Drug balloon dilatation catheter

Abstract

The invention discloses a medicine balloon dilatation catheter which comprises a balloon and a support arranged outside the balloon, the support is in a net pipe shape and can dilate and contract along with the balloon, the dilatation diameter of the support is smaller than the dilatation diameter of the balloon during dilatation, and the dilatation catheter further comprises a medicine coating coated on the outer portion of the balloon. The drug coating comprises a plurality of magnetic drug particles; in a contraction state, the medicine particles are positioned between the balloon and the stent; in the expansion state, part of the sacculus swells out of the stent from the meshes of the stent to form a plurality of protruding parts, and the medicine particles are located on the protruding parts respectively. According to the drug balloon dilatation catheter, under the action of an in-vitro magnetic field, free drug particles generated in the dilatation process of the dilatation catheter can migrate to a vascular intima, meanwhile, the magnetic field can also prevent the drug particles squeezed into a blood vessel from being washed by blood to be separated from the blood vessel, and drug loss in the dilatation process can be reduced. And the stent is arranged outside the balloon, so that the medicine loss of the dilating catheter in the conveying process can be reduced.

Description

Technical Field

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

[0002] Obstruction of the body's arteries is a common condition, such as peripheral artery disease (PAD), which generally refers to lesions of various arteries other than the coronary and intracranial arteries. Currently, one of the main treatments for PAD is angioplasty, using a balloon device to shape the vascular pathway or perform pre- and post-dilation procedures to ensure vascular access after stent deployment.

[0003] Traditional balloons can damage the endothelium while dilating narrowed blood vessels, leading to adverse consequences such as dissection and restenosis. By coating the balloon surface with drugs such as paclitaxel and rapamycin, the proliferation of the endothelium can be inhibited and the adverse consequences of the balloon can be reduced.

[0004] However, existing drug-eluting balloons suffer from low drug transfer efficiency and significant drug loss during vascular delivery and balloon expansion. One of the research directions for drug-eluting balloon dilation catheters is to efficiently transfer the drug from the balloon surface to the patient's vascular endothelium during surgery. Summary of the Invention

[0005] The purpose of the present invention is to provide a drug balloon dilatation catheter that can reduce the loss of drugs during the delivery and expansion process to improve the efficiency of drug transfer to blood vessels in order to solve the problems in the prior art.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] A drug balloon dilatation catheter comprises a balloon and a stent coated on the outside of the balloon, wherein the stent has a mesh tubular structure and can expand and contract with the balloon, and when expanded, the expanded diameter of the stent is smaller than the expanded diameter of the balloon. The dilatation catheter also comprises a drug coating coated on the outside of the balloon, wherein the drug coating comprises a plurality of magnetic drug particles; in a contracted state, the drug particles are all located between the balloon and the stent; in an expanded state, portions of the balloon bulge out from the various meshes of the stent to the outside of the stent to form a plurality of protrusions, and the drug particles are respectively located on each of the protrusions.

[0008] In some embodiments, the drug particles include a magnetic material, a drug that inhibits intimal hyperplasia, and a carrier.

[0009] In some embodiments, the mass ratio of the magnetic material, the drug, and the carrier is (2.8-3.2):(1.8-2.2):(4.8-5.2).

[0010] In some embodiments, the magnetic material is ferroferric oxide;

[0011] and / or, the drug is paclitaxel or rapamycin;

[0012] And / or, the carrier is a degradable polymer material.

[0013] In some embodiments, the drug coating has a thickness of 0.06 mm to 0.8 mm.

[0014] In some embodiments, the size of a single drug particle is 200 nm-500 um.

[0015] In some embodiments, the size of a single drug particle is 500 nm-250 um.

[0016] In some embodiments, the drug particles are spherical, or spherical in shape with a pointed end facing away from the balloon.

