Drug balloon and preparation method thereof

Abstract

The invention discloses a drug balloon and a preparation method thereof.The drug balloon prepared through the method comprises a catheter, a balloon body and a coating, a sunken drug storage part is arranged on the surface of the balloon body, the section of the bottom of the drug storage part is in an inverted triangle shape, and when the balloon body is in a full state, the drug storage part is changed into a protruding part from a sunken part, and the section of the top of the drug storage part is in a regular triangle shape. The medicine storage part can be coated with the medicine through precise printing, the medicine in the medicine storage part is protected by the fat-soluble medicine on the outer layer, the influence of blood flow flushing on the medicine coating is reduced, the loss of the medicine coating during conveying is reduced, and the transfer rate of the medicine coating is increased. According to the structure of the medicine storage part, on the premise that the outer diameter is not increased, the surface area of the balloon is increased, the medicine loading capacity is improved, the trafficability of the balloon is not affected, when the medicine balloon is in a full state, the medicine storage part is changed from a concave part to a convex part, the convex tip can break stubborn calcified thrombus, the medicine release rate and hemodynamics are improved, and the medicine is rapidly released and directly reaches lesion.

Description

Technical Field

[0001] The present invention relates to a balloon catheter, and particularly to a drug balloon, belonging to the technical field of medical devices. Background Art

[0002] For vascular stenosis diseases, there are currently three main interventional treatment methods: simple balloon dilation, stent implantation, and drug balloon. Among them, the drug balloon is an upgrade of simple balloon treatment, using a single drug coating. Compared with stent implantation, the drug balloon has the following advantages: uniform drug distribution, which can evenly release the drug to the intima of the blood vessel wall; no polymer coating, which can avoid the inflammatory reaction induced by the polymer coating and reduce the occurrence of late thrombosis; no need to implant a stent, which can avoid the implantation of foreign bodies, retain the original anatomical structure of the blood vessel, and reserve the opportunity for subsequent treatment for patients when necessary; it can shorten the dual antiplatelet time and reduce the incidence of bleeding complications; simple operation, good passability, and high surgical success rate.

[0003] Although the drug balloon has the above advantages, there are currently some problems, such as: the drug balloon is coated with a drug coating on its surface, resulting in an increase in volume, making it difficult to reach distal small blood vessels or complex curved lesions; the thrombus calcification at the vascular stenosis is severe, and the thrombus still exists or the residual amount is large after balloon dilation; the drug on the balloon surface is likely to fall off during the processes of balloon delivery, dilation, pressure relief, and withdrawal (including being washed away by high-speed blood flow and worn by friction with the blood vessel wall). The fallen drug coating, especially some carriers that are not soluble in blood, will exist in the form of large particles and flow to distal small blood vessels with the blood, posing a great risk of occluding distal blood vessels. Therefore, the drug balloon with a single drug coating of a common structure can no longer meet the treatment of current complex lesions. Summary of the Invention

[0004] The purpose of the present invention is to provide a drug balloon and its preparation method that solve the problems of poor passability of the drug balloon, low coating firmness, single performance, and difficulty in breaking stubborn thrombus. The technical solution is as follows:

[0005] A drug balloon includes a catheter, a balloon body, and a coating. A sunken drug storage part is arranged on the surface of the balloon body, and the cross-section of the bottom of the drug storage part is an inverted triangle.

[0006] Further, the shape of the drug storage part is a triangular prism shape or a conical shape.

[0007] Further, the depth of the drug storage part is 0.1 - 50 microns; if the depth of the drug storage part is less than 0.1 micron, the drug storage amount is insufficient, and when the balloon body is filled, the protruding tip of the drug storage part cannot play a role in breaking stubborn calcified thrombus; if the depth of the drug storage part is greater than 50 microns, when the balloon body is filled, it is difficult for the drug storage part to protrude, and the protruding tip of the drug storage part may cause harm to the blood vessel.

[0008] Furthermore, when the bladder is in a filled state, the medicine storage part changes from concave to convex, and the top cross-section of the medicine storage part is an equilateral triangle.

[0009] Furthermore, the concave is a radial concave, and the convex is a radial convex.

