Drug delivery device preparation method and drug delivery device

Abstract

The present invention discloses a method for preparing a drug delivery device and a drug delivery device. The monodisperse drug particles in the drug delivery device prepared by the present invention have a stronger binding force with the balloon surface, increasing the contact surface area with the balloon surface while significantly reducing the contact area with blood vessels during delivery, thereby reducing frictional resistance and drug shedding. Furthermore, because the drug particles are monodisperse, drug particles that fall off during expansion also fall off individually, preventing the formation of multiple drug particle aggregates, thereby avoiding vascular embolism caused by oversized particles. Furthermore, by providing a lubricant layer, the present invention significantly reduces frictional resistance during delivery, making delivery to distal tortuous and narrow blood vessels easier, while also reducing vascular damage caused by excessive pushing force.

Description

Technical field

[0001] The present invention relates to the technical field of vascular disease treatment, in particular to the technical field of a preparation method of a drug delivery device and a drug delivery device. [Background Technology]

[0002] Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction and peripheral arterial disease.

[0003] Percutaneous angioplasty and percutaneous endovascular stenting are innovative technologies for treating vascular stenosis, significantly improving treatment outcomes for patients with atherosclerotic disease. However, drug-eluting stents still face risks such as in-stent restenosis and late stent thrombosis. Furthermore, due to their rigid metal structure and susceptibility to fracture, drug-eluting stents remain less effective in treating tortuous intracranial and lower extremity vessels.

[0004] To address the drawbacks of drug-eluting stents, "intervention-free" drug-eluting balloons have been invented for the treatment of atherosclerosis. These balloons utilize an angioplasty procedure with an anti-proliferative drug coated on the balloon surface. The drug is then delivered to the target lesion via a balloon catheter. Upon balloon expansion, the anti-proliferative drug is transferred to the vessel wall, thereby permanently inhibiting the proliferation of vascular smooth muscle, reducing vascular stenosis, and achieving a therapeutic effect. However, current drug-eluting balloons still face the following challenges: 1) Poor drug coating durability leads to significant drug loss during delivery. Studies have shown that about 80% of the drugs in drug-eluting balloons currently on the market are lost during the delivery process (J Am Coll Cardiol Intv. 2020, 13(24)2840–2849.); a large amount of drugs are lost before reaching the lesion site. For tortuous lesions and diffuse long lesions, it is difficult to deliver and transfer an effective amount of drugs, resulting in poor therapeutic effects; 2) The drug coating produces a large number of particles during the delivery and expansion process, and the size of the shed particles is as high as 300μm or more, which can easily cause vascular embolism and "slow blood flow" and "no reflow" phenomena. "Slow blood flow" and "no reflow" phenomena are associated with poor clinical effects, and can easily cause embolic stroke in intracranial arteries with thinner blood vessels, and increase the amputation rate of lower limb arteries, seriously affecting the treatment effect; 3) The balloon is relatively hard and the friction resistance of the drug coating is large. For tortuous blood vessels, the drug balloon is difficult to deliver to the lesion site, resulting in treatment failure; these problems all restrict the clinical effect of drug-eluting balloons.

[0005] Existing drug coating methods, such as drip coating, dip coating, ultrasonic spray coating, and gas-assisted spray coating, produce drug coatings in which drug particles adhere to each other, forming sheet-like or film-like aggregates. Even if individual drug particles are small, they can break off during delivery or expansion, often forming large aggregates that can inevitably cause embolism in distal blood vessels. [Summary of the invention]

[0006] The purpose of the present invention is to solve the problems in the prior art and to propose a drug delivery device preparation method and a drug delivery device, in which the drug particles have a stronger binding force with the balloon surface, which greatly reduces the contact area with the blood vessels during delivery, reduces frictional resistance, and reduces drug shedding.

