技术领域technical field
本发明属于医疗器械领域，涉及载药器械及其制备方法。The invention belongs to the field of medical devices, and relates to a drug-loaded device and a preparation method thereof.
背景技术Background technique
腔内介入治疗相对于传统开放手术治疗具有创伤小、恢复快、并发症发生率低、疗效高等优点，逐渐成为血管外科医生治疗血管类病变的首选方式。Compared with traditional open surgery, endovascular interventional therapy has the advantages of less trauma, faster recovery, lower incidence of complications, and higher efficacy. It has gradually become the first choice for vascular surgeons to treat vascular lesions.
药物洗脱球囊(Drug Eluting Balloon，简称：DEB)属于腔内介入治疗方法之一，其原理是：将活性药物涂布于可扩张球囊表面，将可扩张球囊输送至人体病变部位后充压扩张，使得活性药物释放至血管壁并发挥药效。在DEB的生产过程中，需要将已涂布药物的可扩张球囊折翼并卷绕后套入保护套管中。Drug Eluting Balloon (Drug Eluting Balloon, referred to as: DEB) is one of the methods of intracavitary interventional therapy. The pressure expands, so that the active drug is released to the blood vessel wall and exerts its drug effect. During the production process of DEB, it is necessary to fold and wrap the drug-coated inflatable balloon into a protective sleeve.
药物洗脱支架(Drug Eluting Stent，简称：DES)也属于一种微创手术治疗方法，其原理是在裸支架表面涂布药物涂层，再将DES输送至人体病变部位并扩张，药物自涂层之中缓慢释放，持续发挥药效。DES在到达病变部位后，通常需要普通的可扩张球囊辅助扩张。因此，在DES的生产过程中，需要将DES压握到已折翼并卷绕的可扩张球囊外部，再将压握好的可扩张球囊和DES共同套入保护套管中。Drug Eluting Stent (DES for short) is also a minimally invasive surgical treatment method. Its principle is to apply a drug coating on the surface of the bare stent, and then deliver the DES to the lesion of the human body and expand it. It is released slowly in the layer and continues to exert its medicinal effect. After DES reaches the lesion site, it usually requires a common expandable balloon to assist in dilation. Therefore, in the production process of the DES, it is necessary to crimp the DES to the outside of the folded and wound expandable balloon, and then put the crimped expandable balloon and the DES into the protective sleeve together.
对于上述的载药式器械，保护套管具有保护药物涂层的作用，能避免药物涂层在生产、运输过程中遭到破坏。同时，保护套管可以将载药器械束缚至较小的外径尺寸，利于载药器械顺利通过迂曲的人体血管。For the above-mentioned drug-loaded device, the protective sleeve has the function of protecting the drug coating and can prevent the drug coating from being damaged during production and transportation. At the same time, the protective sleeve can bind the drug-loaded device to a smaller outer diameter, which is beneficial for the drug-loaded device to pass through the tortuous human blood vessels smoothly.
实际生产过程中，为了减小载药器械的轮廓尺寸，应选用内径较小的保护套管套设在载药器械的外部并紧紧束缚载药器械。但是，在将保护套管套设至载药器械外部的过程中，载药器械表面的药物涂层与保护套管内壁之间的摩擦不仅会破坏药物涂层，还会损伤器械本体。例如，导致可扩张球囊发生褶皱并损坏可扩张球囊本体，进而降低DEB的有效性；或者造成DES与可扩张球囊发生相对移位，进而影响DES在病变部位的定位和扩张，降低DES的安全性。In the actual production process, in order to reduce the outline size of the drug-loaded device, a protective sleeve with a smaller inner diameter should be used to cover the outside of the drug-loaded device and tightly bind the drug-loaded device. However, during the process of sheathing the protective sleeve to the outside of the drug-loaded device, the friction between the drug coating on the surface of the drug-loaded device and the inner wall of the protective sleeve will not only damage the drug coating, but also damage the device body. For example, causing folds and damage to the expandable balloon body, thereby reducing the effectiveness of DEB; or causing relative displacement between the DES and the expandable balloon, thereby affecting the positioning and expansion of the DES in the lesion, reducing the effectiveness of the DES security.
而内径较大的保护套管则会增大载药器械的轮廓尺寸，降低载药器械在人体管腔的通过性。并且，由于内径较大的保护套管对载药器械的约束力较低，会导致其对DEB的折翼的束缚力较弱，当DEB被置入人体，卷绕的折翼被高速的血流冲刷散开，也会导致原本被折翼覆盖的药物大量损失；或者导致原来压握在可扩张球囊上的DES在到达病变位置前脱落或者扩张，对病人造成伤害。However, a protective sleeve with a larger inner diameter will increase the outline size of the drug-loaded device and reduce the passage of the drug-loaded device in the human body lumen. Moreover, due to the lower binding force of the protective sleeve with a larger inner diameter on the drug-loaded device, it will cause weaker binding force on the DEB flaps. If the flow scours and disperses, it will also cause a large loss of the drug originally covered by the flap; or cause the DES that was originally pressed on the expandable balloon to fall off or expand before reaching the lesion, causing injury to the patient.
发明内容Contents of the invention
基于此，有必要提供一种载药器械，带有尺寸适宜的保护套管，该保护套管不仅可以将载药器械束缚至较小的外部轮廓，还能避免保护套管与药物涂层之间的摩擦力损伤药物涂层或者器械本体。Based on this, it is necessary to provide a drug-loaded device with an appropriately sized protective sleeve that can not only constrain the drug-loaded device to a smaller external profile, but also avoid the gap between the protective sleeve and the drug coating. The friction between them can damage the drug coating or the device body.
本发明提供的载药器械，包括器械本体及设于所述器械本体表面的药物涂层。所述载药器械具有收缩状态及扩张状态。所述载药器械在所述收缩状态时的外径较所述载药器械在所述扩张状态时的外径小。所述保护套管套设于所述载药器械的外部。所述保护套管由高分子材料制成。所述保护套管可在有机溶剂中发生溶胀。The drug-loaded device provided by the present invention includes a device body and a drug coating on the surface of the device body. The drug-loaded device has a contracted state and an expanded state. The outer diameter of the drug-loaded device in the contracted state is smaller than the outer diameter of the drug-loaded device in the expanded state. The protective sleeve is sheathed on the outside of the drug-loaded device. The protective sleeve is made of polymer material. The protective sleeve can swell in organic solvents.
在其中一个实施例中，所述保护套管在所述溶胀后的内径与所述保护套管在所述溶胀前的内径之比范围为(1.1～2)：1。本发明将所述保护套管在所述溶胀后的内径与所述保护套管在所述溶胀前的内径之比定义为所述保护套管的内径的溶胀度。溶胀度范围为(1.1～2)：1时，所述保护套管在溶胀后可以顺利地套设至器械本体的表面；并且可以减少保护套管在套设至器械本体的表面后，恢复至溶胀前的内径并紧紧束缚器械本体所需的时间。In one of the embodiments, the ratio of the inner diameter of the protective sleeve after swelling to the inner diameter of the protective sleeve before swelling is in the range of (1.1˜2):1. In the present invention, the ratio of the inner diameter of the protective sleeve after swelling to the inner diameter of the protective sleeve before swelling is defined as the degree of swelling of the inner diameter of the protective sleeve. The range of swelling degree is (1.1～2): when 1, the protective sleeve can be successfully sleeved on the surface of the device body after swelling; and it can reduce the recovery of the protective sleeve to the surface of the device body after being sleeved The inner diameter before swelling and the time required to tightly bind the device body.
在其中一个实施例中，所述高分子材料选自硅胶、聚烯烃、聚氨酯及聚氨酯改性聚合物中的至少一种。In one embodiment, the polymer material is selected from at least one of silica gel, polyolefin, polyurethane and polyurethane modified polymer.
在其中一个实施例中，所述有机溶剂选自甲醇、乙醇、丙酮、氯仿、四氢呋喃、二甲基亚砜或者碳原子个数范围为5个至16个的液态有机烷烃中的至少一种。In one embodiment, the organic solvent is at least one selected from methanol, ethanol, acetone, chloroform, tetrahydrofuran, dimethyl sulfoxide, or liquid organic alkanes with carbon atoms ranging from 5 to 16.
在其中一个实施例中，所述药物涂层包括活性药物。所述活性药物选自抗内膜增生药物、抗凝血药物、抗血小板粘附药物、抗感染药物、抗菌药物、抗炎症反应药物、抗过敏药物或者抗肿瘤药物中的至少一种。In one of the embodiments, the drug coating includes an active drug. The active drug is selected from at least one of anti-intimal hyperplasia drugs, anticoagulant drugs, anti-platelet adhesion drugs, anti-infection drugs, antibacterial drugs, anti-inflammatory drugs, anti-allergic drugs or anti-tumor drugs.
在其中一个实施例中，所述抗内膜增生药物选自依维莫司、雷帕霉素、紫杉醇、多西紫杉醇、紫杉酚、紫杉醇衍生物、普罗布考或者秋水仙碱中的至少一种。所述抗凝血药物选自肝素、华法林钠或者维生素K拮抗剂中的至少一种。所述抗血小板粘附药物选自阿司匹林、前列腺素、丹酚酸、硝酸脂类药物、赖氨匹林或者潘生丁中的至少一种。所述抗感染药物选自氨苄青霉素、头孢霉素、磺胺嘧啶或者硫酸链霉素中的至少一种。所述抗菌药物选自壳聚糖及其衍生物、头孢西丁、萘啶酸或者吡哌酸中的至少一种。所述抗肿瘤药物选自柔红霉素、阿霉素、卡铂或者大环内酯类中的至少一种。In one embodiment, the anti-intimal hyperplasia drug is selected from at least one of everolimus, rapamycin, paclitaxel, docetaxel, paclitaxel, paclitaxel derivatives, probucol or colchicine A sort of. The anticoagulant drug is selected from at least one of heparin, warfarin sodium or vitamin K antagonist. The anti-platelet adhesion drug is selected from at least one of aspirin, prostaglandin, salvianolic acid, nitrate lipid drug, lysine or dipyridamole. The anti-infection drug is selected from at least one of ampicillin, cephalosporin, sulfadiazine or streptomycin sulfate. The antibacterial drug is at least one selected from chitosan and its derivatives, cefoxitin, nalidixic acid or pipemidic acid. The antitumor drug is selected from at least one of daunorubicin, doxorubicin, carboplatin or macrolides.
在其中一个实施例中，所述活性药物选自雷帕霉素、雷帕霉素衍生物、紫杉醇或者紫杉醇衍生物中的至少一种。In one embodiment, the active drug is selected from at least one of rapamycin, rapamycin derivatives, paclitaxel or paclitaxel derivatives.
在其中一个实施例中，所述药物涂层还包括载体。所述载体选自含极性基团的小分子有机物或者高分子聚合物中的至少一种。所述极性基团包括-OH、-SO3H、-NH2、-NHR或者-COOH。In one of the embodiments, the drug coating further includes a carrier. The carrier is selected from at least one of small molecular organic substances containing polar groups or high molecular polymers. The polar group includes -OH, -SO3 H, -NH2 , -NHR or -COOH.
在其中一个实施例中，所述小分子有机物选自阿魏酸钠、L-苯丙氨酸、苯甲酸盐、蛋氨酸、脯氨酸、赖氨酸、亮氨酸、羟丙基-β-环糊精、山梨醇、L-缬氨酸、烟酰胺、乙酰胺、葡甲胺、L-异亮氨酸、葡萄糖、麦芽糖、吐温80、甘露醇、卵磷脂、色氨酸、L-苏氨酸、水杨酸、对氨基水杨酸钠、肝素钠或者维生素C中的至少一种。In one of the embodiments, the small molecule organic matter is selected from sodium ferulate, L-phenylalanine, benzoate, methionine, proline, lysine, leucine, hydroxypropyl-β -Cyclodextrin, Sorbitol, L-Valine, Nicotinamide, Acetamide, Meglumine, L-Isoleucine, Glucose, Maltose, Tween 80, Mannitol, Lecithin, Tryptophan, L - At least one of threonine, salicylic acid, sodium p-aminosalicylate, sodium heparin or vitamin C.
在其中一个实施例中，所述高分子聚合物选自聚乙二醇、聚赖氨酸、透明质酸钠、泊洛沙姆、聚乙烯基吡罗烷酮、聚乙烯醇、聚氧化乙烯、聚丙烯酸酯、聚丙烯酰胺、聚乳酸、聚乙醇酸、聚己内酯、聚乙交酯、乙交酯-丙交酯共聚物、聚二恶烷酮、聚羟基脂肪酸酯、聚三亚甲基碳酸酯、聚氨酯或者聚醚氨酯中的至少一种。In one of the embodiments, the polymer is selected from polyethylene glycol, polylysine, sodium hyaluronate, poloxamer, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide , polyacrylate, polyacrylamide, polylactic acid, polyglycolic acid, polycaprolactone, polyglycolide, glycolide-lactide copolymer, polydioxanone, polyhydroxyalkanoate, polysanya At least one of methyl carbonate, polyurethane or polyether urethane.