[0010] Furthermore, the concave is an axial concave, and the convex is an axial convex.

[0011] A preparation method of a drug balloon comprises the following steps:

[0012] Step 1) Dissolve the active drug in its respective drug solvent, and obtain a drug coating solution after ultrasonic oscillation;

[0013] Step 2) Inflate the drug balloon with a medicine storage part on its surface for standby;

[0014] Step 3) Apply the obtained drug coating solution to the surface of the balloon and the medicine storage part;

[0015] Step 4) After the drug coating solution on the surface of the balloon and the medicine storage part dries, apply the second-layer drug coating solution to the surface of the balloon and the medicine storage part again to obtain a drug balloon coated with a drug coating.

[0016] Furthermore, in Step 3) and Step 4), when applying the obtained drug coating solution to the medicine storage part, the application is carried out by means of precision printing because the medicine storage part is too small and only a special machine can be used for precision printing to apply the drug to the medicine storage part.

[0017] Furthermore, the drug in the second-layer drug coating solution is liposoluble, which can effectively prevent the drug in the medicine storage part from falling off.

[0018] Furthermore, the drugs applied to the medicine storage part are water-soluble, liposoluble and amphiphilic drugs.

[0019] Furthermore, the functions of the drug coating include anti-cell proliferation, anticoagulation and anti-thrombosis.

[0020] Furthermore, the hardness of the material at the medicine storage part is greater than the hardness of the material at other parts of the balloon surface.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows. For the drug balloon prepared by the preparation method of the present invention, through precise printing, drugs can be coated in the drug storage part. The outer layer of lipophilic drugs protects the drugs in the drug storage part, reduces the influence of blood flow scouring on the drug coating, reduces the loss during the delivery of the drug coating, and increases the transfer rate of the drug coating. The structure of the drug storage part can increase the surface area of the balloon without increasing the outer diameter, improve the drug loading capacity, and does not affect the passability of the balloon, and can reach the position of small vessel lesions at the distal end. When the drug balloon is in the inflated state, the drug storage part changes from concave to convex, and the protruding tip can break stubborn calcified thrombi, increase the drug release rate and hemodynamics, enable the drug to be released quickly and directly reach the lesion. The drug coating prepared by the present invention contains a variety of drugs, which can exert multiple effects and meet various requirements of clinical practice. Description of the Drawings

[0022] Figure 1 It is a schematic structural diagram of the inflated state of the drug balloon;

[0023] Figure 2 It is a schematic structural diagram of the inflated state of the drug balloon;

[0024] Figure 3 It is a schematic structural diagram of the inflated state of the drug balloon with a triangular prism-shaped drug storage part;

[0025] Figure 4 It is a schematic diagram of a partial drug coating of Example 2;

[0026] Figure 5 It is a schematic diagram of a partial drug coating of Example 3;

[0027] Figure 6 It is a schematic diagram of a partial drug coating of Example 4;

[0028] In the figure, 1 is a catheter, 2 is a balloon body, and 3 is a drug storage part. Detailed Embodiments

[0029] The following further illustrates the present invention with reference to the drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the embodiments cited are not intended to limit the present invention.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the description of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0031] The experimental methods used in the following embodiments are all conventional methods unless otherwise specified. The materials, reagents, etc. used in the following embodiments can be obtained from commercial channels unless otherwise specified.

[0032] All the balloon specifications used in the examples and comparative examples are the same: the balloon diameter is 4 mm and the balloon length is 20 mm.

[0033] Example 1

[0034] Figure 1 and Figure 2 As shown, when the balloon 2 is in the inflated state, a radially concave drug storage part 3 is arranged on the surface of the balloon body. The balloon 2 is sent to the blood vessel lesion, and the balloon 2 is inflated to make the balloon 2 in the full state. At this time, the radially concave drug storage part 3 on the surface of the balloon body bulges reversely under the action of pressure, and a radially protruding drug storage part 3 is formed on the surface of the balloon body. The tip of the drug storage part 3 can break stubborn calcified thrombus and release the drug to the affected area at the same time.

