mg / mL) was added to 10 mL of cationic polymer solution, stirred at room temperature for 3 h, centrifuged at 12000 g for 30 min, and the precipitate was washed 3 times with ultrapure water to obtain nanomedicine.

[0154] Poly(sulfosuccinimide) succinic acid BS(PEG)5 was dissolved in DMSO to prepare a 20 mg / mL stock solution, which was then added dropwise to 20 mL of PBS buffer to achieve a final concentration of 2.5 mg / mL. 1 mL of the nanomedicine (1 mg / mL) was slowly added dropwise to the PBS buffer containing BS(PEG)5. The mixture was stirred at room temperature for 30 min, centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain the NHS-modified nanomedicine.

[0155] S500. The nano-drug is coated onto the surface of the balloon by ultrasonic atomization spraying to obtain a drug coating:

[0156] A 5 wt% nanoparticle solution was prepared using polyacrylic acid, degassed, and then sprayed onto the surface of the balloon using ultrasonic atomization. The drug flow rate was 0.05 mL / min; the ultrasonic power was 3.0 W; and the spraying cycle was 4 times to obtain the drug coating.

[0157] Example 5

[0158] A method for preparing a drug coating, comprising:

[0159] S100, Preparation of drug-loaded nanoparticles:

[0160] Prepare a PBS solution (7 mg / mL, pH 7.4) as the first aqueous phase solution;

[0161] 5 mL of PLGA polymer solution (12 mg / mL) was mixed with a 3.5 mg solution of paclitaxel in dichloromethane to form the organic phase.

[0162] The first aqueous solution was added to the organic phase, and the mixture was treated with a probe ultrasonic emulsifier (80% power, 0.5s sonication, 0.5s interval) for 15 seconds under ice bath to fully emulsify it, thus obtaining a reverse emulsion.

[0163] The reverse emulsion was added to 50 mL of the second aqueous phase solution (2 wt% PVA aqueous solution), and the mixture was stirred thoroughly at 800 rpm until the organic solvent was completely evaporated. Large particles were removed by centrifugation at 2000 g for 5 min. The supernatant was then centrifuged at 12000 g for 30 min to obtain nanoparticles. These nanoparticles were washed three times with ultrapure water to remove excess PVA, and then resuspended in 2 mL of ultrapure water to obtain drug-loaded nanoparticles.

[0164] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0165] Dissolve an appropriate amount of silk fibroin in 10 mL of deionized water to prepare a 1.5 wt% elastin solution.

[0166] 2 mL of drug-loaded nanoparticles (3 mg / mL) were added to the elastin solution and stirred at room temperature for 1 h to mix thoroughly, thus obtaining a protein mixture.

[0167] The crosslinking agent (genipin) was dissolved in a water / ethanol mixture to obtain a 1.5% crosslinking agent solution;

[0168] The cross-linking agent solution was slowly added dropwise to the protein mixture, stirred at room temperature for 8 hours, centrifuged at 12000g for 30 minutes, the precipitate was washed three times with ultrapure water and freeze-dried to obtain the PLGA-protein intermediate.

[0169] S300. The PLGA-protein intermediate is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained.

[0170] Dopamine was added to Tris buffer (50 mM, pH = 8.5) to obtain a dopamine solution with a dopamine concentration of 3.5 mg / mL.

[0171] 10 mg of PLGA-protein intermediate was added to 10 mL of dopamine solution and stirred openly at room temperature for 8 hours, during which the solution gradually turned dark brown. Then, the mixture was centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain the polydopamine-encapsulated intermediate.

[0172] S400. The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0173] PEI was added to Tris buffer (50 mM, pH = 8.5) at a concentration of 3 mg / mL to obtain a cationic polymer solution.

[0174] PEI25K was dissolved in methanol, and 4-(bromomethyl)phenylboronic acid was added. The molar ratio of PEI to phenylboronic acid was 1:0.3. The reaction was carried out at 60℃ for 12 h. After the reaction was completed, the product was added dropwise to ice-cold diethyl ether to precipitate. This process was repeated three times to obtain PEI-PBA.

