A drug-coated delivery device

Abstract

A drug coating delivery device includes a delivery device body, a balloon is arranged on the delivery device body, a drug coating is coated on the surface of the balloon, a drug coating solution is mixed by an anti-proliferative drug, an excipient, a stabilizer and a crystallization solvent, the drug coating is coated on the surface of the balloon by a drug coating method, the drug coating method includes clamping, inflating, primer coating, hair throwing, segmented coating, installing a protective sleeve, drying, the drug coating delivery device prepared by the different coating method has higher drug coating firmness than the drug coating delivery device prepared by the traditional coating method, thus, drug loss in the delivery process can be greatly reduced, more drugs can be delivered to the target diseased blood vessels, drug utilization rate and clinical use effect are improved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical devices, and particularly relates to a drug coating delivery device. BACKGROUND

[0002] Drug coated balloon (DCB) is a kind of drug delivery device based on catheter, which has been gradually widely applied in the field of vascular intervention as a new interventional therapy technology. In recent years, DCB has been increasingly used to treat primary vascular lesions, and the preliminary results are satisfactory.

[0003] However, the current drug coating delivery device inevitably has some problems, and the core technical problem is that the drug coating has poor firmness, the drug is easily lost before reaching the target lesion blood vessel, and the drug utilization rate is low, thereby affecting the clinical effect. SUMMARY

[0004] The purpose of the present application is to provide a drug coating delivery device to solve the problems raised in the background.

[0005] To achieve the above purpose, the present application provides the following technical scheme:

[0006] A drug coating delivery device comprises a delivery device body, a balloon is arranged on the delivery device body, a drug coating is coated on the surface of the balloon, the drug coating solution is mixed by an anti-proliferative drug, an excipient, a stabilizer and a crystallization solvent, the drug coating is coated on the surface of the balloon by a drug coating method, and the drug coating method comprises the following steps:

[0007] (1) clamping: clamping both ends of the drug coating delivery device on a driving mechanism;

[0008] (2) inflation: inflating the balloon to 2 atm-4 atm;

[0009] (3) primer coating: driving the delivery device body to rotate around the center line at a rotating speed v1, and at the same time, the surface of the balloon is coated with the first layer of drug coating from the left end to the right end of the balloon;

[0010] (4) hair removal: drying the first layer of drug coating at room temperature, when the solidification degree of the first layer of drug coating reaches the surface dryness (the surface dryness in the present application is also referred to as touch dryness, which refers to the stage that the wet coating film has reached the surface dryness), driving the delivery device body to rotate around the center line at a rotating speed v2, and the rotating time is T;

[0011] (5) segmentally coating so that coating segment one and coating segment two are formed on the surface of the balloon, the coating segment one and the coating segment two are connected, the sum of the lengths of the coating segment one and the coating segment two is equal to the length of the balloon, the coating thickness of the coating segment one is d1, the coating thickness of the coating segment two is d2, d1>d2 2， d1>d2;

[0012] (6) installing a protective sleeve, the inner surface of the protective sleeve is previously dip-coated with a drug coating solution, the protective sleeve is sleeved on the coating segment one from the end away from the coating segment two until the protective sleeve covers the surface of the balloon completely;

[0013] (7) drying, the drug coating delivery device is placed in a constant temperature and humidity drying oven for drying, the drying temperature is 40

[0014] ±2℃, and the humidity is 60%±5%.

[0015] The segmental coating comprises the following steps:

[0016] (1) coating the drug coating solution on 1 / n of the length of the balloon from left to right, and the coating thickness is d1-d2;

[0017] (2) coating the drug coating solution on the whole length of the balloon from left to right, and the coating thickness is d2.

[0018] The n≥3 / 2, and n≤3.

[0019] The anti-proliferative drug is one or more of sirolimus, gemcitabine and daunorubicin; the excipient is one or more of magnesium stearate, sodium stearate and zinc stearate; the stabilizer is dibutylhydroxytoluene and / or phytic acid; the crystallization solvent comprises a first solvent and a second solvent, the first solvent is acetone, and the second solvent is one or more of acetic acid, tetrahydrofuran, acetonitrile and n-propyl acetate.

