Drug balloon and its preparation method

Abstract

The present invention discloses a drug balloon, which comprises a balloon body and a coating. The coating includes a drug layer and a protective layer; the drug layer covers the balloon body, and the protective layer covers the outside of the drug layer to protect the drug on the drug layer from being washed away by blood. The present invention also discloses a preparation method of the above drug balloon. For the drug balloon involved in the present invention, its protective layer can better protect the drug from being washed away by blood, so as to improve the release of a sufficient amount of drug to the action site after the drug balloon reaches the designated position, with better treatment effect, and is convenient for production, basically without increasing the process and without additional production equipment.

Description

Technical Field

[0001] The present invention belongs to the field of medical devices, and in particular relates to a drug balloon and a preparation method thereof. Background Art

[0002] Cardiovascular stenosis is one of the main causes of coronary heart disease. Percutaneous Coronary Intervention (PCI) is an important means for treating cardiovascular stenosis. With the increasing number of stents used, the problem of in-stent restenosis (ISR) has become increasingly serious. 5-60% of the treated patients will experience vascular restenosis in the short and medium term, which severely restricts the development of PCI.

[0003] In recent years, a new technology for preventing vascular restenosis after interventional treatment - drug balloon - has emerged. It is a technology that coats an anti-vascular intimal hyperplasia drug on the surface of the balloon. When the balloon reaches the diseased blood vessel wall and is inflated and filled, it comes into contact with the intima of the blood vessel wall, and the drug is rapidly released under pressure and transferred to the local blood vessel wall. The drug plays a role in anti-vascular intimal hyperplasia locally, thereby preventing restenosis after vascular intervention. Research on its clinical application shows that the drug balloon shows good efficacy when treating ISR lesions, and can be used to treat small vessel lesions, bifurcation lesions, some primary lesions of tubular arteries, and patients who cannot tolerate or are not suitable for long-term oral dual antiplatelet drugs (Expert Group on Clinical Application of Drug-Coated Balloons, Expert Consensus on Clinical Application of Drug-Coated Balloons, Chinese Journal of Interventional Cardiology, 2016, Vol. 24, No. 2, pp. 61-67).

[0004] Since when the drug balloon is in the inflated and filled state, the drug balloon will block blood flow, so its continuous filling time can only be about 40 seconds at most, otherwise it may cause myocardial ischemia. This requires the drug to be rapidly released within a short time to reach the required dose. Summary of the Invention

[0005] In order to solve the problem of the drug balloon releasing a sufficient drug dose, the present invention provides a drug balloon, which includes a balloon body and a coating. The coating includes a drug layer and a protective layer; the drug layer covers the balloon body; the protective layer covers the outside of the drug layer and is used to protect the drug on the drug layer from being washed away by blood.

[0006] Furthermore, the balloon body has at least one flap. The flap has an inner surface and an outer surface; the balloon body has a folded state and an inflated state; in the folded state, the inner surface of the flap is folded inside, and the outer surface of the flap is exposed outside, so that the cross-section of the balloon body is reduced.

[0007] Further, the protective layer only covers the drug layer on the outer surface of the folded wings.

[0008] Preferably, there are 3 to 5 folded wings.

[0009] In a specific embodiment, in the inflated state, the cross-section of the balloon body is circular.

[0010] In another specific embodiment, in the inflated state, a concave structure appears on the balloon body, enabling blood to flow through the balloon body via the concave structure.

[0011] Further, the concave structure is arranged between the folded wings.

[0012] Preferably, except for the concave structure, the entire body of the balloon body is covered with drugs.

[0013] Further, the concave structure is parallel to the axis of the balloon body.

[0014] Further, a developer line is provided at the bottom of the concave structure; the developer line has the same extending direction as the concave structure.

[0015] In a specific embodiment, a developer element is provided on the balloon body; the developer element is annular.

[0016] Further, developer elements are provided at both the proximal end and the distal end of the balloon body.

[0017] Preferably, in the inflated state, the concave structure is located on the surface of the cross-section of the balloon body.

[0018] Preferably, in the folded state, a part of the drug is folded inside and does not contact the blood vessel wall.

[0019] Preferably, in the inflated state, the drug folded inside is exposed.

[0020] Preferably, the entire body of the balloon body is covered with a drug layer, that is, the surface of the balloon body is covered with drugs 360°.

