Preparation method and application of drug coating on the surface of drug balloon

Abstract

The present invention provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps: dissolving a drug and a carrier in a solvent to respectively configure a supersaturated solution and an unsaturated solution; using the supersaturated solution and the unsaturated solution to dip-coat and spray the balloon in turn; the number of spraying is 5-200 times. The present invention can first coat a layer of drug crystal nuclei on the balloon surface by dip-coating, which helps to form ideal crystals in the subsequent spraying process, can better control the growth of crystals generated by spraying, and improve the firmness of the drug coating. The drug balloon prepared by the method can be used for the treatment of stenosis of the lumen of blood vessels, urethra, and ureter, and plays a role in inhibiting restenosis of the lumen.

Description

Technical Field

[0001] The invention relates to the technical field of drug balloons, and in particular to a preparation method and application of a drug coating on the surface of a drug balloon. Background Art

[0002] In recent years, the concept of interventional non-implantation has attracted more and more attention for the treatment of vascular stenosis. Drug-eluting balloon is a therapeutic balloon drug release technology developed on the basis of balloon dilatation or angioplasty. This technology is to coat the surface of the balloon with drugs that have anti-restenosis effects. When the drug-eluting balloon reaches the dilation position to dilate the blood vessel during the dilatation surgery, the drugs on the surface of the balloon will also adhere to the blood vessel wall and enter the blood vessel, playing a role in inhibiting the restenosis of the blood vessel.

[0003] At present, there are many methods for preparing the surface drug coating of drug-eluting balloons, but not all preparation methods can produce stable and effective drug crystal coatings. When the balloon is delivered to the target lesion in the blood vessel, the drug coating will undergo a blood flow flushing process, and the drug coating will fall off during this process, resulting in a reduction in the initial drug delivered to the target lesion, making the drug's ability to inhibit restenosis poor. Summary of the invention

[0004] Therefore, the technical problem to be solved by the present invention is to overcome the defect in the prior art that the surface drug coating of the drug balloon is easily detached when it is delivered to the target lesion location in the blood vessel, resulting in a reduction in the initial drug delivered to the target lesion location and poor ability of the drug to inhibit restenosis.

[0005] To this end, the present invention provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0006] Dissolving the drug and the carrier in a solvent to prepare a supersaturated solution and an unsaturated solution respectively;

[0007] The balloon can be dip-coated and spray-coated with a supersaturated solution and an unsaturated solution in sequence; the spraying times are 5-200 times.

[0008] Preferably, the spraying times is 10-25 times.

[0009] Optionally, the dipping time is 1-30 min.

[0010] Optionally, during dipping, the dipping is carried out while stirring, and the stirring speed is 10-200rps.

[0011] Optionally, the balloon is dried after dipping, the drying temperature is 30-70° C., and the drying time is 1-30 min.

[0012] Optionally, the balloon is placed on a sprayer for spraying immediately after drying.

[0013] Optionally, the spraying flow rate during spraying is 0.5-1 mL / h.

[0014] Optionally, the drug is selected from at least one of paclitaxel, rapamycin, a paclitaxel derivative and a rapamycin derivative.

[0015] Optionally, the carrier is selected from at least one of phenolic compounds, pyrone compounds, sugar alcohol compounds, plasticizers, amphiphilic polymers, amide compounds, nonionic surfactants, and nonionic contrast agents. Specifically, the phenolic compounds include tea polyphenols, tocopherol, catechol, gallic acid, eugenol, grape polyphenols and / or thymol; the pyrone compounds include maltol, ethyl maltol, coumarin, tartaric acid, flavonoids and / or flavonoid compounds; the sugar alcohol compounds include maltitol, xylitol, sorbitol, erythritol, mannitol and / or sucralose; the plasticizer includes dibutyl phthalate (DBP), dioctyl phthalate (D The invention relates to an aqueous solution of at least one alkylene oxide (alkylene oxide), wherein the amphiphilic polymer comprises polyisobutylene-1-poly (N,N-dimethylacrylamide), polyethyleneimine, polylactic acid-glycolic acid copolymer (PLGA) and / or polyvinyl pyrrolidone; the amide compound comprises urea, N,N-dimethylformamide, N,N-dimethylacetamide and / or stearic acid amide; the nonionic surfactant comprises polysorbate, sorbitan fatty acid, polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether, polyoxyethylene-polyoxyethylene copolymer and / or pluronic; the nonionic contrast agent comprises iopamidol, iohexol and / or iopromide.

