WO2021258743A1

WO2021258743A1 - Drug delivery device, preparation method therefor, and drug delivery system

Info

Publication number: WO2021258743A1
Application number: PCT/CN2021/075462
Authority: WO
Inventors: 岳斌; 贾婧玮
Original assignee: 上海明悦医疗科技有限公司
Priority date: 2020-06-23
Filing date: 2021-02-05
Publication date: 2021-12-30
Also published as: CN111481813A; CN111481813B

Abstract

A drug delivery device (100), a preparation method therefor, and a drug delivery system, the device comprising: a catheter body (102), a balloon (103) provided at the distal end of the catheter body (102), and a pressure monitoring and regulating device (110) connected to a filling cavity (1021) and drug delivery cavity (1022) of the catheter body (102). The shape of the balloon (103) after filling allows same to attach to an inner wall of a target chamber; at least one drug delivery port (1023) is provided at the distal end of the drug delivery cavity (1022); and a drug is directly delivered by the drug delivery ports (1023) to the outer surface of the balloon (103), and acts directly on the inner wall of the target chamber by means of the outer surface of the balloon (103) that is adaptively attached. The drug delivery efficiency and drug utilization rate are high, and the pore size and number of the drug delivery ports (1023) match the viscosity of a drug. The described device is configured to deliver a drug at a certain flow volume under a certain pressure of drug injection. Therefore, under the monitoring and/or regulation of the pressure monitoring and regulating device (110), a drug can be delivered at the rated pressure and flow rate. In addition, the described device is suitable for different drug delivery requirements of different natural chambers, and facilitates uniform drug delivery.

Description

药物输送装置及其制备方法和药物输送***Drug delivery device, preparation method thereof and drug delivery system

技术领域Technical field

本发明涉及医疗器械领域，具体涉及一种药物输送装置及其制备方法和药物输送***。The present invention relates to the field of medical equipment, in particular to a drug delivery device, a preparation method thereof, and a drug delivery system.

背景技术Background technique

在临床治疗上，通过给药载体可以将药物输送至动物体尤其是人体的多个自然腔道内，例如生殖自然腔道、呼吸道(鼻管、咽管、气管和支气管)、消化道(食管和直肠)或其他自然腔道。这些治疗中均需要将药物均匀快速地给至目标腔道内壁，且大部分情况下，还要求药物有效利用，尽量减少浪费。目前市面上的给药载体存在各种各样的缺陷，如给药效率和药物利用率低、无法均匀给药，且给药载体容易对目标腔道造成二次损伤等，无法满足治疗需求和使用需求。In clinical treatment, drugs can be delivered to multiple natural cavities in animals, especially humans, through drug delivery carriers, such as reproductive natural cavities, respiratory tract (nasal tube, pharyngeal tube, trachea and bronchus), digestive tract (esophagus and esophagus). Rectum) or other natural cavity. In these treatments, it is necessary to uniformly and quickly give drugs to the inner wall of the target cavity, and in most cases, effective use of drugs is also required to minimize waste. The current drug delivery carriers on the market have various defects, such as low drug delivery efficiency and drug utilization, inability to uniformly administer drugs, and drug delivery carriers are likely to cause secondary damage to the target cavity, etc., which cannot meet the needs of treatment and treatment. Usage requirements.

例如市面上的一种药物输送装置，位于导管本体远端的球囊为双层结构，以折叠形态进入目标腔道后，通过导管本体的给药腔向内外球囊的夹层之间填充药物，填充的药物从外层球囊的出口流出，作用于目标腔道内壁。For example, in a drug delivery device on the market, the balloon at the distal end of the catheter body has a double-layer structure. After entering the target lumen in a folded form, the drug is filled between the inner and outer balloons through the drug delivery cavity of the catheter body. The filled medicine flows out from the outlet of the outer balloon and acts on the inner wall of the target lumen.

基于上述现有技术，发明人发现现有技术中的药物输送装置至少存在以下技术问题：首先，由于球囊的夹层空间有限，且球囊充盈后会导致夹层空间被进一步压缩，大量药物滞留于夹层中，造成药物浪费、药物利用率较低、可操作性不佳；进一步导致了操作时间延长，增加了患者不必要的痛苦。其次，球囊的双层结构还导致药物输送装置的整体外径较大，尤其是球囊部分，较难***目标腔道，可能对目标腔道造成损伤。此外，现有技术的药物输送装置在球囊充盈后，导管本体的远端端部超出球囊较多，容易刮伤目标腔道内壁，造成二次损伤。Based on the above-mentioned prior art, the inventor found that the prior art drug delivery device has at least the following technical problems: First, because the dissection space of the balloon is limited, and after the balloon is filled, the dissection space will be further compressed, and a large amount of drugs will stay in In the interlayer, the waste of medicines, low utilization of medicines, and poor operability are caused; furthermore, the operation time is prolonged and unnecessary pain for the patient is increased. Secondly, the double-layer structure of the balloon also causes the overall outer diameter of the drug delivery device to be larger, especially the balloon part, which is difficult to insert into the target cavity, which may cause damage to the target cavity. In addition, in the prior art drug delivery device, after the balloon is filled, the distal end of the catheter body protrudes more than the balloon, which easily scratches the inner wall of the target lumen, causing secondary damage.

同时，现有药物输送装置的导管本体多采用硅胶等软质材料，支撑性较差，进入目标腔道时需要器械辅助，不仅增加了使用难度，还可能给患者带来一定生理痛苦。且由于不同患者的目标腔道的曲度不同，可能出现曲度较大时，即使在器械辅助下依旧无法***目标腔道的情况。At the same time, the catheter body of the existing drug delivery device mostly uses soft materials such as silica gel, which has poor supportability and requires instrument assistance when entering the target cavity, which not only increases the difficulty of use, but may also cause certain physiological pain to the patient. And because the curvature of the target channel of different patients is different, it may happen that the target channel cannot be inserted into the target channel even with the aid of the instrument when the curvature is large.

发明内容Summary of the invention

本发明的目的是提供一种药物输送装置及其制备方法和药物输送***，可以实现不同自然腔道内给药，给药效率和药物利用率较高且给药较为均匀。The purpose of the present invention is to provide a drug delivery device, a preparation method thereof, and a drug delivery system, which can realize drug delivery in different natural cavities, with high drug delivery efficiency and drug utilization, and more uniform drug delivery.

为了实现上述目的，根据本发明的第一方面提供了一种药物输送装置，所述药物输送装置包括导管本体、球囊和压力监测及调节装置，所述导管本体和所述球囊相互连接，所述球囊设置在所述导管本体的远端，所述导管本体具有相互隔离的充盈腔和给药腔，所述充盈腔包裹所述给药腔，所述充盈腔用于向所述球囊输送充盈介质，所述充盈腔与所述给药腔均与所述压力监测及调节装置连接，所述球囊充盈后的形状贴附于目标腔道内壁，且所述给药腔的远端设置至少一给药口，所述给药腔通过所述给药口将药物输送至所述球囊的外表面，所述给药口的孔径、所述给药口的数量与所述药物的粘度相匹配，被配置为在一定的所述药物的注射压力下，所述药物能够以一定的体积流量进行输送，其中，所述给药口的孔径、所述给药口的数量、所述药物的注射压力和所述药物的体积流量满足下述公式：In order to achieve the above objective, according to the first aspect of the present invention, a drug delivery device is provided. The drug delivery device includes a catheter body, a balloon, and a pressure monitoring and adjusting device, the catheter body and the balloon are connected to each other, The balloon is arranged at the distal end of the catheter body, and the catheter body has a filling cavity and a drug delivery cavity that are isolated from each other. The balloon transports the filling medium, the filling cavity and the drug delivery cavity are both connected to the pressure monitoring and regulating device, and the filled shape of the balloon is attached to the inner wall of the target lumen, and the drug delivery cavity is far away At least one dosing port is provided at the end, the dosing cavity delivers the drug to the outer surface of the balloon through the dosing port, the aperture of the dosing port, the number of the dosing port and the drug It is configured to deliver the drug at a certain volume flow under a certain injection pressure of the drug, wherein the aperture of the administration port, the number of the administration port, and the The injection pressure of the drug and the volume flow rate of the drug satisfy the following formula:

D ₂*0.8≤D _实≤D ₂*1.2 D ₂ * 0.8≤D _solid ≤D ₂ * 1.2

其中，Q为所述药物的体积流量(mL/s)；μ为所述药物的粘度(mPa.s)；p为所述药物的注射压力(atm)；L ₁为所述给药腔的长度(mm)；L ₂为所述给药腔的壁厚(mm)；n为所述给药口的数量；D ₁为所述给药腔的内径(mm)；D ₂为所述给药口的理论孔径(mm)；D _实为所述给药口的实际孔径(mm)。 Wherein, Q is the volume flow of the drug (mL/s); μ is the viscosity of the drug (mPa.s); p is the injection pressure (atm) _{of the drug; L 1} is the drug delivery cavity Length (mm); L ₂ is the wall thickness of the administration cavity (mm); n is the number of the administration ports; D ₁ is the inner diameter of the administration cavity (mm); D ₂ is the administration cavity Theoretical aperture (mm) _{of the drug port; D is} actually the actual aperture (mm) of the drug port.

可选的，所述给药腔的长度配置为200mm～300mm，所述给药腔的壁厚配置为0.1mm～1.0mm，所述给药口的孔径、所述给药口的数量与所述药物的粘度相匹配，被布置为在以0.5atm～1atm的压力注射所述药物时，所述药物在60s内的流量不小于3mL。Optionally, the length of the dosing cavity is configured to be 200 mm to 300 mm, the wall thickness of the dosing cavity is configured to be 0.1 mm to 1.0 mm, the aperture of the dosing port, the number of the dosing port, and the The viscosity of the medicine matches, and is arranged such that when the medicine is injected at a pressure of 0.5 atm to 1 atm, the flow rate of the medicine in 60 seconds is not less than 3 mL.

可选的，所述药物包括凝胶类药物、血浆类药物或水溶液类药物，所述给药口的数量设置为一个，所述给药口设置于所述给药腔的端面且所述给药口的孔径与所述给药腔的内径一致，其中：Optionally, the drug includes a gel drug, a plasma drug or an aqueous solution drug, the number of the administration port is set to one, the drug administration port is set on the end surface of the drug administration cavity and the drug administration The aperture of the medicine port is the same as the inner diameter of the medicine cavity, wherein:

当所述药物的粘度为2500mPa.s～10000mPa.s时，所述给药口的孔径为2.0mm～3.0mm；When the viscosity of the drug is 2500mPa.s～10000mPa.s, the aperture of the administration port is 2.0mm～3.0mm;

当所述药物的粘度为500mPa.s～2500mPa.s时，所述给药口的孔径为1.5mm～2.0mm；When the viscosity of the drug is 500mPa.s～2500mPa.s, the aperture of the administration port is 1.5mm～2.0mm;

当所述药物的粘度为100mPa.s～500mPa.s时，所述给药口的孔径为1.0mm～1.5mm；When the viscosity of the drug is 100 mPa.s to 500 mPa.s, the aperture of the administration port is 1.0 mm to 1.5 mm;

当所述药物的粘度为0.5mPa.s～100mPa.s时，所述给药口的孔径为0.5mm～1.0mm。When the viscosity of the drug is 0.5 mPa.s to 100 mPa.s, the aperture of the administration port is 0.5 mm to 1.0 mm.

可选的，当所述药物的粘度为0.1mPa.s～100mPa.s时，所述给药口的孔径为0.1mm～0.5mm，所述给药口的数量至少为两个，所述至少两个给药口设置于所述导管本体的远端的外环面，布置为在以2atm～4atm的压力注射所述药物时，所述药物呈喷雾状流出。Optionally, when the viscosity of the drug is 0.1 mPa.s-100 mPa.s, the aperture of the administration port is 0.1 mm-0.5 mm, the number of the administration port is at least two, and the at least Two administration ports are arranged on the outer ring surface of the distal end of the catheter body, and are arranged so that when the medicine is injected at a pressure of 2 atm-4 atm, the medicine flows out in a spray shape.

可选的，所述给药口的出药方向与所述导管本体的中轴线呈30°～150°夹角。Optionally, the medicine dispensing direction of the drug delivery port and the central axis of the catheter body form an angle of 30° to 150°.

可选的，所述导管本体的远端具有曲度。Optionally, the distal end of the catheter body has a curvature.

可选的，所述导管本体的远端的端部光滑且相对充盈后的所述球囊向内凹进。Optionally, the distal end of the catheter body is smooth and recessed inward relative to the inflated balloon.

根据本发明的第二方面提供了一种药物输送***，所述药物输送***包括鞘管和本发明的任一技术方案所述的药物输送装置；所述药物输送装置用于装载于所述鞘管内，以通过所述鞘管输送所述药物输送装置。According to the second aspect of the present invention, a drug delivery system is provided, the drug delivery system includes a sheath tube and the drug delivery device according to any one of the technical solutions of the present invention; the drug delivery device is used to be loaded on the sheath Inside the tube to deliver the drug delivery device through the sheath.

可选的，所述鞘管的远端设置有刻度标识。Optionally, a scale mark is provided at the distal end of the sheath.

可选的，所述药物输送***还包括固定件，所述固定件设置于所述鞘管的近端，用于固定所述鞘管与所述导管的相对位置。Optionally, the drug delivery system further includes a fixing member disposed at the proximal end of the sheath tube for fixing the relative position of the sheath tube and the catheter.

可选的，所述药物输送***还包括导丝，所述导丝可活动地***所述药物输送装置的内部，以支撑所述药物输送装置。Optionally, the drug delivery system further includes a guide wire that can be movably inserted into the drug delivery device to support the drug delivery device.

可选的，所述导丝包括导丝本体和锁定接头，所述锁定接头设置于所述导丝本体的近端，所述导丝本体的远端短于所述导管本体。Optionally, the guide wire includes a guide wire body and a locking joint, the locking joint is disposed at the proximal end of the guide wire body, and the distal end of the guide wire body is shorter than the catheter body.

