Drug coating balloon catheter and preparation method thereof

Abstract

The invention belongs to the technical field of medical instruments. The invention discloses a drug coating balloon catheter and a preparation method thereof. In one aspect, a drug coated balloon catheter includes a catheter with a balloon; a drug coating at least comprising an inner coating and an outer coating is arranged on the outer wall of the balloon, and the inner coating and the outer coating are provided with drug active ingredients and different carriers respectively; when the balloon is expanded, the inner coating and the outer coating are separated from the balloon through the state change of the temperature-sensitive carrier of the inner coating under the body temperature environment of a patient and the hydration effect, and the outer coating is used for promoting corresponding active pharmaceutical ingredients to be transferred into target tissues through the carrier of the outer coating when the outer coating is separated from the balloon. On the other hand, the invention provides a preparation method of the drug coating balloon catheter. The preparation method has the advantages that the adhesiveness of the drug coating on the balloon can be effectively improved so as to reduce the delivery loss, and the release rate of the drug coating on diseased tissues can be improved so as to improve the drug transfer capacity.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and more particularly to a drug-coated balloon catheter and a preparation method thereof. Background Art

[0002] With the rapid development of medical technology and in-depth research into the pathological mechanisms of natural luminal stenosis in the human body, drug-coated medical devices have emerged as a vital tool in modern medicine, occupying an increasingly important position in this field. Drug-coated balloons, in particular, are a typical example of this approach. Their advantages in localized targeted drug release have led to their widespread application in treating conditions such as vascular stenosis. As interventional therapy devices, the core mechanism of action of drug-coated balloons is to achieve precise treatment of diseased tissues through localized targeted drug release.

[0003] Drug coating is a key technical indicator for drug-coated balloon catheters. Currently, there are many methods for its preparation, but not all methods can produce stable and effective drug coatings. The adhesion of the drug-loaded coating on a drug-coated balloon catheter is directly related to the drug release kinetics in the body, which in turn has a significant impact on the therapeutic effect. If the drug-loaded coating has poor adhesion, when the balloon is delivered to the target lesion, the drug coating will undergo a process of scouring by the fluid or water flow in the tissue. This process often causes the drug coating to fall off, significantly reducing the amount of drug delivered to the target lesion, thereby reducing the drug treatment effect. If the adhesion of the drug-loaded coating is improved, the binding strength of the drug molecules to the balloon surface will increase, which can significantly reduce the delivery loss of the balloon catheter. However, it will also make it difficult for the drug-coated balloon to release the drug immediately when it reaches the target lesion, and more of the drug will remain on the balloon surface, thus affecting the therapeutic effect. By increasing the drug loading of the balloon coating, the local drug absorption can be significantly increased. However, excessive drug concentration and dosage can easily lead to toxic reactions and affect patient health.

[0004] Although there are many optional drug formulations and preparation methods, in actual use, problems such as the adhesion of the drug coating, the high loss rate during drug delivery, and the insufficient drug release efficiency during the short-term expansion of the balloon make it difficult to fully meet the clinical needs for precise drug delivery, thereby increasing the risk of restenosis.

[0005] Therefore, the above problems become technical problems that need to be solved urgently. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a drug-coated balloon catheter that can effectively improve the adhesion of the drug coating on the balloon to reduce delivery losses and can increase the release rate of the drug coating on the diseased tissue to enhance the drug transfer capacity.

[0007] Another object of the present invention is to provide a method for preparing the drug-coated balloon catheter.

[0008] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are adopted:

[0009] In one aspect, the present invention provides a drug-coated balloon catheter, comprising a catheter with a balloon; a drug coating comprising at least an inner coating and an outer coating is provided on the outer wall of the balloon, wherein both the inner coating and the outer coating have active pharmaceutical ingredients and different carriers;

[0010] The inner coating layer is a mixture of a pharmaceutically active ingredient and a temperature-sensitive carrier in a predetermined ratio. The temperature-sensitive carrier is solid at room temperature and, when used as a pharmaceutical carrier at room temperature, is used to increase the adhesion of the pharmaceutically active ingredient to the balloon. The temperature-sensitive carrier changes state under body temperature and hydration to reduce the adhesion of the pharmaceutically active ingredient to the balloon, thereby promoting the detachment of the pharmaceutically active ingredient from the balloon surface.

[0011] Among them, in the drug coating, when the balloon expands, the inner coating together with the outer coating changes state under the patient's body temperature environment and hydration through the temperature-sensitive carrier of the inner coating and detaches from the balloon. When detaching from the balloon, the outer coating is used to promote the transfer of the corresponding active drug ingredients into the target tissue through its carrier.

[0012] Preferably, when the drug coating is two-layered, it is composed of an inner coating coated on the outer wall of the balloon and an outer coating coated on the inner coating, and the outer coating is a mixture of a pharmaceutical active ingredient and a non-temperature-sensitive carrier in a preset ratio, wherein:

[0013] When the balloon is expanded, the temperature-sensitive carrier of the inner coating layer is used to cause the active pharmaceutical ingredient coated on the outer wall of the balloon to detach from the balloon together with the outer coating layer under the patient's body temperature and hydration environment. When the inner coating layer and the outer coating layer detach from the balloon together, the outer coating layer promotes the transfer of the active pharmaceutical ingredient of the outer coating layer into the target tissue through the predetermined water solubility or compatibility of the non-temperature-sensitive carrier. For example, when the non-temperature-sensitive carrier is a hydrophilic non-temperature-sensitive carrier, the water solubility of the non-temperature-sensitive carrier promotes the active pharmaceutical ingredient of the outer coating layer to detach from the inner coating layer, and then transfer into the target tissue via active transport. When the non-temperature-sensitive carrier is a hydrophobic non-temperature-sensitive carrier, the similar compatibility between the non-temperature-sensitive carrier and the cell wall promotes the active pharmaceutical ingredient of the outer coating layer to detach from the inner coating layer, and then transfer into the target tissue via active transport.

[0014] Preferably, in the inner coating layer, the preset mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1-10):(10-1).

[0015] Preferably, in the outer coating layer, the preset mass ratio of the active pharmaceutical ingredient to the temperature-insensitive carrier is (1-10):(10-1).

[0016] Preferably, when the drug coating is two-layered, it is composed of an inner coating coated on the outer wall of the balloon and an outer coating coated on the inner coating, wherein:

[0017] The inner coating also includes a non-temperature-sensitive carrier, which is a mixture of a pharmaceutical active ingredient, a temperature-sensitive carrier, and a non-temperature-sensitive carrier in a predetermined ratio. When the balloon is expanded, the temperature-sensitive carrier in the inner coating is used to cause the pharmaceutical active ingredient coated on the outer wall of the balloon, together with the non-temperature-sensitive carrier and the outer coating, to detach from the balloon under the patient's body temperature and hydration. Simultaneously, the pharmaceutical active ingredient in the inner coating is transferred into the target tissue under the effect of the predetermined water solubility or compatibility of the non-temperature-sensitive carrier.

[0018] The outer coating is a mixture of active pharmaceutical ingredients and a non-temperature-sensitive carrier in a preset proportion. When the inner coating drug and the outer coating are separated from the balloon together, the active pharmaceutical ingredients in the outer coating are transferred into the target tissue under the promotion of the predetermined water solubility or compatibility of its non-temperature-sensitive carrier.

[0019] Preferably, in the inner coating layer, the preset mass ratio of the temperature-sensitive carrier to the temperature-insensitive carrier is (2-1):(2-1).

[0020] Preferably, in the inner coating layer, the mass ratio of the preset proportions of the active pharmaceutical ingredient, the temperature-sensitive carrier, and the non-temperature-sensitive carrier is (1-10):(2-1):(2-1); in the outer coating layer, the mass ratio of the preset proportions of the active pharmaceutical ingredient and the non-temperature-sensitive carrier is (1-10):(10-1).

