Internal arteriovenous fistula stenosis treatment balloon for drug delivery based on groove nick wires

Abstract

The invention relates to an internal arteriovenous fistula stenosis treatment balloon for drug delivery based on groove nick wires, the nick wires are arranged on the outer surface of a balloon stent, and sustained-release drugs for diffusion treatment are stored in the nick wires, so that the balloon can carry more sustained-release drugs, and the balloon stent is more convenient to use. And the medicine is delivered to the deep layer of the blood vessel wall by embedding the indentation wires into the blood vessel wall. Through the protection of the indentation wires, the drug can be prevented from being scratched by the blood vessel wall or diluted and dissolved by the blood in the conveying process, the sustained-release drug can be protected to the maximum extent, the drug loss is avoided, the lasting release property is kept, and the release treatment can be continuously carried out; the problems that a common drug balloon is limited in drug delivery depth and insufficient in drug local retention time are solved, the drug can play a role in inhibiting proliferation of cells with wider vascular walls, the effects of relieving vascular stenosis and inhibiting relapse of the vascular stenosis are further achieved, pains of patients can be relieved, and the medical cost can be saved.

Description

Technical Field

[0001] The present disclosure relates to the technical field of medical stents, and in particular to a balloon for treating arteriovenous fistula stenosis based on grooved scored wires for drug delivery and an application method thereof. Background Art

[0002] The "drug-eluting balloon" is considered one of the representative treatment options for "intervention without implantation" and has become a "must-fight" for medical device companies. The drug-eluting balloon is only a carrier of the drug and a means of transporting the drug to the lesion site.

[0003] As attached Figure 1 The drug-eluting balloon shown is a medical device used to deliver drugs directly to specific sites in the body. It is often used intravascularly to deliver drugs to narrowed or blocked sites of blood vessels through catheter technology to treat vascular diseases such as coronary artery disease. The design of the drug-eluting balloon allows the release of drugs when the balloon is inflated, thereby increasing the concentration of drugs in the target area while reducing systemic side effects. This technology combines the advantages of balloon angioplasty and local drug therapy, aiming to improve treatment effectiveness and reduce recurrence rates.

[0004] Most traditional drug-eluting balloons are DCB balloons, or drug-coated balloons, where the drug for treating lesions is coated on the outer surface of the balloon. When the balloon reaches the "destination", the balloon expands and fills, so that the drug coated on the outer surface of the balloon fits tightly with the vascular endothelium. After the drug is released locally, the balloon is withdrawn from the body. However, this type of DCB balloon has the following obvious technical defects in clinical use:

[0005] First, traditional drug balloons can only deliver drugs to the shallow layer of the blood vessel wall and can only inhibit the proliferation of cells in the shallow part. For example, for the stenosis of hemodialysis arteriovenous fistula, the blood vessel wall is often thickened significantly. If the DCB drug delivery depth is not deep enough, the stenosis may still recur in the short term after the drug balloon dilation.

[0006] Second, the drug coating on the traditional drug balloon will be scraped by the introduction sheath and the blood vessel wall during the delivery process, thus causing varying degrees of drug coating loss;

[0007] Third, the drug coated on the traditional drug balloon can only adhere to the blood vessel surface through a limited expansion time. The absorption time is limited and it is easier to be washed off by the blood flow. The amount of drug remaining in the blood vessel wall is limited, which affects the therapeutic effect. If the traditional drug balloon is used multiple times to increase drug retention, it will not only increase time and cost, but also increase the dose of drug that is shed into the systemic circulation, increasing the risk of drug toxicity and side effects. Summary of the invention

[0008] In order to solve the above problems, the present application proposes a balloon for treating arteriovenous fistula stenosis based on grooved scored wire for drug delivery and an application method thereof.