[0020] In the drug coating solution, the weight ratio of the anti-proliferative drug to the excipient is (0.5-200):1.

[0021] In the drug coating solution, the weight ratio of the anti-proliferative drug to the stabilizer is (0.5-200):1.

[0022] The areal density of the anti-proliferative drug in the drug coating is 0.1-50 μg / mm 2 .

[0023] The v1=40-60 rpm,

[0024] The v2=150-200 rpm.

[0025] The T is 5-10s.

[0026] The beneficial technical effects of the present application relative to the prior art are:

[0027] The drug coating delivery device prepared by the different coating method has higher drug coating firmness than the drug coating delivery device prepared by the traditional coating method, thus, the drug loss during delivery can be greatly reduced and more drugs can be delivered to the target diseased blood vessels, and the drug utilization rate is improved. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is a structural schematic diagram of a balloon catheter of double-lumen structure (OTW);

[0029] Figure 2 is a structural schematic diagram of a balloon catheter of rapid exchange (Rx) structure;

[0030] Figure 3 is a schematic diagram of a driving device and a coating device;

[0031] Figure 4 is a coating photo prepared by the coating method of Example 3;

[0032] Figure 5 is a coating photo prepared by the coating method of Comparative Example 2;

[0033] The drawings show that the drug coating delivery device has the following advantages: DETAILED DESCRIPTION

[0034] The present application will be further described below in combination with the drawings and specific examples.

[0035] The outer shape of the drug coating delivery device is shown in Figure 1 and Figure 2 respectively, Figure 1 and Figure 2 are structural schematic diagrams of a balloon catheter of double-lumen structure (OTW) and a balloon catheter of rapid exchange (Rx) structure respectively; both of the drug coating delivery devices of the two structures are provided with a tip, a balloon, a shaft and a catheter seat, and the structures of the balloon catheter of double-lumen structure (OTW) and the balloon catheter of rapid exchange (Rx) structure are prior art, thus, the present application will not be described in detail.

[0036] As shown in the drawings, the driving device includes a bracket 1, a motor 2, a jaw one 3, a jaw two 6, a mounting seat 7, the jaw one 3 is connected with the output shaft of the motor 2, the jaw two 6 is mounted on the mounting seat 7 through a bearing, the bracket 1 is used for supporting the motor 2, the coating device 5, the jaw one 3 and the jaw two 6 are all prior art, thus, the present application will not be described in detail.Figure 3 The drug coating delivery device is only schematically shown.

[0037] The two ends of the drug coating delivery device are clamped on the first clamp 3 and the second clamp 6. After the balloon is inflated, the drug coating delivery device is driven to rotate by the motor 2, and at the same time, the balloon surface is coated by the coating device 5.

[0038] Example One:

[0039] 210 mg of sirolimus, 4 mg of magnesium stearate, 3 mg of butylated hydroxytoluene, 35 ml of acetone, 26 ml of acetic acid and 8 ml of tetrahydrofuran are mixed to prepare a drug coating solution; in a ten-thousand-level clean environment, the coating is performed by the following method:

[0040] (1) Clamping: the two ends of the drug coating delivery device are clamped on the driving mechanism;

[0041] (2) Inflation: the balloon is inflated to 2 atm to 4 atm;

[0042] (3) Primer coating: the delivery device body is driven to rotate around the center line at a speed of 40 rpm, and at the same time, the balloon surface is coated with the first layer of drug coating from the left end to the right end, forming the first layer of drug coating;

[0043] (4) Hair removal: the first layer of drug coating is dried at room temperature, and when the solidification degree of the first layer of drug coating reaches the surface dryness, the delivery device body is driven to rotate around the center line at a speed of 150 rpm, and the rotation time is 5 s;

[0044] (5) Sectional coating: the drug coating solution is coated from left to right on 2 / 3 of the length of the balloon, and the coating thickness is 3 μm;

[0045] The drug coating solution is coated from left to right on the entire length of the balloon, and the coating thickness is 12 μm.