可选的，所述药物输送***还包括压力监测及调节装置，所述充盈腔与所述压力监测及调节装置连接。Optionally, the drug delivery system further includes a pressure monitoring and regulating device, and the filling cavity is connected to the pressure monitoring and regulating device.

可选的，所述药物输送***还包括牵引绳，所述牵引绳内置于所述导管本体的侧壁中，所述牵引绳的远端端部固定于所述导管本体的内部的远端，所述牵引绳的近端与一活动部件连接，由所述活动部件的动作牵引所述牵引绳，并带动所述导管本体的远端的端部一同移动以弯曲。Optionally, the drug delivery system further includes a traction rope, the traction rope is built into the side wall of the catheter body, and the distal end of the traction rope is fixed to the inner distal end of the catheter body, The proximal end of the traction rope is connected with a movable component, and the traction rope is pulled by the action of the movable component, and the distal end of the catheter body is driven to move together to bend.

可选的，所述活动部件为滑杆，通过推动所述滑杆牵引所述牵引绳，并带动所述导管本体的远端的端部一同移动以弯曲。Optionally, the movable component is a sliding rod, and the pulling rope is pulled by pushing the sliding rod, and the distal end of the catheter body is driven to move together to bend.

根据本发明的第三方面提供了一种药物输送装置的制备方法，用于制备本发明的任一技术方案所述的药物输送装置，包括如下步骤：According to the third aspect of the present invention, a method for preparing a drug delivery device is provided. The method for preparing the drug delivery device according to any technical solution of the present invention includes the following steps:

步骤一、准备一外导管和一内导管；Step 1: Prepare an outer catheter and an inner catheter;

步骤二、将所述外导管与一球囊连接，所述球囊位于所述外导管的远端，且所述外导管的远端预留超出所述球囊的一超出区段；Step 2: Connect the outer catheter to a balloon, the balloon is located at the distal end of the outer catheter, and the distal end of the outer catheter is reserved for an overhanging section beyond the balloon;

步骤三、将所述内导管***所述外导管，并将所述内导管的远端与所述超出区段的至少部分区段通过加热熔融粘接，形成粘接段。Step 3: Insert the inner catheter into the outer catheter, and heat and melt the distal end of the inner catheter and at least a part of the protruding section to form an adhesive section.

可选的，所述超出区段的长度为15mm～20mm。Optionally, the length of the excess section is 15mm-20mm.

可选的，在步骤三中，所述粘接段的长度为12mm～17mm。Optionally, in step 3, the length of the bonding section is 12 mm to 17 mm.

可选的，若所述导管本体的远端端部光滑且相对充盈后的所述球囊向内凹进，则所述制备方法还包括以下步骤：Optionally, if the distal end of the catheter body is smooth and recessed inward relative to the filled balloon, the preparation method further includes the following steps:

步骤四、将所述内导管的远端与所述超出区段一起向内弯折进入所述球囊内部；Step 4: Bend the distal end of the inner catheter and the overhanging section inwardly into the balloon;

步骤五、若准备的所述内导管和所述外导管的远端端面皆贯通，则所述给药口为所述内导管的远端端面的开口，若准备的所述内导管或所述外导管之一的远端端面封闭，则所述给药口通过在所述粘接段的远端端面和/或外环面上扎孔得到，所述给药口的孔径通过所用针孔的尺寸控制。 Step 5. If the prepared inner catheter and the outer catheter are both penetrated, the drug delivery port is the opening of the distal end of the inner catheter, if the prepared inner catheter or the inner catheter The distal end surface of one of the outer catheters is closed, then the drug delivery port is obtained by piercing a hole on the distal end surface and/or outer ring surface of the bonding section, and the aperture of the drug delivery port passes through the needle hole used. Size control.

可选的，若所述药物输送装置用于雾化给药，则所述制备方法还包括步骤：Optionally, if the drug delivery device is used for atomized administration, the preparation method further includes the steps:

步骤四、若准备的所述内导管和所述外导管的远端的端面皆贯通，则将所述粘接段的远端的端面加热熔融封闭，接着在所述粘接段的远端外环面上扎孔得到所述给药口，若准备的所述内导管或所述外导管之一的远端端面封闭，则直接在所述粘接段的远端外环面上扎孔得到所述给药口，所述给药口的孔径通过所用针孔的尺寸控制。 Step 4. If the prepared inner catheter and the outer catheter are both penetrated, the end face of the distal end of the bonding section is heated to melt and seal, and then the distal end of the bonding section is outside the A hole is pierced on the ring surface to obtain the drug delivery port. If the distal end surface of one of the prepared inner catheter or the outer catheter is closed, a hole is directly pierced on the outer ring surface of the distal end of the bonding section to obtain the drug delivery port. For the administration port, the aperture of the administration port is controlled by the size of the needle hole used.

在本发明提供的药物输送装置及其制备方法和药物输送***中，所述药物输送装置和所述药物输送***包括导管本体、位于导管本体远端的球囊以及压力监测及调节装置。所述导管本体具有相互隔离的充盈腔和给药腔，所述充盈腔包裹于所述给药腔，所述充盈腔用于向所述球囊内部输送充盈介质，所述球囊充盈后的形状贴附于目标腔道内壁，且所述给药腔的远端设置至少一给药口，所述药物可以直接经所述给药口流经球囊外表面作用于目标腔道内壁，无需设置双层球囊给药，给药效率和药物利用率较高。特别的，所述充盈腔与所述给药腔分别与所述压力监测及调节装置连接，所述压力监测及调节装置用于监测和/或调节所述球囊内部的压力和注射所述药物的压力，且所述给药口的孔径和数量与药物的粘度相匹配，被配置为在一定的注射所述药物的压力下，所述药物能够以一定的体积流量进行输送，使得在所述压力监测及调节装置的监测和/或调节下，所述药物能够以额定的压力和流量经所述给药口输送至目标腔道内壁，适用于不同自然腔道的不同给药需求，有助于提高药物释放率和均匀给药。In the drug delivery device and the preparation method thereof and the drug delivery system provided by the present invention, the drug delivery device and the drug delivery system include a catheter body, a balloon located at the distal end of the catheter body, and a pressure monitoring and regulating device. The catheter body has a filling cavity and a drug delivery cavity that are isolated from each other, the filling cavity is wrapped in the drug delivery cavity, and the filling cavity is used to deliver the filling medium into the balloon. The shape is attached to the inner wall of the target lumen, and the distal end of the drug delivery cavity is provided with at least one drug delivery port. The drug can directly flow through the drug delivery port through the outer surface of the balloon and act on the inner wall of the target lumen. The double-layer balloon is set for drug delivery, and the drug delivery efficiency and drug utilization rate are high. In particular, the filling cavity and the drug delivery cavity are respectively connected to the pressure monitoring and regulating device, and the pressure monitoring and regulating device is used for monitoring and/or regulating the pressure inside the balloon and injecting the drug The pressure of the drug delivery port and the number of apertures match the viscosity of the drug, and the drug is configured to deliver the drug at a certain volume flow under a certain pressure for injecting the drug. Under the monitoring and/or adjustment of the pressure monitoring and regulating device, the drug can be delivered to the inner wall of the target cavity through the drug delivery port at a rated pressure and flow rate, which is suitable for different drug delivery requirements of different natural channels, which is helpful To improve the drug release rate and uniform administration.

优选的，本发明的球囊的外表面具有涂层，所述涂层能够降低球囊表面的药物吸附和/或使药物沿球囊的外表面浸润扩散，因此能够进一步促进均匀给药，并提高药物利用率。Preferably, the outer surface of the balloon of the present invention has a coating, which can reduce drug adsorption on the surface of the balloon and/or allow the drug to infiltrate and diffuse along the outer surface of the balloon, thereby further promoting uniform administration and Improve drug utilization.

优选的，由于所述给药口和/或所述涂层的设置，本发明的球囊可优选设置为单层球囊，与现有技术的双层球囊相比，药物直接经给药口作用于目标腔道内壁，无需流经夹层，提高了给药效率和药物利用率，且球囊的外表面优选具有涂层，能够使药物沿球囊的外表面浸润扩散，因此能够进一步促进均匀给药。单层球囊折叠后的整体外径也较小，较易通过目标腔道，降低了目标腔道损伤的几率。单层球囊也具有更好的顺应性，贴壁效果好，能够更好地贴合自然腔道的形状改变，可以提升药物的释放率。Preferably, due to the setting of the administration port and/or the coating, the balloon of the present invention can be preferably configured as a single-layer balloon. Compared with the double-layer balloon of the prior art, the drug is directly administered The mouth acts on the inner wall of the target lumen without flowing through the interlayer, which improves the efficiency of drug delivery and the utilization rate of the drug. The outer surface of the balloon is preferably coated to allow the drug to infiltrate and diffuse along the outer surface of the balloon, thereby further promoting Administer evenly. The overall outer diameter of the single-layer balloon after folding is also small, which makes it easier to pass through the target cavity, which reduces the probability of damage to the target cavity. The single-layer balloon also has better compliance, good adhesion effect, can better fit the shape change of the natural cavity, and can improve the release rate of the drug.

优选的，本发明的导管本体的远端光滑且在所述球囊充盈后，不超出邻近的球囊区域，即相对充盈后的所述球囊向内凹进，因此能够防止球囊充盈时导管本体的远端端部刮伤目标腔道内壁，避免造成二次损伤。Preferably, the distal end of the catheter body of the present invention is smooth and does not exceed the adjacent balloon area after the balloon is inflated, that is, the balloon is recessed inward relative to the inflated balloon, so that it can prevent the balloon from being inflated. The distal end of the catheter body scratches the inner wall of the target lumen to avoid secondary damage.

优选的，本发明的导丝本体远端短于导管本体，能够防止导丝的远端戳伤导管本体和目标腔道内壁，且导丝本体的近端具有锁定接头，能够防止所述导丝本体的近端端部埋入所述导管本体的内部，方便取出导丝。Preferably, the distal end of the guide wire body of the present invention is shorter than the catheter body, which can prevent the distal end of the guide wire from puncturing the inner wall of the catheter body and the target lumen, and the proximal end of the guide wire body has a locking joint to prevent the guide wire The proximal end of the body is embedded in the catheter body to facilitate the removal of the guide wire.

优选的，本发明的药物输送***还包括牵引绳，所述牵引绳内置于导管本体的侧壁，其远端固定于所述导管本体的内部的远端，近端与一活动部件连接，从而在所述药物输送装置进入弯曲的自然腔道时，可由所述活动部件的动作牵引所述牵引绳，并带动所述导管本体的远端端部一同移动弯曲，以适应自然腔道的弯曲形状，从而可以更为顺畅地进入目标腔道，无需额外器械辅助，有助于减少医生的操作难度，以及降低患者的生理痛苦。Preferably, the drug delivery system of the present invention further includes a traction rope built into the side wall of the catheter body, the distal end of which is fixed to the inner distal end of the catheter body, and the proximal end is connected to a movable component, thereby When the drug delivery device enters the curved natural cavity, the traction rope can be pulled by the action of the movable component, and the distal end of the catheter body is driven to move and bend together to adapt to the curved shape of the natural cavity , So that it can enter the target cavity more smoothly, without the aid of additional equipment, which helps to reduce the difficulty of the doctor's operation and reduce the physiological pain of the patient.

附图说明Description of the drawings

本领域的普通技术人员将会理解，提供的附图用于更好地理解本发明，而不对本发明的范围构成任何限定。其中：Those of ordinary skill in the art will understand that the accompanying drawings are provided for a better understanding of the present invention, and do not constitute any limitation on the scope of the present invention. in:

图1a为本发明一实施例的药物输送***的结构示意图；Figure 1a is a schematic structural diagram of a drug delivery system according to an embodiment of the present invention;

图1b为本发明一实施例的药物输送***(可调弯)的结构示意图；Figure 1b is a schematic structural diagram of a drug delivery system (adjustable bend) according to an embodiment of the present invention;

图1c示意性地示出了药物(黑色虚线)从根据本发明一实施例的药物输送***的给药口喷出后沿球囊外表面(黑色实线)的浸润和扩散；Figure 1c schematically shows the infiltration and diffusion of the drug (black dotted line) along the outer surface of the balloon (black solid line) after being ejected from the drug delivery port of the drug delivery system according to an embodiment of the present invention;

图1d为本发明一实施例的药物输送***的另一结构示意图，其中，示出了压力监测及调节装置；Figure 1d is another structural schematic diagram of a drug delivery system according to an embodiment of the present invention, in which a pressure monitoring and regulating device is shown;

图2为本发明一实施例的药物输送***的导丝的结构示意图；2 is a schematic structural diagram of a guide wire of a drug delivery system according to an embodiment of the present invention;

图3a-3f为本发明一实施例的药物输送装置的给药口的结构示意图；3a-3f are structural schematic diagrams of a drug delivery port of a drug delivery device according to an embodiment of the present invention;

图4a为本发明一实施例的药物输送装置(雾化给药)的结构示意图；Figure 4a is a schematic structural diagram of a drug delivery device (aerosolized drug delivery) according to an embodiment of the present invention;

图4b为本发明一实施例的雾化给药口的结构示意图；4b is a schematic diagram of the structure of an atomized drug delivery port according to an embodiment of the present invention;

图5a-5c为本发明一实施例的球囊的结构示意图；5a-5c are schematic diagrams of the structure of a balloon according to an embodiment of the present invention;

图6a-6b为本发明一实施例的药物输送装置的制备方法的示意图；6a-6b are schematic diagrams of a preparation method of a drug delivery device according to an embodiment of the present invention;

图7a为本发明一实施例的lgQ残差的正态概率图；Fig. 7a is a normal probability diagram of lgQ residuals according to an embodiment of the present invention;

图7b为本发明一实施例的lgQ残差的频率分布直方图；Figure 7b is a histogram of the frequency distribution of lgQ residuals according to an embodiment of the present invention;

图7c为本发明一实施例的lgQ残差与拟合值图；Fig. 7c is a diagram of lgQ residuals and fitted values according to an embodiment of the present invention;

图7d为本发明一实施例的lgQ残差与观测值顺序图。Fig. 7d is a sequence diagram of lgQ residuals and observations according to an embodiment of the present invention.