[0021] Further, the raw materials used for the protective layer include a protective agent and a first solvent; the protective agent is selected from at least one of iopromide, polyvinylpyrrolidone, polysorbate, and polyethylene glycol.

[0022] Further, the ratio relationship between the protective agent and the first solvent is that 5 - 50 mg of the protective agent corresponds to each milliliter of the first solvent.

[0023] Further, the first solvent is selected from at least one of water, methanol, ethanol, acetone, isopropanol, tetrahydrofuran, acetonitrile, ethyl acetate, and methyl formate.

[0024] Further, the raw materials used in the drug layer include a drug and a second solvent.

[0025] Further, the drug is selected from at least one of taxanes and macrolides.

[0026] Preferably, the drug is selected from at least one of paclitaxel, docetaxel, albumin-bound paclitaxel, rapamycin, everolimus, temsirolimus, zotarolimus, biolimus, and tacrolimus.

[0027] Further, the ratio of the drug to the second solvent is 5 - 50 mg of the drug per milliliter of the second solvent.

[0028] Further, the second solvent is selected from at least one of water, methanol, ethanol, acetone, isopropanol, tetrahydrofuran, acetonitrile, ethyl acetate, and methyl formate.

[0029] Further, the raw materials used in the drug layer further include a protective agent.

[0030] Further, the ratio of the drug, the protective agent, and the second solvent contained in the raw materials used in the drug layer is such that the mass ratio of the drug to the protective agent is 1:2 to 2:1, and 5 - 50 mg of the sum of the drug and the protective agent corresponds to each milliliter of the second solvent.

[0031] Further, the raw materials used in the drug layer include 5 parts by weight of the drug, 10 parts by weight of the protective agent, and 5 mg of the sum of the drug and the protective agent corresponds to each milliliter of the second solvent; or

[0032] 7 parts by weight of the drug, 10 parts by weight of the protective agent, and 15 mg of the sum of the drug and the protective agent corresponds to each milliliter of the second solvent; or

[0033] 10 parts by weight of the drug, 10 parts by weight of the protective agent, and 25 mg of the sum of the drug and the protective agent corresponds to each milliliter of the second solvent; or

[0034] 15 parts by weight of the drug, 10 parts by weight of the protective agent, and 40 mg of the sum of the drug and the protective agent corresponds to each milliliter of the second solvent; or

[0035] 20 parts by weight of the drug, 10 parts by weight of the protective agent, and 50 mg of the sum of the drug and the protective agent corresponds to each milliliter of the second solvent.

[0036] Further, the raw materials used in the drug layer are paclitaxel, iopromide, and ethanol; or rapamycin, iopromide, and ethanol.

[0037] Preferably, the raw materials used in the drug layer are 20 parts by weight of paclitaxel, 10 parts by weight of iopromide, and 40 mg of the sum of paclitaxel and iopromide corresponds to each milliliter of ethanol; or

[0038] 5 parts of paclitaxel and 10 parts of iopromide, and the sum of 25 mg of paclitaxel and iopromide per milliliter of ethanol; or

[0039] 10 parts of rapamycin and 10 parts of iopromide, and the sum of 10 mg of rapamycin and iopromide per milliliter of ethanol.

[0040] Furthermore, the material of the balloon body is Pebax or nylon.

[0041] Furthermore, the drug layer is covered on the balloon body by means of soaking extraction and / or ultrasonic spraying.

[0042] Furthermore, the protective layer is covered outside the drug layer by means of soaking extraction and / or ultrasonic spraying.

[0043] The present invention also provides a preparation method of the drug balloon as described above, comprising the following steps:

[0044] Step 1: Take the drug and the second solvent according to the ratio, mix them evenly to obtain the drug layer solution; take the protective agent and the first solvent according to the ratio, mix them evenly to obtain the protective layer solution;

[0045] Step 2: Coat the drug layer solution obtained in Step 1 on the surface of the balloon body in the inflated state by means of soaking extraction and / or ultrasonic spraying to form the drug layer;

[0046] Step 3: Fold the balloon body with the drug layer covered on its surface obtained in Step 2;

[0047] Step 4: Coat the protective layer solution obtained in Step 1 on the surface of the balloon body in the folded state obtained in Step 3 by means of soaking extraction and / or ultrasonic spraying to form the protective layer.

[0048] Furthermore, the drug layer solution prepared in Step 1 further includes the protective agent taken according to the ratio.

