CN117258122A

CN117258122A - Injection balloon and injection balloon slow release system

Info

Publication number: CN117258122A
Application number: CN202311141624.0A
Authority: CN
Inventors: 朱笑蒙; 徐思祺; 谢建
Original assignee: Xinyezhou Shanghai Medical Equipment Co ltd
Current assignee: Xinyezhou Shanghai Medical Equipment Co ltd
Priority date: 2022-12-09
Filing date: 2023-08-29
Publication date: 2023-12-22
Also published as: CN117065189A; CN117224822A

Abstract

The invention provides an injection balloon and an injection balloon slow release system, comprising: a delivery catheter, at least one set of drug delivery assemblies, and a balloon assembly; a delivery catheter comprising a first channel for delivering a drug and a second channel for flow-through inflation and deflation that are not in communication with each other; the second channel and the first channel are two independent channels which are not communicated and are independently controlled; the drug delivery assembly comprises at least one delivery structure and a drug delivery cavity, wherein the delivery structure comprises drug delivery holes, and the drug delivery holes in the group are communicated with the drug delivery cavity. Therefore, the transfer rate of the medicine is improved, meanwhile, due to the specific arrangement of the medicine release holes, accurate medicine administration can be realized, and the requirement on the expansion pressure of the balloon is small, so that the pressure of medicine injection cannot be influenced due to the expansion pressure of the balloon; the targeted drug delivery can be realized, and the drug delivery can be realized for multiple times.

Description

Injection balloon and injection balloon slow release system

Technical Field

The invention relates to the technical field of medical instruments, in particular to an injection balloon and an injection balloon slow release system.

Background

The medicine releasing saccule is one kind of medicine combining saccule with coated vascular micro inhibitor, such as taxol, rapamycin, etc. The medicine can release a certain dose of medicine to the tunica media and even the adventitia of the blood vessel in a short time (< 60 s) in a direct contact mode, and plays a role in inhibiting regeneration of pathological cells for a long time. This approach avoids to some extent the case of drug eluting stent implantation, and this approach to the absence of an implant avoids the risk of stent rupture and thrombosis, and also avoids the need for long term drug administration. However, the limited release time results in an effective drug release rate of less than 10%, which is also a direction and difficulty in this technology to be improved.

The perfusion balloon is a porous balloon, and the drug is injected on the surface of the inner wall of the blood vessel through micropores in the mode of injection administration, and is also transferred below the inner wall of the blood vessel through tissue absorption. Disadvantages: 1) The balloon pressure is small, and the expansion pressure is insufficient; 2) The effective transfer rate of the medicine is still not high, the loss of the medicine in the process of catheter delivery is large, and the injection of the medicine is accurate in dosage and needs to be improved; 3) If high-pressure expansion is used to increase the drug transfer rate, the risk of tearing the arterial endothelium and causing a memory thrombus is likely to occur. Therefore, rebound may still occur during balloon evacuation from the vessel, further stenosis or occlusion may occur, in which case the drug balloon, while releasing the drug, does not effectively address the problem of coronary occlusion, and stent intervention is required.

Therefore, there is a need to provide an injection balloon that can increase the drug transfer rate without causing arterial endothelial tear due to excessive balloon pressure.

Disclosure of Invention

The invention aims to solve the technical problems that in the traditional medicine balloon, the medicine transfer rate is low, the medicine cannot be accurately administrated, and the balloon inflation pressure is high, so that adverse effects are generated.

The present embodiment provides an injection balloon including: a delivery catheter, at least one set of drug delivery assemblies, and a balloon assembly; a delivery catheter having a proximal portion and a distal portion, the delivery catheter comprising a first passageway for delivering a drug and a second passageway for flow-through inflation and deflation that are not in communication with each other, at least the first passageway adjacent the distal portion being of a multi-lumen structure comprising a plurality of independent drug delivery passageways for delivering a drug; the second channel and the first channel are two independent channels which are not communicated and are independently controlled; at least one set of drug delivery assemblies, said drug delivery assemblies comprising at least one delivery structure and a dosing chamber, said delivery structure comprising drug delivery apertures, said drug delivery apertures of said set being in communication with said dosing chamber; balloon assembly: at least one balloon configured to change between a folded configuration and an unfolded configuration by inflation and deflation; in the folded configuration, the drug release assemblies are individually enclosed in the balloon; in the unfolding configuration, the expansion force of the balloon drives the drug release component to move to a preset target area, and the drug is conveyed to the target area through the drug delivery channel by independently applying corresponding control force.

Optionally, the first channel and the drug release component are disposed on an outer surface of the balloon, or the first channel and the drug release component are disposed on an inner surface of the balloon.

Optionally, when the first channel and the drug release component are arranged on the outer surface of the balloon, and when the drug release holes of the drug release component are in a row of hole structures, the drug release holes face the balloon expansion direction; or the direction of the drug release hole forms a certain angle with the expansion direction of the balloon; when the medicine release holes of the medicine release component are of a multi-row hole structure, an included angle is formed between the axial directions of the holes of each row of hole structure.

Optionally, the drug release component is a hollow wire, and a drug release hole is arranged on the hollow wire; preferably, the inner diameter of the drug release hole is smaller than the inner diameter of the drug administration cavity; preferably, the internal diameter of the dosing chamber is ≡1 μm, for example 1, 2, 3, 4, 5 μm; preferably, the inner diameter of the administration cavity is more than or equal to 3 mu m; more preferably, the inner diameter of the dosing chamber is not less than 0.1mm, even more preferably, the inner diameter of the dosing hole has a size in the range of 2 μm to 500. Mu.m, preferably 2 μm to 200. Mu.m, even more preferably 50 μm to 150. Mu.m; the ratio of the inner diameter to the outer diameter of the dosing cavity is 0.1-0.9, more preferably, the ratio of the inner diameter to the outer diameter of the dosing cavity is 0.4-0.8; the inner diameter of the administration hole is smaller than the inner diameter of the administration cavity; preferably, the inner diameter of the administration hole is smaller than 0.5 times of the inner diameter of the administration cavity, and the inner diameter of the administration hole is smaller than or equal to 0.01mm.

Optionally, the medicine release component is a triangle hollow structure, one surface of the triangle hollow structure is connected with the saccule, and the other two surfaces of the triangle hollow structure are respectively provided with medicine release holes.

Preferably, the delivery catheter is further provided with a pressure filling and releasing control unit and a drug delivery control unit, a circulation pressure filling and releasing channel formed by the second channel and the balloon is controlled by the pressure filling and releasing control unit, and the first channel and the balloon are respectively controlled by the drug delivery control unit; the pressure-filling and pressure-releasing control unit and the drug delivery control unit can control the force-giving amount by a pump and the like; the first channel of the delivery catheter is a plurality of independent drug delivery channels, and drug delivery channels are independent from proximal to distal;

preferably, when a completely independent mode of drug delivery is adopted, the radial dimension and the axial dimension of each drug delivery channel are consistent;

preferably, the injection balloon may be a rapid exchange structure or a full exchange structure;

preferably, the injection balloon is further connected with a catheter Hub (Hub) connected with the first channel for delivering a drug, preferably the catheter Hub is of a double luer (2-Way Hub) or a triple luer (3-Way Hub) or even a multiple luer design; a luer fitting on the catheter hub is connected to a valve, connector, syringe or pressure filling device through which a particular medication is given into the infusion path, which medication is a designated medication system.

Alternatively, the spacing between each drug delivery aperture is at least 0.5mm, for example 0.5, 0.6, 0.7, 0.8, 0.9mm; the diameter of the balloon is 1.2-14mm, such as 1.2, 1.5, 2, 2.5, 3mm, the length of the balloon is 10-80mm, such as 10, 20, 30, 40, 50, 60, 70, 80, 90mm, and the drug release component is in two, three or four rows.

Optionally, the injection balloon further comprises a puncture part, wherein the puncture part is communicated with the drug release hole, and the puncture part is in a needle-shaped structure; preferably, the height of the piercing section is 0.1mm-2mm, such as 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.1, 1.2, 1.4, 1.6, 1.8, 2mm, and the diameter is 10 μm-500 μm, such as 10, 20, 30, 40, 50, 60, 70, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, 500 μm.

Alternatively, the balloon is pressurized at a pressure in the range of 3 to 30atm, preferably 8 to 24atm, such as 8, 10, 12, 14, 16, 18, 20, 22, 24atm.

Optionally, the drug delivery assembly has a rigid catheter providing the fixed lumen required for the delivery structure and a flexible catheter configured to provide flexibility to the drug delivery catheter;

Preferably, the drug delivery catheter of the drug release assembly comprises a hard catheter and a soft catheter along the axial direction of the balloon, wherein the hard catheter and the soft catheter are arranged at intervals in sections; preferably, the number of soft catheters is one less than the number of hard catheters;

preferably, the puncture structure is arranged on the hard catheter;

preferably, the hard catheter of the front section and the hard catheter of the rear section are different in the circumferential direction of the balloon along the circumferential direction of the balloon so as to form staggered arrangement;

preferably, the size of the hard catheter and the axial size of the soft catheter are 0.5-20 mm;

optionally, the injection balloon further comprises a drug coating, the drug of which may be the same as or different from the drug delivered in the first channel.

The embodiment also provides an injection balloon slow release system, which comprises the injection balloon and a drug system,

the pharmaceutical system comprises a pharmaceutical particle and/or a pharmaceutical carrier; the drug particles and/or the drug carrier can be mixed with a solution to form a drug solution, the drug solution being delivered to a target tissue site;

preferably, the drug particles are crystalline drug crystals which are delivered into the tissue to enable sustained drug release, the drug particles have a particle size of 1 to 1000 μm, preferably, the drug particles have a particle size of 1 to 150 μm, more preferably, the drug particles have a particle size of 1 to 50 μm; the slow release period of the drug crystal is between one week and 6 months;

Preferably, the drug carrier is a drug sustained-release microsphere prepared by mixing a degradable polymer material and a drug, the diameter of the drug sustained-release microsphere is 1-1000 mu m, preferably, the diameter of the drug sustained-release microsphere is 1-150 mu m, more preferably, the diameter of the drug sustained-release microsphere is 1-50 mu m; the slow release period is between 1 week and 6 months;

preferably, the drug carrier has pores in which the drug is contained, the drug is slowly released from the pores, the diameter of the drug carrier is 1 to 1000 μm, preferably, the diameter of the drug carrier is 1 to 150 μm, more preferably, the diameter of the drug carrier is 1 to 50 μm; the slow release period is between 1 week and 6 months;

preferably, the polymer degradable material used in the drug carrier comprises: one of polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), carbon dioxide polymer (PPC), polybutylene succinate (PBS), aliphatic aromatic polyester Ecoflex (PBAT), polytrimethylene terephthalate (PPT), poly beta-hydroxyalkanoate (PHA), poly epsilon-caprolactone (PCL), poly p-dioxanone (PPDO), or a copolymer or blend of any of a plurality of polymers thereof;

Preferably, the pharmaceutical system is a pharmaceutical particle, or a pharmaceutical carrier or composition comprising pharmaceutical particles, comprising one or more therapeutic substances, diagnostic substances, a drug, a therapeutic composition, a diagnostic composition, physiologically active agents, a biochemical active agent, one or more living cells, DNA, RNA, nucleic acids, cell carriers for delivering genetic material into a target site, anti-inflammatory agents, an anti-restenosis agent, a cell proliferation inhibitor, smooth muscle proliferation inhibitor, paclitaxel, rapamycin, everolimus, vasoactive agents, vasodilators, vasoconstrictors, antibiotics, anticoagulants, platelet aggregation inhibitors, anti-fibrosis agents, alpha reductase inhibitors, pharmaceutically acceptable carriers, lipid-based carriers, and any combination thereof;

preferably, a coating layer is arranged on the drug carrier, the drug is arranged in the coating layer to form slow release, and the coating layer can be dissolved; the slow release period is between 1 week and 6 months;

preferably, the drug carrier is a sphere, bar or sheet; preferably, the drug crystals are spherical, polygonal, bar or sheet.

