Balloon dilatation catheters and drug delivery devices

Abstract

The present invention relates to a balloon dilatation catheter and a drug delivery device, comprising a catheter body and a balloon fixed on the catheter body, wherein a linear body is arranged on the outside of the balloon, the linear body extends from the proximal end to the distal end of the balloon along the outer surface of the balloon, and the two ends of the linear body are connected to the catheter body; wherein the surface of the linear body and / or the balloon carries a drug. The linear body increases the pressure on the blood vessel wall, so that the drug on the linear body and / or the balloon can better penetrate into the blood vessel, improve the transfer rate of the drug, and the linear body can further support the blood vessel wall, thereby enhancing the dilation effect of the blood vessel.

Description

Technical Field

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

[0002] From the 1970s to the present, coronary interventional treatment technology has evolved from the initial percutaneous balloon angioplasty (POBA) to the placement of bare metal stents (BMS) and drug-eluting stents (DES). Patients have benefited greatly, but new problems have also arisen. Although DES has significantly reduced the incidence of in-stent restenosis, it is still impossible to completely avoid the occurrence of restenosis. It will not only lead to the recurrence of angina symptoms, but also cause acute coronary syndrome in some patients. Once DES restenosis occurs, treatment is more difficult. In addition, DES-induced delayed endothelial healing, late stent malapposition, in-stent thrombosis, and new atherosclerosis have become new problems that affect clinical prognosis.

[0003] In recent years, drug-coated balloons (DCBs) have been introduced, which can treat severe coronary artery lesions, improve coronary blood supply and vascular function, and leave no permanent implants in the blood vessels, thus avoiding a series of problems caused by stent implantation and providing the possibility for diseased blood vessels to receive re-treatment. Its significant and unique advantages include:

[0004] (1) Direct contact with the vessel wall allows the drug to be released evenly to the damaged area of ​​the vessel wall rather than just the area covered by the stent;

[0005] (2) When the vessel wall is damaged, the neointimal process is most active at this time, and the concentration of drugs in the vessel wall is the highest, which can effectively inhibit intimal hyperplasia; in the later stage, the concentration of drugs in the vessel wall is greatly reduced, which is conducive to the endothelialization process and reduces the risk of thrombosis;

[0006] (3) Drug release is independent of the polymer matrix, which reduces the occurrence of inflammatory response;

[0007] (4) Simplified the surgical process, shortened the radiation exposure time and the amount of contrast agent used, and improved the safety of interventional treatment;

[0008] (5) In small vessel lesions, tortuous lesions, and bifurcation lesions, DCB has a high pass rate and no metal skeleton. After treatment, the original anatomical morphology of the blood vessel is maintained to the greatest extent possible, reducing the impact on the blood flow pattern. When treating in-stent stenosis, the problem of double-layer stents reducing the vessel lumen is avoided;

[0009] (6) Avoiding the insertion of foreign bodies, thus preserving the opportunity for follow-up treatment when necessary;

[0010] (7) It can shorten the duration of taking dual antiplatelet drugs, thereby reducing the occurrence of bleeding complications and lowering medical costs. It is especially suitable for patients who are intolerant to platelet therapy and those who have recently received surgical treatment.

[0011] However, current drug-coated balloons still have problems with low drug release and utilization. Summary of the invention

[0012] In order to solve the above technical problems, the purpose of the present invention is to provide a balloon dilatation catheter and a drug delivery device, which can use the linear body on the outside of the balloon to safely and effectively squeeze the blood vessel wall. On the one hand, it can further support the blood vessel wall, and on the other hand, the drug can better penetrate into the blood vessel wall, thereby improving the release and utilization rate of the drug.

[0013] To achieve the above-mentioned purpose, the present invention provides a balloon dilatation catheter, comprising a catheter body and a balloon fixed on the catheter body; a linear body is arranged on the outside of the balloon, the linear body extends from the proximal end to the distal end of the balloon along the outer surface of the balloon, and both ends of the linear body are connected to the catheter body, and at least one end of the linear body is movably connected to the catheter body; wherein the surface of the linear body and / or the balloon carries drugs.

[0014] Optionally, one end of the linear body is movably connected to a tube section of the catheter body located on the proximal side of the balloon, and the other end of the linear body is fixedly connected to a tube section of the catheter body located on the distal side of the balloon.

[0015] Optionally, the catheter body includes a connecting sleeve, the connecting sleeve is arranged on one side of the proximal end of the balloon, the connecting sleeve has a mounting cavity, the one end of the linear body is arranged in the mounting cavity, and the one end of the linear body is movably connected or fixedly connected to the mounting cavity;

[0016] When the one end of the linear body is fixedly connected to the mounting cavity, the connecting sleeve is used to move relative to the balloon;

[0017] When the one end of the linear body is movably connected to the mounting cavity, the connecting sleeve is used to move or remain stationary relative to the balloon.

[0018] Optionally, the catheter body further comprises an outer tube and an inner tube, wherein the inner tube is inserted into the outer tube; the proximal end of the balloon is connected to the outer tube, and the distal end is connected to the inner tube;

[0019] The other end of the linear body is fixedly connected to the tube section of the inner tube extending from the distal end of the balloon; the connecting sleeve is arranged on the outer tube, and one end of the linear body is inserted into the connecting sleeve from the connecting sleeve toward one end of the balloon and then movably or fixedly connected to the mounting cavity.

[0020] Optionally, the cross-sectional shape of the linear body is circular, and the diameter of the linear body is 0.1 mm to 0.35 mm.

[0021] Optionally, the outer surface of the thread-shaped body is smooth, or the outer surface of the thread-shaped body on a side facing away from the balloon is formed with continuous or spaced protrusions.

[0022] Optionally, the protrusion has a sawtooth shape.