[0049] Furthermore, Step 3 is to fold the balloon body with the drug layer covered on its surface obtained in Step 2 after the drug layer is dried; the temperature for drying the drug layer is from room temperature to 60 °C.

[0050] Furthermore, the drying time is 3 - 30 minutes.

[0051] Furthermore, Step 3 specifically is to inflate the balloon body with the drug layer covered on its surface obtained in Step 2 to an internal pressure of 1 - 3 atm, and then fold it under the condition of 40 - 60 °C.

[0052] Furthermore, the time for pressing the crease is 60 - 600 seconds.

[0053] Beneficial effects:

[0054] 1. During the process of delivering the drug balloon in the blood vessel, the blood will impact the surface of the drug balloon, which is likely to cause the drug on it to fall off. The existence of the protective layer can better protect the drug from being washed away by the blood, thereby enabling the drug balloon to release a sufficient amount of drug to the action site after reaching the designated position. Since the protective layer is located on the outermost layer, it will be impacted by the blood first and partially or completely fall off. When the protective layer falls off, the drug layer is exposed. Although it will also be impacted by the blood, the time when it is impacted by the blood is delayed, thus avoiding or reducing the loss of the drug during the delivery process. Coupled with the folding design, the drug balloon of the present invention has a double insurance to avoid the drug from falling off during the delivery process: one comes from the protective layer; the other comes from covering part of the drug on the inner surface of the flap. The flap is beneficial to protecting the drug folded inside from being washed away by the blood flow, thereby avoiding drug loss.

[0055] 2. The drug balloon is covered with drugs in a 360° manner, enabling the entire circumference of the blood vessel to receive the drug, resulting in better treatment effects and more convenient production.

[0056] 3. The cross-section of the balloon body being circular is beneficial for fitting with the blood vessel.

[0057] 4. In the inflated state, the cross-section of the balloon body shows that there are depressions between the flaps, which is beneficial for blood flow to pass through, thereby appropriately extending the duration of continuous inflation and enhancing the drug effect.

[0058] 5. The material is Pebax, semi-compliant, with good wall adhesion performance. It is applicable to the blockage of cardiac stents. The balloon can be inserted into the blocked part to expand it, and the drug on the surface of the balloon can be coated with a drug for promoting endothelial cell growth.

[0059] 6. The material is nylon, relatively hard, non-compliant, and is more suitable for dilation before stent implantation.

[0060] 7. The preparation method of the present invention is simple. Especially when the raw materials and their ratios of the protective layer and the drug layer only differ in that the drug layer contains drugs while the protective layer does not, when preparing the protective layer, only a part of the solution needs to be taken out before adding the drug as the raw material for preparing the protective layer, without adding an additional process for preparing the protective layer solution. Description of the Drawings

[0061] Figure 1 is a schematic structural diagram of a drug balloon according to the present invention in a folded state.

[0062] Figure 2 is a schematic structural diagram of the drug balloon not fully folded during the preparation process.

[0063] Figure 3It is a schematic structural diagram of the drug balloon in the inflated state in Example 1.

[0064] Figure 4 It is a schematic structural diagram of the drug balloon in the inflated state in Example 2.

[0065] Figure 5 It is a schematic structural diagram of a partial view of the radiopaque wire and the recessed structure in Example 2. Detailed implementation manners

[0066] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. The protection scope of the present invention is not limited to the following embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be conceived by those skilled in the art are included in the present invention, and the scope of protection is defined by the appended claims.

[0067] Example 1

[0068] Figure 1-3 A specific embodiment of the drug balloon involved in the present invention is shown. Among them, Figure 2 It shows a state when the drug balloon has not been fully folded during the preparation process, and at this time, the protective layer has not covered the drug layer. In this embodiment, the drug balloon includes a balloon body 1 and a coating. The coating is divided into a protective layer 7 and a drug layer 2. The surface of the balloon body 1 is covered with drugs 360°. The balloon body 1 has three flaps 3. In the present invention, the number of flaps 3 is not limited to three. In the folded state, the drugs covered on the inner surface of the flap 3 are folded inside and thus do not contact the blood vessel wall, thereby ensuring that this part of the drugs will not be consumed during the process of the balloon body 1 passing through the blood vessel. In the inflated state, as Figure 3 shown, the drugs covered on the inner surface of the flap 3 are exposed, and together with the remaining drugs (including the drugs covered on the outer surface of the flap 3), they contact the blood vessel wall and exert their medicinal effects. In this embodiment, the cross-section of the balloon body 1 is circular to fit the blood vessel, so that more drugs act on the blood vessel.