According to the injection balloon provided by the embodiment, the single first channel is arranged, so that the transfer rate of the medicine is improved, meanwhile, due to the specific arrangement of the medicine release holes, accurate medicine administration can be realized, the requirement on the expansion pressure of the balloon is low, and the pressure of medicine injection cannot be influenced due to the expansion pressure of the balloon; the targeted drug delivery can be realized, and the drug delivery can be realized for multiple times.

Compared with the prior art, the invention has the following advantages:

1. high-efficiency drug transfer capacity: compared with an application balloon (DCB), the drug is not lost in the process of catheter delivery, and the injection of the drug can be precisely dosed and repeated.

2. Sustainable therapeutic effect: the drug-loaded microspheres have sustained drug release in addition to a single drug. The release period can reach 1 week to 6 months, and is continuously controllable.

3. The operation is simple and convenient: the circumferential distribution structure of the microneedles is non-directional. This eliminates the need for the physician to adjust the position of the catheter during the procedure. The drug can be uniformly absorbed on the vessel wall to achieve the expected clinical effect.

Drawings

Those of ordinary skill in the art will appreciate that the figures are provided for a better understanding of the present invention and do not constitute any limitation on the scope of the present invention. Wherein:

Fig. 1A is a schematic view of a device for realizing drug delivery using a balloon according to the first embodiment;

FIG. 1B is a cross-sectional view of the portion A-A of the device of FIG. 1A for effecting drug delivery using a balloon;

fig. 2A is a schematic view of a device for realizing drug delivery using a balloon according to the first embodiment;

FIG. 2B is a cross-sectional view of the device of FIG. 2A in one direction using a balloon to effect drug delivery;

FIG. 2C is a cross-sectional view of the device of FIG. 2A in a collapsed state for drug delivery using a balloon;

fig. 2D is a cross-sectional view of another device for achieving drug delivery using a balloon according to the first embodiment in a folded state;

FIG. 3 is a schematic illustration of drug delivery and drug delivery of the device of FIG. 2A utilizing a balloon to effect drug delivery;

FIG. 4A is a view of the structure of the lancing assembly;

FIG. 4B is a schematic illustration of another alternative piercing assembly configuration;

FIG. 4C is a schematic illustration of another alternative piercing assembly configuration;

FIG. 5A is a schematic view of another piercing assembly according to an embodiment;

FIG. 5B is a schematic view of another piercing assembly according to the first embodiment;

FIG. 5C is a schematic view of another piercing assembly according to the first embodiment;

FIG. 5D illustrates the deployment of another puncture assembly according to the first embodiment in the circumferential direction of the balloon;

FIG. 5E is a schematic view illustrating a position relationship between a puncture assembly and a balloon according to another embodiment;

fig. 6A is a schematic view of a device for realizing drug delivery by using a balloon according to the second embodiment;

FIG. 6B is a cross-sectional view of the device of FIG. 6A in a collapsed state for drug delivery using a balloon;

fig. 7 is a schematic view of a device for realizing drug delivery using a balloon according to a third embodiment;

fig. 8A is a schematic view of a drug delivery device according to a fourth embodiment;

fig. 8B is a schematic view of another drug delivery device according to the fourth embodiment;

fig. 9 is a schematic view of a drug delivery device provided in fifth embodiment;

fig. 10 is a schematic view of another drug delivery device according to the fifth embodiment;

fig. 11 is an exemplary view of a drug delivery device provided in the sixth embodiment;

FIG. 12 is a schematic view of the tissue of an esophageal balloon device according to the eighth embodiment after in vitro injection;

fig. 13 is a schematic view of a prostatic urethra device according to the eighth embodiment;

fig. 14 is a schematic view of another prostatic urethra device according to the eighth embodiment;

fig. 15 is a schematic view of the tissue after in vitro injection using the prostatic urethra device according to the ninth embodiment;

fig. 16 is a schematic view showing the overall structure of an injection balloon according to the tenth embodiment;

Fig. 17A is a schematic cross-sectional view of a balloon portion of an injection balloon of the tenth embodiment;

fig. 17B is a schematic cross-sectional view of a balloon portion of another injection balloon of the tenth embodiment;

FIG. 17C is a schematic cross-sectional view of a balloon portion of another injection balloon according to the tenth embodiment;

fig. 18A is a schematic view of an injection balloon according to the tenth embodiment;

fig. 18B is a schematic view of another injection balloon according to the tenth embodiment;

fig. 18C is a schematic view of another injection balloon according to the tenth embodiment;

FIG. 19 is a schematic view of a drug delivery assembly of the injection balloon shown in FIG. 18;

fig. 20 is a schematic view showing the overall structure of another injection balloon according to the tenth embodiment;

FIG. 21A is a schematic view showing an example of a drug carrier according to the eleventh embodiment;

fig. 21B is a schematic view showing a second example of the drug carrier provided in the eleventh embodiment.

In the accompanying drawings:

1-a delivery catheter, 11-a first channel, 111-a drug delivery channel, 12-a second channel, 121-a groove;

2-puncture assembly, 21-puncture structure, 211-puncture part, 2111-puncture wall, 2112-puncture cavity, 2113-puncture plane, 212-drug release hole, 213-puncture blade, 2131-drug release part, 22-drug delivery cavity, 221-base, 2211-through hole, 222-drug delivery catheter, 2221-hard catheter, 2222-soft catheter;

3-balloon assembly, 31-balloon, 311-fold wings, 312-fold wing space, 32-guide catheter;

4-drug delivery assembly, 41-release structure, 411-drug delivery orifice, 42-drug delivery cavity, 421-drug delivery cavity, 422-drug delivery orifice;

a 5-balloon assembly, a 51-balloon,

6-drug release assembly, 61-release structure, 611-puncture part, 612-drug release hole, 63-base;

7-balloon assembly, 71-balloon;

10-coating structure;

the height of the H-folding wing space, the height of the H1-puncture structure and the height of the H2-administration cavity;

100-drug carrier, 101-microwells.

Detailed Description

Other advantages and effects of the present invention will become apparent to those skilled in the art from the following disclosure, which describes the embodiments of the present invention with reference to specific examples. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention. It is to be understood that the terms "center," "longitudinal," "transverse," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," and the like are directional or positional relationships as indicated based on the drawings, merely to facilitate describing the invention and simplify the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus are not to be construed as limiting the invention. Furthermore, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first", "a second", etc. may explicitly or implicitly include one or more such feature. In the description of the present invention, unless otherwise indicated, the meaning of "a plurality" is two or more.

It should be noted that, unless explicitly stated or limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art in a specific case. The "distal end" herein is the end that is remote from the operator, and the "proximal end" is the end that is close to the operator. Hereinafter, "device" refers to "a device for achieving drug delivery using a balloon".

First, the applicant first elucidated the authoring process of the present application.

The earliest prior drug delivery catheters for vascular delivery had balloon-like structures. When the balloon is inflated, the outer surface of the balloon contacts the inner surface of the vessel and may deliver some drug or therapeutic composition to the vessel wall. The drug may be delivered by adhering some of the drug or therapeutic composition to the intimal layer upon contact with the drug-coated outer surface of the balloon, or by dissolving the drug in the blood and diffusing the drug into the intimal layer, wherein the drug may act as a biologic therapy to reduce or prevent proliferation of vascular epithelial cells and the resultant restenosis of the treated vascular site. A common problem with such prior art drug delivery catheters is that during insertion of the catheter into the vasculature and movement of the catheter within the vasculature to reach the treatment site, the drug or therapeutic composition coating the outer surface of the balloon is exposed to the blood contained in the vasculature, which may cause some of the drug or active ingredient in the therapeutic composition to dissolve or disperse in the blood before the balloon reaches the desired treatment site. For this reason, the dual balloon structures mentioned in the prior art, one balloon being used to deliver a drug, the other balloon being inflated or deflated upon inflation and deflation. The applicant finds that the balloon used for delivering the medicine in the double-balloon structure expands or contracts after multiple thinking, and the balloon with the function of inflation and deflation pressure can also expand or contract. The precise control is divided into the following steps: the core of our inventors is the desire to achieve the latter two types of precise control, namely control of the region of drug delivery, control of the amount of drug delivered (i.e. the effective rate of transfer of the drug), control of the target depth of drug delivery to the target region.

For this reason, the applicant has learned through several thoughts and several verifications that the functionality of drug delivery catheters is divided into: delivering the drug to the target area. The applicant has considered providing a folded balloon which in its deployed state delivers the drug to the target area and by providing a separate drug delivery channel, this preliminary core idea is: the balloon is configured to change between a folded configuration and an unfolded configuration through a pressure filling and releasing channel, and the pressure filling and releasing channel and the drug releasing hole which are communicated with the drug administration cavity form a drug administration channel, and the two channels are two independent channels which are not communicated and are independently controlled. In the folded configuration, the drug release assembly is enclosed in the balloon; in the deployed configuration, the inflation force of the balloon moves the drug delivery assembly to a predetermined target area, and the drug is delivered to the target area through the independent drug delivery channel by the separate application of a corresponding control force. The core thought has the advantages that double saccules are not needed, and the effect of accurate drug delivery can be achieved only by one saccule. The drug delivery channel may be provided in plurality, the movement of the drug may be controlled by one drug delivery control unit, and the delivery of the drug to different depths of the target area may be controlled by adjusting the amount of force. The drug delivery channels can be provided with a plurality of drug delivery control units, and the movement of the drugs in each drug delivery channel can be controlled by different drug delivery control units, so that different drugs can be input, different input drugs can be controlled to enter different areas, the depths of the drugs can be controlled to enter different areas, and the drug delivery of different input drugs (different doses) for different times can be controlled. In this way, the injection of the drug is precisely dosed, multiple times. The above is merely an example, and one of the above precise control modes may be selected for control during example operations.

In addition, it is also noted that the medicament of the present application is a broad concept. The drug may be a drug-containing body or composition comprising one or more therapeutic substances, diagnostic substances, a drug, a therapeutic composition, a diagnostic composition, a physiologically active agent, a biochemical active agent, one or more living cells, DNA, RNA, nucleic acid, a cell carrier for delivering genetic material into a target site, an anti-inflammatory agent, an anti-restenosis agent, a cell proliferation inhibitor, a smooth muscle proliferation inhibitor, paclitaxel, rapamycin, everolimus, a vasoactive agent, a vasodilator, a vasoconstrictor, an antibiotic, an anticoagulant, a platelet aggregation inhibitor, an anti-fibrosis agent, a pharmaceutically acceptable carrier, a lipid-based carrier, and any combination thereof. Furthermore, the drug may also be an alpha reductase inhibitor, e.g. finasteride, dutasteride. For example, the drug may be spherical particles, slow release drug-loaded bars or sheets having a diameter of 1-1000 μm, and the drug delivery control unit may be configured to load the drug with a delivery force to control the delivery of the drug through the drug delivery channel to the target area, and/or to a depth corresponding to the target area. The drug release function can be continuously performed by drug-carrying microspheres or sheets, etc. in addition to the single drug. The release period can reach 1 week to 6 months, and is continuously controllable. It should be understood that the spherical particles, the slow-release medicine carrying bars or sheets are made of degradable emulsion polymers, and in particular, pores exist in the spherical particles, the slow-release medicine carrying bars or sheets, and medicines are carried in the pores, or the spherical particles are slow-release medicines prepared by mixing medicines with high polymer materials, or the spherical particles are medicine crystals, so that the slow release of the medicines is realized.

