CN110882473B - Medicinal balloon catheter and preparation method thereof - Google Patents

Abstract

The invention discloses a medicine balloon catheter, and belongs to the field of medical instruments and advanced manufacturing. A drug balloon catheter comprising a balloon and at least one drug coating covering the surface of the balloon; the drug coating is divided into a low drug content coating and a high drug content coating, wherein the high drug content coating is composed of an active drug or the active drug and a carrier, and the low drug content coating is composed of the active drug and the carrier. The invention has the following advantages: the medicine balloon catheter with the coatings with different medicine contents provided by the invention can effectively reduce the medicine loss of the medicine balloon in the conveying process in the operation, reduce the medicine loss of the outermost layer and the far end of the balloon, reduce the medicine residue on the surface and the near end of the balloon in the withdrawing process of the medicine balloon after the operation, and reduce the medicine damage to the non-target lesion part.

Description

Medicinal balloon catheter and preparation method thereof

Technical Field

The invention relates to a medicine balloon catheter and a preparation method thereof, belonging to the technical field of medical instruments and advanced manufacturing.

Background

Percutaneous Transluminal Angioplasty (PTA) has gone through the stages of bare balloons, bare metal stents, drug eluting stents, drug coated balloons since the last 70 s. The Drug Coated Balloon (DCB) can effectively inhibit smooth muscle cell hyperproliferation so as to reduce restenosis incidence on one hand, and does not need to be placed into a stent on the other hand, thereby reducing inflammation reaction of blood vessel intima, reducing thrombosis risk in the stent, shortening duplex antiplatelet time and reducing bleeding risk. In addition, in clinical studies of coronary artery disease, DCB shows better efficacy and safety in treating in-stent restenosis, small vessel lesions, bifurcation lesions, and also is suitable for patients at high risk of bleeding, patients who are taking oral anticoagulation drugs, or patients who have recently undergone surgical operations. DCB also achieves better therapeutic effects in the treatment of primary stenosis of peripheral vessels and in-stent restenosis. DCB is becoming a hotspot for research with its "interventional non-implantation" advantage.

Braun corporation, b.germany, introduced the first generation of drug balloons to date, and drug balloons from several companies were marketed at home and abroad. The drug balloon of Braun company utilizes iopromide as a contrast agent as a carrier and paclitaxel as a drug coating to be coated on a balloon catheter for treating coronary restenosis, the hydrophilic property of iopromide can improve the transfer rate of lipid-soluble drug paclitaxel to vascular tissues, and the effectiveness of the product in clinical use is ensured. Therefore, improvements to excipients and coating structures in subsequent DCB development are still in need of continuous progress.

Patent 201810399893.X protects a drug balloon comprising a balloon and a drug coating on the balloon surface, the drug coating comprising a drug and an excipient; its characterized in that, the medicine coating includes near-end coating, middle section coating and distal end coating, near-end coating with the medicine carrying density of one in the distal end coating is greater than the medicine carrying density of middle section coating, and the medicine carrying density of another is not less than the medicine carrying density of middle section coating. This patent does not consider that in actual surgical procedures, the length of the drug balloon is generally selected to be longer than that of the diseased vessel, and the distal or proximal end of the balloon with high drug loading density may be more in contact with the non-diseased region of the vessel during surgery, and therefore may not achieve its intended effect.

Patent 201710625381.6 discloses a drug balloon having a protective layer covering the drug layer for protecting the drug on the drug layer from being washed away by blood; patent 201610600900.9 discloses a drug-loaded balloon, in which the content of active drug is gradually decreased from the surface of the balloon, and the content of drug compound is gradually increased from the surface of the balloon; patent 201410837705.9 discloses a drug eluting balloon catheter, wherein the drug-loaded coating layer is designed to have at least two layers, and the drug-loaded amount of each layer of the drug-loaded coating layer decreases from inside to outside. The three patents all consider the situation that the surface layer medicine of the medicine balloon catheter is washed away by blood in the conveying process, but do not consider the situation that the medicine remains on the balloon after the medicine balloon is withdrawn from the body, and do not disclose a method for reducing the medicine residue on the balloon.