[0069] The crease of the flap 3 is parallel to the axis of the balloon body 1. The axis of the balloon body 1 is a catheter passing through the balloon body 1. Ring-shaped radiopaque elements are provided at both the proximal and distal ends of the balloon body 1.

[0070] The material of the balloon body 1 is Pebax or nylon; the drugs are selected from at least one of taxanes and macrolides, such as paclitaxel, docetaxel, albumin-bound paclitaxel, rapamycin, everolimus, temsirolimus, zotarolimus, biolimus or tacrolimus.

[0071] Example 2

[0072] Figure 4Another drug balloon of the present invention is shown. In its inflated state, the cross-section of the balloon body 1 shows depressions 4 provided between adjacent folding wings. The function of the depressions 4 is that even in the inflated state, the drug balloon does not completely block blood flow, so that the duration of continuous inflation can be extended, providing more time for drug release, and thus achieving better effects. The rest of the design is the same as that of Example 1, both covering the drug 360° and having folding wings 3. The number of depressions 4 is the same as the number of folding wings 3.

[0073] Example 3

[0074] In the inflated state, depressions are provided on the surface of the cross-section of the balloon body, which is beneficial for blood flow to pass through. Different from Example 2, the depressions are not limited to the depressions between the folding wings. The rest is the same as Example 2.

[0075] Example 4

[0076] As Figure 5 shown, in this embodiment, both the bottom 41 and the side 42 of the depression structure are parallel to the axis of the balloon body. The axis of the balloon body is the catheter 5 passing through the center of the balloon body. The radiopaque wire 6 is provided on the bottom 41 and is also parallel to the catheter 5. The rest is the same as Example 2.

[0077] Example 5

[0078] In this embodiment, the radiopaque wire in Example 4 is replaced by annular radiopaque elements provided at the proximal and distal ends of the balloon body, and the rest is the same as Example 4.

[0079] Preparation of the drug balloon in Example 6

[0080] Example 6.1

[0081] Step 1: Take paclitaxel and methanol, mix them evenly to prepare a methanol solution containing 5 mg / ml of paclitaxel, that is, the drug layer solution; take iopromide and ethanol, mix them evenly to prepare an ethanol solution containing 5 mg / ml of iopromide, that is, the protective layer solution.

[0082] Step 2: Coat the drug layer solution obtained in Step 1 onto the surface of the balloon body in the inflated state by ultrasonic spraying to form a drug layer.

[0083] Step 3: After air-drying the drug layer at room temperature, inflate the balloon body with the drug layer on its surface obtained in Step 2 to an internal pressure of 1 atm, and then fold it at 60°C for 60 seconds.

[0084] Step 4: Coat the protective layer solution obtained in Step 1 onto the surface of the balloon body in the folded state obtained in Step 3 by ultrasonic spraying to form a protective layer covering the drug layer, and obtain the drug balloon prepared in Example 6.1.

[0085] Example 6.2

[0086] Step 1: Take paclitaxel, dissolve it in ethanol, mix evenly, and prepare an ethanol solution containing 10 mg / ml of paclitaxel, which is the drug layer solution; take iopromide and 75% ethanol aqueous solution, mix evenly, and prepare an ethanol aqueous solution containing 10 mg / ml of iopromide, which is the protective layer solution.

[0087] Step 2: Use the dipping method to coat the drug layer solution obtained in Step 1 on the surface of the balloon body in the inflated state to form a drug layer.

[0088] Step 3: After drying the drug layer at 60 °C, inflate the balloon body with the drug layer on its surface obtained in Step 2 to an internal pressure of 2 atm, and then fold it at 40 °C for 600 seconds.

[0089] Step 4: Use the dipping method to coat the protective layer solution obtained in Step 1 on the surface of the balloon body in the folded state obtained in Step 3 to form a protective layer covering the drug layer, and obtain the drug balloon prepared in Example 6.2.

[0090] Example 6.3

[0091] Step 1: Take iopromide and ethanol, mix evenly, and prepare an ethanol solution containing 15 mg / ml of iopromide, which is the protective layer solution; take a part of the protective layer solution, add paclitaxel to it so that the mass ratio of paclitaxel to iopromide is 1:1, and mix evenly to obtain the drug layer solution.