[0009] On the one hand, the present application provides a balloon for treating arteriovenous fistula stenosis based on groove scored wire for drug delivery, comprising a push rod, a balloon, and a balloon stent arranged outside the balloon, wherein:

[0010] The balloon stent is provided with a plurality of protruding scoring wires, which are used to embed the scoring wires into the blood vessel wall through the expansion of the balloon when the balloon stent reaches the stenotic site of the internal fistula, so as to deliver the sustained-release drug for treating the stenosis of the internal fistula to the deep layer of the blood vessel wall;

[0011] A groove is provided in the scored wire, and a crystalline sustained-release drug is stored in the groove;

[0012] The grid spacing of the balloon stent is positively correlated with the sustained-release parameter of the sustained-release drug.

[0013] As an optional embodiment of the present application, optionally, the cross-sectional structure of the scored wire satisfies:

[0014] The caliber of the end in contact with the blood vessel wall is smaller than the caliber of the other end away from the blood vessel wall.

[0015] As an optional embodiment of the present application, optionally, the balloon stent is made of nylon.

[0016] As an optional embodiment of the present application, optionally, the cross-sectional structure of the scored wire is:

[0017] Trapezoidal groove, annular groove, triangular groove or rectangular groove.

[0018] The scored wire material has a certain elasticity and can deform under a certain pressure, flattening the groove and releasing the drug in the groove.

[0019] As an optional embodiment of the present application, optionally, the sustained-release drug is placed into the scored wire in the following manner:

[0020] According to the cross-sectional structure of the scored wire, after crystallization shaping, the obtained sustained-release drug crystals are placed in the scored wire.

[0021] As an optional embodiment of the present application, optionally, the sustained-release drug is placed into the scored wire in the following manner:

[0022] The balloon stent is placed in the liquid mixture of the sustained-release drug, crystallized under crystallization conditions, and after surface smoothing treatment, sustained-release drug crystals placed in the scored wire are obtained.

[0023] As an optional embodiment of the present application, optionally, the sustained-release drug is a drug that inhibits cell proliferation, such as paclitaxel and sirolimus;

[0024] The grid spacing of the balloon stent is 2-4 mm.

[0025] As an optional embodiment of the present application, optionally, the scoring wires are arranged at equal intervals;

[0026] The linear spacing between the scored wires is maintained at least at 0.5-1.0 mm.

[0027] On the other hand, the present application provides an application method of a balloon for treating arteriovenous fistula stenosis based on grooved scored wire for drug delivery, comprising the following steps:

[0028] Clean the balloon stent and keep the scoring wire clean;

[0029] placing a crystalline sustained-release drug into the scored wire;

[0030] The balloon surface is smoothed to ensure a smooth transition between the sustained-release drug crystals and the outer surface of the balloon stent;

[0031] Inserting the mesh balloon into a predetermined position in the blood vessel, and controlling the release according to the sustained-release parameters of the sustained-release drug;

[0032] Release control is complete and the mesh balloon is retracted.

[0033] Technical effects of the present invention:

[0034] The present application provides scored wires on the outer surface of the balloon stent, and stores the sustained-release drug for diffusion therapy in the scored wires in a crystalline form, so that the balloon can carry a larger amount of sustained-release drug. The scored wires can protect the drug from being scraped by the blood vessel wall or diluted and dissolved by the blood during the delivery process, thereby maximizing the protection of the sustained-release drug and avoiding drug loss.

[0035] The scored wire drug delivery method of the present invention can deliver the drug to the target site of the blood vessel along with the mesh balloon and then release the drug. The scored wire can embed the drug into the blood vessel wall so that the drug resides deep in the blood vessel. The sustained-release drug can maintain a long-lasting release and diffuse into the surrounding tissue, inhibiting more extensive cell proliferation in the blood vessel wall, enhancing and prolonging the therapeutic effect, and solving the risk of short-term recurrence of stenosis after traditional drug balloon dilation, which can reduce pain for patients and save medical costs.

[0036] Further features and aspects of the present disclosure will become apparent from the following detailed description of exemplary embodiments with reference to the attached drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate exemplary embodiments, features, and aspects of the disclosure and, together with the description, serve to explain the principles of the disclosure.

