A drug-coated balloon catheter and its preparation method

Abstract

This invention belongs to the field of medical device technology. This invention discloses a drug-coated balloon catheter and its preparation method. On one hand, a drug-coated balloon catheter includes a catheter with a balloon; the outer wall of the balloon is provided with a drug coating comprising at least an inner coating and an outer coating, both the inner and outer coatings carrying active pharmaceutical ingredients and different carriers; when the balloon inflates, the inner coating, together with the outer coating, detaches from the balloon under the influence of the patient's body temperature and hydration through a state change caused by the temperature-sensitive carrier of the inner coating; the outer coating, upon detachment from the balloon, facilitates the transfer of the corresponding active pharmaceutical ingredient into the target tissue via its carrier. On the other hand, a method for preparing a drug-coated balloon catheter is provided. This invention has the advantages of effectively improving the adhesion of the drug coating to the balloon to reduce delivery loss and increasing the release rate of the drug coating on diseased tissue to enhance drug transfer capability.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and more specifically, to a drug-coated balloon catheter and its preparation method. Background Technology

[0002] With the rapid development of medical technology and in-depth research into the pathological mechanisms of stenosis in the human body's natural cavities, drug-eluting medical devices have emerged and become important tools in the modern medical field, occupying an increasingly important position. Drug-eluting balloons, in particular, are a typical example, widely used in the treatment of diseases such as vascular stenosis due to their advantage of localized targeted drug release. As an interventional therapeutic device, the core mechanism of action of drug-eluting balloons lies in achieving precise treatment of diseased tissues through localized targeted drug release.

[0003] Drug coating is a key technical indicator of drug-coated balloon catheters. Currently, there are many methods for its preparation, but not all methods can produce a stable and effective drug coating. The adhesion of the drug-loaded coating on the balloon catheter directly affects the drug release kinetics in vivo, thus significantly impacting therapeutic efficacy. If the drug-loaded coating adhesion is poor, when the balloon is delivered to the lesion target, the drug coating will undergo a process of being washed away by intratissue fluid or water flow. This process often leads to drug coating detachment, resulting in a significant reduction in the amount of drug delivered to the lesion target, thereby reducing the therapeutic effect. Improving the adhesion of the drug-loaded coating increases the binding strength between drug molecules and the balloon surface, significantly reducing delivery loss. However, this can also make it difficult for the drug-coated balloon to release the drug immediately upon reaching the lesion target, leaving more residue on the balloon surface, thus affecting the therapeutic effect. Increasing the drug load of the balloon coating can significantly increase local drug absorption; however, excessively high drug concentrations can easily lead to toxic reactions and affect patient health.

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

[0005] Therefore, the above-mentioned problems have become urgent technical challenges that need to be addressed. 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 loss and improve the release rate of the drug coating on the diseased tissue to enhance drug transfer capability.

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

[0008] To achieve the above-mentioned objectives of this invention, the following technical solution is adopted:

[0009] On one hand, 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 the inner coating and the outer coating both contain a drug active ingredient and each contain a different carrier;

[0010] The inner coating is a mixture of active pharmaceutical ingredient and temperature-sensitive carrier in a preset ratio. The temperature-sensitive carrier is solid at room temperature and is used as a drug carrier at room temperature to increase the adhesion between the active pharmaceutical ingredient and the balloon. The temperature-sensitive carrier undergoes a state change under body temperature and hydration to reduce the adhesion between the active pharmaceutical ingredient and the balloon, thereby causing the active pharmaceutical ingredient to detach from the balloon surface.

[0011] In the drug coating, when the balloon expands, the inner coating, together with the outer coating, detaches from the balloon through a state change caused by the temperature-sensitive carrier of the inner coating under the influence of the patient's body temperature and hydration. When the outer coating detaches from the balloon, it is used to promote the transfer of the corresponding active drug ingredient into the target tissue through its carrier.

[0012] Preferably, when the drug coating is a two-layer coating, it consists of an inner coating layer covering the outer wall of the balloon and an outer coating layer covering the inner coating layer. The outer coating layer is a mixture of the active pharmaceutical ingredient and a non-temperature-sensitive carrier mixed in a predetermined ratio, wherein:

[0013] When the balloon inflates, the temperature-sensitive carrier in the inner coating, under the patient's body temperature and hydration, facilitates the detachment of the active pharmaceutical ingredient (API) coated on the outer wall of the balloon, along with the outer coating, from the balloon. When the API detaches from the balloon along with the outer coating, the outer coating, through the predetermined water solubility or compatibility of its non-temperature-sensitive carrier, promotes the translocation of the API into the target tissue. For example, when the non-temperature-sensitive carrier is hydrophilic, the API of the outer coating detaches from the inner coating due to the water solubility of the non-temperature-sensitive carrier, and is then translocated into the target tissue via active transport. When the non-temperature-sensitive carrier is hydrophobic, the API of the outer coating detaches from the inner coating due to the similar compatibility between the non-temperature-sensitive carrier and the cell wall, and is then translocated into the target tissue via active transport.

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

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

[0016] Preferably, when the drug coating is a two-layer coating, it consists of an inner coating layer covering the outer wall of the balloon and an outer coating layer covering the inner coating layer, wherein:

[0017] The inner coating also includes a non-temperature-sensitive carrier. The inner coating is a mixture of the active pharmaceutical ingredient and the temperature-sensitive and non-temperature-sensitive carriers in a preset ratio. When the balloon is inflated, the temperature-sensitive carrier of the inner coating, under the patient's body temperature and hydration, causes the active pharmaceutical ingredient coated on the outer wall of the balloon, along with the non-temperature-sensitive carrier and the outer coating, to detach from the balloon. At the same time, the active pharmaceutical ingredient of the inner coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of the non-temperature-sensitive carrier.

