Balloon drug coating, preparation method thereof and drug coating balloon

Abstract

The invention discloses a balloon drug coating, a preparation method thereof and a drug coating balloon, the coating is of a double-layer structure, and a sacrificial layer and a drug-loaded adhesion layer are sequentially arranged on the surface of a balloon base body; the sacrificial layer is a water-soluble polymer layer, and the adhesion layer loaded with the medicine is a cholesterol modified polyelectrolyte layer loaded with the medicine. Wherein the sacrificial layer located on the inner side can effectively reduce adhesion between the medicine coating and the balloon so as to improve the transfer rate, and the adhesion layer on the outer side can effectively load the medicine and can achieve efficient medicine transfer and adhesion of the diseased region in the transient contact process. In a simulated physiological shearing environment, the coating can be kept on the surface of vascular tissue for a period of time, and the stability and retention effect of the drug coating in the vascular wall are remarkably improved. According to the transfer adhesion type coating strategy, the problem of low medicine utilization rate caused by medicine loss in an existing balloon medicine coating technology is effectively solved.

Description

Technical Field

[0001] The present invention belongs to the technical field of interventional medical devices, and in particular relates to a balloon drug coating, a preparation method thereof, and a drug-coated balloon. Background Art

[0002] Drug-coated balloon (DCB) is an important interventional treatment technology for current clinical angioplasty. It is widely used to dilate narrowed blood vessels, especially in the treatment of coronary artery disease. During vascular reconstruction, mechanical damage may damage the endothelial barrier and induce smooth muscle cell proliferation, eventually leading to restenosis. In order to inhibit this process, anti-cell proliferation drugs (such as paclitaxel or rapamycin) are usually evenly applied to the surface of the balloon. When the balloon is expanded, the drug can quickly enter the vascular wall tissue and continue to act, thereby effectively inhibiting the occurrence of restenosis. Compared with other coronary artery interventional treatment technologies, DCB has the advantage of leaving no permanent objects, which is expected to accelerate arterial healing, retain and restore normal vascular function early, and eliminate stent thrombosis and restenosis.

[0003] However, DCB still faces some technical challenges. The ideal coating should not only have sufficient stability to prevent the drug from falling off during treatment, but also be able to quickly and effectively transfer the drug to the blood vessel wall. Normally, the contact time between DCB and the blood vessel wall is only a few seconds to a few minutes. In this short time window, the transfer and retention of the drug are extremely critical. However, during the use of the coating, due to poor transfer adhesion with the tissue and continuous blood flow impact, the drug is easily washed away or falls off, thereby affecting the effective retention of the drug at the lesion site, and ultimately leading to insufficient treatment effect. Therefore, improving the adhesion and retention of the drug coating on the blood vessel wall and reducing the loss of the drug have become key issues that need to be urgently addressed in drug-coated balloon technology. Summary of the invention

[0004] In view of the problems existing in the prior art, the present invention provides a balloon drug coating, a preparation method thereof and a drug-coated balloon. The coating adopts a double-layer structure, and the inner layer of the balloon is a water-soluble polymer layer to reduce the adhesion between the drug coating and the balloon to improve the transfer rate. The outer layer of the balloon adopts a cholesterol-modified polyelectrolyte as an adhesion layer, wherein cholesterol, as a natural component in the body, has good compatibility with cell membrane lipids. The adhesion layer can effectively load the drug and achieve efficient drug transfer and adhesion to the lesion site during a short contact process. At the same time, under a simulated physiological shear environment, the coating can remain on the surface of the vascular tissue for a period of time, significantly improving the stability and retention effect of the drug coating in the vascular wall. This transfer adhesion type coating strategy effectively solves the problem of low drug utilization rate caused by drug loss in the existing balloon drug coating technology.

[0005] The technical solution adopted by the present invention is as follows:

[0006] A balloon drug coating is a double-layer structure, in which a sacrificial layer and a drug-loaded adhesion layer are sequentially arranged on the surface of a balloon substrate; the sacrificial layer is a water-soluble polymer layer, and the drug-loaded adhesion layer is a cholesterol-modified polyelectrolyte layer loaded with drugs.