[0016] Optionally, the solvent is selected from at least one of water, alcohol compounds, aliphatic hydrocarbon compounds, ether compounds, halogenated hydrocarbon compounds, ketone compounds, tetrahydrofuran, and acetonitrile.

[0017] Optionally, the mass ratio of the drug to the carrier in the supersaturated solution is (0.1-80):1; the mass ratio of the drug to the carrier in the unsaturated solution is (0.1-100):1.

[0018] A method for preparing a surface drug coating of a drug balloon. The prepared drug balloon is used for luminal treatment at the locations of blood vessels, urethra, ureter, and Eustachian tube; the blood vessels include coronary vessels, peripheral vessels, intracranial vessels, and arteriovenous fistula vessels; the urethra includes the urethra at the penis, prostate, bulb, and membranous parts.

[0019] The technical solution of the present invention has the following advantages:

[0020] 1. The present invention provides a method for preparing a surface drug coating of a drug balloon. Compared with the spray coating method commonly used in the current coating preparation of drug balloons, the present invention uses dip coating and spray coating in combination. By dip coating, a layer of drug crystal nuclei can be first coated on the surface of the balloon, which helps to form ideal crystals in the subsequent spraying process, can better control the growth of crystals generated by spraying, and improve the firmness of the drug coating.

[0021] 2. The present invention provides a method for preparing a surface drug coating of a drug balloon. The preparation method is simple and only requires simple dipping and spraying to obtain a drug coating of an ideal crystal form, and the preparation cost is low. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 This is a crystal structure diagram of the drug coating on the surface of the drug balloon provided in Example 1 of the present invention; the scale in the figure is 20 μm;

[0024] Figure 2 This is a crystal structure diagram of the drug coating on the surface of the drug balloon provided in Example 2 of the present invention; the scale in the figure is 20 μm. DETAILED DESCRIPTION

[0025] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0026] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0027] The balloon in the embodiment of the present invention is a homemade balloon made of nylon material, and the specific preparation method is as follows:

[0028] Preforming: The two ends of the balloon tube are stretched thin, and a certain proportion of bubble length is reserved in the middle to obtain a preformed balloon;

[0029] Mold molding: Place the preformed balloon into a balloon mold for blow molding, and inject nitrogen into the preformed balloon. The temperature of the balloon mold is controlled at 110-120°C, and the pressure of the nitrogen in the preformed balloon is 300-400psi.

[0030] Paclitaxel, catalog number P815862, was purchased from Maclean;

[0031] Mannitol, catalog number M6266, was purchased from Maclean;

[0032] Maltol was purchased from Maclean with the product number M813318;

[0033] Tea polyphenols were purchased from Maclean with the product number T821916;

[0034] Rapamycin was purchased from Maclean with catalog number R817296.

[0035] Example 1

[0036] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0037] Prepare the dipping solution: weigh 300 mg of paclitaxel and 10 mg of mannitol, dissolve them in 10 mL of acetone, stir for 1 min, and ultrasonicate for 20 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0038] Prepare the spray solution: weigh 80 mg of paclitaxel and 15 mg of maltol and dissolve them in 6 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0039] Dip coating: The dipping solution was stirred continuously at a speed of 50 rps, and then the balloon was placed in the dipping solution and kept stirring for 5 minutes. The balloon was taken out and then placed in an oven and dried at 40°C for 3 minutes.

[0040] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 0.5 mL / h and the number of spraying times is 10 times.