[0018] The outer coating is a mixture of the active pharmaceutical ingredient and a non-temperature-sensitive carrier in a preset ratio. When the drug in the inner coating is released from the balloon along with the outer coating, the active pharmaceutical ingredient in the outer coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of the non-temperature-sensitive carrier.

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

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

[0021] Preferably, when the drug coating is a three-layer coating, it consists of an inner coating layer covering the outer wall of the balloon, a middle coating layer covering the inner coating layer, and an outer coating layer covering the outer wall of the middle coating layer. The inner coating layer is a mixture of active drug ingredient and temperature-sensitive carrier, the middle coating layer is a mixture of active drug ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier in a preset ratio, and the outer coating layer is a mixture of active drug ingredient and non-temperature-sensitive carrier in a preset ratio.

[0022] Wherein: when the balloon expands, the temperature-sensitive carrier of the inner coating, under the patient's body temperature and hydration, is used to detach the active pharmaceutical ingredient coated on the outer wall of the balloon from the balloon; when the middle coating acts as a drug carrier at room temperature, it is used to increase the adhesion stability between the outer and inner coatings. In addition, under the patient's body temperature and hydration, the temperature-sensitive carrier of the middle coating is used to detach the active pharmaceutical ingredient coated on the inner coating along with the outer coating from the inner coating. At the same time, the active pharmaceutical ingredient of the middle coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of its non-temperature-sensitive carrier; when the outer coating detaches from the inner coating, the active pharmaceutical ingredient of the outer coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of its non-temperature-sensitive carrier.

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

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

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

[0026] Preferably, in the outer coating, the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive 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, polyvinylpyrrolidone, 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 drug-coated balloon catheter, wherein the preparation method is a spraying method for preparing a drug coating, which includes the following steps:

[0030] S21. Select an appropriate amount of suitable solvent and add it to two mixtures prepared according to a predetermined ratio of a predetermined active pharmaceutical ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier, thereby obtaining two different mixtures. Stir and ultrasonically vibrate the two different mixtures with external equipment to make them dissolve evenly, thereby obtaining inner drug solution A and outer drug solution B.

[0031] S22. Add the inner layer drug solution A to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the inner layer drug solution A of a predetermined thickness on the outer wall of the balloon and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the inner layer coating.

[0032] S23. Add the outer layer drug solution B to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Continue to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner layer coating in step S22, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the outer layer coating.

[0033] S24. Allow the balloon from step S23 to stand and dry for 24 hours, allowing 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 drug-coated balloon catheter, wherein the preparation method is a spraying method for preparing a drug coating, which includes the following steps:

[0035] S31. Select an appropriate amount of suitable solvent and add it to three mixtures prepared according to a predetermined ratio of a predetermined active pharmaceutical ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier, thereby obtaining three different mixtures. Stir and ultrasonically vibrate the three different mixtures with external equipment to make them dissolve evenly, thereby obtaining inner layer drug solution A, outer layer drug solution B and middle layer drug solution C.

[0036] S32. Add the inner layer drug solution A to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the inner layer drug solution A of a predetermined thickness on the outer wall of the balloon and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the inner layer coating.

[0037] S33. Add the intermediate drug solution C to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the intermediate drug solution C of a predetermined thickness on the outer wall of the inner coating in step S32, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the intermediate coating.

[0038] S34. Add the outer layer drug solution B to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Continue to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the middle layer coating in step S33, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the outer layer coating.

[0039] S35. Allow the balloon from step S34 to stand and 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 pharmaceutical ingredient is at least one of the following: antitumor agents, antiproliferative agents, antibiotics, anticoagulants, antithrombotic agents, and anti-inflammatory drugs. For example, the active pharmaceutical ingredient is at least one of sirolimus, paclitaxel, arsenic trioxide, eutrimolimus, zotalimus, everolimus, heparin, tavitolimus, and rapamycin.

[0041] Preferably, the solvent is at least one selected from 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 this invention, a predetermined drug solution is formed by adjusting the ratio of the corresponding active pharmaceutical ingredients and a predetermined temperature-sensitive or non-temperature-sensitive carrier in the inner and outer layers of the drug coating. This drug solution is sprayed onto the outer wall of a balloon in a predetermined sequence to form a drug coating. The drug coating is then delivered to the diseased tissue via a catheter and balloon. When the balloon inflates, the temperature-sensitive carrier in the inner coating undergoes a state change under the patient's body temperature and hydration conditions, reducing the adhesion of the active pharmaceutical ingredients to the balloon. This causes the inner and outer layers of the drug coating to detach from the balloon together. Simultaneously, the outer coating detaches from the balloon... This invention facilitates drug delivery to the target tissue via its carrier, enabling the rapid release of the active pharmaceutical ingredient after delivery to the lesion. This, in turn, enhances the release rate of the drug coating on the lesion, thereby improving drug delivery capability and meeting clinical needs for precise drug delivery to reduce the risk of restenosis. It is suitable for the prevention and treatment of stenosis in natural cavities of the human body, such as the urethra, ureter, Eustachian tube, esophagus, gastrointestinal tract, biliary duct, pancreatic duct, and trachea. Therefore, this invention has the advantages of effectively improving the adhesion of the drug coating to the balloon to reduce delivery loss and increasing the release rate of the drug coating on the lesion to enhance drug delivery capability. Attached Figure Description

[0045] To more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

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

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

[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] Figure descriptions: 10-catheter, 1-connector, 2-anti-bend protective sleeve, 3-outer tube, 4-balloon, 5-drug coating, 6-tip, 20-infusion pump tubing, 30-water bath equipment, 40-simulated endoscope, 50-silicone tubing, 60-waste collection equipment, 70-pressure pump. Detailed Implementation

[0050] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are 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, including 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 both the inner coating and the outer coating contain active pharmaceutical ingredients and different carriers respectively.

