A new drug eluting balloon catheter

Abstract

The present invention provides a drug eluting balloon catheter, comprising a catheter, a balloon body (1) and a balloon surface (2), and also comprising a hydrophilic lipophilic bottom layer (3) and a drug-carrying coating layer (4), wherein the hydrophilic lipophilic bottom layer (3) is located on the balloon surface (2), and the drug-carrying coating layer (4) is located on the hydrophilic lipophilic bottom layer (3), and the drug-carrying coating layer (4) is composed of a polymer and a drug. The drug eluting balloon catheter has the characteristics of simple structure, simple production process, less drug loss during transportation, and less drug residue on the balloon after interventional surgery.

Description

Technical Field

[0001] The present invention relates to a medical device, in particular to a novel drug eluting balloon used for interventional treatment of cardiovascular diseases. Background Art

[0002] The drug eluting balloon catheter is a combination of traditional balloon angioplasty and advanced drug eluting technology. The drug eluting balloon catheter releases drugs immediately during interventional treatment, avoiding the side effects caused by the long-term retention of metal stents and polymer carriers. It is an effective supplement to metal stent angioplasty. It has a good application in the process of restenosis after drug stent implantation and gradually shows its superiority. However, the drug eluting balloon still has the problem that the drug on the drug surface is lost in large quantities during the intervention process, resulting in a low drug loading rate in the lesion tissue and some drugs are still attached to the balloon surface (about 10-20%) due to the existence of surface binding force after interventional treatment, affecting the drug release. Therefore, how to achieve the timely and quantitative release of drugs on the drug eluting balloon at the lesion site is one of the key factors to achieve the therapeutic effect of the drug balloon.

[0003] CN101785900A discloses a drug balloon, in which the balloon is designed to have a non-planar structure with concave and convex outer surface, and drugs are coated on the groove part and flat part of the outer surface of the balloon, and the retention effect of the groove reduces the loss of drugs during the delivery process. This method uses a mold with grooves, and directly makes the balloon have a groove appearance during the balloon molding process, but the groove retention effect of this method will also cause a high amount of drug residue on the balloon surface after treatment, affecting the drug utilization efficiency. On the other hand, this method has high requirements for the balloon molding process, especially the mold processing accuracy is too demanding.

[0004] Chinese patent CN200951251A discloses a double-layer drug eluting balloon catheter, which has a balloon with micropores on the outer surface of the balloon, and the outer balloon is made of PE, PC, PEBAX, etc. The micropores are made by laser drilling or etching technology, and the surface effect of the micropores will also increase the amount of drug residue on the surface of the drug balloon after surgery. The process requires expensive instruments and equipment, and the process is complicated and not suitable for industrial production.

[0005] In addition, Chinese patent CN103990221A discloses a drug eluting balloon device, wherein the polymer layer contains a drug or a drug and an additive, and further discloses an extractable bottom layer structure, which forms a porous structure after extraction, and can reduce the binding force between the drug layer and the balloon surface, and can make the drug layer adhere to the blood vessel wall after falling off in a whole block or in sheets. However, this patent still has the problem of large losses during the intervention process. In terms of process, it selects the extraction after coating spraying, and the extraction process is complicated. The solvent used for extraction may also cause damage to the drug coating. After extraction, the residue of organic solvent on the balloon is also a problem that needs to be solved. Moreover, the drug layer in sheets adhered to the blood vessel wall falls off, which has the risk of causing thrombosis and even endangering life.

[0006] Chinese patent CN204050424U discloses a drug balloon, which uses a double-layer balloon, and the outer surface of the balloon is coated with a water-soluble bottom layer and a biodegradable polymer layer containing drugs in sequence. When the outer layer expands, a solution such as physiological saline will seep out from the balloon wall, dissolving the water-soluble bottom layer, thereby controlling the release of the biodegradable polymer layer containing drugs. The balloon has a complex structure, and physiological saline is injected into the balloon wall. On the one hand, the production process is complicated, and on the other hand, it is difficult for the solution to be stably retained in the balloon wall for a long time. Once the solution seeps out, it will seriously damage the integrity of the coating.