在其中一个实施例中，所述保护套管未溶胀前的轴向长度大于或者等于所述载药器械在所述收缩状态时的轴向长度。所述保护套管未溶胀前的内径小于或者等于所述载药器械在所述收缩状态时的外径。In one embodiment, the axial length of the protective sleeve before swelling is greater than or equal to the axial length of the drug-loaded device in the contracted state. The inner diameter of the protective sleeve before swelling is smaller than or equal to the outer diameter of the drug-loaded device in the contracted state.
在其中一个实施例中，所述保护套管的管体近端及管体远端之间沿所述保护套管的轴向设置至少一个凹槽，且所述凹槽的近端和/或远端具有切口。In one of the embodiments, at least one groove is arranged between the proximal end of the protective sleeve and the distal end of the protective sleeve along the axial direction of the protective sleeve, and the proximal end of the groove and/or The distal end has an incision.
在其中一个实施例中，所述切口沿所述保护套管的轴向的长度范围为5毫米至15毫米。In one embodiment, the length of the incision along the axial direction of the protective sleeve is in the range of 5 mm to 15 mm.
在其中一个实施例中，所述载药器械为介入式器械或者植入式器械。所述介入式器械包括药物球囊导管、造影导管、中心静脉导管、测压导管、导尿管或者一次性介入治疗仪探头。所述植入式器械包括药物洗脱支架、骨钉或者骨板。In one of the embodiments, the drug-loaded device is an interventional device or an implantable device. The interventional device includes a drug balloon catheter, a contrast catheter, a central venous catheter, a pressure measurement catheter, a urinary catheter or a disposable interventional therapy instrument probe. The implantable device includes a drug eluting stent, bone nail or bone plate.
本发明还提供所述带保护套管的载药器械的制作方法，包括以下步骤：The present invention also provides a manufacturing method of the drug-carrying device with a protective sleeve, comprising the following steps:
将所述药物涂层施加在所述器械本体表面，得到所述载药器械；将所述保护套管置于所述有机溶剂中使所述保护套管溶胀，得到溶胀的保护套管；将所述溶胀的保护套管套设于所述载药器械的外部并干燥，得到所述的载药器械。applying the drug coating on the surface of the device body to obtain the drug-loaded device; placing the protective sleeve in the organic solvent to swell the protective sleeve to obtain a swollen protective sleeve; The swollen protective sleeve is sheathed on the outside of the drug-loaded device and dried to obtain the drug-loaded device.
在其中一个实施例中，所述保护套管未溶胀前的轴向长度大于或者等于所述载药器械在所述收缩状态时的轴向长度。所述保护套管未溶胀前的内径小于或者等于所述载药器械在所述收缩状态时的外径。In one embodiment, the axial length of the protective sleeve before swelling is greater than or equal to the axial length of the drug-loaded device in the contracted state. The inner diameter of the protective sleeve before swelling is smaller than or equal to the outer diameter of the drug-loaded device in the contracted state.
在其中一个实施例中，在所述将所述溶胀的保护套管套设于所述载药器械的外部并干燥的步骤之前，所述制备方法还包括去除所述溶胀的保护套管表面的残留的有机溶剂的步骤。In one of the embodiments, before the step of sheathing the swollen protective sleeve on the outside of the drug-carrying device and drying it, the preparation method further includes removing the surface of the swollen protective sleeve. Residual organic solvent step.
在其中一个实施例中，所述保护套管的管体近端及管体远端之间沿所述保护套管的轴向设置至少一个凹槽，在所述去除所述溶胀的保护套管表面的残留的有机溶剂的步骤之后，所述制备方法还包括在所述凹槽的近端和/或远端形成切口的步骤。In one of the embodiments, at least one groove is provided between the proximal end of the protective sleeve and the distal end of the protective sleeve along the axial direction of the protective sleeve. After the step of removing the residual organic solvent from the surface, the preparation method further includes the step of forming an incision at the proximal end and/or the distal end of the groove.
在其中一个实施例中，所述溶胀的时间范围为5分钟至24小时。In one embodiment, the swelling time ranges from 5 minutes to 24 hours.
在其中一个实施例中，所述干燥包括常温晾干、鼓风干燥、真空干燥、冷冻干燥，或者于30℃至60℃加热干燥。In one embodiment, the drying includes air drying at room temperature, blast drying, vacuum drying, freeze drying, or heating drying at 30°C to 60°C.
与现有技术相比较，本发明至少具有以下有益效果：Compared with the prior art, the present invention has at least the following beneficial effects:
(1)本发明提供的载药器械中，保护套管由可被溶剂溶胀的高分子材料制成。在将保护套管套设于载药器械外部的过程中，先通过溶剂溶胀使保护套管内径变大，降低保护套管与载药器械之间的摩擦力，避免损伤载药器械的药物涂层或者器械本体.(1) In the drug-loaded device provided by the present invention, the protective sleeve is made of a polymer material that can be swelled by a solvent. In the process of setting the protective sleeve on the outside of the drug-loaded device, the inner diameter of the protective sleeve is enlarged by solvent swelling to reduce the friction between the protective sleeve and the drug-loaded device and avoid damage to the drug coating of the drug-loaded device. layer or device body.
(2)本发明提供的载药器械中，在保护套管套设于载药器械外部之后，随着保护套管中的溶剂逐渐挥发，保护套管逐渐收缩并最终恢复至初始内径，从而达到紧紧束缚载药器械的目的。(2) In the drug-loaded device provided by the present invention, after the protective sleeve is sheathed on the outside of the drug-loaded device, as the solvent in the protective sleeve gradually volatilizes, the protective sleeve gradually shrinks and finally returns to the original inner diameter, thereby achieving The purpose of tightly binding drug-loaded devices.
(3)本发明提供的载药器械被保护套管束缚至较小的轮廓外径，有利于载药器械在人体内部的弯曲管腔或者狭窄病变部位的可通过性。(3) The drug-loaded device provided by the present invention is constrained by the protective sleeve to a smaller profile outer diameter, which is beneficial to the passage of the drug-loaded device in curved lumens or narrow lesion parts inside the human body.
附图说明Description of drawings
图1为实施例一提供的药物洗脱球囊导管的结构示意图，药物洗脱球囊导管包括药物洗脱球囊本体及保护套管；Figure 1 is a schematic structural view of the drug-eluting balloon catheter provided in Example 1, the drug-eluting balloon catheter includes a drug-eluting balloon body and a protective sleeve;
图2a为图1中的保护套管沿A-A线的剖视图；Figure 2a is a sectional view of the protective sleeve in Figure 1 along the line A-A;
图2b为图1中的保护套管的另一种实施方式沿A-A线的剖视图；Fig. 2b is a cross-sectional view of another embodiment of the protective sleeve in Fig. 1 along line A-A;
图3为实施例四提供的药物洗脱支架的结构示意图。Fig. 3 is a schematic structural view of the drug-eluting stent provided in Example 4.
具体实施方式Detailed ways
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合附图及实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定本发明。In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention.
为了更加清楚地描述球囊导管及血管支架的结构，此处限定术语“近端”及“远端”为介入医疗领域惯用术语。具体而言，在介入医疗领域，“远端”表示手术操作过程中远离操作人员的一端，“近端”表示手术操作过程中靠近操作人员的一端。除非另有定义，本发明所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本发明在说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。In order to describe the structure of the balloon catheter and the vascular stent more clearly, the terms "proximal end" and "distal end" are defined here as commonly used terms in the field of interventional medicine. Specifically, in the field of interventional medicine, "distal end" means the end away from the operator during the surgical operation, and "near end" means the end close to the operator during the surgical operation. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by one of ordinary skill in the technical field of the present invention. The terms used in the description of the present invention are only for the purpose of describing specific embodiments, and are not intended to limit the present invention.
实施例一Embodiment one
请参见图1，实施例一提供的药物洗脱球囊导管100，包括药物洗脱球囊导管本体10及保护套管20。药物洗脱球囊导管本体10包括球囊导管11及药物涂层12。球囊导管11包括具有相对的近端及远端的导管111及设于导管111远端的可扩张球囊112(未充盈)。可扩张球囊112的外表面具有药物涂层12。在可扩张球囊112没有充压膨胀时，可扩张球囊112具有三个卷绕的折翼(图未示出)。近端显影环113及远端显影环114分别设于导管111靠近近端及靠近远端的管体外表面上。Referring to FIG. 1 , a drug-eluting balloon catheter 100 provided in Embodiment 1 includes a drug-eluting balloon catheter body 10 and a protective sleeve 20 . The drug-eluting balloon catheter body 10 includes a balloon catheter 11 and a drug coating 12 . The balloon catheter 11 includes a catheter 111 having opposing proximal and distal ends and an expandable balloon 112 (not inflated) disposed at the distal end of the catheter 111 . The outer surface of the expandable balloon 112 has a drug coating 12 . When the expandable balloon 112 is not inflated, the expandable balloon 112 has three folded flaps (not shown). The proximal developing ring 113 and the distal developing ring 114 are respectively disposed on the outer surface of the catheter 111 near the proximal end and near the distal end.
保护套管20由高分子材料制成。保护套管20套设于可扩张球囊112的外部并限制可扩张球囊112的三个卷绕的折翼展开。保护套管20由硅胶材料制成。该硅胶材料可以在溶剂中溶胀。故，保护套管20在溶剂中溶胀后包裹在可扩张球囊112的外部。保护套管20在溶胀后的内径与保护套管20在溶胀前的内径之比范围为(1.1～2)：1。保护套管20在溶胀后的内径与保护套管20在溶胀前的内径之比定义为保护套管20的内径的溶胀度。溶胀度范围为(1.1～2)：1时，保护套管20在溶胀后可以顺利地套设至可扩张球囊112的表面；并且可以减少保护套管20在套设至可扩张球囊112的表面后，恢复至溶胀前的内径并紧紧束缚可扩张球囊112所需的时间。具体地，本实施例中，保护套管20在溶胀后的内径与保护套管20在溶胀前的内径之比为1.3。The protective sleeve 20 is made of polymer material. The protective sleeve 20 is sleeved on the outside of the expandable balloon 112 and limits the expansion of the three coiled flaps of the expandable balloon 112 . The protective sleeve 20 is made of silicone material. The silica gel material is swellable in a solvent. Therefore, the protective sheath 20 is wrapped around the outside of the expandable balloon 112 after being swollen in the solvent. The ratio of the inner diameter of the protective sleeve 20 after swelling to the inner diameter of the protective sleeve 20 before swelling is in the range of (1.1˜2):1. The ratio of the inner diameter of the protective sleeve 20 after swelling to the inner diameter of the protective sleeve 20 before swelling is defined as the degree of swelling of the inner diameter of the protective sleeve 20 . The swelling degree ranges from (1.1 to 2): when 1, the protective sleeve 20 can be smoothly sleeved on the surface of the expandable balloon 112 after swelling; The time required to return to the pre-swelling inner diameter and tightly bind the expandable balloon 112 after the surface is removed. Specifically, in this embodiment, the ratio of the inner diameter of the protective sleeve 20 after swelling to the inner diameter of the protective sleeve 20 before swelling is 1.3.
保护套管20未溶胀前的轴向长度大于或者等于未充盈的可扩张球囊112的轴向长度，利于保护套管20经过溶胀再恢复至未溶胀前的轴向长度之后，可以完全包裹可扩张球囊112并保护药物涂层12。保护套管20未溶胀前的内径小于或者等于未充盈的可扩张球囊112的外径，利于保护套管20经过溶胀再恢复至未溶胀前的外径之后，可以将可扩张球囊112紧密束缚至较小的轮廓外径。优选地，本实施例中，保护套管20未溶胀前的轴向长度大于未充盈的可扩张球囊112的轴向长度。保护套管20未溶胀前的内径大致等于未充盈的可扩张球囊112的外径。The axial length of the protective sleeve 20 before swelling is greater than or equal to the axial length of the uninflated expandable balloon 112, which is beneficial for the protective sleeve 20 to fully wrap the expandable balloon 112 after being swollen and then restored to the axial length before swelling. The balloon 112 is inflated and the drug coating 12 is protected. The inner diameter of the protective sheath 20 before swelling is smaller than or equal to the outer diameter of the unfilled expandable balloon 112, which is beneficial for the expandable balloon 112 to be tightly packed after the protective sheath 20 is swollen and then restored to the outer diameter before swelling. Bound to smaller profile OD. Preferably, in this embodiment, the axial length of the protective sheath 20 before swelling is greater than the axial length of the inflatable balloon 112 . The uninflated inner diameter of the protective sheath 20 is approximately equal to the outer diameter of the uninflated expandable balloon 112 .