Patent 201711062396.2 discloses a drug balloon dilatation catheter in which the concentration of the active drug in the drug coating on the surface of the balloon dilatation catheter decreases linearly from the proximal end to the distal end of the balloon. The patent considers that blood flows from the proximal end of the balloon to the distal end of the balloon, and the direction of the blood flow scouring the balloon; it does not take into account that the relative flow of blood as the drug balloon travels within the guiding catheter is actually from the distal end to the proximal end of the balloon; in the operation of the medicine balloon, the time of flushing by blood flow after the balloon extends out of the guiding catheter and before the balloon is expanded is quite short, so the expected effect of the balloon is difficult to achieve due to the coating characteristics, and if the dosage of the proximal end of the balloon is too high, the toxic reaction of the proximal tissue can be caused.

The above prior art has the following technical problems:

1. due to the scouring action of blood in the conveying process of the drug balloon, part of the coating falls off, so that the active drug is scoured off before the balloon reaches a target lesion blood vessel; after the drug balloon is withdrawn, the coating on the balloon does not fall off completely, so that part of the active drug remains on the balloon.

2. The flow direction of the medicine on the medicine balloon is divided into three parts: the first part is transferred to the target lesion vessel by tissue adsorption; the second part is that the medicine is gathered in the downstream vascular tissue due to the blood scouring action during the balloon conveying and withdrawing process; and the third part is that the balloon still remains on the balloon after the balloon is withdrawn from the body. Only the first part is effectively utilized by the tissues, and the drugs in the second part not only cause unnecessary waste, but also can poison downstream tissues to cause tissue necrosis.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: the coating structure is reasonably arranged, and the distribution of the drugs in the coating is optimized, so that the loss and the drug residue of the drugs are reduced, the utilization rate of the drugs is improved, and the toxic effect of the drugs on downstream tissues is avoided.

In order to achieve the purpose, the invention adopts the following technical scheme.

A drug balloon catheter comprising a balloon and at least one drug coating covering the surface of the balloon; the drug coating is divided into a low drug content coating and a high drug content coating, wherein the high drug content coating is composed of an active drug or the active drug and a carrier, and the low drug content coating is composed of the active drug and the carrier. Contact connection between different drug coatings.

The first embodiment of the present invention: the low drug content coating is located on the inner side and the outer side of the high drug content coating, wherein the inner side is the side close to the surface of the balloon, and the outer side is the side far away from the surface of the balloon. In this manner, the active drug content in the coating increases and then decreases from the balloon surface outward, with areas of the low drug content coating located immediately adjacent the outer surface of the balloon and the outermost layer of the coating, and areas of the high drug content coating located in the middle of the coating, as shown in fig. 1C in cross-section.

Second embodiment of the present invention: the low drug content coating is located at both ends of the high drug content coating, both ends being located towards the proximal and distal ends of the balloon. In this manner, the active drug content in the coating increases from the proximal end of the balloon to the distal end and then decreases, with low drug content coating regions at the ends of the balloon and high drug content coating regions in the middle of the balloon, as shown in fig. 2C in cross-section.

The third embodiment of the present invention: the low drug content coating is located on the inner side, the outer side and two ends of the high drug content coating, wherein the inner side is the side close to the surface of the balloon, the outer side is the side far away from the surface of the balloon, and the two ends are the positions facing the near end and the far end of the balloon. In this manner, the active agent content in the coating increases from the proximal end of the balloon to the distal end and then decreases, and the active agent content in the coating increases from the proximal end of the balloon to the distal end and then decreases, with the low drug content coating region being located proximate the outer surface of the balloon and the outermost layer of the coating, and the high drug content coating region being located in the middle of the coating. The cross-sectional view is shown in fig. 3C.

The active drug includes but is not limited to one or more of rapamycin, zotarolimus, tacrolimus, paclitaxel, dexamethasone and derivatives thereof.

The carrier comprises one or more of polyhydric alcohol, phospholipid, organic acid salt, laurocapram, urea, polyester substances, poloxamer, iopromide, polyvinylpyrrolidone and tween.

The ratio of the drug content of the low drug content coating to the mass of the coating is as follows: 10 to 60 percent. This ratio is used to distinguish low drug content coatings from high drug content coatings, where low content coatings can reduce drug loss and high content coatings can make efficient use of the drug.

The proportion of the drug content of the high drug content coating in the mass of the coating is as follows: 50 to 100 percent.

The mass of the high-drug-content coating accounts for 60-90% of the sum of the mass of the low-drug-content coating and the mass of the high-drug-content coating.