[0046] (6) Installing the protective sleeve: the inner surface of the protective sleeve is previously dip-coated with the drug coating solution, and the dip-coating thickness is 1 μm; the protective sleeve is sleeved from the left end of the balloon until the protective sleeve covers the entire surface of the balloon;

[0047] (7) Drying: the drug coating delivery device is placed in a constant temperature and humidity drying oven for drying, and the drying temperature is 40

[0048] ± 2 ℃, and the humidity is 60% ± 5%.

[0049] Example Two:

[0050] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0051] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0052] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0053] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 40 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0054] (4) Spinning: Dry the first layer of drug coating at room temperature. When the first layer of drug coating is surface dry, drive the conveying device body to rotate around its center line at a speed of 180 rpm for 5 seconds.

[0055] (5) Apply the drug coating solution in segments, applying it from left to right to 2 / 3 of the balloon length, with a coating thickness of 3 μm;

[0056] The drug coating solution was applied to the entire length of the balloon from left to right, with a coating thickness of 12 μm.

[0057] (6) Install the protective sleeve. The inner surface of the protective sleeve is pre-coated with a drug coating solution with a coating thickness of 1 μm. Put the protective sleeve on the left end of the balloon until the protective sleeve completely covers the surface of the balloon.

[0058] (7) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0059] ±2℃, humidity 60%±5%.

[0060] Example 3:

[0061] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0062] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0063] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0064] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 40 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0065] (4) Spinning: Dry the first layer of drug coating at room temperature. When the first layer of drug coating is surface dry, drive the conveying device body to rotate around its center line at a speed of 200 rpm for 5 seconds.

[0066] (5) Apply the drug coating solution in segments, applying it from left to right to 2 / 3 of the balloon length, with a coating thickness of 3 μm;

[0067] The drug coating solution was applied to the entire length of the balloon from left to right, with a coating thickness of 12 μm.

[0068] (6) Install the protective sleeve. The inner surface of the protective sleeve is pre-coated with a drug coating solution with a coating thickness of 1 μm. Put the protective sleeve on the left end of the balloon until the protective sleeve completely covers the surface of the balloon.

[0069] (7) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0070] ±2℃, humidity 60%±5%.

[0071] Example 4:

[0072] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0073] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0074] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0075] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 60 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0076] (4) Spinning: Dry the first layer of drug coating at room temperature. When the first layer of drug coating is surface dry, drive the conveying device body to rotate around its center line at a speed of 150 rpm for 5 seconds.

[0077] (5) Apply the drug coating solution in segments, applying it from left to right to 2 / 3 of the balloon length, with a coating thickness of 3 μm;

[0078] The drug coating solution was applied to the entire length of the balloon from left to right, with a coating thickness of 12 μm.

[0079] (6) Install the protective sleeve. The inner surface of the protective sleeve is pre-coated with a drug coating solution with a coating thickness of 1 μm. Put the protective sleeve on the left end of the balloon until the protective sleeve completely covers the surface of the balloon.

[0080] (7) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0081] ±2℃, humidity 60%±5%.

[0082] Example 5:

[0083] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0084] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0085] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0086] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 60 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0087] (4) Spinning: Dry the first layer of drug coating at room temperature. When the first layer of drug coating is surface dry, drive the conveying device body to rotate around its center line at a speed of 180 rpm for 5 seconds.

[0088] (5) Apply the drug coating solution in segments, applying it from left to right to 2 / 3 of the balloon length, with a coating thickness of 3 μm;

[0089] The drug coating solution was applied to the entire length of the balloon from left to right, with a coating thickness of 12 μm.

[0090] (6) Install the protective sleeve. The inner surface of the protective sleeve is pre-coated with a drug coating solution with a coating thickness of 1 μm. Put the protective sleeve on the left end of the balloon until the protective sleeve completely covers the surface of the balloon.