[0038] Figure 1 Shown is a schematic diagram of the application of a traditional drug balloon;

[0039] Figure 2 Shown is a schematic diagram of the application structure of the balloon with drug-scored wire of the present invention;

[0040] Figure 3 It is a schematic diagram showing a state in which the balloon of the present invention enters a blood vessel and the balloon stent is not expanded and squeezes the blood vessel wall;

[0041] Figure 4 It is a schematic diagram showing the state in which the balloon of the present invention enters a blood vessel and the balloon stent expands and squeezes the blood vessel wall;

[0042] Figure 5 Shown is a release control table of different sustained-release drugs and corresponding sustained-release parameters of the present invention;

[0043] Figure 6 Shown is a schematic diagram of the structure of one of the scored wires of the present invention on a balloon stent;

[0044] Figure 7 Shown is a schematic diagram of the structure of another notched wire on a balloon stent according to the present invention. DETAILED DESCRIPTION

[0045] Various exemplary embodiments, features and aspects of the present disclosure will be described in detail below with reference to the accompanying drawings. The same reference numerals in the accompanying drawings represent elements with the same or similar functions. Although various aspects of the embodiments are shown in the accompanying drawings, the drawings are not necessarily drawn to scale unless otherwise specified.

[0046] The word “exemplary” is used exclusively herein to mean “serving as an example, example, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments.

[0047] In addition, in order to better illustrate the present disclosure, numerous specific details are given in the following specific embodiments. It should be understood by those skilled in the art that the present disclosure can also be implemented without certain specific details. In some examples, means, components and circuits well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present disclosure.

[0048] Example 1

[0049] like Figure 2As shown, on one hand, the present application proposes a balloon for treating arteriovenous fistula stenosis based on groove scored wire for drug delivery, comprising a push rod 1, a balloon 2, and a balloon support 3 arranged outside the balloon, wherein:

[0050] The balloon stent 3 is provided with a plurality of protruding notched wires 4, which are used to embed the notched wires 4 into the blood vessel wall through balloon expansion when the balloon stent reaches the stenotic site of the internal fistula, so as to deliver the sustained-release drug for treating the stenosis of the internal fistula to the deep layer of the blood vessel wall;

[0051] The scored wire 4 is provided with a groove, and the crystalline sustained-release drug 5 is stored in the groove;

[0052] The grid spacing of the balloon stent 3 is positively correlated with the sustained-release parameter of the sustained-release drug.

[0053] As an optional embodiment of the present application, optionally, the cross-sectional structure of the scored wire 4 satisfies:

[0054] The caliber of the end in contact with the blood vessel wall is smaller than the caliber of the other end away from the blood vessel wall.

[0055] The push rod 1, the balloon 2 and the balloon support 3 arranged outside the balloon can be combined with, for example, an attached Figure 1 The traditional drug balloon is understood.

[0056] The present invention designs a mesh drug deep balloon, the mesh support of which needs to be provided with a network of scored wires for placing drugs, drug crystals are placed in the network of scored wires, and are released after being transported to the target part of the blood vessel along with the mesh drug deep balloon.

[0057] The drug balloon should cover at least 2 mm near or far from the pre-treated site. DCB release: Slowly pressurize to the named pressure (or to a higher pressure), and then maintain it for a sufficient time (for example, paclitaxel. 30 seconds is enough to release the drug, but extending it to 120 seconds is better to reduce the incidence of dissection).

[0058] As for the specific sustained-release drug 5, the doctor or other user can select the balloon model according to the sustained-release parameters of the sustained-release drug.

[0059] According to the diffusivity of the drug (a release table can be configured for reference, such as Figure 5 A sustained-release reference table as shown in the figure) is used to set the grid spacing of the mesh drug deep balloon. For example, the drug release of paclitaxel may reach one millimeter, so the network spacing is maintained at about two millimeters.

[0060] Therefore, the present invention provides scored wires on the outer surface of the balloon stent, and stores the sustained-release drug for diffusion therapy in the scored wires in a crystalline form, so that the balloon can carry a larger amount of sustained-release drug. The scored wires can protect the drug from being scraped by the blood vessel wall or diluted and dissolved by the blood during the delivery process, thereby maximizing the protection of the sustained-release drug and avoiding drug loss.