保护套管20的管体近端及管体远端之间沿保护套管20的轴向设置至少一个凹槽。凹槽在垂直于保护套管20的轴向的截面的形状可以为V形(如图2a)、C形(如图2b)或者其他形状。凹槽的近端及远端之中的至少一端具有切口。切口沿保护套管20的轴向的长度范围为5毫米至15毫米。优选地，本实施例中，保护套管20的管体近端及管体远端之间沿保护套管20的轴向设置第一凹槽(图未示出)及第二凹槽(图未示出)。第一凹槽及第二凹槽围绕保护套管20的中心轴呈对称设置。第一凹槽的近端具有第一切口21。第二凹槽的近端具有第二切口(图未示出)。第一切口21沿保护套管20的轴向的长度及第二切口沿保护套管20的轴向的长度均为10毫米。At least one groove is provided between the proximal end and the distal end of the protective sleeve 20 along the axial direction of the protective sleeve 20 . The cross section of the groove perpendicular to the axial direction of the protective sleeve 20 may be V-shaped (as shown in FIG. 2a ), C-shaped (as shown in FIG. 2b ) or other shapes. At least one of the proximal end and the distal end of the groove has a cutout. The length of the cut along the axial direction of the protective sleeve 20 ranges from 5 mm to 15 mm. Preferably, in this embodiment, a first groove (not shown in the figure) and a second groove (not shown in the figure) are arranged between the proximal end of the protective sleeve 20 and the distal end of the protective sleeve 20 along the axial direction of the protective sleeve 20. not shown). The first groove and the second groove are arranged symmetrically around the central axis of the protective sleeve 20 . The proximal end of the first groove has a first notch 21 . The proximal end of the second groove has a second cutout (not shown). The length of the first cutout 21 along the axial direction of the protective sleeve 20 and the length of the second cutout along the axial direction of the protective sleeve 20 are both 10 mm.
本实施例提供的药物洗脱球囊导管100的制备方法如下：The preparation method of the drug-eluting balloon catheter 100 provided in this embodiment is as follows:
第一步：以紫杉醇作为抗组织增生活性药物，将其与苯甲酸钠载体混合后溶于乙醇中配制药物涂层溶液。对球囊规格为4.0毫米×40毫米的PTA球囊导管进行等离子预处理。将药物涂层溶液喷涂至PTA球囊导管的可扩张球囊表面。常温晾干。再通过球囊折翼机将可扩张球囊折为三个翼并卷绕，得到药物洗脱球囊导管本体10。Step 1: Paclitaxel is used as an active anti-proliferation drug, which is mixed with sodium benzoate carrier and dissolved in ethanol to prepare a drug coating solution. Plasma pretreatment was performed on PTA balloon catheters with a balloon size of 4.0 mm × 40 mm. The drug coating solution is sprayed onto the expandable balloon surface of the PTA balloon catheter. Allow to dry at room temperature. Then, the expandable balloon is folded into three wings by a balloon wing folding machine and wound to obtain the drug-eluting balloon catheter body 10 .
第二步：在原始内径为0.043英寸、原始长度为70毫米的硅胶管的管体近端及管体远端之间沿硅胶管的轴向刻出两个凹槽，且两个凹槽围绕硅胶管的中心轴呈对称设置。然后将硅胶管置于乙醇溶剂中溶胀60分钟，测得硅胶管内径溶胀度为1.3。取出已经溶胀的硅胶管。将硅胶管内、外表面残留的乙醇溶剂常温吹干。用刀片将每个的凹槽的近端沿硅胶管的轴向切开一个轴向长度约为10毫米的切口，得到硅胶材料制成的保护套管20。Step 2: Carve two grooves along the axial direction of the silicone tube between the proximal end and the distal end of the silicone tube with an original inner diameter of 0.043 inches and an original length of 70 mm, and the two grooves surround The central axis of the silicone tube is arranged symmetrically. Then the silicone tube was swelled in an ethanol solvent for 60 minutes, and the swelling degree of the inner diameter of the silicone tube was measured to be 1.3. Remove the swollen silicone tubing. Dry the residual ethanol solvent on the inner and outer surfaces of the silicone tube at room temperature. Cut the proximal end of each groove with a blade along the axial direction of the silicone tube to make an incision with an axial length of about 10 mm to obtain a protective sleeve 20 made of silicone material.
第三步：将第一步得到的折翼卷绕后的药物洗脱球囊导管本体10的可扩张球囊112经由第二步的切口插入第二步得到的保护套管20之中，之后常温晾干2小时，直至保护套管20收缩至原始尺寸(即，内径为0.043英寸、长度为70毫米)，包装、灭菌，得到本实施例的药物洗脱球囊导管100。Step 3: insert the expandable balloon 112 of the drug-eluting balloon catheter body 10 obtained in the first step into the protective sleeve 20 obtained in the second step through the incision in the second step, and then Dry at room temperature for 2 hours until the protective sleeve 20 shrinks to the original size (ie, the inner diameter is 0.043 inches, and the length is 70 mm), then package and sterilize to obtain the drug-eluting balloon catheter 100 of this embodiment.
本实施例提供的药物洗脱球囊导管100，在使用时，只要操作者沿着凹槽的切口将保护套管20撕开并自可扩张球囊112的表面去除，即可连接外部球囊扩张压力泵，行普通的球囊扩张术。The drug-eluting balloon catheter 100 provided in this embodiment can be connected with an external balloon as long as the operator tears the protective sleeve 20 along the incision of the groove and removes it from the surface of the expandable balloon 112 during use. Dilation pressure pump, line common balloon dilation.
可以理解的是，本实施例提供的制备方法中，第一步和第二步的前后顺序可以互换。即，先制作保护套管20，再制作药物洗脱球囊导管本体10，后将药物洗脱球囊导管本体10的可扩张球囊112插入保护套管20之中，之后干燥、包装、灭菌，也可达到本发明的目的。It can be understood that, in the preparation method provided in this embodiment, the order of the first step and the second step can be interchanged. That is, first make the protective sleeve 20, then make the drug-eluting balloon catheter body 10, then insert the expandable balloon 112 of the drug-eluting balloon catheter body 10 into the protective sleeve 20, then dry, pack, and extinguish. Bacteria can also achieve the purpose of the present invention.
可以理解的是，本实施例提供的制备方法中，第二步包括将硅胶管内、外表面残留的乙醇溶剂常温吹干的步骤，在其他实施例中，也可以不包括此步骤。即，在其他实施例中，在取出已经溶胀的硅胶管之后，可以直接用刀片将硅胶管的凹槽的近端沿硅胶管的轴向切开一个轴向长度约为10毫米的切口，也可得到硅胶材料的保护套管20。然后将第一步得到的折翼卷绕后的药物洗脱球囊导管本体10的可扩张球囊112经由切口插入保护套管20之中，之后干燥、包装、灭菌，也可达到本发明的目的。It can be understood that, in the preparation method provided in this embodiment, the second step includes the step of drying the ethanol solvent remaining on the inner and outer surfaces of the silicone tube at room temperature, and in other embodiments, this step may not be included. That is, in other embodiments, after taking out the swollen silicone tube, the proximal end of the groove of the silicone tube can be directly cut with a blade along the axial direction of the silicone tube to make an incision with an axial length of about 10 mm. A protective sleeve 20 of silicone material is available. Then insert the expandable balloon 112 of the drug-eluting balloon catheter body 10 obtained in the first step into the protective sheath 20 through the incision, and then dry, pack and sterilize to achieve the present invention. the goal of.
可以理解的是，为避免影响药物洗脱球囊导管100的有效性，本实施例提供的制备方法中，带有药物涂层12的可扩张球囊112位于保护套管20的不具有切口的管体部分之中。It can be understood that, in order to avoid affecting the effectiveness of the drug-eluting balloon catheter 100, in the preparation method provided in this embodiment, the expandable balloon 112 with the drug coating 12 is located in the body part.
实施例二Embodiment two
本实施例提供的药物洗脱球囊导管的结构与实施例一提供的药物洗脱球囊导管的结构基本相同。区别之处在于，本实施例中，可扩张球囊的折翼数量为四个。保护套管的管体近端及管体远端之间沿保护套管的轴向设置三个凹槽。每个凹槽的远端具有切口。切口沿保护套管的轴向的长度为5毫米。并且保护套管的材料与实施例一的保护套管的材料不同。The structure of the drug-eluting balloon catheter provided in this embodiment is basically the same as that of the drug-eluting balloon catheter provided in Embodiment 1. The difference is that, in this embodiment, the number of flaps of the expandable balloon is four. Three grooves are arranged between the proximal end and the distal end of the protective sleeve along the axial direction of the protective sleeve. The distal end of each groove has an incision. The length of the incision in the axial direction of the protective sleeve is 5 mm. And the material of the protective sleeve is different from that of the protective sleeve in the first embodiment.
本实施例提供的药物洗脱球囊导管的制备方法如下：The preparation method of the drug-eluting balloon catheter provided in this embodiment is as follows:
第一步：以雷帕霉素作为抗组织增生活性药物，将其与苯甲酸钠载体及聚乙二醇载体混合后溶于甲醇中配制药物涂层溶液。对球囊规格为5.0毫米×60毫米的PTA球囊导管进行等离子预处理。将药物涂层溶液喷涂至PTA球囊导管的可扩张球囊表面。常温晾干。再通过球囊折翼机将可扩张球囊折为四个翼并卷绕，得到药物洗脱球囊导管本体。The first step: using rapamycin as an active anti-proliferation drug, mixing it with a sodium benzoate carrier and a polyethylene glycol carrier, and then dissolving it in methanol to prepare a drug coating solution. Plasma pretreatment was performed on PTA balloon catheters with a balloon size of 5.0 mm × 60 mm. The drug coating solution is sprayed onto the expandable balloon surface of the PTA balloon catheter. Allow to dry at room temperature. Then, the expandable balloon is folded into four wings by a balloon wing folding machine and wound to obtain the main body of the drug-eluting balloon catheter.
第二步：将原始内径为0.049英寸、原始长度为90毫米的聚乙烯管的管体近端及管体远端之间沿聚乙烯管的轴向刻出三个凹槽，且三个凹槽围绕聚乙烯管的中心轴呈对称设置。然后将聚乙烯管置于正庚烷溶剂中溶胀24小时，测得聚乙烯管内径溶胀度为2。取出已经溶胀的聚乙烯管。将聚乙烯管内、外表面残留的正庚烷溶剂常温吹干。用刀片将每个凹槽的远端沿聚乙烯管的轴向切开一个轴向长度约为5毫米的切口，得到聚乙烯材料制成的保护套管。Step 2: Carve three grooves along the axial direction of the polyethylene pipe between the proximal end and the distal end of the polyethylene pipe with an original inner diameter of 0.049 inches and an original length of 90 mm, and the three grooves The grooves are arranged symmetrically around the central axis of the polyethylene pipe. Then the polyethylene pipe was placed in n-heptane solvent to swell for 24 hours, and the inner diameter swelling degree of the polyethylene pipe was measured to be 2. Remove the swollen polyethylene tubing. Dry the n-heptane solvent remaining on the inner and outer surfaces of the polyethylene tube at room temperature. Use a blade to cut the distal end of each groove along the axial direction of the polyethylene tube into an incision with an axial length of about 5 mm to obtain a protective sleeve made of polyethylene material.
第三步：将第一步得到的折翼卷绕后的药物洗脱球囊导管本体的可扩张球囊经由第二步的切口插入第二步得到的保护套管中，并确保可扩张球囊位于保护套管的不具有切口的管体部分之中。之后于30℃鼓风干燥24小时，直至保护套管收缩至原始尺寸(即，内径为0.049英寸、长度为90毫米)。包装、灭菌，得到本实施例的药物洗脱球囊导管。Step 3: Insert the expandable balloon of the drug-eluting balloon catheter body obtained in the first step into the protective sleeve obtained in the second step through the incision in the second step, and ensure that the expandable balloon The bladder is located in the body portion of the protective sheath that has no cutouts. After that, it was air-dried at 30° C. for 24 hours until the protective sleeve shrunk to its original size (ie, the inner diameter was 0.049 inch and the length was 90 mm). Pack and sterilize to obtain the drug-eluting balloon catheter of this embodiment.