[ embodiment one ]

Referring to fig. 1 to 3, fig. 1A is a schematic diagram of a device for implementing drug delivery by using a balloon according to a first embodiment of the present invention; FIG. 1B is a cross-sectional view of the portion A-A of the device of FIG. 1A for effecting drug delivery using a balloon; fig. 2A is a schematic view of a device for realizing drug delivery using a balloon according to the first embodiment; FIG. 2B is a cross-sectional view of the device of FIG. 2A in one direction using a balloon to effect drug delivery; FIG. 2C is a cross-sectional view of the device of FIG. 2A in a collapsed state for drug delivery using a balloon; fig. 2D is a cross-sectional view of another device for achieving drug delivery using a balloon according to the first embodiment in a folded state; fig. 3 is a schematic illustration of drug delivery and fluid delivery of the device of fig. 2A using a balloon to effect drug delivery.

The first embodiment provides a device for realizing drug delivery by using a balloon. The device comprises: a delivery catheter 1, a plurality of sets of puncture assemblies 2, and a balloon assembly 3.

Referring to fig. 1A and 1B, a delivery catheter 1 has a proximal portion and a distal portion. The delivery catheter 1 comprises a first channel 11 for delivering the drug and a second channel 12 for flow-through inflation and deflation, which are not in communication with each other. At least the first channel 11 near the distal end portion is a multi-lumen structure comprising a plurality of individual drug delivery channels 111 for delivering a drug. In this way, accurate delivery of the medicament may be achieved by controlling the first channel 11 or the medicament delivery channel 111 to connect to a graduated syringe or additional auxiliary device. For example, a medication control unit may preferably be provided on the first channel 11. The medication delivery control unit may be one, connected to the three medication delivery channels by one and the same connection tube, and the medication is pressed into the three medication delivery channels by one connection tube. Of course, the number of the drug delivery control units can be three, and the drug delivery control units are respectively connected to the three drug delivery channels through respective connecting pipes, and in this case, the drug delivery control units can independently control different pressure values, the time, the duration and the like of the force. A pressure charge and discharge control unit may be provided on the second channel 12. The second channel 12 may be a connecting pipe, and the pressure filling and releasing control unit is connected with the second channel 12, and adopts liquid to realize pressure filling and releasing. The control of the pressure filling and releasing can adopt conventional technologies such as a pressure filling and releasing valve, and the like, and the details are not repeated herein. The distal end portion of the first channel 11 is, for example, three or four separate drug delivery channels 111, and the proximal end portions of the several drug delivery channels 111 may be in communication with one lumen or may be separately provided, for example, the first channel 11 is a plurality of drug delivery channels 111 separately provided. The first channel 11 is also provided with a first luer interface, and the first luer interface is respectively connected with catheter cavities corresponding to the plurality of drug delivery channels through a catheter. Preferably, the outer diameter or inner diameter of the first channel 11 is smaller than the outer diameter or inner diameter of the second channel 12.

Referring to fig. 1A, 2A and 2B, each of the plurality of sets of spike assemblies 2 includes at least one spike structure 21 and a drug administration cavity 22. The puncturing structure 21 includes a puncturing portion 211 and a drug release aperture 212, the drug release aperture 212 in the set communicates with the drug delivery cavity 22, and the drug delivery cavity 22 communicates with the corresponding drug delivery channel 111. When in use, the puncture part 211 is penetrated into the tissue, so that the liquid medicine can be injected into the tissue, the loss of the liquid medicine is prevented, the accurate medicine release is realized, and the treatment efficiency is improved. The medicine can be accurately conveyed to the target area, and necessary conditions are provided for quantitative, constant-speed and constant-pressure conveying of the medicine. In the first embodiment, the puncture assemblies 2 are three or four groups to match the drug delivery channels 111. The puncturing structure 21 and the dosing chamber 22 of the puncturing assembly 2 may be of various structures, as will be described in more detail below. The combination of the puncture assembly 2 and the balloon 31 may be various, as will be described in detail below. The administration cavity 2 may be a tube formed of a metal material, and its cross section may be circular, rectangular, or other shapes.

Referring to fig. 1 to 3, the balloon assembly 3 includes at least one balloon 31. Balloon 31 may be a compliant balloon, a non-compliant balloon, or a semi-compliant balloon. Preferably, the balloon assembly 3 further comprises a guide catheter 32. The distal end of the balloon 31 is connected to a guide catheter 32 to seal the distal end of the balloon 31. The proximal end of the balloon 31 is either sealingly or unsealably connected to the guide catheter 32. When in sealed connection, as shown in fig. 1B, the guide catheter 32 is spaced from the second channel 12. The guide catheter 32 is disposed inside the second channel 12 when it is not in sealed connection. The axial direction of the guide catheter 32 is arranged parallel to the axial direction of the second channel 12. The proximal end of the guide catheter 32 is the proximal end of the device. The proximal end of the balloon 31 is connected to the distal portion of the second channel 12 and the lumen of the balloon 31 communicates with the second channel 12. Notably, the balloon 31 is configured to change between a folded configuration and an unfolded configuration. As shown in fig. 2C, in the folded configuration, the multiple groups of puncture assemblies 2 are individually wrapped in the balloon 31, so that the puncture assemblies 2 can be individually wrapped in the balloon 31, and interaction between each group of puncture assemblies 2 is prevented. Inflation of the balloon 31 causes the puncture portions 211 of the multiple sets of puncture assemblies 2 to bulge by pressurizing the second passageway 12 to inflate the balloon 31 in the deployed configuration. As shown in fig. 3, the medicine is configured to be delivered to the target area by an external force (the external force may be a force controlled by the medicine delivery control unit) through the plurality of medicine delivery paths 111, the medicine delivery chamber 22 corresponding to each medicine delivery path 111, and the medicine release hole 212 through which the medicine delivery chamber 22 communicates, respectively.

Preferably, balloon 31 has a balloon lumen 9 and a balloon outer surface. The outer surface of the balloon 31 may be folded to form a plurality of pairs of folding wings 311 circumferentially disposed along the guide catheter 32, each pair of oppositely disposed folding wings 311 forming a folding wing space 312, and the puncture assemblies 2 of the sets are respectively accommodated in the adapted folding wing spaces 312. As shown in fig. 2C, in the present embodiment, the outer surface of the balloon is folded into three pairs of folding wings 311, and these folding wings 311 are circumferentially disposed around the guiding catheter 32, so that the puncture assemblies 2 of the groups can be circumferentially arranged, and the direction of the puncture assemblies 2 on the device can be non-directional, which makes the doctor need not to adjust the position of the catheter during the operation, greatly reduces the operation difficulty of the doctor, and improves the treatment efficiency. The drug can be absorbed uniformly in the circumferential direction of the tissue cavity (target site) to achieve the desired clinical effect. One group of puncture assemblies 2 corresponds to one folding wing space 312, and in the folded state, one group of puncture assemblies 2 is folded in the corresponding folding wing space 312. In general, the balloon may have shape memory properties when manufactured by the process, i.e., the balloon has shape memory properties of the folded wing spaces 312 when manufactured. The balloon lumen 9 is connected to a second channel 12. The balloon lumen 9 is filled with liquid during inflation to control the deployment of the balloon outer surface. The inner cavity 9 of the balloon is decompressed during decompression, and the balloon is folded.

Preferably, the dosing chamber 22 includes a base 221, an upper surface of the base 221 and other peripheral surfaces (other peripheral surfaces refer to peripheral surfaces excluding the upper surface) form a relatively fixed dosing chamber, the upper surface of the base 221 is provided with a through hole 2211 communicating with the drug release hole 212 along the length direction of the balloon 31, the puncture structure 21 is fixedly disposed on the upper surface of the base 221, and the drug release hole 212 communicates with the dosing chamber through the through hole 2211. The base 221 may be made of metal, which is not flexible, and the size of the space is relatively fixed. When the external force controlled by the drug delivery control unit is used for carrying out drug delivery operation through the base 221, the through hole 2211 and the drug release hole 212, the size of the channel is not greatly changed because the space of the base 221, the through hole 2211 and the drug release hole 212 is relatively fixed, so that the external force controlled by the drug delivery control unit can be better controlled, the precision is higher, and the drug delivery amount is more accurate. Of course, in other embodiments, the base 221 is not limited to a metal material, and may be a hard and non-deformable material. Alternatively, in other embodiments, the upper surface of the base 221 is made of a hard material, such as a metal material, so as to ensure that each piercing structure 21 can be protruded with the same amount of pressure when the balloon 31 is inflated. The cross-section of the base 221 may be a hollow circular, hollow rectangular or other shaped hollow cavity.

Preferably, as shown in fig. 2A and 2B, the administration lumen 22 is provided on the outer surface of the balloon 31. Specifically, the other peripheral surface of the base 221 includes a lower surface fixedly attached to the outer surface of the balloon 31, and drives the base 221 to move outwards along with the expansion of the balloon 31 in the deployed configuration, so as to drive the puncture portion 211 provided on the upper surface of the base 221 to protrude. The base 221 is connected with the balloon 31 in a bonding mode, so that the connection stability of the base 221 and the balloon 31 is ensured.

Referring to fig. 2C, the height H of the folded wing space 312 is not smaller than the sum of the height H2 of the base 221 and the height H1 of the puncture structure 21, so that the folded state of the whole balloon catheter is radially small, and meanwhile, smooth conveying of the balloon can be ensured, the puncture structure 21 can be ensured not to be damaged, and more applicable scenes can be ensured. Preferably, along the axial direction of the device, the distance between the end parts of the folding wings 311 (each group of folding wings 311) on two sides of the puncture structure 21 and the puncture structure 21 is equal, so that the circumferential stress of the balloon 31 is uniform in the conveying process of the device, the conveying stability is good, and the puncture structure 21 can be better protected and is not easy to break or skew. Similarly, along the circumferential direction of the device, the folding wings 311 of each group are symmetrically arranged, and each group of side penetrating assemblies 2 are symmetrically arranged, so that the circumferential stress uniformity of the balloon 31 is further ensured.

Preferably, the number of the puncture structures 21 of each group of puncture assemblies 2 is plural, and the puncture structures are arranged at intervals along the length direction of the base 221, the top of the puncture part 21 is a tip, and the end of the puncture part 21 encloses the drug release hole 212. Preferably, each piercing structure 21 in each set of piercing assemblies 2 is equally spaced.

Preferably, the delivery catheter is further provided with a pressure-filling and pressure-releasing control unit and a drug delivery control unit (not shown in the figure), the pressure-filling and releasing channels formed by the second channel 12 and the balloon 31 are controlled by the pressure-filling and releasing control unit, and the first channel 11 and the balloon 31 are controlled by the drug delivery control unit.

Preferably, a first luer interface is disposed on the first channel 11, and the first luer interface is connected to catheter lumens corresponding to the plurality of drug delivery channels through a catheter respectively.

Preferably, as shown in fig. 1B, a groove 121 is provided along the radial direction of the second channel 12, the groove 121 is provided extending along the axial direction of the second channel 12, and the groove 121 is used for accommodating the first channel 11, so that the radial dimension of the non-balloon portion of the device is smaller. Furthermore, by arranging this, the first channel 11 can be located closer to the axis of the second channel 12, and the bending radius is reduced, so that the overall flexibility is better. Further, the radius of the groove 121 is not smaller than the outer diameter of the first channel 11. Further, the depth of the groove 121 may be not smaller than the outer radius of the first channel 11, so that the first channel 11 is more stable in structure and better in integrity when being accommodated in the groove 121. Of course, the depth of the groove 121 may be set to be larger than the outer radius of the first passage 11 according to practical requirements. The number of the grooves 121 is not limited. In actual use, the first channel 11 may or may not be placed at the recess 121. It is also within the scope of the present invention if the first channel 11 is not placed at the recess 121.