[0035] Example 2

[0036] Dissolve 200 mg of heparin in 20 ml of pure water and 200 mg of paclitaxel in 20 ml of absolute ethanol to obtain 10 mg / ml sodium heparin aqueous solution and 10 mg / ml paclitaxel ethanol solution respectively. Use a drug coating printing machine to print the sodium heparin drug solution onto the grooves on the balloon surface, and then spray the paclitaxel drug solution onto the balloon surface and dry it.

[0037] Example 3

[0038] Dissolve 200 mg of heparin in 20 ml of pure water, 200 mg of paclitaxel in 20 ml of absolute ethanol, and 200 mg of bivalirudin in 20 ml of absolute ethanol to obtain 10 mg / ml sodium heparin aqueous solution, 10 mg / ml paclitaxel ethanol solution and 10 mg / ml bivalirudin ethanol solution respectively. Use a drug coating printing machine to print the sodium heparin and bivalirudin drug solutions onto the grooves on the balloon surface respectively, then spray the paclitaxel ethanol solution and dry it.

[0039] Example 4

[0040] Dissolve 200 mg of heparin in 20 ml of pure water, 200 mg of argatroban in 20 ml of absolute ethanol, 200 mg of bivalirudin in 20 ml of absolute ethanol, and 200 mg of paclitaxel in 20 ml of absolute ethanol to obtain 10 mg / ml sodium heparin aqueous solution, 10 mg / ml argatroban ethanol solution, 10 mg / ml bivalirudin ethanol solution and 10 mg / ml paclitaxel ethanol solution respectively. Use a drug coating printing machine to print the first three drug solutions onto the grooves on the balloon surface respectively, and then spray the paclitaxel drug solution onto the balloon surface and dry it.

[0041] Example 5

[0042] Dissolve 200 mg of paclitaxel in 20 ml of absolute ethanol to obtain a 10 mg / ml paclitaxel ethanol solution. Use a drug-coated printing machine to print the paclitaxel liquid medicine onto the grooves on the surface of the balloon, and then spray the paclitaxel liquid medicine onto the surface of the balloon and dry it.

[0043] Example 6

[0044] Dissolve 200 mg of heparin in 20 ml of pure water, 200 mg of argatroban in 20 ml of absolute ethanol, 200 mg of bivalirudin in 20 ml of absolute ethanol, and 200 mg of paclitaxel in 20 ml of absolute ethanol to obtain a 10 mg / ml heparin sodium aqueous solution, a 10 mg / ml argatroban ethanol solution, a 10 mg / ml bivalirudin ethanol solution, and a 10 mg / ml paclitaxel ethanol solution respectively. Use an ultrasonic spraying machine to spray the first three drug solutions onto the surface of the balloon respectively and dry them.

[0045] Example 7

[0046] Dissolve 200 mg of paclitaxel in 20 ml of absolute ethanol to obtain a 10 mg / ml paclitaxel ethanol solution. Use an ultrasonic spraying machine to spray the paclitaxel liquid medicine onto the surface of the balloon and dry it.

[0047] Example 8

[0048] Use a laser diameter gauge to detect the pleated outer diameter of the drug-coated balloon samples (diameter 4.0 mm, length 20 mm) prepared in Examples 2-5 and Examples 6-7. The test results are shown in the following table.

[0049] Table 1 Detection results of the pleated outer diameter of the balloon

[0050] Group Pleated outer diameter (mm) Example 1 1.10 Example 2 1.12 Example 3 1.14 Example 4 1.07 Comparative Example 1 1.20 Comparative Example 2 1.16

[0051] The drug balloon samples prepared in Examples 2-5 and Examples 6-7 were divided into groups a, b, c, and d. For group a, the drug content m1 of the drug balloon was directly measured. For group b, through an in vitro test model, simulating the process of using the drug balloon in the human body, a 1:1 human pipeline model was adopted, with the guiding catheter as the delivery path, and the end of the pipeline model was connected to the release medium (PBS buffer containing 85% ethanol). The water flow rate was controlled by a peristaltic pump. The drug balloon in group b was delivered to the designated vascular position through a guide wire, the drug balloon was withdrawn, then the balloon part was cut from the end of the pipeline and dried, placed in a glass container, a quantitative solvent was added, and after ultrasonic oscillation, the drug content m2 was measured. The drug balloon in group c reached the designated vascular position through a guide wire, then the balloon was inflated, maintained at a pressure of 10 atm for 60 s, and the drug balloon was withdrawn. Then the balloon part was cut from the end of the pipeline and dried, and the drug content m3 was measured. The microparticle analyzer was used to test the eluate generated during the simulated use process of the drug balloon in group b. According to the light obscuration method in the general rules (0903) for the inspection of insoluble particles in the fourth part of the Chinese Pharmacopoeia 2020 edition, 50 ml of the eluate was aspirated for detection. The drug content was measured by high performance liquid chromatography:

[0052] The test results are shown in the following table.