[0091] (7) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0092] ±2℃, humidity 60%±5%.

[0093] Example 6:

[0094] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0095] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0096] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0097] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 60 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0098] (4) Spinning: Dry the first layer of drug coating at room temperature. When the first layer of drug coating is surface dry, drive the conveying device body to rotate around its center line at a speed of 200 rpm for 5 seconds.

[0099] (5) Apply the drug coating solution in segments, applying it from left to right to 2 / 3 of the balloon length, with a coating thickness of 3 μm;

[0100] The drug coating solution was applied to the entire length of the balloon from left to right, with a coating thickness of 12 μm.

[0101] (6) Install the protective sleeve. The inner surface of the protective sleeve is pre-coated with a drug coating solution with a coating thickness of 1 μm. Put the protective sleeve on the left end of the balloon until the protective sleeve completely covers the surface of the balloon.

[0102] (7) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0103] ±2℃, humidity 60%±5%.

[0104] Comparative Example 1:

[0105] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0106] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0107] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0108] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 40 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0109] (4) Apply the drug coating solution in segments, applying it from left to right to 2 / 3 of the balloon length, with a coating thickness of 3 μm;

[0110] The drug coating solution was applied to the entire length of the balloon from left to right, with a coating thickness of 12 μm.

[0111] (5) Install the protective sleeve. The inner surface of the protective sleeve is pre-coated with a drug coating solution with a coating thickness of 1 μm. Put the protective sleeve on the left end of the balloon until the protective sleeve completely covers the surface of the balloon.

[0112] (6) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0113] ±2℃, humidity 60%±5%.

[0114] Comparative Example 2:

[0115] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0116] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0117] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0118] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 40 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0119] (4) Spinning: Dry the first layer of drug coating at room temperature. When the first layer of drug coating is surface dry, drive the conveying device body to rotate around its center line at a speed of 200 rpm for 5 seconds.

[0120] (5) Apply coating along the entire length of the balloon, with a coating thickness of 15 μm;

[0121] (6) Install the protective sleeve. The inner surface of the protective sleeve is pre-coated with a drug coating solution with a coating thickness of 1 μm. Put the protective sleeve on the left end of the balloon until the protective sleeve completely covers the surface of the balloon.

[0122] (7) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0123] ±2℃, humidity 60%±5%.

[0124] Comparative Example 3:

[0125] Prepare a drug coating solution by mixing 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran; apply the solution in a Class 10,000 cleanroom using the following method:

[0126] (1) Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism;

[0127] (2) Inflation: Inflate the balloon to 2 atm to 4 atm;

[0128] (3) Primer: Drive the delivery device body to rotate around its center line at a speed of 40 rpm. At the same time, apply the first layer of coating to the surface of the balloon from the left end to the right end to form the first layer of drug coating.

[0129] (4) Spinning: Dry the first layer of drug coating at room temperature. When the first layer of drug coating is surface dry, drive the conveying device body to rotate around its center line at a speed of 200 rpm for 5 seconds.

[0130] (5) Apply the drug coating solution in segments, applying it from left to right to 2 / 3 of the balloon length, with a coating thickness of 3 μm;

[0131] The drug coating solution was applied to the entire length of the balloon from left to right, with a coating thickness of 12 μm.

[0132] (6) Install the protective cover by putting the protective cover on the left end of the balloon until the protective cover completely covers the surface of the balloon.

[0133] (7) Drying: Place the drug coating delivery device in a constant temperature and humidity drying oven for drying at a temperature of 40°C.

[0134] ±2℃, humidity 60%±5%.

[0135] Coating adhesion test:

[0136] To simulate actual surgical procedures, the drug-coated balloons from Examples 1-6 and Comparative Examples 1-3 were used to deliver drugs through an in vitro simulation model. Then, the residual drug content on the drug coating in each example and comparative example was tested after delivering simulated blood vessels of the same length and specifications.