[0007] To achieve the above object, the present invention provides a method for preparing a drug delivery device, comprising the following steps:

[0008] Step S1, selecting a suitable balloon body according to the requirements, adhering a nuclear pore membrane to the surface of the balloon body, wherein the nuclear pore membrane is provided with a plurality of through holes;

[0009] Step S2, selecting a suitable active drug alone or selecting a suitable active drug solution and an excipient and dissolving them in a solvent to prepare a drug solution;

[0010] Step S3, then coating the above-mentioned drug solution on the surface of the balloon body so that the drug solution is dispersed in the pores of the nucleopore membrane. When the drug solution slowly evaporates, the active drug precipitates and crystallizes or deposits to form particles. Before the drug solution completely evaporates, the nucleopore membrane is removed.

[0011] Step S4: leaving it to dry to obtain the drug delivery device.

[0012] Preferably, the solvent is selected from at least one of ethanol, butanol, acetone, tetrahydrofuran, cyclohexane, dichloromethane, ethyl acetate, propyl acetate, methyl acetate, butyl acetate, carbon tetrachloride, butanone, benzene, n-heptane, n-hexane, methanol, toluene, xylene, cyclohexanone, and dioxane.

[0013] Preferably, the balloon body is in an inflated state during the coating preparation process, and the inflation pressure of the balloon body during the coating preparation process is lower than its nominal pressure.

[0014] Preferably, in step S3, the balloon body after removing the nuclear pore membrane is immersed again in the active drug solution for further crystallization. The active drug particles formed on the surface of the balloon body through the pores of the nuclear pore membrane in the previous step serve as crystallization nuclei, while no active drug particles are formed in the area covered by the nuclear pore membrane and crystals cannot be precipitated. The active drug particles formed by re-immersion in the active drug solution are still single-particle dispersed drug particles.

[0015] Preferably, the thickness of the nuclear pore membrane is 6 μm-50 μm, the pore size is 0.01 μm-100 μm, and the porosity is 1%-90%.

[0016] Preferably, the active drug is at least one of rapamycin, rapamycin derivatives, dexamethasone, paclitaxel, taxol, docetaxel, probucol, colchicine, heparin, warfarin sodium, vitamin K antagonists, aspirin, prostaglandins, salvianolic acid, nitrates, lysine, dipyridamole, ampicillin, cephalosporins, sulfadiazine, streptomycin sulfate, cefoxitin, nalidixic acid, pipemidic acid, daunorubicin, doxorubicin, carboplatin, and macrolides.

[0017] Preferably, the excipient is one or more of lacamine salt, citric acid, resveratrol, polybutyl methacrylate, stearamide, isooctyl palmitate, linoleic acid, linolenic acid, glyceryl monooleate, iohexol, iopromide, urea, sorbitol, polysorbate, trihexyl citrate, phospholipids, ropizine matrix, cholesterol, vitamin E, vitamin E polyethylene glycol succinate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polybutylene succinate, polyhydroxyalkanoate, polycaprolactone, polyethylene adipate, polyhydroxybutyrate valerate copolymer, polyvinyl pyrrolidone, polyvinyl alcohol, poloxamer, and Tween.

[0018] Another object of the present invention is to propose a drug delivery device prepared by the drug delivery device preparation method described in any of the above items, comprising an expandable and contractible balloon body and a drug coating provided on the surface of the balloon body, wherein the drug coating comprises a plurality of drug particles provided on the surface of the balloon body, the drug particles are distributed independently of each other, and the drug particles contain active drug ingredients.

[0019] Preferably, the drug coating further comprises a lubricant layer provided on the surface of the balloon body, the drug particles are distributed in the lubricant layer, and the lubricant layer is at least one of a hydrophilic lubricant sodium stearyl fumarate and a hydrophobic lubricant stearic acid, magnesium stearate, and zinc stearate.

[0020] Preferably, the drug particles have a size of less than or equal to 25 μm.

[0021] Preferably, the drug particles have a size of less than or equal to 20 μm.

[0022] Preferably, the drug particles have a size of less than or equal to 10 μm.