[0023] Optionally, the number of the linear bodies is one or more, and the plurality of linear bodies are evenly or unevenly arranged around the longitudinal axis of the balloon.

[0024] To achieve the above-mentioned purpose, the present invention also provides a drug delivery device, comprising a catheter body and a balloon fixed on the catheter body; a linear body is arranged on the outside of the balloon, and the linear body extends from the proximal end to the distal end of the balloon along the outer surface of the balloon, and both ends of the linear body are connected to the catheter body; wherein the surface of the linear body and / or the balloon carries drugs.

[0025] Optionally, the height of the cross section of the linear body is 0.1 mm to 0.35 mm.

[0026] The above-mentioned balloon dilatation catheter and drug delivery device can be used for interventional treatment of peripheral blood vessels or coronary arteries, especially for interventional treatment of coronary arteries. The linear body on the outside of the balloon can further provide safe and effective support to the diseased blood vessel wall, thereby achieving better blood vessel dilation effect. In addition, the device can avoid damage such as intimal tearing, dissection, and acute occlusion caused by balloon dilatation, thereby improving the safety of the device.

[0027] When the above-mentioned balloon dilatation catheter and drug delivery device are loaded with drugs through the thread-shaped body on the outside of the balloon, the thread-shaped body can better squeeze the blood vessel wall as the balloon expands, allowing the drug to better penetrate into the blood vessel wall, thereby improving the release and utilization rate of the drug, thereby better inhibiting intimal hyperplasia, reducing restenosis in the blood vessel, and improving the medical effect.

[0028] The above-mentioned balloon dilatation catheter and drug delivery device are loaded with drugs and supported by linear bodies, especially linear bodies with a cross-sectional height (such as diameter) of 0.1mm to 0.35mm, so that the parts contacted by the linear bodies only cause slight and safe damage to the endothelium of the blood vessel wall, and are safer.

[0029] The above-mentioned balloon dilatation catheter and drug delivery device enable the linear body to adapt to the moving position as the balloon expands by making at least one end of the linear body movable, thereby effectively preventing the linear body from affecting the balloon expansion, ensuring that the balloon can be fully opened, and improving the reliability of the device. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Those skilled in the art will appreciate that the accompanying drawings are provided for a better understanding of the present invention and do not constitute any limitation on the scope of the present invention.

[0031] Figure 1 is a schematic structural diagram of a balloon dilatation catheter in a preferred embodiment of the present invention;

[0032] Figure 2 is a schematic diagram of two symmetrically arranged linear bodies disposed outside the balloon in a preferred embodiment of the present invention;

[0033] Figure 3 It is a partial schematic diagram of the proximal end of the linear body in the preferred embodiment of the present invention being movable in the mounting cavity;

[0034] Figure 4 It is a partial schematic diagram of a preferred embodiment of the present invention in which the connecting sleeve is movable on the outer tube;

[0035] Figure 5a is a schematic diagram of a linear body with a smooth surface in a preferred embodiment of the present invention;

[0036] Figure 5b is a schematic diagram of a linear body having straight serrations on its surface in a preferred embodiment of the present invention;

[0037] Figure 5c is a schematic diagram of a linear body having oblique sawtooth on its surface in a preferred embodiment of the present invention;

[0038] Figure 6 is a schematic diagram of balloon folding in a preferred embodiment of the present invention;

[0039] Figure 7 It is a schematic diagram of the balloon dilatation catheter in the preferred embodiment of the present invention being delivered into the lesion site and in use after the balloon is dilated;

[0040] Figure 8 This is a schematic diagram of the use state of the linear body squeezing the blood vessel wall in the preferred embodiment of the present invention, observed from the direction perpendicular to the axis of the blood vessel. Figure 1 ;

[0041] Fig. 9 is a schematic diagram of a preferred embodiment of the present invention, in which a linear body is observed from an isometric view direction to compress a blood vessel wall in use;

[0042] Fig.10 This is a schematic diagram of the use state of the linear body squeezing the blood vessel wall in the preferred embodiment of the present invention, observed from the direction perpendicular to the axis of the blood vessel. Figure 2 .

[0043] The following are the descriptions of the reference numerals:

[0044] 1-catheter body; 11-inner tube; 12-outer tube; 121-proximal outer tube; 122-distal outer tube; 123-guidewire port; 124-catheter identification band; 2-balloon; 21-balloon folding wing; 3-thread body; 31-distal end of thread body; 32-proximal end of thread body; 4-proximal connector; 5-stress diffusion tube; 6-development marker; 13-connecting sleeve; 14-installation cavity; 15-head; 10-blood vessel; 20-lesion.

[0045] The same or similar reference numerals in the drawings represent the same or similar components. DETAILED DESCRIPTION

[0046] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the illustrations provided in the present embodiment only illustrate the basic concept of the present invention in a schematic manner, and the illustrations only show the components related to the present invention rather than drawing according to the number, shape and size of the components in the actual implementation. The type, quantity and proportion of each component in the actual implementation can be a random change, and the component layout type may also be more complicated.

[0047] In addition, each embodiment of the following description has one or more technical features, but this does not mean that the user of the present invention must implement all the technical features in any embodiment at the same time, or can only implement part or all of the technical features in different embodiments separately. In other words, under the premise that implementation is possible, those skilled in the art can selectively implement part or all of the technical features in any embodiment according to the disclosure of the present invention and according to design specifications or actual needs, or selectively implement a combination of part or all of the technical features in multiple embodiments, thereby increasing the flexibility of the implementation of the present invention.