Preferably, the device can be used for delivering a drug carrier 100, the drug carrier 100 contains a drug, and when the drug carrier 100 is injected into a tissue, the drug carrier 100 can slowly release the drug in the tissue, thereby achieving the purpose of continuously treating the tissue. Further, the radial dimension of the piercing assembly of the device is larger than the radial dimension of the drug carrier 100, e.g. the diameter of the piercing assembly is larger than the diameter of the drug carrier 100, thereby enabling the drug carrier 100 to pass through the piercing assembly into the tissue. Preferably, the radial dimension of the puncture assembly is greater than 1000 μm, preferably greater than 200 μm.

Puncture assembly

The shape, material, and dimensions of the piercing structure, and the combination of the piercing structure and the administration cavity 22 will be described in this section, but the piercing structure is not limited thereto and is within the scope of the present application as long as the structure to pierce the tissue can be achieved.

Referring to fig. 2B, the puncture structure 211 includes a puncture portion 211 and a drug release hole 212, wherein the puncture portion 211 includes a puncture wall 2111, a puncture cavity 2112, and a puncture surface 2113. The piercing surface 2113 is a surface on the top of the piercing portion 211, that is, a surface that is to be pierced when piercing tissue.

Preferably, as shown in FIGS. 4A and 4C, thePiercing surface 2113May be a plane, the piercing surface 2113 being at an angle a of 5-85 deg. to a plane perpendicular to the axial direction of the piercing structure 211 for better penetration into tissue. For example, when the angle a is 5 degrees, the top of the drug delivery device is a tip, and the end part is surrounded by a drug delivery hole. Of course, the piercing surface 2113 may be a surface having a certain curvature, such as a concave surface or a convex surface. As shown in fig. 4B, the piercing surface 2113 may be a conical surface, and the angle a of the conical surface may be 25 ° to 75 °. The piercing surface 2113 may also be a prismatic surface to match actual use requirements.

Preferably, the saidPiercing wall 2111May be cylindrical, conical, bottom cylindrical top conical, or stepped. As shown in fig. 4C, the thickness of the puncture wall 2111 does not change along the axial direction thereof, so that the puncture assembly is uniformly stressed during the puncture process and the delivery pressure of the drug from the delivery process is unchanged. Alternatively, the thickness of the puncture wall 2111 in the axial direction thereof is gradually reduced, for example, the taper formed by the reduction of the thickness is 0 to 10 °, so that the top size of the puncture portion 211 is smaller, or the thickness thereof is gradually increased, so that the size of the puncture cavity 2112 is gradually reduced, so that the delivery pressure in drug delivery is increased, and the injection pressure is increased. Alternatively, the inside of the puncture wall 2111 is stepped, and the radial dimension of the inside decreases as the puncture wall approaches the top But can be stepped to increase the pressure of drug delivery. The puncture cavity 2112 may be cylindrical, conical, stepped, or the like. The ratio of the inner radial dimension to the outer radial dimension of the piercing wall 2111 is 0.2 to 0.8, for example, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, etc. For example, the piercing wall 2111 may have an inner radial dimension of 0.2mm, 0.5mm, or 0.8mm, and an outer radial dimension of 1mm. The puncture wall 2111 has an inner radial dimension of 0.8mm and an outer radial dimension of 1.5mm, 2mm, 4mm, etc. Preferably, the inner diameter of the piercing wall 2111 has a size ranging from about 2 μm to about 500 μm, preferably from about 2 μm to about 200 μm, more preferably from about 50 μm to about 150 μm, and may be, for example, about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150 μm, etc., although smaller or larger sizes are also possible. Optionally, thePiercing wall 2111The puncture cavity is a slit formed along the puncture wall body, the cross sections of the puncture wall body are distributed in a triangular opposite mode, and the puncture cavity is formed in the middle of the puncture wall body, and the third embodiment can be referred to specifically.

The number of the puncture parts 211 may be set according to the actual practice, and may be arranged longitudinally along the balloon, circumferentially, or the like. Thus, the number of the puncture parts 211 is numerous, the distribution breadth and density of the puncture parts are improved, simultaneous administration of multiple points at the same time can be realized, the administration uniformity is improved, the treatment is more effective, and a better restenosis preventing treatment effect can be achieved.

Preferably, the saidDrug release hole 212The opening may be formed along the axial direction of the puncture part 211, as shown in fig. 4A, or may be formed along the radial direction of the puncture part 211, or the opening angle of the drug release hole 212 may be any angle, and the opening of the drug release hole 212 is oriented in the angular direction between the axial direction and the radial direction. When opening axially, radially or at any angle, the openings may be one or more, for example, as shown in fig. 4B, 2-4 openings are radially oriented. The drug delivery aperture 212 may be circular, oval, rectangular, or other polygonal shape, etc. The drug release hole can be an elongated opening or a groove-shaped openingA mouth, etc. Such openings may or may not be spaced apart in longitudinal rows along the length of the base 221, and the number of rows (if used) may be any suitable number in the range of 2-30 rows (although in some embodiments a number of rows above 30 may be used), as desired, and in particular, may be provided according to the size of the openings, according to the type and chemical/physical characteristics of the pharmaceutical or therapeutic composition, the size and depth of access to the target area, etc.

Preferably, the saidMaterial of the puncture part 2The alloy may be made of a hard material, for example, a metal material, and more preferably, nickel-titanium alloy, stainless steel, cobalt-chromium alloy, or the like. More preferably, the polymer material may include: nylon, ABS, resin, PEEK, TPE, TPU, PLA, photoresist, etc., and a biopolymer material such as silk fibroin. The metal material can be manufactured through the working procedures of laser etching, machining, acid washing, polishing, grinding and the like, and is pointed or forms a sharp cutting edge; the high polymer material can be manufactured in a 3D printing mode, and has the advantages of high precision and high processing speed. The high polymer material can also be manufactured by a mould casting/demoulding mode, and has the advantages of high strength and mass production.

Preferably, the saidPiercing section 2 and administration cavity 22In connection, the administration cavity 22 may be circular, oval, rectangular, etc. in cross-section. More preferably, the height h1 of the puncture part 2 is between 0.1 and 1.5mm, and the height h2 of the administration cavity is between 0.1 and 0.5 mm. The ratio of the wall thickness T of the dosing chamber to the outer diameter D (transverse dimension W) is 0.06-0.8, preferably the ratio of the wall thickness T of the dosing chamber to the outer diameter D (transverse dimension W) is 0.05-0.45.

Preferably, the puncture part 2 and the administration cavity 22 may be connected by welding or bonding. The distance between the individual piercing portions 2 is preferably smaller than the radial dimension of the piercing portions. More preferably, the distance between the respective piercing portions 2 is preferably 0.5 to 5mm, and preferably, may be 1 to 2mm, so that the injected medicine can be uniformly distributed in the tissue.

Preferably, the administration cavity 22, such as the base 221, may be made of a hard material, such as a metal material or a polymer material, so as to provide a foundation for the penetration structure 21 to uniformly penetrate into the tissue. In this embodiment, the base 221 is, for example, a tube, the base 221 has a cylindrical structure, and the entire cylindrical structure is made of hard materials such as metal. The length of the base 221 is smaller than the axial length of the balloon 31. In another embodiment, the portion of the upper surface of the base 221 connected to the puncture part 2 is made of hard material, and the other portion of the upper surface is made of flexible material to form a hose. The administration cavity 22 and the balloon 31 are fixed on the surface of the balloon in an adhesive curing manner and are uniformly arranged in the circumferential direction. When the connecting portion is made of a hard material such as metal, plasma treatment may be performed first, or welding or adhesive connection may be performed by polishing. When the connecting part is a flexible hose, the connecting part is connected by adopting a welding or gluing mode. The structure of the administration cavity may be cylindrical, oval, rectangular, or polygonal. Referring to fig. 5A, the base 221 is, for example, a plate-like structure, the administration cavity 22 further includes an administration tube 222, and the base 221 may be disposed on the administration tube 222, for example, by being adhered. The length of the plate-like structure is smaller than the axial length of the balloon 31, the width of the plate-like structure is not smaller than the diameter of the administration cavity 22 of the spike assembly 2, and the thickness of the plate-like structure is not smaller than the wall thickness of the administration cavity 22 of the spike assembly 2. More preferably, the plate-like structure may also have a curvature, for example, the surface of the plate-like structure in contact with the balloon 31 has a curvature towards the balloon 31, thereby enabling a tighter connection of the plate-like structure with the balloon 31. For example, the curvature of the plate-like structure toward the balloon 31 coincides with the curvature of the balloon 31. The balloon folding can embed the puncture assembly between the two folded balloon wings through the custom-made equipment, so that the vascular injury during the instrument delivery can be avoided. In this embodiment, the original folded state of the balloon can be realized through the balloon folding wings, and the balloon can recover the folded state after the balloon is decompressed due to the memory of the balloon folding, so that the balloon can be ensured to effectively cover and cover each group of puncture assemblies.

Preferably, as shown in fig. 5B and 5C, the administration catheter 222 of the puncture assembly 2 includes a hard catheter 2221 and a soft catheter 2222 along the axial direction of the balloon 31, and the hard catheter 2221 and the soft catheter 2222 are arranged at a segmented interval. For example, two sections of hard catheter 2221 and one section of soft catheter 2222 are included. Of course, the number of the hard catheters and the soft catheters is not limited. Preferably, the number of soft catheters 2222 is one less than the number of hard catheters 2221. The piercing structure 21 is preferably disposed on the rigid catheter 2221 so that the rigid catheter provides the desired stiffness and strength for the piercing assembly 2 to penetrate tissue. The flexible catheter 2222 is configured to provide flexibility to the delivery catheter 22 to enhance the passability of the device and facilitate delivery of the device. Further, the flexible catheter 2222 can be bent, and can be extended in a non-axial direction on the surface of the balloon 31; the placement of the flexible catheter 2222 also provides a precondition for the misalignment of the outer puncture assembly 2. Preferably, as shown in fig. 5D-5E, the hard catheter 2222 of the previous stage is different from the hard catheter 2222 of the next stage in the circumferential direction of the balloon 31 along the circumferential direction of the balloon 31 (fig. 5D is a schematic view of deployment of the drug delivery catheter 22 along the circumferential direction of the balloon 31) so as to form an offset arrangement. In fig. 5D, the solid line indicates that one of the hard catheter sections 2221 is circumferentially arranged at one angle, and the broken line indicates that the other hard catheter section 2221 is circumferentially arranged at the other angle. So set up, can make in the circumference direction of longer sacculus 31, along a catheter of dosing, puncture assembly 2 can misplace in different circumference, and then make circumference dosing even, improve injection efficiency. Similarly, the drug delivery assembly 4 may have a rigid catheter that provides the fixed lumen required for the delivery structure 41 (61) and a flexible catheter. The solution of the drug release assembly 4 may refer to the structure of the puncture assembly 2, and will not be described herein.

Preferably, the administration cavity 22 is connected to the first channel 11. For example, the outer diameter of the first channel 11 is adapted to the inner diameter of the dosing chamber 22; alternatively, the inner diameter of the first channel 11 is adapted to the outer diameter of the dosing chamber 22.

Preferably, in the connection between the puncture assembly 2 and the balloon 31, the puncture assembly 2 may be disposed outside the balloon 31, and in particular, in the first embodiment. May also be provided inside the balloon 31, and reference is made to embodiment two.

The conveying catheter is also provided with a pressure-filling and pressure-releasing control unit and a drug delivery control unit, and the flow-through pressure-filling and pressure-releasing channel formed by the second channel and the balloon and the drug delivery channel are respectively controlled by the pressure-filling and pressure-releasing control unit and the drug delivery control unit. The pressure filling and releasing control unit and the medicine delivery control unit can control the force applied by the pump and the like, and can also be manually controlled by medical staff.