[0017] In some embodiments, the stent includes a main body portion and connecting portions respectively arranged at both ends of the main body portion to be connected to the balloon, the main body portion includes a longitudinal rod extending in the longitudinal direction, and a plurality of the longitudinal rods are arranged at intervals along the circumferential direction, the main body portion also includes a transverse rod connected between each adjacent two longitudinal rods, and a plurality of the transverse rods between each adjacent two longitudinal rods are arranged at intervals along the longitudinal direction, a mesh is formed between each adjacent two longitudinal rods and each adjacent two transverse rods, and each of the longitudinal rods and the transverse rod can expand and contract with the balloon.

[0018] In some embodiments, the drug coating is respectively coated in the mesh area formed between each two adjacent longitudinal rods and each two adjacent transverse rods of the balloon.

[0019] In some embodiments, the connecting portion includes a connecting rod extending along the longitudinal direction, and a plurality of the connecting rods are arranged at intervals along the circumferential direction. In each connecting portion, the number of the connecting rods is not greater than the number of the longitudinal rods, and one end of each of the connecting rods is connected to or integrally arranged with a different longitudinal rod, and the connecting rods can expand and contract with the balloon.

[0020] In some embodiments, the dilatation catheter further includes a protective film covering the outside of the stent, and the protective film is made of a degradable polymer material.

[0021] Due to the application of the above technical solution, the present invention has the following advantages over the prior art: in the drug balloon dilatation catheter of the present invention, the drug particles are magnetic. Under the action of an in vitro magnetic field, the free drug particles generated during the dilatation process of the dilatation catheter will migrate to the vascular endothelium and be quickly wrapped or absorbed by the endothelium. At the same time, the magnetic field can also prevent some drug particles squeezed into the blood vessels from being washed out of the blood vessels by the blood, which can reduce the loss of drugs during balloon dilatation and increase the efficiency of drug transfer. Moreover, in addition to enhancing the ability of the balloon to dilate calcified lesions, the provision of a stent outside the balloon also allows the drug particles to be located between the balloon and the stent during the dilatation catheter delivery process. The stent can isolate the blood from the drug particles, reducing the scouring of the drug particles by the blood, thereby reducing the loss of drugs during delivery. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is a front view schematic diagram of the drug-eluting balloon dilatation catheter of this embodiment when not expanded;

[0023] Figure 2 for Figure 1 A partial enlarged schematic diagram in the middle;

[0024] Figure 3 for Figure 1 A partial enlarged schematic diagram of point B in the middle;

[0025] Figure 4 is a front view schematic diagram of the drug-eluting balloon dilatation catheter of this embodiment in an expanded state;

[0026] Figure 5 is a side view schematic diagram of the drug-eluting balloon dilatation catheter of this embodiment in an expanded state;

[0027] Figure 6 This is one of the schematic diagrams of the morphology of drug particles in the drug balloon dilatation catheter of this embodiment;

[0028] Figure 7 This is the second schematic diagram of the morphology of drug particles in the drug-eluting balloon dilatation catheter of this embodiment;

[0029] Figure 8 Schematic diagram of the microscopic morphology of drug particles in the drug balloon dilatation catheter of this embodiment;

[0030] Figure 9 This is a schematic diagram of the morphology of drug particles in a blood vessel when the drug balloon dilatation catheter of this embodiment is in an expanded state;

[0031] Figure 10 This is a schematic diagram of the microsphere transfer rate when the drug particles of this embodiment are prepared according to different mass ratios of ferroferric oxide, paclitaxel and polyglycolide;

[0032] Figure 11 This is a schematic diagram of drug transfer rates when ferrosoferric oxide, paclitaxel, and polyglycolide are prepared at different mass ratios in the drug particles of this embodiment;

[0033] Figure 12 This is a schematic diagram showing the number of days the drug concentration is maintained above 1 μmol / L when the drug particles of this embodiment are prepared according to different mass ratios of ferroferric oxide, paclitaxel, and polyglycolide;

[0034] Figure 13 This is a schematic diagram of drug transfer rates when the drug particles of this embodiment are prepared with polyglycolide at a mass fraction of 50% and ferrosoferric oxide and paclitaxel at different mass ratios;

[0035] Figure 14 Schematic diagram of drug transfer rate for drug particles of different particle sizes in this embodiment;

[0036] Figure 15 This is a schematic diagram of the number of days the drug concentration is maintained above 1 μmol / L for different particle sizes of the drug particles in this embodiment.