[0048] As used in this specification, the singular forms "one", "an" and "the" include plural objects, unless the content clearly indicates otherwise. As used in this specification, the meaning of "multiple" generally includes two or more, unless the content clearly indicates otherwise. As used in this specification, "distal end" generally refers to the end that first enters the body, and "proximal end" is the end opposite to the "distal end". As used in this specification, the term "or" is generally used with the meaning including "and / or", unless the content clearly indicates otherwise. It should also be understood that the present invention repeats reference numbers and / or letters in various embodiments. This repetition is for the purpose of simplicity and clarity, and does not itself indicate the relationship between the various embodiments and / or configurations discussed. It will also be understood that when an element is referred to as "connecting" another element, it can be directly connected to another element, or one or more intermediate elements can be present.

[0049] Figure 1 The schematic diagram of the structure of the balloon dilatation catheter provided by the preferred embodiment of the present invention. Figure 1 As shown, this embodiment provides a balloon dilatation catheter (i.e., a drug delivery device), including a catheter body 1 and a balloon 2 fixed on the catheter body 1; wherein a linear body 3 is arranged on the outside of the balloon 2, and the linear body 3 extends from the proximal end of the balloon 2 to the distal end along the outer surface of the balloon 2, and the two ends of the linear body 3 are connected to the catheter body 1. Specifically, one end of the linear body 3 is connected to the tube section of the catheter body 1 located on the distal side of the balloon 2, and the other end is connected to the tube section of the catheter body 1 located on the proximal side of the balloon 2. Here, the linear body 3 refers to a slender member, and the shape of the slender member is not limited, such as strip, belt, filament or sheet, and its cross section can be square, triangular, etc. Preferably, the linear body 3 is a circular slender member, which causes less damage to the endothelium of the blood vessel wall. The linear body 3 is made of medical metal material or medical polymer material, and there is no special requirement for the selected medical polymer material or medical metal material. For example, the medical metal material used to prepare the linear body 3 is at least one of medical stainless steel, medical cobalt-based alloy, medical nickel-titanium alloy and medical magnesium alloy. For another example, the medical polymer material used to prepare the linear body 3 is at least one of polyethylene terephthalate (PET), a block copolymer of polyamide and polyether (Pebax), polypropylene and polyurethane.

[0050] The surface of the thread 3 and / or the balloon 2 carries drugs. The arrangement of the drugs on the balloon 2 and / or the thread 3 is not particularly limited, for example, the drugs are prepared by electrostatic spraying, atomization spraying, dipping, dripping or crystal self-growth. In addition, the drugs on the surface of the thread 3 and / or the balloon 2 can be a simple drug, or a mixture of a drug and a carrier matrix. The drugs can be selected according to demand, such as anti-proliferative, anti-hyperplastic, anti-restenotic, anti-inflammatory, antibacterial, anti-tumor, anti-mitotic, anti-metastatic, anti-thrombotic, anti-osteoporotic, anti-angiogenic, anti-cell, and anti-microtubule drugs. Drugs include, but are not limited to, rapamycin and its derivatives (including zotarolimus, everolimus, biolimus, 7-O-desmethylrapamycin, temsirolimus, rufolimus, etc.), paclitaxel, paclitaxel derivatives, docetaxel, angiostatin, angiopeptin, aspirin, acemetacin, dexamethasone, corticosterone, prednisolone, budesonide, estrogen, selective estrogen receptor modulators, hormones, sulfasalazine, 5-fluorouracil, amino Pterin, aminosalicylic acid, aescin, antimycotic, arsenic trioxide, aristolochic acid, scutellariae, ginkgo biloba, endostatin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, antibody anticancer drugs, doxorubicin, levofloxacin, hydroxycamptothecin, vinblastine, vincristine, cisplatin, thymidine kinase inhibitor antibiotics (particularly actinomycin-D), strontium ranelate, cyclosporine A, cyclosporine C, brefeldin A, bisphosphonates. Further, the drug is preferably a combination of one or more of rapamycin, rapamycin derivatives, paclitaxel, and paclitaxel derivatives. The carrier matrix can be iopromide, iopamidol, iohexol, shellac, urea, lecithin, polylactic acid, polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), chitosan, gelatin, glucose, polyarginine, tri-n-hexyl butyryl citrate (BTHC), Tween 80, etc. One or more combinations.

[0051] The longitudinal axis of the unfolded linear body 3 is parallel or non-parallel to the longitudinal axis of the unfolded balloon 2. Preferably, the longitudinal axis of the unfolded linear body 3 is parallel to the longitudinal axis of the unfolded balloon 2, that is, after the balloon 2 is expanded, the linear body 3 is also expanded, and the extension direction of the unfolded linear body 3 is parallel to the longitudinal axis of the expanded balloon 2. With this design, the balloon 2 is not easily affected by the linear body 3 and can be fully opened or contracted, and the reliability of use is better. It should also be understood here that the "parallel" does not mean that the two (i.e., the linear body and the balloon) are completely parallel. Those of ordinary skill in the art should know that in actual applications, a deviation between the longitudinal axis of the unfolded linear body 3 and the longitudinal axis of the unfolded balloon 2 is allowed.

[0052] Next, combine Figures 7 to 9 , the working principle of the balloon dilatation catheter of this embodiment is further explained.