[0052] The inner coating is a mixture of active pharmaceutical ingredient and temperature-sensitive carrier in a preset ratio. The temperature-sensitive carrier is solid at room temperature and is used as a drug carrier at room temperature to increase the adhesion between the active pharmaceutical ingredient and the balloon 4. The temperature-sensitive carrier undergoes a state change under body temperature and hydration to reduce the adhesion between the active pharmaceutical ingredient and the balloon 4, thereby causing the active pharmaceutical ingredient to detach from the surface of the balloon 4.

[0053] In the drug coating 5, when the balloon 4 is inflated, the inner coating and the outer coating are separated from the balloon 4 by a state change caused by the temperature-sensitive carrier of the inner coating under the patient's body temperature environment and hydration. When the outer coating is separated from the balloon 4, it is used to promote the transfer of the corresponding drug active ingredients into the target tissue through its carrier.

[0054] Specifically, when the drug coating 5 is a two-layer coating, it consists of an inner coating layer covering the outer wall of the balloon 4 and an outer coating layer covering the inner coating layer. The outer coating layer is a mixture of the active pharmaceutical ingredient and a non-temperature-sensitive carrier mixed in a preset ratio, wherein:

[0055] When the balloon 4 expands, the temperature-sensitive carrier of the inner coating, under the patient's body temperature and hydration, facilitates the removal of the active pharmaceutical ingredient coated on the outer wall of the balloon 4, along with the outer coating, from the balloon 4. When the drug in the inner coating is removed from the balloon 4 along with the outer coating, the outer coating, through the predetermined water solubility or compatibility of its non-temperature-sensitive carrier, promotes the transfer of the active pharmaceutical ingredient into the target tissue.

[0056] This invention involves adjusting the ratio of the corresponding active pharmaceutical ingredients and a predetermined temperature-sensitive or non-temperature-sensitive carrier in the inner and outer coatings of the drug coating 5 to form a predetermined drug solution. This drug solution is then sprayed onto the outer wall of the balloon 4 in a predetermined sequence to form the drug coating 5. The drug coating 5 is then delivered to the diseased tissue via the catheter 10 and the balloon 4. When the balloon 4 inflates, the temperature-sensitive carrier in the inner coating undergoes a state change under the patient's body temperature and hydration conditions, reducing the adhesion of the active pharmaceutical ingredients to the balloon 4, thereby promoting drug delivery. The inner coating of the drug coating 5, together with its outer coating, detaches from the balloon 4. Simultaneously, as the outer coating detaches from the balloon 4, it facilitates drug transport into the target tissue through its carrier, thereby enabling the active drug ingredient to be rapidly released after delivery to the lesion tissue. This promotes the release rate of the drug coating 5 on the lesion tissue, enhancing drug transport capability and meeting the clinical need for precise drug delivery to reduce the risk of restenosis. It is suitable for the prevention and treatment of stenosis in natural cavities of the human body, such as the urethra, ureter, eustachian tube, esophagus, gastrointestinal tract, biliary duct, pancreatic duct, and trachea.

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

[0058] S21. Select an appropriate amount of suitable solvent and add it to two mixtures prepared according to a predetermined ratio of a predetermined active pharmaceutical ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier, thereby obtaining two different mixtures. Stir and ultrasonically vibrate the two different mixtures with external equipment to make them dissolve evenly, thereby obtaining inner drug solution A and outer drug solution B.

[0059] S22. Add the inner layer drug solution A to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the inner layer drug solution A of a predetermined thickness on the outer wall of the balloon 4 and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the inner layer coating.

[0060] S23. Add the outer layer drug solution B to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Continue to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner layer coating in step S22, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the outer layer coating.

[0061] S24. Allow the balloon 4 from step S23 to stand and dry for 24 hours, so that the drug on the outer wall of the balloon 4 can dry naturally to a predetermined degree to prepare the drug coating 5.

[0062] Specifically, in the inner coating layer, the predetermined mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1-10):(10-1); in the outer coating layer, the predetermined mass 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, polyvinylpyrrolidone, dextran, polysorbate, stearic acid, acrylic acid, stearic acid, methylcellulose, triethyl butyryl citrate, and polymethacrylate. The active pharmaceutical ingredient is at least one of the following: antitumor agents, antiproliferative agents, antibiotics, anticoagulants, antithrombotic agents, and anti-inflammatory drugs. For example, the active pharmaceutical ingredient is at least one of sirolimus, paclitaxel, arsenic trioxide, eutrimolimus, zotalimus, everolimus, heparin, tavitolimus, and rapamycin. The balloon 4 is made of at least one of the following: nylon material, nylon elastomer Pebax material, polyethylene material, and polyurethane material. The solvent is at least one of the following: 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 is 10:1; in the outer coating, the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier is a predetermined ratio of 10:1. 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 material, nylon elastomer Pebax material, polyethylene material, and polyurethane material, and the solvent is a mixture of acetone and methanol.

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

[0066] 1) Add 0.5g paclitaxel and 0.05g methyl stearate to a mixed solvent of 10mL methanol and 10mL acetone, and use a predetermined external device to stir and sonicate to dissolve evenly, thereby obtaining inner layer drug solution A;

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

[0068] 3) Add 0.5g paclitaxel and 0.05g urea to a mixed solvent of 10mL methanol and 10mL acetone, and stir and sonicate using a predetermined external device to dissolve evenly, thereby obtaining the outer drug solution B;

[0069] 4) Add the outer layer drug solution B obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, spray the outer layer drug solution B of the inner layer coating obtained in step 2) for another 10 layers with a predetermined thickness. After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the predetermined degree to obtain the outer layer coating.