[0023] The present invention provides a method for preparing a drug delivery device and a drug delivery device with the following beneficial effects: The monodisperse drug particles in the drug delivery device have a stronger binding force with the balloon surface, increasing the contact surface area with the balloon surface while significantly reducing the contact area with the blood vessels during delivery, thereby reducing frictional resistance and drug shedding. Furthermore, because the drug particles are monodisperse, the drug particles that fall off during expansion also fall off individually, without forming multiple drug particle aggregates. This prevents vascular embolism caused by excessively large particle size, whereas conventional drug balloon drug particles fall off in the form of flake-like particle aggregates, resulting in large drug particles that are highly susceptible to vascular embolism. Furthermore, by providing a lubricant layer, the present invention significantly reduces frictional resistance during delivery, making it easier to deliver the drug to distal, tortuous, and narrow blood vessels while reducing vascular damage caused by excessive pushing force.

[0024] The features and advantages of the present invention will be described in detail through embodiments with reference to the accompanying drawings.

Brief Description of the Drawings

[0025] Figure 1 It is a structural schematic diagram of a drug delivery device of the present invention.

[0026] Figure 2 It is a partially enlarged structural schematic diagram of a drug delivery device of the present invention.

[0027] Figure 3 This is a microscope image of surfactant drug particles in a drug delivery device of the present invention after magnification 500 times.

[0028] In the figure: 1-balloon body, 2-drug coating, 21-drug particles, 22-lubricant layer. [Specific implementation method]

[0029] To make the objectives, technical solutions, and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and examples. However, it should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the scope of the present invention. In addition, in the following description, descriptions of well-known structures and technologies are omitted to avoid unnecessary confusion of the present invention.

[0030] In the description of the present invention, it should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it may be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it may be directly connected to the other element or indirectly connected to the other element.

[0031] In the description of the present invention, it should be noted that the terms "center", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, or the orientations or positional relationships in which the inventive product is usually placed when in use. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", "third" and the like are only used to distinguish the description and cannot be understood as indicating or implying relative importance. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of such features. In the description of the present invention, "multiple" means two or more, unless otherwise clearly and specifically defined. "Several" means one or more, unless otherwise clearly and specifically defined.

[0032] In the description of the present invention, it should also be noted that, unless otherwise expressly specified or limited, the terms "disposed," "installed," "connected," and "connected" should be understood in a broad sense. For example, they may refer to fixed connections, detachable connections, or integral connections; they may refer to mechanical connections or electrical connections; they may refer to direct connections or indirect connections through an intermediate medium; and they may refer to internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on the specific circumstances.

[0033] Example 1:

[0034] The present invention provides a method for preparing a drug delivery device, comprising the following steps:

[0035] Step S1: Take a balloon body 1 and carefully attach a nuclear pore membrane with a thickness of 10 μm, a pore size of 5 μm, and a porosity of 80% to the surface of the balloon body 1;

[0036] Step S2, dissolving rapamycin, polyvinylpyrrolidone, and poly(lactic-co-glycolic acid) (PLGA) in acetone to concentrations of 20 mg / ml, 15 mg / ml, and 20 mg / ml, respectively, to prepare a drug solution;

[0037] Step S3: Then, the above-mentioned drug solution is coated on the surface of the balloon body 1 to make the drug concentration reach 2 μg / mm 2The drug solution is dispersed in the pores of the nucleopore membrane and then dried in a vacuum oven at room temperature. As the drug solution slowly evaporates, the active drug precipitates, crystallizes, or deposits to form particles. The nucleopore membrane is removed before the drug solution completely evaporates. The precise spraying or coating parameters required to achieve the desired drug concentration require multiple experiments. This method is a common procedure familiar to those skilled in the art.

[0038] Step S4: drying overnight, packaging, and ethylene oxide sterilization to obtain the drug delivery device.

[0039] Preferably, the balloon body 1 is in an inflated state during the coating preparation process, and the inflation pressure of the balloon body 1 during the coating preparation process is lower than its nominal pressure. For example, if the nominal pressure of the balloon is 6 atm, the inflation pressure of the balloon during the coating preparation process can be 1 atm, 2 atm, 3 atm, 4 atm, or 5 atm.