[0053] like Figure 7 As shown, the balloon dilatation catheter is sent to the location of the lesion in the blood vessel by conventional operation means and after the location is confirmed to be correct, external gas or liquid is introduced into the balloon 2 to make the balloon 2 expand after being filled, thereby achieving the purpose of dilating the blood vessel 10, and finally making the balloon 2 and the lesion 20 of the blood vessel 10 effectively fit. Figure 8-10 As shown, during the expansion of the balloon 2, the linear bodies 3 on the outside of the balloon 2 can further support the inner wall of the diseased blood vessel 10 when subjected to the radial outward force of the balloon 2, thereby enhancing the support force of the balloon dilatation catheter on the diseased blood vessel 10, and achieving a better expansion effect of the blood vessel. At the same time, through the expansion of the balloon 2, the linear bodies 3 further squeeze the blood vessel wall, and through the squeezing effect between the linear bodies 3 and the blood vessel wall, the squeezing force of the balloon 2 on the blood vessel wall is increased, so that the linear bodies 3 and / or the drugs on the surface of the balloon 2 can better penetrate into the blood vessel wall, thereby improving the release and utilization rate of the drugs. It should be understood that in a traditional balloon dilatation catheter, although the balloon surface fits the blood vessel wall, the balloon surface is smooth and the pressure applied to the blood vessel wall is limited. Therefore, the drugs cannot better penetrate into the blood vessel wall, and the transfer rate of the drugs is low. The present invention uses the thread 3 on the outside of the balloon to squeeze the blood vessel wall, thereby increasing the force of the balloon on the blood vessel wall. This force enables the drug on the balloon 2 and / or thread 3 to better penetrate into the blood vessel wall, thereby increasing the transfer rate of the drug. In addition, the thread 3 is relatively small in size (preferably a filament with a cross-sectional height of 0.1 mm to 0.35 mm, such as a filament with a diameter of 0.1 mm to 0.35 mm), and even if the diseased part of the blood vessel it contacts is damaged, the damage is slight and safe, so the safety is good.

[0054] Further, both ends of the linear body 3 are fixedly connected to the catheter body 1, or one end is connected to the catheter body 1 and the other end is movably connected to the catheter body 1, or both ends of the linear body 3 are movably connected to the catheter body 1. Preferably, one end of the linear body 3 is fixedly connected to the catheter body 1 and the other end is movably connected to the catheter body 1, so that the linear body 3 can move with the expansion and contraction of the balloon 2. It should be understood that when both ends of the linear body 3 are fixedly connected to the catheter body 1, the length of the portion of the linear body 3 located at the proximal and distal ends of the balloon 2 should ensure a certain amount of elongation to prevent the balloon 2 from being restrained by the linear body 3 during expansion. Further, the minimum length of the linear body 3 is greater than the length of the unilateral contour line from the proximal end to the distal end of the expanded balloon 2 to prevent the expansion of the balloon 2 from being affected by the linear body 3 due to the length of the linear body 3 being too short. In this embodiment, in order not to increase the folded size of the balloon 2, to increase the reliability of use, and to reduce the difficulty of manufacturing, it is preferred that one end of the linear body 3 is movably connected to the catheter body 1, and the other end is fixedly connected to the catheter body 1. In this case, the linear body 3 itself can move with the expansion and contraction of the balloon 2, which can better ensure that the balloon 2 is opened, contracted or folded.

[0055] Further, such as Figure 1 As shown, the tube section of the catheter body 1 extending out of the distal end of the balloon 2 is defined as the head 15. The length of the head 15 is usually not long, and it is difficult to design a movable head 15. In order to overcome this difficulty, it is preferred that the proximal end 32 of the linear body 3 is movably connected to the tube section of the catheter body 1 located on the proximal side of the balloon 2, and the distal end 31 of the linear body 3 is fixedly connected to the tube section of the catheter body 1 located on the distal side of the balloon 2. The movable connection method between the proximal end 32 of the linear body 3 and the catheter body 1 is not limited, and the fixed connection method between the distal end 31 and the catheter body 1 is also not limited. Further, the distal end 31 of the linear body 3 is welded to the tube section (head 15) of the catheter body 1 located on the distal side of the balloon 2, which is convenient in process and low in manufacturing difficulty.

[0056] The present invention has no particular requirement on the number of the thread bodies 3, which can be one or more, and the multiple thread bodies 3 are evenly or unevenly arranged around the longitudinal axis of the balloon 2. Figure 2 As shown, the number of the thread bodies 3 is multiple, more preferably 2 to 6, and the multiple thread bodies 3 are evenly or unevenly distributed around the longitudinal axis of the balloon 2, preferably evenly distributed. Here, the "evenly" or "unevenly" usually refers to the use state after deployment.

[0057] Continue reading Figure 1 The catheter body 1 includes an inner tube 11 and an outer tube 12. The inner tube 11 is inserted into the outer tube 12 and a medium cavity is formed between the inner tube 11 and the outer tube 12. The gas or liquid used to fill the balloon 2 is passed into the medium cavity, and the gas or liquid enters and exits the balloon 2 through the medium cavity. The inner cavity of the inner tube 11 is used to insert a guide wire. The proximal end of the balloon 2 is connected to the outer tube 12, and the distal end is connected to the inner tube 11. The distal end 31 of the thread-like body 3 is connected to the tube section of the inner tube 11 extending out of the distal end of the balloon 2, for example, by welding. The proximal end 32 of the thread-like body 3 is connected to the tube section of the outer tube 12 adjacent to the proximal end of the balloon 2.

[0058] Further Figure 3 and Figure 4As shown, the catheter body 1 also includes a connecting sleeve 13, which is arranged on one side of the proximal end of the balloon 2 and sleeved on the outer tube 12. The connecting sleeve 13 has a mounting cavity 14, and the proximal end 32 of the linear body 3 is arranged in the mounting cavity 14, and the proximal end 32 of the linear body 3 is movably connected or fixedly connected to the mounting cavity 14. When the proximal end 32 of the linear body 3 is fixedly connected to the mounting cavity 14, the connecting sleeve 13 can be movably sleeved on the outer tube 12, so that the connecting sleeve 13 can be movable relative to the balloon 2 (i.e., the outer tube 12). When the proximal end 32 of the linear body 3 is movably connected to the mounting cavity 14, the connecting sleeve 13 can be movably sleeved on the outer tube 12, and can also be fixedly sleeved on the outer tube 12, that is, the connecting sleeve 13 can be movable or fixed, and it is preferred that the connecting sleeve 13 is fixedly arranged at this time.