[0037] Among them: 1. outer tube; 2. inner tube; 3. balloon; 31. protrusion; 4. bracket; 41. longitudinal rod; 42. transverse rod; 43. connecting rod; 5. tip tube; 6. drug particles; 61. magnetic material; 62. drug; 63. carrier; 7. developing ring. DETAILED DESCRIPTION

[0038] The technical solutions of the present invention will be described clearly and completely below with reference to the accompanying drawings. It is apparent that the embodiments described are only a portion of the embodiments of the present invention, not all of them. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are intended to fall within the scope of protection of the present invention.

[0039] In the description of the present invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," "outer," and the like, indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, or are the orientations or positional relationships in which the patented product is typically placed when in use. These terms are intended solely to facilitate the description of the present invention and to simplify the description, and are not intended to indicate or imply that the device or component referred to must have a specific orientation, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limitations on the present invention. Furthermore, the terms "first," "second," and "third," etc., are used solely to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0040] Unless otherwise specified, the proximal end and distal end mentioned in the present invention have the same meaning in terms of direction, that is, in the use state, the distal end is the end away from the operator, and the proximal end is the end close to the operator. The operator controls the drug balloon dilatation catheter at the proximal end.

[0041] like Figure 1 and Figure 4 As shown, the drug balloon dilatation catheter of the present invention includes an outer tube 1, an inner tube 2, a balloon 3, a stent 4 and a drug coating.

[0042] The proximal portion of the inner tube 2 is inserted into the lumen of the outer tube 1 , and the distal portion of the inner tube 2 is sheathed with a tip tube 5 .

[0043] Balloon 3 is sheathed over inner tube 2, with its proximal end connected to the distal end of outer tube 1, and its distal end connected to the proximal end of tip tube 5. Stent 4 is wrapped around balloon 3, with its proximal end connected to the proximal end of balloon 3, and its distal end connected to the distal end of balloon 3. Balloon 3, outer tube 1, tip tube 5, and stent 4 can all be connected by adhesive bonding or hot melt.

[0044] The balloon 3 is a semi-compliant balloon, and the diameter of the balloon 3 can increase with the increase of the pressure in the balloon cavity of the balloon 3. The balloon 3 can be made of nylon 12 material.

[0045] Stent 4 has a reticular tubular structure that expands and contracts with balloon 3. During expansion, the expanded diameter of stent 4 is smaller than that of balloon 3. The restraint of stent 4 allows balloon 3 to maintain an optimal expanded length and diameter within the vessel. Furthermore, due to the restraint of stent 4, balloon 3 expands gently and evenly during expansion, preventing premature or excessive expansion of the vessel and reducing the radial and longitudinal forces exerted by balloon 3 on the vessel wall. Furthermore, stent 4 also serves as a positioning mechanism, preventing balloon 3 from rotating or deflecting relative to the diseased vessel, ensuring uniform shear forces on the vessel wall and minimizing vascular damage and complications.

[0046] Specifically, the stent 4 includes a main body and a connecting portion. The connecting portions are respectively arranged at the distal end and the proximal end of the main body. The connecting portions at both ends of the main body are respectively connected to the balloon 3.

[0047] The main body includes longitudinal rods 41 and transverse rods 42, both of which can expand and contract with the balloon 3. The longitudinal rods 41 extend longitudinally, and multiple longitudinal rods 41 are spaced circumferentially. The transverse rods 42 connect between every two adjacent longitudinal rods 41, and multiple transverse rods 42 are spaced longitudinally between every two adjacent longitudinal rods 41. Thus, a mesh is formed between every two adjacent longitudinal rods 41 and every two adjacent transverse rods 42.