实施例三Embodiment Three
本实施例提供的药物洗脱球囊导管的结构与实施例一提供的药物洗脱球囊导管的结构基本相同。区别之处在于，本实施例中，可扩张球囊的折翼数量为六个。保护套管的管体近端及管体远端之间沿保护套管的轴向设置一个凹槽。凹槽的近端及远端均具有切口。切口沿保护套管的轴向的长度为15毫米。并且保护套管的材料与实施例一的保护套管的材料不同。The structure of the drug-eluting balloon catheter provided in this embodiment is basically the same as that of the drug-eluting balloon catheter provided in Embodiment 1. The difference is that in this embodiment, the number of flaps of the expandable balloon is six. A groove is arranged between the proximal end of the protective sleeve and the distal end of the protective sleeve along the axial direction of the protective sleeve. Both the proximal end and the distal end of the groove have cutouts. The length of the incision in the axial direction of the protective sleeve is 15 mm. And the material of the protective sleeve is different from that of the protective sleeve in the first embodiment.
本实施例提供的药物洗脱球囊导管的制备方法如下：The preparation method of the drug-eluting balloon catheter provided in this embodiment is as follows:
第一步：以紫杉醇作为抗组织增生活性药物，将其与聚乙二醇载体混合后溶于丙酮中配制药物涂层溶液。对球囊规格为6.0毫米×80毫米的PTA球囊导管进行等离子预处理。将药物涂层溶液刷涂至PTA球囊导管的可扩张球囊表面。常温晾干。再通过球囊折翼机将可扩张球囊折为六个翼并卷绕，得到药物洗脱球囊导管本体。Step 1: Paclitaxel is used as an anti-tissue hyperplasia active drug, which is mixed with a polyethylene glycol carrier and dissolved in acetone to prepare a drug coating solution. Plasma pretreatment was performed on PTA balloon catheters with a balloon size of 6.0 mm × 80 mm. Brush the drug coating solution onto the expandable balloon surface of the PTA balloon catheter. Allow to dry at room temperature. Then, the expandable balloon is folded into six wings by a balloon wing folding machine and wound to obtain the main body of the drug-eluting balloon catheter.
第二步：在原始内径为0.053英寸、原始长度为110毫米的聚氨酯管的管体近端及管体远端之间沿硅胶管的轴向刻出一个凹槽。然后将聚氨酯管置于四氢呋喃溶剂中溶胀5分钟，测得聚氨酯管内径溶胀度为1.1。取出已经溶胀的聚氨酯管。将聚氨酯管内外表面残留的四氢呋喃溶剂常温吹干。用刀片将凹槽的近端及远端均沿聚氨酯管的轴向切开一个轴向长度约为15毫米的切口，得到聚氨酯材料制成的保护套管。Step 2: Carve a groove along the axial direction of the silicone tube between the proximal end and the distal end of the polyurethane tube with an original inner diameter of 0.053 inches and an original length of 110 mm. Then the polyurethane tube was swelled in tetrahydrofuran solvent for 5 minutes, and the swelling degree of the inner diameter of the polyurethane tube was measured to be 1.1. Remove the swollen polyurethane tubing. Dry the residual tetrahydrofuran solvent on the inner and outer surfaces of the polyurethane tube at room temperature. A slit with an axial length of about 15 mm is cut along the axial direction of the polyurethane tube at both the proximal end and the distal end of the groove with a blade to obtain a protective sleeve made of polyurethane material.
第三步：将第一步得到的折翼卷绕后的药物洗脱球囊导管本体的可扩张球囊经由第二步的切口插入第二步得到的保护套管中，并确保可扩张球囊位于保护套管的不具有切口的管体部分之中。之后于45℃真空干燥5min，直至保护套管收缩至原始尺寸(即，内径为0.053英寸、长度为110毫米)，包装、灭菌，得到本实施例的带保护套管的药物洗脱球囊导管。Step 3: Insert the expandable balloon of the drug-eluting balloon catheter body obtained in the first step into the protective sleeve obtained in the second step through the incision in the second step, and ensure that the expandable balloon The bladder is located in the body portion of the protective sheath that has no cutouts. Then vacuum-dry at 45°C for 5 minutes until the protective sleeve shrinks to the original size (that is, the inner diameter is 0.053 inches and the length is 110 mm), packaged and sterilized to obtain the drug-eluting balloon with a protective sleeve of this embodiment catheter.
实施例四Embodiment Four
请参见图3，实施例四提供的药物洗脱支架300，包括药物洗脱支架本体30及保护套管40。药物洗脱支架本体30具有收缩状态及扩张状态。药物洗脱支架本体30在收缩状态时的外径较药物洗脱支架本体30在扩张状态时的外径小。药物洗脱支架本体30通过压握机或者其他工装夹具压握在可扩张球囊50(未充盈)外部。在可扩张球囊50没有充压膨胀时，可扩张球囊50具有三个卷绕的折翼(图未示出)。保护套管40紧密套设于药物洗脱支架本体30的外部，并限制可扩张球囊50的卷绕的折翼展开。Referring to FIG. 3 , the drug-eluting stent 300 provided in the fourth embodiment includes a drug-eluting stent body 30 and a protective sleeve 40 . The drug-eluting stent body 30 has a contracted state and an expanded state. The outer diameter of the drug-eluting stent body 30 in the contracted state is smaller than the outer diameter of the drug-eluting stent body 30 in the expanded state. The drug-eluting stent body 30 is crimped on the outside of the expandable balloon 50 (not inflated) by a crimping machine or other fixtures. When the expandable balloon 50 is not inflated, the expandable balloon 50 has three folded flaps (not shown). The protective sleeve 40 is tightly sleeved on the outside of the drug-eluting stent body 30 and limits the expansion of the coiled flaps of the expandable balloon 50 .
药物洗脱支架本体30包括裸支架31及设于裸支架31外表面的药物涂层32。The drug eluting stent body 30 includes a bare stent 31 and a drug coating 32 disposed on the outer surface of the bare stent 31 .
保护套管40由硅胶材料制成。该硅胶材料可在溶剂中发生溶胀。故，保护套管40在溶剂中溶胀后紧密包裹在药物洗脱支架本体30的外部。保护套管40在溶胀前的轴向长度大于或者等于药物洗脱支架本体30在收缩状态时的轴向长度，利于保护套管40完全包裹收缩状态的药物洗脱支架本体30。保护套管40未溶胀前的内径小于或者等于药物洗脱支架本体30在收缩状态时的外径，利于保护套管40将收缩状态的药物洗脱支架本体30紧密束缚至较小的轮廓外径。优选地，在本实施例中，保护套管40的轴向长度大于药物洗脱支架本体30在收缩状态时的轴向长度。保护套管40未溶胀前的内径等于药物洗脱支架本体30在收缩状态时的外径。The protective sleeve 40 is made of silicone material. The silicone material is swellable in solvents. Therefore, the protective sleeve 40 is tightly wrapped on the outside of the drug-eluting stent body 30 after being swollen in the solvent. The axial length of the protective sleeve 40 before swelling is greater than or equal to the axial length of the drug-eluting stent body 30 in the contracted state, which is beneficial for the protective sleeve 40 to completely wrap the drug-eluting stent body 30 in the contracted state. The inner diameter of the protective sleeve 40 before swelling is smaller than or equal to the outer diameter of the drug-eluting stent body 30 in the contracted state, which is beneficial for the protective sleeve 40 to tightly bind the drug-eluting stent body 30 in the contracted state to a smaller profile outer diameter . Preferably, in this embodiment, the axial length of the protective sleeve 40 is greater than the axial length of the drug-eluting stent body 30 in the contracted state. The inner diameter of the protective sleeve 40 before swelling is equal to the outer diameter of the drug-eluting stent body 30 in a contracted state.
保护套管40的管体近端及管体远端之间沿保护套管40的轴向设置至少一个凹槽，且凹槽的近端及远端之中的至少一端具有切口。切口沿保护套管40的轴向的长度范围为5毫米至15毫米。优选地，本实施例中，保护套管40的管体近端及管体远端之间沿保护套管40的轴向设置第一凹槽(图未示出)及第二凹槽(图未示出)。第一凹槽及第二凹槽围绕保护套管40的中心轴呈轴向对称。第一凹槽的近端具有第一切口41。第二凹槽42的近端具有第二切口(图未示出)。第一切口41沿保护套管40的轴向的长度及第二切口沿保护套管40的轴向的长度均为10毫米。At least one groove is provided between the proximal end and the distal end of the protective sleeve 40 along the axial direction of the protective sleeve 40 , and at least one of the proximal end and the distal end of the groove has a cutout. The length of the cut along the axial direction of the protective sleeve 40 ranges from 5 mm to 15 mm. Preferably, in this embodiment, a first groove (not shown in the figure) and a second groove (not shown in the figure) are arranged between the proximal end of the protective sleeve 40 and the distal end of the protective sleeve 40 along the axial direction of the protective sleeve 40. not shown). The first groove and the second groove are axially symmetrical around the central axis of the protection sleeve 40 . The proximal end of the first groove has a first notch 41 . The proximal end of the second groove 42 has a second cutout (not shown). The length of the first cutout 41 along the axial direction of the protective sleeve 40 and the length of the second cutout along the axial direction of the protective sleeve 40 are both 10 mm.
本实施例提供的药物洗脱支架300的制备方法如下：The preparation method of the drug-eluting stent 300 provided in this embodiment is as follows:
第一步：以雷帕霉素作为抗组织增生活性药物，将其与聚乳酸载体混合后溶于四氢呋喃中配制药物涂层溶液。将药物涂层溶液滴涂在规格为4.0毫米×38毫米的铁基合金支架表面，于30℃鼓风干燥至恒重，得到药物洗脱支架本体30。然后对球囊规格为4.0毫米×40毫米的球囊导管进行等离子预处理。再通过球囊折翼机将球囊导管的可扩张球囊折为三个翼并卷绕。采用压握机将药物洗脱支架本体30压握在可扩张球囊50的外部。The first step: using rapamycin as an anti-tissue hyperplasia drug, mixing it with a polylactic acid carrier and dissolving it in tetrahydrofuran to prepare a drug coating solution. The drug-eluting stent body 30 was obtained by drip-coating the drug coating solution on the surface of the iron-based alloy stent with a size of 4.0 mm×38 mm, and blowing and drying at 30° C. until constant weight. A balloon catheter with a balloon size of 4.0 mm x 40 mm was then plasma pretreated. Then, the expandable balloon of the balloon catheter is folded into three wings by a balloon wing folding machine and coiled. A crimping machine is used to crimp the drug-eluting stent body 30 on the outside of the expandable balloon 50 .
第二步：将原始内径为0.044英寸、原始长度为70毫米的硅胶管的管体近端及管体远端之间沿硅胶管的轴向刻出两个凹槽，且两个凹槽围绕硅胶管的中心轴呈对称设置。然后将硅胶管置于乙醇溶剂中溶胀60分钟，测得硅胶管内径溶胀度为1.4。取出已经溶胀的硅胶管。将硅胶管内、外表面残留的乙醇溶剂常温吹干。用刀片将每个凹槽的近端沿硅胶管的轴向切开一个轴向长度约为10毫米的切口，得到硅胶材料制成的保护套管40。Step 2: Carve two grooves along the axial direction of the silicone tube between the proximal end and the distal end of the silicone tube with an original inner diameter of 0.044 inches and an original length of 70 mm, and the two grooves surround The central axis of the silicone tube is arranged symmetrically. Then the silicone tube was swelled in ethanol solvent for 60 minutes, and the swelling degree of the inner diameter of the silicone tube was measured to be 1.4. Remove the swollen silicone tubing. Dry the residual ethanol solvent on the inner and outer surfaces of the silicone tube at room temperature. Cut the proximal end of each groove with a blade along the axial direction of the silicone tube to make an incision with an axial length of about 10 mm to obtain a protective sleeve 40 made of silicone material.
第三步：将第一步得到的压握在可扩张球囊50表面的药物洗脱支架本体30经由第二步的切口插入第二步得到的保护套管40中，并确保药物洗脱支架本体30位于保护套管的不具有切口的管体部分之中。之后于60℃鼓风干燥1小时，直至保护套管40收缩至原始尺寸(即，内径为0.044英寸、长度为70毫米)。包装、灭菌，得到本实施例的药物洗脱支架300。The third step: insert the drug-eluting stent body 30 obtained in the first step and pressed on the surface of the expandable balloon 50 into the protective sleeve 40 obtained in the second step through the incision in the second step, and ensure that the drug-eluting stent The body 30 is located in the body portion of the protective sleeve that has no cutouts. Afterwards, air-dry at 60° C. for 1 hour until the protective sleeve 40 shrinks to the original size (ie, the inner diameter is 0.044 inch, and the length is 70 mm). Package and sterilize to obtain the drug-eluting stent 300 of this embodiment.
本实施例提供的药物洗脱支架300，在使用时，只要操作者沿着凹槽的切口将保护套管40撕开并自药物洗脱支架本体30的表面去除，即可进行普通的支架植入术。For the drug-eluting stent 300 provided in this embodiment, when in use, as long as the operator tears the protective sleeve 40 along the incision of the groove and removes it from the surface of the drug-eluting stent body 30, ordinary stent implantation can be performed. into surgery.