The drug loading rate of the active drug on the surface of the balloon per unit area is 0.5-10 mu g/mm². The drug loading per unit area is a value obtained by dividing the total drug loading on the balloon by the total surface area.

A preparation method of a drug balloon catheter comprises the following steps:

s1, preparing a coating solution with low drug content, wherein the drug accounts for 10-60% of the solute by mass;

s2, preparing a coating solution with high drug content, wherein the drug accounts for 50-100% of the solute by mass;

s3, spraying the low-drug-content coating solution to a preset area of the low-drug-content coating on the surface of the balloon catheter, and drying to obtain a low-drug-content coating;

s4, spraying the high-drug-content coating solution to a preset area of the high-drug-content coating, and drying to obtain the high-drug-content coating; the high-drug-content coating preset area is positioned on the surface of the balloon catheter or the surface of the dried low-drug-content coating;

s5, spraying the low-drug-content coating solution to a preset area of a preset low-drug-content coating according to the requirement, and drying to obtain another low-drug-content coating; the low-drug-content coating preset area is positioned on the surface and/or two ends of the high-drug-content coating;

the solute mass in the above step is the sum of the mass of the active drug and the mass of the carrier. Wherein the active drug includes but is not limited to one or more of rapamycin, zotarolimus, tacrolimus, paclitaxel, dexamethasone and derivatives thereof; the carrier comprises one or more of polyhydric alcohol, phospholipid, organic acid salt, laurocapram, urea, polyester substances, poloxamer, iopromide, polyvinylpyrrolidone and tween.

The method of spraying is by ultrasonic spraying, which is a routine operation in the art.

According to the invention, by optimizing the structure of the drug coating, the problems of drug loss and drug residue on the balloon in the process of surgical delivery of the drug balloon are effectively reduced, and the drug loss and drug residue on the balloon in the delivery process cannot be eliminated in the prior art.

Because the outer surface of the balloon coating is mainly washed by blood in the delivery process, the invention can reduce the dosage loss of the balloon before the balloon is delivered to the target lesion position by reducing the drug content of the outermost coating in the balloon coating. The blood-washed balloon is mainly the bottom coating closest to the balloon in the balloon coating in the withdrawing process, and the medicine remained on the balloon is positioned in the bottom coating closest to the balloon, so that the medicine content of the bottom layer is reduced, the dosage of the blood-washed balloon to the downstream blood vessel in the withdrawing process can be effectively reduced, the toxic and side effects of the medicine on the downstream tissue can be reduced, and on the other hand, the utilization rate of the medicine can be improved on the premise of ensuring the effective utilization of the medicine. There are three embodiments of the present invention, each of which is illustrated in fig. 1, 2 and 3. The scheme in fig. 3 has the advantages of the schemes in fig. 1 and fig. 2, so that the content of the drug on the balloon is further reduced, and the utilization rate of the drug is improved.

The invention has the following advantages: the medicine balloon catheter with the coatings with different medicine contents provided by the invention can effectively reduce the medicine loss of the medicine balloon in the conveying process in the operation, reduce the medicine loss of the outermost layer and the far end of the balloon, reduce the medicine residue on the surface and the near end of the balloon in the withdrawing process of the medicine balloon after the operation, and reduce the medicine damage to the non-target lesion part.

Drawings

The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.

FIG. 1A is a schematic view showing the structure of the first coating method of the present invention

FIG. 1B is a cross-sectional view of a first coating mode of the present invention

FIG. 1C is a schematic cross-sectional view of a first coating mode of the present invention

FIG. 2A is a schematic view showing the structure of the second coating method of the present invention

FIG. 2B is a cross-sectional view of a second coating mode of the present invention

FIG. 2C is a schematic cross-sectional view of a second coating mode of the present invention

FIG. 3A is a schematic view showing the structure of the third coating method of the present invention

FIG. 3B is a cross-sectional view of a third coating mode of the present invention

FIG. 3C is a schematic cross-sectional view of a third coating method of the present invention

The respective symbols in the figure are as follows: 1-high drug content coating, 2-low drug content coating

Detailed Description

Example 1

Firstly, raw materials:

1. medicine preparation: paclitaxel, yunnan hande biotechnology limited;

2. carrier: PEG1000, dow chemistry;

3. medical grade ethanol, Shanghai Aladdin Biotechnology GmbH.