[0048] Preferably, the connection position of each transverse rod 42 on the two adjacent longitudinal rods 41 is at different positions in the longitudinal direction. Along the circumferential direction, the adjacent ends of the two adjacent transverse rods 42 are connected, or connected to the same position of the longitudinal rod 41. The two adjacent transverse rods 42 are symmetrically arranged relative to the longitudinal rod 41 to which they are connected. In this way, after the stent 4 is expanded with the balloon 3, its cross section is approximately circular. Each transverse rod 42 can be an S-shaped structure, such as Figure 1 and Figure 2 shown.

[0049] The diameter height of the longitudinal rod 41 and the transverse rod 42 is 0.05mm-0.35mm, preferably 0.1mm-0.2mm. The width of the longitudinal rod 41 is 50% wider than the width of the transverse rod 42. In this embodiment, the width of the transverse rod 42 is 0.15mm.

[0050] The connecting portion includes a connecting rod 43 extending longitudinally, and a plurality of connecting rods 43 are arranged at intervals along the circumferential direction. The end of each connecting rod 41 is connected to the end of a different longitudinal rod 41 or is integrally arranged. The connecting rod 43 can also expand and contract with the balloon 3.

[0051] In each connecting portion, the number of connecting rods 43 is not greater than the number of longitudinal rods 41 . In this embodiment, in each connecting portion, the number of connecting rods 43 is half of the number of longitudinal rods 41 .

[0052] The structure of the connecting rod 43 can be a straight line, a wavy line, an S-shaped structure, etc., preferably an S-shaped structure, such as Figure 1 and Figure 3 As shown, this makes the connecting rod 43 deform relatively more along with the balloon 3 .

[0053] The diameter and height of the connecting rod 43 are 0.05 mm to 0.35 mm, preferably 0.1 mm to 0.2 mm.

[0054] The longitudinal rod 41 , the transverse rod 42 and the connecting rod 43 are all made of nickel titanium material.

[0055] The drug coating is applied to the exterior of the balloon 3. Specifically, the drug coating is applied to the mesh regions formed between each two adjacent longitudinal rods 41 and each two adjacent transverse rods 42 of the balloon 3. The drug coating is bonded to the surface of the balloon 3 via an excipient. In this embodiment, the excipient may be magnesium stearate.

[0056] The drug coating includes a plurality of drug particles 6. In the contracted state, the drug particles 6 are located between the balloon 3 and the stent 4. Thus, when the dilatation catheter is transported in the blood vessel, the blood and the drug particles 6 can be separated by the stent 4, thereby avoiding drug loss during the transport process. In the expanded state, parts of the balloon 3 bulge out from the mesh of the stent 4 to the outside of the stent 4, thereby forming a plurality of protrusions 31. Each drug particle 6 is located on the protrusion 31, so that each drug particle 6 contacts the blood vessel wall and is directly squeezed into the vascular endothelium. Figure 4 and Figure 5 shown.

[0057] The drug particles 6 can be spherical, such as Figure 6 Alternatively, the drug particles 6 may be spherical with a pointed end facing away from the balloon 3, as shown in FIG. Figure 7 shown.

[0058] The drug particles 6 are magnetic. Specifically, Figure 8 As shown, drug particles 6 include a magnetic material 61, a drug 62 for inhibiting intimal hyperplasia, and a carrier 63. Magnetic material 61 can be ferrosoferric oxide. Drug 62 can be paclitaxel or rapamycin. Carrier 63 can be a biodegradable polymer material such as PLLA, PGA, or PGLA.

[0059] The mass ratio of the magnetic material 61, the drug 62 and the carrier 63 is (2.8-3.2):(1.8-2.2):(4.8-5.2). Preferably, the mass ratio of the magnetic material 61, the drug 62 and the carrier 63 is 3:2:5.

[0060] Specific examples are given below:

[0061] A total of 20 g of ferroferric oxide, paclitaxel, and polyglycolide were prepared according to mass ratios of 1:1:8, 2:1:7, 2:2:6, 3:2:5, 3:3:4, 4:3:3, 4:4:2, and 0:2:8, respectively. Specifically, ferroferric oxide in a set ratio was first dissolved in 70 mL of dichloromethane, and then paclitaxel and polyglycolide in a set ratio were added. Drug particles 6 with a particle size of (10±2) μm were prepared by a double emulsion method. Finally, the prepared drug particles 6 were coated on the outside of the balloon 3 to form a drug coating.