[0007] Therefore, it is necessary to provide a drug eluting balloon catheter that can not only reduce drug loss during delivery, reduce postoperative drug residues on the balloon surface, and improve drug use efficiency, but also has a simple processing technology, is safe to use, and is suitable for industrial production. Summary of the invention

[0008] In order to solve the above technical problems, the present invention provides a novel drug eluting balloon catheter, which has the characteristics of simple structure, simple production process, less drug loss during delivery, and less drug residue on the balloon after interventional surgery.

[0009] A drug eluting balloon catheter comprises a catheter, a balloon body 1 and a balloon surface 2, characterized in that it also comprises a hydrophilic lipophilic base layer 3 and a drug-loaded coating 4, wherein the hydrophilic lipophilic base layer 3 is located on the balloon surface 2, and the drug-loaded coating 4 is located on the hydrophilic lipophilic base layer 3, and the drug-loaded coating 4 is composed of a polymer and a drug.

[0010] The bottom layer 3 is a polymer material layer having hydrophilic and lipophilic properties, such as Figure 1As shown, the polymer material has both hydrophilic groups and lipophilic groups. The bottom layer forms a separation layer between the drug-loaded coating and the balloon. Since the binding force between the drug and the balloon surface is relatively strong due to the surface effect, it can prevent the drug in the drug-loaded coating from contacting the balloon surface, reduce the binding force of the drug layer, facilitate the rapid release of the drug layer, and can reduce the drug residue caused by the surface effect between the drug and the balloon. The bottom layer material should have hydrophilic and lipophilic properties. The bottom layer material can be one or several of polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, poly stearate, phospholipids, polycitrate. The thickness of the bottom layer is preferably 0.1-2 μm. The bottom layer cannot be too thick, otherwise it will affect the overall delivery performance of the drug balloon. If it is too thin, the effect of isolating the balloon from the drug cannot be achieved.

[0011] The average molecular weight of the hydrophilic and lipophilic polymer of the bottom layer is preferably Mv>50K (where Mv is the viscosity-average molecular weight and K is the unit of quantity "thousand"). The hydrophilicity of the hydrophilic and lipophilic polymer with this range of molecular weights is reduced, and it is not easy to fall off when used as the bottom layer. Especially when the drug balloon coating has a multi-layer structure, it can ensure that the bottom layer is difficult to dissolve within a short period of time (1 minute after the balloon is opened) during the treatment of the drug balloon, and can maintain good stability within a short period of time. If the bottom layer falls off locally, it is easy to cause the drug-loaded layer to break off, affecting the transfer of the drug to the diseased tissue. Among them, it is more preferably 70K<Mv<150K, because when the molecular weight is too large, the viscosity of the polymer in the blood vessel is large, which affects blood flow and is easy to block blood vessels, endangering the life and health of patients.

[0012] The preferred technical solution of the present invention further includes a hydrophilic and lipophilic surface layer 5. The surface layer is a polymer material layer. The surface layer wraps the surface of the drug-loaded coating and forms a protective layer on the surface of the drug-loaded coating, which can reduce the loss of the drug during transportation. When the balloon is transported to the diseased position, the surface layer is basically completely dissolved, achieving the protection of the drug-loaded coating without affecting the release of the drug in the drug coating. The surface layer material should have good hydrophilic and lipophilic properties. Because the drug-eluting balloon catheter needs to pass through a relatively long blood vessel during transportation to reach the stenosis position, at this time, a large amount of the drug is often lost after being washed by the blood flow, which not only results in a low drug loading rate in the diseased tissue, but also easily causes toxic and side effects. The surface layer can play a role in protecting the drug coating during the transportation of the drug balloon, and can also not affect the release of the drug when it reaches the diseased position. The surface layer material can be one or several of polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, poly stearate, phospholipids, polycitrate. The thickness of the surface layer is 0.1-2 μm. The surface layer is not too thick. When the drug balloon reaches the transportation position, it is difficult for the surface layer to be completely dissolved. If the surface layer is too thin, it is difficult to achieve the effect of protecting the drug layer.