[0175] Prepare a PBS buffer containing PEI-PBA (2 mg / mL), add 1 mL of polydopamine-encapsulated intermediate (5 mg / mL) to 10 mL of PEI-PBA buffer, stir at room temperature for 2 h, centrifuge at 12000 g for 30 min, and wash the precipitate three times with ultrapure water to obtain phenylboronic acid-modified nanomedicine.

[0176] S500. The nano-drug is coated onto the surface of the balloon by ultrasonic atomization spraying to obtain a drug coating:

[0177] A 4 wt% nanoparticle solution was prepared using polyacrylic acid, degassed, and then sprayed onto the surface of the balloon using ultrasonic atomization. The drug flow rate was 0.04 mL / min; the ultrasonic power was 2.5 W; and the spraying cycle was 5 times to obtain the drug coating.

[0178] Comparative Example 1

[0179] This comparative study prepared a drug-loaded core + adhesion layer structure of nanomedicine, which does not contain an elastin layer;

[0180] S100, Preparation of drug-loaded nanoparticles:

[0181] Prepare a PBS solution (10 mg / mL, pH 7.4) as the first aqueous phase solution;

[0182] A 5 mL PLGA polymer solution (lactic acid:glycolic acid = 50:50, molecular weight 10000 kDa, 10 mg / mL) was mixed with a 2.5 mg colchicine solution in dichloromethane to form the organic phase.

[0183] The first aqueous solution was added to the organic phase, and the mixture was treated with a probe ultrasonic emulsifier (80% power, 0.5s sonication, 0.5s interval) for 15 seconds under ice bath to fully emulsify it, thus obtaining a reverse emulsion.

[0184] The reverse emulsion was added to 50 mL of the second aqueous phase solution (1 wt% PVA aqueous solution), and the mixture was stirred thoroughly at 800 rpm until the organic solvent was completely evaporated. Large particles were removed by centrifugation at 2000 g for 5 min. The supernatant was then centrifuged at 12000 g for 30 min to obtain nanoparticles. These nanoparticles were washed three times with ultrapure water to remove excess PVA, and then resuspended in 2 mL of ultrapure water to obtain drug-loaded nanoparticles.

[0185] S300. The drug-loaded nanoparticles are added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained.

[0186] Dopamine was added to Tris buffer (50 mM, pH = 8.5) to obtain a dopamine solution with a dopamine concentration of 1 mg / mL.

[0187] 5 mg of drug-loaded nanoparticles were added to 10 mL of dopamine solution and stirred openly at room temperature for 6 hours, during which the solution gradually turned dark brown. The solution was then centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain the polydopamine-encapsulated intermediate.

[0188] S400. The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0189] PEI (25 kDa) was added to Tris buffer (50 mM, pH = 8.5), where the PEI concentration was 2 mg / mL, to obtain a cationic polymer solution;

[0190] 1 mL of polydopamine-encapsulated intermediate (5 mg / mL) was added to 10 mL of cationic polymer solution, stirred at room temperature for 2 h, centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain nanomedicine.

[0191] S500. The nano-drug is coated onto the surface of the balloon by ultrasonic atomization spraying to obtain a drug coating:

[0192] A 2 wt% nanoparticle solution was prepared using polyacrylic acid, degassed, and then sprayed onto the surface of the balloon using ultrasonic atomization. The drug flow rate was 0.02 mL / min; the ultrasonic power was 1.0 W; and the spraying cycle was 6 times to obtain the drug coating.

[0193] Comparative Example 2

[0194] This comparative study prepared a nanomedicine with a drug-loaded core, an elastin layer, and a polydopamine layer structure, without a cationic polymer layer.

[0195] S100, Preparation of drug-loaded nanoparticles:

[0196] Prepare a PBS solution (10 mg / mL, pH 7.4) as the first aqueous phase solution;

[0197] A 5 mL PLGA polymer solution (lactic acid:glycolic acid = 50:50, molecular weight 10000 kDa, 10 mg / mL) was mixed with a 2.5 mg colchicine solution in dichloromethane to form the organic phase.