[0021] Preferably, when the drug coating is three-layered, it is composed of an inner coating coated on the outer wall of the balloon, a middle coating coated on the inner coating, and an outer coating coated on the outer wall of the middle coating, and the inner coating is a mixture of a pharmaceutically active ingredient and a temperature-sensitive carrier, the middle coating is a mixture of a pharmaceutically active ingredient, a temperature-sensitive carrier, and a non-temperature-sensitive carrier in a preset ratio, and the outer coating is a mixture of a pharmaceutically active ingredient and a non-temperature-sensitive carrier in a preset ratio;

[0022] Among them: when the balloon is expanded, the temperature-sensitive carrier of the inner coating is used to make the active pharmaceutical ingredients coated on the outer wall of the balloon detach from the balloon under the patient's body temperature environment and hydration; the middle coating is used to increase the adhesion stability between the outer coating and the inner coating when serving as a drug carrier at room temperature; in addition, the temperature-sensitive carrier of the middle coating is used to make the active pharmaceutical ingredients coated on the inner coating detach from the inner coating together with the outer coating under the patient's body temperature environment and hydration, and at the same time, the active pharmaceutical ingredients of the middle coating are transferred into the target tissue under the promotion of the predetermined water solubility or compatibility of its non-temperature sensitive carrier; when the outer coating is separated from the inner coating, the active pharmaceutical ingredients of the outer coating are transferred into the target tissue under the promotion of the predetermined water solubility or compatibility of its non-temperature sensitive carrier.

[0023] Preferably, in the inner coating layer, the preset mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1-10):(10-1).

[0024] Preferably, in the middle layer coating, the preset mass ratio of the temperature-sensitive carrier to the temperature-insensitive carrier is (2-1):(2-1).

[0025] Preferably, in the middle coating layer, the preset mass ratio of the active pharmaceutical ingredient, the temperature-sensitive carrier, and the non-temperature-sensitive carrier is (1-10):(2-1):(2-1).

[0026] Preferably, in the outer coating layer, the preset mass ratio of the active pharmaceutical ingredient to the temperature-insensitive carrier is (1-10):(10-1).

[0027] Preferably, the temperature-sensitive carrier is at least one of methyl palmitate, methyl stearate, polyethylene glycol-15 hydroxystearate, quaternized chitosan, pentaerythritol ethoxylate, gelatin, and polyethylene glycol-polylactic acid copolymer.

[0028] Preferably, the non-temperature-sensitive carrier is at least one of iohexol, iopromide, urea, sorbitol, polyvinyl pyrrolidone, dextran, polysorbate, stearic acid, acrylic acid, stearic acid, methylcellulose, triethyl butyryl citrate, and polymethacrylate.

[0029] On the other hand, the present invention provides a method for preparing a balloon catheter using the above-mentioned drug coating, which is a spraying method for preparing the drug coating, comprising the following steps:

[0030] S21. Selecting an appropriate amount of a suitable solvent and adding it to two mixtures of a predetermined pharmaceutical active ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier in a predetermined ratio, thereby obtaining two different mixed solutions. Stirring and ultrasonically vibrating the two different mixed solutions by external equipment to uniformly dissolve them, thereby obtaining an inner layer drug solution A and an outer layer drug solution B.

[0031] S22, adding inner layer drug solution A to an external spraying device and adjusting the spraying parameters of the spraying device according to preset standards, spraying the inner layer drug solution A to a predetermined thickness on the outer wall of the balloon, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain an inner layer coating;

[0032] S23, adding the outer layer drug solution B to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, continuing to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner coating layer in step S22, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the outer coating layer;

[0033] S24. The balloon in step S23 is left to dry for 24 hours to allow the drug on the outer wall of the balloon to dry naturally to a predetermined degree to prepare a drug coating.

[0034] Preferably, the present invention also provides a method for preparing a balloon catheter using the drug coating, which is a spraying method for preparing the drug coating, comprising the following steps:

[0035] S31. Selecting an appropriate amount of a suitable solvent and adding it to three mixtures of a predetermined pharmaceutical active ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier in predetermined proportions, thereby obtaining three different mixed solutions. Stirring and ultrasonically vibrating the three different mixed solutions using an external device to uniformly dissolve them, thereby obtaining an inner layer drug solution A, an outer layer drug solution B, and a middle layer drug solution C.

[0036] S32, adding inner layer drug solution A to an external spraying device and adjusting the spraying parameters of the spraying device according to preset standards, spraying the inner layer drug solution A to a predetermined thickness on the outer wall of the balloon, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain an inner layer coating;

[0037] S33, adding the middle layer drug solution C to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, spraying the middle layer drug solution C to a predetermined thickness on the outer wall of the inner layer coating in step S32, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the middle layer coating;

[0038] S34, adding the outer layer drug solution B to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, continuing to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the middle layer coating in step S33, waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the outer layer coating;

[0039] S35. The balloon in step S34 is left to dry for 24 hours to dry the drug on the outer wall of the balloon to a predetermined degree to prepare a drug coating.

[0040] Preferably, the active ingredient of the drug is at least one of an antitumor agent, an antiproliferative agent, an antibiotic, an anticoagulant, an antithrombotic, and an anti-inflammatory drug, for example, the active ingredient of the drug is at least one of sirolimus, paclitaxel, arsenic trioxide, izolimus, zotarolimus, everolimus, heparin, tavilimus, and rapamycin.

[0041] Preferably, the solvent is at least one of toluene, acetonitrile, ethanol, dichloromethane, tetrahydrofuran, ethyl acetate, chloroform, acetone, and methanol.

[0042] Preferably, the balloon is made of at least one of nylon material, nylon elastomer Pebax material, polyethylene material, and polyurethane material.

[0043] Compared with the prior art, the present invention has the following beneficial effects:

[0044] In the present invention, a predetermined drug solution is formed by adjusting the ratio of the corresponding active pharmaceutical ingredients of the inner and outer coatings of the drug coating and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier. The drug solution is sprayed on the outer wall of the balloon in a predetermined order to form a drug coating. The drug coating is then delivered to the diseased tissue through the cooperation of the catheter and the balloon. When the balloon expands, the temperature-sensitive carrier of the inner coating changes state under the patient's body temperature environment and hydration to reduce the adhesion of the active pharmaceutical ingredients to the balloon, thereby causing the inner coating of the drug coating to detach from the balloon together with its outer coating. At the same time, the outer coating detaches from the balloon. At the same time, the carrier is used to promote the transfer of drugs into the target tissue, so that the active ingredients of the drugs are quickly released after being transported to the diseased tissue, thereby promoting the release rate of the drug coating on the diseased tissue to improve the drug transfer ability, meeting the clinical demand for precise drug delivery to reduce the risk of restenosis, and being suitable for the prevention and treatment of stenosis of natural cavities of the human body such as the urethra, ureter, Eustachian tube, esophagus, gastrointestinal tract, bile duct, pancreatic duct, and tracheal lumen; therefore, the present invention has the advantages of being able to effectively improve the adhesion of the drug coating on the balloon to reduce delivery losses, and being able to increase the release rate of the drug coating on the diseased tissue to improve the drug transfer ability. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0046] Figure 1 This is a schematic structural diagram of a drug-coated balloon catheter according to the present invention;

[0047] Figure 2 is a schematic diagram of a balloon of a drug-coated balloon catheter according to the present invention in a deflated state;

[0048] Figure 3 This is a schematic diagram of an in vitro simulation experiment of a drug-coated balloon catheter according to the present invention;

[0049] Description of the drawings: 10-catheter, 1-connector, 2-anti-folding protective sleeve, 3-outer tube, 4-balloon, 5-drug coating, 6-tip, 20-infusion pump pipeline, 30-water bath equipment, 40-simulated endoscope, 50-silicone tube, 60-waste liquid collection equipment, 70-pressure pump. DETAILED DESCRIPTION

[0050] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0051] like Figures 1 to 3 As shown, this embodiment provides a drug-coated balloon catheter, comprising a catheter 10 with a balloon 4; a drug coating 5 comprising at least an inner coating and an outer coating is provided on the outer wall of the balloon 4, and the inner coating and the outer coating both contain active pharmaceutical ingredients and different carriers;

[0052] The inner coating layer is a mixture of a pharmaceutical active ingredient and a temperature-sensitive carrier in a predetermined ratio. The temperature-sensitive carrier is solid at room temperature and, when used as a pharmaceutical carrier at room temperature, is used to increase the adhesion of the pharmaceutical active ingredient to the balloon 4. The temperature-sensitive carrier changes state under body temperature and hydration to reduce the adhesion of the pharmaceutical active ingredient to the balloon 4, thereby promoting the detachment of the pharmaceutical active ingredient from the surface of the balloon 4.