实施例五Embodiment five
本实施例提供的药物洗脱支架的结构与实施例四提供的药物洗脱支架的结构基本相同。区别之处在于，本实施例中，药物洗脱支架的裸支架的材料与实施例四提供的药物洗脱支架的裸支架的材料不同。保护套管的管体近端及管体远端之间沿保护套管的轴向设置一个凹槽。凹槽的远端具有切口。切口沿保护套管的轴向的长度为15毫米。并且保护套管的材料与实施例四的保护套管的材料不同。The structure of the drug-eluting stent provided in this embodiment is basically the same as that of the drug-eluting stent provided in Embodiment 4. The difference is that, in this embodiment, the material of the bare stent of the drug-eluting stent is different from that of the bare stent of the drug-eluting stent provided in Embodiment 4. A groove is arranged between the proximal end of the protective sleeve and the distal end of the protective sleeve along the axial direction of the protective sleeve. The distal end of the groove has an incision. The length of the incision in the axial direction of the protective sleeve is 15 mm. And the material of the protective sleeve is different from that of the protective sleeve in the fourth embodiment.
本实施例提供的药物洗脱支架的制备方法如下：The preparation method of the drug-eluting stent provided in this embodiment is as follows:
第一步：以依维莫司作为抗组织增生活性药物，将其与聚己内酯载体混合后溶于乙醇中配制药物涂层溶液。将药物涂层溶液滴涂在规格为5.0毫米×58毫米的纯铁支架表面，于30℃鼓风干燥至恒重，得到药物洗脱支架本体。对球囊规格为5.0毫米×60毫米的球囊导管进行等离子预处理。再通过球囊折翼机将球囊导管的可扩张球囊折为三个翼并卷绕。采用压握机将药物洗脱支架本体压握在可扩张球囊的外部。The first step: using everolimus as an anti-tissue hyperplasia active drug, mixing it with a polycaprolactone carrier and dissolving it in ethanol to prepare a drug coating solution. The drug coating solution was drip-coated on the surface of a pure iron stent with a specification of 5.0 mm×58 mm, and dried at 30° C. to a constant weight to obtain a drug-eluting stent body. Plasma pretreatment was performed on balloon catheters with a balloon size of 5.0 mm x 60 mm. Then, the expandable balloon of the balloon catheter is folded into three wings by a balloon wing folding machine and coiled. A crimping machine is used to crimp the main body of the drug-eluting stent on the outside of the expandable balloon.
第二步：将原始内径为0.049英寸、原始长度为70毫米的聚乙烯管的管体近端及管体远端之间沿聚乙烯管的轴向刻出一个凹槽。然后将聚乙烯管置于丙酮溶剂中溶胀30分钟，测得聚乙烯管内径溶胀度为1.1。取出已经溶胀的聚乙烯管。将聚乙烯管内、外表面残留的丙酮溶剂常温吹干。用刀片将凹槽的远端沿聚乙烯管的轴向切开一个轴向长度约为15毫米的切口，得到聚乙烯材料制成的保护套管。Step 2: Carve a groove along the axial direction of the polyethylene pipe between the proximal end and the distal end of the polyethylene pipe with an original inner diameter of 0.049 inches and an original length of 70 mm. Then the polyethylene pipe was swelled in acetone solvent for 30 minutes, and the swelling degree of the inner diameter of the polyethylene pipe was measured to be 1.1. Remove the swollen polyethylene tubing. Dry the acetone solvent remaining on the inner and outer surfaces of the polyethylene tube at room temperature. Use a blade to cut the distal end of the groove along the axial direction of the polyethylene tube into an incision with an axial length of about 15 mm to obtain a protective sleeve made of polyethylene material.
第三步：将第一步得到的压握在可扩张球囊外部的药物洗脱支架本体经由第二步的切口插入第二步得到的保护套管中，并确保药物洗脱支架本体位于保护套管的不具有切口的管体部分之中。之后于常温晾干24小时，直至保护套管收缩至原始尺寸(即，内径为0.049英寸、长度为70毫米)。包装、灭菌，得到本实施例的药物洗脱支架。Step 3: Insert the body of the drug-eluting stent obtained in the first step and pressed outside the expandable balloon into the protective sleeve obtained in the second step through the incision in the second step, and ensure that the body of the drug-eluting stent is in the protective sleeve. In the body portion of the sleeve that does not have cutouts. Afterwards, it was dried at room temperature for 24 hours until the protective sleeve shrunk to its original size (ie, the inner diameter was 0.049 inch and the length was 70 mm). Pack and sterilize to obtain the drug-eluting stent of this embodiment.
实施例六Embodiment six
本实施例提供的药物洗脱支架的结构与实施例四提供的药物洗脱支架的结构基本相同。区别之处在于，本实施例中，保护套管的管体近端及管体远端之间沿保护套管的轴向设置三个凹槽。凹槽的近端及远端均具有切口。切口沿保护套管的轴向的长度为5毫米。并且保护套管的材料与实施例四的保护套管的材料不同。The structure of the drug-eluting stent provided in this embodiment is basically the same as that of the drug-eluting stent provided in Embodiment 4. The difference is that in this embodiment, three grooves are provided between the proximal end and the distal end of the protective sleeve along the axial direction of the protective sleeve. Both the proximal end and the distal end of the groove have cutouts. The length of the incision in the axial direction of the protective sleeve is 5 mm. And the material of the protective sleeve is different from that of the protective sleeve in the fourth embodiment.
本实施例提供的药物洗脱支架的制备方法如下：The preparation method of the drug-eluting stent provided in this embodiment is as follows:
第一步：以紫杉醇作为抗组织增生活性药物，将其与烟酰胺载体混合后溶于丙酮中配制药物涂层溶液。将药物涂层溶液刷涂在规格为6.0毫米×78毫米的纯铁支架表面，于30℃鼓风干燥至恒重，得到药物洗脱支架本体。对球囊规格为6.0毫米×80毫米的球囊导管进行等离子预处理。再通过球囊折翼机将球囊导管的可扩张球囊折为三个翼并卷绕。采用压握机将药物洗脱支架本体压握在可扩张球囊的外部。Step 1: Paclitaxel is used as an anti-tissue hyperplasia active drug, which is mixed with nicotinamide carrier and then dissolved in acetone to prepare a drug coating solution. The drug-eluting stent body was obtained by brush-coating the drug-eluting solution on the surface of a pure iron stent with a size of 6.0 mm×78 mm, and drying at 30° C. by blasting to constant weight. Plasma pretreatment was performed on balloon catheters with a balloon size of 6.0 mm x 80 mm. Then, the expandable balloon of the balloon catheter is folded into three wings by a balloon wing folding machine and coiled. A crimping machine is used to crimp the main body of the drug-eluting stent on the outside of the expandable balloon.
第二步：将原始内径为0.053英寸、原始长度为110毫米的聚氨酯管的管体近端及管体远端之间沿聚氨酯管的轴向刻出两个凹槽，且两个凹槽围绕聚氨酯管的中心轴呈对称设置。然后将聚氨酯管置于氯仿溶剂中溶胀30分钟，测得聚氨酯管内径溶胀度为1.6。取出已经溶胀的聚氨酯管。将聚氨酯管内、外表面残留的氯仿溶剂常温吹干。用刀片将每个凹槽的近端及远端均沿硅胶管的轴向切开一个轴向长度约为10毫米的切口，得到聚氨酯材料制成的保护套管。Step 2: Carve two grooves along the axial direction of the polyurethane tube between the proximal end and the distal end of the polyurethane tube with an original inner diameter of 0.053 inches and an original length of 110 mm, and the two grooves surround The central axis of the polyurethane tube is arranged symmetrically. Then the polyurethane tube was swelled in chloroform solvent for 30 minutes, and the swelling degree of the inner diameter of the polyurethane tube was measured to be 1.6. Remove the swollen polyurethane tubing. Dry the residual chloroform solvent on the inner and outer surfaces of the polyurethane tube at room temperature. A slit with an axial length of about 10 mm was cut at the proximal and distal ends of each groove along the axial direction of the silicone tube with a blade to obtain a protective sleeve made of polyurethane material.
第三步：将第一步得到的压握在可扩张球囊外部的药物洗脱支架本体经由第二步的切口插入第二步得到的保护套管中，并确保药物洗脱支架本体位于保护套管的不具有切口的管体部分之中。之后于60℃加热12小时，直至保护套管收缩至原始尺寸(即，内径为0.053英寸、长度为110毫米)。包装、灭菌，得到本实施例的药物洗脱支架。Step 3: Insert the body of the drug-eluting stent obtained in the first step and pressed outside the expandable balloon into the protective sleeve obtained in the second step through the incision in the second step, and ensure that the body of the drug-eluting stent is in the protective sleeve. In the body portion of the sleeve that does not have cutouts. It was then heated at 60° C. for 12 hours until the protective sleeve shrunk to its original dimensions (ie, 0.053 inch inner diameter and 110 mm length). Pack and sterilize to obtain the drug-eluting stent of this embodiment.
对比例一Comparative example one
对比例一的药物洗脱球囊导管的结构与实施例一提供的药物洗脱球囊导管的结构基本相同。区别之处在于，对比例一的保护套管的材料与实施例一的保护套管的材料不同。The structure of the drug-eluting balloon catheter in Comparative Example 1 is basically the same as the structure of the drug-eluting balloon catheter provided in Example 1. The difference lies in that the material of the protective sleeve of Comparative Example 1 is different from that of the protective sleeve of Example 1.
对比例一的药物洗脱球囊导管的制备方法如下：The preparation method of the drug-eluting balloon catheter of Comparative Example 1 is as follows:
第一步：以紫杉醇作为抗组织增生活性药物，将其与苯甲酸钠载体混合后溶于乙醇中配制药物涂层溶液。对球囊规格为4.0毫米×40毫米的PTA球囊导管进行等离子预处理。将药物涂层溶液喷涂至PTA球囊导管的可扩张球囊表面。常温晾干。再通过球囊折翼机将可扩张球囊折为三个翼并卷绕，得到药物洗脱球囊导管本体。Step 1: Paclitaxel is used as an active anti-proliferation drug, which is mixed with sodium benzoate carrier and dissolved in ethanol to prepare a drug coating solution. Plasma pretreatment was performed on PTA balloon catheters with a balloon size of 4.0 mm × 40 mm. The drug coating solution is sprayed onto the expandable balloon surface of the PTA balloon catheter. Allow to dry at room temperature. Then, the expandable balloon is folded into three wings by a balloon wing folding machine and wound to obtain the main body of the drug-eluting balloon catheter.
第二步：将第一步得到的药物洗脱球囊导管本体的可扩张球囊插入内径为0.043英寸、长度为70毫米的聚四氟乙烯管中，发现可扩张球囊近端产生褶皱现象，无法正常使用。Step 2: Insert the expandable balloon of the drug-eluting balloon catheter body obtained in the first step into a polytetrafluoroethylene tube with an inner diameter of 0.043 inches and a length of 70 mm. Wrinkles were found at the proximal end of the expandable balloon , cannot be used normally.
第三步：按照第一步相同的步骤制作药物洗脱球囊导管本体，并将药物洗脱球囊导管本体的可扩张球囊插入内径为0.044英寸、长度为70毫米的聚四氟乙烯管之中，包装、灭菌，得到对比例一的药物洗脱球囊导管。Step 3: Make the drug-eluting balloon catheter body according to the same steps as the first step, and insert the expandable balloon of the drug-eluting balloon catheter body into a Teflon tube with an inner diameter of 0.044 inches and a length of 70 mm Among them, package and sterilize to obtain the drug-eluting balloon catheter of Comparative Example 1.
对比例二Comparative example two
对比例二的药物洗脱球囊导管的结构与实施例一提供的药物洗脱球囊导管的结构基本相同。区别之处在于，对比例二的保护套管的材料与实施例一的保护套管的材料不同。The structure of the drug-eluting balloon catheter in Comparative Example 2 is basically the same as the structure of the drug-eluting balloon catheter provided in Example 1. The difference lies in that the material of the protective sleeve of Comparative Example 2 is different from that of the protective sleeve of Example 1.