[0198] The first aqueous solution was added to the organic phase, and the mixture was treated with a probe ultrasonic emulsifier (80% power, 0.5s sonication, 0.5s interval) for 15 seconds under ice bath to fully emulsify it, thus obtaining a reverse emulsion.

[0199] The reverse emulsion was added to 50 mL of the second aqueous phase solution (1 wt% PVA aqueous solution), and the mixture was stirred thoroughly at 800 rpm until the organic solvent was completely evaporated. Large particles were removed by centrifugation at 2000 g for 5 min. The supernatant was then centrifuged at 12000 g for 30 min to obtain nanoparticles. These nanoparticles were washed three times with ultrapure water to remove excess PVA, and then resuspended in 2 mL of ultrapure water to obtain drug-loaded nanoparticles.

[0200] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0201] Dissolve an appropriate amount of silk fibroin in 10 mL of deionized water to prepare a 2 wt% elastin solution.

[0202] 2 mL of drug-loaded nanoparticles (2 mg / mL) were added to the elastin solution and stirred at room temperature for 1 h to mix thoroughly, thus obtaining a protein mixture.

[0203] The crosslinking agent (genipin) was dissolved in a water / ethanol mixture to obtain a 1% crosslinking agent solution;

[0204] The cross-linking agent solution was slowly added dropwise to the protein mixture, stirred at room temperature for 12 hours, centrifuged at 12000g for 30 minutes, the precipitate was washed three times with ultrapure water and freeze-dried to obtain the PLGA-protein intermediate.

[0205] S300. The PLGA-protein intermediate is added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate is obtained.

[0206] Dopamine was added to Tris buffer (50 mM, pH = 8.5) to obtain a dopamine solution with a dopamine concentration of 1 mg / mL.

[0207] 10 mg of PLGA-protein intermediate was added to 10 mL of dopamine solution and stirred openly at room temperature for 6 hours, during which the solution gradually turned dark brown. The solution was then centrifuged at 12000 g for 30 min, and the precipitate was washed three times with ultrapure water to obtain polydopamine-encapsulated nanomedicine.

[0208] S500. The nano-drug is coated onto the surface of the balloon by ultrasonic atomization spraying to obtain a drug coating:

[0209] A 2 wt% nanoparticle solution was prepared using polyacrylic acid, degassed, and then sprayed onto the surface of the balloon using ultrasonic atomization. The drug flow rate was 0.02 mL / min; the ultrasonic power was 1.0 W; and the spraying cycle was 6 times to obtain the drug coating.

[0210] Comparative Example 3

[0211] This comparative study prepared a nanomedicine with a drug-loaded core, an elastin layer, and a PEI layer structure, without a polydopamine layer.

[0212] A method for preparing a drug coating, comprising:

[0213] S100, Preparation of drug-loaded nanoparticles:

[0214] Prepare a PBS solution (10 mg / mL, pH 7.4) as the first aqueous phase solution;

[0215] A 5 mL PLGA polymer solution (lactic acid:glycolic acid = 50:50, molecular weight 10000 kDa, 10 mg / mL) was mixed with a 2.5 mg colchicine solution in dichloromethane to form the organic phase.

[0216] The first aqueous solution was added to the organic phase, and the mixture was treated with a probe ultrasonic emulsifier (80% power, 0.5s sonication, 0.5s interval) for 15 seconds under ice bath to fully emulsify it, thus obtaining a reverse emulsion.

[0217] The reverse emulsion was added to 50 mL of the second aqueous phase solution (1 wt% PVA aqueous solution), and the mixture was stirred thoroughly at 800 rpm until the organic solvent was completely evaporated. Large particles were removed by centrifugation at 2000 g for 5 min. The supernatant was then centrifuged at 12000 g for 30 min to obtain nanoparticles. These nanoparticles were washed three times with ultrapure water to remove excess PVA, and then resuspended in 2 mL of ultrapure water to obtain drug-loaded nanoparticles.

[0218] S200. The drug-loaded nanoparticles are mixed with an elastin solution to obtain a protein mixture. A cross-linking agent solution is slowly added dropwise to the protein mixture to obtain a PLGA-protein intermediate.

[0219] Dissolve an appropriate amount of silk fibroin in 10 mL of deionized water to prepare a 2 wt% elastin solution.