[0007] In the above technical solution, further, the water-soluble polymer is generally one or more of polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), polyethylene glycol (PEG); preferably PVP, with a weight average molecular weight of 20,000Da-100,000Da;

[0008] Furthermore, the cholesterol-modified polyelectrolyte is a polyelectrolyte covalently modified with cholesterol molecules through a chemical reaction, wherein:

[0009] The chemical reaction may be one or more of amidation reaction, Schiff base reaction, etherification reaction, addition reaction, etc.;

[0010] The polyelectrolyte is usually one or more of branched polyethyleneimine, linear polyethyleneimine, polyacrylamide, chitosan, gelatin, etc., preferably branched polyethyleneimine;

[0011] The method for preparing the balloon drug coating comprises the following steps:

[0012] Prepare a water-soluble polymer solution: dissolve the water-soluble polymer in a mixed solution of ethanol and water, wherein the volume fraction of ethanol in the mixed solution is 50-80%, preferably 80%;

[0013] Preparation of a cholesterol-modified polyelectrolyte solution: covalently modifying cholesterol molecules onto the polyelectrolyte through a chemical reaction, and dissolving the cholesterol molecules in an organic solvent; the solvent is one or more of dichloromethane, tetrahydrofuran, ethyl acetate, ethanol, and methanol;

[0014] Preparation of active drug solution: active drugs include anti-proliferation, anti-inflammatory, anti-thrombotic, anti-migration or endothelial repair-promoting substances, hydrophilic drugs are dissolved in aqueous solution, and lipophilic drugs are dissolved in organic solution; the hydrophilic drugs include one or more of plasmid DNA (pDNA), microRNA (miRNA), small interfering RNA (siRNA), proteins and their analogs, the aqueous solution is one or more of aqueous solution, Tris-EDTA buffer (TE), phosphate buffered saline (PBS); the lipophilic drugs include one or more of rapamycin (sirolimus), paclitaxel, everolimus, tacrolimus and their derivatives or analogs, and the organic solution is one or more of dichloromethane, tetrahydrofuran, methanol, ethanol, etc.;

[0015] Preparation of drug coating: The water-soluble polymer solution is deposited on the surface of the balloon matrix by spraying to form a sacrificial layer, and then the cholesterol-modified polyelectrolyte solution and the active drug solution are deposited on the surface of the sacrificial layer by blending single-channel ultrasonic spraying or non-blending double-channel ultrasonic spraying to obtain a drug-loaded adhesion layer, thereby obtaining the balloon drug coating.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The present invention provides a drug coating strategy with a sacrificial layer and an adhesion layer. On the one hand, the sacrificial layer reduces the interaction with the balloon to improve the transfer effect. On the other hand, the cholesterol-modified polyelectrolyte adhesion layer increases the binding force between the material and the blood vessel wall through multiple action mechanisms, which not only effectively improves the transfer rate and retention time of the drug, but also significantly improves the stability of the coating in a high-flow blood environment.

[0018] (1) Excellent transferability of drug coating: The coating system adopts a sacrificial layer structure, which can be quickly dissolved or removed during operation, effectively reducing the adhesion between the coating material and the balloon surface, thereby improving the transfer efficiency of the coating to the blood vessel wall during balloon inflation.

[0019] (2) Stability of drug coating: In order to enhance the stability of the coating material in the blood environment, the present invention uses a cholesterol-modified polyelectrolyte material in the adhesion layer. This design not only improves the hydrophobicity of the coating, reduces the swelling and detachment of the material near the blood vessel wall, but also reduces the premature release or loss of the drug in the coating during transportation.

[0020] (3) Extensive drug loading: Cholesterol-modified polyelectrolytes are used as drug loading layers, which can load different drugs through a variety of action mechanisms. They can not only effectively encapsulate hydrophilic charged active drug molecules, but also lipophilic active drug molecules. Compared with the common single-action mechanism coatings in the prior art, this design enables the coating to have higher flexibility in drug encapsulation and delivery, and is compatible with a wider range of drug types.