[0092] Step 2: Use the ultrasonic spraying method to coat the drug layer solution obtained in Step 1 on the surface of the balloon body in the inflated state to form a drug layer.

[0093] Step 3: After air-drying the drug layer at room temperature, inflate the balloon body with the drug layer on its surface obtained in Step 2 to an internal pressure of 2 atm, and then fold it at 50 °C for 120 seconds.

[0094] Step 4: Use the ultrasonic spraying method to coat the protective layer solution obtained in Step 1 on the surface of the balloon body in the folded state obtained in Step 3 to form a protective layer covering the drug layer, and obtain the drug balloon prepared in Example 6.3.

[0095] Example 6.4

[0096] Step 1: Take iopromide and tetrahydrofuran, mix evenly, and prepare a tetrahydrofuran solution containing 15 mg / ml of iopromide, which is the protective layer solution; take a part of the protective layer solution, add rapamycin to it so that the mass ratio of rapamycin to iopromide is 2:1, and mix evenly to obtain the drug layer solution.

[0097] Step 2: Coat the surface of the balloon body in a filled state with the drug layer solution obtained in Step 1 by ultrasonic spraying to form a drug layer;

[0098] Step 3: After drying the drug layer at 50 °C, inflate the balloon body with the drug layer on its surface obtained in Step 2 to an internal pressure of 3 atm, and then fold it at 45 °C for 400 seconds;

[0099] Step 4: Coat the surface of the balloon body in a folded state obtained in Step 3 with the protective layer solution obtained in Step 1 by ultrasonic spraying to form a protective layer covering the drug layer, and obtain the drug balloon prepared in Example 6.4.

[0100] Example 6.5

[0101] Step 1: Take iopromide and ethyl acetate, mix them evenly, and prepare an ethyl acetate solution containing 30 mg / ml of iopromide, which is the protective layer solution; Take a part of the protective layer solution, add tacrolimus to it so that the mass ratio of tacrolimus to iopromide is 2:1, and mix evenly to obtain the drug layer solution;

[0102] Step 2: Coat the surface of the balloon body in a filled state with the drug layer solution obtained in Step 1 by ultrasonic spraying to form a drug layer;

[0103] Step 3: After drying the drug layer at 60 °C, inflate the balloon body with the drug layer on its surface obtained in Step 2 to an internal pressure of 2 atm, and then fold it at 45 °C for 300 seconds;

[0104] Step 4: Coat the surface of the balloon body in a folded state obtained in Step 3 with the protective layer solution obtained in Step 1 by ultrasonic spraying to form a protective layer covering the drug layer, and obtain the drug balloon prepared in Example 6.5.

[0105] Comparative Example 1

[0106] Without a protective layer, the rest is the same as in Example 6, that is, it includes the drug balloons prepared in Comparative Examples 1.1 to 1.5.

[0107] Experimental Example 1 Shedding Rate Experiment

[0108] 1. Experimental Purpose

[0109] Study the shedding rate of the drug of the drug balloon of the present invention and its relationship with the shedding rate of the protective agent.

[0110] 2. Experimental Method

[0111] 2.1 Preparation of the Drug Shedding Blood Vessel Model

[0112] Select a blood vessel model that complies with the standard of "ASTM F2394–07(2013) Guide for the Measurement of the Integrity of Balloon-Expandable Vascular Stents Mounted on Delivery Systems", place it in a 37 °C water bath for 1 h, block the outlet end of the model with a rubber stopper, insert a guiding catheter at the inlet end, insert a guide wire into the guiding catheter, and inject simulated blood into the simulated blood vessel pipeline and the guiding catheter, but do not let the simulated liquid flow out.

[0113] 2.2 Simulation of the use of drug balloons

[0114] Insert the guide wire into the guide wire lumen of the drug balloon catheter, push the drug balloon catheter along the guide wire to simulate surgical application, and push the drug balloons prepared in Examples 6.1 to 6.5 and Comparative Examples 1.1 to 1.5 to the target position respectively, but do not expand the drug balloon, fix the drug balloon catheter, and keep it for 90 s.

[0115] 2.3 Calculation of the remaining amount of drug

[0116] Withdraw the drug balloon, elute the remaining drug and protective agent on the drug balloon, measure the volume V1 of the eluate, use HPLC to measure the concentrations of the drug and the protective agent in the eluate, which are c1 and c2 respectively, and calculate the amount of the remaining drug on the balloon: m1 = V1·c1.