[0053] Among them, in the drug coating 5, when the balloon 4 expands, the inner coating together with the outer coating changes state under the patient's body temperature environment and hydration through the temperature-sensitive carrier of the inner coating and detaches from the balloon 4. When detaching from the balloon 4, the outer coating is used to promote the transfer of the corresponding active drug ingredients into the target tissue through its carrier.

[0054] Specifically, when the drug coating 5 is two-layered, it is composed of an inner coating coated on the outer wall of the balloon 4 and an outer coating coated on the inner coating, and the outer coating is a mixture of the active pharmaceutical ingredient and the non-temperature-sensitive carrier in a preset ratio, wherein:

[0055] When the balloon 4 expands, the temperature-sensitive carrier of the inner coating is used to make the active pharmaceutical ingredients coated on the outer wall of the balloon 4 detach from the balloon 4 together with the outer coating under the patient's body temperature environment and hydration; when the inner coating drug detaches from the balloon 4 together with the outer coating, the outer coating promotes the transfer of the active pharmaceutical ingredients of the outer coating into the target tissue through the predetermined water solubility or compatibility of its non-temperature-sensitive carrier.

[0056] The present invention forms a predetermined drug solution by adjusting the ratio of the corresponding active pharmaceutical ingredients of the inner and outer coatings of the drug coating 5 and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier. The drug solution is sprayed on the outer wall of the balloon 4 in a predetermined order to form a drug coating 5. The drug coating 5 is then delivered to the diseased tissue through the cooperation of the catheter 10 and the balloon 4. When the balloon 4 expands, the temperature-sensitive carrier of the inner coating changes state under the patient's body temperature environment and hydration to reduce the adhesion of the active pharmaceutical ingredient to the balloon 4, thereby promoting the drug to The inner coating of the drug coating 5 is separated from the balloon 4 together with its outer coating. At the same time, the outer coating promotes the transfer of drugs into the target tissue through its carrier when it is separated from the balloon 4, so that the active ingredients of the drug are quickly released after being delivered to the diseased tissue, thereby promoting the release rate of the drug coating 5 on the diseased tissue to improve the drug transfer ability, meeting the clinical demand for precise drug delivery to reduce the risk of restenosis, and is suitable for the prevention and treatment of stenosis of natural cavities of the human body such as the urethra, ureter, Eustachian tube, esophagus, gastrointestinal tract, bile duct, pancreatic duct, and tracheal lumen.

[0057] The present invention also provides a method for preparing a drug-coated balloon catheter, which is a spraying method for preparing the drug coating 5, comprising the following steps:

[0058] S21. Selecting an appropriate amount of a suitable solvent and adding it to two mixtures of a predetermined pharmaceutical active ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier in a predetermined ratio, thereby obtaining two different mixed solutions. Stirring and ultrasonically vibrating the two different mixed solutions by external equipment to uniformly dissolve them, thereby obtaining an inner layer drug solution A and an outer layer drug solution B.

[0059] S22, adding inner layer drug solution A to an external spraying device and adjusting the spraying parameters of the spraying device according to preset standards, spraying the inner layer drug solution A to a predetermined thickness on the outer wall of the balloon 4, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain an inner layer coating;

[0060] S23, adding the outer layer drug solution B to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, continuing to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner coating layer in step S22, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the outer coating layer;

[0061] S24 , standing the balloon 4 in step S23 to dry for 24 hours, so that the drug on the outer wall of the balloon 4 is naturally dried to a predetermined degree to prepare a drug coating 5 .

[0062] Specifically, in the inner coating layer, the mass ratio of the preset ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1-10):(10-1); in the outer coating layer, the mass ratio of the preset ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is (1-10):(10-1). The temperature-sensitive carrier is at least one of methyl palmitate, methyl stearate, polyethylene glycol-15 hydroxystearate, quaternized chitosan, pentaerythritol ethoxylate, gelatin, and polyethylene glycol-polylactic acid copolymer. The non-temperature-sensitive carrier is at least one of iohexol, iopromide, urea, sorbitol, polyvinyl pyrrolidone, dextran, polysorbate, stearic acid, acrylic acid, stearic acid, methylcellulose, triethyl butyryl citrate, and polymethacrylate. The active pharmaceutical ingredient is at least one of an anti-tumor agent, an antiproliferative agent, an antibiotic, an anticoagulant, an antithrombotic agent, and an anti-inflammatory drug. For example, the active pharmaceutical ingredient is at least one of sirolimus, paclitaxel, arsenic trioxide, euclidinium, zotarolimus, everolimus, heparin, taviromus, and rapamycin. The balloon 4 is made of at least one of nylon, Pebax, a nylon elastomer, polyethylene, and polyurethane. The solvent is at least one of toluene, acetonitrile, ethanol, dichloromethane, tetrahydrofuran, ethyl acetate, chloroform, acetone, and methanol.

[0063] Example 1

[0064] In this embodiment, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier in the inner coating layer is 10:1; the mass ratio of the active pharmaceutical ingredient to the temperature-insensitive carrier in the outer coating layer is 10:1. The temperature-sensitive carrier is methyl stearate. The temperature-insensitive carrier is urea. The active pharmaceutical ingredient is paclitaxel. The balloon 4 is made of at least one of nylon, Pebax, a nylon elastomer, polyethylene, and polyurethane, and the solvent is a mixture of acetone and methanol.

[0065] In this embodiment, inner layer drug solution A is a mixture of 0.5 g paclitaxel, 0.05 g methyl stearate, 10 mL methanol, and 10 mL acetone, and outer layer drug solution B is a mixture of 0.5 g paclitaxel, 0.05 g urea, 10 mL methanol, and 10 mL acetone. The drug coating 5 of this embodiment is prepared by the following method steps:

[0066] 1) adding 0.5 g of paclitaxel and 0.05 g of methyl stearate to a mixed solvent of 10 mL of methanol and 10 mL of acetone, and performing stirring and ultrasonic vibration using a predetermined external device to uniformly dissolve the mixture, thereby obtaining an inner layer drug solution A;

[0067] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spraying flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spraying solution is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%, and the spraying amount is a predetermined thickness for spraying one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0068] 3) adding 0.5 g of paclitaxel and 0.05 g of urea to a mixed solvent of 10 mL of methanol and 10 mL of acetone, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve the mixture, thereby obtaining an outer layer drug solution B;

[0069] 4) adding the outer drug solution B obtained in step 3) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spray solution is sprayed on the outer wall of the inner coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer coating is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer coating;

[0070] 5) Drying the balloon 4 obtained in step 4) for 24 hours to dry the drug coating on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then folding the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fixing and storing them with an outer balloon protective cover, the structure of which is as follows: Figure 2 shown.

[0071] Example 2

[0072] In this embodiment, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier in the inner coating layer is 5:1; the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier in the outer coating layer is 5:1. The temperature-sensitive carrier is methyl palmitate. The non-temperature-sensitive carrier is dextran. The active pharmaceutical ingredient is sirolimus. The balloon 4 is made of at least one of nylon, Pebax, a nylon elastomer, polyethylene, and polyurethane, and the solvent is acetone.