[0070] 5) Dry the balloon 4 obtained in step 4) for 24 hours to allow the drug coating on the outer wall of the balloon 4 to dry to a predetermined degree to form the drug coating 5, thereby obtaining a drug-coated balloon catheter with the drug coating 5. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 flaps, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As 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 is 5:1; the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier in the outer coating 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 material, nylon elastomer Pebax material, polyethylene material, and polyurethane material, and the solvent is acetone.

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

[0074] 1) Add 0.5g sirolimus and 0.1g methyl palmitate to 20mL acetone solvent, and use predetermined external equipment to stir and sonicate to dissolve evenly, thereby obtaining inner layer drug solution A;

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

[0076] 3) Add 0.5g sirolimus and 0.1g dextran to 20mL acetone, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining the outer drug solution B;

[0077] 4) Add the outer layer drug solution B obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, spray the outer layer drug solution B of the inner layer coating obtained in step 2) for another 10 layers with a predetermined thickness. After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the predetermined degree to obtain the outer layer coating.

[0078] 5) Dry the balloon 4 obtained in step 4) for 24 hours to allow the drug coating on the outer wall of the balloon 4 to dry to a predetermined degree to form the drug coating 5, thereby obtaining a drug-coated balloon catheter with the drug coating 5. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 flaps, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As 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 is 1:10; and the mass ratio of the active pharmaceutical ingredient to the non-temperature-sensitive carrier in the outer coating 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 material, nylon elastomer Pebax material, polyethylene material, and polyurethane material, and the solvent is toluene.

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

[0082] 1) Add 0.05g heparin and 0.5g quaternized chitosan to 20mL of toluene solvent, and use predetermined external equipment to stir and ultrasonically vibrate to dissolve evenly, thereby obtaining inner layer drug solution A;

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

[0084] 3) Add 0.05g heparin and 0.5g iohexol to 20mL of toluene solvent, and use a predetermined external device to stir and sonicate to dissolve evenly, thereby obtaining the outer drug solution B;

[0085] 4) Add the outer layer drug solution B obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, spray the outer layer drug solution B of the inner layer coating obtained in step 2) for another 10 layers with a predetermined thickness. After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the predetermined degree to obtain the outer layer coating.

[0086] 5) Dry the balloon 4 obtained in step 4) for 24 hours to allow the drug coating on the outer wall of the balloon 4 to dry to a predetermined degree to form the drug coating 5, thereby obtaining a drug-coated balloon catheter with the drug coating 5. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 flaps, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As shown.

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

[0088] The inner coating also includes a non-temperature-sensitive carrier. The inner coating is a mixture of the active pharmaceutical ingredient and the temperature-sensitive carrier and the non-temperature-sensitive carrier in a preset ratio. When the balloon 4 is inflated, the temperature-sensitive carrier of the inner coating, under the patient's body temperature environment and hydration, is used to cause the active pharmaceutical ingredient coated on the outer wall of the balloon 4 to detach from the balloon 4 along with the non-temperature-sensitive carrier and the outer coating. At the same time, the active pharmaceutical ingredient of the inner coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect 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 ratio. When the drug in the inner coating is released from the balloon 4 along with the outer coating, the active pharmaceutical ingredients in the outer coating are transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of the 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 a drug coating 5, comprising the following steps:

[0091] S21. Select an appropriate amount of suitable solvent and add it to two mixtures prepared according to a predetermined ratio of a predetermined active pharmaceutical ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier, thereby obtaining two different mixtures. Stir and ultrasonically vibrate the two different mixtures with external equipment to make them dissolve evenly, thereby obtaining inner drug solution A and outer drug solution B.

[0092] S22. Add the inner layer drug solution A to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the inner layer drug solution A of a predetermined thickness on the outer wall of the balloon 4 and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the inner layer coating.

[0093] S23. Add the outer layer drug solution B to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Continue to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner layer coating in step S22, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the outer layer coating.

[0094] S24. Allow the balloon 4 from step S23 to stand and dry for 24 hours, so that the drug on the outer wall of the balloon 4 can dry naturally to a predetermined degree to prepare the drug coating 5.

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

[0096] Example 4

[0097] In this embodiment, in the inner coating layer, the mass ratio of temperature-sensitive carrier to non-temperature-sensitive carrier is 2:2, and the mass ratio of active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 1:2:2; in the outer coating layer, the mass ratio of active pharmaceutical ingredient to 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 material, nylon elastomer Pebax material, polyethylene material, and polyurethane material, and the solvent is a mixture of acetone and methanol.

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

[0099] 1) Add 0.5g paclitaxel, 1.0g methyl stearate and 1.0g urea to a mixed solvent of 10mL methanol and 10mL acetone, and stir and sonicate using a predetermined external device to dissolve evenly, thereby obtaining inner layer drug solution A.

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

[0101] 3) Add 0.05g paclitaxel and 0.5g urea to a mixed solvent of 10mL methanol and 10mL acetone, and stir and sonicate using a predetermined external device to dissolve evenly, thereby obtaining the outer drug solution B;

[0102] 4) Add the outer layer drug solution B obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, continue to spray 10 layers of the outer layer drug solution B of the predetermined thickness on the outer wall of the inner layer coating obtained in step 2). After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the 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. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 flaps, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As shown.