[0040] Example 2:

[0041] This embodiment provides another method for preparing a drug delivery device, comprising the following steps:

[0042] Step S1: Take a balloon body 1 and carefully attach a nuclear pore membrane with a thickness of 10 μm, a pore size of 5 μm, and a porosity of 80% to the surface of the balloon body 1;

[0043] Step S2, dissolving paclitaxel, polyvinylpyrrolidone, and poly(lactic-co-glycolic acid) (PLGA) in acetone to concentrations of 20 mg / ml, 15 mg / ml, and 20 mg / ml, respectively, to prepare a drug solution;

[0044] Step S3: Then, the above-mentioned drug solution is coated on the surface of the balloon body 1 to make the drug concentration reach 2 μg / mm 2 , so that the drug solution is dispersed in the pores of the nuclear pore membrane, and placed in a vacuum oven to dry at room temperature. When the drug solution slowly evaporates, the active drug precipitates and crystallizes or deposits to form particles. Before the drug solution completely evaporates, the nuclear pore membrane is removed;

[0045] Step S4: drying overnight, packaging, and ethylene oxide sterilization to obtain the drug delivery device.

[0046] Example 3:

[0047] This embodiment provides another method for preparing a drug delivery device, comprising the following steps:

[0048] Step S1: Take a balloon body 1 and carefully attach a nuclear pore membrane with a thickness of 10 μm, a pore size of 5 μm, and a porosity of 80% to the surface of the balloon body 1;

[0049] Step S2, dissolving rapamycin in acetone at a concentration of 20 mg / ml to prepare a drug solution;

[0050] Step S3: Then, the above-mentioned drug solution is coated on the surface of the balloon body 1 to make the drug concentration reach 2 μg / mm 2 , so that the drug solution is dispersed in the pores of the nuclear pore membrane, and placed in a vacuum oven to dry at room temperature. When the drug solution slowly evaporates, the active drug precipitates and crystallizes or deposits to form particles. Before the drug solution completely evaporates, the nuclear pore membrane is removed;

[0051] Step S4: drying overnight, packaging, and ethylene oxide sterilization to obtain the drug delivery device.

[0052] Example 4:

[0053] This embodiment provides another method for preparing a drug delivery device, comprising the following steps:

[0054] Step S1: Take a balloon body 1 and carefully attach a nuclear pore membrane with a thickness of 10 μm, a pore size of 5 μm, and a porosity of 80% to the surface of the balloon body 1;

[0055] Step S2, dissolving rapamycin in a mixed solvent of ethyl acetate and n-heptane at a concentration of 20 mg / ml to prepare a drug solution;

[0056] Step S3, the above-mentioned drug solution is coated on the surface of the balloon body 1, so that the drug solution is dispersed in the pores of the nucleopore membrane, and the balloon body 1 is placed in a vacuum oven for drying at room temperature. When the drug solution slowly evaporates, the active drug precipitates crystals or deposits to form particles. Before the drug solution completely evaporates, the nucleopore membrane is removed, and the balloon body 1 is immersed in rapamycin solution (the solvent is ethyl acetate, the concentration is 40 mg / ml) for 5 minutes, and then taken out. The drug concentration is 3 μg / mm 2 ;

[0057] Step S4: drying overnight, packaging, and ethylene oxide sterilization to obtain the drug delivery device.

[0058] Embodiment 5:

[0059] This embodiment provides another method for preparing a drug delivery device, comprising the following steps:

[0060] Step S1: Take a balloon body 1 and carefully attach a nuclear pore membrane with a thickness of 10 μm, a pore size of 5 μm, and a porosity of 80% to the surface of the balloon body 1;

[0061] Step S2, dissolving rapamycin, polyvinyl pyrrolidone, and poly(lactic-co-glycolic acid) (PLGA) in acetone at a concentration of 20 mg / ml to prepare a drug solution;

[0062] Step S3, the above-mentioned drug solution is coated on the surface of the balloon body 1, so that the drug solution is dispersed in the pores of the nucleopore membrane, and the balloon body 1 is placed in a vacuum oven for drying at room temperature. When the drug solution slowly evaporates, the active drug precipitates crystals or deposits to form particles. Before the drug solution completely evaporates, the nucleopore membrane is removed, and the balloon body 1 is immersed in rapamycin solution (the solvent is ethyl acetate, the concentration is 40 mg / ml) for 5 minutes, and then taken out. The drug concentration is 3 μg / mm 2 After the solution is completely evaporated, a sodium stearyl fumarate solution (the solvent is a mixed solvent of ethanol and water, the concentration is 30 mg / ml) is drop-coated or ultrasonically sprayed on the balloon surface to a coating thickness of 10 μm to prepare a lubricant layer;

[0063] Step S4: drying overnight, packaging, and ethylene oxide sterilization to obtain the drug delivery device.