[0041] Example 2

[0042] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0043] Prepare the dipping solution: weigh 300 mg of paclitaxel and 10 mg of mannitol, dissolve them in 10 mL of acetone, stir for 1 min, and ultrasonicate for 20 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0044] Prepare the spray solution: weigh 80 mg of paclitaxel and 15 mg of maltol and dissolve them in 6 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0045] Dip coating: The dipping solution was stirred continuously at a speed of 50 rps, and then the balloon was placed in the dipping solution and kept stirring for 5 minutes. The balloon was taken out and then placed in an oven and dried at 40°C for 3 minutes.

[0046] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 0.5 mL / h and the number of spraying times is 15 times.

[0047] Example 3

[0048] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0049] Prepare the dipping solution: weigh 300 mg of paclitaxel and 10 mg of mannitol, dissolve them in 10 mL of acetone, stir for 1 min, and ultrasonicate for 20 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0050] Prepare the spray solution: weigh 80 mg of paclitaxel and 15 mg of maltol and dissolve them in 6 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0051] Dip coating: The dipping solution was stirred continuously at a speed of 50 rps, and then the balloon was placed in the dipping solution and kept stirring for 5 minutes. The balloon was taken out and then placed in an oven and dried at 40°C for 3 minutes.

[0052] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 0.5 mL / h and the number of spraying times is 20 times.

[0053] Example 4

[0054] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0055] Prepare the dipping solution: weigh 300 mg of paclitaxel and 10 mg of mannitol, dissolve them in 10 mL of acetone, stir for 1 min, and ultrasonicate for 20 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0056] Prepare the spray solution: weigh 80 mg of paclitaxel and 15 mg of maltol and dissolve them in 6 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0057] Dip coating: The dipping solution was stirred continuously at a speed of 50 rps, and then the balloon was placed in the dipping solution and kept stirring for 5 minutes. The balloon was taken out and then placed in an oven and dried at 40°C for 3 minutes.

[0058] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 0.5 mL / h and the number of spraying times is 25 times.

[0059] Example 5

[0060] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0061] Prepare the dipping solution: weigh 200 mg of paclitaxel and 10 mg of tea polyphenols and dissolve them in 10 mL of ethyl acetate, stir for 1 min, and ultrasonicate for 10 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0062] Prepare the spray solution: weigh 100 mg of paclitaxel and 30 mg of tea polyphenols and dissolve them in 10 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0063] Dip coating: The dipping solution was stirred continuously at a speed of 50 rps, and then the balloon was placed in the dipping solution and kept stirring for 5 minutes. The balloon was taken out and then placed in an oven and dried at 40°C for 1 minute.

[0064] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 1 mL / h and the number of spraying times is 20 times.

[0065] Example 6

[0066] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0067] Prepare the dipping solution: weigh 200 mg of paclitaxel and 10 mg of tea polyphenols and dissolve them in 10 mL of ethyl acetate, stir for 1 min, and ultrasonicate for 10 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0068] Prepare the spray solution: weigh 100 mg of paclitaxel and 30 mg of tea polyphenols and dissolve them in 10 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0069] Dip coating: The dipping solution was stirred continuously at a speed of 50 rps, and then the balloon was placed in the dipping solution and kept stirring for 5 minutes. The balloon was taken out and then placed in an oven and dried at 40°C for 1 minute.

[0070] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 1 mL / h and the number of spraying times is 25 times.

[0071] Example 7

[0072] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0073] Prepare the dipping solution: weigh 200 mg of rapamycin and 10 mg of tea polyphenols and dissolve them in 10 mL of ethyl acetate, stir for 1 min, and perform ultrasonic dipping for 10 min at a frequency of 60 Hz and a temperature of 35°C.

[0074] Prepare the spray solution: weigh 100 mg of rapamycin and 30 mg of tea polyphenols and dissolve them in 10 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35 °C.

[0075] Dip coating: The dipping solution was stirred continuously at a speed of 50 rps, and then the balloon was placed in the dipping solution and kept stirring for 5 minutes. The balloon was taken out and then placed in an oven and dried at 40°C for 1 minute.