[0061] The scored wire drug delivery method of the present invention can deliver the drug to the target site of the blood vessel along with the mesh balloon and then release the drug. The scored wire can maintain a long-lasting release of the drug, and can continuously perform release treatment, avoiding multiple balloon stent treatments, reducing pain for patients and saving medical costs.

[0062] As an optional embodiment of the present application, optionally, the balloon stent is made of nylon.

[0063] As an optional embodiment of the present application, optionally, the cross-sectional structure of the scored wire is:

[0064] Trapezoidal groove, annular groove, triangular groove or rectangular groove.

[0065] like Figure 3 and Figure 4 As shown, the method and size of scoring the wires on the surface of the mesh stent are not limited by the present invention.

[0066] The cross-sectional structure of the scored wire can be a trapezoidal groove, a dovetail groove, an annular groove, a spherical groove, a triangular groove, a rectangular groove, etc. As long as the sustained-release drug crystals can be wrapped and embedded in the scored wire, it can be prevented from falling off the bracket. The size of the outer portion of the scored wire, that is, the size of the surface outlet, should be smaller than the size of the bottom of the scored wire, so that the drug crystals can be stuck in the scored wire to prevent the crystals from slipping out during transportation.

[0067] The specific scoring wire can be processed by the stent manufacturer. The network distance of the stent can be referred to in the attached document of this application. Figure 5 The table information in .

[0068] In the present invention, there are two ways to put the drug crystal into the scored wire:

[0069] As an optional embodiment of the present application, optionally, the sustained-release drug is placed into the scored wire in the following manner:

[0070] According to the cross-sectional structure of the scored wire, after crystallization shaping, the obtained sustained-release drug crystals are placed in the scored wire.

[0071] The first method is to crystallize the drug according to the cross-sectional structure of the scored wire, and shape the crystal according to the cross-sectional structure of the scored wire. The size of the crystal should be smaller than the size of the scored wire, so that it is easy to fit the crystal into the scored wire. The specific placement can be done by the corresponding staff (for example, by key slot), or it can be made under low temperature conditions.

[0072] As an optional embodiment of the present application, optionally, the sustained-release drug is placed into the scored wire in the following manner:

[0073] The balloon stent is placed in the liquid mixture of the sustained-release drug, crystallized under crystallization conditions, and after surface smoothing treatment, sustained-release drug crystals placed in the scored wire are obtained.

[0074] Another method is to use natural crystallization. Put the liquid fraction of the sustained-release drug into a container and set the corresponding crystallization conditions. Put the balloon stent into the liquid, set the corresponding crystallization points in the scored wire, and perform natural crystallization to fill the space where the scored wire is located. In this way, the drug crystals are placed. Then the stent surface can be smoothed.

[0075] The crystallization steps are as follows:

[0076] First, ensure that the concentration of the drug solution is appropriate to avoid oversaturation, which may lead to rapid or uneven crystallization. Then, slowly add the drug solution to the crystallization vessel that has been preheated to the appropriate temperature to control the crystallization rate.

[0077] Then, the solution is slowly cooled to promote the orderly arrangement of drug molecules and the formation of crystal nuclei. During the cooling process, a stirrer can be used to gently stir to help the crystal nuclei grow evenly and prevent aggregation. When the solution reaches the target temperature, it is maintained for a period of time to ensure that the drug molecules have enough time to fill the crystal space.

[0078] Finally, pure drug crystals are obtained through filtering, washing and drying steps. Throughout the process, parameters such as the pH value, temperature and stirring speed of the solution are monitored to ensure the smooth progress of the crystallization process.

[0079] The present invention can provide artificial crystal nuclei in the scored wire to facilitate crystallization.

[0080] As an optional embodiment of the present application, optionally, the sustained-release drug is paclitaxel;

[0081] The grid spacing of the balloon stent is 2-4 mm.