[0013] The carrier material of the drug-loaded coating 4 and the surface layer 5 are both hydrophilic and lipophilic polymers, and the average molecular weight is preferably Mv<40K. The drug-loaded coating needs to be completely released within 1 minute after the balloon is opened, and the polymer needs to have good hydrophilicity, so the polymer is required to have a low molecular weight; the surface layer plays a role in protecting the drug coating during balloon delivery. At the same time, when the balloon is delivered to the lesion, the surface layer must be completely dissolved, so the surface layer should also have good solubility and also requires a low molecular weight. Among them, 1K is more preferred. <Mv<40K。

[0014] The carrier material of the drug-loaded coating 4 is a mixed layer of hydrophilic and lipophilic polymers and drugs. The drug-loaded coating is located between the surface layer and the bottom layer. The carrier material of the drug-loaded coating has hydrophilic and lipophilic properties to ensure that the drug can be released to the blood vessel wall in a timely and effective manner after the balloon adheres to the wall. The drug loading of the drug-loaded coating is preferably 1-5 μg / mm 2 The coating thickness is preferably 1-50 μm. The drug loading and thickness of each drug-loaded coating are the preferred ranges of a large number of experiments. The drug loading of each drug-loaded coating should not be too high, which will have a greater side effect on the human body, and too low a drug loading will not achieve the therapeutic effect. The thickness of each drug-loaded coating should not be too large, otherwise it will affect the firmness of the coating. In addition, the drug-loaded coating is preferably applied to the entire effective support range after the balloon is opened, and the cones at both ends of the balloon should not be coated to avoid affecting the overall drug content of the balloon.

[0015] The carrier material of the drug-loaded coating is fully mixed with one or more drugs such as paclitaxel, rapamycin and its derivatives, abciximab, etc., dissolved in methanol, ethanol, acetone, dichloromethane, acetonitrile, tetrahydrofuran, and the coating is loaded onto the balloon surface by spraying, dipping, coating, or folded wing injection. The carrier material of the drug-loaded coating is one or two of polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids, and polycitrate, and the average molecular weight is preferably Mv<40K, more preferably 1K <Mv<40K。

[0016] The drug-loaded coating is composed of one or more of the above-mentioned carrier materials and drugs. The carrier material of the drug-loaded coating is preferably the same as that of the bottom layer, and the preferred weight ratio of the drug to the carrier material is 1:10-10:1. Among them, the preferred polymer molecular weight, drug loading, components and coating thickness of the present invention can ensure that the drug can be safely released within 1 minute and effectively transferred to the blood vessel wall; the type and content of the drug can also achieve the effect of treating vascular lesions.

[0017] The bottom layer is selected with a higher molecular weight material to reduce the hydrophilicity of the bottom layer material, which can reduce the risk of coating falling off due to the dissolution of local bottom layer materials when the balloon is opened. The drug-loaded coating and surface layer are required to have a small molecular weight and good hydrophilicity, which is conducive to the timely and effective release of drugs to the lesion site after the balloon is opened.

[0018] The present invention further provides a method for preparing a drug eluting balloon catheter, comprising:

[0019] First, the surface of the balloon is pretreated using plasma cleaning technology, and then a base layer is sprayed with a thickness of 0.1-2μm;

[0020] Then spray the drug-loaded coating with a thickness of 1-50μm and a drug loading of 1μg / mm 2 -5μg / mm 2 ;

[0021] After the coating is dry, it is folded, rolled up and then sprayed with a surface layer with a thickness of 0.1-2μm.

[0022] Specifically, the present invention first pre-treats the balloon surface, and uses plasma cleaning technology to clean the debris on the balloon surface. Preferably, the plasma cleaning uses an inert gas, such as argon, neon, etc., with a power of 10KHz-100KHz. During cleaning, the pressure in the working chamber is 0.01atm-0.3atm, and the cleaning time is 5-30min.

[0023] Preparation process of bottom layer 3: weigh a certain mass of carrier material and dissolve it in an organic solvent, let it stand until it is completely dissolved to obtain a bottom layer coating liquid, and then use a dipping, spraying or coating process to form a layer of carrier material coating on the balloon surface, and vacuum dry it at room temperature to obtain a balloon catheter with a bottom layer.

[0024] Preparation process of drug-loaded coating: weigh a certain mass of carrier material and drug, and dissolve them in an organic solvent, then apply the prepared drug-loaded spray liquid on the surface of the base layer by dipping, spraying or coating, and control the thickness of the drug-loaded coating to the above range.