[0059] In some embodiments, Figure 3 As shown, the proximal end 32 of the linear body 3 is movable in the installation cavity 14, and the connecting sleeve 13 is fixedly arranged. During preparation, the proximal end 32 of the linear body 3 is inserted into the connecting sleeve 13 from the connecting sleeve 13 toward one end of the balloon 2 and then movably connected with the installation cavity 14. At this time, the axial length of the installation cavity 14 along the outer tube 12 is the movable distance of the linear body 3. This distance needs to ensure that the balloon 2 can be smoothly opened, contracted or folded. At the same time, the opening at one end of the installation cavity 14 can prevent the proximal end 32 of the linear body 3 from escaping from the connecting sleeve 13. Therefore, when the balloon 2 is unfolded, the proximal end 32 of the linear body 3 can move in the direction of the balloon 2 (i.e., toward the distal end) in the mounting cavity 14, ensuring that the balloon 2 can be fully opened and will not be constrained by the linear body 3. At the same time, the unfolded balloon 2 exerts a radial outward force on the linear body 3, ensuring that the linear body 3 fits the blood vessel wall (i.e., ensuring the pressure on the blood vessel wall), providing effective support for the blood vessel wall, and the proximal end 32 of the linear body 3 is constrained by the mounting cavity 14 and will not fall off from the mounting cavity 14. When the balloon 2 is folded, the proximal end 32 of the linear body 3 can move in the direction away from the balloon 2 (i.e., the proximal end), but will not exceed the length of the mounting cavity 14, ensuring that the linear body 3 will not hang upside down on the catheter and the blood vessel wall. Further, the size (diameter) of the proximal end of the linear body 3 is slightly larger than the size (diameter) of the rest of the part.

[0060] In some embodiments, Figure 4As shown, the proximal end 32 of the linear body 3 is immobile in the installation cavity 14, and the connecting sleeve 13 is movably arranged. During preparation, the proximal end 32 of the linear body 3 is also inserted from the connecting sleeve 13 toward one end of the balloon 2 and fixedly connected to the installation cavity 14. At this time, the moving distance of the connecting sleeve 13 along the axial direction of the outer tube 12 is the movable distance of the linear body 3, and this distance needs to ensure that the balloon 2 can be smoothly opened, shrunk or folded. Further, when the proximal end 32 of the linear body 3 is fixedly connected to the connecting sleeve 13, a heat shrinking method can be used for connection, that is, the connecting sleeve 13 is designed as a heat shrink tube. The working principle of this design is similar to the above, that is, when the balloon 2 is unfolded, the connecting sleeve 13 moves toward the balloon 2, driving the proximal end 32 of the linear body 3 to move toward the balloon 2, ensuring that the balloon 2 can be fully opened, and the proximal end 32 of the linear body 3 is fixed to the installation cavity 14 and will not fall off from the installation cavity 14. In addition, when the balloon 2 is folded, the connecting sleeve 13 moves away from the balloon 2 , so that the proximal end 32 of the linear body 3 also moves away from the balloon 2 , which will not affect the folding of the balloon 2 .

[0061] Furthermore, the thread body 3 is preferably a circular filament, which causes less damage to the endothelium of the blood vessel wall, and the diameter of the circular filament is preferably 0.10mm to 0.35mm, and more preferably 0.15mm to 0.25mm. Furthermore, the diameter of the proximal end of the thread body 3 is larger than the diameter of the rest of the thread body 3, and the diameter of the proximal end is 0.12mm to 1.0mm, and more preferably 0.17mm to 0.90mm, for example 0.12mm to 0.50mm, and more preferably 0.17mm to 0.40mm. When the cross section of the thread body 3 is non-circular, the height of the cross section is preferably 0.10mm to 0.35mm, and more preferably 0.15mm to 0.25mm.

[0062] Furthermore, the outer surface of the linear body 3 is smooth and cylindrical in shape as a whole ( Figure 8 ), or a triangular prism ( Fig.10 ). Or, Figure 5b and Figure 5c As shown, the outer surface of the side of the linear body 3 facing away from the balloon 4 is uneven, and the uneven surface is used to fit the blood vessel wall, so that the protrusions on the surface of the linear body 3 further increase the pressure on the blood vessel wall, so that the drug can better penetrate into the blood vessel wall. The present invention does not limit the shape of the protrusions, including but not limited to a sawtooth shape. Preferably, the shape of the protrusion is a sawtooth shape, for example Figure 5b Straight sawtooth type, or Figure 5cIt should be understood that the linear body 3 with uneven surface is configured to cause slight and safe damage to the inner wall of the blood vessel, which can ensure the safety of use. In addition, the advantage of the oblique sawtooth is that the catheter will not scratch the non-lesioned blood vessel when withdrawing from the blood vessel, which is safer. In addition, the protrusions can be distributed continuously, for example Fig.10 The triangular prism shown, or the protrusions are spaced apart along the length direction of the linear body, for example Figure 5b and Figure 5c The serrated surface shown.

[0063] In this embodiment, the balloon dilatation catheter has a folded state and an expanded state; when the balloon 2 is expanded or inflated, the balloon dilatation catheter is in the expanded state; before the balloon 2 is expanded or inflated, the balloon dilatation catheter is in the folded state. After folding, the number of folding wings 21 of the balloon 2 is at least two, which can be arranged at equal angles or unequal angles. For example Figure 6 As shown, the balloon 2 has three folding wings 21 arranged at equal angles. Furthermore, when the balloon 2 is folded, the linear body 3 may be wrapped by the folding wings 21 or not. In particular, when there are multiple linear bodies 3, all the linear bodies 3 are wrapped by the folding wings 21, or part of them are wrapped, or none of them are wrapped. The present invention does not limit the size of the balloon 2, and it can be set according to actual treatment needs. For example, in coronary artery interventional treatment, the diameter of the balloon 2 after expansion is preferably 1.5mm to 4.0mm, and the length is preferably 6mm to 40mm.