[0117] 2.4 Calculation of the shedding rate

[0118] Calculate the shedding rate of the drug according to the following formula: shedding rate of the drug = (nominal drug content - m1) / nominal drug content·100%.

[0119] 3. Experimental results

[0120] The specific experimental results are shown in Table 1.

[0121] Table 1 Experimental results of the shedding rates of Examples 6.1 to 6.5 and each comparative example

[0122]

[0123] As can be seen from Table 1, compared with the drug balloons prepared in Comparative Examples 1.1 to 1.5, the shedding rates of the drug balloons prepared in Examples 6.1 to 6.5 are significantly lower than those of Comparative Examples 1.1 to 1.5 respectively, and P>0.05.

[0124] 4. Experimental conclusion

[0125] Under the protection of the protective layer, the shedding rate of the drug of the drug balloon prepared by the present invention can be significantly reduced.

[0126] Experimental Example 2 Release rate experiment

[0127] 1. Experimental purpose

[0128] Study the drug release rate of the drug in the drug balloon of the present invention and its relationship with the peeling rate of the protective layer.

[0129] 2. Experimental methods

[0130] 2.1 Preparation of the drug release blood vessel model

[0131] Select two blood vessel models that meet the standards of "ASTM F2394–07 (2013) Guide for the Measurement of the Integrity of Balloon-Expandable Vascular Stents Mounted on Delivery Systems", place them in a 37°C water bath and keep for 1 h. Select the porcine coronary artery as the target position, place it between the two selected blood vessel models, connect one end to the outlet end of one model (Model 1) and the other end to the inlet end of the other model (Model 2) to form a connected simulated blood vessel pipeline. Block the outlet end of Model 2 with a rubber stopper, insert a guiding catheter into the inlet end of Model 1, insert a guide wire into the guiding catheter, inject simulated blood into the simulated blood vessel pipeline and the guiding catheter, but do not let the simulated liquid flow out.

[0132] 2.2 Simulated use of the drug balloon

[0133] Insert the guide wire into the guide wire lumen of the drug balloon catheter, push the drug balloon catheter along the guide wire to simulate surgical application, and push the drug balloons prepared in Examples 6.1 to 6.5 and Comparative Examples 1.1 to 1.5 to the target position, that is, the porcine coronary artery. Do not expand the drug balloon first, fix the drug balloon catheter and keep it for 90 s. Then, use liquid to expand the drug balloon to make the internal hydraulic pressure of the drug balloon reach the nominal pressure. The expansion transition stretch ratio of the drug balloon (i.e., the ratio of the drug balloon diameter to the blood vessel diameter) is about 1.10 - 1.20 to make the drug balloon and the porcine coronary artery adhere to the wall. Keep the expansion for 30 - 60 s, then contract and withdraw the drug balloon. During the test, the expansion and retraction can be carried out no more than 3 times as needed, and the number of expansions should be recorded.

[0134] 2.3 Calculation of the remaining drug amount Wash the remaining drug on the drug balloon;

[0135] Measure the volume V2 of the eluate, measure the drug concentration c2 in the eluate using HPLC, and calculate the amount of the remaining drug on the drug balloon: m2 = V2·c2.

[0136] 2.4 Calculation of the drug release rate

[0137] Calculate the drug release rate according to the following formula: Drug release rate = [Drug nominal content - (m1 - m2)] / Drug nominal content · 100%.

[0138] 3. Experimental results

[0139] The specific experimental results are shown in Table 2.

[0140] Table 2 Experimental results of drug release rates of Examples 6.1 to 6.5 and each comparative example

[0141] Drug release rate (%) at 30 s of dilation Drug release rate (%) at 60 s of dilation Example 6.1 68 80 Comparative Example 1.1 55 66 Example 6.2 70 88 Comparative Example 1.2 58 69 Example 6.3 74 90 Comparative Example 1.3 59 70 Example 6.4 71 88 Comparative Example 1.4 53 65 Example 6.5 69 85 Comparative Example 1.5 56 62

[0142] As can be seen from Table 2, at 30 s and 60 s of dilation, compared with the drug balloons prepared in Comparative Examples 1.1 to 15, the drug release rates in the drug balloons prepared in Examples 6.1 to 6.5 are all higher.