附图标记说明：100-药物输送装置；101-连接件；1011-充盈支路；1012-给药支路；102-导管本体；102a-外导管；102b-内导管；102c-超出区段；1021-充盈腔；1022-给药腔；1023-给药口；103-球囊；104-鞘管；1041-刻度标识；105-固定件；106-导丝；1061-导丝本体；1062-锁定接头；107-牵引绳；108-滑杆；110-压力监测及调节装置。Description of Reference Signs: 100-drug delivery device; 101-connector; 1011-filling branch; 1012-drug branch; 102-catheter body; 102a-outer catheter; 102b-inner catheter; 102c-extra section; 1021-filling cavity; 1022-dose cavity; 1023-dose port; 103-balloon; 104-sheath; 1041-graduation mark; 105-fixture; 106-guide wire; 1061-guide wire body; 1062- Locking joint; 107-towing rope; 108-sliding rod; 110-pressure monitoring and adjusting device.

具体实施方式detailed description

为使本发明的内容更加清楚易懂，以下结合说明书附图和实施例对本发明作进一步说明。但可以理解，本发明并不局限于下面所描述的具体实施例，本领域的技术人员所熟知的一般替换也涵盖在本发明的保护范围内。需说明的是，附图均采用非常简化的形式且均使用非精准的比例，仅用以方便、明晰地辅助说明本发明实施例的目的。In order to make the content of the present invention clearer and easier to understand, the present invention will be further described below in conjunction with the accompanying drawings and embodiments of the specification. However, it can be understood that the present invention is not limited to the specific embodiments described below, and general replacements well known to those skilled in the art are also covered by the protection scope of the present invention. It should be noted that the drawings all adopt a very simplified form and all use imprecise proportions, which are only used to conveniently and clearly assist in explaining the purpose of the embodiments of the present invention.

应该理解，在以下的描述中，可以基于附图进行关于在各部件“上”和“下”的指代。诸如“在…之下”、“在…下面”、“下面的”、“上面的”等空间术语，其目的是容易地描述附图中所示的一个部件和另一个部件的位置关系，除图中所示的方位之外，空间关系术语可以包括使用或操作中的装置的各种不同的方位。装置可以以其它方式定位，例如旋转90度或在其它方位，并且通过在此使用的空间关系描述进行相应的解释。It should be understood that, in the following description, references to “upper” and “lower” of each component may be made based on the drawings. Spatial terms such as "below", "below", "below", "above" and other spatial terms are used to easily describe the positional relationship between one component and another component shown in the drawings, except In addition to the orientation shown in the figure, the spatial relationship terminology can include various different orientations of the device in use or operation. The device can be positioned in other ways, such as rotated 90 degrees or in other orientations, and explained accordingly through the description of the spatial relationship used here.

还应理解，在以下的描述中，“近端”和“远端”是从使用该医疗器械的医生角度来看相对于彼此的元件或动作的相对方位、相对位置、方向，尽管“近端”和“远端”并非是限制性的，但是“近端”通常指该医疗设备在正常操作过程中靠近医生的一端，而“远端”通常是指首先进入患者体内的一端。It should also be understood that in the following description, "proximal end" and "distal end" refer to the relative position, relative position, and direction of elements or actions relative to each other from the perspective of the doctor using the medical device, although the "proximal end" "" and "distal" are not restrictive, but "proximal" usually refers to the end of the medical device that is close to the doctor during normal operation, and "distal" usually refers to the end that first enters the patient's body.

本发明的核心思想是提供一种药物输送装置及其制备方法和药物输送***，所述药物输送装置包括导管本体、球囊和压力监测及调节装置。所述导管本体和所述球囊相互连接，所述球囊位于所述导管本体的远端，所述导管本体具有相互隔离的充盈腔和给药腔，所述充盈腔包裹于所述给药腔，所述充盈腔与所述给药腔均与所述压力监测及调节装置连接。所述充盈腔用于充盈所述球囊，所述球囊充盈后的形状贴附于目标腔道内壁。所述给药腔的远端设置至少一给药口，所述给药腔通过所述给药口将药物输送至所述球囊的外表面，所述给药口的孔径、所述给药口的数量与所述药物的粘度相匹配，被配置为在一定的注射所述药物的压力下，所述药物能够以一定的体积流量进行输送，其中，所述给药口的孔径、所述给药口的数量、注射所述药物的压力和所述药物的体积流量满足下述公式：The core idea of the present invention is to provide a drug delivery device, a preparation method thereof, and a drug delivery system. The drug delivery device includes a catheter body, a balloon, and a pressure monitoring and regulating device. The catheter body and the balloon are connected to each other, the balloon is located at the distal end of the catheter body, and the catheter body has a filling cavity and a drug delivery cavity that are isolated from each other, and the inflation cavity is wrapped in the drug delivery Cavity, the filling cavity and the drug delivery cavity are both connected with the pressure monitoring and regulating device. The filling cavity is used for filling the balloon, and the inflated shape of the balloon is attached to the inner wall of the target lumen. At least one drug delivery port is provided at the distal end of the drug delivery cavity, the drug delivery cavity delivers the drug to the outer surface of the balloon through the drug delivery port, the aperture of the drug delivery port, and the drug delivery port The number of ports matches the viscosity of the drug, and is configured to deliver the drug at a certain volume flow under a certain pressure for injecting the drug, wherein the aperture of the drug delivery port, the The number of administration ports, the pressure for injecting the drug, and the volume flow rate of the drug satisfy the following formula:

D ₂*0.8≤D _实≤D ₂*1.2 D ₂ * 0.8≤D _solid ≤D ₂ * 1.2

其中，Q为所述药物的体积流量(mL/s)；μ为所述药物的粘度(mPa.s)；p为注射所述药物的压力(atm)；L ₁为所述给药腔的长度(mm)；L ₂为所述给药腔的壁厚(mm)；n为所述给药口的数量；D ₁为所述给药腔的内径(mm)；D ₂为所述给药口的理论孔径(mm)；D _实为所述给药口的实际孔径(mm)。 Wherein, Q is the volume flow of the drug (mL/s); μ is the viscosity of the drug (mPa.s); p is the pressure (atm) at which the drug is injected; L ₁ is the volume of the drug delivery cavity Length (mm); L ₂ is the wall thickness of the administration cavity (mm); n is the number of the administration ports; D ₁ is the inner diameter of the administration cavity (mm); D ₂ is the administration cavity Theoretical aperture (mm) _{of the drug port; D is} actually the actual aperture (mm) of the drug port.

上述公式为经验公式，即用于建立变量之间相关关系的数学表达式，各参数间的计算关系是数学意义上的而非物理意义上的。因此，在采用上述经验公式进行计算时，采用各参数在上述规定单位下的数值进行计算。The above formula is an empirical formula, that is, a mathematical expression used to establish the correlation between variables, and the calculation relationship between the parameters is in a mathematical sense rather than a physical sense. Therefore, when the above empirical formula is used for calculation, the numerical value of each parameter in the above specified unit is used for calculation.

由于所述球囊充盈后的形状贴附于目标腔道内壁，即具有顺应性，从而所述药物可以从所述给药腔经所述给药口流经球囊的外表面直接作用于目标腔道内壁，给药效率和药物利用率较高，且在所述压力监测及调节装置的监测和/或调节下，所述药物经额定的压力和流量输送至目标腔道内壁，用于不同自然腔道的不同给药需求，有助于均匀给药。所述球囊的外表面还优选地设置有涂层，所述涂层与所述药物的特性相匹配，以降低球囊表面的药物吸附和/或使所述药物沿所述球囊的外表面浸润扩散，因此能够进一步促进均匀给药，并提高药物利用率。Since the shape of the balloon after inflation is attached to the inner wall of the target lumen, it is compliant, so that the drug can flow from the administration cavity through the administration port through the outer surface of the balloon and directly act on the target. The inner wall of the cavity has high drug delivery efficiency and drug utilization, and under the monitoring and/or adjustment of the pressure monitoring and regulating device, the drug is delivered to the inner wall of the target cavity at a rated pressure and flow rate for different purposes. The different drug delivery requirements of the natural cavity help uniform drug delivery. The outer surface of the balloon is also preferably provided with a coating that matches the characteristics of the drug to reduce the adsorption of the drug on the balloon surface and/or make the drug follow the outer surface of the balloon. The surface is infiltrated and diffused, so it can further promote uniform drug delivery and improve drug utilization.

以下结合附图1a-7d和具体实施例对本发明一实施例的药物输送装置及其制备方法和药物输送***进行详细描述。The following describes in detail a drug delivery device, a preparation method thereof, and a drug delivery system according to an embodiment of the present invention with reference to the accompanying drawings 1a-7d and specific embodiments.

请参考图1a，其为本发明一实施例的药物输送***的结构示意图。如图1a所示，所述药物输送***包括药物输送装置100。药物输送装置100包括导管本体102、球囊103和压力监测及调节装置110(参见图1d)，导管本体102和球囊103连接，球囊103设置在导管本体102的远端，导管本体102具有相互隔离的充盈腔1021和给药腔1022，充盈腔1021包裹给药腔1022，充盈腔1021和给药腔1022分别与所述压力监测及调节装置110连接。充盈腔1021用于向球囊103输送充盈介质，球囊103充盈后能够贴附目标腔道内壁。给药腔1022的远端设置至少一给药口1023(见下文及图3a-图3e)，给药腔1022通过给药口1023将药物输送至球囊103的外表面，给药口1023的孔径和数量与所述药物的粘度相匹配，被配置为在一定的注射所述药物的压力下，所述药物能够以一定的体积流量进行输送，其中，给药口1023的孔径、给药口1023的数量、注射所述药物的压力和所述药物的体积流量满足下述公式(公式1和公式2)：Please refer to FIG. 1a, which is a schematic structural diagram of a drug delivery system according to an embodiment of the present invention. As shown in FIG. 1a, the drug delivery system includes a drug delivery device 100. The drug delivery device 100 includes a catheter body 102, a balloon 103, and a pressure monitoring and adjusting device 110 (see Figure 1d). The catheter body 102 is connected to the balloon 103. The balloon 103 is arranged at the distal end of the catheter body 102. The catheter body 102 has The filling cavity 1021 and the drug delivery cavity 1022 are isolated from each other, the filling cavity 1021 wraps the drug delivery cavity 1022, and the filling cavity 1021 and the drug delivery cavity 1022 are respectively connected to the pressure monitoring and regulating device 110. The filling cavity 1021 is used to deliver the filling medium to the balloon 103, and the balloon 103 can be attached to the inner wall of the target lumen after being filled. At least one drug delivery port 1023 is provided at the distal end of the drug delivery cavity 1022 (see below and Figures 3a-3e). The drug delivery cavity 1022 delivers the drug to the outer surface of the balloon 103 through the drug delivery port 1023. The pore size and number match the viscosity of the drug, and it is configured to deliver the drug at a certain volume flow under a certain pressure for injecting the drug. The number of 1023, the pressure of the injection of the drug, and the volume flow of the drug satisfy the following formulas (Formula 1 and Formula 2):

D ₂*0.8≤D _实≤D ₂*1.2 (公式2) D ₂ * 0.8≤D _solid ≤D ₂ * 1.2 (Equation 2)

其中，Q为所述药物的体积流量(mL/s)；μ为所述药物的粘度(mPa.s)；L为所述给药腔的长度(mm)；p为注射所述药物的压力(atm)；L ₂为所述给药腔的壁厚(mm)；n为所述给药口的数量；D ₁为所述给药腔的内径(mm)；D ₂为所述给药口的理论孔径(mm)；D _实为所述给药口的实际孔径(mm)。 Wherein, Q is the volume flow rate of the drug (mL/s); μ is the viscosity of the drug (mPa.s); L is the length of the dosing cavity (mm); p is the pressure at which the drug is injected (atm); L ₂ is the wall thickness of the dosing cavity (mm); n is the number of the dosing ports; D ₁ is the inner diameter of the dosing cavity (mm); D ₂ is the dosing Theoretical aperture (mm) _{of the port; D is} actually the actual aperture (mm) of the dosing port.

由于球囊103充盈后的形状贴附于目标腔道内壁，即具有顺应性，所述药物可以从给药腔1022经给药口1023流经球囊103的外表面直接作用于目标腔道内壁，给药效率和药物利用率较高。特别的，由于所述压力监测及调节装置110可监测和/或调节药物注射过程中球囊103内部以及给药腔1022的压力，所述药物可经额定的压力和流量输送至目标腔道内壁，适用于不同自然腔道的不同给药需求，有助于均匀给药以及避免压力过高对目标腔道内壁造成二次损伤。例如，在一自然腔道的给药中，可设置一定的注射压力(如1.0atm)，实现均匀注射，也可设置注射压力上限(如2.0atm)，在注射压力超过上限时，自动调节充盈腔1021压力，或停止注射，使压力保持在可接受范围，避免压力过高对目标腔道内壁造成二次损伤。Since the filled shape of the balloon 103 is attached to the inner wall of the target lumen, that is, it has compliance. The drug can flow from the administration cavity 1022 through the administration port 1023 through the outer surface of the balloon 103 and directly act on the inner wall of the target lumen. , The drug delivery efficiency and drug utilization rate are high. In particular, since the pressure monitoring and adjusting device 110 can monitor and/or adjust the pressure inside the balloon 103 and the administration cavity 1022 during the drug injection process, the drug can be delivered to the inner wall of the target cavity at a rated pressure and flow rate. , It is suitable for different drug delivery requirements of different natural cavities, helps uniform drug delivery and avoids secondary damage to the inner wall of the target cavity caused by excessive pressure. For example, in the administration of a natural cavity, a certain injection pressure (such as 1.0atm) can be set to achieve uniform injection, or an upper limit of injection pressure (such as 2.0atm) can be set, and when the injection pressure exceeds the upper limit, the filling can be automatically adjusted The pressure in the cavity 1021, or stop the injection, keep the pressure in an acceptable range, and avoid the secondary damage to the inner wall of the target cavity caused by the excessive pressure.