[0064] Continue reading Figure 1The balloon dilatation catheter also includes a proximal connector 4, which is connected to the proximal end of the catheter body 1, specifically connected to the proximal end of the outer tube 12, and the outer tube 12 can be connected to the proximal connector 4 through a stress diffusion tube 5. Further, the outer tube 12 includes a proximal outer tube 121 and a distal outer tube 122, and the distal end of the proximal outer tube 121 is connected to the proximal end of the distal outer tube 122. The balloon dilatation catheter can be a coaxial integral exchange type (Over The Wire, OTW) or a rapid exchange type (RapidExchange System), and the specific exchange form is not limited. In this embodiment, a guide wire port 123 is provided between the proximal outer tube 121 and the distal outer tube 122, and the guide wire is inserted into the inner tube 11 through the guide wire port 123. Further, the inner tube 11 is provided with a development mark 6 on the tube section inside the balloon 2, and the development mark 6 is usually two, one of which corresponds to the proximal position of the balloon 2, and the other corresponds to the distal position of the balloon 2. The developing mark 6 is made integrally with the inner tube 11, and a part of the inner tube 11 is made of developing material, or the developing mark 6 is made separately from the inner tube 11, such as forming a developing ring separately and embedding the developing ring on the inner tube 11. Furthermore, a catheter marking band 124 is provided on the proximal outer tube 121 to mark the length of the balloon dilatation catheter entering the body.

[0065] Next, the balloon dilatation catheter of the present invention is further described in combination with experimental data and experimental results to further highlight the characteristics and features of the above embodiments, but the following preparation method should not constitute a limitation on the present invention.

[0066] Example 1

[0067] A balloon dilatation catheter without carrying drugs is first provided, wherein the filaments are thin wires with a diameter of 0.151 mm, the number of the thin wires is 2, the material of the thin wires is medical stainless steel, and the surface of the thin wires is smooth.

[0068] Then, a drug solution is prepared: the drug paclitaxel and the carrier matrix iopromide are dissolved in a solvent and mixed to obtain a drug solution; wherein the solvent is ethanol and water, and the specific formula of the drug solution is shown in Table 1.

[0069] Table 1: Drug solution formulation

[0070]

[0071] Then, the drug solution is sprayed on the surface of the bare balloon provided with filaments by atomization spraying to obtain a drug-loaded balloon dilatation catheter.

[0072] Afterwards, the balloon is folded (eg, by a balloon folding machine), the balloon folding wing 21 has three wing pieces arranged at equal angles, and one filament is wrapped by the balloon folding wing 21 .

[0073] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0074] Example 2

[0075] First, a balloon dilatation catheter without carrying drugs is provided, wherein the number of filaments is 3, the diameter of the filaments is 0.210 mm, the material of the filaments is medical stainless steel, and the surface of the filaments is straight serrated.

[0076] Then, a drug solution is prepared: the drug rapamycin and the carrier matrix polylactic acid are dissolved in a solvent and mixed to obtain a drug solution; wherein the solvent is ethyl acetate, and the specific formula of the drug solution is shown in Table 2.

[0077] Table 2: Drug solution formulation

[0078] Components substance concentration drug Rapamycin 4mg / ml Carrier Polylactic acid 4mg / ml

[0079] Then, the drug solution is sprayed on the surface of the bare balloon provided with filaments by atomization spraying to obtain a drug-loaded balloon dilatation catheter.

[0080] Afterwards, the balloon is folded, and the balloon folding wings 21 have three wings arranged at equal angles, wherein all the filaments are wrapped by the balloon folding wings.

[0081] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0082] Example 3

[0083] First, a balloon dilatation catheter without carrying drugs is provided, wherein the number of filaments is 4, the diameter of the filaments is 0.160 mm, the material of the filaments is polyethylene terephthalate (PET), and the surface of the filaments is smooth.

[0084] Then, a drug solution is prepared: the drug paclitaxel and the carrier matrix iopromide are dissolved in a solvent and mixed to obtain a drug solution; wherein the solvent is ethanol and water, and the specific formula of the drug solution is shown in Table 1.

[0085] Then, the drug solution is sprayed on the surface of the bare balloon provided with filaments by atomization spraying to obtain a drug-loaded balloon dilatation catheter.

[0086] Afterwards, the balloon is folded, and the balloon folding wings 21 have four wings arranged at equal angles, wherein all the filaments are wrapped by the balloon folding wings.

[0087] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0088] Example 4

[0089] First, a drug solution is prepared: the drug paclitaxel and the carrier matrix iopromide are dissolved in a solvent and mixed to obtain a drug solution; wherein the solvent is ethanol and water, and the specific formula of the drug solution is shown in Table 1.

[0090] Then, four filaments were selected, the filament diameter was 0.210 mm, the filament material was a block copolymer of polyamide and polyether (Pebax), and the drug solution was sprayed on the surface of the filaments by atomization spraying to obtain drug-loaded filaments.

[0091] After obtaining the drug-loaded filaments, a balloon dilatation catheter is prepared, wherein the filaments are the drug-loaded filaments described above, the number of the filaments is 4, and the surface of the filaments is a straight serrated shape.

[0092] Afterwards, the balloon is folded, and the balloon folding wings 21 have four wings arranged at equal angles, wherein all the filaments are wrapped by the balloon folding wings.

[0093] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0094] Example 5

[0095] First, a drug solution is prepared: the drug paclitaxel and the carrier matrix iopromide are dissolved in a solvent and mixed to obtain a drug solution; wherein the solvent is ethanol and water, and the specific formula of the drug solution is shown in Table 1.