[0021] (4) Adhesion and retention of drug coating at the lesion site: In order to enhance the adhesion of the coating material to the blood vessels, the present invention uses a cholesterol-modified polyelectrolyte material in the adhesion layer. Cholesterol, as a natural lipid molecule, shows compatibility and biocompatibility with cell membranes. By introducing polyelectrolyte and cholesterol groups at the same time, the interaction between the coating and the blood vessel wall is significantly enhanced. This design greatly prolongs the retention time of the drug coating in the blood vessel, and maintains sufficient adhesion even in a shear flow environment, ensuring the effective release of the drug at the treatment site. Compared with traditional coatings in the prior art (such as those that rely solely on electrostatic or hydrophobic effects), the present invention enhances the stability of the coating in a high-flow blood environment through the combination of multiple forces (including but not limited to electrostatic interactions, hydrophobic interactions, and lipid compatibility), significantly improving the transfer efficiency and retention time of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is the chemical structural formula of the target product of the cholesterol-modified polyelectrolyte material in step 2 of Example 1-4;

[0023] Figure 2 The H NMR spectrum of the target product of the cholesterol-modified polyelectrolyte material in step 2 of Example 1-4;

[0024] Figure 3 The scanning electron microscope images of the drug coating surfaces obtained in step 4 of Examples 1-4 and Comparative Example 1;

[0025] Figure 4 This is a body photograph of the drug-coated balloon prepared in Example 1.

[0026] Figure 5 It is a statistical diagram of the substrate residual rate and tissue transfer rate of the drug coating in the in vitro vascular transfer adhesion test of Examples 1-4 and Comparative Example 1;

[0027] Figure 6 It is a statistical diagram of the tissue adhesion residual rate of the drug coating in the in vitro vascular adhesion stability test of Examples 1-4;

[0028] Figure 7 The expression of related proteins in tissues 14 days after in vivo intervention with drug-coated balloons in Example 3 and Comparative Example 1. DETAILED DESCRIPTION

[0029] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with Examples and Comparative Examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. Those skilled in the art will make modifications or equivalent substitutions based on the understanding of the technical scheme of the present invention, without departing from the spirit and scope of the technical scheme of the present invention, and all should be included in the protection scope of the present invention.

[0030] In the present invention, unless otherwise specified, all reagents and drugs used are purchased from common commercial sources. The plasmid DNA (pDNA) encoding pIRES2-EGFP-VEGFA (species: rat) was provided by Qingfeng Biotechnology Co., Ltd. in Changsha, China.

[0031] Example 1

[0032] Step 1: Dissolve the 40,000Da polymer PVP in 80% ethanol solution at a concentration of 10mg / mL, and spray it on the flat surface at a liquid injection rate of 25μL / min for subsequent transfer adhesion test, and set the heating stage temperature to 40°C; spray it on the balloon at a liquid injection rate of 5μL / min for subsequent balloon characterization and verification, and use a heating lamp to heat to accelerate solvent evaporation.

[0033] Step 2: The cholesterol-modified polyelectrolyte in this example is a branched polyethyleneimine (PEI) modified with cholesterol hydrophobicity. Chol ). The modified polymer molecules are mainly obtained by the amidation reaction between cholesterol chloride (Chol) and polyethyleneimine (PEI) amine groups. The specific steps are briefly described as follows: First, 1g PEI is completely dissolved in 25mL of anhydrous dichloromethane, and an appropriate amount of triethylamine (TEA) is added as an acid-binding agent, and the mixture is placed in an ice bath and stirred vigorously; then 10mL of Chol in anhydrous dichloromethane solution is slowly added to the mixed solution through a titration funnel under nitrogen protection, wherein the molar ratio of the amount of Chol to the monomer of PEI in the reactant is controlled to be 0.03:1, and the dropping time is controlled within 30 minutes; after the reaction is completed, the mixed solution is continued to be stirred in an ice bath for 6 hours, and then transferred to room temperature and stirred for 6 hours; after the reaction is completed, the dichloromethane solvent is removed by vacuum distillation. Finally, the residual precipitate is dissolved in dichloromethane, and slowly added to acetone to remove unreacted TEA and Chol, and dried under vacuum conditions for 3 hours to obtain the target product, which is recorded as PEI Chol -1.

[0034] The chemical structure of the synthesized product was analyzed by H-NMR spectroscopy.

[0035] The synthesized product was stored at -20°C until used, and dichloromethane was used as the solvent.

[0036] Step 3: Dissolve fish sperm DNA (FS-DNA) at a concentration of 10 mg / mL in TE buffer (pH = 8.0) for flat spraying; mix FS-DNA and pDNA in a mass ratio of 1:1 and dissolve them in TE buffer (pH = 8.0) at a concentration of 2 mg / mL for balloon spraying.