[0064] Comparative Example 1

[0065] (1) Rapamycin, polyvinylpyrrolidone, and poly(lactic-co-glycolic acid) (PLGA) were dissolved in acetone at concentrations of 20 mg / ml, 15 mg / ml, and 20 mg / ml, respectively.

[0066] (2) Take a balloon and spray the above drug solution on the balloon surface by drop coating or ultrasonic spraying to make the drug concentration reach 2 μg / mm 2 After packaging and ethylene oxide sterilization, a drug-coated balloon catheter is obtained.

[0067] Coating fastness test

[0068] Simulating the actual surgical procedure, the drug delivery devices in the examples and comparative examples were passed through an in vitro simulation model (with PBS as the fluidity), and then the residual drug content on the product after delivery was tested using high performance liquid chromatography (HPLC). The coating firmness of the product was calculated using the following formula:

[0069]

[0070] Obtain the following table:

[0071] Firmness Example 1 98.7％ Example 2 97.9％ Example 3 98.2％ Example 4 98.4％ Example 5 99.3％ Comparative Example 1 33％

[0072] The table above shows that Examples 1-5 exhibited a high firmness of 97.9% to 99.3%, indicating a drug loss of only 0.7% to 2.1% during simulated delivery. This significantly outperforms the 33% firmness of the sheet or film-like drug coating in Comparative Example 1, which exhibited a drug loss of 67% during delivery. This demonstrates that the monodisperse drug particles in the drug delivery device prepared by the present invention exhibit stronger binding forces with the balloon surface. The monodisperse drug particles increase their specific surface area in contact with the balloon surface, significantly reducing their contact area with the blood vessel during delivery, thereby lowering frictional resistance and minimizing drug shedding.

[0073] Insoluble particulate matter test

[0074] To simulate an actual surgical procedure, the drug delivery devices described in the examples and comparative examples were run through an in vitro simulation model (using PBS as the fluidity). Upon delivery to the target site, the balloon was inflated to nominal pressure and held for 1 minute. The balloon was then withdrawn, and the fluid flowing through the system was collected. A particle analyzer was used to measure the size and number of insoluble particles released during the delivery and expansion process. The data obtained are shown in the following table:

[0075]

[0076] From the insoluble particle test data, no insoluble particles ≥25 μm and ≥100 μm were detected in Examples 1-5, and the number of shed particles was even smaller. The maximum size of the insoluble particles in Comparative Example 1 was above 100 μm, indicating that the drug delivery device prepared by the present invention has a unique monodisperse drug particle structure, and the particles shed are also individually shed, and multiple drug particle aggregates are not formed, thereby avoiding vascular embolism caused by excessively large particle size.

[0077] Coating friction test

[0078] Using a push force tester, the drug delivery devices in the examples and comparative examples were pushed to a predetermined position, and the maximum push force during the pushing process was recorded. The data obtained are shown in the following table:

[0079] Maximum pushing resistance (N) Example 1 0.43 Example 2 0.51 Example 3 0.40 Example 4 0.44 Example 5 0.32 Comparative Example 1 1.6

[0080] It can be seen that the pushing resistance of Examples 1-5 is greatly reduced compared with that of Comparative Example 1, indicating that the coating friction resistance of the drug delivery device prepared by the present invention is smaller than that of the traditional drug coating, and it is easier to deliver to the tortuous and narrow blood vessels at the distal end; at the same time, the friction force of Example 5 after adding the lubricant coating is significantly reduced, reducing the vascular damage caused by excessive pushing force.

