WO2016176804A1 - Biodegradable polymer film monolayer metal covered stent - Google Patents

Biodegradable polymer film monolayer metal covered stent Download PDF

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WO2016176804A1
WO2016176804A1 PCT/CN2015/078198 CN2015078198W WO2016176804A1 WO 2016176804 A1 WO2016176804 A1 WO 2016176804A1 CN 2015078198 W CN2015078198 W CN 2015078198W WO 2016176804 A1 WO2016176804 A1 WO 2016176804A1
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stent
film
biodegradable polymer
layer
polymer film
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PCT/CN2015/078198
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French (fr)
Chinese (zh)
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聂绍平
王晓
师树田
甄雷
胡平
齐宏旭
李齐方
殷光中
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聂绍平
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Priority to PCT/CN2015/078198 priority Critical patent/WO2016176804A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents

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  • the invention belongs to the technical field of medical instruments, and particularly relates to a biodegradable polymer film single-layer metal-coated stent.
  • the stent graft also known as the stent graft, consists of a stent and a thin layer of membrane, which refers to the inner or outer part of the bare metal stent or the artificial graft of the membrane material; the support function of the stent and the membrane coverage Function, which acts as a closed ruptured or perforated blood vessel, and can also be used to block an aneurysm or arterial spasm.
  • the stent graft retains the support function of the common stent and has the characteristics of a membranous material, which can effectively improve the abnormal hemodynamics of the diseased blood vessel.
  • stent grafts In the treatment of acute and chronic vascular injury and peripheral vascular disease, stent grafts have been widely used. In addition to coronary perforation, coronary artery fistula, true aneurysm, aortic dissection, aortic ulcer, aortic pseudoaneurysm, aortic rupture, aortic distorted, and other researchers use it for percutaneous angioplasty, Transjugular intrahepatic portosystemic shunt, dialysis tubal pseudoaneurysm, congenital aortic coarctation combined with patent ductus arteriosus.
  • Coronary perforation is one of the serious complications of vascular interventional therapy.
  • the incidence of coronary perforation is increasing.
  • the incidence rate is as high as 0.5% to 3.0%.
  • the rates of death, cardiac tamponade, myocardial infarction, and emergency surgery were 10%, 31%, 34%, and 39%, respectively.
  • the stent graft can act as an artificial barrier to isolate the vessel wall and blood, and is very suitable for the treatment of coronary perforation.
  • the placement of the stent graft during severe perforation can effectively block the fracture and reduce the mortality.
  • stent grafts have become one of the necessary devices for the treatment of serious complications in the catheterization room.
  • stent grafts can also be used to seal coronary aneurysms or coronary spasm, for thrombosis or degenerative saphenous vein bridge lesions also have a certain Advantage.
  • peripheral vascular disease there have also been reports of the use of stent grafts for the treatment of pseudoaneurysms, arteriovenous fistulas, vascular stenosis and occlusive disease, and the establishment of artificial dialysis tracts.
  • the early film-coated materials are mainly polyethylene, nylon, polyester, polyurethane and ePTFE. They are gradually degraded due to their inability to degrade, which is not conducive to cell adhesion, and easily cause intimal hyperplasia, stenosis of the lumen and adverse reactions caused by foreign bodies.
  • biodegradable polymer materials represented by polylactic acid (PLA), polyglycolic acid, PCL and modified copolymers thereof are increasingly used in the field of tissue engineering. This type of material can be broken down in the body, involved in the body's metabolism, and eventually excreted.
  • the clinical coronary stent graft is the JOSTENT GraftMaster preloaded stent graft system manufactured by Abbott Vascular Instruments GmbH.
  • the system uses a "sandwich" design that holds a layer of ePTFE film between two layers of 316 stainless steel tubular engraved metal brackets for a balloon-expandable bracket.
  • ePTFE is made by stretching PTFE to 400 degrees and can withstand stretching up to 4 times, thus meeting the basic requirements of stent expansion and film integrity.
  • the system provides five working lengths of 9mm, 12mm, 16mm, 19mm and 26mm, thickness 0.3mm, diameter range 3.0 ⁇ 5.0mm, lesion through 0.0118 inch outer diameter, rated burst pressure 12 ⁇ 14atm, outer diameter 1.5 ⁇ after crimping 1.7mm. It is generally recommended to use a 7F guide catheter for release, but a large lumen guide catheter with a lumen of ⁇ 0.070 inches is also compatible.