[0073] In this embodiment, the inner layer drug solution A is a mixture of 0.5 g sirolimus, 0.1 g methyl palmitate, and 20 mL acetone, and the outer layer drug solution B is a mixture of 0.5 g sirolimus, 0.1 g dextran, and 20 mL acetone. The drug coating 5 of this embodiment is prepared by the following method steps:

[0074] 1) adding 0.5 g of sirolimus and 0.1 g of methyl palmitate to 20 mL of acetone solvent, and performing stirring and ultrasonic vibration using a predetermined external device to uniformly dissolve, thereby obtaining an inner layer drug solution A;

[0075] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spraying flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spraying solution is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%, and the spraying amount is a predetermined thickness for spraying one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0076] 3) adding 0.5 g of sirolimus and 0.1 g of dextran to 20 mL of acetone solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve, thereby obtaining an outer layer drug solution B;

[0077] 4) adding the outer drug solution B obtained in step 3) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spray solution is sprayed on the outer wall of the inner coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer coating is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer coating;

[0078] 5) Drying the balloon 4 obtained in step 4) for 24 hours to dry the drug coating on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then folding the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fixing and storing them with an outer balloon protective cover, the structure of which is as follows: Figure 2 shown.

[0079] Example 3

[0080] In this embodiment, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier in the inner coating layer is 1:10; the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier in the outer coating layer is 1:10. The temperature-sensitive carrier is quaternized chitosan. The non-temperature-sensitive carrier is iohexol. The active pharmaceutical ingredient is heparin. The balloon 4 is made of at least one of nylon, Pebax, a nylon elastomer, polyethylene, and polyurethane, and the solvent is toluene.

[0081] In this embodiment, the inner layer drug solution A is a mixture of 0.05g heparin, 0.5g quaternized chitosan, and 20mL toluene, and the outer layer drug solution B is a mixture of 0.05g heparin, 0.5g iohexol, and 20mL toluene. The drug coating 5 of this embodiment is prepared by the following method steps:

[0082] 1) adding 0.05 g of heparin and 0.5 g of quaternized chitosan to 20 mL of toluene solvent, and performing stirring and ultrasonic vibration using a predetermined external device to uniformly dissolve, thereby obtaining an inner layer drug solution A;

[0083] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spraying flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spraying solution is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%, and the spraying amount is a predetermined thickness for spraying one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0084] 3) adding 0.05 g of heparin and 0.5 g of iohexol to 20 mL of toluene solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve, thereby obtaining an outer layer drug solution B;

[0085] 4) adding the outer drug solution B obtained in step 3) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spray solution is sprayed on the outer wall of the inner coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer coating is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer coating;

[0086] 5) Drying the balloon 4 obtained in step 4) for 24 hours to dry the drug coating on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then folding the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fixing and storing them with an outer balloon protective cover, the structure of which is as follows: Figure 2 shown.

[0087] like Figures 1 to 3 As shown, in the present invention, when the drug coating 5 is two-layered, the drug coating 5 is composed of an inner coating layer coated on the outer wall of the balloon 4 and an outer coating layer coated on the inner coating layer, wherein:

[0088] The inner coating also includes a non-temperature-sensitive carrier. The inner coating is a mixture of a pharmaceutical active ingredient, a temperature-sensitive carrier, and a non-temperature-sensitive carrier in a predetermined ratio. When the balloon 4 is expanded, the temperature-sensitive carrier of the inner coating is used to cause the pharmaceutical active ingredient coated on the outer wall of the balloon 4 to be detached from the balloon 4 together with the non-temperature-sensitive carrier and the outer coating under the patient's body temperature and hydration. At the same time, the pharmaceutical active ingredient of the inner coating is transferred into the target tissue under the effect of the predetermined water solubility or compatibility of the non-temperature-sensitive carrier.

[0089] The outer coating is a mixture of active pharmaceutical ingredients and a non-temperature-sensitive carrier in a preset proportion. When the inner coating drug and the outer coating are separated from the balloon 4, the active pharmaceutical ingredients of the outer coating are transferred into the target tissue under the promotion of the predetermined water solubility or compatibility of its non-temperature-sensitive carrier.

[0090] The present invention also provides a method for preparing a drug-coated balloon catheter, which is a spraying method for preparing the drug coating 5, comprising the following steps:

[0091] S21. Selecting an appropriate amount of a suitable solvent and adding it to two mixtures of a predetermined pharmaceutical active ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier in a predetermined ratio, thereby obtaining two different mixed solutions. Stirring and ultrasonically vibrating the two different mixed solutions by external equipment to uniformly dissolve them, thereby obtaining an inner layer drug solution A and an outer layer drug solution B.

[0092] S22, adding inner layer drug solution A to an external spraying device and adjusting the spraying parameters of the spraying device according to preset standards, spraying the inner layer drug solution A to a predetermined thickness on the outer wall of the balloon 4, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain an inner layer coating;

[0093] S23, adding the outer layer drug solution B to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, continuing to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner coating layer in step S22, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the outer coating layer;

[0094] S24 , standing the balloon 4 in step S23 to dry for 24 hours, so that the drug on the outer wall of the balloon 4 is naturally dried to a predetermined degree to prepare a drug coating 5 .

[0095] Specifically, in the inner coating layer, the mass ratio of the preset proportions of the temperature-sensitive carrier and the non-temperature-sensitive carrier is (2-1):(2-1), and the mass ratio of the preset proportions of the active pharmaceutical ingredient, the temperature-sensitive carrier, and the non-temperature-sensitive carrier is (1-10):(2-1):(2-1); in the outer coating layer, the mass ratio of the preset proportions of the active pharmaceutical ingredient and the non-temperature-sensitive carrier is (1-10):(10-1).

[0096] Example 4

[0097] In this embodiment, the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier in the inner coating layer is 2:2, and the mass ratio of the active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 1:2:2. In the outer coating layer, the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is 1:10. The temperature-sensitive carrier is methyl stearate. The non-temperature-sensitive carrier is urea. The active pharmaceutical ingredient is paclitaxel. The balloon 4 is made of at least one of nylon, Pebax, a nylon elastomer, polyethylene, and polyurethane, and the solvent is a mixture of acetone and methanol.

[0098] In this embodiment, inner layer drug solution A is a mixture of 0.5 g paclitaxel, 1.0 g methyl stearate, 1.0 g urea, 10 mL methanol, and 10 mL acetone, and outer layer drug solution B is a mixture of 0.05 g paclitaxel, 0.5 g urea, 10 mL methanol, and 10 mL acetone. The drug coating 5 of this embodiment is prepared by the following method steps:

[0099] 1) 0.5 g of paclitaxel, 1.0 g of methyl stearate, and 1.0 g of urea were added to a mixed solvent of 10 mL of methanol and 10 mL of acetone, and stirred and ultrasonically shaken by a predetermined external device to achieve uniform dissolution, thereby obtaining an inner layer drug solution A.

[0100] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spraying flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spraying solution is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%. The spraying thickness is a preset thickness of one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0101] 3) adding 0.05 g of paclitaxel and 0.5 g of urea to a mixed solvent of 10 mL of methanol and 10 mL of acetone, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve the mixture, thereby obtaining an outer layer drug solution B;

[0102] 4) The outer layer drug solution B obtained in step 3) is added to the pipeline channel of the external ultrasonic atomizing sprayer, and the spraying parameters are adjusted: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spray solution is sprayed on the outer wall of the inner layer coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer layer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer layer coating is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer layer coating.

[0103] 5) Dry the balloon 4 obtained in step 4) for 24 hours to dry the drug on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then fold the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fix and store them with an outer balloon protective cover. The structure is as follows: Figure 2 shown.