[0081] Example 6:

[0082] See Figure 1 、 Figure 2 and Figure 3This embodiment provides a drug delivery device made by the method for making a drug delivery device described in any of the above embodiments, comprising an expandable and contractible balloon body 1 and a drug coating 2 disposed on the surface of the balloon body 1. The drug coating 2 includes a plurality of drug particles 21 disposed on the surface of the balloon body 1. The drug particles 21 are independently distributed and contain an active pharmaceutical ingredient. The monodisperse drug particles in the drug delivery device prepared by the present invention have a stronger binding force with the balloon surface, increase the contact surface area with the balloon surface, and significantly reduce the contact area with blood vessels during delivery, thereby reducing frictional resistance and drug shedding. Furthermore, because the drug particles are monodisperse, the drug particles that fall off during expansion are individually shed, rather than forming multiple drug particle aggregates. This prevents excessively large particles from causing vascular embolism. In contrast, drug particles from conventional drug balloons fall off in the form of flake-like aggregates, resulting in large drug particles that are highly susceptible to vascular embolism.

[0083] See Figure 1 、 Figure 2 The drug coating 2 further includes a lubricant layer 22 disposed on the surface of the balloon body 1. The drug particles 21 are distributed within the lubricant layer 22, with the drug particles 21 protruding from the lubricant layer 22. The lubricant layer 22 comprises at least one of a hydrophilic lubricant sodium stearyl fumarate and a hydrophobic lubricant selected from stearic acid, magnesium stearate, and zinc stearate. The provision of the lubricant layer significantly reduces frictional resistance during delivery, facilitating delivery to distal, tortuous, and narrow blood vessels while minimizing vascular damage caused by excessive pushing force.

[0084] Preferably, the size of the drug particles 21 is less than or equal to 25 μm. In another optional embodiment, the size of the drug particles 21 is less than or equal to 20 μm; in another optional embodiment, the size of the drug particles 21 is less than or equal to 10 μm.

[0085] Preferably, the drug particles 21 are drug crystals / amorphous particles formed by a single active drug or are drug particles formed by mixing an active drug with an excipient.

[0086] Preferably, the active drug is at least one of rapamycin, rapamycin derivatives, dexamethasone, paclitaxel, taxol, docetaxel, probucol, colchicine, heparin, warfarin sodium, vitamin K antagonists, aspirin, prostaglandins, salvianolic acid, nitrates, lysine, dipyridamole, ampicillin, cephalosporins, sulfadiazine, streptomycin sulfate, cefoxitin, nalidixic acid, pipemidic acid, daunorubicin, doxorubicin, carboplatin, and macrolides.

[0087] Preferably, the excipient is one or more of lacamine salt, citric acid, resveratrol, polybutyl methacrylate, stearamide, isooctyl palmitate, linoleic acid, linolenic acid, glyceryl monooleate, iohexol, iopromide, urea, sorbitol, polysorbate, trihexyl citrate, phospholipids, ropizine matrix, cholesterol, vitamin E, vitamin E polyethylene glycol succinate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polybutylene succinate, polyhydroxyalkanoate, polycaprolactone, polyethylene adipate, polyhydroxybutyrate valerate copolymer, polyvinyl pyrrolidone, polyvinyl alcohol, poloxamer, and Tween.

[0088] Working process of the present invention:

[0089] During operation of the drug delivery device of the present invention, the balloon body 1 is in a contracted state during delivery. When the drug delivery device is delivered to the vascular lesion, the balloon body 1 is expanded, and the drug particles 21 adhere to the inner wall of the blood vessel, so that the drug particles 21 can directly act on the inner wall of the blood vessel to treat the vascular lesion.

[0090] It should be noted that although the above embodiments have been described herein, this does not limit the scope of patent protection of the present invention. Therefore, based on the innovative concept of the present invention, changes and modifications to the embodiments described herein, or equivalent structural or equivalent process transformations made using the contents of the present invention's description and drawings, and direct or indirect application of the above technical solutions to other related technical fields, are all included in the scope of protection of the present invention's patent.