When the sacculus is in a folded state, the sacculus is in a state of wrapping each group of puncture assemblies; when the balloon is in an unfolding state, the balloon is inflated to drive each group of puncture assemblies to protrude out of the balloon. Therefore, when the saccule is in a folding state, the saccule can be conveyed into a focus, and the saccule is in the folding state and covers each group of puncture assemblies, so that a blood vessel is not damaged in the intervention process; and after the balloon is decompressed, the balloon is restored to a folded state, each group of puncture assemblies is driven to withdraw from the target area and cover each group of puncture assemblies, so that the damage to tissues in the balloon withdrawing process is avoided, each group of puncture assemblies can be prevented from being left in the tissues, and the safety in the operation process is improved. It will be appreciated that when the balloon is fully deployed, additional delivery channels of drug are provided through the drug delivery port and injected into the target area via the drug delivery channel as the balloon is inflated, completing the delivery.

The liquid is configured for fluid communication and pressure relief and for administration, and may be, but is not limited to, physiological saline with a drug or drug carrier. Also, the separation between two liquids (e.g., oil and water) that do not mix is known as "liquid-liquid phase separation," which is critical to the function of many proteins. The applicant has also found that "liquid-liquid phase separation" can be applied in the apparatus. The "liquid-liquid phase separation" principle is used to separate the liquid and the drug or drug carrier, which are first pumped into the chamber through one or more channels. If the density of the drug or drug carrier is relatively light with respect to the liquid, the liquid containing more drug or drug carrier content is ejected from the drug delivery assembly and delivered to the target area by a corresponding controlled force applied separately. The first channel 11 may also be a rigid material.

Delivery catheter

In this section, the shape, material, size, and combination of the first channel and the administration cavity are described in terms of the positional relationship between the first channel and the second channel, but the first channel is not limited to this, and any structure that can achieve drug delivery is within the scope of the present application.

The first channel 11 is used for delivering a drug (it is understood that the drug may be a liquid drug) from the proximal end to the distal end of the first channel 11. The first channel 11 is a multi-lumen structure comprising a plurality of individual drug delivery channels 111 for delivering a drug, at least in said first channel 11 near the distal end portion. For example, the first channel 11 may be a plurality of separate drug delivery channels, and the drug delivery channels may be separate from the proximal end to the distal end. In the process of delivering the drugs, the drugs can be respectively delivered from the drug delivery channels, so that the respective drug delivery is realized. Preferably, when a completely independent mode of drug delivery is adopted, the radial dimension and the axial dimension of each drug delivery channel are consistent, so that conditions for realizing the drug delivery with the same speed and the same pressure are provided. Of course, to accommodate therapeutic requirements, the completely independent drug delivery channels may also be non-uniform in radial or axial dimensions, thereby enabling different pressures and rates of drug delivery. For another example, the proximal portion of the first channel 11 may include a total channel and the distal portion may include a plurality of separate drug delivery channels 111, and when a drug is desired to be delivered, the drug may be delivered from the total channel and delivered through the separate drug delivery channels 111.

The material of the first channel 11 is preferably a hose material, for example, one or a combination of elastomers such as polyamide, polyimide, block polyether amide, polyurethane, and silica gel, and the material is not limited to the above materials in practical use.

Balloon assembly

The balloon assembly may be a rapid exchange structure or a coaxial structure: the tube body of the rapid exchange structure is provided with a side hole through which a guide wire can pass; the coaxial structure tube body consists of single-cavity or multi-cavity tubes with the same or different lengths, and the manufacturing process is relatively simple. The materials of the balloon component are mainly as follows: polymer plastics, metal parts, hydrophilic coatings, etc., and the manufacturing process thereof includes but is not limited to: stretch blow molding, coaxial extrusion, laser/thermal welding, injection molding, adhesive processes, and the like.

The connector may comprise two or three luer connectors, each having a separate chamber, and may be secured to the catheter tip by injection molding or gluing. In a first embodiment, the cavities in the luer are in communication with the drug delivery channel simultaneously and separately; and the additional cavity is communicated with the pressure transfusion channel, and the cavity and the pressure transfusion channel are mutually independent and mutually noninterfere.

Folding wing

Preferably, the folding wings do not overlap. When the diameter of the saccule is 2-6 mm, the folding wings are 3-5 pairs; when the diameter of the saccule is 4-12 mm, the folding wings are 5-6 pairs; when the diameter of the balloon is 10-30 mm, the folded wings are 6-12 pairs.

[ example two ]

Referring to fig. 6A to 6B, fig. 6A is a schematic diagram of a device for implementing drug delivery by using a balloon according to a second embodiment; fig. 6B is a cross-sectional view of the device of fig. 6A in a folded state using a balloon to effect drug delivery.

The second embodiment is different from the first embodiment in that the device for delivering the drug by using the balloon has a different structure, and further, the puncture assembly and the balloon are combined in a different manner. The same parts of the apparatus of the second embodiment as those of the first embodiment will not be described, and only the differences will be described below.

As shown in fig. 6A and 6B, unlike the first embodiment, the administration cavity 22 is provided on the inner surface of the balloon 31. Specifically, the base 221 is disposed within the inner surface of the balloon 31. The upper surface of base 221 and sacculus 31 internal surface fixed laminating setting are provided with the hole that supplies puncture structure 21 to wear out on the sacculus 31, and puncture structure 21 wears out the hole protruding locates the internal surface of sacculus 31. In the folded configuration, the protruding piercing structures 21 are disposed within the folded wing spaces 312 formed by the folded wings; in the deployed configuration, as the balloon 31 expands, the base 221 is moved outwardly, thereby driving the protruding piercing structure 21 to extend out of the folded wing space 312, and the folded wing space 312 becomes smaller or is expanded and disappears.

As shown in fig. 6A, the height H of the folded wing space 312 should be set to be not less than the protruding height H3 of the puncture structure 21 protruding from the inner surface of the balloon 31. The bases 221 of each group of puncture assemblies 2 are respectively arranged circumferentially along the guide catheter 32, the bases 221 being supported by the guide catheter 32 in the folded configuration; in the deployed configuration, the base 221 is moved away from the guide catheter 32 as the balloon 31 is inflated.

[ example III ]

Referring to fig. 7, fig. 7 is a schematic diagram of a device for realizing drug delivery by using a balloon according to a third embodiment.

The third embodiment is different from the first and second embodiments in that the device for delivering a drug using a balloon has a different structure, and further, the puncture assembly has a different structure. The same parts of the apparatus of the third embodiment as those of the first and second embodiments will not be described again, and only the differences will be described below.

Referring to fig. 7, the lancing structure 21 of each set of lancing assemblies 2 is a pair of lancing blades 213. The pair of puncture blades 213 are respectively composed of two long blades, and the two long blades are respectively arranged on the base and are enclosed to form a long medicine release hole 2131, thereby improving the medicine administration efficiency. In addition, because the wholeness of blade is good, the blade is difficult for droing, and then reduces the risk that the puncture subassembly falls into the tissue. The pair of puncture blades 213 extend along the length direction of the balloon 31, and the length of the puncture blades 213 can be set according to actual requirements. The blade is of a structure with a wide bottom and a narrow upper end, and the cutter head part is positioned at the upper end. The transverse-longitudinal ratio of the blade is 0.05-1, and preferably, the transverse-longitudinal ratio of the blade is 0.1-0.25.

[ example IV ]

Referring to fig. 8A to 8B, fig. 8A is a schematic view of a drug delivery device according to a fourth embodiment; fig. 8B is a schematic view of another drug delivery device according to the fourth embodiment.

The fourth embodiment differs from the fifth embodiment in that the drug delivery device of the fourth embodiment does not include the first channel and the drug delivery cavity, and the release structure of the drug release component is a protruding through hole. The fourth embodiment differs from the first to third embodiments in that the drug delivery device of the fourth embodiment does not include the first channel and the drug delivery cavity. The same parts of the device of the fourth embodiment as those of the first embodiment will not be described, and only the differences will be described below.

The drug delivery device provided in the fourth embodiment includes: a delivery catheter (not shown in fig. 8), at least one set of drug delivery assemblies 6, and a balloon assembly 7.

The drug delivery assembly 6 comprises at least one release structure 61 and a dosing cavity 62, the release structure 61 comprises a puncture 611 and a drug delivery hole 612, and the drug delivery holes 611 in the group are communicated with the dosing cavity 62. It should be appreciated that in this embodiment, the administration cavity 62 is the same cavity as the pressure filling and relieving cavity. The chamber is for filling with a drug carrier of a drug and/or a liquid of a drug, the liquid being configured for flow-through inflation and pressure relief and for administration of the drug, the liquid filling the balloon to bring the balloon to inflation, the balloon being in a deployed configuration, the liquid effecting administration by individual application of a corresponding control force through an administration channel (e.g. a drug release orifice of embodiment one communicating with the chamber, the chamber communicating with a corresponding second channel 12). Preferably, the drug release assembly 6 further includes a base 63, the base 63 has a plate shape, and the puncture part 611 is disposed on the base; preferably, the base 63 is integrally formed with all of the release structures 61. The material of the release structure 61 and the base 63 may be at least one of polymer, inorganic silicon, metal, etc. Preferably, the outer diameter of the release structure 61 is greater than the inner diameter of the base 63, and the inner diameter of the release structure 61 is less than the inner diameter of the base 63. Of course, the release structure 61 and the base 63 may be fixed into a whole by an adhesive, welding, etc., and then may be directly and fixedly mounted on the outer side wall or the inner surface of the balloon 71 by an adhesive, welding, etc., and then the release structure 61 is provided with a drug release channel and the base 63 is provided with a through hole by laser drilling, so that the stability of the subsequent drug release process may be ensured. In fig. 8A, the base 63 is located on the outer surface of the balloon 31. The susceptor 63 may be a plate-shaped substrate. Of course, in other embodiments, the base 63 may not be limited to a plate-like substrate, but may be used to mount or secure the release structure 61. The base 63 may be integrally formed with the release structure 61 or may be formed separately.

Balloon assembly 7: at least comprising a balloon 71, said balloon 71 being configured to change between a folded configuration and an unfolded configuration by means of an inflation and deflation; in the folded configuration, the drug release assemblies are individually enclosed in the balloon; in the deployed configuration, the inflation force of the balloon 71 moves the drug delivery assembly 6 to a predetermined target area, and the drug is delivered to the target area through the drug delivery channel by the individual application of a corresponding control force. The folded and unfolded configurations are described with particular reference to the first embodiment.

Referring to fig. 8B, the difference from fig. 8A is that the base 63 may be located in the balloon 31, the upper surface of the base 63 is fixedly attached to the inner surface of the balloon 71, the release structure 61 in the drug release assembly 6 protrudes from the inner surface of the balloon 71, and in the folded configuration, the protruding release structure 61 is disposed in the accommodating space formed by the folded wings; in the deployed configuration, as the balloon 71 expands, the release structure 61 moves outwardly, thereby driving the protruding release structure 61 to extend out of the receiving space, which becomes smaller or is expanded and disappears. Similarly, the liquid is configured for fluid communication and pressure relief and for administration, and the liquid may be, but is not limited to, physiological saline to which a drug or drug carrier is added.

Preferably, the pressure filling and releasing channel and the drug administration channel are two independent channels which are not communicated and are independently controlled, the drug release components are multiple groups, and the drug release components in the groups control the movement of the drug through a plurality of drug delivery control units or the same drug delivery control unit.

Preferably, the pressure filling and releasing channels and the administration channels are provided in one and the same chamber, the drug release assembly is provided in multiple sets, the chambers contain a liquid of a drug carrier or composition of a drug, the liquid is configured for circulation, pressure filling and administration, the liquid fills the balloon to drive the balloon to expand, the balloon is in an expanded configuration, and the liquid is administered through the administration channels by applying a corresponding control force alone.

Preferably, the balloon assembly further comprises a guide catheter, the balloon is attached to the guide catheter in a sealing way, the balloon is folded to form a plurality of folding wings which are circumferentially arranged along the guide catheter, each pair of oppositely arranged folding wings form a folding wing space, and the drug release assemblies are respectively accommodated in the matched folding wing spaces.