[0025] After the coating is dried, the balloon is folded and rolled, and a surface layer is further prepared on the surface of the drug-loaded coating. The preparation process of the surface layer is the same as that of the bottom layer.

[0026] Plasma cleaning technology is used to reduce the interface effect that affects the adhesion of the coating, as well as the physical impact of plasma, making the balloon surface rougher and increasing the firmness of the combination of the coating and the balloon surface. The use of optimal process parameters can ensure that impurities on the balloon surface are completely cleaned, and can also avoid long-term physical impact of plasma on the balloon surface, which affects the mechanical properties of the balloon.

[0027] The multi-layer drug eluting coating balloon of the present invention has the following effects:

[0028] (1) The bottom layer can reduce the direct contact between the drug and the balloon surface, reduce the drug residue on the balloon surface after interventional treatment, maximize the release of the drug when the balloon reaches the lesion, and optimize the therapeutic effect of the drug; at the same time, the multi-layer drug design of the present invention can ensure the firmness of the combination of the drug-loaded coating and the bottom layer;

[0029] (2) The surface layer can reduce drug loss during the delivery of the drug-eluting balloon and prevent the drug components from being released prematurely in the blood;

[0030] (3) Compared with a single-layer drug-loaded coating, the present invention has high drug bioavailability and low toxic side effects. When used in combination with the bottom layer and the surface layer of the present invention, the beneficial effects are more significant.

[0031] (4) In addition, the present invention has a simple structure, is easy to process, has a high pass rate, and is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Schematic diagram of the structure of hydrophilic and lipophilic polymers

[0033] Figure 2 The coating structure of a drug eluting balloon containing a base layer and a drug-loaded coating layer

[0034] Figure 3 Diagram of the coating structure of a drug eluting balloon containing a base layer, a drug-loaded coating layer, and a top layer

[0035] Figure 4 Drug release diagram of a drug eluting balloon containing a base layer, a drug-loaded coating layer, and a top layer

[0036] Among them, 1 is the balloon body, 2 is the balloon surface, 3 is the bottom layer, 4 is the drug-loaded coating, and 5 is the surface layer. DETAILED DESCRIPTION

[0037] The invention is explained below in conjunction with specific implementation schemes and drawings, but the invention is not limited thereto.

[0038] Example 1

[0039] like Figure 2 As shown, first, the surface of the balloon is pretreated by plasma cleaning technology, and then the impurities on the balloon surface are cleaned by plasma cleaning technology. Preferably, the plasma cleaning uses an inert gas, such as argon, with a power of 50KHz, a pressure of 0.1atmatm in the working chamber during cleaning, and a cleaning time of 10min. Then, polyethylene glycol with good hydrophilicity and lipophilicity is used as the bottom material (such as Figure 1As shown, the polymer material has both hydrophilic groups and lipophilic groups), and then a polyethylene glycol base layer with a molecular weight of 70K is sprayed, with a thickness of 1μm, and then a drug-loaded coating layer of a polyethylene glycol with a molecular weight of 15K and paclitaxel is sprayed, with a drug loading of 2.5μg / mm 2 , thickness is 10μm; after the coating is dry, fold it finally.

[0040] Example 2

[0041] like Figure 3 As shown, first, the surface of the balloon is pretreated by plasma cleaning technology, and the plasma cleaning technology is used to clean the debris on the balloon surface. Preferably, the plasma cleaning uses an inert gas, such as neon, with a power of 10KHz, a pressure of 0.01atm in the working chamber during cleaning, and a cleaning time of 5min. Then, a hydrophilic and lipophilic poly stearate is used as the bottom material (such as Figure 1 As shown, the polymer material has both hydrophilic groups and lipophilic groups), a layer of poly stearate with a molecular weight of 51K is sprayed, the thickness is 2μm, and then a layer of stearate with a molecular weight of 5K and paclitaxel mixed drug-loaded coating is sprayed, and the drug loading is 1μg / mm 2 , with a thickness of 50μm; after the coating is dried, it is folded, rolled up and then sprayed with a layer of 2K polyglycerol ester with a molecular weight of 2μm.