[0037] Step 4: The solution in step 2 and the solution in step 3 are respectively sucked into two 5 mL injectors, where PEI Chol The N / P ratio with DNA was 3:1, and the adhesion layer was prepared by bilateral spraying on the basis of step 1. The liquid inlet speed was controlled to be consistent, and the plane was sprayed at a liquid inlet speed of 15 μL / min for subsequent transfer adhesion test, and the heating stage temperature was set to 40°C, where the plane was a polyurethane (TPU) substrate with a diameter of 8 mm; the balloon was sprayed at a liquid inlet speed of 3 μL / min for subsequent balloon characterization and verification, where the balloon was a balloon with a diameter of 1.5 mm prepared by Gui Chuang Tongqiao Medical Technology Co., Ltd., and a heating lamp was used to heat and accelerate the evaporation of the solvent, and finally a coating with a double-layer structure was obtained.

[0038] Example 2

[0039] The preparation process is basically the same as that in Example 1, except that the molar ratio of the amount of Chol added to the monomer of PEI in the reactant is controlled to be 0.05:1 in step 2, and the target product obtained in step 2 is recorded as PEI Chol -2. The concentrations of other solutions and the coating preparation methods are exactly the same as those in Example 1.

[0040] Example 3

[0041] The preparation process is basically the same as that in Example 1, except that the molar ratio of the amount of Chol added to the monomer of PEI in the reactant is controlled to be 0.15:1 in step 2, and the target product obtained in step 2 is recorded as PEI Chol -3. The concentrations of other solutions and the coating preparation methods are exactly the same as those in Example 1.

[0042] Example 4

[0043] The preparation process is basically the same as that in Example 1, except that the molar ratio of the amount of Chol added to the monomer of PEI in the reactant is controlled to be 0.35:1 in step 2, and the target product obtained in step 2 is recorded as PEI Chol -3. The concentrations of other solutions and the coating preparation methods are exactly the same as those in Example 1.

[0044] Comparative Example 1

[0045] The preparation process is basically the same as that in Example 1, the only difference is that cholesterol modification is not performed in step 2, and the concentrations of other solutions and the coating preparation method are exactly the same as those in Example 1.

[0046] Comparative Example 2

[0047] The preparation process is basically the same as that in Example 1, the only difference is that step 1 is not carried out, that is, the sacrificial layer is not sprayed, and the concentrations of other solutions and the coating preparation method are exactly the same as those in Example 1.

[0048] Comparative Example 3

[0049] The preparation process is basically the same as that of Comparative Example 1, the only difference is that step 1 is not carried out, that is, the sacrificial layer is not sprayed, and the concentrations of other solutions and the coating preparation method are exactly the same as those in Comparative Example 1.

[0050] Figure 1 The figure is a schematic diagram of the chemical structure of the target product synthesized in step 2 of Example 1-4. Branched PEI contains primary amine, secondary amine and tertiary amine at the same time, and the theoretical ratio is 1:2:1, among which the primary amine shows the highest chemical reactivity, so cholesterol in this chemical structure mainly reacts with the primary amine in PEI for modification.

[0051] Figure 2 This is the H NMR spectrum of the target product synthesized in step 2 of Example 1-4, which proves the successful synthesis of cholesterol hydrophobically modified polyelectrolyte PEI. After normalizing the NMR peak attributed to PEI, it can be found that the NMR peak intensity attributed to cholesterol gradually increases with the increase of cholesterol feed ratio.

[0052] Figure 3 The scanning electron microscope images of the surface morphology of the target drug coating obtained in step 4 of Examples 1-4 and Comparative Example 1 show that as the amount of hydrophobic cholesterol introduced gradually increases, the coating surface has more undulations and the roughness gradually increases.

[0053] Figure 4 This is a three-dimensional photograph of the drug-coated balloon prepared in Example 1. It can be clearly found through observation that there is a translucent coating on the surface of the balloon.

[0054] Performance Verification

[0055] In vitro transfer adhesion assay:

[0056] The 8mm diameter TPU sprayed with different embodiments and comparative examples of drug coatings was soaked in PBS for 1 minute to simulate the wet environment of the drug coating during transportation to the lesion. It was then fixed to the upper pressure head of the universal testing machine with double-sided tape, and a fresh porcine aorta pre-wetted with PBS was placed above the lower pressure head. Subsequently, the TPU substrate coated with the drug coating was pressed on the aorta with a pressure of 1atm using a universal testing machine at a descent rate of 20mm / min, and kept for 1 minute to simulate the process of contact between the drug coating balloon expansion and the lesion tissue. Then, the upper pressure head was raised at a speed of 20mm / min until the two were separated, the TPU substrate and the porcine aorta were removed and gently rinsed with PBS to remove the drug coating that fell off or was not adhered. Finally, a stereomicroscope was used to take pictures of the coating remaining on the substrate and the coating adhered to the porcine aorta, and the drug coating substrate residue and tissue transfer rate were counted by image analysis software (ImageJ).