[0096] Then, three filaments are selected. The filament material is a medical cobalt-based alloy. The drug solution is sprayed on the surface of the filaments by atomization spraying to obtain drug-loaded filaments.

[0097] After obtaining the drug-loaded filaments, a balloon dilatation catheter is prepared, wherein the filaments are the drug-loaded filaments described above, the filament diameters are 0.155 mm, the number of filaments is 3, and the filament surfaces are smooth.

[0098] Afterwards, the balloon is folded, and the balloon folding wings 21 have three wings arranged at equal angles, wherein all the filaments are wrapped by the balloon folding wings.

[0099] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0100] Example 6

[0101] First, a drug solution is prepared: the drug paclitaxel and the carrier matrix iopromide are dissolved in a solvent and mixed to obtain a drug solution; wherein the solvent is ethanol and water, and the specific formula of the drug solution is shown in Table 1.

[0102] Then, the drug solution is sprayed on the balloon surface by atomization spraying to obtain a drug-loaded balloon.

[0103] After obtaining the drug-loaded balloon, a balloon dilatation catheter is prepared, wherein the filaments have no drug-loaded coating, the number of filaments is 3, the diameter of the filaments is 0.245 mm, the filament material is a medical cobalt-based alloy, and the surface of the filaments is an oblique serrated shape.

[0104] Afterwards, the balloon is folded, and the folding wings of the balloon have three wings arranged at equal angles, wherein all the filaments are wrapped by the folding wings of the balloon.

[0105] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0106] Example 7

[0107] First, prepare a drug solution: dissolve the drug rapamycin and the carrier matrix polylactic acid in a solvent and mix them to obtain a drug solution; wherein the solvent is ethyl acetate, and the specific formula of the drug solution is shown in Table 2.

[0108] Then, the drug solution is sprayed on the balloon surface by atomization spraying to obtain a drug-loaded balloon.

[0109] After obtaining the drug-loaded balloon, a balloon dilatation catheter is prepared, wherein the filaments have no drug-loaded coating, the filament diameter is 0.105 mm, the number of filaments is 4, the filament material is a block copolymer of polyamide and polyether (Pebax), and the filament surface is smooth.

[0110] Afterwards, the balloon is folded, and the folding wings of the balloon have four wings arranged at equal angles, wherein all the filaments are wrapped by the folding wings of the balloon.

[0111] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0112] Example 8

[0113] Firstly, a balloon dilatation catheter without carrying drugs is provided, wherein the number of filaments is 3, the diameter of the filaments is 0.349 mm, the material of the filaments is medical cobalt-based alloy, and the surface of the filaments is oblique serrated.

[0114] Then, a drug solution is prepared: the drug rapamycin and the carrier matrix lecithin are dissolved in a solvent, mixed, and a drug solution is obtained; wherein the solvent is ethanol, and the specific formula of the drug solution is shown in Table 3.

[0115] Table 3 Drug solution formula

[0116] Components substance concentration drug Rapamycin 5mg / ml Carrier Lecithin 5mg / ml

[0117] Then, the drug solution is sprayed on the surface of the bare balloon provided with filaments by atomization spraying to obtain a drug-loaded balloon dilatation catheter.

[0118] Afterwards, the balloon is folded, and the folding wings of the balloon have three wings arranged at equal angles, wherein all the filaments are wrapped by the folding wings of the balloon.

[0119] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0120] Example 9

[0121] First, prepare a drug solution: dissolve the drug rapamycin and the carrier matrix lecithin in a solvent and mix them to obtain a drug solution; wherein the solvent is ethanol, and the specific formula of the drug solution is shown in Table 3.

[0122] Then, the drug solution is sprayed on the balloon surface by atomization spraying to obtain a drug-loaded balloon.

[0123] After obtaining the drug-loaded balloon, a balloon dilatation catheter is prepared, wherein the filaments have no drug-loaded coating, the number of the filaments is 4, the diameter of the filaments is 0.250 mm, the material of the filaments is medical cobalt-based alloy, and the surface of the filaments is straight serrated.

[0124] Afterwards, the balloon is folded, and the folding wings of the balloon have four wings arranged at equal angles, wherein all the filaments are wrapped by the folding wings of the balloon.

[0125] Finally, the folded balloon is placed into a protective sleeve for fixation, and a drug-loaded balloon dilatation catheter is obtained after sterilization.

[0126] Example 10

[0127] Animal experiments were conducted on the above examples, and the drug concentrations in tissue blood vessels obtained are shown in Table 4.

[0128] In addition, the animal experiment also added control example 1 and control example 2:

[0129] In comparative example 1, the diameter of the filament is 0.710 mm, and the rest is the same as in example 1;

[0130] In control example 2, the filament diameter is 0.653 mm, and the rest is the same as in embodiment 2.

[0131] 1) Experimental content

[0132] Healthy domestic white pigs were selected as the animal model, and balloon dilatation catheters were implanted in the coronary arteries to evaluate drug release at different time points after implantation and the overall device safety.

[0133] 2) Experimental results

[0134] First, the safety of the drug balloon loaded with filaments was evaluated. According to the observation of experimental pigs during and after the operation, the balloon dilatation catheters in Examples 1-9 caused little damage to the endothelium of the blood vessel wall, and there was no obvious damage, while the balloon dilatation catheters in Control Examples 1 and 2 caused obvious tearing of the endothelium of the blood vessel wall, which may be due to the excessive compression of the blood vessel wall by the filament diameter. Therefore, the reasonable control of the size of the filament can ensure that slight damage only occurs at the compression point, and will not cause serious damage to the endothelium of the blood vessel wall, and the middle membrane of the blood vessel wall can remain intact without obvious damage. Therefore, the use of the balloon dilatation catheter of the present invention is safe.