[0042] Example 3

[0043] like Figure 3 As shown, first, the surface of the balloon is pretreated by plasma cleaning technology, and the plasma cleaning technology is used to clean the debris on the balloon surface. Preferably, the plasma cleaning uses an inert gas, such as argon, with a power of 50KHz, a pressure of 0.1atm in the working chamber during cleaning, and a cleaning time of 10min. Then, lipophilic and hydrophilic dextran is used as the bottom material (such as Figure 1 As shown, the polymer material has both hydrophilic groups and lipophilic groups), a layer of 150K molecular weight dextran bottom layer with a thickness of 0.1 μm is sprayed, and then a layer of 39K molecular weight dextran and rapamycin mixed drug-loaded coating layer is sprayed, and the drug loading amount is 2.5 μg / mm 2 , with a thickness of 1μm; after the coating is dried, it is folded, and finally rolled up and sprayed with a layer of polycitrate with a molecular weight of 39K and a thickness of 0.1μm.

[0044] Example 4

[0045] like Figure 3As shown, first, the surface of the balloon is pretreated by plasma cleaning technology, and the plasma cleaning technology is used to clean the debris on the balloon surface. Preferably, the plasma cleaning uses an inert gas, such as neon, with a power of 100KHz, a pressure of 0.3atm in the working chamber during cleaning, and a cleaning time of 30min. Then, lipophilic and hydrophilic chitosan is used as the bottom material (such as Figure 1 As shown, the polymer material has both hydrophilic groups and lipophilic groups), a layer of chitosan with a molecular weight of 200K and a thickness of 0.2μm is sprayed, and then a layer of drug-loaded coating with a molecular weight of 20K polyxylitol and abciximab mixed is sprayed, and the drug loading amount is 5μg / mm 2 , with a thickness of 6μm; after the coating is dried, it is folded, and finally rolled up and sprayed with a layer of 10K polyxylitol surface layer with a thickness of 0.8μm.

[0046] Comparative experiment 1

[0047] First, the surface of the balloon is pretreated by plasma cleaning technology, and the plasma cleaning technology is used to clean the debris on the balloon surface. Preferably, the plasma cleaning uses an inert gas, such as argon, with a power of 50KHz, a pressure of 0.1atmatm in the working chamber during cleaning, and a cleaning time of 10min. Then, a drug-loaded coating of a mixture of polyglycerol ester with a molecular weight of 50K and paclitaxel is sprayed, and the drug loading is 2.5μg / mm 2 , thickness is 18μm; after the coating is dry, fold it finally.

[0048] Comparative experimental results

[0049] In order to verify the drug loss during the delivery process of the drug eluting balloon catheter of the above implementation scheme, the folded and pressed balloon catheter was delivered to the designated position of the abdominal aorta of a New Zealand white rabbit weighing about 2.0±0.5 kg, and after being fully moistened, it was pressurized and opened, and the balloon catheter was placed at the lesion position for about 1 minute. The balloon was then removed, the drug residue rate remaining on the balloon was measured, and the drug content transferred into the abdominal aorta of the New Zealand rabbit was determined within a specified time. The drug loss rate during the delivery process was calculated based on this residue.

[0050] To verify the absorption of the drug by tissues, the balloon was implanted in the iliac artery of a New Zealand white rabbit and the balloon was inflated at 16 atm. The pressure was maintained for 1 minute, and the balloon was removed after decompression. After 1 hour of blood flushing, the rabbit died suddenly, and the drug concentration in the tissue and the drug residue rate on the balloon were measured.

[0051] For tissue drug absorption rate, the blood vessels at the balloon dilation site were dissected and obtained, ground and fixed to 2 ml, and then the drug content in the solution was determined using a liquid chromatograph, and the tissue drug absorption rate was calculated.

[0052] For the drug residue rate of the balloon, the used balloon was taken out, cut and ground, and then the volume was fixed to 2 ml. Then, the drug content in the solution was determined using a liquid chromatograph, and the drug residue rate was calculated.

[0053] The above detection liquid chromatograph use conditions are:

[0054] Detector: UV detector;

[0055] Column: SB-Aq C 18 5μm 250×4.6mm;

[0056] Mobile phase: methanol: acetonitrile: water = 23:41:36;

[0057] Column temperature: 30°C;

[0058] Detection wavelength: 227nm;

[0059] Flow rate: 1.5 ml / min;

[0060] Injection volume: 10 μL.