对比例二的药物洗脱球囊导管的制备方法如下：The preparation method of the drug-eluting balloon catheter of Comparative Example 2 is as follows:
第一步：以紫杉醇作为抗组织增生活性药物，将其与苯甲酸钠载体混合后溶于乙醇中配制药物涂层溶液。对球囊规格为4.0毫米×40毫米的PTA球囊导管进行等离子预处理。将药物涂层溶液喷涂至PTA球囊导管的可扩张球囊表面。常温晾干。再通过球囊折翼机将可扩张球囊折为三个翼并卷绕，得到药物洗脱球囊导管本体。Step 1: Paclitaxel is used as an active anti-proliferation drug, which is mixed with sodium benzoate carrier and dissolved in ethanol to prepare a drug coating solution. Plasma pretreatment was performed on PTA balloon catheters with a balloon size of 4.0 mm × 40 mm. The drug coating solution is sprayed onto the expandable balloon surface of the PTA balloon catheter. Allow to dry at room temperature. Then, the expandable balloon is folded into three wings by a balloon wing folding machine and wound to obtain the main body of the drug-eluting balloon catheter.
第二步：将第一步得到的药物洗脱球囊导管本体的可扩张球囊插入原始内径为2毫米、长度为140毫米、热收缩比例为2：1的聚烯烃热缩管中。Step 2: Insert the expandable balloon of the drug-eluting balloon catheter body obtained in the first step into a polyolefin heat-shrinkable tube with an original inner diameter of 2 mm, a length of 140 mm, and a heat shrinkage ratio of 2:1.
第三步：将带有聚烯烃热缩管的药物洗脱球囊导管于125℃加热90秒使聚烯烃热缩管受热收缩，包装、灭菌，得到对比例二的药物洗脱球囊导管。Step 3: Heat the drug-eluting balloon catheter with polyolefin heat-shrinkable tube at 125°C for 90 seconds to shrink the polyolefin heat-shrinkable tube, pack and sterilize, and obtain the drug-eluting balloon catheter of Comparative Example 2 .
对比例三Comparative example three
对比例三的药物洗脱支架的结构与实施例四提供的药物洗脱支架的结构基本相同。区别之处在于，对比例三的保护套管的材料与实施例四的保护套管的材料不同，并且对比例三的保护套管上不具有轴向设置的凹槽。The structure of the drug-eluting stent in Comparative Example 3 is basically the same as the structure of the drug-eluting stent provided in Example 4. The difference is that the material of the protective sleeve of Comparative Example 3 is different from that of the protective sleeve of Example 4, and the protective sleeve of Comparative Example 3 does not have axially arranged grooves.
对比例三的药物洗脱支架的制备方法如下：The preparation method of the drug-eluting stent of Comparative Example 3 is as follows:
第一步：以雷帕霉素作为抗组织增生活性药物，将其与聚乳酸载体混合后溶于四氢呋喃中配制药物涂层溶液。将药物涂层溶液滴涂在规格为4.0毫米×38毫米的铁基合金支架表面，于30℃鼓风干燥至恒重，得到药物洗脱支架本体。然后对球囊规格为4.0毫米×40毫米的球囊导管进行等离子预处理。再通过球囊折翼机将球囊导管的可扩张球囊折为三个翼并卷绕。采用压握机将药物洗脱支架本体压握在可扩张球囊的外部。The first step: using rapamycin as an anti-tissue hyperplasia drug, mixing it with a polylactic acid carrier and dissolving it in tetrahydrofuran to prepare a drug coating solution. The drug coating solution was drip-coated on the surface of an iron-based alloy stent with a size of 4.0 mm×38 mm, and dried at 30° C. by blasting to constant weight to obtain a drug-eluting stent body. A balloon catheter with a balloon size of 4.0 mm x 40 mm was then plasma pretreated. Then, the expandable balloon of the balloon catheter is folded into three wings by a balloon wing folding machine and coiled. A crimping machine is used to crimp the main body of the drug-eluting stent on the outside of the expandable balloon.
第二步：将第一步得到的压握在可扩张球囊外部的药物洗脱支架本体插入原始内径为0.044英寸、长度为70毫米的聚四氟乙烯管之中，发现药物洗脱支架本体与可扩张球囊之间发生轴向偏移，测得轴向偏移的距离约为8毫米。Step 2: Insert the body of the drug-eluting stent obtained in the first step and held outside the expandable balloon into a polytetrafluoroethylene tube with an original inner diameter of 0.044 inches and a length of 70 mm, and find that the body of the drug-eluting stent Axial offset occurs between the expandable balloon and the measured axial offset distance is about 8 mm.
第三步：按照第一步相同的步骤制作压握在可扩张球囊外部的药物洗脱支架本体，并将压握在可扩张球囊外部的药物洗脱支架本体插入内径为0.045英寸、长度为70毫米的聚四氟乙烯管之中，包装、灭菌，得到对比例三的药物洗脱支架。Step 3: Follow the same steps as the first step to make the drug-eluting stent body crimped outside the expandable balloon, and insert the drug-eluting stent body crimped outside the expandable balloon with an inner diameter of 0.045 inches and a length of 0.045 inches. into a 70mm polytetrafluoroethylene tube, packaged, and sterilized to obtain the drug-eluting stent of Comparative Example 3.
可扩张球囊本体检测Inflatable balloon body detection
分别测量实施例一提供的药物洗脱球囊导管的可扩张球囊、及对比例二的药物洗脱球囊导管的可扩张球囊的外观及直径。具体方法如下：分别去掉实施例一提供的药物洗脱球囊导管的可扩张球囊表面的保护套管、及对比例二的药物洗脱球囊导管的可扩张球囊表面的保护套管，将可扩张球囊表面的药物涂层用已被纯化水润湿的无尘布轻轻擦去，采用结晶紫染色的造影剂溶液(例如：碘帕醇溶液、碘海醇溶液、碘普罗胺溶液、碘美普尔溶液、碘喷托溶液、碘佛醇溶液、碘曲仑溶液或者碘克沙醇溶液)将可扩张球囊扩张至名义压力(名义压力是指球囊导管达到包装上所标称的直径时所需的扩张压)。将扩张后的可扩张球囊置于3D显微镜下观察外观，并于20倍放大条件下测量可扩张球囊的实际直径，将其与可扩张球囊的名义直径对比(名义直径是指球囊导管包装上所标称的直径)。可扩张球囊在名义压力下的实际直径测试结果如表2所示。The appearance and diameter of the expandable balloon of the drug-eluting balloon catheter provided in Example 1 and the expandable balloon of the drug-eluting balloon catheter provided in Comparative Example 2 were respectively measured. The specific method is as follows: respectively remove the protective sleeve on the expandable balloon surface of the drug-eluting balloon catheter provided in Example 1 and the protective sleeve on the expandable balloon surface of the drug-eluting balloon catheter in Comparative Example 2, Gently wipe off the drug coating on the surface of the expandable balloon with a lint-free cloth moistened with purified water, and use crystal violet dyed contrast medium solution (such as: iopamidol solution, iohexol solution, iopromide solution, etc.) solution, iomeprol solution, iodopentol solution, ioversol solution, iotrolan solution, or iodixanol solution) to inflate the expandable balloon to the nominal pressure (nominal pressure refers to the balloon catheter reaching the pressure indicated on the package). dilation pressure required for the weighed diameter). Place the expanded expandable balloon under a 3D microscope to observe its appearance, measure the actual diameter of the expandable balloon under 20 times magnification, and compare it with the nominal diameter of the expandable balloon (the nominal diameter refers to the nominal diameter on the catheter package). The test results of the actual diameter of the expandable balloon under the nominal pressure are shown in Table 2.
表2可扩张球囊在名义压力下的实际直径测试结果Table 2 Test results of the actual diameter of the expandable balloon under nominal pressure
表1结果表明：在名义压力下，实施例一提供的药物洗脱球囊导管的可扩张球囊的实际直径为4002.2μm，与球囊规格为4.0毫米×40毫米的PTA球囊导管的名义直径基本相同。对比例二的药物洗脱球囊导管的可扩张球囊的实际直径为3267.5μm，远低于球囊规格为4.0毫米×40毫米的PTA球囊导管的名义直径。The results in Table 1 show that: under the nominal pressure, the actual diameter of the expandable balloon of the drug-eluting balloon catheter provided in Example 1 is 4002.2 μm, which is the same as the nominal diameter of the PTA balloon catheter with a balloon specification of 4.0 mm×40 mm. The diameters are basically the same. The actual diameter of the expandable balloon of the drug-eluting balloon catheter in Comparative Example 2 is 3267.5 μm, which is much lower than the nominal diameter of the PTA balloon catheter with a balloon specification of 4.0 mm×40 mm.
3D显微镜观察结果显示，实施例一提供的药物洗脱球囊导管的可扩张球囊在充盈状态下，位于可扩张球囊中段的有效区域呈规则的圆柱形。对比例二的药物洗脱球囊导管的可扩张球囊在充盈状态下，可扩张球囊的各段区域发生明显变形。3D microscope observation results show that when the expandable balloon of the drug-eluting balloon catheter provided in Example 1 is inflated, the effective area located in the middle section of the expandable balloon has a regular cylindrical shape. When the expandable balloon of the drug-eluting balloon catheter of Comparative Example 2 is inflated, each section of the expandable balloon is obviously deformed.
以上结果表明，实施例一提供的药物洗脱球囊导管中，保护套管在溶胀后包裹在可扩张球囊外部，既不会损伤药物洗脱球囊导管的可扩张球囊本体，也不影响可扩张球囊置入人体后的充盈扩张。The above results show that in the drug-eluting balloon catheter provided in Example 1, the protective sleeve is wrapped around the expandable balloon after swelling, which neither damages the expandable balloon body of the drug-eluting balloon catheter, nor It affects the filling and expansion of the expandable balloon after it is placed in the human body.
总药量测试对比Total Drug Dose Test Comparison
药物洗脱球囊导管总药量是指负载在药物洗脱球囊导管的可扩张球囊表面的药物涂层中活性药物的总含量。一般通过多个药物洗脱球囊导管的总药量的分布来评价药物洗脱球囊导管的制备方法的稳定性。The total drug amount of the drug-eluting balloon catheter refers to the total content of active drugs loaded on the drug coating on the expandable balloon surface of the drug-eluting balloon catheter. Generally, the stability of the preparation method of the drug-eluting balloon catheter is evaluated by the distribution of the total drug amount of multiple drug-eluting balloon catheters.
分别按照实施例一、对比例一和对比例二的制备方法，制备每组5个的三组药物洗脱球囊导管样品(以下简称DEB样品)。制备过程中，施加在三组DEB样品的可扩张球囊表面的药物涂层溶液完全相同。然后分别检测三组DEB样品的总药量，以评价由不同材料制成的保护套管对制备方法稳定性的影响。According to the preparation methods of Example 1, Comparative Example 1 and Comparative Example 2, respectively, three groups of 5 drug-eluting balloon catheter samples (hereinafter referred to as DEB samples) were prepared. During the preparation process, the drug coating solution applied on the surface of the expandable balloon of the three groups of DEB samples was exactly the same. Then the total amount of the three groups of DEB samples were detected to evaluate the influence of protective sleeves made of different materials on the stability of the preparation method.
具体检测方法为：将三组DEB样品去掉保护套管之后，分别浸泡在刚好完全浸没DEB样品的甲醇中。超声使药物涂层溶解于甲醇中。再利用高效液相色谱(简称HPLC)分析甲醇中的紫杉醇浓度，并根据甲醇体积，计算每个DEB样品的紫杉醇总药量。紫杉醇总药量＝甲醇中的紫杉醇浓度×甲醇体积。The specific detection method is: remove the protective sleeves of the three groups of DEB samples, and soak them in methanol that just completely submerges the DEB samples. Sonication dissolves the drug coating in methanol. The concentration of paclitaxel in methanol was analyzed by high performance liquid chromatography (HPLC for short), and the total dosage of paclitaxel in each DEB sample was calculated according to the volume of methanol. The total dose of paclitaxel = the concentration of paclitaxel in methanol × the volume of methanol.
HPLC检测条件为：日本岛津LC-20A型高效液相色谱仪。色谱柱：美国安捷伦ZOBAXSB-C18柱(4.6×250毫米，5μm)。柱温：30℃。流动相：甲醇：乙腈：水＝230:360:410。流速：1.0mL/min。紫外检测器。检测波长：227nm。三组DEB样品的总药量检测结果如表1所示。HPLC detection conditions are: Japan Shimadzu LC-20A high performance liquid chromatography. Chromatographic column: American Agilent ZOBAXSB-C18 column (4.6×250 mm, 5 μm). Column temperature: 30°C. Mobile phase: methanol: acetonitrile: water = 230:360:410. Flow rate: 1.0 mL/min. UV detector. Detection wavelength: 227nm. The results of the total drug dose detection of the three groups of DEB samples are shown in Table 1.
表1 DEB样品的总药量检测结果Table 1 The detection results of the total drug dose of DEB samples
由表1可知：It can be seen from Table 1 that:
(1)通过实施例一的制备方法制备的5个样品的平均总药量为1073.42，明显高于通过对比例一及对比例二的制备方法制备的5个样品的平均总药量。(1) The average total drug amount of the 5 samples prepared by the preparation method of Example 1 was 1073.42, which was significantly higher than the average total drug amount of the 5 samples prepared by the preparation methods of Comparative Example 1 and Comparative Example 2.