[0137] Test equipment: Shimadzu LC-15C / LC-16 high performance liquid chromatograph.

[0138] Chromatographic conditions (Sirolimus): C18 column, 150×4.6 mm; diluent: acetonitrile; mobile phase: acetonitrile:water (65:35); column temperature: 60℃; detection wavelength: 280 nm; flow rate: 1 mL / min; injection volume: 20 μL.

[0139] The coating adhesion of the product was calculated using the following formula: Coating adhesion = (Residual drug content / Initial drug content on the balloon surface) × 100%. The test results are shown in Table 1.

[0140] Table 1 also shows the uniformity of the drug coating thickness prepared by Examples 1-6 and Comparative Examples 1-3.

[0141]

[0142]

[0143] The difference between Examples 1-6 is that the rotation speeds in the spinning and base coating processes are different. The difference between Comparative Examples 1-3 and Example 3 is that Comparative Example 1 omits the spinning process; Comparative Example 2 omits the segmented coating process; and the inner surface of the protective sleeve in Comparative Example 3 is not pre-coated with a drug coating solution.

[0144] The coating thickness uniformity includes three progressively decreasing levels: uniform, relatively uniform, and non-uniform. Figure 4 and Figure 5 The images show the coatings prepared by the coating methods of Example 3 and Comparative Example 2, respectively. It is clear that pre-coating the inner surface of the protective sleeve with a drug coating can effectively improve the uniformity of the drug coating thickness on the balloon.

[0145] As shown in Table 1, the drug adhesion of Examples 1-6 all reached over 90%, while the coating adhesion of Comparative Examples 1-3 was only 84.3%, 86.7%, and 84.9%, respectively. This indicates that by incorporating methods such as spinning, segmented application, and pre-immersion of the drug coating solution inside the protective sleeve in the drug application method, the adhesion of the drug coating can be effectively improved.

[0146] When the drug coating solution composition is consistent, consisting of 210 mg sirolimus, 4 mg magnesium stearate, 3 mg butylated hydroxytoluene, 35 ml acetone, 26 ml acetic acid, and 8 ml tetrahydrofuran, the optimal coating adhesion can be obtained by using a lower rotation speed of 40 rpm for priming and a higher rotation speed of 200 rpm for spin coating. This is because priming at 40 rpm ensures the uniformity of the first drug coating layer, avoiding breakpoints and peeling, and also prevents the first drug coating layer from detaching from the balloon surface during rotation. Once it cures to the desired consistency... When dry, rotating the conveying device at a high speed can roughen the surface of the first layer of drug coating in the semi-dry state. The higher the speed, the better the roughness, which can better ensure the adhesion between the first layer of drug coating and the drug solution applied in the segmented coating process. However, the speed in the swirl process cannot be too high. When the speed exceeds 200 rpm, the firmness of the drug coating tends to decrease. This is because when swirl is performed at too high a speed, the first layer of drug coating will completely peel off from the surface of the balloon over a large area, thus failing to achieve the technical effect of increased firmness.

[0147] When the primer is applied at 60 rpm, the coating solution cannot effectively adhere to the balloon surface during the primer application process, resulting in a decrease in the adhesion of the first coating layer. The shaving process further reduces the adhesion of the first coating layer. Therefore, even if the subsequent processes are the same, the final coating adhesion is still somewhat reduced.

[0148] By comparing Comparative Example 2 and Example 3, it can be seen that the segmented coating process can enhance the coating's adhesion to a certain extent. The segmented coating method makes the thickness of the drug solution applied to both ends of the balloon inconsistent. When the protective sleeve is put on the end with the thicker coating on the balloon, the protective sleeve will carry the drug from the thicker end to the thinner end, thereby forming a uniform coating on the balloon surface. Because the coating thickness is uniform, the stress generated during the coating drying process is small, and therefore the final coating has good adhesion.