[0104] Example 5

[0105] In this embodiment, in the inner coating layer, the mass ratio of temperature-sensitive carrier to non-temperature-sensitive carrier is 2:1, and the mass ratio of active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 5:2:1; in the outer coating layer, the mass ratio of active pharmaceutical ingredient to 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 material, nylon elastomer Pebax material, polyethylene material, and polyurethane material, and the solvent is acetone.

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

[0107] 1) Add 0.5g sirolimus, 0.2g methyl palmitate and 0.1g dextran to 20mL acetone solvent, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining inner layer drug solution A.

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

[0109] 3) Add 0.6g sirolimus and 0.4g dextran to 20mL acetone solvent, and use a predetermined external device to stir and sonicate to dissolve evenly, thereby obtaining the outer drug solution B;

[0110] 4) Add the outer layer drug solution B obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, continue to spray 10 layers of the outer layer drug solution B of the predetermined thickness on the outer wall of the inner layer coating obtained in step 2). After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the 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. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 flaps, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As shown.

[0112] Example 6

[0113] In this embodiment, in the inner coating layer, the mass ratio of temperature-sensitive carrier to non-temperature-sensitive carrier is 1:1, and the mass ratio of active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is 10:1:1; in the outer coating layer, the mass ratio of active pharmaceutical ingredient to 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 material, nylon elastomer Pebax material, polyethylene material, and polyurethane material, and the solvent is toluene.

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

[0115] 1) Add 0.5g heparin, 0.05g quaternized chitosan and 0.05g iohexol to 20mL toluene solvent, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining inner layer drug solution A.

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

[0117] 3) Add 0.5g heparin and 0.05g iohexol to 20mL toluene solvent, and use a predetermined external device to stir and sonicate to dissolve evenly, thereby obtaining the outer drug solution B;

[0118] 4) Add the outer layer drug solution B obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, continue to spray 10 layers of the outer layer drug solution B of the predetermined thickness on the outer wall of the inner layer coating obtained in step 2). After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the 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. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 flaps, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As shown.

[0120] like Figures 1 to 3As shown, in this invention, when the drug coating 5 is a three-layer coating, it consists of an inner coating layer covering the outer wall of the balloon 4, a middle coating layer covering the inner coating layer, and an outer coating layer covering the outer wall of the middle coating layer. The inner coating layer is a mixture of active drug ingredient and temperature-sensitive carrier, the middle coating layer is a mixture of active drug ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier in a preset ratio, and the outer coating layer is a mixture of active drug ingredient and non-temperature-sensitive carrier in a preset ratio.

[0121] Wherein: when the balloon 4 expands, the temperature-sensitive carrier of the inner coating, under the patient's body temperature and hydration, is used to detach the active pharmaceutical ingredient coated on the outer wall of the balloon 4 from the balloon 4; when the middle coating acts as a drug carrier at room temperature, it is used to increase the adhesion stability between the outer and inner coatings. In addition, under the patient's body temperature and hydration, the temperature-sensitive carrier of the middle coating is used to detach the active pharmaceutical ingredient coated on the inner coating along with the outer coating from the inner coating. At the same time, the active pharmaceutical ingredient of the middle coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of its non-temperature-sensitive carrier; when the outer coating detaches from the inner coating, the active pharmaceutical ingredient of the outer coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect 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 a drug coating 5, comprising the following steps:

[0123] S31. Select an appropriate amount of suitable solvent and add it to three mixtures prepared according to a predetermined ratio of a predetermined active pharmaceutical ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier, thereby obtaining three different mixtures. Stir and ultrasonically vibrate the three different mixtures with external equipment to make them dissolve evenly, thereby obtaining inner layer drug solution A, outer layer drug solution B and middle layer drug solution C.

[0124] S32. Add the inner layer drug solution A to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the inner layer drug solution A of a predetermined thickness on the outer wall of the balloon 4 and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the inner layer coating.

[0125] S33. Add the intermediate drug solution C to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the intermediate drug solution C of a predetermined thickness on the outer wall of the inner coating in step S32, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the intermediate coating.

[0126] S34. Add the outer layer drug solution B to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Continue to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the middle layer coating in step S33, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the outer layer coating.

[0127] S35. Allow the balloon 4 from step S34 to stand and dry for 24 hours to dry the drug on the outer wall of the balloon 4 to a predetermined degree to prepare the drug coating 5.

[0128] Specifically, in the inner coating layer, the predetermined mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier is (1–10):(10–1); in the middle coating layer, the predetermined mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier is (2–1):(2–1), and the predetermined mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier to the non-temperature-sensitive carrier is (1–10):(2–1):(2–1); in the outer coating layer, the predetermined mass 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 the following: iohexol, iopromide, urea, sorbitol, polyvinylpyrrolidone, dextran, polysorbate, stearic acid, acrylic acid, stearic acid, methylcellulose, triethyl butyryl citrate, and polymethacrylate.

[0129] Specifically, the catheter 10 includes an outer tube 3, one end of which is a tip 6. The balloon 4 is located on the end of the outer tube 3 near 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-bend protective sleeve 2.