Second, preparation method

S1, preparing a low-drug-content coating solution, respectively weighing 100mg of paclitaxel and 100mg of PEG1000, and dissolving into 10ml of medical grade ethanol to obtain the low-drug-content coating solution, wherein the drug accounts for 50% of the solute by mass.

S2, preparing a coating solution with high drug content, respectively weighing 160mg of paclitaxel and 40mg of PEG1000, and dissolving into 10ml of medical grade ethanol to obtain the coating solution with high drug content, wherein the drug accounts for 80% of the solute by mass.

S3, spraying the low-drug-content coating solution on the surface of the balloon for 2 times by an ultrasonic spraying method, and drying to obtain a low-drug-content coating which is a bottom-layer drug coating.

And S4, spraying the high-drug-content coating solution on the bottom layer obtained in the step S3 by an ultrasonic spraying method, spraying for 10 times, and drying to obtain a high-drug-content coating which is a middle-layer drug coating.

And S5, spraying the low-drug-content coating solution on the middle layer obtained in the step S4 by an ultrasonic spraying method for 2 times, and drying to obtain a low-drug-content coating which is a surface-layer drug coating.

In this example, the structure of the coating is shown in fig. 1A to 1C, and the mass of the high drug content coating accounts for 70% of the total mass of all the drug coatings (the sum of the masses of the bottom drug coating, the middle drug coating, and the top drug coating). The drug loading rate of the active drug on the surface of the balloon per unit area is 2 mu g/mm²。

Example 2

Firstly, raw materials:

1. medicine preparation: rapamycin, fujiangurui pharmaceutical co;

2. carrier: lecithin, Shanghai Aladdin Biotechnology Ltd;

3. medical grade ethanol, Shanghai Aladdin Biotechnology GmbH.

Second, preparation method

S1, preparing a low-drug-content coating solution, respectively weighing 20mg of rapamycin and 180mg of lecithin, and dissolving into 10ml of medical-grade ethanol to obtain the low-drug-content coating solution, wherein the drug accounts for 10% of the solute by mass.

S2, preparing a coating solution with high drug content, weighing 100mg of rapamycin and 100mg of lecithin respectively, and dissolving into 10ml of medical grade ethanol to obtain the coating solution with high drug content, wherein the drug accounts for 50% of solute mass.

S3, spraying the low-drug-content coating solution to the areas of 1cm at the near end and the far end of the surface of the balloon by an ultrasonic spraying method, spraying for 10 times, and drying to obtain the low-drug-content coating.

And S4, spraying the high-drug-content coating solution to the non-sprayed middle area of the balloon surface of the S3 by an ultrasonic spraying method, and spraying for 10 times, namely drying to obtain the high-drug-content coating.

In this example, the structure of the coating layer is shown in fig. 2A to 2C, and the mass of the high drug content coating layer accounts for 60% of the total mass of all the drug coating layers (the sum of the masses of the low drug content coating layers on both sides and the middle high drug content coating layer). The drug loading rate of the active drug on the surface of the balloon per unit area is 10 mu g/mm²。

Example 3

Firstly, raw materials:

1. medicine preparation: tacrolimus, fujiarkui pharmaceutical co;

2. carrier: polyvinylpyrrolidone, Shanghai Allantin Biotechnology Ltd;

3. medical grade ethanol, Shanghai Aladdin Biotechnology GmbH.

Second, preparation method

S1, preparing a low-drug-content coating solution, respectively weighing 120mg of tacrolimus and 80mg of polyvinylpyrrolidone, and dissolving into 10ml of medical grade ethanol to obtain the low-drug-content coating solution, wherein the drug accounts for 60% of the solute by mass.

S2, preparing a coating solution with high drug content, weighing 200mg of tacrolimus, and dissolving into 10ml of medical grade ethanol to obtain the coating solution with low drug content, wherein the drug accounts for 100% of the solute by mass.

S3, spraying the low-drug-content coating solution on the surface of the balloon by an ultrasonic spraying method for 1 time, and drying to obtain a low-drug-content coating which is a bottom-layer drug coating.

And S4, spraying the high-drug-content coating solution to the middle area of the drug coating bottom layer obtained in the step S3 by adopting an ultrasonic spraying method, wherein the middle area is 1cm away from each of two ends of the balloon. Spraying for 15 times, and drying to obtain a high-drug-content coating as a middle-layer drug coating.

And S5, spraying the coating solution with low drug content on the surface of the drug coating obtained in the step S4 again by adopting an ultrasonic spraying method, spraying for 1 time, and drying to obtain the coating with low drug content, namely the surface drug coating.