[0104] Example 5

[0105] In this embodiment, the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier in the inner coating layer is 2:1, and the mass ratio of the active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 5:2:1. In the outer coating layer, the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is 6:4. The temperature-sensitive carrier is methyl palmitate. The non-temperature-sensitive carrier is dextran. The active pharmaceutical ingredient is sirolimus. The balloon 4 is made of at least one of nylon, Pebax, a nylon elastomer, polyethylene, and polyurethane, and the solvent is acetone.

[0106] In this embodiment, the inner layer drug solution A is a mixture of 0.5 g sirolimus, 0.2 g methyl palmitate, 0.1 g dextran, and 20 mL acetone, and the outer layer drug solution B is a mixture of 0.6 g sirolimus, 0.4 g dextran, and 20 mL acetone. The drug coating 5 of this embodiment is prepared by the following method steps:

[0107] 1) 0.5 g of sirolimus, 0.2 g of methyl palmitate, and 0.1 g of dextran were added to 20 mL of acetone solvent, and stirred and ultrasonically vibrated by a predetermined external device to achieve uniform dissolution, thereby obtaining an inner layer drug solution A.

[0108] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spraying flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spraying solution is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%. The spraying thickness is a preset thickness of one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0109] 3) adding 0.6 g of sirolimus and 0.4 g of dextran to 20 mL of acetone solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve, thereby obtaining an outer layer drug solution B;

[0110] 4) The outer layer drug solution B obtained in step 3) is added to the pipeline channel of the external ultrasonic atomizing sprayer, and the spraying parameters are adjusted: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spray solution is sprayed on the outer wall of the inner layer coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer layer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer layer coating is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer layer coating.

[0111] 5) Dry the balloon 4 obtained in step 4) for 24 hours to dry the drug on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then fold the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fix and store them with an outer balloon protective cover. The structure is as follows: Figure 2 shown.

[0112] Example 6

[0113] In this embodiment, the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier in the inner coating layer is 1:1, and the mass ratio of the active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 10:1:1. In the outer coating layer, the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is 10:1. The temperature-sensitive carrier is quaternized chitosan. The non-temperature-sensitive carrier is iohexol. The active pharmaceutical ingredient is heparin. The balloon 4 is made of at least one of nylon, Pebax, a nylon elastomer, polyethylene, and polyurethane, and the solvent is toluene.

[0114] In this embodiment, the inner layer drug solution A is a mixture of 0.5 g heparin, 0.05 g quaternized chitosan, 0.05 g iohexol, and 20 mL toluene, and the outer layer drug solution B is a mixture of 0.5 g heparin, 0.05 g iohexol, and 20 mL toluene. The drug coating 5 of this embodiment is prepared by the following method steps:

[0115] 1) 0.5 g of heparin, 0.05 g of quaternized chitosan, and 0.05 g of iohexol were added to 20 mL of toluene solvent, and stirred and ultrasonically vibrated by a predetermined external device to uniformly dissolve the mixture, thereby obtaining an inner layer drug solution A.

[0116] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spraying flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spraying solution is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%. The spraying thickness is a preset thickness of one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0117] 3) adding 0.5 g of heparin and 0.05 g of iohexol to 20 mL of toluene solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve the mixture, thereby obtaining an outer layer drug solution B;

[0118] 4) The outer layer drug solution B obtained in step 3) is added to the pipeline channel of the external ultrasonic atomizing sprayer, and the spraying parameters are adjusted: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The spray solution is sprayed on the outer wall of the inner layer coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer layer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer layer coating is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer layer coating.

[0119] 5) Dry the balloon 4 obtained in step 4) for 24 hours to dry the drug on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then fold the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fix and store them with an outer balloon protective cover. The structure is as follows: Figure 2 shown.

[0120] like Figures 1 to 3As shown, in the present invention, when the drug coating 5 is three-layered, it is composed of an inner coating layer coated on the outer wall of the balloon 4, a middle coating layer coated on the inner coating layer, and an outer coating layer coated on the outer wall of the middle coating layer, and the inner coating layer is a mixture of a drug active ingredient and a temperature-sensitive carrier, the middle coating layer is a mixture of a drug active ingredient, a temperature-sensitive carrier, and a non-temperature-sensitive carrier in a preset ratio, and the outer coating layer is a mixture of a drug active ingredient and a non-temperature-sensitive carrier in a preset ratio;

[0121] Among them: when the balloon 4 is expanded, the temperature-sensitive carrier of the inner coating is used to separate the active pharmaceutical ingredients coated on the outer wall of the balloon 4 from the balloon 4 under the patient's body temperature environment and hydration; the middle coating is used to increase the adhesion stability between the outer coating and the inner coating when serving as a drug carrier at room temperature; in addition, the temperature-sensitive carrier of the middle coating is used to separate the active pharmaceutical ingredients coated on the inner coating together with the outer coating from the inner coating under the patient's body temperature environment and hydration, and at the same time, the active pharmaceutical ingredients of the middle coating are transferred into the target tissue under the promotion of the predetermined water solubility or compatibility of its non-temperature-sensitive carrier; when the outer coating is separated from the inner coating, the active pharmaceutical ingredients of the outer coating are transferred into the target tissue under the promotion of the predetermined water solubility or compatibility of its non-temperature-sensitive carrier.

[0122] The present invention also provides a method for preparing a drug-coated balloon catheter, which is a spraying method for preparing the drug coating 5, comprising the following steps:

[0123] S31. Selecting an appropriate amount of a suitable solvent and adding it to three mixtures of a predetermined pharmaceutical active ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier in predetermined proportions, thereby obtaining three different mixed solutions. Stirring and ultrasonically vibrating the three different mixed solutions using an external device to uniformly dissolve them, thereby obtaining an inner layer drug solution A, an outer layer drug solution B, and a middle layer drug solution C.

[0124] S32, adding inner layer drug solution A to an external spraying device and adjusting the spraying parameters of the spraying device according to preset standards, spraying the inner layer drug solution A to a predetermined thickness on the outer wall of the balloon 4, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain an inner layer coating;

[0125] S33, adding the middle layer drug solution C to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, spraying the middle layer drug solution C to a predetermined thickness on the outer wall of the inner layer coating in step S32, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the middle layer coating;

[0126] S34, adding the outer layer drug solution B to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, continuing to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the middle layer coating in step S33, waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the outer layer coating;

[0127] S35 , leaving the balloon 4 in step S34 to dry for 24 hours, so that the drug on the outer wall of the balloon 4 dries to a predetermined degree to prepare a drug coating 5 .

[0128] Specifically, in the inner coating layer, the mass ratio of the preset ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1-10):(10-1); in the middle coating layer, the mass ratio of the preset ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier is (2-1):(2-1), and the mass ratio of the preset ratio of the active pharmaceutical ingredient, the temperature-sensitive carrier, and the non-temperature-sensitive carrier is (1-10):(2-1):(2-1); in the outer coating layer, the mass ratio of the preset ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is (1-10):(10-1). The temperature-sensitive carrier is at least one of methyl palmitate, methyl stearate, polyethylene glycol-15 hydroxystearate, quaternized chitosan, pentaerythritol ethoxylate, gelatin, and polyethylene glycol-polylactic acid copolymer. The non-temperature sensitive carrier is at least one of iohexol, iopromide, urea, sorbitol, polyvinyl pyrrolidone, dextran, polysorbate, stearic acid, acrylic acid, stearic acid, methylcellulose, triethyl butyryl citrate, and polymethacrylate.

[0129] Specifically, the catheter 10 includes an outer tube 3 and one end of the outer tube 3 is a tip 6, wherein the balloon 4 is provided on the end of the outer tube 3 close to the tip 6, and a connector 1 is provided on the end of the outer tube 3 away from the tip 6 through an anti-folding protective sleeve 2.

[0130] Example 7

[0131] In this embodiment, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier in the inner coating layer is 1:10; in the middle coating layer, the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier is 2:2, and the mass ratio of the active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 1:2:2; in the outer coating layer, the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is 1:10. The active pharmaceutical ingredient is paclitaxel, the temperature-sensitive carrier is methyl stearate, the non-temperature-sensitive carrier is urea, and the solvent is a mixture of acetone and methanol.