[0143] 4. Experimental conclusion

[0144] The drug release rate in the drug balloon prepared by the present invention is relatively high. This is related to the relatively low drug shedding rate of the present invention. Due to the protection of the protective layer, the drug shedding rate is reduced, so that when the drug balloon reaches the target position and starts to work (the drug balloon is inflated and in a filled state), more drugs are retained on the drug balloon, thereby increasing the release rate.

[0145] The preferred specific embodiments of the present invention have been described in detail above. Only for the purpose of illustrating the technical concept and characteristics of the present invention, the purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly, and it is not intended to limit the protection scope of the present invention. It should be understood that those of ordinary skill in the art can make many modifications and variations based on the concept of the present invention without creative labor. Therefore, all technical solutions that can be obtained by those skilled in the art in the technical field of the present invention based on the concept of the present invention through logical analysis, reasoning or limited experiments should be within the protection scope determined by the claims.

Claims

1. A drug balloon, characterized in that It includes a balloon body and a coating, and the coating includes a drug layer and a protective layer; the drug layer covers the balloon body; the protective layer covers outside the drug layer to protect the drug on the drug layer from being washed away by blood; The balloon body has at least one flap, and the flap has an inner surface and an outer surface; The balloon body has a folded state and an inflated state; in the folded state, the inner surface of the flap is folded inside, and the outer surface of the flap is exposed outside, so that the cross-section of the balloon body is reduced; In the inflated state, a concave structure appears on the balloon body, so that blood can flow through the balloon body via the concave structure; The concave structure is arranged between the flaps and is parallel to the axis of the balloon body; A radiopaque wire is arranged at the bottom of the concave structure; the radiopaque wire is in the same extending direction as the concave structure; The protective layer is composed of a protective agent, and the protective agent is selected from iopromide; The drug layer is composed of a drug; The protective layer only covers outside the drug layer on the outer surface of the flap; The number of the flaps is 3 to 5; Except for the concave structure, the whole body of the balloon body is covered with the drug; A radiopaque element is arranged on the balloon body; the radiopaque element is annular; Radiopaque elements are arranged at both the proximal end and the distal end of the balloon body; In the folded state, a part of the drug is folded inside and does not contact the blood vessel wall; In the inflated state, the drug folded inside is exposed; The whole body of the balloon body is covered with the drug layer, that is, the surface of the balloon body is covered with the drug at 360°; The drug is selected from at least one of paclitaxel, docetaxel, albumin-bound paclitaxel, rapamycin, everolimus, and tacrolimus; The material of the balloon body is Pebax or nylon; The preparation method of the drug balloon is characterized by including the following steps: Step 1: Take the drug and a second solvent according to the ratio, mix them evenly to obtain a drug layer solution; take the protective agent and a first solvent according to the ratio, mix them evenly to obtain a protective layer solution; Step 2: Coat the drug layer solution obtained in Step 1 on the surface of the balloon body in the inflated state by means of dipping and / or ultrasonic spraying to form a drug layer; Step 3: Fold the balloon body with the drug layer on its surface obtained in Step 2; Step 4: Coat the protective layer solution obtained in Step 1 on the surface of the balloon body in the folded state obtained in Step 3 by means of dipping and / or ultrasonic spraying to form a protective layer.

2. The drug balloon according to claim 1, wherein The ratio relationship between the protective agent and the first solvent is that 5-50 mg of the protective agent corresponds to each milliliter of the first solvent.

3. The drug balloon according to claim 1, characterized in that, The first solvent is selected from at least one of water and ethanol.

4. The drug balloon according to claim 1, characterized in that, The ratio relationship between the drug and the second solvent is that 5-50 mg of the drug corresponds to each milliliter of the second solvent.

5. The drug balloon according to claim 1, characterized in that, The second solvent is selected from at least one of water and ethanol.

6. The drug balloon according to claim 1, wherein Step 3 is to fold the balloon body with the drug layer on its surface obtained in Step 2 after the drug layer is dried, and the temperature for drying the drug layer is from room temperature to 60°C.

7. The drug balloon according to claim 6, characterized in that, The drying time is 3 - 30 minutes.

8. The drug balloon according to claim 1, wherein Specifically, in Step 3, the balloon body with a drug layer on its surface obtained in Step 2 is inflated to an internal pressure of 1 - 3 atm, and then folded at 40 - 60 °C.

9. The drug balloon according to claim 8, wherein The time for pressing the crease is 60 - 600 seconds.

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