[0061] Example Drug loss rate during delivery Tissue drug absorption rate Drug residue rate on balloon Example 1 36％ 21.5％ 9％ Example 2 29％ 23.8％ 11％ Example 3 28％ 24.2％ 10％ Example 4 32％ 26.2％ 11％ Comparative experiment 1 53％ 10.3％ 15％

[0062] Comparative experiment 2

[0063] like Figure 3 As shown, the surface of the balloon is first pretreated by plasma cleaning technology, and then the impurities on the balloon surface are cleaned by plasma cleaning technology. Preferably, the plasma cleaning uses an inert gas, such as argon, with a power of 50KHz, a pressure of 0.1atm in the working chamber during cleaning, and a cleaning time of 10min. Then, a polyethylene glycol base layer is sprayed with a thickness of 1μm, and then a drug-loaded coating of a mixture of polystearate and paclitaxel is sprayed with a drug loading of 2.5μg / mm 2 , with a thickness of 15μm; after the coating is dried, it is folded, and finally rolled up and sprayed with a layer of polyxylitol surface with a thickness of 1μm.

[0064] According to the above preparation method and the molecular weights in the table below, polyethylene glycol, polystearate and polyxylitol are used to prepare the bottom layer, drug-loaded coating layer and surface layer, respectively, and the following different molecular weights are used to prepare drug balloons 1-8.

[0065] In addition, according to the above preparation method and the molecular weight in the table below, non-hydrophilic lipophilic material PLGA and low molecular weight PVP were used to prepare the bottom layer, and polystearate and polyxylitol were used to prepare the drug-loaded coating layer and the surface layer, respectively, to obtain balloons 9 and 10.

[0066] Balloon No. Molecular weight of bottom layer (K) Molecular weight of drug loading coating (K) Surface molecular weight (K) 1 31 0.1 0.1 2 41 0.5 0.5 3 51 1 1 4 71 20 20 5 101 30 30 6 151 39 39 7 201 50 50 8 301 100 100 9 101 30 30 10 20 0.1 0.1

[0067] Comparative experimental results

[0068] To verify the loss of coatings with different molecular weights during the delivery of the drug-eluting balloon catheter in Comparative Experiment 2, the above-mentioned balloon catheter that had been folded and crimped was delivered into the specified position of the abdominal aorta of New Zealand white rabbits weighing about 2.0 ± 0.5 kg. After being fully wetted, it was inflated and opened, and the balloon catheter was placed at the lesion site for about 1 minute. Then, the balloon was taken out, and the weights of the corresponding polyethylene glycol, dextran, and polyxylitol hydrophilic-lipophilic polymers in the remaining bottom layer, drug-loading coating, and surface layer on the balloon were measured.

[0069] The used balloon was taken out and soaked in an organic solvent for soluble polymers. Then, the contents of polyethylene glycol (PLGA and PVP were measured separately for balloons 9 and 10), dextran, and polyxylitol hydrophilic-lipophilic polymers on the balloon surface were extracted and measured respectively, and the residual amounts and corresponding residual rates were calculated:

[0070] Balloon No. Bottom layer residual rate Drug coating residual rate Surface residual rate 1 61％ 8.9％ 0％ 2 72％ 9.3％ 0％ 3 80％ 9.5％ 0％ 4 91％ 10.6％ 0％ 5 93％ 12.5％ 0％ 6 95％ 14.6％ 0.9％ 7 97％ 26.3％ 8.1％ 8 98％ 72％ 46％ 9 99％ 35％ 3％ 10 48％ 5.8％ 0％ Example 1 89％ 9.2％ —

[0071] As can be seen from the above table, when the molecular weight Mv of the hydrophilic-lipophilic polymer in the bottom layer is < 50K, the bottom layer sheds severely. The shedding of the bottom layer without drugs not only does not improve the treatment effect but may even block the ends of small blood vessels, endangering the life and health of patients. When the molecular weight of the drug-loading coating is > 40K, the polymer residue in the drug-loading coating is high and the drug conversion rate is low; when it is less than 1K, it is easy to cause the drug-loading coating to dissolve into the blood during delivery, resulting in a large loss, and not much drug is actually loaded onto the blood vessel wall. When the molecular weight of the surface layer is > 40K, the residual rate of the surface layer polymer is also high, which is not conducive to drug release; when it is less than 1K, the surface layer is easy to dissolve and cannot protect the drug-loading coating during the transfer to the heart during interventional surgery.