[0220] 2 mL of drug-loaded nanoparticles (2 mg / mL) were added to the elastin solution and stirred at room temperature for 1 h to mix thoroughly, thus obtaining a protein mixture.

[0221] The crosslinking agent (genipin) was dissolved in a water / ethanol mixture to obtain a 1% crosslinking agent solution;

[0222] The cross-linking agent solution was slowly added dropwise to the protein mixture, stirred at room temperature for 12 hours, centrifuged at 12000g for 30 minutes, the precipitate was washed three times with ultrapure water and freeze-dried to obtain the PLGA-protein intermediate.

[0223] S300. The PLGA-protein intermediate is added to a cationic polymer solution, and the nanomedicine is obtained after the reaction.

[0224] PEI (25 kDa) was added to Tris buffer (50 mM, pH = 8.5), where the PEI concentration was 2 mg / mL, to obtain a cationic polymer solution;

[0225] 1 mL of PLGA-protein intermediate (5 mg / mL) was added to 10 mL of cationic polymer solution, stirred at room temperature for 2 h, centrifuged at 12000 g for 30 min, and the precipitate was washed 3 times with ultrapure water to obtain nanomedicine.

[0226] S500. The nano-drug is coated onto the surface of the balloon by ultrasonic atomization spraying to obtain a drug coating:

[0227] A 2 wt% nanoparticle solution was prepared using polyacrylic acid, degassed, and then sprayed onto the surface of the balloon using ultrasonic atomization. The drug flow rate was 0.02 mL / min; the ultrasonic power was 1.0 W; and the spraying cycle was 6 times to obtain the drug coating.

[0228] The drug coatings of Examples 1-5 and Comparative Examples 1-3 were tested for various parameters. Fluorescently labeled drugs were used to detect the adhesion and retention rate (retention rate) of the drugs at the target site. Each sample was tested 5 times, and the average retention rate was taken. The test results are shown in Table 1.

[0229] Table 1. Test results of Examples 1-5 and Comparative Examples 1-3

[0230]

[0231]

[0232] Drug release response time refers to the time required for a drug to enter the body and begin to exert its therapeutic effect.

[0233] When drug-loaded nanoparticles are used to create drug films, the 6-hour retention rate is only 38% ± 5% because they cannot adhere strongly to the structure of the blood vessel wall, and their targeting accuracy is limited to the tissue level. However, by using the method described in this application to encapsulate and modify the drug, its targeting accuracy can reach the cellular substructure level, enabling it to bind to specific cellular structures. Furthermore, directly using drug-loaded nanoparticles as drug films results in a duration of treatment of only 2-3 hours, a drug release response time > 60 minutes, unsatisfactory therapeutic effects, and significant drug loss into the bloodstream, leading to high off-target toxicity.

[0234] Conventional drug-eluting balloons, once inserted into a blood vessel, are typically required to reach the target lesion and open within 15-30 seconds. This is because the drug release rate in the blood vessel is too rapid, necessitating the rapid delivery of the balloon to the target site. The drug particles in this application are coated with elastin and an adhesion layer, allowing the drug release rate to be adjusted and extended as needed. This effectively prolongs the opening time of the drug-eluting balloon after entering the blood vessel, reducing drug distribution in non-target areas and lowering surgical risks.

[0235] As can be seen from the test results in Table 1, the retention rate of the drug coating of this application can still be maintained at about 80% after 12 hours, and the treatment duration can reach 2-4 weeks. This indicates that under the complex environment of blood flow scouring and changes in vasodilation, vasoconstriction and shear force, the drug particles can maintain excellent adhesion, have a high drug concentration at the target site and can be continuously released. Reducing the loss of drugs in the blood flow can reduce the risk of thrombosis and embolism, and can also reduce the need for re-intervention due to drug loss, thus reducing the medical burden on patients.