[0076] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 1 mL / h and the number of spraying times is 25 times.

[0077] Example 8

[0078] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0079] Prepare the dipping solution: weigh 200 mg of rapamycin and 2000 mg of tea polyphenols and dissolve them in 10 mL of ethyl acetate, stir for 30 min, and ultrasonicate for 10 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0080] Prepare the spray solution: weigh 100 mg of rapamycin and 1000 mg of tea polyphenols and dissolve them in 10 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0081] Dip coating: The dipping solution was stirred continuously at a speed of 10 rps, and then the balloon was placed in the dipping solution and kept stirring for 1 min. The balloon was taken out and then placed in an oven and dried at 70°C for 1 min.

[0082] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 1 mL / h and the number of spraying times is 5 times.

[0083] Example 9

[0084] This embodiment provides a method for preparing a surface drug coating of a drug balloon, comprising the following steps:

[0085] Prepare the dipping solution: weigh 200 mg of rapamycin and 2.5 mg of tea polyphenols and dissolve them in 10 mL of ethyl acetate, stir for 1 min, and ultrasonicate for 10 min to obtain a supersaturated dipping solution. The ultrasonic frequency is 60 Hz and the temperature is 35°C.

[0086] Prepare the spray solution: weigh 50 mg of rapamycin and 0.5 mg of tea polyphenols and dissolve them in 10 mL of ethanol, stir for 1 min, and ultrasonicate for 10 min to obtain an unsaturated spray solution. The ultrasonic frequency is 60 Hz and the temperature is 35 °C.

[0087] Dip coating: The dipping solution was stirred continuously at a speed of 200 rps, and then the balloon was placed in the dipping solution and kept stirring for 30 minutes. The balloon was taken out and then placed in an oven and dried at 30°C for 30 minutes.

[0088] Spraying: Put the dried balloon into the spray machine immediately and spray it several times with the spray solution. The spraying flow rate is 1 mL / h and the number of spraying times is 200 times.

[0089] Comparative Example 1

[0090] The difference from Example 1 is that dip coating is not used, and a subsequent spray coating method is directly adopted. The rest of the preparation methods and conditions are the same as those in Example 1.

[0091] Comparative Example 2

[0092] The difference from Example 1 is that spraying is not used, and a dipping method is directly adopted. The rest of the preparation methods and conditions are the same as those in Example 1.

[0093] Comparative Example 3

[0094] The difference from Example 3 is that no carrier is included in the spray solution, and the rest of the preparation method and conditions are the same as those in Example 3.

[0095] Test Example 1

[0096] Crystal size measurement:

[0097] The crystal size of the drug coating obtained in Examples 1-9 and Comparative Examples 1-3 was measured by spraying gold on the drug coating on the surface of the drug balloon, and then observing with a scanning electron microscope to measure the size and distribution range of the crystal size. The balloon specification of each example and comparative example was 8.0*40mm, and there were 10 balloons in each example and comparative example. The measurement results are shown in Table 1.

[0098] Table 1. Crystal size distribution measurement results

[0099] Sample Group Size ≥8μm(%) 3μm≤Size<8μm(%) Size<3μm(%) Example 1 79.8 19.0 1.2 Example 2 80.3 16.9 2.8 Example 3 76.5 20.3 3.2 Example 4 79.1 18.8 2.1 Example 5 82.6 15.8 1.6 Example 6 81.9 15.6 2.5 Example 7 80.1 17.1 2.8 Example 8 55.1 20.2 24.7 Example 9 46.3 19.5 34.2 Comparative Example 1 7.1 12.3 80.6 Comparative Example 2 2.1 6.3 91.6 Comparative Example 3 10.3 22.2 67.5

[0100] As can be seen from Table 1, the crystals of the drug coating on the surface of the drug balloon obtained by the present invention have an average proportion of 73.5% of crystals with a size of ≥8μm, and an average proportion of 91.7% of crystals with a size of ≥3μm. It can be seen that most of the drug coating on the surface of the drug balloon has generated large and uniform crystals. For comparative examples 1-3, the average proportion of crystals with a size of ≥8μm is 6.5%, and the average proportion of crystals with a size of ≥3μm is 20.1%, which is relatively small in size relative to the embodiment. Larger crystals remain in the body for a longer time, which is more conducive to long-term inhibition of restenosis of the lumen. Therefore, larger crystals are conducive to the drug taking effect in the body for a longer time.