  • a stent graft to seal the coronary artery, the saphenous vein graft bridge and the perforation of the internal mammary artery.
  • Mulvihill and other studies have shown that the use of this system to block type II or III coronary artery perforation during PCI is not only easy to operate, but also has a high success rate.
  • the system still has many shortcomings: 1 Due to the sandwich design of double-layer metal bracket and ePTFE, the total thickness is up to 0.3mm, and its flexibility and passability are poor. Generally, it is not suitable for treating distal vascular perforations or diameter ⁇ 2.75. Perforation of mm; it is often difficult to deliver the stent to the perforation site when there is severe calcification, severe distortion, or placement into the stent in the proximal section of the perforation. Due to its deliverability Poor, if not released quickly, it is easy to cause cardiac tamponade or even death.
  • the aortic stent graft consists of a single-layer metal stent and a coating material (ePTFE membrane, polyester membrane, and linear polyester membrane)
  • the medical non-absorbent suture is often used to mechanically suture the membrane in a self-expanding manner. (self-expandable) on the stand. Due to the tight connection, the risk of internal hemorrhoids is increased; due to the small diameter of the coronary artery, the outer diameter will be larger after the suture loading method, which cannot meet the clinical needs; in addition, the suture and the covering material are both tolerated due to the expansion of the stent. Large tension, suture fixation also has extremely high requirements on materials, and generally biodegradable materials simply cannot meet the requirements.
  • the full-layer structure of the support beam is made of 316L stainless steel, cobalt-based alloy, nickel-titanium memory alloy or Conichrome alloy; the coating material is ePTFE film, polyester film and linear polyester film.
  • the intracranial stent graft system is a stent graft for the treatment of intracranial aneurysms. It consists of a cobalt-based alloy stent and an ePTFE membrane with a total thickness of 0.13 mm.
  • the Hercules stent graft uses a nickel-titanium memory alloy stent and a linear polyester membrane.
  • the Aegis bifurcated aortic stent graft is made of Conichrome alloy stent and ePTFE membrane; there is a special stent for the Grinking aortic dissection, which adopts a beamless tapered stent and a polyester membrane.
  • stent grafts for the treatment of coronary perforation in China.
  • the coronary artery stent graft system with controlled degradable membrane on the surface of single-layer metal stents has yet to be developed.
  • the object of the present invention is to provide a biodegradable polymer film single-layer metal-coated stent, which solves the problems of large shape, flexibility and poor passability, and poor anti-plugging property of the stent graft in the prior art.
  • a biodegradable polymer film single-layer metal-coated stent comprises a tubular single-layer metal stent body, a braid layer on the surface of the stent, and a coating covering the outside of the stent body; wherein the braid layer is The entire stent body surface is a mesh structure woven by electrospinning; the film is welded to the stent body by heat pressing.
  • the woven layer is an electrospun fibrous material.
  • the film is a degradable film forming material.
  • the degradable film forming material comprises polylactic acid, polyglycolic acid or polycaprolactone.
  • the hot pressing temperature is from 160 ° C to 240 ° C.
  • the biodegradable polymer film single-layer metal-coated stent provided by the invention comprises a single-layer tubular metal stent body, an electrospun woven mesh stent surface woven layer, and a cover body outside the stent body and through the heat
  • the film is welded to the main body of the stent.
  • the mesh is woven by electrospinning technology, which can be used as a supporting skeleton for the film and as a whole to connect the entire film.
  • the surface of the single-layer metal stent can be easily coated by the hot pressing film forming technology.
  • the coated stent provided by the invention has good flexibility and stretchability, can adapt to different types of blood vessels and lesions; has good biocompatibility and vascular compatibility, and is non-toxic to the body and blood vessels.
  • FIG. 1 is a schematic view of a stent body of a biodegradable polymer membrane single-layer metal stent according to the present invention
  • FIG. 2 is a schematic view showing a layer of a stent surface of a biodegradable polymer film single-layer metal stent graft of the present invention
  • FIG. 3 is a schematic overall view of a stent body of a biodegradable polymer membrane single-layer metal stent graft of the present invention.