[0057] The following table shows the statistical data of the substrate residual rate and tissue transfer rate of the drug coating in the in vitro vascular transfer adhesion test of different embodiments and comparative examples. Figure 5 The data statistics of the substrate residual rate and tissue transfer rate of the drug coating in the in vitro vascular transfer adhesion test of Examples 1-4 and Comparative Example 1 containing sacrificial layers. Through data analysis, it can be found that the coating of Comparative Example 1 is almost not transferred, and more than 65% of the coating remains on the surface of the TPU substrate. In contrast, most of the drug coatings of Examples 1-4 are transferred and adhered to the vascular wall, and only about 10% of the coating remains on the surface of the TPU substrate. The above results all show that this drug coating design can effectively improve the transfer adhesion of the drug coating to the tissue by introducing a sacrificial layer and a cholesterol-modified polyelectrolyte adhesion layer. It is also found that the coating with the introduction of the sacrificial layer has a higher tissue transfer rate and a lower substrate residual rate than the coating without the introduction of the sacrificial layer, indicating that due to the introduction of the sacrificial layer with good water solubility, it is quickly dissolved or removed in a humid environment, which helps to reduce the interaction between the coating and the hydrophobic balloon surface, thereby improving the transfer efficiency of the coating to the vascular wall during the balloon expansion process.

[0058]

[0059] In vitro adhesion stability test:

[0060] The adhesion stability of the drug coating on the tissue surface was evaluated using an in vitro simulated dynamic shear flow system. Specifically, the porcine aorta of Examples 1-4 in the above in vitro transfer adhesion test was placed in a circular chamber with an inner diameter of 9 mm and an outer diameter of 13 mm, and each chamber was connected to a beaker through a silicone tube with an inner diameter of 3 mm to form a closed loop. PBS containing 1% penicillin-streptomycin double antibody was further added to the beaker, and it was maintained in a constant temperature water bath at 37°C together with the chamber, and the solution was replaced every 12 hours. This system was connected to a peristaltic pump through a silicone tube to generate the required pulsation and shear stress. The flow rate was controlled to 30 mL / min to simulate the long-term blood flow scouring shear environment faced by the drug coating after transfer in vivo. After exposure to this shear flow environment for 0.5, 1, 2, and 3 days, the porcine aorta in the chamber was removed, and the residual coating on the tissue surface was photographed and recorded using a stereo microscope, and the residual rate of drug coating tissue adhesion in each embodiment was counted by image analysis software (ImageJ).

[0061] Figure 6 The data statistics of the tissue adhesion residual rate of the drug coating in the in vitro vascular adhesion stability test of Examples 1-4 are shown in Figure 1-4. It can be found that the adhered coating gradually falls off over time. After one day of exposure to a dynamic shear flow environment, the tissue adhesion residual rate of Examples 1 and 4 did not exceed 40%. It is speculated that it may be due to the less hydrophobic cholesterol modification in Example 1, which causes its drug coating to adhere to the tissue surface mainly by electrostatic interaction. On the other hand, due to the excessive introduction of cholesterol to consume the amino group in PEI, the positive charge in the polyelectrolyte decreases and the tendency of cholesterol to aggregate inside increases, both of which lead to the failure of long-term adhesion. In contrast, Examples 2 and 3 show better adhesion stability. Even after exposing the porcine aorta to a dynamic shear flow environment for three days, a large amount of drug coating still remains on the tissue surface. Based on these phenomena, we can find that cholesterol modification in the polyelectrolyte helps to increase the adhesion and shear resistance of the material. By balancing the relationship between the positive charge and hydrophobicity of the material, a drug coating with better adhesion stability can be obtained, thereby prolonging the retention time of the drug in the tissue.