[0101] Test Example 2

[0102] The drug coating on the surface of the drug balloon obtained in Examples 1-9 and Comparative Examples 1-3 was respectively tested for its firmness in the blood of animals. The test method was as follows: a balloon with a specification of 8.0*40 mm was taken, and the drug coating was coated on the balloon surface according to the method of Examples 1-9 and Comparative Examples 1-3 to obtain a drug balloon. Five corresponding examples and comparative examples were obtained. The test animal was an ordinary white pig weighing about 30 kg. The drug balloon was introduced through the carotid artery and stopped at the femoral artery of the pig. The balloon was not opened and was taken out after staying. Blood was taken immediately, 1 min, and 3 min after staying, and the drug concentration data in the blood was measured. The test method was as follows:

[0103] Take 50 μL of blood sample, add 5 μg of internal standard drug (the internal standard drug is the drug used in the corresponding embodiment or comparative example), and then add 250 μL of organic solvent (the organic volume is methanol and acetonitrile mixed in a volume ratio of 1:1) to obtain a mixed solution, mix the mixed solution by turbine for 1 min, centrifuge at 4000 r / min for 15 min, obtain the supernatant, dilute the supernatant twice with water for injection, and then test it using liquid chromatography.

[0104] The drug balloon was taken out and collected, placed in a 5 mL brown volumetric flask, and 5 mL of methanol was added. After standing for half an hour, the drug elution solution was obtained. The eluted solution was then tested for drug content using a high performance liquid chromatograph, and the residual drug content rate was calculated, the residual drug content rate = 1-detected drug content / nominal drug content of the drug balloon. The test results are shown in Table 2.

[0105] Table 2. Blood fastness test in animals

[0106]

[0107]

[0108] As shown in Table 2, the drug coating obtained by the present invention has an average proportion of 94.2% of the residual drug on the balloon surface during the blood flushing process in vivo, and no drug concentration is detected in the blood, indicating that very little drug enters the blood, that is, the balloon has less drug washed off by the blood after entering the animal body, and the clinical safety is relatively high. In the comparative example, the average proportion of the residual drug on the balloon surface is 75.13%, and the drug concentration measured after the blood stays is the highest, with an average of about 22.44 ng / mL, a high proportion entering the blood, and a low clinical safety.

[0109] Test Example 3

[0110] The drug coating on the surface of the drug balloon obtained in Examples 1-9 and Comparative Examples 1-3 was tested for firmness in the urethra of animals. The test method was as follows: a balloon with a specification of 8.0*40mm was taken, and the drug coating was applied to the balloon surface according to the methods of Examples 1-9 and Comparative Examples 1-3 to obtain a drug balloon. Five corresponding examples and comparative examples were obtained, and the test animal was a male dog (beagle weighing about 15kg). The drug balloon was passed through the dog's urethra and delivered to the prostate urethra. The balloon was not opened, and the drug balloon was taken out after staying for 1min. The expanded drug balloon was placed in a 5mL brown volumetric flask, 5mL of methanol was added, and the eluted solution of the drug was obtained after standing for half an hour. Then, the eluted solution was measured for drug content using a high performance liquid chromatograph, and the residual drug content rate was calculated, and the residual drug content rate = 1-detected drug content / nominal drug content of the drug balloon. The test results are shown in Table 3.

[0111] Table 3. Results of urethra tests in animals

[0112]

[0113]

[0114] It can be seen from Table 3 that in the process of passing through the urethra, the average residual drug content on the surface of the drug balloon of the present invention accounts for 96.16%, the drug loss is small, and the average drug loss accounts for 3.84%. The average residual drug content on the surface of the balloon of the comparative example accounts for 80.53%, and the average drug loss accounts for 19.47%, indicating that the surface drug coating of the drug balloon obtained by the present invention has less drug loss in the process of passing through the urethra, better drug coating firmness, and higher clinical safety.