  • a biodegradable polymer film single-layer metal-coated stent comprises a tubular single-layer metal stent body 1, a braided layer 2 on the surface of the stent, and a cover on the outside of the stent body 1.
  • Combining electrospinning with hot-pressing film forming a film 3 on the surface of a single-layer metal stent not only enhances the flexibility and passability of the stent, but also ensures the stretchability of the film 3, ensuring that the stent is expanding.
  • the rear film 3 maintains good integrity.
  • the biodegradable film-forming material is used as the film 3, and the film can be completely degraded after the stent is placed for several months and the vascular injury is repaired, which reduces the incidence of stent thrombosis and restenosis.
  • the braided layer 2 can be directly obtained by electrospinning technology, and the tube mesh stent can be directly obtained; the biocompatible, anticoagulant and cell adsorbing materials can also be sprayed onto the surface of the tubular stent, thereby making the stent graft
  • the surface properties are significantly improved.
  • the woven layer 2 is made of an electrospun fiber material.
  • the electrospun fibers generally have a nanometer diameter, a large specific surface area, and high uniformity, and also have the characteristics of light weight, high strength and tensile strength. Receiving electrospinning, getting A non-woven fabric in which fibers are interlaced.
  • the non-woven fabric may be in the form of orientation of fibers or a network structure woven according to a certain rule. The density of the fibers and the size of the diameter determine the size and porosity of the pores in the nonwoven.
  • the single-layer metal-coated stent of the present invention satisfies the requirements for cell adhesion and membrane permeation and mass transfer.
  • the film 3 is a degradable film forming material.
  • the degradable film-forming material is used as the film 3, which can be controlled and decomposed in the living body, participate in the metabolism of the human body, and finally excreted in the body; bio-controlled degradation, after being placed into the stent for several months, repairing the vascular injury, covering The membrane material is completely degraded, reducing the incidence of stent thrombosis and restenosis.
  • Degradable film forming materials include polycaprolactone.
  • the degradable film-forming material includes a degradable polymer material such as polylactic acid (PLA), polyglycolic acid or polycaprolactone (PCL).
  • PCL is a semi-crystalline polymer, which is easily blended with other polymers.
  • PCL is an aliphatic polyester polymer with good biocompatibility, degradable and controllable, and has certain pore and mechanical strength. High toughness.
  • the invention utilizes PCL to prepare a film of a single-layer metal-coated stent, so that the single-layer metal-coated stent has controllable degradation characteristics, flexibility and good stretchability, and can effectively block the arterial fracture and break the blood vessel. After the mouth is completely repaired, the complete degradation of the membrane is achieved, thereby effectively reducing the incidence of stent thrombosis and restenosis.
  • the hot pressing temperature is 160 ° C - 240 ° C, ensuring the composite strength between the film and the stent, while ensuring that the microstructure of the film is not damaged, and enhancing the overall strength of the composite after the composite.

Abstract

Provided is a biodegradable polymer film monolayer metal covered stent, which comprises a tubular monolayer metal stent main body, a knitted layer on the surface of the stent, and a film covering the outside of the stent main body; wherein, the knitted layer is a network structure which is on the surface of the whole stent main body and formed by electrostatic spinning and weaving; and the covering film is welded so as to be integral with the stent main body by hot pressing. The biodegradable polymer film monolayer metal covered stent solves the following problems in the covered stents of the prior art: a relatively large structure, a poor flexibility and passability, a poor antithrombotic property, a long endothelialization progress and a high restenosis rate.

Description

生物可降解高分子膜单层金属覆膜支架Biodegradable polymer membrane single-layer metal stent 技术领域Technical field
本发明属于医疗器械技术领域,具体涉及一种生物可降解高分子膜单层金属覆膜支架。The invention belongs to the technical field of medical instruments, and particularly relates to a biodegradable polymer film single-layer metal-coated stent.
背景技术Background technique
覆膜支架,又称为带膜支架,由支架与薄层的膜共同组成,指裸金属支架内面或外面部分或完全覆盖膜性材料的人工体内移植物;利用支架的支撑功能与膜的覆盖功能,起到封闭破裂或穿孔的血管作用,还可用于封堵动脉瘤或动脉瘘。覆膜支架既保留了普通支架的支撑功能,又具有膜性材料的特性,能有效改善病变血管的异常血流动力学。The stent graft, also known as the stent graft, consists of a stent and a thin layer of membrane, which refers to the inner or outer part of the bare metal stent or the artificial graft of the membrane material; the support function of the stent and the membrane coverage Function, which acts as a closed ruptured or perforated blood vessel, and can also be used to block an aneurysm or arterial spasm. The stent graft retains the support function of the common stent and has the characteristics of a membranous material, which can effectively improve the abnormal hemodynamics of the diseased blood vessel.