Preferably, the drug delivery assemblies are configured for the implantation or injection of a drug into the target area.

Preferably, the release structure further comprises a base, the upper surface and other peripheral surfaces of the base form the drug administration cavity, the upper surface of the base is provided with a through hole communicated with the drug release hole along the length direction of the balloon, and the drug release hole is communicated with the drug administration cavity through the through hole.

Preferably, the release structure further comprises a plurality of puncture parts, the puncture parts are arranged at intervals along the length direction of the base, the top of each puncture part is a tip, and the end part of each puncture part is enclosed to form the drug release hole.

Preferably, the top of the puncture part is a tip, the end part is enclosed to form the drug release hole, and the puncture parts are multiple and are arranged at intervals along the length direction of the base.

Preferably, the puncture part is a pair of puncture blades, the pair of puncture blades are arranged along the length direction of the base, and the pair of puncture blades enclose a strip-shaped medicine release hole. Likewise, the arrangement including the blade may refer to the third embodiment, and will not be described herein.

[ example five ]

Referring to fig. 9 to 10, fig. 9 is a schematic diagram of a drug delivery device according to a fifth embodiment; fig. 10 is a schematic view of another drug delivery device according to the fifth embodiment.

The fifth embodiment differs from the first to third embodiments described above in that the drug delivery assembly 4 of the device for achieving drug delivery using a balloon provided in the fifth embodiment does not include a puncture structure. The same parts of the device of the fifth embodiment as those of the other embodiments will not be described, and only the differences will be described below.

A fifth embodiment provides a drug delivery device comprising: a delivery catheter (not shown in fig. 9), at least one set of drug delivery assemblies 4, and a balloon assembly 5.

The delivery catheter has a proximal portion and a distal portion, the delivery catheter comprising a first channel (not shown in fig. 9) for delivering a drug and a second channel (not shown in fig. 9) for flow-through inflation and deflation, the first channel at least near the distal portion being of a multi-lumen structure comprising a plurality of separate drug delivery channels for delivering a drug.

The drug delivery assembly 4 comprises at least one release structure 41 and a drug delivery cavity 42, wherein the release structure 41 comprises at least a drug delivery hole 411, and the drug delivery holes 411 in the group are communicated with the drug delivery cavity 42. Preferably, the administration cavity 42 further includes an administration cavity 421 and an administration hole 422, and the drug release hole 411 is in communication with the administration cavity 421 through the administration hole 422, and in this case, the drug release hole 411 is located on the balloon 51. Preferably, the dispensing orifice 422 is the same size as the dispensing orifice 411, thereby facilitating drug delivery. Of course, in other embodiments, the sizes of the drug delivery hole 422 and the drug release hole 411 may be different, and may be set according to actual requirements. Further, the radial dimension of the drug delivery chamber 421 is larger than the diameter of the drug delivery hole 422, so as to ensure the stability of the drug delivery pressure. The inner diameter of the drug delivery chamber 421 is 0.1mm or more, for example, 0.2, 0.3, 0.4, etc.; preferably, the inner diameter of the drug administration cavity 421 is equal to or more than 0.3mm; more preferably, the inner diameter of the drug delivery chamber 421 is 0.5mm or more, for example, 0.6, 0.7, 0.8, etc. The ratio of the inner diameter to the outer diameter of the administration cavity 421 is 0.1 to 0.9, and more preferably, the ratio of the inner diameter to the outer diameter of the administration cavity 421 is 0.4 to 0.8. The inner diameter of the dosing hole 422 is smaller than the inner diameter of the dosing chamber 421, preferably the inner diameter of the dosing hole 422 is smaller than 0.5 times the inner diameter of the dosing chamber 421, and the inner diameter of the dosing hole 422 even amounts to below 0.01 mm. Preferably, the inner diameter of the administration hole 422 has a size ranging from about 2 μm to about 500 μm, preferably from about 2 μm to about 200 μm, more preferably from about 50 μm to about 150 μm, and may be, for example, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150 μm, etc., although smaller or larger sizes are also possible. Alternatively, the sizes of the administration cavity 421 and the administration hole 422 may be set by those skilled in the art according to actual circumstances.

The balloon assembly 5 comprises at least one balloon 51, said balloon 51 being configured to change between a folded configuration and an unfolded configuration by means of an inflation and deflation. In the folded configuration, the drug delivery assemblies 4 are individually enclosed in the balloon 51. In the deployed configuration, the inflation force of the balloon 51 drives the drug delivery assembly 4 to move to a predetermined target area, and the drug is delivered to the target area through the separate drug delivery channels by the individual application of corresponding control forces. The folded and unfolded configurations are described with particular reference to the first embodiment.

Preferably, as shown in fig. 9, the first channel and the drug delivery assembly 4 may be disposed on an inner surface of the balloon 51. Therefore, the medicine liquid has an independent channel, the concentration of the medicine liquid is controllable, and the release rate is controllable.

Preferably, as shown in fig. 10, the first channel and the drug release assembly 4 may be disposed on an outer surface of the balloon 51, and the drug release hole communicates with the drug administration cavity. When the balloon 51 is expanded, the drug release component 4 is attached to and presses the tissue, so that the tissue is tightly attached to the pressed tissue, and the pressed tissue is influenced by stress concentration, so that when the drug is released at the position, the drug can be better permeated into the tissue. Preferably, the drug release component 4 may be a hollow wire, and the hollow wire is provided with drug release holes. The inner diameter of the administration cavity 42 is 0.1mm or more, for example, 0.2, 0.3, 0.4, etc.; preferably, the inner diameter of the dosing chamber 42 is greater than or equal to 0.3mm; more preferably, the inner diameter of the administration cavity 42 is 0.5mm or more, for example, 0.6, 0.7, 0.8, etc. The ratio of the inner and outer diameters of the administration cavity 42 is 0.1 to 0.9, more preferably, the ratio of the inner and outer diameters of the administration cavity 42 is 0.4 to 0.8. Preferably, the inner diameter of the drug release hole 411 is smaller than the inner diameter of the drug administration cavity 42, and preferably, the inner diameter of the drug release hole 411 is smaller than 0.5 times the inner diameter of the drug administration cavity 42. The interval between each of the drug delivery holes 411 is 0.1 to 1mm, preferably 0.25 to 0.75mm, for example, 0.25mm, 0.3mm, 0.4mm, 0.45mm, 0.5mm, 0.6mm, etc. Of course, the drug release hole 411 may be larger than 1mm. The administration lumen 42 may be a circular or triangular hollow tube in cross-section. When the administration cavity 42 is circular, the drug release hole 411 on the administration cavity 42 is preferably oriented in the direction in which the balloon 51 is inflated. Of course, in other embodiments, the drug delivery hole 411 in the drug delivery lumen 42 may be angled with respect to the direction of inflation of the balloon 51. Further, in the same circumferential direction of the administration cavity 42, a plurality of drug release holes 411, for example, two drug release holes 411 are formed, so that two rows of drug release holes 411 are formed on the administration cavity 42, thereby increasing the channels for releasing the drug and increasing the dosage. When the cross section of the administration cavity 42 is triangular, both sides of the triangular cylinder preferably have a drug release aperture 411. Reference is made in particular to the following description of embodiment ten.

In this example, the drug delivery assembly 41 may be one or more sets. When the drug release components 41 are multiple groups, the drug release components 41 of the groups control the movement of the drugs through a plurality of drug delivery control units or the same drug delivery control unit, so that the movement force of the drugs can be independently controlled. The release structure may include only the drug release aperture 411, and controlling the force with which the kinetic force of the drug can pass through the drug release aperture 411 may control the force with which the drug enters the target area. Preferably, the aperture of the drug release hole is set from small to large, so that the force of the drug entering the target area can be controlled more conveniently.

In this example, the balloon assembly may further include a guide catheter (not shown in fig. 9) to which the balloon 51 is sealingly attached, and the balloon 51 is folded to form a plurality of folding wings circumferentially arranged along the guide catheter, each pair of oppositely disposed folding wings having a folding wing space in which the drug release assemblies are respectively accommodated.

The drug delivery assemblies 4 are configured to implant or inject a drug into the target area. The release structure also comprises a base, the upper surface and other peripheral surfaces of the base form the drug administration cavity, the upper surface of the base is provided with a through hole communicated with the drug release hole along the length direction of the saccule, and the drug release hole is communicated with the drug administration cavity through the through hole.

Referring to fig. 9, in the case where the administration channel is not provided with a piercing structure, when the external force provided by the drug delivery control unit is sufficiently controllable, the drug delivery member may be directly implanted into the target area or injected into the target area by the external force.

Other structures of the device for achieving drug delivery using a balloon according to this embodiment may refer to the content of the device for achieving drug delivery using a balloon, and will not be described in detail.

[ example six ]

Referring to fig. 11, fig. 11 is a schematic diagram of a drug delivery device according to a sixth embodiment.

The drug delivery device provided in this embodiment six is a device in which a coating structure, such as a drug coating, is applied to the device of embodiments 1 to five. The surface of the saccule can be coated with the medicine, the puncture assembly (or the medicine release assembly) can be coated with the medicine, and the medicine can be coated simultaneously. The medicine and the medicine coating can simultaneously treat the lesion part (such as lesion blood vessel) in two dimensions of a face and a point. Of course, in fig. 11, for convenience of illustration, the dotted line is used to illustrate that the device has a coating structure outside, and does not represent a real coating structure.

Parameters such as thickness, dosage concentration and the like of the coating structure can be set according to actual conditions. For example, the thickness and the dosage concentration of the coating may be matched to the drug solution to effect drug treatment. Furthermore, the drug of the coating may be one drug and the other drug delivered by the balloon puncture assembly or drug delivery assembly. The two medicines are different and matched with each other, so that the auxiliary treatment of the medicines is realized.

[ embodiment seven ]

A method of achieving drug delivery, employing the above-described device to achieve accurate drug delivery, comprising the steps of:

configuring the balloon in a folded configuration;

after the balloon is guided to the target location,

the balloon is inflated by pressurizing the second passageway to assume the deployed configuration: the inflation of the saccule drives the puncture part of the puncture assembly to bulge; or the expansion of the saccule drives the drug release component to cling to the tissue of the target position;

the medicine is respectively delivered to the target area through one or more medicine delivery channels, the corresponding medicine delivery cavity of each medicine delivery channel and the medicine release holes communicated with the medicine delivery cavities.

The balloon may be configured to rotate to a preset position, and then the drug is delivered to the target area through the plurality of drug delivery channels, the drug delivery cavity corresponding to each drug delivery channel, and the drug release hole communicated with the drug delivery cavity, once or multiple times.

After the balloon is decompressed, the balloon is restored to a folded state, and the puncture structure is driven to withdraw from the target area and cover the puncture structure.

[ example ten ]

Percutaneous Transluminal Coronary Angioplasty (PTCA) to open an occluded cardiac coronary artery, to clear blood circulation, and to maintain normal hemodynamic characteristics. During treatment of PTCA, the physician passes through the injection balloon provided in this embodiment to keep the vessel open to reduce the risk of restenosis and elastic recoil. The puncture assembly of the injection saccule is used for penetrating into the intima, and the medicine or the slow-release medicine is directly injected into the intima or the media of the blood vessel, so that the proliferation of the neointima can be inhibited for a long time, and the probability of losing or restenosis of the lumen of the later period can be reduced. Compared with the traditional medicine release balloon (DCB), the drug transfer rate is greatly improved. This embodiment is equally applicable to Percutaneous Transluminal Angioplasty (PTA).