[0130] Example 7

[0131] In this embodiment, in the inner coating layer, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier 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, the temperature-sensitive carrier, and the 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, the inner drug solution A is a mixture of 0.05g paclitaxel, 0.5g methyl stearate, 10mL methanol, and 10mL acetone; the middle drug solution C is a mixture of 0.05g paclitaxel, 0.1g methyl stearate, 0.1g urea, 10mL methanol, and 10mL acetone; and the outer drug solution B is a mixture of 0.05g paclitaxel, 0.5g urea, 10mL methanol, and 10mL acetone. The drug coating 5 in this embodiment is prepared by the following steps:

[0133] 1) Add 0.05g paclitaxel and 0.5g methyl stearate to a mixed solvent of 10mL methanol and 10mL acetone, and stir and sonicate using a predetermined external device to dissolve evenly, thereby obtaining inner layer drug solution A;

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

[0135] 3) Add 0.05g paclitaxel, 0.1g methyl stearate and 0.1g urea to a mixed solvent of 10mL methanol and 10mL acetone, and stir and sonicate using a predetermined external device to dissolve evenly, thereby obtaining the middle layer drug solution C.

[0136] 4) Add the intermediate drug solution C obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, spray the intermediate drug solution C on the outer wall of the inner coating obtained in step 2) with a predetermined thickness of intermediate drug solution C, let it stand for 300s, and wait for the solvent to evaporate to the predetermined degree to obtain the intermediate coating.

[0137] 5) Add 0.05g paclitaxel and 0.5g urea to a mixed solvent of 10mL methanol and 10mL acetone, and stir and sonicate using a predetermined external device to dissolve evenly, thereby obtaining the outer drug solution B.

[0138] 6) Add the outer layer drug solution B obtained in step 5) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, continue to spray 10 layers of the outer layer drug solution B of the predetermined thickness on the outer wall of the intermediate coating obtained in step 4). After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the 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. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 segments, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As shown.

[0140] Example 8

[0141] In this embodiment, in the inner coating layer, the mass ratio of the active pharmaceutical ingredient (API) to the temperature-sensitive carrier is 6:4; in the middle coating layer, the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier is 2:1, and the mass ratio of the API to the temperature-sensitive carrier to the non-temperature-sensitive carrier is 5:2:1; in the outer coating layer, the mass ratio of the API to the non-temperature-sensitive carrier is 6:4. The API 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 drug solution A is a mixture of 0.6g sirolimus, 0.4g methyl palmitate, and 20mL acetone; the middle drug solution C is a mixture of 0.5g sirolimus, 0.2g methyl palmitate, 0.1g dextran, and 20mL acetone; and the outer drug solution B is a mixture of 0.6g sirolimus, 0.4g dextran, and 20mL acetone. The drug coating 5 in this embodiment is prepared by the following steps:

[0143] 1) Add 0.6g sirolimus and 0.4g methyl palmitate to 20mL acetone solvent, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining inner layer drug solution A;

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

[0145] 3) Add 0.5g sirolimus, 0.2g methyl palmitate, and 0.1g dextran to 20mL of acetone, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining the middle layer drug solution C;

[0146] 4) Add the intermediate drug solution C obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, spray the intermediate drug solution C on the outer wall of the inner coating obtained in step 2) with a predetermined thickness of intermediate drug solution C, let it stand for 300s, and wait for the solvent to evaporate to the predetermined degree to obtain the intermediate coating.

[0147] 5) Add 0.6g sirolimus and 0.4g dextran to 20mL acetone, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining the outer drug solution B;

[0148] 6) Add the outer layer drug solution B obtained in step 5) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, continue to spray 10 layers of the outer layer drug solution B of the predetermined thickness on the outer wall of the intermediate coating obtained in step 4). After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the predetermined degree to obtain the outer coating.

[0149] 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. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 segments, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2As shown.

[0150] Example 9

[0151] In this embodiment, in the inner coating layer, the mass ratio of the active pharmaceutical ingredient to the temperature-sensitive carrier 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 to the temperature-sensitive carrier to the 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 composed of 0.5g heparin, 0.05g quaternized chitosan, and 20mL toluene; the middle layer drug solution C is a mixture composed of 0.5g heparin, 0.05g quaternized chitosan, 0.05g iohexol, and 20mL toluene; and the outer layer drug solution B is a mixture composed of 0.5g heparin, 0.05g iohexol, and 20mL toluene. The drug coating 5 in this embodiment is prepared by the following steps:

[0153] 1) Add 0.5g heparin and 0.05g quaternized chitosan to 20mL toluene solvent, and use a predetermined external device to stir and ultrasonically vibrate to dissolve them evenly, thereby obtaining inner layer drug solution A;

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

[0155] 3) Add 0.5g heparin, 0.05g quaternized chitosan and 0.05g iohexol to 20mL toluene solvent, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining the middle layer drug solution C;

[0156] 4) Add the intermediate drug solution C obtained in step 3) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, spray the intermediate drug solution C on the outer wall of the inner coating obtained in step 2) with a predetermined thickness of intermediate drug solution C, let it stand for 300s, and wait for the solvent to evaporate to the predetermined degree to obtain the intermediate coating.

[0157] 5) Add 0.5g heparin and 0.05g iohexol to 20mL toluene solvent, and stir and sonicate using a predetermined external device to dissolve them evenly, thereby obtaining the outer drug solution B;

[0158] 6) Add the outer layer drug solution B obtained in step 5) into the pipeline channel of the external ultrasonic atomizing sprayer, and adjust the spraying parameters: the spraying flow rate is the preset 0.08 mL / min, the nozzle moving speed is the preset 1.5 mm / s, the rotation speed is the preset 200 r / min, and the power is the preset 1.0 W. Under the conditions of temperature 23℃ and relative humidity 50%, continue to spray 10 layers of the outer layer drug solution B of the predetermined thickness on the outer wall of the intermediate coating obtained in step 4). After the spraying is completed, let it stand for 300s to allow the solvent to evaporate to the 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. Then, the balloon 4 and the drug coating 5 are folded and assembled with a base of 5 segments, and fixed and stored with an external balloon protective sleeve. Its structure is as follows. Figure 2 As shown.