In this example, the structure of the coating is shown in fig. 3A to 3C, and the mass of the high drug content coating accounts for 90% of the total mass of all the drug coatings (the sum of the masses of the bottom drug coating, the middle drug coating, and the top drug coating). The drug loading rate of the active drug on the surface of the balloon per unit area is 0.5 mu g/mm²。

Comparative example

Firstly, raw materials:

1. medicine preparation: paclitaxel, yunnan hande biotechnology limited;

2. carrier: PEG1000, dow chemistry;

3. medical grade ethanol, Shanghai Aladdin Biotechnology GmbH.

Second, preparation method

1. Coating solutions of the drug and the carrier are prepared, 160mg of paclitaxel and 40mg of PEG1000 are respectively weighed and dissolved in 10ml of medical grade ethanol to obtain the coating solution, wherein the drug accounts for 80% of the solute by mass.

2. And spraying the coating solution on the surface of the balloon by an ultrasonic spraying method for 14 times, and drying to obtain the drug coating with uniform drug content.

Example 4: in vitro testing

Materials (I) and (II)

The drug-coated balloon catheters prepared in examples 1-3 and comparative examples were tested for drug content, drug loss rate during in vitro delivery, in vitro drug loading rate, and in vitro drug residue rate.

Secondly, a test method comprises the following steps:

1. drug loading per unit area of drug balloon

The amount of drug on the balloon was tested using High Performance Liquid Chromatography (HPLC).

The drug loading per unit area on the surface of the balloon is balloon drug amount/(pi x d x l).

Wherein, d: nominal balloon diameter, mm;

l: nominal balloon length, mm.

2. Drug loss rate during in vitro delivery

Placing the simulated path in a water bath at 37 ℃ for constant temperature, keeping the flow rate of purified water in the path at 300ml/min, conveying the prepared drug balloon catheter to a target position through the simulated path without expanding the balloon, washing the drug balloon for 2min in a folded state by using the purified water, withdrawing the balloon catheter, testing the drug amount on the balloon by using High Performance Liquid Chromatography (HPLC), and obtaining the loss drug amount by subtracting the residual drug amount of the balloon from the initial drug amount.

The rate of drug loss during in vitro delivery is the amount of drug lost/initial amount of drug.

3. Method for testing drug residue rate and drug loading rate in vitro simulation manner

Pig coronary artery blood vessel is used for simulating target blood vessel for in vitro simulation test. Selecting a proper simulated blood vessel according to the over-expansion ratio of 1.10-1.20, placing the simulated path in a water bath at 37 ℃ for constant temperature, keeping the flow rate of purified water in the path at 300ml/min, inserting the prepared medicinal balloon catheter into a simulated target blood vessel (a pig coronary artery blood vessel obtained by dissection) through the simulated path, pressurizing the balloon to about 12atm, maintaining the pressure for 1min, then releasing the pressure of the balloon catheter, taking out the balloon catheter from an in-vitro simulation test system, continuously flushing the target blood vessel for 2min, and collecting target blood vessel tissues and a withdrawn balloon. And respectively testing the content of the residual medicine on the target blood vessel and the saccule by using High Performance Liquid Chromatography (HPLC), and comparing the content with the initial medicine amount of the medicine saccule to obtain the in vitro transfer rate and the in vitro medicine residual rate.

Paclitaxel chromatographic conditions:

an Agilent 1260 high performance liquid testing system;

a chromatographic column: agilent ZORBAX SB-C184.6X 250mm, 5 μm;

mobile phase: methanol, water and acetonitrile at 23: 41: 36;

column temperature: 30 ℃;

the pump flow rate: 1.0 ml/min;

detection wavelength: 227nm ultraviolet detector.

Rapamycin chromatographic conditions:

an Agilent 1260 high performance liquid testing system;

a chromatographic column: agilent ZORBAX SB-C184.6X 250mm, 5 μm;

mobile phase: water and acetonitrile 35: 65;

column temperature: 50 ℃;

the pump flow rate: 1.0 ml/min;

detection wavelength: 278nm ultraviolet detector.