药物注射过程理论上符合泊肃叶流动，假定给药口1023开设于给药腔1022的远端端面且给药口1023的孔径与给药腔1022的内径一致，则根据哈根-泊肃叶(Hagen-Poiseuille)方程(公式4)，体积流量Q、压力p，给药口1023的孔径D ₂、给药腔1022长度L ₁、药物粘度μ的关系如下： The drug injection process theoretically conforms to the Poiseuille flow. Assuming that the administration port 1023 is opened on the distal end of the administration cavity 1022 and the aperture of the administration port 1023 is consistent with the inner diameter of the administration cavity 1022, according to Hagen-Poiseuille (Hagen-Poiseuille) equation (Equation 4), the relationship between volume flow Q, pressure p, aperture D _{2 of} administration port 1023, length L _{1 of} administration cavity 1022, and drug viscosity μ is as follows:

但是，上述理论模型仅适用于给药口1023开设于给药腔1022的远端端面且给药口1023的孔径与给药腔1022的内径一致的情况，而在实际给药过程中，可能于给药腔1022的远端端面开设多个给药口1023，或者于给药腔1022的远端外环面开设给药口1023，因此，上述理论模型难以满足实际使用需求。However, the above-mentioned theoretical model is only applicable to the situation where the administration port 1023 is opened on the distal end surface of the administration cavity 1022 and the aperture of the administration port 1023 is consistent with the inner diameter of the administration cavity 1022. In the actual administration process, it may be The distal end surface of the drug delivery cavity 1022 is provided with multiple drug delivery ports 1023, or the drug delivery port 1023 is provided on the distal outer ring surface of the drug delivery cavity 1022. Therefore, the above-mentioned theoretical model cannot meet actual use requirements.

本实施例中，可对药物注射过程进行全因子试验设计及分析，推导得出经验公式(公式1)，以适用不同的给药口1023开设方式。具体的，选取药物粘度μ，给药口1023孔径D ₂，给药口1023的数量n，给药腔1022长度L ₁，给药腔1022内径D ₁，给药腔1022壁厚L ₂，药物注射压力p等7个因子，分别设置3水平，得到7因子3水平全因子设计，如表1所示。 In this embodiment, a full factorial experiment design and analysis can be performed on the drug injection process, and an empirical formula (formula 1) can be derived to apply different administration port 1023 opening methods. Specifically, select the drug viscosity μ, the aperture D ₂ of the administration port 1023, the number n of the administration port 1023, the length L ₁ of the administration cavity 1022, the inner diameter D ₁ of the administration cavity 1022, the wall thickness L _{2 of the} administration cavity 1022, and the drug 7 factors such as injection pressure p are set at 3 levels respectively, and a 7-factor 3-level full factorial design is obtained, as shown in Table 1.

表1正交实验设计Table 1 Orthogonal experimental design

按照运行序在各因子水平下进行试验，记录相应的流速值，得到药物的体积流量Q。对实验结果进行分析，对各输入输出做对数处理，并进行回归拟合，结果如表2-表4和图7a-图7d所示。Carry out the test at each factor level according to the running sequence, record the corresponding flow rate value, and obtain the volume flow rate Q of the drug. Analyze the experimental results, perform logarithmic processing on each input and output, and perform regression fitting. The results are shown in Table 2-Table 4 and Figure 7a-Figure 7d.

来源source	自由度Degree of freedom	Adj SSAdj SS	Adj MSAdj MS	F值F value	Pr值Pr value
回归return	77	69.728869.7288	9.96139.9613	105.13105.13	0.0000.000
lgμ lgμ	11	52.948252.9482	52.948252.9482	558.82558.82	0.0000.000
lgp lgp	11	1.10091.1009	1.10091.1009	11.6211.62	0.0020.002
lgD1 lgD1	11	8.65518.6551	8.65518.6551	91.3591.35	0.0000.000
lgL1 lgL1	11	0.45790.4579	0.45790.4579	4.834.83	0.0350.035
lgD2 lgD2	11	32.898332.8983	32.898332.8983	347.21347.21	0.0000.000
lgn lgn	11	7.41687.4168	7.41687.4168	78.2878.28	0.0000.000
lgL2 lgL2	11	3.72303.7230	3.72303.7230	39.2939.29	0.0000.000
误差error	3434	3.22153.2215	0.09480.0948	To	To
合计total	4141	72.950372.9503	To	To	To

表2方差分析Table 2 Analysis of variance

SS	R-sqR-sq	R-sq(调整)R-sq (adjustment)	R-sq(预测)R-sq (forecast)
0.3078160.307816	86.58％86.58%	84.67％84.67%	83.11％83.11%

表3模型汇总Table 3 Model summary

表4系数Table 4 Coefficient

由拟合结果分析可知，模型整体Pr值(即表1中的回归Pr值)及各因子项Pr值(即表1和表4中的常量因子、lgμ、lgp、lgD ₁、lgL ₁、lgD ₂、lgn和lgL ₂等因子)均小于0.05，模型有效；残差正态，分布无异常；R-sq，R-sq(调整)，R-sq(预测)均大于80％，表明模型精度较为准确，可较好匹配实验结果，并可用于预测。 The analysis of the fitting results shows that the overall Pr value of the model (ie the regression Pr value in Table 1) and the Pr value of each factor item (ie the constant factors in Tables 1 and 4, lgμ, lgp, lgD ₁ , lgL ₁ , lgD _2. Factors such as lgn and lgL ₂ ) are all less than 0.05, the model is valid; the residuals are normal, and the distribution is normal; R-sq, R-sq (adjusted), and R-sq (forecast) are all greater than 80%, indicating the accuracy of the model It is more accurate, can better match the experimental results, and can be used for prediction.

由此得到下述经验方程(公式3)：From this, the following empirical equation (Equation 3) is obtained:

lgQ＝3.800-1.1654lgμ+1.083lgp+1.188lgD ₁-0.528lgL ₁+3.206lgD ₂+1.225lgn-0.887lgL ₂ (公式3) lgQ=3.800-1.1654lgμ+1.083lgp+1.188lgD ₁ -0.528lgL ₁ +3.206lgD ₂ +1.225lgn-0.887lgL ₂ (Formula 3)

由公式3变形可得到下述经验公式(公式1):The following empirical formula (Equation 1) can be obtained from the transformation of Equation 3:

在实际应用过程中，以公式1所限定的特定数值为基准上下浮动一定范围进行修正，最终可得到下述公式(公式2)：In the actual application process, the specific value defined in formula 1 is used as a reference to float up and down to a certain range for correction, and finally the following formula (formula 2) can be obtained:

本实施例的上述经验拟合模型针对临床实际使用情况设置边界条件(因子水平)，更适用于球囊导管技术领域，能更好地指导实际产品开发工作。特别的，该模型包含了于给药腔1022的远端端面开设多个给药口1023或于给药腔1022的远端外环面开设给药口1023等多种情况，适用范围更广。The above-mentioned empirical fitting model of this embodiment sets boundary conditions (factor levels) for actual clinical use conditions, is more suitable for the technical field of balloon catheters, and can better guide actual product development work. In particular, this model includes multiple situations such as opening multiple drug delivery ports 1023 on the distal end surface of the drug delivery cavity 1022 or opening drug delivery ports 1023 on the distal outer ring surface of the drug delivery cavity 1022, and has a wider range of applications.

优选的，球囊103的外表面设置有涂层，所述涂层与药物的特性相匹配，通过所述涂层可以降低球囊103的外表面的药物吸附和/或使药物沿球囊103的外表面扩散，因此能够进一步促进均匀给药，并提高药物利用率。Preferably, the outer surface of the balloon 103 is provided with a coating, and the coating matches the characteristics of the drug. Through the coating, the drug adsorption on the outer surface of the balloon 103 can be reduced and/or the drug can be moved along the balloon 103. The outer surface of the powder diffuses, so it can further promote uniform drug delivery and improve drug utilization.

在一个实施例中，所述涂层具有浸润性，此处，浸润性指的是涂层的特性与注射到给药腔1022的药物匹配，能够达到浸润药物的效果，使药物沿球囊103的外表面浸润扩散，并均匀作用于目标腔道内壁(如图1c所示)。示例性的，假设药物具有亲水亲油特性，则设置的涂层可相应具有亲水性、亲油性中的一种或多种特性，以使得相应的药物能够沿球囊103的外表面浸润扩散。更具体的，涂层的特性与药物的特性一致。假设药物为水溶液类药物，则所述涂层可为具有亲水性的涂层，例如PVP(聚乙烯基吡咯烷酮)涂层，以实现药物在球囊103的外表面的快速浸润。In one embodiment, the coating has wettability. Here, wettability means that the characteristics of the coating are matched with the drug injected into the drug delivery cavity 1022, which can achieve the effect of infiltrating the drug, so that the drug can be moved along the balloon 103. The outer surface of the infiltration and diffusion, and uniformly act on the inner wall of the target lumen (as shown in Figure 1c). Exemplarily, assuming that the drug has hydrophilic and lipophilic properties, the provided coating may correspondingly have one or more of hydrophilic and lipophilic properties, so that the corresponding drug can infiltrate along the outer surface of the balloon 103 diffusion. More specifically, the properties of the coating are consistent with the properties of the drug. Assuming that the drug is an aqueous drug, the coating may be a hydrophilic coating, such as a PVP (polyvinylpyrrolidone) coating, to achieve rapid infiltration of the drug on the outer surface of the balloon 103.

在另一实施例中，所述涂层具有防粘附性，能够降低球囊103表面的药物吸附，提高药物利用率。例如药物为血浆，则涂层可使用抗凝涂层，以降低血浆在球囊103外表面的吸附，提高药物利用率。再例如药物为干细胞悬液，悬液成分包括大量的水分，则涂层可为疏水涂层，例如PTFE(聚四氟乙烯)涂层，以降低球囊103表面的药物吸附，避免药物成分浪费。In another embodiment, the coating has anti-adhesion properties, which can reduce drug adsorption on the surface of the balloon 103 and improve drug utilization. For example, if the drug is plasma, an anticoagulant coating can be used as the coating to reduce the adsorption of plasma on the outer surface of the balloon 103 and improve the utilization rate of the drug. For another example, the drug is a stem cell suspension, and the suspension component contains a large amount of water. The coating can be a hydrophobic coating, such as a PTFE (polytetrafluoroethylene) coating, to reduce drug adsorption on the surface of the balloon 103 and avoid waste of drug components .

由于给药口1023和/或所述涂层的设置，本实施例的球囊103可优选设置为单层球囊。与双层球囊相比，单层球囊的设置由于不需要预先填充内外囊层之间的夹层，从而可以减少药物用量，提高药物利用率。该单层球囊的设置尤其在治疗药物的费用昂贵时效果显著，能够有效降低医疗成本，减轻患者负担。特别的，具有涂层的单层球囊103适用于向目标腔道内输送抗炎药物、粒细胞集落刺激因子(G-CSF)、人绒毛膜***(HCG)、富血小板血浆(PRP)或干细胞悬液等药物。Due to the setting of the administration port 1023 and/or the coating, the balloon 103 of the present embodiment can be preferably configured as a single-layer balloon. Compared with the double-layer balloon, the single-layer balloon does not need to be pre-filled with the interlayer between the inner and outer balloon layers, which can reduce the amount of medicine and improve the utilization rate of medicine. The setting of the single-layer balloon is particularly effective when the cost of treatment drugs is expensive, and can effectively reduce medical costs and reduce the burden on patients. In particular, the coated single-layer balloon 103 is suitable for delivering anti-inflammatory drugs, granulocyte colony stimulating factor (G-CSF), human chorionic gonadotropin (HCG), and platelet-rich plasma (PRP) into the target lumen. Or stem cell suspension and other drugs.

请继续参考图1a，本实施例的药物输送装置100还包括连接件101，连接件101位于导管本体102的近端，用于与外部装置连接，以输入药物和充盈介质，外部装置例如为医用注射器。可选的，球囊103、导管本体102和连接件101可通过热焊、胶粘或其它方式连接，本发明对此不做限制。Please continue to refer to FIG. 1a, the drug delivery device 100 of this embodiment further includes a connecting piece 101, which is located at the proximal end of the catheter body 102 and is used to connect with an external device for inputting medicine and filling medium. The external device is, for example, a medical syringe. Optionally, the balloon 103, the catheter body 102 and the connecting member 101 may be connected by heat welding, gluing or other means, which is not limited in the present invention.

进一步，充盈腔1021具有位于导管本体102近端的进口和位于导管本体102远端的出口。给药腔1022也具有位于导管本体102近端的进口和位于导管本体102远端的出口，所述给药腔1022的出口与给药口1023连通。连接件101包括充盈支路1011和给药支路1012。其中，充盈支路1011与充盈腔1021的进口连通，用于充盈球囊103，给药支路1012与给药腔1022的进口连通，用于输送药物。药物从所述给药支路1012注入给药腔1022，并经给药腔1022远端的给药口1023流经球囊103的外表面直接作用于目标腔道内壁。Furthermore, the filling cavity 1021 has an inlet located at the proximal end of the catheter body 102 and an outlet located at the distal end of the catheter body 102. The medication cavity 1022 also has an inlet located at the proximal end of the catheter body 102 and an outlet located at the distal end of the catheter body 102, and the outlet of the medication cavity 1022 is in communication with the medication port 1023. The connecting piece 101 includes a filling branch 1011 and a medication branch 1012. Wherein, the filling branch 1011 communicates with the inlet of the filling cavity 1021 for filling the balloon 103, and the drug delivery branch 1012 is connected with the inlet of the drug delivery cavity 1022 for delivering drugs. The medicine is injected into the administration cavity 1022 from the administration branch 1012, and flows through the outer surface of the balloon 103 through the administration port 1023 at the distal end of the administration cavity 1022 and directly acts on the inner wall of the target cavity.