[0062] Under the above different ratios, the corresponding microsphere transfer rates are detailed in Figure 10 The drug transfer rate is shown in Figure 11 The number of days the drug is maintained above 1 μmol / L (the lowest concentration with the best effect of inhibiting smooth muscle cell proliferation) is shown in Figure 12 As shown. Figures 10 to 12It can be seen from the figure that when the mass fraction of polyglycolide in the drug particles 6 is 50%, the comprehensive effect of the formed drug particles 6 is the best.

[0063] When the mass fraction of polyglycolide in drug particles 6 was controlled to be 50%, the proportion of ferric oxide and paclitaxel was adjusted to make the mass ratio of ferric oxide and paclitaxel 2:3, 3:2, and 4:1, respectively, the drug transfer rate was obtained. The results are as follows: Figure 13 As shown. Figure 13 It can be seen that when the mass fraction of polyglycolide in the microspheres is 50%, the drug transfer rate is the highest when the mass ratio of ferrosoferric oxide to paclitaxel is 3:2.

[0064] The thickness of the drug coating is 0.06 mm to 0.8 mm. The size of a single drug particle 6 is 200 nm to 500 μm, preferably 500 nm to 250 μm.

[0065] Specific examples are given below:

[0066] When the mass ratio of the magnetic material 61, the drug 62 and the carrier 63 is 3:2:5, the drug particles 6 are prepared according to the particle sizes of 0.2um, 0.5um, 1um, 10um, 100um, 200um, 250um and 500um respectively, and then the prepared drug particles 6 are coated on the outside of the balloon 3 to form a drug coating.

[0067] The drug transfer rates corresponding to drug particles of different sizes are detailed in Figure 14 The number of days the drug is maintained above 1umol / L is shown in Figure 15 As shown. Figure 14 and Figure 15 It can be seen that the best comprehensive effect is achieved when the size of the single drug particle 6 is 500nm-250um.

[0068] The dilatation catheter may also include a protective film covering the exterior of the stent 4. This protective film is made of a biodegradable polymer and has a thickness of 20 μm. This protective film further reduces drug loss during delivery through the dilatation catheter. When the drug particles 6 have sharp points, they are more likely to pierce the protective film and contact the vessel wall during balloon 3 expansion.

[0069] Development rings 7 are provided on both sides of the drug coating on the inner tube 2 , and the position of the balloon 3 in the blood vessel can be located by the development rings 7 .

[0070] The method of using the medicated balloon dilatation catheter is as follows:

[0071] (1) Before using the drug-eluting balloon dilatation catheter, a circular magnetic field is applied to the lesion site outside the patient's body;

[0072] (2) The balloon 3 and the stent 4 are in a deflated state, and the balloon 3 and the stent 4 are guided to the lesion site in the patient's body. During this process, the drug particles 6 are located between the balloon 3 and the stent 4;

[0073] (3) A filling medium is introduced into the cavity of the balloon 3. The filling medium can be gas or liquid, so that the balloon 3 expands and maintains the expansion. When the balloon 3 expands, the external stent 4 is also driven to expand. Since the expanded diameter of the balloon 3 is larger than the expanded diameter of the stent 4, part of the balloon 3 bulges out from each mesh of the stent 4 to the outside of the stent 4, thereby forming a plurality of protrusions 31. The drug particles 6 are respectively located on each protrusion 31, thereby contacting the blood vessel wall and directly squeezing the drug particles 6 into the blood vessel endothelium. The expanded balloon 3 will enlarge the narrow area, increase the inner diameter of the blood vessel, and improve blood flow and oxygen supply;

[0074] (4) Since ferroferric oxide is added to the drug particles 6, under the action of the magnetic field, the free drug particles 6 generated during the expansion process will migrate to the vascular endothelium and be quickly wrapped or absorbed by the endothelium, such as Figure 9 At the same time, the magnetic field can also prevent the drug particles 6 that are partially squeezed into the blood vessels from being washed out of the blood vessels.