[0160] Comparative Example 1

[0161] This comparative example provides a drug-coated balloon catheter and its preparation method. The inner coating does not contain a temperature-sensitive carrier, and the carrier in the outer coating is a material that has strong adhesion to the balloon. Other conditions are the same as in Example 1.

[0162] Comparative Example 2

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

[0164] Performance Evaluation

[0165] Test 1: Folding Loss Test

[0166] The drug content in the drug-eluting capsules before and after folding was determined by high-performance liquid chromatography (HPLC), and the folding loss rate of the drug-eluting capsules was calculated. The specific calculation formula is as follows:

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

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

[0169]

[0170] The data above shows that the balloon 4 with the inner coating has a relatively lower folding loss rate compared to 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, preventing drug loss during the folding process.

[0171] Test 2: Transport Loss Test

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

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

[0174] The test results are shown in Table 2.

[0175] Table 2. Drug delivery loss rate of different embodiments.

[0176]

[0177] The data above shows that although the delivery loss rate of the balloon 4 with the inner coating is higher than that of the folding loss rate, it is still relatively lower than that of the balloon 4 in Comparative Example 2 without the inner coating. Further analysis reveals that during delivery, the temperature-sensitive carrier in the inner coating of the embodiment begins to change state due to the influence of body temperature. However, because the temperature change is slow during delivery and the balloon 4 remains in a folded state, the drug loss rate remains controllable.

[0178] Test 3: In Vitro Simulation Test

[0179] like Figure 3 An in vitro simulation device was constructed as shown. An external silicone tube 50 was used to simulate the urethra. The silicone tube 50 was immersed in an external water bath device 30, simulating the human body temperature environment at a constant temperature of 37°C. One end of the silicone tube 50 was connected to the sheath of the perfusion pump line 20, simulating the endoscope 40. The other end of the silicone tube 50 was connected to an external waste collection device 60. The water flow rate was controlled by the perfusion pump in the perfusion pump line 20. After the entire pipeline was filled with water, both ends of the drug-coated balloon catheter were connected to an external pressure pump 70 and the sheath, respectively. The drug coating 5 was delivered to the simulated lesion site of the silicone tube 50 through the simulated path of the simulated endoscope 40. After standing for 1 minute to hydrate, the balloon 4 was inflated to the nominal pressure. After simulating release for 1 minute, the pressure was released. After complete depressurization, the drug-coated balloon catheter was withdrawn. The residual drug on the balloon 4 and the drug content at the simulated lesion site of the silicone tube 50 were tested using high performance liquid chromatography (HPLC). The specific calculation formula is as follows:

[0180] Drug residue rate = (Residual drug amount on the balloon / Drug content after folding) * 100%

[0181] Drug transfer rate = (Drug content at the simulated lesion site on 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 embodiments

[0184]

[0185]

[0186] The data above shows that in the in vitro silicone tube 50 experiment, the balloon 4 with the inner coating had a low drug residue and a high drug transfer rate. Specifically, in the comparative example without a temperature-sensitive carrier, the drug adhered firmly to the surface of the balloon 4, making it difficult to detach, resulting in a high drug residue and a low drug transfer rate. However, in the example with the temperature-sensitive carrier, the temperature-sensitive carrier in the inner coating underwent a significant state change during balloon 4 expansion, allowing the drug to detach smoothly from the balloon 4 surface and adhere extensively to the silicone tube 50, thus reducing the drug residue on the balloon 4 surface and increasing the drug transfer rate. In Comparative Example 1, the balloon 4 had a very high adhesion between the drug and the balloon 4, making it difficult for the drug to detach from the balloon 4 surface, resulting in a low drug transfer rate. In Comparative Example 2, the balloon 4 had a weak adhesion between the drug and the balloon 4, making it easy for the drug to detach from the balloon 4 surface. During balloon 4 delivery, a large amount of drug was lost, and very little was ultimately transferred into the silicone tube.

[0187] In summary, the present invention, using the above-described structure and preparation method, has the advantages of effectively improving the adhesion of the drug coating on the balloon to reduce delivery loss and improving the release rate of the drug coating on the diseased tissue to enhance drug transfer capability.

[0188] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate 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 are provided with active pharmaceutical ingredients and different carriers respectively; the outer coating is a mixture of active pharmaceutical ingredients and non-temperature-sensitive carriers mixed in a preset ratio; The inner coating is a mixture of active pharmaceutical ingredients and temperature-sensitive carriers in a preset ratio. The temperature-sensitive carrier is solid at room temperature and is used as a drug carrier at room temperature to increase the adhesion between the active pharmaceutical ingredients and the balloon (4). The temperature-sensitive carrier undergoes a state change under body temperature and hydration to reduce the adhesion between the active pharmaceutical ingredients and the balloon (4), thereby causing the active pharmaceutical ingredients to detach from the surface of the balloon (4). In the drug coating (5), when the balloon (4) expands, the inner coating and the outer coating are separated from the balloon (4) by the temperature-sensitive carrier of the inner coating under the patient's body temperature environment and hydration. When the outer coating is separated from the balloon (4), it is used to promote the transfer of the corresponding drug active ingredients into the target tissue through its carrier.

2. The drug-coated balloon catheter according to claim 1, characterized in that: When the drug is applied When layer (5) is a two-layer structure, it consists of an inner coating layer covering the outer wall of the balloon (4) and an outer coating layer covering the inner coating layer, wherein: When the balloon (4) expands, the temperature-sensitive carrier of the inner coating is used by the patient's body temperature and hydration to cause the active pharmaceutical ingredient on the outer wall of the balloon (4) to detach from the balloon (4) along with the outer coating. When the drug in the inner coating detaches from the balloon (4) along with the outer coating, the outer coating promotes the transfer of the active pharmaceutical ingredient into the target tissue through the water solubility or compatibility of its non-temperature-sensitive carrier.