(2)通过实施例一的制备方法制备的5个样品的总药量的标准差为24.97，明显低于通过对比例一及对比例二的制备方法制备的5个样品的总药量的标准差。(2) The standard deviation of the total drug doses of the 5 samples prepared by the preparation method of Example 1 is 24.97, which is significantly lower than the standard of the total drug doses of the 5 samples prepared by the preparation methods of Comparative Example 1 and Comparative Example 2 Difference.
以上结果表明，通过本发明提供的制备方法制备的DEB样品具有较高的总药量，原因是保护套管溶胀后包裹在可扩张球囊外部，有效降低生产过程中，DEB样品的可扩张球囊插入保护套管时的药物涂层损失。同时，本发明提供的药物洗脱球囊的制备方法稳定性较高，不同DEB样品之间的总药量差异较小，更适于产业化。The above results show that the DEB sample prepared by the preparation method provided by the present invention has a higher total drug dose, because the protective sleeve is swollen and wrapped outside the expandable balloon, which effectively reduces the amount of the expandable balloon in the DEB sample during the production process. Drug coating loss when the balloon is inserted into the protective sheath. At the same time, the preparation method of the drug-eluting balloon provided by the present invention has high stability, and the difference in the total drug amount among different DEB samples is small, which is more suitable for industrialization.
体外模拟输送过程药量损失测试In vitro simulated delivery process drug loss test
对实施例一提供的药物洗脱球囊导管和对比例一的药物洗脱球囊导管进行输送过程药量损失的体外模拟测试。药物洗脱球囊导管的输送过程药量损失是指自药物洗脱球囊导管的可扩张球囊置入导引导管开始，逐渐将可扩张球囊推送至病变部位的目标血管，直至可扩张球囊被充盈之前这一时间段内的药物损失量。输送过程药量损失与可扩张球囊表面的初始药量的比值即为输送过程药量损失率。由于可扩张球囊被置入导引导管之前，需要先移除保护套管，之后原本紧密卷绕的各个折翼开始逐渐向外展开。在可扩张球囊被推送至靶病变位点的过程中，血流的高速冲刷会加速各个折翼的展开过程，导致原本被折翼覆盖的区域的药物涂层直接受到血流冲刷发生脱落。因此，内径较小的保护套管对可扩张球囊的折翼的束缚作用较强，去除保护套管后，折翼展开的速度较慢，维持卷绕状态的折翼对覆盖在折翼之下的药物涂层的保护时间较长，输送过程药量损失率较低。The drug-eluting balloon catheter provided in Example 1 and the drug-eluting balloon catheter in Comparative Example 1 were subjected to an in vitro simulation test of drug loss during delivery. The drug loss during the delivery process of drug-eluting balloon catheter refers to the time when the expandable balloon of drug-eluting balloon catheter is inserted into the guide catheter, and the expandable balloon is gradually pushed to the target blood vessel in the lesion until it can be expanded. The amount of drug lost during the time period before the balloon is inflated. The ratio of drug loss during delivery to the initial drug amount on the surface of the expandable balloon is the rate of drug loss during delivery. Since the protective sheath needs to be removed before the expandable balloon is inserted into the guide catheter, the tightly wound flaps begin to gradually expand outward. When the expandable balloon is pushed to the target lesion site, the high-speed washing of the blood flow will accelerate the unfolding process of each flap, causing the drug coating in the area originally covered by the flap to be directly washed away by the blood flow and fall off. Therefore, the protective sleeve with a smaller inner diameter has a stronger binding effect on the flaps of the expandable balloon. After the protective sleeve is removed, the flaps unfold at a slower speed, and the flaps that maintain the coiled state are covered by the flaps. The protection time of the drug coating underneath is longer, and the loss rate of the drug amount is lower during the delivery process.
用离体猪冠脉血管模拟人体冠状动脉系统的目标血管，在体外模拟血管模型中进行输送过程药量损失的体外模拟测试。考察药物洗脱球囊导管的输送过程损失。具体方法为：分别撕去实施例一和对比例一制备的药物洗脱球囊导管上的保护套管，再分别将药物洗脱球囊导管插入体外模拟血管模型中，沿模拟血管路径输送至目标血管并停留。从药物洗脱球囊导管插入体外模拟血管模型开始计时，90秒后取出药物洗脱球囊导管。分别利用HPLC分析可扩张球囊表面的残余药量，并按下式计算输送过程药物损失率：The target blood vessel of the human coronary artery system is simulated with the isolated porcine coronary blood vessel, and the in vitro simulation test of the drug loss during the delivery process is carried out in the simulated blood vessel model in vitro. Investigate in-process losses for drug-eluting balloon catheters. The specific method is: tear off the protective sleeves on the drug-eluting balloon catheters prepared in Example 1 and Comparative Example 1, respectively insert the drug-eluting balloon catheters into the in vitro simulated blood vessel model, and transport them along the simulated blood vessel path to Target vessel and stay. The timing starts from the time when the drug-eluting balloon catheter is inserted into the simulated blood vessel model in vitro, and the drug-eluting balloon catheter is removed after 90 seconds. Use HPLC to analyze the amount of residual drug on the surface of the expandable balloon, and calculate the drug loss rate during the delivery process according to the following formula:
输送过程药物损失率＝(可扩张球囊表面初始药量－可扩张球囊表面残余药量)/可扩张球囊表面初始药量×100％。Drug loss rate during delivery = (initial drug amount on the surface of the expandable balloon - residual drug amount on the surface of the expandable balloon)/initial drug amount on the surface of the expandable balloon × 100%.
HPLC检测条件为：日本岛津LC-20A型高效液相色谱仪。色谱柱：美国安捷伦ZOBAXSB-C18色谱柱(4.6×250毫米，5μm)。柱温：30℃。流动相：甲醇：乙腈：水＝230:360:410。流速：1.0mL/min。紫外检测器。检测波长：227nm。体外模拟输送过程药量损失测试结果如表3所示。HPLC detection conditions are: Japan Shimadzu LC-20A high performance liquid chromatography. Chromatographic column: American Agilent ZOBAXSB-C18 chromatographic column (4.6×250 mm, 5 μm). Column temperature: 30°C. Mobile phase: methanol: acetonitrile: water = 230:360:410. Flow rate: 1.0 mL/min. UV detector. Detection wavelength: 227nm. Table 3 shows the test results of drug loss during in vitro simulated delivery.
表3体外模拟输送过程药量损失测试结果Table 3 Test results of drug loss during in vitro simulated delivery
表3数据显示：实施例一提供的药物洗脱球囊导管的输送过程药量损失率明显小于对比例一的药物洗脱球囊导管的输送过程药量损失率。说明实施例一提供的药物洗脱球囊导管中，溶胀后包裹在可扩张球囊外部的保护套管能有效减少药物洗脱球囊导管在输送过程中的药量损失。The data in Table 3 shows that the drug loss rate during delivery of the drug-eluting balloon catheter provided in Example 1 is significantly lower than that of the drug-eluting balloon catheter in Comparative Example 1. It illustrates that in the drug-eluting balloon catheter provided in Example 1, the protective sheath wrapped around the expandable balloon after swelling can effectively reduce the drug loss during delivery of the drug-eluting balloon catheter.
药物洗脱支架轮廓尺寸测试Drug Eluting Stent Contour Dimensions Testing
药物洗脱支架的轮廓尺寸是指将药物洗脱支架本体压握在可扩张球囊外部后，药物洗脱支架本体与可扩张球囊整体的轮廓外径。药物洗脱支架的轮廓尺寸由药物洗脱支架本体与可扩张球囊的压握紧密程度决定。药物洗脱支架的轮廓尺寸较小，利于药物洗脱支架顺利通过弯曲复杂血管和狭窄病变部位。同时表明药物洗脱支架本体与可扩张球囊之间压握紧密。故，药物洗脱支架本体与可扩张球囊之间发生相对移位的风险较小，药物洗脱支架本体自可扩张球囊表面脱落的风险较小。The contour size of the drug-eluting stent refers to the overall contour outer diameter of the drug-eluting stent body and the expandable balloon after the drug-eluting stent body is pressed and held outside the expandable balloon. The contour size of the drug-eluting stent is determined by the degree of tightness between the main body of the drug-eluting stent and the expandable balloon. The outline size of the drug-eluting stent is small, which is conducive to the smooth passage of the drug-eluting stent through the curved and complicated blood vessels and the narrow lesion. At the same time, it shows that the main body of the drug-eluting stent and the expandable balloon are pressed tightly. Therefore, the risk of relative displacement between the drug-eluting stent body and the expandable balloon is relatively small, and the risk of the drug-eluting stent body falling off the surface of the expandable balloon is relatively small.
分别按照实施例四和对比例三的制备方法，制备每组5个的两组药物洗脱支架样品(以下简称DES样品)。制备过程中，施加在两组DES样品的铁基合金支架表面的药物涂层溶液完全相同。然后分别测试两组DES样品的轮廓尺寸。测试结果如表4所示：According to the preparation methods of Example 4 and Comparative Example 3, two groups of 5 drug-eluting stent samples (hereinafter referred to as DES samples) were prepared. During the preparation process, the drug coating solutions applied on the surface of the iron-based alloy stents of the two groups of DES samples were exactly the same. Then the contour dimensions of the two groups of DES samples were tested respectively. The test results are shown in Table 4:
表4药物洗脱支架的轮廓尺寸测试结果Table 4 Outline dimension test results of drug-eluting stents
由表4可知：与对比例三的DES样品相比，实施例四提供的DES样品具有较小的轮廓尺寸，且5个DES样品的轮廓尺寸数据较集中。说明实施例四提供的DES样品中，溶胀后包裹在DES外部的保护套管可以使得DES样品的外径较小，充分保护涂层并且减小药物支架的轮廓尺寸，使药物洗脱支架本体及可扩张球囊没有向外扩张的空间。而对比例三为了避免药物涂层与保护套管内壁发生摩擦损伤药物涂层或者避免药物洗脱支架本体与可扩张球囊之间移位，只能使用内径较大的保护套管，导致DES样品的轮廓尺寸较大。故，对比例四的药物洗脱支架本体与可扩张球囊之间的结合力较差，增加药物洗脱支架本体自可扩张球囊外部脱落的风险。It can be seen from Table 4 that compared with the DES sample of Comparative Example 3, the DES sample provided by Example 4 has a smaller outline size, and the outline size data of the 5 DES samples are more concentrated. In the DES sample provided in Example 4, the protective sleeve wrapped on the outside of the DES after swelling can make the outer diameter of the DES sample smaller, fully protect the coating and reduce the outline size of the drug stent, so that the drug-eluting stent body and Expandable balloons have no room to expand outward. In Comparative Example 3, in order to avoid friction between the drug coating and the inner wall of the protective sleeve to damage the drug coating or to avoid displacement between the drug-eluting stent body and the expandable balloon, only a protective sleeve with a larger inner diameter can be used, resulting in DES The outline size of the sample is larger. Therefore, the binding force between the drug-eluting stent body and the expandable balloon in Comparative Example 4 is poor, which increases the risk of the drug-eluting stent body falling off from the expandable balloon.
综上，本发明提供的载药器械中，保护套管由可被溶剂溶胀的高分子材料制成。在将保护套管套设至载药器械外部的过程中，先将高分子材料制成的保护套管在溶剂中溶胀，增加保护套管的内径，以利于载药器械在无摩擦的情况下插入保护套管之中，避免损伤载药器械的药物涂层或者器械本体。然后再通过溶剂挥发，使保护套管在无需机械力、热源等外在因素作用下收缩至初始内径，将载药器械束缚至较小的轮廓外径，利于载药器械顺利通过人体内部的弯曲管腔或者狭窄病变部位。To sum up, in the drug-loaded device provided by the present invention, the protective sleeve is made of a polymer material that can be swelled by a solvent. In the process of sheathing the protective sleeve to the outside of the drug-loaded device, the protective sleeve made of polymer material is first swelled in a solvent to increase the inner diameter of the protective sleeve, so that the drug-loaded device can operate without friction. Insert it into the protective sleeve to avoid damaging the drug coating or the device body of the drug-loaded device. Then, the solvent is volatilized, so that the protective sleeve shrinks to the original inner diameter without mechanical force, heat source and other external factors, and the drug-loaded device is bound to a smaller contour outer diameter, which is conducive to the smooth passage of the drug-loaded device through the bending inside the human body lumen or stenotic lesion.