[0135] Secondly, the drug concentration in tissue blood vessels was evaluated (see Table 4).

[0136] Table 4 Drug concentration in tissue blood vessels (unit: μg / g)

[0137]

[0138] As shown in Table 4, the balloon dilatation catheter of the present invention can play an effective role in drug release, and the drug transfer rate is high. More specifically, in Example 1 to Example 3, the balloon surface and the filament surface are sprayed with drugs, and the filament surface in Example 2 is straight serrated, and the drug concentration in the tissue is relatively higher than that of the filament with a smooth surface. In Example 4 and Example 5, the balloon surface is not sprayed with drugs, and only the filament surface is loaded with drugs. The filament surface in Example 4 is straight serrated, and the drug concentration in the tissue is relatively higher than that of the filament with a smooth surface. In Example 6, Example 7 and Example 9, the balloon surface is sprayed with drugs, and the filament surface is not sprayed with drugs. The filament surface in Example 6 is oblique serrated, and the filament surface in Example 9 is straight serrated, and the drug concentration in the tissue is relatively higher than that of the filament with a smooth surface. It can be seen that the drugs on the surface of the filament and / or balloon 2 can better penetrate into the vascular wall as the filament is squeezed with the vascular wall, the transfer and utilization rate of the drug are high, and the therapeutic effect of the drug is better.

[0139] In summary, the balloon dilatation catheter of the present invention uses a thread-like body to load drugs, thereby increasing the drug loading amount. In particular, the drugs on the surface of the thread-like body and / or the surface of the balloon can better penetrate into the blood vessel wall as the thread-like body and the blood vessel wall are squeezed, so that the drugs can better play their role, effectively prevent intimal hyperplasia, and reduce the probability of restenosis. In addition, the balloon with thread-like bodies on the surface can be used to safely and effectively support the diseased blood vessel wall, thereby avoiding damage such as intimal tearing, dissection, and acute occlusion, and having better safety.

[0140] The above description is only a description of the preferred embodiments of the present invention, and is not intended to limit the scope of the present invention. Any changes or modifications made by a person skilled in the art in the field of the present invention based on the above disclosure shall fall within the protection scope of the present invention.

Claims

1. A balloon dilatation catheter, characterized in that: The invention comprises a catheter body and a balloon fixed on the catheter body; a linear body is arranged on the outside of the balloon, the linear body extends from the proximal end to the distal end of the balloon along the outer surface of the balloon, and both ends of the linear body are connected to the catheter body, and at least one end of the linear body is movably connected to the catheter body; wherein the surface of the linear body and / or the balloon carries medicine; the number of the linear bodies is one or more, and the plurality of the linear bodies are evenly or unevenly arranged around the longitudinal axis of the balloon; One end of the linear body is movably connected to the tube section of the catheter body located on the proximal side of the balloon, and the other end of the linear body is fixedly connected to the tube section of the catheter body located on the distal side of the balloon; The catheter body includes a connecting sleeve, which is arranged on one side of the proximal end of the balloon. The connecting sleeve has an installation cavity, one end of the linear body is arranged in the installation cavity, and one end of the linear body is movably connected or fixedly connected to the installation cavity; when one end of the linear body is fixedly connected to the installation cavity, the connecting sleeve is used to move relative to the balloon; when one end of the linear body is movably connected to the installation cavity, the connecting sleeve is used to move or remain stationary relative to the balloon.

2. The balloon dilatation catheter according to claim 1, characterized in that: The catheter body further comprises an outer tube and an inner tube, wherein the inner tube is inserted into the outer tube; the proximal end of the balloon is connected to the outer tube, and the distal end is connected to the inner tube; The other end of the linear body is fixedly connected to the tube section of the inner tube extending from the distal end of the balloon; the connecting sleeve is arranged on the outer tube, and one end of the linear body is inserted into the connecting sleeve from the connecting sleeve toward one end of the balloon and then movably or fixedly connected to the mounting cavity.

3. The balloon dilatation catheter according to claim 1, characterized in that: The cross-sectional shape of the linear body is circular, and the diameter of the linear body is 0.1 mm to 0.35 mm.

4. The balloon dilatation catheter according to claim 1, characterized in that: The outer surface of the thread-shaped body is smooth, or the outer surface of the thread-shaped body on a side away from the balloon is formed with continuous or spaced protrusions.

5. The balloon dilatation catheter according to claim 4, characterized in that: The protrusion has a sawtooth shape.

6. A drug delivery device, characterized in that: The invention comprises a catheter body and a balloon fixed on the catheter body; a linear body is arranged on the outside of the balloon, the linear body extends from the proximal end to the distal end of the balloon along the outer surface of the balloon, and both ends of the linear body are connected to the catheter body; wherein the surface of the linear body and / or the balloon carries medicine; One end of the linear body is movably connected to the tube section of the catheter body located on the proximal side of the balloon, and the other end of the linear body is fixedly connected to the tube section of the catheter body located on the distal side of the balloon; The catheter body includes a connecting sleeve, which is arranged on one side of the proximal end of the balloon. The connecting sleeve has an installation cavity, one end of the linear body is arranged in the installation cavity, and one end of the linear body is movably connected or fixedly connected to the installation cavity; when one end of the linear body is fixedly connected to the installation cavity, the connecting sleeve is used to move relative to the balloon; when one end of the linear body is movably connected to the installation cavity, the connecting sleeve is used to move or remain stationary relative to the balloon.

7. The drug delivery device according to claim 6, characterized in that The height of the cross section of the linear body is 0.1 mm to 0.35 mm.

8. The drug delivery device according to claim 6, characterized in that The outer surface of the linear body on the side facing away from the balloon is formed with protrusions that are connected in lines or distributed at intervals.

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