[0053] Table 2 Detection results of drug coating firmness

[0054]

[0055] Table 3 Simulated delivery and release results of drug coating

[0056]

[0057] Note: Delivery loss rate = (m2 - m1) / m1 × 100%; Release rate = (m3 - m1) / m1 × 100%

[0058] The above test results show that a drug balloon of the present invention enhances the firmness of the coating, reduces drug loss during the delivery process, and at the same time, the drug can be released to the tissue relatively faster during the inflation process.

[0059] Example 9

[0060] A preparation method of a drug balloon, comprising the following steps:

[0061] Step 1) Dissolve the active drug in its respective drug solvent, and obtain a drug coating solution after ultrasonic oscillation;

[0062] Step 2) Inflate the drug balloon with a drug storage part provided on the surface of the balloon body for standby;

[0063] Step 3) The obtained drug coating solution is applied to the surface of the balloon and is applied to the drug storage part by precision printing. The drug applied to the drug storage part is a water-soluble or lipid-soluble or amphiphilic drug;

[0064] Step 4) After the drug coating solution on the surface of the balloon and in the drug storage part is dried, the second layer of drug coating solution is applied to the surface of the balloon and in the drug storage part to obtain a drug balloon coated with a drug coating.

[0065] The drug in the second layer of drug coating solution is lipid-soluble and can effectively prevent the drug in the drug storage part from falling off.

[0066] The above-described embodiments are merely preferred embodiments given to fully illustrate the present invention. However, the present invention is not limited to the above specific embodiments. The above specific embodiments are merely illustrative and not restrictive. Under the inspiration of the present invention, those of ordinary skill in the art can also make many forms without departing from the spirit and scope protected by the claims of the present invention. These all fall within the protection scope of the present invention.

Claims

1. A drug balloon, comprising a catheter, a balloon body and a coating, characterized in that, A recessed medicine storage part (3) is arranged on the surface of the capsule body (2), and the bottom cross section of the medicine storage part (3) is an inverted triangle.

2. The drug balloon according to claim 1, wherein, The medicine storage part (3) is in the shape of a triangular prism or a cone.

3. A drug balloon according to claim 1, characterized in that, The depth of the medicine storage part (3) is 0.1 - 50 micrometers.

4. A drug balloon according to claim 1, characterized in that, When the capsule body (2) is in a filled state, the medicine storage part (3) changes from a recess to a protrusion, and the top cross section of the medicine storage part (3) is an equilateral triangle.

5. The drug balloon according to claim 4, wherein, The recess is a radial recess, and the protrusion is a radial protrusion.

6. The drug balloon according to claim 4, wherein The recess is an axial recess, and the protrusion is an axial protrusion.

7. A preparation method of a drug balloon, characterized in that, It includes the following steps: Step 1): Dissolve the active drug in its respective drug solvent, and obtain a drug coating solution after ultrasonic oscillation; Step 2): Inflate the drug balloon with a medicine storage part arranged on its surface for standby; Step 3): Apply the obtained drug coating solution to the surface of the balloon and the medicine storage part; Step 4): After the drug coating solution on the surface of the balloon and the medicine storage part dries, apply the second-layer drug coating solution to the surface of the balloon and the medicine storage part again to obtain a drug balloon coated with a drug coating.

8. The preparation method of a drug balloon according to claim 7, characterized in that, In step 3) and step 4), when applying the obtained drug coating solution to the medicine storage part, the application is carried out by means of precision printing.

9. The drug balloon according to claim 7, wherein The drug in the second-layer drug coating solution is liposoluble.

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