并且，本发明通过在保护套管的管体近端及管体远端之间沿保护套管的轴向设置至少一个凹槽，便于操作者在使用前直接撕掉保护套管。由此，在载药器械与保护套管分离时，避免保护套管内表面与载药器械的外表面之间的摩擦力损伤药物涂层或者器械本体。Moreover, the present invention arranges at least one groove along the axial direction of the protective sleeve between the proximal end and the distal end of the protective sleeve, so that the operator can directly tear off the protective sleeve before use. Thus, when the drug-loaded device is separated from the protective sleeve, the frictional force between the inner surface of the protective sleeve and the outer surface of the drug-loaded device is prevented from damaging the drug coating or the device body.
本发明提供的药物洗脱球囊导管，既能通过保护套管将药物洗脱球囊导管的可扩张球囊束缚至较小的外部轮廓，还能避免保护套管与药物涂层之间的摩擦力导致药物涂层或者可扩张球囊本体的损伤。无需加热即可使得可扩张球囊被保护套管紧紧束缚至较小的尺寸，不会造成药物涂层中的药物受热降解或者可扩张球囊本体受热变形。并且在保护套管自可扩张球囊的外部去除后，可扩张球囊的多个折翼能继续紧密卷绕，降低输送过程中血流高速冲刷造成的药物损失。The drug-eluting balloon catheter provided by the present invention can not only constrain the expandable balloon of the drug-eluting balloon catheter to a smaller external profile through the protective sleeve, but also avoid the gap between the protective sleeve and the drug coating. Friction causes damage to the drug coating or the body of the expandable balloon. The expandable balloon can be tightly bound to a smaller size by the protective sleeve without heating, and the drug in the drug coating will not be degraded by heat or the body of the expandable balloon will be deformed by heat. Moreover, after the protective sheath is removed from the outside of the expandable balloon, the multiple flaps of the expandable balloon can continue to be tightly wound, reducing drug loss caused by high-speed blood flow during delivery.
本发明提供的药物洗脱支架，既能通过保护套管将药物洗脱支架本体束缚至较小的外部轮廓，还能避免保护套管与药物涂层之间的摩擦力导致药物涂层，或者药物洗脱支架本体与可扩张球囊之间的移位。无需加热即可使药物洗脱支架本体及可扩张球囊被保护套管紧紧束缚至较小的尺寸，不会造成药物涂层中的药物受热降解或者药物洗脱支架本体及可扩张球囊受热变形。The drug-eluting stent provided by the present invention can not only constrain the body of the drug-eluting stent to a smaller external contour through the protective sleeve, but also avoid the friction between the protective sleeve and the drug coating from causing the drug coating, or Migration between the drug-eluting stent body and the expandable balloon. The drug-eluting stent body and expandable balloon can be tightly bound to a smaller size by the protective sleeve without heating, which will not cause thermal degradation of the drug in the drug coating or the drug-eluting stent body and expandable balloon Heat deformation.
可以理解的是，以上仅以药物洗脱球囊导管及药物洗脱支架对本发明提供的技术方案做了示意性描述，本发明提供的技术方案也可用于其他介入式医疗器械或者植入式医疗器械。所述介入式器械包括造影导管、中心静脉导管、测压导管、导尿管或者一次性介入治疗仪探头。所述植入式器械包括骨钉或者骨板。只要采用可被溶剂溶胀的高分子材料制成保护套管，并将保护套管先在溶剂中溶胀，再套设于前述介入式医疗器械或者植入式医疗器械外部，再使溶剂挥发，即可达到本发明的目的。It can be understood that the technical solutions provided by the present invention are only schematically described with drug-eluting balloon catheters and drug-eluting stents, and the technical solutions provided by the present invention can also be used for other interventional medical devices or implantable medical devices. instrument. The interventional device includes a contrast catheter, a central venous catheter, a pressure measurement catheter, a urinary catheter or a probe of a disposable interventional therapy instrument. The implantable device includes a bone nail or a bone plate. As long as the protective sleeve is made of a solvent-swellable polymer material, the protective sleeve is first swollen in a solvent, and then placed on the outside of the aforementioned interventional medical device or implantable medical device, and then the solvent is volatilized, that is The object of the present invention can be achieved.
还可以理解的是，以上仅以载药器械对本发明提供的技术方案做了示意性描述，本发明提供的技术方案也可用于其他非载药器械。在将本发明提供的技术方案应用于其他非载药器械时，本发明提供的保护套管仍然具有保护器械本体不受损伤的技术效果，并且可将所述非载药器械紧密束缚至较小的轮廓外径，提高所述非载药器械在人体弯曲管腔部位或者狭窄部位的可通过性。It can also be understood that the technical solutions provided by the present invention are only schematically described in terms of drug-loaded devices, and the technical solutions provided by the present invention can also be used in other non-medicated devices. When the technical solution provided by the present invention is applied to other non-medicated devices, the protective sleeve provided by the present invention still has the technical effect of protecting the device body from damage, and can tightly bind the non-medicated device to a smaller size. The outer diameter of the profile improves the passability of the non-drug-loaded device in curved lumen parts or narrow parts of the human body.
以上结合附图对本发明的实施例进行了描述，但是本发明并不局限于上述的具体实施方式。上述的具体实施方式仅仅是示意性的，而不是限制性的。本领域的普通技术人员在本发明的启示下，在不脱离本发明宗旨和权利要求所保护的范围情况下，还可做出很多形式，这些均属于本发明的保护之内。The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above specific implementation manners. The above-mentioned specific embodiments are only illustrative, not restrictive. Under the enlightenment of the present invention, those skilled in the art can also make many forms without departing from the gist of the present invention and the protection scope of the claims, and these all belong to the protection of the present invention.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611262098.3ACN108295359B (en) | 2016-12-30 | 2016-12-30 | Drug-loaded device and preparation method thereof |
| PCT/CN2017/117225WO2018121352A1 (en) | 2016-12-30 | 2017-12-19 | Drug-loading instrument and preparation method therefor |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611262098.3ACN108295359B (en) | 2016-12-30 | 2016-12-30 | Drug-loaded device and preparation method thereof |
| Publication Number | Publication Date |
|---|---|
| CN108295359Atrue CN108295359A (en) | 2018-07-20 |
| CN108295359B CN108295359B (en) | 2021-05-07 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611262098.3AActiveCN108295359B (en) | 2016-12-30 | 2016-12-30 | Drug-loaded device and preparation method thereof |
| Country | Link |
|---|---|
| CN (1) | CN108295359B (en) |
| WO (1) | WO2018121352A1 (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110201243A (en)* | 2019-07-09 | 2019-09-06 | 科睿驰（深圳）医疗科技发展有限公司 | A kind of combination drug coating foley's tube and preparation method thereof |
| WO2020258834A1 (en)* | 2019-06-27 | 2020-12-30 | 山东瑞安泰医疗技术有限公司 | Drug-eluting balloon catheter and preparation method therefor |
| CN113813449A (en)* | 2021-08-30 | 2021-12-21 | 孟繁宇 | Preparation method of nanoparticle rapamycin drug-loaded coating balloon |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109173016A (en)* | 2018-08-01 | 2019-01-11 | 中国医学科学院北京协和医院 | A kind of medicinal balloon catheter and balloon-system |
| CN110743089A (en)* | 2019-12-03 | 2020-02-04 | 浦易（上海）生物技术有限公司 | Medicine balloon protection sleeve and medicine balloon assembly comprising same |
| CN111437070B (en)* | 2020-05-11 | 2024-11-22 | 上海纽脉医疗科技有限公司 | An inner clamp arm control mechanism |
| WO2022089651A1 (en)* | 2020-11-02 | 2022-05-05 | 元心科技(深圳)有限公司 | Long balloon for balloon dilatation stent system, and preparation method for long balloon |
| CN113018649B (en)* | 2021-02-05 | 2022-07-15 | 北京先瑞达医疗科技有限公司 | Drug delivery catheter and preparation method thereof |
| CN114432569B (en)* | 2021-12-31 | 2023-08-29 | 华中科技大学同济医学院附属协和医院 | Surface treatment method and equipment for interventional catheter |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4710181A (en)* | 1985-06-11 | 1987-12-01 | Genus Catheter Technologies, Inc. | Variable diameter catheter |
| US20060036310A1 (en)* | 2004-08-13 | 2006-02-16 | Scimed Life Systems, Inc. | Method to simultaneously load and cover self expanding stents |
| CN102675771A (en)* | 2012-05-10 | 2012-09-19 | 东营东港橡塑有限公司 | Preparation method for automatic-shrinkage insulation protection casing pipe |
| US20150190618A1 (en)* | 2014-01-09 | 2015-07-09 | Medtronic Vascular, Inc. | Balloon Catheter With Elastomeric Sheath and Methods |
| CN104971422A (en)* | 2015-07-16 | 2015-10-14 | 颜玉强 | Medicinal balloon catheter and preparation method thereof |
| US20160096006A1 (en)* | 2014-10-03 | 2016-04-07 | W. L. Gore & Associates, Inc. | Removable covers for drug eluting medical devices |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6533806B1 (en)* | 1999-10-01 | 2003-03-18 | Scimed Life Systems, Inc. | Balloon yielded delivery system and endovascular graft design for easy deployment |
| JP2008289847A (en)* | 2007-04-25 | 2008-12-04 | Sekisui Chem Co Ltd | Balloon catheter |
| CN102665612B (en)* | 2009-11-05 | 2015-04-08 | 宾夕法尼亚大学理事会 | Valve prosthesis |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4710181A (en)* | 1985-06-11 | 1987-12-01 | Genus Catheter Technologies, Inc. | Variable diameter catheter |
| US20060036310A1 (en)* | 2004-08-13 | 2006-02-16 | Scimed Life Systems, Inc. | Method to simultaneously load and cover self expanding stents |
| CN102675771A (en)* | 2012-05-10 | 2012-09-19 | 东营东港橡塑有限公司 | Preparation method for automatic-shrinkage insulation protection casing pipe |
| US20150190618A1 (en)* | 2014-01-09 | 2015-07-09 | Medtronic Vascular, Inc. | Balloon Catheter With Elastomeric Sheath and Methods |
| US20160096006A1 (en)* | 2014-10-03 | 2016-04-07 | W. L. Gore & Associates, Inc. | Removable covers for drug eluting medical devices |
| CN104971422A (en)* | 2015-07-16 | 2015-10-14 | 颜玉强 | Medicinal balloon catheter and preparation method thereof |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020258834A1 (en)* | 2019-06-27 | 2020-12-30 | 山东瑞安泰医疗技术有限公司 | Drug-eluting balloon catheter and preparation method therefor |
| CN110201243A (en)* | 2019-07-09 | 2019-09-06 | 科睿驰（深圳）医疗科技发展有限公司 | A kind of combination drug coating foley's tube and preparation method thereof |
| CN110201243B (en)* | 2019-07-09 | 2021-10-26 | 科睿驰（深圳）医疗科技发展有限公司 | Composite drug coating balloon catheter and preparation method thereof |
| CN113813449A (en)* | 2021-08-30 | 2021-12-21 | 孟繁宇 | Preparation method of nanoparticle rapamycin drug-loaded coating balloon |
| Publication number | Publication date |
|---|---|
| WO2018121352A1 (en) | 2018-07-05 |
| CN108295359B (en) | 2021-05-07 |
| Publication | Publication Date | Title |
|---|---|---|
| CN108295359B (en) | Drug-loaded device and preparation method thereof | |
| AU2019200196B2 (en) | Removable covers for drug eluting medical devices | |
| ES2613587T3 (en) | Medical elution devices | |
| AU2015209714B2 (en) | Coatings for medical devices | |
| WO2018033920A1 (en) | Drug delivery catheter and method of use thereof | |
| CN104971422A (en) | Medicinal balloon catheter and preparation method thereof | |
| WO2016101771A1 (en) | Method for manufacturing dilating catheter of drug balloon, and coiled balloon having flaps | |
| BR112015026397B1 (en) | BALLOON CATHETER | |
| CN115212432B (en) | Medicine carrying saccule | |
| US20240024642A1 (en) | Removable covers for drug eluting medical devices | |
| JP7394836B2 (en) | balloon folding device | |
| HK1237681B (en) | Eluting medical devices | |
| HK1188573B (en) | Eluting medical devices | |
| HK1188573A (en) | Eluting medical devices |
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | Effective date of registration:20221014 Address after:No.136, Medical College Road, Xuhui District, Shanghai 200030 Patentee after:ZHONGSHAN HOSPITAL, FUDAN University Patentee after:LIFETECH SCIENTIFIC (SHENZHEN) Co.,Ltd. Address before:518000 1st-5th Floor of Saiba Research Building, Langshan Second Road, North District of Nanshan High-tech Industrial Park, Shenzhen City, Guangdong Province Patentee before:LIFETECH SCIENTIFIC (SHENZHEN) Co.,Ltd. | |
| TR01 | Transfer of patent right |