Claims

1. A method for preparing a drug delivery device, characterized in that: The following steps are involved: Step S1, selecting a suitable model of balloon body (1) according to the requirements, adhering a nuclear pore membrane to the surface of the balloon body (1), wherein the nuclear pore membrane is provided with a plurality of through-holes, wherein the thickness of the nuclear pore membrane is 6 μm-50 μm, the pore size is 0.01 μm-100 μm, and the porosity is 1%-90%; Step S2, selecting a suitable active drug alone or selecting a suitable active drug solution and an excipient and dissolving them in a solvent to prepare a drug solution; Step S3, then coating the above-mentioned drug solution on the surface of the balloon body (1), so that the drug solution is dispersed in the holes of the nuclear pore membrane. When the drug solution slowly evaporates, the active drug precipitates and crystallizes or deposits to form particles. Before the drug solution completely evaporates, the nuclear pore membrane is removed. The balloon body (1) after removing the nuclear pore membrane is immersed in the active drug solution again for further crystallization. The active drug particles formed on the surface of the balloon body (1) through the holes of the nuclear pore membrane serve as crystal nuclei, while no active drug particles are formed in the area covered by the nuclear pore membrane, and no crystals can be precipitated. The active drug particles formed by immersing the balloon body (1) in the active drug solution again are still single-particle dispersed drug particles. Step S4: leaving it to dry to obtain the drug delivery device.

2. A method for preparing a drug delivery device according to claim 1, characterized in that: The solvent is selected from at least one of ethanol, butanol, acetone, tetrahydrofuran, cyclohexane, dichloromethane, ethyl acetate, propyl acetate, methyl acetate, butyl acetate, carbon tetrachloride, butanone, benzene, n-heptane, n-hexane, methanol, toluene, xylene, cyclohexanone, and dioxane.

3. A method for preparing a drug delivery device according to claim 1, characterized in that: The balloon body (1) is in an inflated state during the coating preparation process, and the inflation pressure of the balloon body (1) during the coating preparation process is lower than its nominal pressure.

4. A method for preparing a drug delivery device according to claim 1, characterized in that: The active drug is at least one of rapamycin, rapamycin derivatives, dexamethasone, paclitaxel, taxol, docetaxel, probucol, colchicine, heparin, warfarin sodium, vitamin K antagonists, aspirin, prostaglandins, salvianolic acid, nitrates, lysine, dipyridamole, ampicillin, cephalosporins, sulfadiazine, streptomycin sulfate, cefoxitin, nalidixic acid, pipemidic acid, daunorubicin, doxorubicin, carboplatin, and macrolides.

5. The method for preparing a drug delivery device according to claim 1, wherein: The excipient is one or more of lacamine salt, citric acid, resveratrol, polybutyl methacrylate, stearamide, isooctyl palmitate, linoleic acid, linolenic acid, monoolein, iohexol, iopromide, urea, sorbitol, polysorbate, trihexyl citrate, phospholipids, ropizine matrix, cholesterol, vitamin E, vitamin E polyethylene glycol succinate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, polybutylene succinate, polyhydroxyalkanoate, polycaprolactone, polyethylene adipate, polyhydroxybutyrate valerate copolymer, polyvinyl pyrrolidone, polyvinyl alcohol, poloxamer, and Tween.

6. A drug delivery device produced by the method for producing a drug delivery device according to any one of claims 1 to 5, characterized in that: The invention comprises an expandable and contractible balloon body (1) and a drug coating (2) provided on the surface of the balloon body (1), wherein the drug coating (2) comprises a plurality of drug particles (21) provided on the surface of the balloon body (1), wherein the drug particles (21) are distributed independently of each other and contain active drug ingredients. The drug coating (2) further comprises a lubricant layer (22) provided on the surface of the balloon body (1), wherein the drug particles (21) are distributed in the lubricant layer (22) and protrude from the lubricant layer (22), and the lubricant layer (22) is at least one of a hydrophilic lubricant sodium stearyl fumarate and a hydrophobic lubricant stearic acid, magnesium stearate, and zinc stearate.

7. A drug delivery device according to claim 6, characterized in that: The drug particles (21) are drug crystals / amorphous particles formed by a single active drug or are drug particles formed by mixing an active drug with an excipient. The size of the drug particles (21) is less than or equal to 10 μm.

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