[0132] In this embodiment, inner layer drug solution A is a mixture of 0.05g paclitaxel, 0.5g methyl stearate, 10mL methanol, and 10mL acetone; middle layer drug solution C is a mixture of 0.05g paclitaxel, 0.1g methyl stearate, 0.1g urea, 10mL methanol, and 10mL acetone; and outer layer drug solution B is a mixture of 0.05g paclitaxel, 0.5g urea, 10mL methanol, and 10mL acetone. The drug coating 5 of this embodiment is prepared by the following method steps:

[0133] 1) adding 0.05 g of paclitaxel and 0.5 g of methyl stearate to a mixed solvent of 10 mL of methanol and 10 mL of acetone, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve the mixture, thereby obtaining an inner layer drug solution A;

[0134] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The inner layer drug solution A is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%. The spraying thickness is a predetermined thickness for spraying one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0135] 3) adding 0.05 g of paclitaxel, 0.1 g of methyl stearate, and 0.1 g of urea to a mixed solvent of 10 mL of methanol and 10 mL of acetone, and performing stirring and ultrasonic vibration using a predetermined external device to uniformly dissolve the mixture, thereby obtaining a middle-layer drug solution C;

[0136] 4) adding the middle-layer drug solution C obtained in step 3) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The middle-layer drug solution C is sprayed on the outer wall of the inner layer coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%, and a layer of the middle-layer drug solution C of a predetermined thickness is continuously sprayed. The mixture is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain a middle-layer coating;

[0137] 5) adding 0.05 g of paclitaxel and 0.5 g of urea to a mixed solvent of 10 mL of methanol and 10 mL of acetone, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve the mixture, thereby obtaining an outer layer drug solution B;

[0138] 6) adding the outer drug solution B obtained in step 5) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The outer drug solution B is sprayed on the outer wall of the middle layer coating obtained in step 4) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer layer is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer coating;

[0139] 7) Dry the balloon 4 obtained in step 6) for 24 hours to dry the drug on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then fold the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fix and store them in an outer balloon protective cover. The structure is as follows: Figure 2 shown.

[0140] Example 8

[0141] In this example, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier in the inner coating layer is 6:4; the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier in the middle coating layer is 2:1, and the mass ratio of the active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 5:2:1; and the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier in the outer coating layer is 6:4. The active pharmaceutical ingredient is sirolimus, the temperature-sensitive carrier is methyl palmitate, the non-temperature-sensitive carrier is dextran, and the solvent is acetone.

[0142] In this embodiment, the inner layer drug solution A is a mixture of 0.6 g sirolimus, 0.4 g methyl palmitate, and 20 mL acetone; the middle layer drug solution C is a mixture of 0.5 g sirolimus, 0.2 g methyl palmitate, 0.1 g dextran, and 20 mL acetone; and the outer layer drug solution B is a mixture of 0.6 g sirolimus, 0.4 g dextran, and 20 mL acetone. The drug coating 5 of this embodiment is prepared by the following method steps:

[0143] 1) adding 0.6 g of sirolimus and 0.4 g of methyl palmitate to 20 mL of acetone solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve, thereby obtaining an inner layer drug solution A;

[0144] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The inner layer drug solution A is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%. The spraying thickness is a predetermined thickness for spraying one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0145] 3) adding 0.5 g of sirolimus, 0.2 g of methyl palmitate, and 0.1 g of dextran to 20 mL of acetone solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve, thereby obtaining a middle layer drug solution C;

[0146] 4) adding the middle-layer drug solution C obtained in step 3) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The middle-layer drug solution C is sprayed on the outer wall of the inner layer coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%, and a layer of the middle-layer drug solution C of a predetermined thickness is continuously sprayed. The mixture is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain a middle-layer coating;

[0147] 5) adding 0.6 g of sirolimus and 0.4 g of dextran to 20 mL of acetone solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve, thereby obtaining an outer layer drug solution B;

[0148] 6) adding the outer drug solution B obtained in step 5) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The outer drug solution B is sprayed on the outer wall of the middle layer coating obtained in step 4) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer layer is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer coating;

[0149] 7) The balloon 4 obtained in step 6) is dried for 24 hours to allow the drug on the outer wall of the balloon 4 to dry to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then the balloon 4 and the drug coating 5 are folded into petals with a petal number of 5, and fixed and stored with an outer balloon protective cover. The structure is as follows Figure 2shown.

[0150] Example 9

[0151] In this embodiment, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier in the inner coating layer is 10:1. In the middle coating layer, the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier is 1:1, and the mass ratio of the active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 10:1:1. In the outer coating layer, the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is 10:1. The active pharmaceutical ingredient is heparin, the temperature-sensitive carrier is quaternized chitosan, the non-temperature-sensitive carrier is iohexol, and the solvent is toluene.

[0152] In this embodiment, the inner layer drug solution A is a mixture of 0.5g heparin, 0.05g quaternized chitosan, and 20mL toluene, the middle layer drug solution C is a mixture of 0.5g heparin, 0.05g quaternized chitosan, 0.05g iohexol, and 20mL toluene, and the outer layer drug solution B is a mixture of 0.5g heparin, 0.05g iohexol, and 20mL toluene. The drug coating 5 of this embodiment is prepared by the following method steps:

[0153] 1) adding 0.5 g of heparin and 0.05 g of quaternized chitosan to 20 mL of toluene solvent, stirring and ultrasonically oscillating the mixture using a predetermined external device to uniformly dissolve the mixture, thereby obtaining an inner layer drug solution A;

[0154] 2) adding the inner layer drug solution A obtained in step 1) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The inner layer drug solution A is sprayed onto the outer wall of the balloon 4 at a temperature of 23° C. and a relative humidity of 50%. The spraying thickness is a predetermined thickness for spraying one layer. During the spraying process, the balloon 4 is pre-inflated to 3 atm and allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the inner layer coating;

[0155] 3) adding 0.5 g of heparin, 0.05 g of quaternized chitosan, and 0.05 g of iohexol to 20 mL of toluene solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve the mixture, thereby obtaining a middle-layer drug solution C;

[0156] 4) adding the middle-layer drug solution C obtained in step 3) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The middle-layer drug solution C is sprayed on the outer wall of the inner layer coating obtained in step 2) at a temperature of 23° C. and a relative humidity of 50%, and a layer of the middle-layer drug solution C of a predetermined thickness is continuously sprayed. The mixture is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain a middle-layer coating;

[0157] 5) adding 0.5 g of heparin and 0.05 g of iohexol to 20 mL of toluene solvent, and performing stirring and ultrasonic vibration by a predetermined external device to uniformly dissolve, thereby obtaining an outer layer drug solution B;

[0158] 6) adding the outer drug solution B obtained in step 5) into the pipeline channel of an external ultrasonic atomizing sprayer, adjusting the spraying parameters: the spray flow rate is a preset 0.08 mL / min, the nozzle movement speed is a preset 1.5 mm / s, the rotation speed is a preset 200 r / min, and the power is a preset 1.0 W. The outer drug solution B is sprayed on the outer wall of the middle layer coating obtained in step 4) at a temperature of 23° C. and a relative humidity of 50%. 10 layers of the outer drug solution B of a predetermined thickness are continuously sprayed. After spraying, the outer layer is allowed to stand for 300 s until the solvent evaporates to a predetermined degree to obtain the outer coating;

[0159] 7) Dry the balloon 4 obtained in step 6) for 24 hours to dry the drug on the outer wall of the balloon 4 to a predetermined degree to form a drug coating 5, thereby obtaining a drug-coated balloon catheter with a drug coating 5, and then fold the balloon 4 and the drug coating 5 into petals with a petal number of 5, and fix and store them in an outer balloon protective cover. The structure is as follows: Figure 2 shown.