[0075] (5) After the vascular dilation is completed, the filling medium in the balloon cavity of the balloon 3 is discharged, so that the balloon 3 and the stent 4 are contracted, and the stent 4 is withdrawn from the patient's body together with the balloon 3.

[0076] The above embodiments are only for illustrating the technical concept and features of the present invention. Their purpose is to enable people familiar with this technology to understand the content of the present invention and implement it. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the scope of protection of the present invention.

Claims

1. A drug-eluting balloon dilatation catheter, comprising a balloon, characterized in that: The catheter further comprises a stent coated on the outside of the balloon, the stent being a mesh tubular structure and capable of expanding and contracting along with the balloon, and having an expanded diameter smaller than the expanded diameter of the balloon during expansion. The dilatation catheter further comprises a drug coating coated on the outside of the balloon, the drug coating comprising a plurality of magnetic drug particles; in a contracted state, the drug particles are located between the balloon and the stent; In the expanded state, parts of the balloon bulge out from the meshes of the stent to form a plurality of protrusions outside the stent, and the drug particles are located on each of the protrusions.

2. The drug-eluting balloon dilatation catheter according to claim 1, characterized in that: The drug particles include magnetic material, drugs for inhibiting vascular intimal hyperplasia and carriers.

3. The drug-eluting balloon dilatation catheter according to claim 2, characterized in that: The mass ratio of the magnetic material, the drug and the carrier is (2.8-3.2):(1.8-2.2):(4.8-5.2).

4. The drug-eluting balloon dilatation catheter according to claim 2, characterized in that: The magnetic material is ferroferric oxide; and / or, the drug is paclitaxel or rapamycin; And / or, the carrier is a degradable polymer material.

5. The drug-eluting balloon dilatation catheter according to claim 1, characterized in that: The thickness of the drug coating is 0.06 mm to 0.8 mm.

6. The drug-eluting balloon dilatation catheter according to claim 1, characterized in that: The size of a single drug particle is 200nm-500um.

7. The drug-eluting balloon dilatation catheter according to claim 6, characterized in that: The size of a single drug particle is 500nm-250um.

8. The drug-eluting balloon dilatation catheter according to claim 1, characterized in that: The drug particles are spherical, or are quasi-spherical with a pointed end, with the pointed end facing away from the balloon.

9. The drug-eluting balloon dilatation catheter according to any one of claims 1 to 8, characterized in that: The stent includes a main body and connecting parts respectively arranged at both ends of the main body to be connected to the balloon, the main body includes a longitudinal rod extending in the longitudinal direction, and a plurality of the longitudinal rods are arranged at intervals along the circumferential direction, the main body also includes a transverse rod connected between each two adjacent longitudinal rods, and a plurality of the transverse rods between each two adjacent longitudinal rods are arranged at intervals along the longitudinal direction, a mesh is formed between each two adjacent longitudinal rods and each two adjacent transverse rods, and each of the longitudinal rods and the transverse rod can expand and contract with the balloon.

10. The drug-eluting balloon dilatation catheter according to claim 9, characterized in that: The drug coating is respectively coated in the mesh area formed between each two adjacent longitudinal rods and each two adjacent transverse rods of the balloon.

11. The drug-eluting balloon dilatation catheter according to claim 9, characterized in that: The connecting portion includes a connecting rod extending along the longitudinal direction, and a plurality of the connecting rods are arranged at intervals along the circumferential direction. In each connecting portion, the number of the connecting rods is not greater than the number of the longitudinal rods, and one end of each of the connecting rods is connected to or integrally arranged with a different longitudinal rod, and the connecting rods can expand and contract with the balloon.

12. The drug-eluting balloon dilatation catheter according to claim 1, characterized in that: The dilatation catheter further comprises a protective film covering the outside of the stent, and the protective film is made of a degradable polymer material.

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