[0072] The inventors found through research that when the molecular weight Mv of the bottom layer is > 50K and the Mv of the drug-loading coating and the surface layer is < 40K, the loss of the bottom layer polymer can be reduced and the drug release of the drug-loading coating can be improved. Moreover, for hydrophilic-lipophilic polymers such as polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, poly(stearic acid ester), and poly(citrate ester), similar technical effects can be achieved.

[0073] In addition, as Figure 4 shown in the figure and the above table, it is the effect diagram of the drug release process of the new drug-eluting balloon catheter. Among them, in the present invention, the preferred molecular weight of the hydrophilic-lipophilic polymer in the bottom layer is 70K < Mv < 150K, and the preferred molecular weights of the hydrophilic-lipophilic polymers in the drug-loading coating and the surface layer are 1K < Mv < 40K. There is no obvious shedding in the bottom layer locally, which will not cause the chipping of the drug-loading layer, improving the loading of the drug to the lesion tissue, and the drug release effect is particularly significant.

[0074] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A drug eluting balloon catheter, comprising a catheter, a balloon body (1) and a balloon surface (2), characterized in that: The balloon also includes a hydrophilic lipophilic bottom layer (3) and a drug-loaded coating layer (4), wherein the hydrophilic lipophilic bottom layer (3) is located on the balloon surface (2), and the drug-loaded coating layer (4) is located on the hydrophilic lipophilic bottom layer (3), wherein the drug-loaded coating layer (4) is composed of a polymer and a drug, and wherein the bottom layer (3) is composed of one or more of the following hydrophilic lipophilic polymers: Polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids, polycitrate; The average molecular weight Mv of the hydrophilic and lipophilic polymer of the bottom layer (3) satisfies 70K <Mv<150K; The drug-carrying coating (4) is composed of one or more of the following hydrophilic and lipophilic polymers: Polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids, polycitrate; The average molecular weight of the hydrophilic and lipophilic polymer of the drug-carrying coating (4) is 1K <Mv<40K; The drug is one or more of paclitaxel, rapamycin and its derivatives, and abciximab.

2. The drug eluting balloon catheter according to claim 1, characterized in that: It also includes a hydrophilic and lipophilic surface layer (5).

3. The drug eluting balloon catheter according to claim 2, characterized in that: The surface layer (5) is composed of one or more of the following hydrophilic and lipophilic polymers: Polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol esters, chitosan, chitin, dextran, polystearate, phospholipids, polycitrate.

4. The drug eluting balloon catheter according to claim 3, characterized in that: The average molecular weight Mv of the hydrophilic and lipophilic polymer of the surface layer (5) is less than 40K.

5. The drug eluting balloon catheter according to claim 4, characterized in that: The average molecular weight of the hydrophilic and lipophilic polymer of the surface layer (5) is 1K <Mv<40K。 6. The drug eluting balloon catheter according to claim 1, characterized in that: The thickness of the bottom layer (3) is 0.1-2 μm, and the thickness of the drug-carrying coating layer (4) is 1-50 μm.

7. The drug eluting balloon catheter according to any one of claims 2 to 5, characterized in that: The thickness of the surface layer (5) is 0.1-2 μm.

8. The drug eluting balloon catheter according to claim 1, characterized in that: The drug loading amount of the drug-loaded coating (4) is 1-5 μg / mm 2 .

9. A method for preparing a drug eluting balloon catheter as claimed in any one of claims 1 to 8, characterized in that: First, the surface of the balloon is pretreated by plasma cleaning technology, and then a base layer (3) is sprayed with a thickness of 0.1-2 μm; then a drug-loaded coating (4) is sprayed with a thickness of 1-50 μm and a drug loading of 1 μg / mm 2 -5μg / mm 2 After the coating is dried, it is folded, rolled up and then sprayed with a surface layer (5) with a thickness of 0.1-2 μm.

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