[0115] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. A method for preparing a surface drug coating of a drug balloon, characterized in that: The steps include: Dissolving the drug and the carrier in a solvent to prepare a supersaturated solution and an unsaturated solution respectively; The balloon can be dip-coated and sprayed with a supersaturated solution and an unsaturated solution in sequence; the number of spraying is 5-200 times; The drug is selected from at least one of paclitaxel, rapamycin, paclitaxel derivatives and rapamycin derivatives; The carrier is selected from at least one of phenolic compounds, pyrone compounds, sugar alcohol compounds, plasticizers, amphiphilic polymers, amide compounds, nonionic surfactants, and nonionic contrast agents; The solvent is selected from at least one of water, alcohol compounds, aliphatic hydrocarbon compounds, ether compounds, halogenated hydrocarbon compounds, ketone compounds, tetrahydrofuran, and acetonitrile; When paclitaxel is selected as the drug, the sugar alcohol compound in the carrier does not include xylitol.

2. The method for preparing a surface drug coating of a drug balloon according to claim 1, characterized in that: The dipping time is 1-30 min.

3. The method for preparing a surface drug coating of a drug balloon according to claim 1 or 2, characterized in that: During dipping, the coating is carried out while stirring, and the stirring speed is 10-200rps.

4. The method for preparing a surface drug coating of a drug balloon according to claim 1 or 2, characterized in that: After dipping, the balloon is dried at a temperature of 30-70° C. for a time of 1-30 min.

5. The method for preparing a surface drug coating of a drug balloon according to claim 4, characterized in that: After drying, the balloon is immediately placed on the sprayer for spraying.

6. The method for preparing a surface drug coating of a drug balloon according to claim 1 or 2, characterized in that: The spraying flow rate during spraying is 0.5-1mL / h.

7. The method for preparing a surface drug coating of a drug balloon according to claim 1 or 2, characterized in that: The phenolic compounds include tea polyphenols, tocopherol, catechol, gallic acid, eugenol, grape polyphenols and / or thymol; the pyrone compounds include maltol, ethyl maltol, coumarin, tartaric acid, flavonoids and / or flavonoid compounds; the sugar alcohol compounds include maltitol, xylitol, sorbitol, erythritol, mannitol and / or sucralose; the plasticizers include dibutyl phthalate (DBP), dioctyl phthalate (DOP), epoxidized soybean oil, tricresyl phosphate, triphenyl phosphate, dioctyl sebacate or chlorinated paraffin; the two The affinity polymer includes polyisobutylene-1-poly (N, N-dimethylacrylamide), polyethyleneimine, polylactic acid-glycolic acid copolymer (PLGA) and / or polyvinyl pyrrolidone; the amide compound includes urea, N, N-dimethylformamide, N, N-dimethylacetamide and / or stearic acid amide; the non-ionic surfactant includes polysorbate, sorbitan fatty acid, polyoxyethylene fatty acid ester, polyoxyethylene fatty alcohol ether, polyoxyethylene-polyoxyethylene copolymer and / or pluronic; the non-ionic contrast agent includes iopamidol, iohexol and / or iopromide.

8. The method for preparing a surface drug coating of a drug balloon according to claim 1 or 2, characterized in that: The mass ratio of the drug to the carrier in the supersaturated solution is (0.1-80):1; the mass ratio of the drug to the carrier in the unsaturated solution is (0.1-100):

1.

9. The method for preparing a surface drug coating of a drug balloon according to any one of claims 1 to 8 is used to prepare products for lumen treatment of blood vessels, urethra, ureter, and Eustachian tube; the blood vessels include coronary vessels, peripheral blood vessels, intracranial blood vessels, and arteriovenous fistula vessels; the urethra includes the urethra in the penis, prostate, bulb, and membranous parts.

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