[0160] Comparative Example 1

[0161] This comparative example provides a drug-coated balloon catheter and a preparation method thereof, which does not have an inner coating layer containing a temperature-sensitive carrier, and the carrier in the outer coating layer is a material having strong adhesion to the balloon, and other conditions are the same as those in Example 1.

[0162] Comparative Example 2

[0163] This comparative example provides a drug-coated balloon catheter and a preparation method thereof, which does not have an inner coating layer containing a temperature-sensitive carrier, and the carrier in the outer coating layer is a material with weak adhesion to the balloon. Other conditions are the same as those in Example 1.

[0164] Performance evaluation

[0165] Test 1: Folding loss test

[0166] The drug content of the drug balloon samples before and after folding was measured using high performance liquid chromatography (HPLC), and the folding loss rate of the drug balloon was calculated. The specific calculation formula is:

[0167] Folding loss rate = (drug content before folding - drug content after folding) / drug content before folding * 100% The test results are shown in Table 1

[0168] Table 1 Folding loss rate of drug balloons in different embodiments

[0169]

[0170] The above data show that the balloon 4 with the inner coating has a relatively lower folding loss rate than the balloon 4 in Comparative Example 2. This indicates that in a dry state, the inner coating can increase the adhesion of the drug to the surface of the balloon 4, thereby preventing drug loss during the folding process.

[0171] Test 2: Transmission loss test

[0172] like Figure 3 As shown, an in vitro simulation device is constructed, an external silicone tube 50 is used to simulate the urethra, and the silicone tube 50 is immersed in an external water bath device 30 to simulate the human body temperature environment in a constant temperature water bath at 37°C. One end of the silicone tube 50 is connected to the sheath of the irrigating pump pipeline 20 to simulate the endoscope 40, and the other end of the silicone tube 50 is connected to the external waste liquid collection device 60. The water flow rate is controlled by the irrigating pump of the irrigating pump pipeline 20. After the entire pipeline is filled with water, the two ends of the drug-coated balloon catheter are respectively connected to the external pressure pump 70 and the sheath, and the drug coating 5 is delivered to the simulated lesion of the silicone tube 50 through the simulated path of the simulated endoscope 40. After standing for 1 minute to hydrate, a part of the balloon 4 is cut out from the end of the pipeline and dried. The residual drug content on the balloon 4 is tested using a high performance liquid chromatography (HPLC). The specific calculation formula is:

[0173] Delivery loss rate = [(drug content after folding - residual drug content of balloon after delivery) / drug content after folding] * 100%

[0174] The test results are shown in Table 2

[0175] Table 2 Drug balloon delivery loss rate in different embodiments

[0176]

[0177] The above data demonstrates that while the delivery loss rate of the inner-coated balloon 4 increases compared to the folded balloon 4, it remains relatively low compared to the uncoated balloon 4 in Comparative Example 2. Further analysis reveals that during delivery, the temperature-sensitive carrier in the inner coating of this embodiment begins to change state due to the influence of body temperature. However, because the temperature changes slowly during delivery and the balloon 4 remains folded, the drug loss rate remains manageable.

[0178] Test 3: In vitro simulation test

[0179] like Figure 3 As shown, an in vitro simulation device is constructed, using an external silicone tube 50 to simulate the urethra, immersing the silicone tube 50 in an external water bath device 30, simulating the human body temperature environment in a 37°C constant temperature water bath, connecting one end of the silicone tube 50 to simulate the endoscope 40 and the sheath of the perfusion pump pipeline 20, and connecting the other end of the silicone tube 50 to the external waste liquid collection device 60. The water flow rate is controlled by the perfusion pump of the perfusion pump pipeline 20. After the entire pipeline is filled with water, the two ends of the drug-coated balloon catheter are respectively connected to the external pressure pump 70 and the sheath, and the drug coating 5 is transported to the simulated lesion of the silicone tube 50 through the simulated path of the simulated endoscope 40. After standing for 1 minute to hydrate, the balloon 4 is expanded to the nominal pressure, and the pressure is released after 1 minute of simulated release. After the pressure is completely released, the drug-coated balloon catheter is withdrawn, and the residual drug amount on the balloon 4 and the drug content in the simulated lesion of the silicone tube 50 are tested using a high performance liquid chromatography (HPLC). The specific calculation formula is:

[0180] Drug residual rate = residual drug content on the balloon / drug content after folding * 100%

[0181] Drug transfer rate = drug content in the simulated lesion of the silicone tube / drug content after folding * 100%

[0182] The test results are shown in Table 3

[0183] Table 3 Drug residue rate and drug transfer rate in different examples

[0184]

[0185]

[0186] The above data demonstrate that, in the in vitro silicone tube 50 experiments, the balloon 4 containing the inner coating exhibited low drug residue and a high drug transfer efficiency. Specifically, the comparative balloon 4 without the temperature-sensitive carrier exhibited high drug residue and a low drug transfer efficiency because the drug adhered firmly to the balloon 4 surface and was difficult to remove. In contrast, the balloon 4 in the embodiment with the temperature-sensitive carrier experienced a significant change in state during the balloon 4 expansion process, allowing the drug on the balloon 4 to smoothly detach from the balloon 4 surface and adhere to the silicone tube 50 in large quantities. This reduced the drug residue on the balloon 4 surface and increased the drug transfer efficiency. The balloon 4 in comparative example 1 had a high drug adhesion to the balloon 4, making it difficult for the drug to detach from the balloon 4 surface, resulting in a low drug transfer efficiency. The balloon 4 in comparative example 2 had a low drug adhesion to the balloon 4, making it easy for the drug to detach from the balloon 4 surface. This resulted in significant drug loss during balloon 4 delivery, and the amount ultimately transferred into the silicone tube was very small.

[0187] In summary, the present invention adopts the above-mentioned structure and preparation method, which has the advantages of being able to effectively improve the adhesion of the drug coating on the balloon to reduce delivery loss, and being able to increase the release rate of the drug coating on the diseased tissue to enhance the drug transfer capacity.

[0188] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the above embodiments, it should be understood by those skilled in the art that the technical solutions described in the above embodiments can still be modified, or some or all of the technical features therein can be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A drug-coated balloon catheter comprising a catheter (10) with a balloon (4); characterized in that: A drug coating (5) comprising at least an inner coating and an outer coating is provided on the outer wall of the balloon (4), and both the inner coating and the outer coating carry active pharmaceutical ingredients and different carriers; The inner coating layer is a mixture of a pharmaceutical active ingredient and a temperature-sensitive carrier mixed in a preset ratio, and the temperature-sensitive carrier is solid at room temperature and is used to increase the adhesion of the pharmaceutical active ingredient to the balloon (4) when used as a pharmaceutical carrier at room temperature. The temperature-sensitive carrier changes state under body temperature and hydration to reduce the adhesion of the pharmaceutical active ingredient to the balloon (4), thereby promoting the separation of the pharmaceutical active ingredient from the surface of the balloon (4); Among them, in the drug coating (5), when the balloon (4) is expanded, the inner coating together with the outer coating changes state under the patient's body temperature environment and hydration through the temperature-sensitive carrier of the inner coating and detaches from the balloon (4). When detaching from the balloon (4), the outer coating is used to promote the transfer of the corresponding active pharmaceutical ingredient into the target tissue through its carrier.

2. The drug-coated balloon catheter according to claim 1, characterized in that: When the drug coating (5) is two-layered, it is composed of an inner coating layer coated on the outer wall of the balloon (4) and an outer coating layer coated on the inner coating layer, and the outer coating layer is a mixture of a drug active ingredient and a non-temperature-sensitive carrier in a preset ratio, wherein: When the balloon (4) is expanded, the temperature-sensitive carrier of the inner coating layer is used to make the active pharmaceutical ingredient coated on the outer wall of the balloon (4) detach from the balloon (4) together with the outer coating layer under the patient's body temperature environment and hydration; when the inner coating layer drug detaches from the balloon (4) together with the outer coating layer, the outer coating layer promotes the transfer of the active pharmaceutical ingredient of the outer coating layer into the target tissue through the predetermined water solubility or compatibility of its non-temperature-sensitive carrier.