较佳的，导管本体102的远端端部光滑，防止导管本体102的远端刮伤目标腔道内壁。这里，“光滑”指的是端部例如是没有凸起的平面或曲面。进一步，球囊103充盈后，导管本体102的远端端部相对球囊103向内凹进，以防止导管本体102的远端戳伤目标腔道内壁，进一步提高使用安全性。优选的，导管本体102的远端超出球囊103的长度小于等于3mm，这里是指在导管本体102与球囊103的远端的连接点距离导管本体102的远端端部的距离小于等于3mm，优选的，小于等于3mm且大于等于1mm。Preferably, the distal end of the catheter body 102 is smooth to prevent the distal end of the catheter body 102 from scratching the inner wall of the target lumen. Here, "smooth" means that the end portion is, for example, a flat surface or a curved surface without protrusions. Furthermore, after the balloon 103 is filled, the distal end of the catheter body 102 is recessed inward relative to the balloon 103 to prevent the distal end of the catheter body 102 from damaging the inner wall of the target lumen, thereby further improving the safety of use. Preferably, the length of the distal end of the catheter body 102 beyond the balloon 103 is less than or equal to 3mm, which means that the distance between the connection point of the catheter body 102 and the distal end of the balloon 103 and the distal end of the catheter body 102 is less than or equal to 3mm , Preferably, less than or equal to 3mm and greater than or equal to 1mm.

可选的，导管本体102选用具有适中硬度(80A～30D)的医用塑料，例如聚酰胺、Pebax、聚氨酯、PE、PVC或硅胶等材料，或者选择两种或两种以上这些材料的混合物或复合材料。可选的，导管本体102的制作材料中可添加B超显影剂，例如钨，硫酸钡等。Optionally, the catheter body 102 is selected from medical plastics with moderate hardness (80A-30D), such as materials such as polyamide, Pebax, polyurethane, PE, PVC, or silicone, or a mixture or composite of two or more of these materials Material. Optionally, a B-ultrasound developer, such as tungsten, barium sulfate, etc., can be added to the material of the catheter body 102.

请继续参考图1a，本实施例的药物输送***还包括鞘管104，用于装载并输送药物输送装置100。具体的，药物输送装置100装载于鞘管104内，由鞘管104引导药物输送装置100进入目标腔道。药物输送***还可包括固定件105，固定件105位于鞘管104的近端，用于固定鞘管104与药物输送装置100的相对位置，防止药物输送装置100滑动。鞘管104的远端可设置刻度标识1041，刻度标识1041的长度可设置为4cm～10cm，以方便判断药物输送装置100进入目标腔道的尺寸及位置。优选的，鞘管104选用摩擦系数较小的材料，例如PTFE、FEP及HDPE等材料中的一种或其组合。可选的，鞘管材料中可添加B超显影剂，例如钨，硫酸钡等。Please continue to refer to FIG. 1a, the drug delivery system of this embodiment further includes a sheath 104 for loading and delivering the drug delivery device 100. Specifically, the drug delivery device 100 is loaded in the sheath 104, and the sheath 104 guides the drug delivery device 100 into the target lumen. The drug delivery system may further include a fixing member 105 located at the proximal end of the sheath tube 104 for fixing the relative position of the sheath tube 104 and the drug delivery device 100 to prevent the drug delivery device 100 from sliding. The distal end of the sheath 104 may be provided with a scale mark 1041, and the length of the scale mark 1041 may be set to 4 cm to 10 cm to facilitate the determination of the size and position of the drug delivery device 100 entering the target cavity. Preferably, the sheath tube 104 uses a material with a relatively small friction coefficient, such as one or a combination of PTFE, FEP, HDPE and other materials. Optionally, a B-mode ultrasound imaging agent, such as tungsten, barium sulfate, etc., can be added to the sheath tube material.

请参考图1b，其在图1a基础上增加了可调弯功能，主要通过内置于导管本体102侧壁的牵引绳107实现。牵引绳107的远端固定于导管本体102内部，近端连接至一可活动的滑杆108(或其他活动部件)。推动滑杆108(或其他活动部件)时，牵引绳107可带动导管本体102的远端一同移动弯曲，实现弯度调节目的。牵引绳107的外径尺寸可为0.1mm～1.0mm，材料可选用具有较高强度及韧性的金属材料(例如不锈钢，镍合金等)或高分子纤维材料(例如PE、PP、PET、PA等材料中的一种或其组合)。Please refer to FIG. 1b, which adds an adjustable bending function on the basis of FIG. The distal end of the traction rope 107 is fixed inside the catheter body 102, and the proximal end is connected to a movable sliding rod 108 (or other movable components). When the sliding rod 108 (or other movable parts) is pushed, the traction rope 107 can drive the distal end of the catheter body 102 to move and bend together, so as to achieve the purpose of adjusting the curvature. The outer diameter of the traction rope 107 can be 0.1mm～1.0mm, and the material can be metal materials with higher strength and toughness (such as stainless steel, nickel alloy, etc.) or polymer fiber materials (such as PE, PP, PET, PA, etc.) One or a combination of materials).

请参考图2，其为本发明一实施例的药物输送***的导丝106的结构示意图。如图2所示，可选的，本发明实施例的药物输送***还包括导丝106，所述导丝106用于可活动地***药物输送装置100的内部(即给药腔1022内部)，例如导丝106由药物输送装置100的近端***药物输送装置100内部的给药腔1022，用于支撑药物输送装置100进入目标腔道。较佳的，导丝106包括导丝本体1061，导丝本体1061的远端短于导管本体102，能够防止导丝本体1061损伤药物输送装置100的远端及目标腔道内壁。且导丝本体1061的近端可具有锁定接头1062，锁定接头1062比药物输送装置100的近端的开口宽，使用时锁定接头1062卡设于药物输送装置100的近端，以防止导丝本体1061的近端埋入药物输送装置100内，并方便取出导丝本体1061。Please refer to FIG. 2, which is a schematic structural diagram of a guide wire 106 of a drug delivery system according to an embodiment of the present invention. As shown in FIG. 2, optionally, the drug delivery system of the embodiment of the present invention further includes a guide wire 106 for movably inserting into the drug delivery device 100 (that is, inside the drug delivery cavity 1022), For example, the guide wire 106 is inserted into the drug delivery cavity 1022 inside the drug delivery device 100 from the proximal end of the drug delivery device 100 to support the drug delivery device 100 to enter the target cavity. Preferably, the guide wire 106 includes a guide wire body 1061, and the distal end of the guide wire body 1061 is shorter than the catheter body 102, which can prevent the guide wire body 1061 from damaging the distal end of the drug delivery device 100 and the inner wall of the target lumen. Moreover, the proximal end of the guide wire body 1061 may have a locking joint 1062, which is wider than the opening of the proximal end of the drug delivery device 100. When in use, the locking joint 1062 is clamped on the proximal end of the drug delivery device 100 to prevent the guide wire body The proximal end of 1061 is embedded in the drug delivery device 100, and the guide wire body 1061 can be easily taken out.

请参考图3a-图3e，其为本发明一实施例的药物输送***的药物输送装置100的给药口1023的结构示意图。如图3a-图3e所示，给药腔1022的远端设置有至少一个给药口1023，以便药物从给药腔1022中流出，给药口1023的位置、大小及数量由药物成分、粘度等特性，以及临床所需给药效果决定。粘度较小，给药量小的药物可使用多个小尺寸给药口1023，以实现均匀给药需求；粘度大的药物需要使用单个大尺寸给药口1023，以实现快速给药。例如图3a所示，设置一个给药口1023，或者如图3b-图3e所示，设置多个给药口1023，例如设置有两个、四个或八个。给药口1023可设置于导管本体102的顶部(如图3f所示,导管本体102的远端端面的俯视图)和/或侧部(如图3a-3e所示，导管本体102的侧视图)，所述顶部指的是导管本体102的远端端面(横截面)，特别适用于目标部位为腔体的给药需求，所述侧部指的是导管本体102的远端外环面(轴向或周向外表面)，特别适用于目标部位为自然腔道的给药需求。侧部的多个给药口1023沿导管本体102的轴向排列(如图3c所示)，和/或沿导管本体102的周向排列(如图3d所示)，可以排列成一排或多排(如图3e所示)。给药口1023的最大尺寸(孔径)范围可为0.1mm-3.0mm，例如0.2mm，0.3mm，0.5mm，1mm，1.5mm，1.8mm，2.0mm，2.5mm或3.0mm。Please refer to FIGS. 3a to 3e, which are structural schematic diagrams of the drug delivery port 1023 of the drug delivery device 100 of the drug delivery system according to an embodiment of the present invention. As shown in Figures 3a-3e, the distal end of the dosing cavity 1022 is provided with at least one dosing port 1023 so that the medicine can flow out of the dosing cavity 1022. The position, size and quantity of the dosing port 1023 are determined by the composition and viscosity of the drug. And other characteristics, as well as the clinical need to determine the effect of administration. For drugs with small viscosity and small dosage, multiple small-sized dosing ports 1023 can be used to achieve uniform administration requirements; drugs with high viscosity need to use a single large-sized dosing port 1023 to achieve rapid administration. For example, as shown in Fig. 3a, one drug delivery port 1023 is provided, or as shown in Figs. 3b to 3e, a plurality of drug delivery ports 1023 are provided, for example, two, four or eight are provided. The drug delivery port 1023 can be provided on the top of the catheter body 102 (as shown in Figure 3f, the top view of the distal end of the catheter body 102) and/or the side (as shown in Figures 3a-3e, the side view of the catheter body 102) The top refers to the distal end surface (cross-section) of the catheter body 102, which is particularly suitable for drug delivery requirements where the target site is a cavity, and the side refers to the distal outer ring surface (axis) of the catheter body 102. Toward or circumferentially outward surface), it is especially suitable for the drug delivery requirements where the target site is a natural cavity. The multiple administration ports 1023 on the side are arranged along the axial direction of the catheter body 102 (as shown in FIG. 3c), and/or arranged along the circumferential direction of the catheter body 102 (as shown in FIG. 3d), and may be arranged in one row or more Row (as shown in Figure 3e). The maximum size (aperture) of the administration port 1023 may range from 0.1 mm to 3.0 mm, such as 0.2 mm, 0.3 mm, 0.5 mm, 1 mm, 1.5 mm, 1.8 mm, 2.0 mm, 2.5 mm or 3.0 mm.

在一自然腔道的给药过程中，给药腔1022的长度配置为200mm～300 mm，给药腔1022的壁厚配置为0.1mm～1.0mm，给药口1023的孔径、给药口1023的数量与所述药物的粘度相匹配，被布置为在以0.5atm～1atm的压力注射所述药物时，所述药物在60s内的流量不小于3mL。所述药物包括凝胶类药物、血浆类药物或水溶液类药物，给药口1023的数量优选设置为一个，并设置于给药腔1022的端面，且给药口1023的孔径与给药腔1022的内径一致。常规使用条件下，假设手动注射药物的压力恒定为1atm，给药腔1022长度为200mm～300mm，由经验拟合方程(公式1和公式2)可知，为满足60s内流量Q≥3mL(优选为不小于3mL，且不超过50mL)，所述药物的粘度和给药口1023的尺寸关系如下：In the process of drug delivery in a natural cavity, the length of the drug delivery cavity 1022 is configured to be 200mm to 300 mm, the wall thickness of the drug delivery cavity 1022 is configured to be 0.1mm to 1.0mm, the aperture of the drug delivery port 1023, the drug delivery port 1023 The quantity of the drug matches the viscosity of the drug, and is arranged such that when the drug is injected at a pressure of 0.5 atm to 1 atm, the flow rate of the drug in 60 seconds is not less than 3 mL. The medicines include gel medicines, plasma medicines or aqueous medicines. The number of the administration port 1023 is preferably set to one, and is arranged on the end surface of the administration cavity 1022, and the aperture of the administration port 1023 is the same as that of the administration cavity 1022. The inner diameter is the same. Under normal conditions of use, assuming that the pressure of the manual injection of drugs is constant at 1 atm, and the length of the administration cavity 1022 is 200mm～300mm, it can be known from the empirical fitting equation (formula 1 and formula 2) that the flow rate Q≥3mL in 60s (preferably is Not less than 3 mL and not more than 50 mL), the viscosity of the drug and the size of the administration port 1023 are related as follows:

对于高粘度的药物，粘度μ的范围为2500mPa.s～10000mPa.s，给药口1023的孔径D ₂可为2.0mm～3.0mm，药物例如为具有缓释作用的载药凝胶(通常具有较高的粘度)，例如由海藻酸盐、明胶、果胶、纤维素衍生物、淀粉及其衍生物、β-环糊精、聚维酮、聚乙烯醇、聚丙烯酸或凡士林等构建的载药凝胶； For high-viscosity drugs, the viscosity μ ranges from 2500mPa.s to 10000mPa.s, and the pore diameter D _{2 of the} administration port 1023 can be 2.0mm to 3.0mm. The drug is, for example, a drug-loaded gel with a slow-release effect (usually with (Higher viscosity), such as alginate, gelatin, pectin, cellulose derivatives, starch and its derivatives, β-cyclodextrin, povidone, polyvinyl alcohol, polyacrylic acid or petroleum jelly, etc. Medicated gel

例如，β-环糊精载药凝胶，粘度μ为2500mPa.s～3000mPa.s，给药口1023的孔径D ₂设置为2.0mm时，长度设置为200mm时，可在60s内完成4mL注射； For example, β-cyclodextrin drug-loaded gel, viscosity μ is 2500mPa.s～3000mPa.s, when the aperture D _{2 of the} administration port 1023 is set to 2.0mm, when the length is set to 200mm, 4mL injection can be completed in 60s ；

又例如，凡士林，粘度μ为9000mPa.s～10000mPa.s，给药口1023的孔径设置为3.0mm时，长度设置为200mm时，可在60s内完成6mL注射。For another example, petroleum jelly has a viscosity μ of 9000 mPa.s to 10000 mPa.s, when the aperture of the administration port 1023 is set to 3.0 mm, and the length is set to 200 mm, 6 mL injection can be completed in 60 seconds.