[0062] In vivo drug delivery effect test:

[0063] Considering the transfer adhesion and adhesion stability of the drug coating, the drug-coated balloons of Example 3 and Comparative Example 1 were selected for in vivo drug delivery effect verification. In short, the drug-coated balloons of Example 3 and Comparative Example 1 were delivered to the abdominal aorta model of balloon injury in rats, and then expanded to a balloon pressure of 4 atmospheres, and then the blood vessels were pressed for one minute and withdrawn, and compared with the normal group and the injury group (pure balloon injury, no drug-coated balloon was used for treatment). The corresponding blood vessels were taken out on the 14th day after surgery, and the expression of the active drug molecule pDNA target protein in the tissue was quantitatively analyzed by Western Blot (WB) method.

[0064] Figure 7 The expression of related proteins in tissues 14 days after in vivo intervention of the drug-coated balloon of Example 3 and Comparative Example 1. By comparison, it was found that after 14 days after in vivo balloon intervention, the expression of vascular endothelial growth factor (VEGF) protein related to the active drug molecule pDNA loaded by the coating of Example 3 was the highest, more than three times that of the injury group and the comparative example 1 group. The protein and gene expression related to Comparative Example 1 was equivalent to that of the pure balloon injury group. At the same time, the protein expression of endothelial-specific functional protein endothelial nitric oxide synthase (eNOs) in the Example 3 group was also more than 7 times that of the injury group and the comparative example 1 group. These results show that this coating material design strategy can effectively improve the retention of the drug coating in the tissue, thereby promoting the successful delivery of the drug and the realization of the therapeutic effect.

Claims

1. A balloon drug coating, characterized in that: It is a double-layer structure, in which a sacrificial layer and a drug-loaded adhesion layer are sequentially arranged on the surface of the balloon matrix; the sacrificial layer is a water-soluble polymer layer, and the drug-loaded adhesion layer is a cholesterol-modified polyelectrolyte layer loaded with drugs.

2. The balloon drug coating according to claim 1, characterized in that: The water-soluble polymer is one or more of polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), and polyethylene glycol (PEG).

3. The balloon drug coating according to claim 1, characterized in that: The cholesterol-modified polyelectrolyte is a polyelectrolyte covalently modified with cholesterol molecules through a chemical reaction, wherein: The chemical reaction is one or more of amidation reaction, Schiff base reaction, etherification reaction and addition reaction; the polyelectrolyte is one or more of branched polyethyleneimine, linear polyethyleneimine, polyacrylamide, chitosan and gelatin.

4. The method for preparing the balloon drug coating according to any one of claims 1 to 3, characterized in that: The following steps are involved: preparing a water-soluble polymer solution: dissolving the water-soluble polymer in a mixed solution of ethanol and water; Preparation of a cholesterol-modified polyelectrolyte solution: cholesterol molecules are covalently modified onto the polyelectrolyte by chemical reaction and dissolved in an organic solvent; Preparation of active drug solution: Active drugs include anti-proliferative, anti-inflammatory, anti-thrombotic, anti-migratory or endothelial repair promoting substances, hydrophilic drugs are dissolved in aqueous solvents, and lipophilic drugs are dissolved in organic solvents; Preparation of drug coating: The water-soluble polymer solution is deposited on the surface of the balloon matrix by spraying to form a sacrificial layer, and then the cholesterol-modified polyelectrolyte solution and the active drug solution are deposited on the surface of the sacrificial layer by blending single-channel ultrasonic spraying or non-blending double-channel ultrasonic spraying to obtain a drug-loaded adhesion layer, thereby obtaining the balloon drug coating.

5. The method for preparing a balloon drug coating according to claim 4, characterized in that: The volume fraction of ethanol in the mixed solution is 50-80%.

6. The method for preparing a balloon drug coating according to claim 4, characterized in that: The hydrophilic drugs include one or more of plasmid DNA (pDNA), microRNA (miRNA), small interfering RNA (siRNA), proteins and their analogs, and the lipophilic drugs include one or more of rapamycin (sirolimus), paclitaxel, everolimus, tacrolimus and their derivatives or analogs.

7. The method for preparing a balloon drug coating according to claim 4, characterized in that: The aqueous solvent is one or more of an aqueous solution, a Tris-EDTA buffer (TE), and a phosphate buffered saline (PBS).

8. The method for preparing a balloon drug coating according to claim 4, characterized in that: The organic solvent is one or more of dichloromethane, tetrahydrofuran, methanol and ethanol.

9. A drug-coated balloon, characterized in that: Contains a coating as described in any one of claims 1 to 3.

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