3. The drug-coated balloon catheter according to claim 2, characterized in that: In the inner coating layer, the preset mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1-10):(10-1).

4. The drug-coated balloon catheter according to claim 3, characterized in that: In the outer coating layer, the preset mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is (1-10):(10-1).

5. The drug-coated balloon catheter according to claim 1, characterized in that: When the drug coating (5) is two-layered, it is composed of an inner coating layer coated on the outer wall of the balloon (4) and an outer coating layer coated on the inner coating layer, wherein: The inner coating layer also includes a non-temperature-sensitive carrier, and the inner coating layer is a mixture of a pharmaceutical active ingredient, a temperature-sensitive carrier, and a non-temperature-sensitive carrier in a preset ratio. When the balloon (4) is expanded, the temperature-sensitive carrier of the inner coating layer is used to make the pharmaceutical active ingredient coated on the outer wall of the balloon (4) detach from the balloon (4) together with the non-temperature-sensitive carrier and the outer coating layer under the patient's body temperature environment and hydration. At the same time, the pharmaceutical active ingredient of the inner coating layer is transferred into the target tissue under the promotion effect of the predetermined water solubility or compatibility of the non-temperature-sensitive carrier. The outer coating is a mixture of a drug active ingredient and a non-temperature-sensitive carrier in a preset ratio. When the inner coating drug and the outer coating are separated from the balloon (4), the drug active ingredient of the outer coating is transferred into the target tissue under the promotion of the predetermined water solubility or compatibility of the non-temperature-sensitive carrier.

6. The drug-coated balloon catheter according to claim 5, characterized in that: In the inner coating layer, the preset mass ratio of the temperature-sensitive carrier to the temperature-insensitive carrier is (2-1):(2-1).

7. The drug-coated balloon catheter according to claim 5, characterized in that: In the inner coating layer, the mass ratio of the preset proportions of the active pharmaceutical ingredient, the temperature-sensitive carrier, and the non-temperature-sensitive carrier is (1-10):(2-1):(2-1); in the outer coating layer, the mass ratio of the preset proportions of the active pharmaceutical ingredient and the non-temperature-sensitive carrier is (1-10):(10-1).

8. The drug-coated balloon catheter according to claim 1, characterized in that: When the drug coating (5) is three-layered, it is composed of an inner coating layer coated on the outer wall of the balloon (4), a middle coating layer coated on the inner coating layer, and an outer coating layer coated on the outer wall of the middle coating layer, and the inner coating layer is a mixture of a drug active ingredient and a temperature-sensitive carrier, the middle coating layer is a mixture of a drug active ingredient, a temperature-sensitive carrier, and a non-temperature-sensitive carrier in a preset ratio, and the outer coating layer is a mixture of a drug active ingredient and a non-temperature-sensitive carrier in a preset ratio; Wherein: when the balloon (4) is expanded, the temperature-sensitive carrier of the inner coating layer is used to separate the active pharmaceutical ingredient coated on the outer wall of the balloon (4) from the balloon (4) under the patient's body temperature environment and hydration; when the middle coating layer is used as a pharmaceutical carrier at room temperature, it is used to increase the adhesion stability between the outer coating layer and the inner coating layer; in addition, the temperature-sensitive carrier of the middle coating layer is used to separate the active pharmaceutical ingredient coated on the inner coating layer together with the outer coating layer from the inner coating layer under the patient's body temperature environment and hydration, and at the same time, the active pharmaceutical ingredient of the middle coating layer is transferred into the target tissue under the promotion effect of the predetermined water solubility or compatibility of its non-temperature-sensitive carrier; when the outer coating layer is separated from the inner coating layer, the active pharmaceutical ingredient of the outer coating layer is transferred into the target tissue under the promotion effect of the predetermined water solubility or compatibility of its non-temperature-sensitive carrier.

9. The drug-coated balloon catheter according to claim 8, characterized in that: In the inner coating layer, the preset mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1-10):(10-1).

10. The drug-coated balloon catheter according to claim 8, characterized in that: In the middle layer coating, the preset mass ratio of the temperature-sensitive carrier and the non-temperature-sensitive carrier is (2-1):(2-1).

11. The drug-coated balloon catheter according to claim 8, characterized in that: In the middle coating layer, the preset mass ratio of the active pharmaceutical ingredient, the temperature-sensitive carrier, and the non-temperature-sensitive carrier is (1-10):(2-1):(2-1).

12. The drug-coated balloon catheter according to claim 8, characterized in that: In the outer coating layer, the preset mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is (1-10):(10-1).

13. The drug-coated balloon catheter according to claim 8, characterized in that: The temperature-sensitive carrier is at least one of methyl palmitate, methyl stearate, polyethylene glycol-15 hydroxystearate, quaternized chitosan, pentaerythritol ethoxylate, gelatin, and polyethylene glycol-polylactic acid copolymer.

14. The drug-coated balloon catheter according to claim 8, characterized in that: The non-temperature sensitive carrier is at least one of iohexol, iopromide, urea, sorbitol, polyvinyl pyrrolidone, dextran, polysorbate, stearic acid, acrylic acid, stearic acid, methylcellulose, triethyl butyryl citrate, and polymethacrylate.

15. A method for preparing a drug-coated balloon catheter according to any one of claims 1 to 7, characterized in that: The preparation method is a spraying method for preparing a drug coating (5), which comprises the following steps: S21. Selecting an appropriate amount of a suitable solvent and adding it to two mixtures of a predetermined pharmaceutical active ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier in a predetermined ratio, thereby obtaining two different mixed solutions. Stirring and ultrasonically vibrating the two different mixed solutions by external equipment to uniformly dissolve them, thereby obtaining an inner layer drug solution A and an outer layer drug solution B. S22, adding the inner layer drug solution A to an external spraying device and adjusting the spraying parameters of the spraying device according to a preset standard, spraying the inner layer drug solution A to a predetermined thickness on the outer wall of the balloon (4), and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain an inner layer coating; S23, adding the outer layer drug solution B to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, continuing to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner coating layer in step S22, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the outer coating layer; S24, leaving the balloon (4) prepared in step S23 to dry for 24 hours, so that the drug on the outer wall of the balloon (4) is naturally dried to a predetermined degree to prepare a drug coating (5).

16. A method for preparing a drug-coated balloon catheter according to any one of claims 8 to 14, characterized in that: The preparation method is a spraying method for preparing a drug coating (5), which comprises the following steps: S31. Selecting an appropriate amount of a suitable solvent and adding it to three mixtures of a predetermined pharmaceutical active ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier in predetermined proportions, thereby obtaining three different mixed solutions. Stirring and ultrasonically vibrating the three different mixed solutions using an external device to uniformly dissolve them, thereby obtaining an inner layer drug solution A, an outer layer drug solution B, and a middle layer drug solution C. S32, adding the inner layer drug solution A to an external spraying device and adjusting the spraying parameters of the spraying device according to a preset standard, spraying the inner layer drug solution A to a predetermined thickness on the outer wall of the balloon (4), and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain an inner layer coating; S33, adding the middle layer drug solution C to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, spraying the middle layer drug solution C to a predetermined thickness on the outer wall of the inner layer coating in step S32, and waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the middle layer coating; S34, adding the outer layer drug solution B to the external spraying equipment and adjusting the spraying parameters of the spraying equipment according to the preset standard, continuing to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the middle layer coating in step S33, waiting for 1-300 seconds for the solvent to evaporate to a predetermined degree to obtain the outer layer coating; S35. The balloon (4) prepared in step S34 is allowed to stand and dry for 24 hours, so that the drug on the outer wall of the balloon (4) is dried to a predetermined degree to prepare a drug coating (5).

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