在急慢性血管损伤和外周血管病变的治疗中,覆膜支架得到了广泛的应用。除冠状动脉穿孔、冠状动脉瘘、真性动脉瘤、主动脉夹层、主动脉溃疡、主动脉假性动脉瘤、主动脉破裂、主动脉迂曲外,还有学者将其用于经皮血管成形术、经颈静脉肝内门腔分流术、透析管道假性动脉瘤、先天性主动脉缩窄合并动脉导管未闭的治疗。In the treatment of acute and chronic vascular injury and peripheral vascular disease, stent grafts have been widely used. In addition to coronary perforation, coronary artery fistula, true aneurysm, aortic dissection, aortic ulcer, aortic pseudoaneurysm, aortic rupture, aortic distorted, and other scholars use it for percutaneous angioplasty, Transjugular intrahepatic portosystemic shunt, dialysis tubal pseudoaneurysm, congenital aortic coarctation combined with patent ductus arteriosus.
冠状动脉穿孔是血管介入治疗的严重并发症之一,随着复杂病变介入治疗的增多和新技术与新器械的发展,冠状动脉穿孔的发生率有日益增高的趋势。随着支架、旋切、旋磨等新器械与新技术的应用,其发生率高达0.5%~3.0%。在带膜支架问世以前,其死亡、心脏压塞、心肌梗死与急诊外科手术率分别为10%、31%、34%和39%。研究证实,覆膜支架能起到隔离血管壁和血液的人工屏障作用,非常适用于处理冠状动脉穿孔。严重穿孔时置入覆膜支架能有效封堵破口,降低死亡率。目前,覆膜支架已成为处理导管室严重并发症的必备器械之一。 Coronary perforation is one of the serious complications of vascular interventional therapy. With the increase of interventional treatment of complex lesions and the development of new technologies and new devices, the incidence of coronary perforation is increasing. With the application of new devices and new technologies such as stenting, rotary cutting and rotary grinding, the incidence rate is as high as 0.5% to 3.0%. Before the advent of the stent, the rates of death, cardiac tamponade, myocardial infarction, and emergency surgery were 10%, 31%, 34%, and 39%, respectively. Studies have confirmed that the stent graft can act as an artificial barrier to isolate the vessel wall and blood, and is very suitable for the treatment of coronary perforation. The placement of the stent graft during severe perforation can effectively block the fracture and reduce the mortality. At present, stent grafts have become one of the necessary devices for the treatment of serious complications in the catheterization room.
除了用于冠状动脉管壁不连续性损伤(如破裂或穿孔)外,覆膜支架还可用于封堵冠状动脉瘤或冠状动脉瘘,用于血栓或退行性大隐静脉桥病变也具有一定的优势。在外周血管疾病中,也有将覆膜支架用于处理假性动脉瘤、动静脉瘘、血管狭窄与闭塞性疾病、以及人工透析道的建立的病例报道。In addition to coronary artery wall discontinuities (such as rupture or perforation), stent grafts can also be used to seal coronary aneurysms or coronary spasm, for thrombosis or degenerative saphenous vein bridge lesions also have a certain Advantage. In peripheral vascular disease, there have also been reports of the use of stent grafts for the treatment of pseudoaneurysms, arteriovenous fistulas, vascular stenosis and occlusive disease, and the establishment of artificial dialysis tracts.
早期的覆膜材料主要是聚乙烯、尼龙、涤纶、聚氨酯和ePTFE等,由于无法降解,不利于细胞黏附,容易引起内膜增生、管腔狭窄以及异物所引起的不良反应,因而已逐渐被淘汰。目前,以聚乳酸(PLA)、聚羟基乙酸、PCL以及其改性共聚物等为代表的生物可降解高分子材料,越来越在组织工程领域中得到广泛应用。这类材料可在生物体内分解,参与人体的新陈代谢,并最终排出体外。The early film-coated materials are mainly polyethylene, nylon, polyester, polyurethane and ePTFE. They are gradually degraded due to their inability to degrade, which is not conducive to cell adhesion, and easily cause intimal hyperplasia, stenosis of the lumen and adverse reactions caused by foreign bodies. . At present, biodegradable polymer materials represented by polylactic acid (PLA), polyglycolic acid, PCL and modified copolymers thereof are increasingly used in the field of tissue engineering. This type of material can be broken down in the body, involved in the body's metabolism, and eventually excreted.