[0082] The drug balloon should cover at least 2 mm near or far from the pre-treated site. DCB release: Slowly pressurize to the nominal pressure (or to a higher pressure), and then maintain it for a sufficient time (30 seconds is enough to fully release the drug, but extending it to 120 seconds is better to reduce the incidence of dissection).

[0083] As an optional embodiment of the present application, optionally, the scoring wires are arranged at equal intervals;

[0084] The linear spacing between the scored wires is maintained at least at 0.5-1.0 mm.

[0085] like Figure 5 As shown, the grid spacing of the deep drug mesh balloon can be set according to the diffusivity of the drug (a release table can be configured for reference). For example, the drug release of paclitaxel may reach one millimeter, so the network spacing is maintained at about two millimeters. Here, a grid expansion control formula for the deep drug mesh balloon can be set for the doctor's reference.

[0086] Different sustained-release drugs need to control and select the corresponding balloon model and size according to their sustained-release parameters.

[0087] In order to determine the grid spacing of the drug balloon according to the sustained release rate of the drug in the blood vessel, the following key factors need to be considered:

[0088] 1. Physical and chemical properties of drugs: including drug solubility, molecular weight, stability, etc. These properties determine the rate and mode of drug release.

[0089] 2. Physiological characteristics of blood vessels: blood flow velocity, thickness and permeability of blood vessel walls will affect the release and distribution of drugs.

[0090] 3. Selection of sustained-release materials: Select appropriate sustained-release materials, such as the type and thickness of polymer, to control the rate of drug release.

[0091] 4. Balloon design: The shape, size, mesh size and density of the balloon, these design parameters directly affect the uniformity and efficiency of drug release.

[0092] 5. Clinical needs: Determine the rate and duration of drug release based on the therapeutic goals and clinical requirements of drug release.

[0093] Based on the above factors, the following steps can be performed to determine the grid spacing of the drug balloon:

[0094] - Experimental testing: The effect of different grid spacing on drug release rate was evaluated through in vitro release experiments and in vivo pharmacokinetic studies.

[0095] -Mathematical modeling: Use the pharmacokinetic principle to establish a mathematical model to simulate the drug release process in blood vessels and predict the drug release curve under different grid spacing.

[0096] -Optimize design: According to experimental data and model prediction results, adjust the grid spacing to achieve the expected drug release rate and distribution effect.

[0097] Ultimately, by comprehensively considering drug properties, vascular physiology, sustained-release materials, balloon design, and clinical needs, an appropriate grid spacing can be determined to ensure that the sustained-release rate of the drug in the blood vessels meets the therapeutic requirements.

[0098] The material hardness of the scored wire allows the scored wire to be embedded in the blood vessel wall and allows it to deform under a certain pressure, making the groove smaller and allowing the drug to be squeezed out of the groove to achieve the purpose of release.

[0099] The above sustained-release parameters can be determined by a physician or based on the drug's kinetics in the blood vessels.

[0100] In specific implementation, it can be mixed with magnesium stearate in advance for sustained release, and the matrix can be used to assist in sustained release.

[0101] It should be noted that although the above-mentioned sustained-release drugs are introduced as examples, those skilled in the art will understand that the present disclosure should not be limited thereto. In fact, the user can flexibly set the sustained-release parameters of the corresponding drug according to the actual application scenario, as long as the technical functions of the present application can be realized according to the above-mentioned technology.

[0102] In addition, the requirement for the scored wire 4 is that the top size of the scored wire 4 is smaller than the bottom size, so that when the scored wire 4 contacts the blood vessel wall, the head (top) of the scored wire 4 can be easily embedded in the blood vessel wall.

[0103] As for the groove for accommodating the sustained-release drug 5, the opening size is kept larger than the bottom size to facilitate the sustained release of the drug.

[0104] Can be combined with Figure 6 and attached Figure 7 The structures of other shapes are not described in detail in this embodiment.

[0105] Example 2

[0106] Based on the implementation principle of the embodiment, the present application, on the other hand, proposes another configuration structure of the scoring wire.