Referring to fig. 16 to 20 and fig. 9 and 10, fig. 16 is a schematic view showing the overall structure of an injection balloon according to a tenth embodiment; fig. 17A is a schematic cross-sectional view of a balloon portion of an injection balloon of the tenth embodiment; fig. 17B is a schematic cross-sectional view of a balloon portion of another injection balloon of the tenth embodiment; FIG. 17C is a schematic cross-sectional view of a balloon portion of another injection balloon according to the tenth embodiment; fig. 18A is a schematic view of an injection balloon according to the tenth embodiment; fig. 18B is a schematic view of another injection balloon according to the tenth embodiment; fig. 18C is a schematic view of another injection balloon according to the tenth embodiment; FIG. 19 is a schematic view of a drug delivery assembly according to a tenth embodiment; fig. 20 is a schematic view showing the overall structure of another injection balloon according to the tenth embodiment. Fig. 9 is a schematic view of a drug delivery device provided in fifth embodiment; fig. 10 is a schematic view of another drug delivery device according to the fifth embodiment.

This embodiment is illustrated schematically using the apparatus provided in embodiment five.

In this embodiment, as shown in fig. 16, the injection balloon may be a rapid exchange structure, and further includes a developing ring, a connecting tube, a hypotube and a catheter Hub, and the catheter Hub is designed as a 2-Way Hub. This configuration can improve the passage of the entire catheter in the blood vessel.

The injection balloon comprises a delivery catheter (not shown in fig. 9), at least one set of drug release assemblies 4, and a balloon assembly 5. Preferably, as shown in fig. 18A to 18C, balloon specifications: the drug delivery assembly 4 may be in one, two, three, four, six, etc. rows of diameter 1.2-14mm and length 10-80 mm. The delivery catheter has a proximal portion and a distal portion, the delivery catheter comprising a first channel (not shown in fig. 9) for delivering a drug and a second channel (not shown in fig. 9) for flow-through inflation and deflation, the first channel at least near the distal portion being of a multi-lumen structure comprising a plurality of separate drug delivery channels for delivering a drug.

The drug delivery assembly 4 comprises at least one release structure 41 and a drug delivery cavity 42, wherein the release structure 41 comprises at least a drug delivery hole 411, and the drug delivery holes 411 in the group are communicated with the drug delivery cavity 42. Preferably, the administration cavity 42 further includes an administration cavity 421 and an administration hole 422, and the release hole 411 communicates with the administration cavity 421 through the administration hole 422. It should be understood that the first channel and the drug delivery assembly 4 may be disposed on the outer surface of the balloon 51, or the first channel and the drug delivery assembly 4 may be disposed on the inner surface of the balloon 51. The drug delivery aperture 411 and drug administration aperture 422 are shown as a result when the first passageway and drug delivery assembly 4 may be disposed on the outer surface of the balloon 51. When the first channel and the drug release component 4 may also be disposed on the inner surface of the balloon 51, the drug release hole 411 is a hole disposed on the balloon 51. Preferably, the injection balloon further comprises a puncture part, the puncture part is communicated with the drug release hole 411, and the puncture part is in a needle-shaped structure.

The first channel and the drug delivery assembly 4 may be disposed on an outer surface of the balloon 51. Preferably, the drug delivery module 4 may be a hollow wire, and the hollow wire is provided with a drug delivery hole 411. The inner diameter of the administration cavity 42 is 1 μm or more, for example, 2, 3, 4 μm or more; preferably, the inner diameter of the dosing chamber 42 is greater than or equal to 3 μm; more preferably, the inner diameter of the administration cavity 42 is 0.1mm or more, for example, 0.2, 0.3, 0.4mm or the like. The ratio of the inner and outer diameters of the administration cavity 42 is 0.1 to 0.9, more preferably, the ratio of the inner and outer diameters of the administration cavity 42 is 0.4 to 0.8. The inner diameter of the drug delivery hole 411 is smaller than the inner diameter of the drug delivery cavity 42, and preferably, the inner diameter of the drug delivery hole 411 is smaller than 0.5 times the inner diameter of the drug delivery cavity 42. The interval between each of the drug delivery holes 411 is 0.1 to 1mm, preferably 0.25 to 0.75mm, for example, 0.25mm, 0.3mm, 0.4mm, 0.45mm, 0.5mm, 0.6mm, etc. Of course, the drug release hole 411 may be larger than 1mm. The administration cavity 42 may be a circular or triangular hollow tube. The outer diameter of the circular hollow tube may be 0.20 to 0.34mm. As shown in fig. 18A, when the administration cavity 42 is circular, the drug release hole 411 on the administration cavity 42 is preferably oriented in the direction in which the balloon 51 is inflated. Of course, in other embodiments, as shown in fig. 18B, the drug release hole 411 in the drug delivery cavity 42 may have an angle with the direction of the expansion of the balloon 51, for example, the direction of the expansion of the balloon is the radial direction of the balloon, and the axial direction of the drug release hole forms an angle with the radial direction of the balloon. For example at an acute angle. The drug delivery holes may be arranged in a row of holes along the axial direction of the drug delivery cavity 42, and may be arranged in a two-row or three-row hole structure. Further, as shown in fig. 18C, in the same circumferential direction of the drug delivery cavity 42, there are a plurality of drug release holes 411, that is, when the drug release holes of the drug release assembly are of a multi-row hole structure, there are included angles between the hole axial directions of each row of hole structures, for example, two (or two rows of) drug release holes 411, so that two rows of drug release holes 411 are formed on the drug delivery cavity 42, and thus a drug release channel is increased and thus the dosage is increased. The directions of the two rows of holes face to the outer side of the balloon and form a certain angle of 5-30 degrees with the normal direction of the balloon. The medicine release component 4 is of a triangular hollow structure, one surface of the triangular hollow structure is connected with the saccule, and the other two surfaces of the triangular hollow structure are respectively provided with medicine release holes. I.e. when the cross-section of the dosing chamber 42 is triangular, both sides of the triangular cylinder preferably have a drug release aperture 411. As shown in FIG. 19, when the administration cavity 42 is a triangular hollow tube, the openings of the triangular hollow tube are double-row, the openings are positioned on two sides of the top edge of the hollow tube, and the outer diameter of the triangular hollow tube can be 0.20-0.34 mm.

In this embodiment, the spacing between each of the drug delivery holes 411 is at least 0.5mm.

Preferably, the injection balloon further comprises a puncture part, the puncture part is communicated with the drug release hole 411, and the puncture part is in a needle-shaped structure. The height of the puncture part is 0.1mm-2mm, preferably the height of the puncture part is less than 0.5mm. The height of the micro needle is adjusted according to different positions, so that the micro needle can be ensured to be only penetrated into an inner membrane or a middle membrane of the inner wall without penetrating through the tube wall, the operation risk of a doctor is reduced, and the safety of a patient is ensured. It can be understood that the diameter of the end part of the microneedle, which is close to the balloon, is larger than the diameter of the needle tip, so that the needle tip of the microneedle can conveniently penetrate into the inner wall, and the connection between the microneedle and the balloon or the base can be ensured to be stable.

In the application, the balloon with the puncture assembly can be applied to the treatment of intravascular diseases (balloon specification: diameter 1.2-14mm, length 10-200 mm) and the treatment of non-intravascular diseases (balloon specification: diameter 5-50mm, length 20-200 mm); the puncture assembly has the following dimensions: the height is 0.1-2.0mm, the diameter is 10-500 μm, and the drug delivery efficiency can be improved.

Preferably, when the balloon 52 is stamped, the pressure of the balloon 52 is in the range of 3-30 atm, so that the pressure of the balloon 52 is not too high to cause endothelial tear, and meanwhile, effective treatment and drug delivery can be realized.

Preferably, the injection balloon further comprises a drug coating, the drug of which may be the same as or different from the drug delivered in the first channel. Reference is made in particular to embodiment six.

Preferably, the injection balloon comprises a catheter Hub (Hub) connected to the first channel for delivering a drug, preferably the catheter Hub is of a double luer (2-Way Hub) or a tri luer (3-Way Hub) or even a multiple luer design; a luer fitting on the catheter hub may be connected to a valve, connector, syringe or pressure filler, through which a particular medication is given into the infusion channel, which medication is the prescribed medication system.

Furthermore, the injection balloon can be a whole-course exchange structure besides a rapid exchange structure. In addition to the inner tube, outer tube, balloon and drug delivery scoring structures, a development ring is provided in the balloon and a catheter Hub (Hub) is provided for a special 3-Way Hub design, as shown in fig. 20. This structure can improve the handling of the catheter in the blood vessel. The injection balloon of the tenth embodiment is applicable to a general balloon filling device, and the balloon filling device is connected with a drug interface on a catheter seat, and a special drug is given to an infusion channel through the balloon filling device, wherein the drug is a specified drug system, for example, a specified liquid medicine or a specified drug microsphere.

Preferably, the drug delivery assembly 4 may have a rigid catheter that provides the fixed lumen required for the delivery structure 41 (61) as well as a flexible catheter. The scheme of the drug delivery assembly 4 may refer to the structure as shown in fig. 5B to 5E. Along the axial direction of the balloon 31, the administration tube of the drug release assembly 4 comprises a hard tube and a soft tube, and the hard tube and the soft tube are arranged at intervals in sections. For example, comprising two sections of hard catheter and one section of soft catheter. Of course, the number of the hard catheters and the soft catheters is not limited. Preferably, the number of soft catheters is one less than the number of hard catheters. The piercing structure is preferably disposed on a rigid catheter. The soft catheter is arranged to provide flexibility for the drug delivery catheter, so that the trafficability of the device is improved, and the delivery of the device is facilitated. In addition, the provision of a flexible catheter provides a precondition for the offset placement of the drug delivery assembly 4. Preferably, as shown in fig. 5D-5E, the hard catheter of the previous stage is different from the hard catheter of the next stage in the circumferential direction of the balloon 51 along the circumferential direction of the balloon 31 (fig. 5D is a schematic view of deployment of the drug delivery catheter along the circumferential direction of the balloon 51) to form an offset deployment. In fig. 5D, the solid line indicates that one of the hard catheters is circumferentially disposed at one angle, and the broken line indicates that the other hard catheter is circumferentially disposed at the other angle. So set up, can make in the circumference direction of longer sacculus 51, along a catheter of dosing, medicine release subassembly 4 can misplace in different circumference, and then make circumference dosing even, improve injection efficiency. Preferably, the hard catheter has a size, preferably the soft catheter has an axial size of 0.5 to 20mm.

The tenth embodiment also provides an injection balloon sustained release system comprising the injection balloon as described in any one of the above and a drug system comprising drug particles and/or a drug carrier; the drug particles can be dissolved in tissue fluid, the drug particles are dissolved into drug liquid, and the drug liquid escapes from the drug carrier in the tissue so as to realize slow release. Furthermore, the injection balloon adopted by the injection balloon slow-release system comprises a puncture part, and the drug system enters the inside of the tissue through the puncture part, so that the drug slow release of 1 week to 6 months is realized. Preferably, the radial dimension of the medicine outlet hole of the puncture part is larger than the radial dimension of the medicine carrier.

Test verification

Tables 1 and 2 show test results of the drug implanted in the blood vessel using the drug system of this example.

Tissue: blood vessel

The drug particles adopt Sirolimus drug

The drug carrier adopts PLA substrate, and the drug carrier carries Sirolimus drug.

Table 1 shows a comparison of drug delivery rate and tissue drug content of the drug system according to the present embodiment

Table 2 is a table showing the comparison of the drug efficacy time of the drug system according to the present example

	Effective time of the medicine	Prior Art
			Liquid medicine	For 28 days	For 28 days
Medicine ball	Not less than 100 days	n/a

The transfer rate of the medicine can reach more than 79%, and the effect of inhibiting tissue proliferation for a long time can be realized.

[ example eleven ]

Referring to fig. 21A to 21B, fig. 21A is a schematic diagram showing an example of a drug system according to an eleventh embodiment; fig. 21B is a schematic diagram showing a second example of the drug system according to the eleventh embodiment.