对于较高粘度的药物，粘度μ的范围为500mPa.s～2500mPa.s，给药口1023的孔径D ₂可为1.5mm～2.0mm，药物例如为***凝胶、透明质酸钠凝胶、羧甲基壳聚糖凝胶、***凝胶、HGH生长素凝胶、阿司匹林凝胶、布洛芬凝胶、利多卡因凝胶、盐酸奥布卡因凝胶、复方苯佐卡因凝胶、芬太尼凝胶或其他凝胶状药物； For pharmaceutical higher viscosity, μ is a viscosity range of 500mPa.s ~ 2500mPa.s, oral administration of D 1023 is the aperture ₂ may be 1.5mm ~ 2.0mm, drugs such as estradiol gel, sodium hyaluronate condensate Gel, carboxymethyl chitosan gel, progesterone gel, HGH auxin gel, aspirin gel, ibuprofen gel, lidocaine gel, obucaine hydrochloride gel, compound benzocaine Due to gel, fentanyl gel or other gel-like drugs;

例如，***凝胶，粘度μ为500mPa.s～700mPa.s，给药口1023的孔径D ₂设置为1.5mm时，长度设置为200mm时，可在30s内完成2.5mL注射，60s内至少完成5ml注射； For example, estradiol gel, μ is the viscosity 500mPa.s ~ 700mPa.s, oral administration of D ₂ disposed aperture 1023 is 1.5mm, the length is set to 200mm, the injection can be completed in 2.5mL 30s, 60s inner Complete at least 5ml injection;

又例如，利多卡因凝胶，粘度μ为2300mPa.s～2500mPa.s，给药口1023 的孔径D ₂设置为2.0mm时，长度设置为200mm时，可在60s内完成5mL注射。 For another example, lidocaine gel has a viscosity μ of 2300 mPa.s to 2500 mPa.s, when the aperture D _{2 of the} administration port 1023 is set to 2.0 mm, and the length is set to 200 mm, 5 mL injection can be completed within 60 seconds.

对于中等粘度的药物，粘度μ的范围为100mPa.s～500mPa.s，给药口1023的孔径D ₂可为1.0mm～1.5mm，长度设置为200mm时，药物例如为高浓度甘油溶液类或甘露醇等； For drugs with medium viscosity, the viscosity μ ranges from 100 mPa.s to 500 mPa.s, the pore diameter D _{2 of the} administration port 1023 can be 1.0 mm to 1.5 mm, and when the length is set to 200 mm, the drug is, for example, a high-concentration glycerin solution or Mannitol etc.;

例如，甘露醇，粘度μ为100mPa.s～150mPa.s，给药口1023的孔径D2设置为1.0mm时，长度设置为200mm时，可在60s内完成5ml注射；For example, when mannitol has a viscosity μ of 100mPa.s～150mPa.s, when the aperture D2 of the administration port 1023 is set to 1.0mm, when the length is set to 200mm, 5ml injection can be completed within 60s;

又例如，高浓度甘油润滑剂，粘度μ为400mPa.s～500mPa.s，给药口1023的孔径D ₂设置为1.5mm时，长度设置为200mm时，可在60s内至少完成5mL注射。 For another example, a high-concentration glycerin lubricant with a viscosity μ of 400 mPa.s to 500 mPa.s, when the aperture D _{2 of the} administration port 1023 is set to 1.5 mm, and when the length is set to 200 mm, at least 5 mL injection can be completed within 60 seconds.

对于较低粘度的水溶液类或甘油溶液类等药物，或者气体，粘度μ的范围为0.5mPa.s～100mPa.s，给药口1023的孔径可为0.5mm～1.0mm，药物例如为干细胞悬液、羊水、血浆、PRP(富血小板血浆)、***注射剂、孕激素、人绒毛膜***注射剂、***释放激素激动剂、枸橼酸西地那非、他莫昔芬、骨髓间充质干细胞、人脐带华通胶间充质干细胞、月经血子宫内膜干细胞、高压氧或臭氧等气体；For drugs with lower viscosity such as aqueous or glycerol solutions, or gases, the viscosity μ ranges from 0.5 mPa.s to 100 mPa.s, and the pore diameter of the administration port 1023 can be 0.5 mm to 1.0 mm. The drug is, for example, a stem cell suspension. Fluid, amniotic fluid, plasma, PRP (platelet rich plasma), progesterone injection, progesterone, human chorionic gonadotropin injection, gonadotropin releasing hormone agonist, sildenafil citrate, tamoxifen, bone marrow Mesenchymal stem cells, human umbilical cord Huatong glue mesenchymal stem cells, menstrual blood endometrial stem cells, hyperbaric oxygen or ozone and other gases;

例如，血浆，粘度μ为1.1mPa.s～1.3mPa.s，给药口1023的孔径D ₂置为0.5mm时，长度设置为200mm时，可在20s内完成10mL注射，60s内至少完成30ml注射； For example, plasma, μ is the viscosity of 1.1mPa.s ~ 1.3mPa.s, oral administration of D ₂ opposite the aperture 1023 is 0.5mm, the length is set to 200mm, the injection can be completed in 10mL 20s, 60s completed within at least 30ml injection;

又例如，甘油润滑剂，粘度μ为90mPa.s～100mPa.s，给药口1023的孔径D ₂设置为1.0mm时，长度设置为200mm时，可在60s内完成5mL注射。 For another example, when a glycerin lubricant has a viscosity μ of 90 mPa·s-100 mPa·s, when the aperture D _{2 of the} administration port 1023 is set to 1.0 mm, and the length is set to 200 mm, a 5 mL injection can be completed within 60 seconds.

可见，可以根据所用药物不同，选用具有相应的给药口规格的药物输送装置，在减少药物浪费的同时，可以在额定时间内完成药物输送，避免操作时间过长；而且，随着需要注射的药物的粘度降低，可相应降低给药腔1022的尺寸，以及相应的导管本体102及鞘管104的尺寸，进一步提升药物输送装置100在目标腔道内的通过性。It can be seen that a drug delivery device with corresponding dosing port specifications can be selected according to the different drugs used. While reducing drug waste, the drug delivery can be completed within the rated time, avoiding excessive operation time; and, as the injection is required The decrease in the viscosity of the drug can reduce the size of the drug delivery cavity 1022 and the corresponding sizes of the catheter body 102 and the sheath 104 to further improve the passability of the drug delivery device 100 in the target lumen.

请参考图4a和4b，在一实施例中，药物输送装置100被配置为用于雾化给药。例如，当所述药物的粘度为0.1mPa.s～100mPa.s时，给药口1023的孔径为0.1mm～0.5mm，给药口1023的数量至少为两个，设置于导管本体102的远端的端面或外环面，布置为在以2atm～4atm的压力注射所述药物时，所述药物呈喷雾状流出，可在最大限度节省药物的同时，实现均匀雾化给药，特别适用于在内镜下针对自然腔道中的病灶部位进行定向给药。例如，给药口1023分布在导管本体102的外环面，能够向四周定向给药，可用于气管等自然腔道给药。Referring to FIGS. 4a and 4b, in one embodiment, the drug delivery device 100 is configured for aerosolized drug delivery. For example, when the viscosity of the drug is 0.1 mPa.s to 100 mPa.s, the aperture of the drug delivery port 1023 is 0.1 mm to 0.5 mm, and the number of drug delivery ports 1023 is at least two, which are provided at the far end of the catheter body 102. The end surface or outer ring surface of the end is arranged so that when the drug is injected at a pressure of 2atm-4atm, the drug flows out in a spray form, which can save the drug to the maximum while achieving uniform atomized drug delivery. It is especially suitable for Under the endoscopy, targeted drug delivery is directed at the lesion site in the natural cavity. For example, the drug delivery ports 1023 are distributed on the outer circumferential surface of the catheter body 102, and can be used to administer drugs in all directions, and can be used for drug delivery in natural cavities such as trachea.

优选的，给药口1023出药方向与导管本体102的中轴线呈30°～150°夹角分布，所述至少两个给药口1023的出药方向可以一致，以实现定向给药，出药方向也可以不一致，以保证药物可喷洒至各个方向。Preferably, the drug delivery direction of the drug delivery port 1023 and the central axis of the catheter body 102 are distributed at an angle of 30° to 150°, and the drug delivery directions of the at least two drug delivery ports 1023 can be the same to achieve directional drug delivery. The direction of the medicine can also be inconsistent to ensure that the medicine can be sprayed in all directions.

给药口1023可环绕导管本体102的外环面分布，即如图4a-图4b所示的导管本体102的双侧(上下两侧)均具有雾化给药口1023，以实现均匀雾化给药。在另一实施例中，优选的，针对定向给药，导管本体102的远端可设置一定曲度(例如，导管本体102的远端设置为具有一定弧度)，给药口1023可设置于导管本体102的单侧，即靠近曲率中心的一侧或远离曲率中心的一侧，以实现定向给药。The drug delivery ports 1023 can be distributed around the outer ring surface of the catheter body 102, that is, as shown in Figs. 4a-4b, both sides (upper and lower sides) of the catheter body 102 have atomized drug delivery ports 1023 to achieve uniform atomization. Administration. In another embodiment, preferably, for directional drug delivery, the distal end of the catheter body 102 can be provided with a certain curvature (for example, the distal end of the catheter body 102 is set to have a certain curvature), and the drug delivery port 1023 can be provided on the catheter. One side of the body 102, that is, the side close to the center of curvature or the side far away from the center of curvature, can achieve targeted drug delivery.

请参考图5a-图5c，其为本发明一实施例的球囊103的结构示意图。如图5a-图5c所示，球囊103可为低硬度顺应性球囊，其充盈后的形状可贴合目标腔道内壁。球囊103可选用较低硬度(70A～30D)的医用塑料，例如聚酰胺、Pebax、聚氨酯、PE、PVC或硅胶等材料，或者选择两种或两种以上这些材料的混合物或复合材料。Please refer to FIGS. 5a-5c, which are schematic diagrams of the balloon 103 according to an embodiment of the present invention. As shown in Figs. 5a-5c, the balloon 103 can be a low-hardness compliant balloon, and its inflated shape can fit the inner wall of the target lumen. The balloon 103 can be selected from medical plastics with lower hardness (70A-30D), such as materials such as polyamide, Pebax, polyurethane, PE, PVC, or silicone, or a mixture or composite material of two or more of these materials.

请参考图6a-图6b，其为本发明一实施例的一种药物输送装置100的制备方法的示意图，包括如下步骤：Please refer to FIGS. 6a-6b, which are schematic diagrams of a method for preparing a drug delivery device 100 according to an embodiment of the present invention, which includes the following steps:

步骤一、准备一外导管102a和一内导管102b；Step 1: Prepare an outer catheter 102a and an inner catheter 102b;

步骤二、将外导管102a与一球囊103连接，球囊103位于外导管102a的远端，且外导管102a的远端预留超出球囊103的一超出区段102c；Step 2: Connect the outer catheter 102a to a balloon 103, the balloon 103 is located at the distal end of the outer catheter 102a, and the distal end of the outer catheter 102a is reserved beyond the balloon 103 by an overhanging section 102c;

步骤三、将内导管102b***外导管102a，并将内导管102b的远端与超出区段102c的至少部分区段通过加热熔融粘接，形成粘接段。Step 3: Insert the inner catheter 102b into the outer catheter 102a, and heat and melt the distal end of the inner catheter 102b and at least part of the section beyond the section 102c to form a bonding section.

可见，在制作完成后，外导管102a和内导管102b将构成导管本体102，外导管102a和内导管102b之间的间隙形成充盈腔1021，内导管102b的内腔为给药腔1022。优选的，超出区段102c的长度为15mm～20mm。优选的，在步骤三中，所述粘接段的长度为12mm～17mm。It can be seen that after the production is completed, the outer catheter 102a and the inner catheter 102b will constitute the catheter body 102, the gap between the outer catheter 102a and the inner catheter 102b will form a filling cavity 1021, and the inner cavity of the inner catheter 102b will be the drug delivery cavity 1022. Preferably, the length of the beyond section 102c is 15mm-20mm. Preferably, in step 3, the length of the bonding section is 12mm-17mm.

在一实施例中，所述制备方法用于制作导管本体102的远端端部相对充盈后的球囊103向内凹进的药物输送装置100，还包括下述步骤：In one embodiment, the preparation method is used to manufacture the drug delivery device 100 in which the distal end of the catheter body 102 is recessed inward relative to the filled balloon 103, and further includes the following steps:

步骤四、将内导管102b的远端与超出区段102c一起向内弯折进入球囊103内部；此处，“向内弯折”是指沿着内导管102b的轴线方向向近端弯折。 Step 4. Bend the distal end of the inner catheter 102b and the overhanging section 102c inward into the balloon 103; here, "inward bending" refers to bending proximally along the axial direction of the inner catheter 102b .

步骤五、若准备的内导管102b和外导管102a的远端端面皆贯通，则给药口1023为内导管102b远端端面的开口，若准备的内导管102b或外导管102a之一的远端端面封闭，则给药口1023通过在所述粘接段的远端端面和/或外环面扎孔得到，给药口1023的孔径通过所用针孔的尺寸控制。 Step 5. If the prepared inner catheter 102b and outer catheter 102a are both penetrated, the drug delivery port 1023 is the opening of the distal end of the inner catheter 102b. If the inner catheter 102b or the distal end of one of the outer catheter 102a is prepared If the end surface is closed, the drug delivery port 1023 is obtained by piercing a hole on the distal end surface and/or the outer ring surface of the bonding section, and the aperture of the drug delivery port 1023 is controlled by the size of the needle hole used.