[0236] In Comparative Example 1, the drug, without an elastin layer, had a slightly higher initial retention rate than Comparative Examples 2 and 3. However, after a period of time, with changes in vascular dilation and contraction, a large number of drug particles detached from the blood vessels and lost their adhesive ability, thus significantly reducing the later retention rate. Comparative Examples 2 and 3, respectively, contained drugs coated only with polydopamine and PEI, exhibiting some adhesion to blood vessels, but significantly less than the adhesive effect achieved by using both in combination. Therefore, this application, by designing an elastin interlayer and a polydopamine + PEI adhesive layer, significantly improves the long-term adhesion performance of the drug coating within blood vessels, sustainably maintaining the drug concentration at therapeutic levels, prolonging the duration of drug action, and effectively enhancing therapeutic efficacy.

[0237] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A method for preparing a drug coating, characterized in that, The drug coating includes a nanomedicine, which comprises, from the inside out, drug-loaded nanoparticles, an elastin layer, and an adhesive layer. The adhesive layer includes a polydopamine coating and a cationic polymer coating. In the nanomedicine, the thickness ratio of the elastin layer, the polydopamine coating, and the cationic polymer coating is (4-6):3:(1-3). The components of the elastin layer include at least one of silk fibroin or spider silk fibroin; The preparation method includes: Elastin was dissolved in water to prepare an elastin solution with a concentration of 1-5%. Drug-loaded nanoparticles were added to the elastin solution and the mixture was stirred at room temperature to obtain a protein mixture. The crosslinking agent is dissolved in a water / ethanol mixture to obtain a crosslinking agent solution with a concentration of 0.5-2%. The cross-linking agent solution was added dropwise to the protein mixture, and the mixture was stirred at room temperature for 8-15 hours. After the reaction, the mixture was centrifuged, washed, and freeze-dried to obtain the PLGA-protein intermediate. The cross-linking agent included at least one of genipin or glutaraldehyde. The PLGA-protein intermediate was added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate was obtained. The polydopamine-encapsulated intermediate was added to a cationic polymer solution, and the resulting reaction yielded a nanomedicine. The nanomedicine is coated onto the surface of the capsule by ultrasonic atomization spraying or electrostatic self-assembly to obtain a drug coating.

2. The method for preparing a drug coating according to claim 1, characterized in that, The cationic polymer coating comprises at least one of polyethyleneimine, poly-L-lysine, chitosan, and poly-β-amino ester.

3. The method for preparing a drug coating according to claim 1, characterized in that, The surface of the nanomedicine is further modified with at least one of the following: NHS groups, aldehyde groups, isothiocyanate groups, and phenylboronic acid groups.

4. The method for preparing a drug coating according to claim 1, characterized in that, The PLGA-protein intermediate was added to a dopamine solution, and after the reaction, a polydopamine-encapsulated intermediate was obtained, comprising: Dopamine was added to Tris buffer to prepare a dopamine solution with a concentration of 0.5-2 mg / mL; The PLGA-protein intermediate was added to the dopamine solution and stirred at room temperature for 4-8 hours. After the reaction, the mixture was centrifuged and washed to obtain the polydopamine-encapsulated intermediate.

5. The method for preparing a drug coating according to claim 1, characterized in that, The polydopamine-encapsulated intermediate is added to a cationic polymer solution, and the reaction yields a nanomedicine comprising: The cationic polymer was added to Tris buffer to prepare a cationic polymer solution with a concentration of 1-4 mg / mL; The polydopamine-encapsulated intermediate was added to the cationic polymer solution, and the mixture was stirred at room temperature for 1-3 hours. After the reaction, the mixture was centrifuged and washed to obtain the nanomedicine.

6. The method for preparing a drug coating according to claim 1, characterized in that, The drug-loaded nanoparticles are PLGA drug-loaded nanoparticles, and their preparation method includes: Prepare the first aqueous phase solution; The PLGA polymer was mixed with a drug solution to obtain an organic phase; The first aqueous solution was added to the organic phase and fully emulsified to obtain a reverse emulsion. The reverse emulsion was added to the second aqueous phase solution, and the mixture was stirred and emulsified thoroughly. The emulsion was then centrifuged to obtain PLGA drug-loaded nanoparticles.

7. A drug-eluting balloon, characterized in that, The surface of the drug-eluting balloon is covered with a drug coating prepared by the preparation method according to any one of claims 1-3.

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