[0149] Furthermore, by comparing Comparative Example 3 and Example 3, it can be seen that by pre-coating the protective sleeve with the drug solution and then putting the protective sleeve on the balloon, it is helpful to improve the coating's firmness and prevent drug loss. This is because the inner surface of the protective sleeve is coated with the drug coating solution, and when putting on the protective sleeve, it is easier to carry the drug coating from the thicker end of the balloon to the thinner end. This, together with the segmented coating step, is more conducive to the uniformity of the coating, thereby reducing the stress generated during the coating drying process and obtaining a coating with better firmness.

[0150] The drug coating delivery device prepared by the present invention through different coating methods has a higher drug coating firmness than the drug coating delivery device prepared by traditional coating methods. Therefore, it can significantly reduce drug loss during delivery and deliver more drug to the target lesion blood vessel, thereby improving drug utilization and clinical efficacy.

[0151] The drug coating delivery device of the present invention can be used in, but is not limited to, peripheral blood vessels, coronary blood vessels, intracranial blood vessels, etc.

[0152] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A drug coating delivery device, comprising a delivery device body, wherein a balloon is disposed on the delivery device body, the surface of the balloon is coated with a drug coating, the drug coating solution being composed of an anti-proliferative drug, excipients, stabilizers and a crystallization solvent, the drug coating being applied to the surface of the balloon by a drug coating method, characterized in that, The drug coating method includes: Clamping: Clamp both ends of the drug coating delivery device onto the drive mechanism; Inflate: Inflate the balloon to 2 atm to 4 atm; Primer: Drive the delivery device body to rotate around its center line at a speed of v1, and at the same time, apply a first layer of coating to the surface of the balloon from the left end to the right end to form a first layer of drug coating. The first drug coating layer is dried at room temperature by spinning. When the first drug coating layer reaches surface dryness, the conveying device body is driven to rotate around its center line at a speed of v2 for a duration of T. The coating is applied in segments, forming a coating segment 1 and a coating segment 2 on the surface of the balloon. The coating segment 1 and the coating segment 2 are connected, and the sum of the lengths of the coating segment 1 and the coating segment 2 is equal to the length of the balloon. The coating thickness of the coating segment 1 is d1, and the coating thickness of the coating segment 2 is d2, where d1 > d2. Install the protective cover, the inner surface of which is pre-coated with a drug coating solution. Put the protective cover on from the end of the coating section one that is away from the coating section two until the protective cover completely covers the surface of the balloon. Drying: The drug coating delivery device is placed in a constant temperature and humidity drying oven for drying at a temperature of 40±2℃ and a humidity of 60%±5%. v1 = 40-60 rpm; v2 = 150-200 rpm; T = 5-10 s.

2. The drug coating delivery device according to claim 1, characterized in that, The segmented coating process includes the following steps: (1) Apply the drug coating solution from left to right for 1 / n of the balloon length, with a coating thickness of d1-d2; (2) The drug coating solution is applied to the entire length of the balloon from left to right, with a coating thickness of d2.

3. The drug coating delivery device according to claim 2, characterized in that, The condition is that n ≥ 3 / 2 and n ≤ 3.

4. The drug coating delivery device according to claim 1, characterized in that, The anti-proliferative drug is one or more of sirolimus, gemcitabine, and daunorubicin; the excipient is one or more of magnesium stearate, sodium stearate, zinc stearate, and stearamide; the stabilizer is butylated hydroxytoluene and / or phytic acid; the crystallization solvent includes a first solvent and a second solvent, wherein the first solvent is acetone, and the second solvent is one or more of acetic acid, tetrahydrofuran, acetonitrile, and n-propyl acetate.

5. A drug coating delivery device according to claim 1, characterized in that, In the drug coating solution, the weight ratio of the antiproliferative drug to the excipient is (0.5-200):

1.

6. The drug coating delivery device according to claim 1, characterized in that, In the drug coating solution, the weight ratio of the antiproliferative drug to the stabilizer is (0.5-200):

1.

7. A drug coating delivery device according to claim 1, characterized in that, The areal density of the antiproliferative drug in the drug coating is 0.1–50 μg / mm². 2 .

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