The eleventh embodiment provides a drug system, where the drug system is delivered by using the devices of the first to tenth embodiments, so as to achieve the purpose of delivering the drug system to the target location, and delivering the drug into the target location, so as to achieve the corresponding therapeutic effect of the drug.

The drug system may be drug particles and/or drug carrier 100 that can be mixed with a solution to form a drug solution that is delivered to the target tissue site. The drug carrier 100 has pores that are capable of carrying a drug, such as drug particles, that the drug carrier 100 is delivered into a target tissue, it being understood that the drug particles can be dissolved in a tissue fluid, such as physiological saline, and that the drug particles are dissolved as a drug fluid that escapes from the drug carrier 100 in the tissue to achieve a sustained release. Preferably, the drug particles are crystalline drug crystals which are delivered into the tissue to enable sustained drug release, the drug particles have a particle size of 1 to 1000 μm, preferably the drug particles have a particle size of 1 to 150 μm, more preferably the drug particles have a particle size of 1 to 50 μm, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 μm; the slow release period of the drug crystal is between one week and 6 months. It is understood that the sustained release of a drug is related to the content of the drug, the molecular structure of the drug carrier, the molecular weight, the porosity of the drug carrier, and the like. In this example, the applicant obtained the ideal sustained release drug by screening the molecular structure, molecular weight (i.e., the material selected for the drug) and porosity of the drug carrier. The slow release period may be between 1 week and 6 months.

When the drug system employs drug particles, the drug particles are mixed by a delivery fluid (e.g., saline, etc.) to form a suspension for delivery into the target tissue. The rate of drug delivery, the amount of drug can be as described above. It will be appreciated that the drug particles may be a broad concept of a drug, for example, the drug may be a drug for treating luminal stenosis. Alternatively, the drug may be a drug-containing body or composition comprising one or more therapeutic substances, diagnostic substances, a drug, a therapeutic composition, a diagnostic composition, a physiologically active agent, a biochemical active agent, one or more living cells, DNA, RNA, nucleic acid, a cellular carrier for delivering genetic material into a target site, an anti-inflammatory agent, an anti-restenosis agent, a cell proliferation inhibitor, a smooth muscle proliferation inhibitor, paclitaxel, rapamycin, everolimus, a vasoactive agent, a vasodilator, a vasoconstrictor, an antibiotic, an anticoagulant, a platelet aggregation inhibitor, an anti-fibrosis agent, a pharmaceutically acceptable carrier, a lipid-based carrier, and any combination thereof. Furthermore, the drug may also be an alpha reductase inhibitor, e.g. finasteride, dutasteride.

Referring to fig. 21A, preferably, the drug carrier is a drug-releasing microsphere formed by mixing a degradable polymer material with a drug, the diameter of the drug-releasing microsphere is 1-1000 μm, preferably, the diameter of the drug-releasing microsphere is 1-150 μm, for example, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150 μm, etc., more preferably, the diameter of the drug-releasing microsphere is 1-50 μm, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 μm; the slow release period is between 1 week and 6 months. Preferably, the drug carrier has pores in which the drug is contained, the drug is slowly released from the pores, the diameter of the drug carrier is 1 to 1000 μm, preferably the diameter of the drug carrier is 1 to 150 μm, more preferably the diameter of the drug carrier is 1 to 50 μm, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 μm; the slow release period is between 1 week and 6 months. Preferably, the drug carrier 100 has a plurality of micropores 101, where the micropores 101 are disposed in the drug carrier 100 with or without through holes, so as to be capable of accommodating the drug. Of course, in other embodiments, the size of the micropores 101 may be smaller than the size of the drug. Preferably, the drug carrier can also be a drug sustained-release microsphere prepared by mixing a polymer degradable material and a drug, and the drug is in a tissue because the drug concentration in the drug sustained-release microsphere is high, so that the drug can be released. When the apparatus of embodiments one to ten is used for transporting a drug carrier, the transport efficiency is high as compared to transporting drug particles, and the transport control unit may configure the amount of transport force loaded onto the spherical microparticles to control the transport of the spherical microparticles to the target area through the drug transport channel and/or to control the duration of transport to the target area and/or to control the depth of transport to the target area. The material of the drug carrier can be a high molecular biodegradable material. The polymeric biodegradable materials include, but are not limited to: polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), carbon dioxide polymer (PPC), polybutylene succinate (PBS), aliphatic aromatic polyester Ecoflex (PBAT), polytrimethylene terephthalate (PPT), poly beta-hydroxyalkanoate (PHA), poly epsilon-caprolactone (PCL), poly p-dioxanone (PPDO), or a copolymer or blend of any of a plurality of polymers thereof. Preferably, the content of each component in the blend of any of the plurality of polymers is from 0 to 100%.

Referring to fig. 21B, the shape of the drug carrier may be other structures, not limited to a sphere. For example, the drug carrier may be a sustained release drug-carrying bar or sheet, the drug delivery control unit may configure the amount of delivery force loaded onto the sustained release drug-carrying bar or sheet to control delivery of the sustained release drug-carrying bar or sheet to the target area through the drug delivery channel, and the material of the bar or sheet may be a polymeric biodegradable material. The arrangement of the bars and the sheets is carried out according to the actual medicine carrying requirement.

Preferably, a coating layer can be further arranged on the drug carrier, and the drug is arranged in the coating layer. The coating layer can be dissolved, so that the slow release of the drug carrier is realized, and the slow release period is 1 week to 6 months.

The drug carrier 100 may perform a drug release function continuously. The release period is between 1 week and 6 months.

Preferably, the diameter of the drug release hole is larger than that of the drug system, so that the drug system can be conveniently output.

Test verification

Tables 1 and 2 show the results of experiments with the drug system of this example implanted in the prostate gland.

Tissue: prostate gland

The drug particles adopt Sirolimus drug

	Effective time of the medicine	Prior Art
			Liquid medicine	For 28 days	For 28 days
Medicine ball	Not less than 90 days	n/a

This example is performed by injecting the drug particles or drug carrier into the prostate gland using the apparatus of example nine, with an injection pressure injection balloon, an injection rate injection balloon. The drug transfer rate can reach more than 80%, and the effect of inhibiting tissue proliferation for a long time can be realized.

[ example twelve ]

The twelfth embodiment provides a medical minimally invasive system comprising the apparatus of any of the first to tenth embodiments, and comprising the drug system of the eleventh embodiment. That is, the device in the above-described embodiments one to ten is used for delivering the drug system described in the eleventh embodiment, and thus, drug delivery is achieved by the device, and further, delivery of the drug is achieved, thereby providing a precondition for sustained release of the drug system.

Preferably, the device of any one of the first to tenth embodiments comprises a drug delivery control unit configurable to the magnitude of the delivery force applied to the drug to control delivery of the drug to the target area through the drug delivery channel.

Claims

1. An injection balloon, comprising: a delivery catheter, at least one set of drug delivery assemblies, and a balloon assembly;

a delivery catheter having a proximal portion and a distal portion, the delivery catheter comprising a first passageway for delivering a drug and a second passageway for flow-through inflation and deflation that are not in communication with each other, at least the first passageway adjacent the distal portion being of a multi-lumen structure comprising a plurality of independent drug delivery passageways for delivering a drug; the second channel and the first channel are two independent channels which are not communicated and are independently controlled;

at least one set of drug delivery assemblies, said drug delivery assemblies comprising at least one delivery structure and a dosing chamber, said delivery structure comprising drug delivery apertures, said drug delivery apertures of said set being in communication with said dosing chamber;

balloon assembly: at least one balloon configured to change between a folded configuration and an unfolded configuration by inflation and deflation; in the folded configuration, the drug release assemblies are individually enclosed in the balloon; in the unfolding configuration, the expansion force of the balloon drives the drug release component to move to a preset target area, and the drug is conveyed to the target area through the drug delivery channel by independently applying corresponding control force.

2. The injection balloon of claim 1, wherein the first channel and the drug release assembly are disposed on an outer surface of the balloon or the first channel and the drug release assembly are disposed on an inner surface of the balloon; preferably, the pressure of the balloon is in the range of 3 to 30atm when the balloon is pressurized.

3. The injection balloon of claim 1, wherein when the first channel and the drug release assembly are disposed on an outer surface of the balloon, the drug release holes of the drug release assembly face in a direction of inflation of the balloon when the drug release holes are in a row of hole structures; or the direction of the drug release hole forms a certain angle with the expansion direction of the balloon; when the medicine release holes of the medicine release component are of a multi-row hole structure, an included angle is formed between the axial directions of the holes of each row of hole structure.

4. The injection balloon of claim 3, wherein the drug release assembly is a hollow wire with drug release holes disposed thereon; preferably, the inner diameter of the drug release hole is smaller than the inner diameter of the drug administration cavity; preferably, the inner diameter of the dosing cavity is more than or equal to 1 mu m, preferably, the inner diameter of the dosing cavity is more than or equal to 3 mu m; more preferably, the inner diameter of the dosing chamber is not less than 0.1mm, even more preferably, the inner diameter of the dosing hole has a size in the range of 2 μm to 500. Mu.m, preferably 2 μm to 200. Mu.m, even more preferably 50 μm to 150. Mu.m; the ratio of the inner diameter to the outer diameter of the dosing cavity is 0.1-0.9, more preferably, the ratio of the inner diameter to the outer diameter of the dosing cavity is 0.4-0.8; the inner diameter of the administration hole is smaller than the inner diameter of the administration cavity; preferably, the inner diameter of the administration hole is smaller than 0.5 times of the inner diameter of the administration cavity, and the inner diameter of the administration hole is less than or equal to 0.01mm;

Preferably, the medicine release component is a triangular hollow structure, one surface of the triangular hollow structure is connected with the balloon, and the other two surfaces of the triangular hollow structure are respectively provided with medicine release holes.

5. The injection balloon of claim 1, wherein the delivery catheter is further provided with a pressure filling and releasing control unit and a drug delivery control unit, a passage for circulation and pressure filling and releasing formed by the second passage and the balloon is controlled by the pressure filling and releasing control unit, and a first passage and the balloon are respectively controlled by the drug delivery control unit; the pressure-filling and pressure-releasing control unit and the drug delivery control unit can control the force-giving amount by a pump and the like; the first channel of the delivery catheter is a plurality of independent drug delivery channels, and drug delivery channels are independent from proximal to distal;

preferably, the injection balloon comprises a catheter Hub (Hub) connected to the first channel for delivering a drug, preferably the catheter Hub is of a double luer (2-Way Hub) or a tri luer (3-Way Hub) or even a multiple luer design; a luer fitting on the catheter hub is connected to a valve, connector, syringe or pressure filling device through which a particular medication is given into the infusion path, which medication is a designated medication system.

6. The injection balloon of any one of claim 1, wherein a spacing between each drug release aperture is at least 0.5mm; the diameter of the balloon is 1.2-14mm, the length of the balloon is 10-80mm, and the drug release components are arranged in two rows, three rows or four rows.

7. The injection balloon of any one of claims 1-6, further comprising a puncture in communication with the drug delivery aperture, the puncture having a needle-like configuration; preferably, the height of the puncture part is 0.1mm-2mm, and the diameter is 10 μm-500 μm.

8. The injection balloon of any one of claims 1, wherein the drug delivery assembly has a rigid catheter that provides a fixed lumen required for the delivery structure and a flexible catheter that is configured to provide flexibility to the drug delivery catheter;

preferably, the puncture structure is arranged on the hard catheter;

preferably, the size of the hard catheter and the axial size of the soft catheter are 0.5-20 mm.

9. The injection balloon of any one of claim 1, further comprising a drug coating, wherein a drug of the drug coating may be the same as or different from a drug delivered in the first channel.

10. An injection balloon sustained release system comprising an injection balloon as claimed in any one of claims 1 to 9 and a drug system comprising drug particles and/or a drug carrier; the drug particles and/or the drug carrier can be mixed with a solution to form a drug solution, the drug solution being delivered to a target tissue site;