Tacrolimus chromatographic conditions:

an Agilent 1260 high performance liquid testing system;

a chromatographic column: agilent Eclipse XDB-C84.6X 150mm, 5 μm;

mobile phase: 0.05mol/L potassium dihydrogen phosphate solution (containing 0.2 percent of polyoxyethylene lauryl ether) and acetonitrile 50: 50;

column temperature: 50 ℃;

the pump flow rate: 1.5 ml/min;

detection wavelength: a 210nm ultraviolet detector.

Third, experimental results

As can be seen from Table 1, compared with the comparative example, the loss rate of the drug-coated balloon in the in-vitro delivery process after the coating structure is optimized is remarkably reduced; the in vitro transfer rate is improved; the in vitro drug residue rate is obviously reduced. The expected drug balloon delivery process can reduce the drug loss of the balloon before delivery to a target lesion, and effectively reduce the drug amount flushed by blood to a downstream blood vessel in the balloon withdrawal process; on the other hand, the utilization rate of the medicine can be improved on the premise of ensuring the effective utilization (high transfer rate) of the medicine.

TABLE 1 in vitro transfer and in vivo tissue drug concentration test Experimental results

The above listing of a series of detailed descriptions is merely a detailed description of possible embodiments of the present invention and is not intended to limit the scope of the invention, and one skilled in the art may devise many other modifications and embodiments that will fall within the spirit and scope of the principles disclosed herein. More specifically, various variations and modifications are possible in the component parts and/or arrangements of the subject combination arrangement within the scope of the disclosure, the drawings and the appended claims. In addition to variations and modifications in the component parts and/or arrangements, other uses will also be apparent to those skilled in the art.

Claims (7)

1. A drug balloon catheter characterized by: comprises a balloon and at least one drug coating layer covered on the surface of the balloon; the drug coating is divided into a low drug content coating and a high drug content coating; the high-drug-content coating consists of an active drug or the active drug and a carrier, and the low-drug-content coating consists of the active drug and the carrier;

the structure of the low-drug-content coating and the high-drug-content coating is any one of the following structures:

the structure I is that the low-drug-content coating is positioned on the inner side and the outer side of the high-drug-content coating, wherein the inner side is the side close to the surface of the balloon, and the outer side is the side far away from the surface of the balloon;

the low-drug-content coating is positioned on the inner side, the outer side and two ends of the high-drug-content coating, the inner side is the side close to the surface of the balloon, the outer side is the side far away from the surface of the balloon, and the two ends are positions towards the near end and the far end of the balloon;

the drug content of the low drug content coating accounts for 10-60% of the mass of the coating; the proportion of the drug content of the high drug content coating in the mass of the coating is as follows: 50 to 100 percent.

2. A drug balloon catheter as in claim 1 wherein: the active medicine is one or more of rapamycin, zotarolimus, tacrolimus, paclitaxel, dexamethasone and derivatives thereof.

3. A drug balloon catheter as in claim 2 wherein: the carrier is one or more of polyalcohol, phospholipid, organic acid salt, laurocapram, urea, polyester substances, poloxamer, iopromide, polyvinylpyrrolidone and tween.

4. A drug balloon catheter as in claim 1 wherein: the mass of the high-drug-content coating accounts for 60-90% of the sum of the mass of the low-drug-content coating and the mass of the high-drug-content coating.

5. A drug balloon catheter as in claim 1 wherein: the drug loading rate of the active drug on the surface of the balloon per unit area is 0.5-10 mu g/mm²。

6. A method of manufacturing a drug balloon catheter as in any of claims 1 to 5, comprising the steps of:

s1, preparing a coating solution with low drug content, wherein the drug accounts for 10-60% of the solute by mass;

s2, preparing a coating solution with high drug content, wherein the drug accounts for 50-100% of the solute by mass;

s3, spraying the low-drug-content coating solution to a preset area of the low-drug-content coating on the surface of the balloon catheter, and drying to obtain a low-drug-content coating;

s4, spraying the high-drug-content coating solution to a preset area of the high-drug-content coating, and drying to obtain the high-drug-content coating; the high-drug-content coating preset area is positioned on the surface of the balloon catheter or the surface of the dried low-drug-content coating;

s5, spraying the low-drug-content coating solution to a preset area of a preset low-drug-content coating according to the requirement, and drying to obtain another low-drug-content coating; the predetermined region of the low drug content coating is located on the surface and/or at both ends of the high drug content coating.

7. The method for preparing a drug balloon catheter according to claim 6, wherein the method comprises the following steps: the spraying method is ultrasonic spraying.

Images