[0107] The balloon surface has a layer of raised mesh hard structure 6 arranged on a rib on the mesh surface (made of nylon or other materials), the scored wire 4 is integrally formed on the mesh hard structure, and the crystalline sustained-release drug 5 is still placed in the scored wire 4.

[0108] During expansion, these bulges can be squeezed into the blood vessel wall, like a scored silk capsule, penetrating deep into the blood vessel. The dissolution depth is estimated to be about 0.5 mm. The density needs to be a little denser. If allowed, after the drug is implanted in a dotted manner, it can be diffused deep inside. It should be combined with paclitaxel, and then the density of the network can be determined based on the diffusion range of these drugs in the blood vessel wall.

[0109] Example 3

[0110] Based on the implementation principle of Example 1, on the other hand, the present application proposes an application method of a balloon for treating arteriovenous fistula stenosis based on grooved scored wire for drug delivery, comprising the following steps:

[0111] Clean the balloon stent and keep the scoring wire clean;

[0112] placing a crystalline sustained-release drug into the scored wire;

[0113] The balloon surface is smoothed to ensure a smooth transition between the sustained-release drug crystals and the outer surface of the balloon stent;

[0114] Inserting the mesh balloon into a predetermined position in the blood vessel, and controlling the release according to the sustained-release parameters of the sustained-release drug;

[0115] Release control is complete and the mesh balloon is retracted.

[0116] The above steps may be implemented in combination with the operating steps of the existing drug balloon, and may be implemented specifically in combination with the parameters or principles in Example 1.

[0117] The embodiments of the present disclosure have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and changes will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A balloon for treating arteriovenous fistula stenosis based on grooved scored wire for drug delivery, characterized in that: It includes a push rod, a balloon and a balloon support arranged outside the balloon, wherein: The balloon stent is provided with a plurality of protruding scoring wires, which are used to embed the scoring wires into the blood vessel wall through the expansion of the balloon when the balloon stent reaches the stenotic site of the internal fistula, so as to deliver the sustained-release drug for treating the stenosis of the internal fistula to the deep layer of the blood vessel wall; A groove is provided in the scored wire, and a crystalline sustained-release drug is stored in the groove; The grid spacing of the balloon stent is positively correlated with the sustained-release parameter of the sustained-release drug.

2. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The balloon stent is made of nylon.

3. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The cross-sectional structure of the scored wire satisfies: The caliber of the end in contact with the blood vessel wall is smaller than the caliber of the other end away from the blood vessel wall.

4. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The cross-sectional structure of the scored wire is preferably a V-shaped groove.

5. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The distribution shape of the scored wire on the outer surface of the balloon stent is: Grid, spiral, parallel lines or matrix.

6. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The method of inserting the sustained-release drug into the scored wire is: According to the cross-sectional structure of the scored wire, after crystallization shaping, the obtained sustained-release drug crystals are placed in the scored wire.

7. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The method of inserting the sustained-release drug into the scored wire is: The balloon stent is placed in the liquid mixture of the sustained-release drug, crystallized under crystallization conditions, and after surface smoothing treatment, sustained-release drug crystals placed in the scored wire are obtained.

8. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The sustained-release drug is a drug and matrix that inhibits cell proliferation, including paclitaxel or sirolimus; The grid spacing of the balloon stent is 2-4 mm.

9. The arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to claim 1, characterized in that: The notched wires are arranged at equal intervals; The linear spacing between the scored wires is maintained at least at 0.5-1.0 mm.

10. A method for using the arteriovenous fistula stenosis treatment balloon based on grooved scored wire for drug delivery according to any one of claims 1 to 9, characterized in that: The steps include: Clean the balloon stent and keep the scoring wire clean; placing a crystalline sustained-release drug into the scored wire; The balloon surface is smoothed to ensure a smooth transition between the sustained-release drug crystals and the outer surface of the balloon stent; Inserting the mesh balloon into a predetermined position in the blood vessel, and controlling the release according to the sustained-release parameters of the sustained-release drug; Release control is complete and the mesh balloon is retracted.

Images