在实际制作过程中，若准备的内导管102b和外导管102a的远端端面皆贯通，可仅执行上述步骤一至步骤三，以获得常规的药物输送装置100。此时，所述药物输送装置100的导管本体102的远端端部未相对充盈后的所述球囊103向内凹进，给药口1023为所述粘接段的远端端面的开口。若准备的内导管102b和外导管102a的远端端面之一封闭，可仅执行上述步骤一至步骤三、以及步骤五，以获得常规的药物输送装置100。此时，所述药物输送装置100的导管本体102的远端端部未相对充盈后的所述球囊103向内凹进，给药口1023通过在所述粘接段的远端端面和/或外环面扎孔得到。若准备的内导管102b和外导管102a的远端端面皆贯通，可仅执行上述步骤一至步骤四，以获得一种药物输送装置100，此时，导管本体102的远端端部相对充盈后的所述球囊103向内凹进，且给药口1023为所述粘接段的远端端面的开口。若准备的内导管102b和外导管102a的远端端面之一封闭，可执行上述步骤一至步骤五，以获得一种药物输送装置100，此时，导管本体102的远端端部相对充盈后的所述球囊103向内凹进，且给药口1023通过在所述粘接段的远端端面和/或外环面扎孔得到。In the actual manufacturing process, if the prepared inner catheter 102b and outer catheter 102a have both through the distal end surfaces, only the above steps 1 to 3 can be performed to obtain the conventional drug delivery device 100. At this time, the distal end of the catheter body 102 of the drug delivery device 100 is not recessed inward relative to the filled balloon 103, and the administration port 1023 is the opening of the distal end surface of the adhesive section. If one of the distal end surfaces of the prepared inner catheter 102b and outer catheter 102a is closed, only the above steps 1 to 3, and step 5 can be performed to obtain the conventional drug delivery device 100. At this time, the distal end of the catheter body 102 of the drug delivery device 100 is not recessed inward relative to the filled balloon 103, and the drug delivery port 1023 passes through the distal end surface of the adhesive section and/ Or pierce the outer ring surface. If the prepared inner catheter 102b and outer catheter 102a have both through the distal end surfaces, only the above steps 1 to 4 can be performed to obtain a drug delivery device 100. At this time, the distal end of the catheter body 102 is relatively inflated. The balloon 103 is recessed inward, and the drug delivery port 1023 is an opening on the distal end surface of the bonding section. If one of the prepared inner catheter 102b and outer catheter 102a has a closed distal end surface, the above steps 1 to 5 can be performed to obtain a drug delivery device 100. At this time, the distal end of the catheter body 102 is relatively inflated. The balloon 103 is recessed inward, and the drug delivery port 1023 is obtained by piercing a hole on the distal end surface and/or the outer ring surface of the bonding section.

在执行上述步骤四的实施例中，球囊103充盈后向导管远端和向四周扩张，进一步使得导管本体102的远端端部相对充盈后的所述球囊103向内凹进，避免导管本体102的远端刮伤目标腔道内壁。In the embodiment of performing step 4 above, the balloon 103 expands toward the distal end of the catheter and the surroundings after being inflated, so that the distal end of the catheter body 102 is recessed inward relative to the inflated balloon 103 to avoid the catheter The distal end of the body 102 scratches the inner wall of the target cavity.

还在一实施例中，所述制备方法用于制备用于雾化给药的药物输送装置100，还包括下述步骤：In still another embodiment, the preparation method is used to prepare the drug delivery device 100 for atomized administration, and further includes the following steps:

步骤四、若准备的内导管102b和外导管102a的远端端面皆贯通，则将所述粘接段的远端端面加热熔融封闭，接着在所述粘接段的外环面扎孔得到给药口1023，若准备的内导管102b或外导管102a之一的远端端面封闭，则给药口1023通过在所述粘接段的远端外环面扎孔得到，给药口1023的孔径通过所用针孔的尺寸控制。 Step 4. If the prepared inner tube 102b and outer tube 102a are both penetrated, the distal end surface of the bonding section is heated and melted and sealed, and then a hole is pierced on the outer ring surface of the bonding section. The medicine port 1023, if the distal end surface of one of the prepared inner catheter 102b or the outer catheter 102a is closed, the drug administration port 1023 is obtained by piercing the outer ring surface of the distal end of the bonding section. The aperture of the drug administration port 1023 Controlled by the size of the pinhole used.

以下以图1a-图7d所示的较佳的实施例说明本发明的药物输送装置100和药物输送***的工作原理。Hereinafter, the working principle of the drug delivery device 100 and the drug delivery system of the present invention will be described with the preferred embodiments shown in FIGS. 1a-7d.

工作时，球囊103初始处于折叠状态，并与导管本体102一起被装载于鞘管104之中。使用时，鞘管104首先进入目标腔道，然后在导丝106的支撑下，缓慢向前推送药物输送装置100，并在目标腔道曲度变化时，推动滑杆108，由滑杆108带动牵引绳107，从而带动导管本体102的远端端部一起移动弯曲。在观测到球囊103到达合适位置后，回撤鞘管104，使球囊103暴露于目标腔道中。导管本体102设置有充盈腔1021和给药腔1022。通过充盈腔1021向球囊103内注射一定体积的液体(无菌水，生理盐水等)或气体(空气等)，使其充盈并顺应目标腔道内部结构进行形变。然后拔出导丝106，并由给药腔1022注射所需药物，药物经由设置在导管本体102远端端面的给药口1023流出，并流经球囊103的外表面作用于目标腔道内壁，药物利用率较高。在给药的过程中同时通过与充盈腔1021和给药腔1022连接的压力监测及装置110监测和调节充盈腔1021和给药腔1022内的压力，可均匀给药，以及当压力超过预定值时，降低药物注射速率、停止注射药物和/或回抽部分药物，防止压力过大对目标腔道造成损伤。本实施例中，由于球囊103的外表面设置有涂层，所述涂层例如浸润性涂层，流出的药物将沿球囊103的外表面浸润扩散，并作用于目标腔道内壁，或者所述涂层例如防粘附涂层或者抗凝涂层，将减少药物在球囊103表面的吸附，进一步促进了均匀给药，并提高了药物利用率。In operation, the balloon 103 is initially in a folded state, and is loaded into the sheath 104 together with the catheter body 102. In use, the sheath 104 first enters the target lumen, and then slowly pushes the drug delivery device 100 forward under the support of the guide wire 106, and when the curvature of the target lumen changes, the sliding rod 108 is pushed and driven by the sliding rod 108 The pulling rope 107 drives the distal end of the catheter body 102 to move and bend together. After observing that the balloon 103 reaches the proper position, the sheath 104 is withdrawn to expose the balloon 103 to the target lumen. The catheter body 102 is provided with a filling cavity 1021 and a drug delivery cavity 1022. A certain volume of liquid (sterile water, physiological saline, etc.) or gas (air, etc.) is injected into the balloon 103 through the filling cavity 1021, so that it is filled and deformed to conform to the internal structure of the target cavity. Then the guide wire 106 is pulled out, and the required drug is injected from the drug delivery cavity 1022. The drug flows out through the drug delivery port 1023 provided on the distal end surface of the catheter body 102, and flows through the outer surface of the balloon 103 to act on the inner wall of the target lumen. , The drug utilization rate is high. In the process of drug delivery, the pressure monitoring and device 110 connected to the filling cavity 1021 and the drug delivery cavity 1022 is used to monitor and adjust the pressure in the filling cavity 1021 and the drug delivery cavity 1022 at the same time, so that the drug can be uniformly administered, and when the pressure exceeds a predetermined value At this time, reduce the drug injection rate, stop the drug injection and/or withdraw part of the drug to prevent excessive pressure from causing damage to the target cavity. In this embodiment, since the outer surface of the balloon 103 is provided with a coating, such as an infiltrating coating, the drug flowing out will infiltrate and diffuse along the outer surface of the balloon 103 and act on the inner wall of the target lumen, or The coating, such as an anti-adhesion coating or an anti-coagulation coating, will reduce the adsorption of the drug on the surface of the balloon 103, further promote uniform administration, and improve the utilization rate of the drug.

综上所述，在本发明的药物输送装置及其制备方法和药物输送***中，所述药物输送装置和所述药物输送***包括导管本体、球囊和压力监测及调节装置，所述球囊设置在所述导管本体的远端，所述导管本体具有相互隔离的充盈腔和给药腔，所述充盈腔和所述给药腔均与所述压力监测及调节装置连接。所述充盈腔用于充盈所述球囊，所述给药腔的远端设置至少一给药口，所述球囊充盈后的形状贴附于目标腔道内壁。药物可通过设置于所述导管本体的给药口直接输送至球囊外表面，经所述球囊的外表面作用于目标腔道内壁，给药效率和药物利用率较高。特别地，所述给药口的孔径和数量与所述药物的粘度相匹配并满足经验公式(公式1和公式2)，在所述压力监测及调节装置的监测和调节下，所述药物可经额定的压力和流量输送至目标腔道内壁，有助于均匀给药以及避免压力过大损伤目标腔道。所述球囊的外表面优选具有涂层，所述涂层被配置为与所述药物的特性相匹配，能够使所述药物沿球囊的外表面扩散，从而进一步促进均匀给药，并可减少药物吸附，提升药物利用率。In summary, in the drug delivery device and the preparation method thereof and the drug delivery system of the present invention, the drug delivery device and the drug delivery system include a catheter body, a balloon, and a pressure monitoring and adjusting device. It is arranged at the distal end of the catheter body, and the catheter body has a filling cavity and a drug delivery cavity that are isolated from each other, and both the inflation cavity and the drug delivery cavity are connected to the pressure monitoring and regulating device. The filling cavity is used to fill the balloon, and at least one drug delivery port is arranged at the distal end of the drug delivery cavity, and the filled shape of the balloon is attached to the inner wall of the target cavity. The drug can be directly delivered to the outer surface of the balloon through the drug delivery port provided in the catheter body, and act on the inner wall of the target lumen through the outer surface of the balloon, and the drug delivery efficiency and drug utilization rate are high. In particular, the aperture and number of the administration port match the viscosity of the drug and meet the empirical formula (Formula 1 and Formula 2). Under the monitoring and adjustment of the pressure monitoring and regulating device, the drug can be The rated pressure and flow rate are delivered to the inner wall of the target cavity, which helps to evenly administer the drug and avoid excessive pressure from damaging the target cavity. The outer surface of the balloon preferably has a coating, and the coating is configured to match the characteristics of the drug, so that the drug can be diffused along the outer surface of the balloon, thereby further promoting uniform administration, and Reduce drug adsorption and improve drug utilization.

所述球囊还优选为单层球囊，没有流经夹层造成的药物损耗，提高了药物利用率，折叠后的整体外径也较小，较易***目标腔道，降低了目标腔道损伤的几率，且规避了双层球囊的夹层被压缩而给药困难的问题。The balloon is also preferably a single-layer balloon. There is no drug loss caused by the interlayer, which improves the utilization rate of the drug. The overall outer diameter after folding is also small, which is easier to insert into the target cavity and reduces the damage of the target cavity. It also avoids the problem that the dissection of the double-layer balloon is compressed and the drug delivery is difficult.

特别地，所述导管本体的远端的端部光滑且相对充盈后的球囊向内凹进，能够避免对目标腔道造成二次伤害，以及所述药物输送***还可包括导丝，所述导丝的导丝本体的长度短于药物输送装置，且近端具有锁定接头的设置大为提高了使用安全性和便捷性。In particular, the distal end of the catheter body is smooth and recessed inward relative to the filled balloon, which can avoid secondary damage to the target lumen, and the drug delivery system may also include a guide wire, so The length of the guide wire body of the guide wire is shorter than that of the drug delivery device, and the provision of a locking joint at the proximal end greatly improves the safety and convenience of use.

又及，所述药物输送***还可包括牵引绳，所述牵引绳内置于导管本体的侧壁，所述牵引绳的远端端部固定于所述导管本体的内部的远端，近端与一活动部件连接，由所述活动部件的动作牵引所述牵引绳，并带动所述导管本体的远端端部一同移动弯曲，从而可顺利进入目标腔道，减少患者痛苦。Furthermore, the drug delivery system may further include a traction rope, the traction rope is built into the side wall of the catheter body, and the distal end of the traction rope is fixed to the inner distal end of the catheter body, and the proximal end is connected to the inner end of the catheter body. A movable part is connected, and the traction rope is pulled by the action of the movable part, and the distal end of the catheter body is driven to move and bend together, so as to smoothly enter the target cavity and reduce the pain of the patient.

上述描述仅是对本发明一些实施例的描述，并非对本发明范围的任何限定，本发明领域的普通技术人员根据上述揭示内容做的任何变更、修饰，均属于本发明的保护范围。The foregoing description is only a description of some embodiments of the present invention, and does not limit the scope of the present invention in any way. Any changes or modifications made by a person of ordinary skill in the field of the present invention based on the foregoing disclosure shall fall within the protection scope of the present invention.