3. The drug-coated balloon catheter according to claim 2, characterized in that: Inner coating In this process, the 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: outer coating In this process, the 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 a two-layer coating, it consists of an inner coating layer covering the outer wall of the balloon (4) and an outer coating layer covering the inner coating layer, wherein: The inner coating also includes a non-temperature-sensitive carrier. The inner coating is a mixture of the active pharmaceutical ingredient and the temperature-sensitive carrier and the non-temperature-sensitive carrier in a preset ratio. When the balloon (4) is expanded, the temperature-sensitive carrier of the inner coating is used to cause the active pharmaceutical ingredient covered on the outer wall of the balloon (4) to detach from the balloon (4) together with the non-temperature-sensitive carrier and the outer coating under the patient's body temperature environment and hydration. At the same time, the active pharmaceutical ingredient of the inner coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of the non-temperature-sensitive carrier. When the drug in the inner coating detaches from the balloon (4) along with the outer coating, the active pharmaceutical ingredient in the outer coating is transferred into the target tissue under the predetermined water solubility or compatibility promotion effect of its non-temperature-sensitive carrier.

6. The drug-coated balloon catheter according to claim 5, characterized in that: Inner coating In this process, the mass ratio of the temperature-sensitive carrier to the non-temperature-sensitive carrier is (2~1):(2~1).

7. The drug-coated balloon catheter according to claim 5, characterized in that: Inner coating In the middle layer, the mass ratio of the drug active ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier is (1~10):(2~1):(2~1); in the outer coating layer, the mass ratio of the drug active ingredient to 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 is applied When layer (5) is three layers, it consists of an inner coating layer covering the outer wall of the balloon (4), a middle coating layer covering the inner coating layer, and an outer coating layer covering the outer wall of the middle coating layer. The inner coating layer is a mixture of active pharmaceutical ingredient and temperature-sensitive carrier, and the middle coating layer is a mixture of active pharmaceutical ingredient, temperature-sensitive carrier, and non-temperature-sensitive carrier in a preset ratio. Wherein: when the balloon (4) expands, the temperature-sensitive carrier of the inner coating is used to detach 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 is used as a drug carrier at room temperature, it is used to increase the adhesion stability between the outer coating and the inner coating. In addition, the temperature-sensitive carrier of the middle coating is used to detach the active pharmaceutical ingredient coated on the inner coating together with the outer coating from the inner coating under the patient's body temperature environment and hydration. At the same time, the active pharmaceutical ingredient of the middle coating is transferred into the target tissue under the water solubility or compatibility promotion effect of its non-temperature-sensitive carrier; when the outer coating detaches from the inner coating, the active pharmaceutical ingredient of the outer coating is transferred into the target tissue under the water solubility or compatibility promotion effect of its non-temperature-sensitive carrier.

9. The drug-coated balloon catheter according to claim 8, characterized in that: Inner coating In this process, the 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 intermediate coating, the preset mass ratio of temperature-sensitive carrier to non-temperature-sensitive carrier is (2~1):(2~1).

11. The drug-coated balloon catheter according to claim 8, characterized in that: In the intermediate coating layer, the mass ratio of the drug active ingredient, temperature-sensitive carrier, and 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, the 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 the following: iohexol, iopromide, urea, sorbitol, polyvinylpyrrolidone, 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 includes the following steps: S21. Select an appropriate amount of suitable solvent and add it to two mixtures prepared according to a predetermined ratio of a predetermined active pharmaceutical ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier, thereby obtaining two different mixtures. Stir and ultrasonically vibrate the two different mixtures with external equipment to make them dissolve evenly, thereby obtaining inner drug solution A and outer drug solution B. S22. Add the inner layer drug solution A to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the inner layer drug solution A of a predetermined thickness on the outer wall of the balloon (4) and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the inner layer coating. S23. Add the outer layer drug solution B to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Continue to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the inner layer coating in step S22, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the outer layer coating. S24. Let the balloon (4) from step S23 stand and dry for 24 hours, so that the drug on the outer wall of the balloon (4) dries naturally to a predetermined degree to prepare the 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 includes the following steps: S31. Select an appropriate amount of suitable solvent and add it to three mixtures prepared according to a predetermined ratio of a predetermined active pharmaceutical ingredient and a predetermined temperature-sensitive carrier or a non-temperature-sensitive carrier, thereby obtaining three different mixtures. Stir and ultrasonically vibrate the three different mixtures with external equipment to make them dissolve evenly, thereby obtaining inner layer drug solution A, outer layer drug solution B and middle layer drug solution C. S32. Add the inner layer drug solution A to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the inner layer drug solution A of a predetermined thickness on the outer wall of the balloon (4) and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the inner layer coating. S33. Add the intermediate drug solution C to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Spray the intermediate drug solution C of a predetermined thickness on the outer wall of the inner coating in step S32, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the intermediate coating. S34. Add the outer layer drug solution B to the external spraying equipment and adjust the spraying parameters of the spraying equipment according to the preset standard. Continue to spray the outer layer drug solution B of a predetermined thickness on the outer wall of the middle layer coating in step S33, and wait 1-300s for the solvent to evaporate to a predetermined degree to obtain the outer layer coating. S35. The balloon (4) from step S34 is left to stand and dry for 24 hours to dry the drug on the outer wall of the balloon (4) to a predetermined degree to prepare the drug coating (5).

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