Claims

一种药物输送装置，其特征在于，包括导管本体、球囊和压力监测及调节装置，所述导管本体和所述球囊相互连接，所述球囊设置在所述导管本体的远端，所述导管本体具有相互隔离的充盈腔和给药腔，所述充盈腔包裹所述给药腔，所述充盈腔用于向所述球囊输送充盈介质，所述充盈腔与所述给药腔均与所述压力监测及调节装置连接，所述球囊充盈后的形状贴附于目标腔道内壁，且所述给药腔的远端设置至少一给药口，所述给药腔通过所述给药口将药物输送至所述球囊的外表面，所述给药口的孔径、所述给药口的数量与所述药物的粘度相匹配，被配置为在一定的所述药物的注射压力下，所述药物能够以一定的体积流量进行输送，其中，所述给药口的孔径、所述给药口的数量、所述药物的注射压力和所述药物的体积流量满足下述公式：A drug delivery device, characterized in that it comprises a catheter body, a balloon, and a pressure monitoring and adjusting device, the catheter body and the balloon are connected to each other, and the balloon is arranged at the distal end of the catheter body, and The catheter body has a filling cavity and a medication cavity that are isolated from each other, the filling cavity envelops the medication cavity, the filling cavity is used to deliver the filling medium to the balloon, the filling cavity and the medication cavity Both are connected to the pressure monitoring and regulating device, the filled balloon is attached to the inner wall of the target cavity, and at least one drug delivery port is provided at the distal end of the drug delivery cavity, and the drug delivery cavity passes through the The drug delivery port delivers the drug to the outer surface of the balloon, and the aperture of the drug delivery port and the number of the drug delivery port match the viscosity of the drug, and are configured to be at a certain level of the drug. Under injection pressure, the drug can be delivered with a certain volume flow rate, wherein the aperture of the drug delivery port, the number of drug delivery ports, the injection pressure of the drug and the volume flow rate of the drug meet the following requirements formula:

其中，Q为所述药物的体积流量(mL/s)；μ为所述药物的粘度(mPa.s)；p为所述药物的注射压力(atm)；L1为所述给药腔的长度(mm)；L2为所述给药腔的壁厚(mm)；n为所述给药口的数量；D1为所述给药腔的内径(mm)；D2为所述给药口的理论孔径(mm)；D _实为所述给药口的实际孔径(mm)。 Wherein, Q is the volume flow of the drug (mL/s); μ is the viscosity of the drug (mPa.s); p is the injection pressure (atm) of the drug; L1 is the length of the dosing cavity (mm); L2 is the wall thickness of the dosing cavity (mm); n is the number of the dosing port; D1 is the inner diameter of the dosing cavity (mm); D2 is the theoretical of the dosing port Aperture (mm); D _is actually the actual aperture (mm) of the dosing port.
如权利要求1所述的药物输送装置，其特征在于，所述给药腔的长度配置为200mm～300mm，所述给药腔的壁厚配置为0.1mm～1.0mm，所述给药口的孔径、所述给药口的数量与所述药物的粘度相匹配，被布置为在以0.5atm～1atm的压力注射所述药物时，所述药物在60s内的流量不小于3mL。The drug delivery device according to claim 1, wherein the length of the drug delivery cavity is configured to be 200mm to 300mm, the wall thickness of the drug delivery cavity is configured to be 0.1mm to 1.0mm, and the size of the drug delivery port The aperture and the number of the administration ports are matched with the viscosity of the drug, and are arranged such that when the drug is injected at a pressure of 0.5 atm to 1 atm, the flow rate of the drug in 60 seconds is not less than 3 mL.
如权利要求2所述的药物输送装置，其特征在于，所述药物包括凝胶类药物、血浆类药物或水溶液类药物，所述给药口的数量设置为一个，所述给药口设置于所述给药腔的远端端面且所述给药口的孔径与所述给药腔的内径一致，其中：The drug delivery device according to claim 2, wherein the drug comprises a gel drug, a plasma drug or an aqueous solution drug, the number of the administration port is set to one, and the drug administration port is set at The distal end surface of the drug delivery cavity and the aperture of the drug delivery port are consistent with the inner diameter of the drug delivery cavity, wherein:

当所述药物的粘度为2500mPa.s～10000mPa.s时，所述给药口的孔径为2.0mm～3.0mm；When the viscosity of the drug is 2500mPa.s～10000mPa.s, the aperture of the administration port is 2.0mm～3.0mm;

当所述药物的粘度为500mPa.s～2500mPa.s时，所述给药口的孔径为1.5mm～2.0mm；When the viscosity of the drug is 500mPa.s～2500mPa.s, the aperture of the administration port is 1.5mm～2.0mm;

当所述药物的粘度为100mPa.s～500mPa.s时，所述给药口的孔径为1.0mm～1.5mm；When the viscosity of the drug is 100 mPa.s to 500 mPa.s, the aperture of the administration port is 1.0 mm to 1.5 mm;

当所述药物的粘度为0.5mPa.s～100mPa.s时，所述给药口的孔径为0.5mm～1.0mm。When the viscosity of the drug is 0.5 mPa.s to 100 mPa.s, the aperture of the administration port is 0.5 mm to 1.0 mm.
如权利要求1所述的药物输送装置，其特征在于，当所述药物的粘度为0.1mPa.s～100mPa.s时，所述给药口的孔径为0.1mm～0.5mm，所述给药口的数量至少为两个，所述至少两个给药口设置于所述导管本体的远端的外环面，并布置为在以2atm～4atm的压力注射所述药物时，所述药物呈喷雾状流出。The drug delivery device according to claim 1, wherein when the viscosity of the drug is 0.1 mPa.s to 100 mPa.s, the aperture of the drug delivery port is 0.1 mm to 0.5 mm, and the drug delivery The number of ports is at least two, and the at least two administration ports are provided on the outer annular surface of the distal end of the catheter body, and are arranged such that when the drug is injected at a pressure of 2atm-4atm, the drug is present Spray out.
如权利要求4所述的药物输送装置，其特征在于，所述给药口的出药方向与所述导管本体的中轴线呈30°～150°夹角。The drug delivery device according to claim 4, wherein the drug delivery direction of the drug delivery port and the central axis of the catheter body form an angle of 30° to 150°.
如权利要求4所述的药物输送装置，其特征在于，所述导管本体的远端具有曲度。The drug delivery device of claim 4, wherein the distal end of the catheter body has a curvature.
如权利要求1所述的药物输送装置，其特征在于，所述导管本体的远端的端部光滑且相对充盈后的所述球囊向内凹进。The drug delivery device according to claim 1, wherein the distal end of the catheter body is smooth and recessed inward relative to the filled balloon.
如权利要求1-7中任一项所述的药物输送装置，其特征在于，所述球囊的外表面设置有涂层，所述涂层被配置为与所述药物的特性相匹配，以降低球囊表面的药物吸附和/或使所述药物沿所述球囊的外表面浸润扩散：The drug delivery device according to any one of claims 1-7, wherein the outer surface of the balloon is provided with a coating, and the coating is configured to match the characteristics of the drug to To reduce the adsorption of the drug on the surface of the balloon and/or to infiltrate and diffuse the drug along the outer surface of the balloon:

当所述药物为水溶液类时，所述涂层被配置为亲水涂层，制造所述亲水涂层的材料包括聚乙烯吡咯烷酮，聚乙二醇二缩水甘油醚，聚乙烯醇，透明质酸，聚乙二醇中的任一种；When the drug is an aqueous solution, the coating is configured as a hydrophilic coating, and the material for making the hydrophilic coating includes polyvinylpyrrolidone, polyethylene glycol diglycidyl ether, polyvinyl alcohol, and hyaluronic acid Acid, any of polyethylene glycol;

当所述药物为血浆类时，所述涂层被配置为抗凝涂层，制造所述抗凝涂层的材料包括肝素，聚四氟乙烯，硅氧烷中的任一种。When the drug is plasma, the coating is configured as an anticoagulation coating, and the material for manufacturing the anticoagulation coating includes any one of heparin, polytetrafluoroethylene, and siloxane.
一种药物输送***，其特征在于，包括鞘管和如权利要求1-8中的任一项所述的药物输送装置；所述药物输送装置装载于所述鞘管内，以通过所述鞘管输送所述药物输送装置。A drug delivery system, comprising a sheath and the drug delivery device according to any one of claims 1-8; the drug delivery device is loaded in the sheath to pass through the sheath The drug delivery device is delivered.
如权利要求9所述的药物输送***，其特征在于，所述鞘管的远端设置有刻度标识。The drug delivery system according to claim 9, wherein the distal end of the sheath tube is provided with scale marks.
如权利要求9所述的药物输送***，其特征在于，还包括固定件，所述固定件设置于所述鞘管的近端，用于固定所述鞘管与所述导管的相对位置。9. The drug delivery system according to claim 9, further comprising a fixing member disposed at the proximal end of the sheath tube for fixing the relative position of the sheath tube and the catheter.
如权利要求9所述的药物输送***，其特征在于，还包括导丝，所述导丝可活动地***所述药物输送装置的给药腔，以支撑所述药物输送装置。9. The drug delivery system of claim 9, further comprising a guide wire, the guide wire movably inserted into the drug delivery cavity of the drug delivery device to support the drug delivery device.
如权利要求12所述的药物输送***，其特征在于，所述导丝包括导丝本体和锁定接头，所述锁定接头设置于所述导丝本体的近端，所述导丝本体的远端短于所述导管本体。The drug delivery system according to claim 12, wherein the guide wire comprises a guide wire body and a locking joint, the locking joint is disposed at the proximal end of the guide wire body, and the distal end of the guide wire body Shorter than the catheter body.
如权利要求9所述的药物输送***，其特征在于，还包括牵引绳，所述牵引绳内置于所述导管本体的侧壁中，所述牵引绳的远端固定于所述导管本体的内部的远端，所述牵引绳的近端与一活动部件连接，由所述活动部件的动作牵引所述牵引绳，并带动所述导管本体的远端的端部一同移动以弯曲。The drug delivery system according to claim 9, further comprising a traction rope, the traction rope is built into the side wall of the catheter body, and the distal end of the traction rope is fixed inside the catheter body The proximal end of the traction rope is connected with a movable part, and the traction rope is pulled by the action of the movable part, and the distal end of the catheter body is driven to move together to bend.
如权利要求14所述的药物输送***，其特征在于，所述活动部件为滑杆，通过推动所述滑杆牵引所述牵引绳，并带动所述导管本体的远端的端部一同移动以弯曲。The drug delivery system of claim 14, wherein the movable component is a sliding rod, and the traction rope is pulled by pushing the sliding rod, and the distal end of the catheter body is driven to move together to bending.
一种药物输送装置的制备方法，用于制备如权利要求1-8中的任一项所述的药物输送装置，其特征在于，包括如下步骤：A method for preparing a drug delivery device for preparing the drug delivery device according to any one of claims 1-8, characterized in that it comprises the following steps:

步骤一、准备一外导管和一内导管；Step 1: Prepare an outer catheter and an inner catheter;

步骤二、将所述外导管与一球囊连接，所述球囊位于所述外导管的远端，且所述外导管的远端预留超出所述球囊的一超出区段；Step 2: Connect the outer catheter to a balloon, the balloon is located at the distal end of the outer catheter, and the distal end of the outer catheter is reserved for an overhanging section beyond the balloon;

步骤三、将所述内导管***所述外导管，并将所述内导管的远端与所述超出区段的至少部分区段通过加热熔融粘接，形成粘接段。Step 3: Insert the inner catheter into the outer catheter, and heat and melt the distal end of the inner catheter and at least a part of the protruding section to form an adhesive section.
如权利要求16所述的药物输送装置的制备方法，其特征在于，所述超出区段的长度为15mm～20mm。The method for manufacturing a drug delivery device according to claim 16, wherein the length of the overhanging section is 15 mm to 20 mm.
如权利要求16所述的药物输送装置的制备方法，其特征在于，在步骤三中，所述粘接段的长度为12mm～17mm。The method for preparing a drug delivery device according to claim 16, wherein in step 3, the length of the bonding section is 12 mm to 17 mm.
如权利要求16所述的药物输送装置的制备方法，其特征在于，若所述导管本体的远端的端部光滑且相对充盈后的所述球囊向内凹进，则所述制备方法还包括以下步骤：The preparation method of the drug delivery device according to claim 16, wherein if the distal end of the catheter body is smooth and is recessed inward relative to the filled balloon, the preparation method is further It includes the following steps:

步骤四、将所述内导管的远端与所述超出区段一起向内弯折进入所述球囊内部；Step 4: Bend the distal end of the inner catheter and the overhanging section inwardly into the balloon;

步骤五、若准备的所述内导管和所述外导管的远端端面皆贯通，则所述给药口为所述内导管的远端端面的开口，若准备的所述内导管或所述外导管之一的远端端面封闭，则所述给药口通过在所述粘接段的远端的端面和/或外环面扎孔得到，所述给药口的孔径通过所用针孔的尺寸控制。Step 5. If the prepared inner catheter and the outer catheter are both penetrated, the drug delivery port is the opening of the distal end of the inner catheter, if the prepared inner catheter or the inner catheter The distal end surface of one of the outer catheters is closed, then the drug delivery port is obtained by piercing the end surface and/or the outer ring surface of the distal end of the bonding section, and the aperture of the drug delivery port passes through the needle hole used. Size control.
如权利要求16所述的药物输送装置的制备方法，其特征在于，若所述药物输送装置用于雾化给药，则所述制备方法还包括以下步骤：The method for preparing a drug delivery device according to claim 16, wherein if the drug delivery device is used for atomized administration, the preparation method further comprises the following steps:

步骤四、若准备的所述内导管和所述外导管的远端端面皆贯通，则将所述粘接段的远端端面加热熔融封闭，接着在所述粘接段的远端的外环面上扎孔得到所述给药口，若准备的所述内导管或所述外导管之一的远端的端面封闭，则直接在所述粘接段的远端的外环面上扎孔得到所述给药口，所述给药口的孔径通过所用针孔的尺寸控制。Step 4. If the prepared inner catheter and the outer catheter are both penetrated, the distal end of the bonding section is heated and melted and sealed, and then the outer ring at the distal end of the bonding section Puncture a hole on the surface to obtain the administration port, if the prepared inner catheter or one of the outer catheter is closed at the distal end surface, directly punch a hole on the outer ring surface of the distal end of the bonding section The administration port is obtained, and the aperture of the administration port is controlled by the size of the needle hole used.