目前,用于临床的冠状动脉覆膜支架有雅培血管仪器公司(Abbott Vascular Instruments Deutschland GmbH)生产的JOSTENT GraftMaster预装带膜支架系统。该系统采用“三明治”设计,在两层316不锈钢管状雕刻金属支架之间夹持一层ePTFE覆膜,为球囊膨胀式(balloon-expandable)支架。ePTFE为PTFE加热到400度后拉伸而成,可耐受4倍以内的拉伸,因而可满足支架扩张和覆膜完整等基本要求。该系统提供9mm、12mm、16mm、19mm和26mm等五个工作长度,厚度0.3mm,直径范围3.0~5.0mm,病变通过外径0.018英寸,额定爆破压12~14atm,压握后外径1.5~1.7mm。一般推荐使用7F指引导管释放,但内腔≥0.070英寸的大腔指引导管也多可兼容。国外有使用覆膜支架封堵自身冠状动脉、大隐静脉移植桥和乳内动脉穿孔的报道。Mulvihill等研究显示,采用该系统堵闭PCI术中II型或III型冠状动脉穿孔不仅操作便捷、成功率也较高。Currently, the clinical coronary stent graft is the JOSTENT GraftMaster preloaded stent graft system manufactured by Abbott Vascular Instruments Deutschland GmbH. The system uses a "sandwich" design that holds a layer of ePTFE film between two layers of 316 stainless steel tubular engraved metal brackets for a balloon-expandable bracket. ePTFE is made by stretching PTFE to 400 degrees and can withstand stretching up to 4 times, thus meeting the basic requirements of stent expansion and film integrity. The system provides five working lengths of 9mm, 12mm, 16mm, 19mm and 26mm, thickness 0.3mm, diameter range 3.0~5.0mm, lesion through 0.0118 inch outer diameter, rated burst pressure 12~14atm, outer diameter 1.5~ after crimping 1.7mm. It is generally recommended to use a 7F guide catheter for release, but a large lumen guide catheter with a lumen of ≥ 0.070 inches is also compatible. There are reports of using a stent graft to seal the coronary artery, the saphenous vein graft bridge and the perforation of the internal mammary artery. Mulvihill and other studies have shown that the use of this system to block type II or III coronary artery perforation during PCI is not only easy to operate, but also has a high success rate.
但该系统仍存在诸多缺点:①由于采用双层金属支架与ePTFE的夹心设计,总厚度高达0.3mm,其柔顺性与通过性均较差,一般不适用于处理远段血管穿孔或直径<2.75mm的穿孔;当穿孔的近段存在严重钙化、严重扭曲或已置入支架时,往往很难将带膜支架送至穿孔部位。由于其释放性(deliverability)较 差,若无法迅速释放,极易导致心脏压塞甚至死亡。②由于覆膜材料ePTFE无法有效降解,很难完全内皮化,有可能增加迟发血栓风险。动物实验显示,与普通支架相比,置入ePTFE带膜支架后完全内皮覆盖时间更长。Gercken等的研究显示,置入覆膜支架后,即便常规使用联合抗血小板治疗(阿司匹林和抵克力得或氯吡格雷治疗)1个月,置入后支架血栓的发生率仍高达5.7%(4/78,多发生在术后7~70天),远高于裸金属支架达0.3%~1.9%。③置入覆膜支架后的再狭窄率高出31.6%,且多位于支架边缘,如支架边缘和中央的发生率分别为29.8%和8.8%。还存在价格昂贵(每套约合2.4万元),且完全依赖国外进口,很难实现常规备货的问题。However, the system still has many shortcomings: 1 Due to the sandwich design of double-layer metal bracket and ePTFE, the total thickness is up to 0.3mm, and its flexibility and passability are poor. Generally, it is not suitable for treating distal vascular perforations or diameter <2.75. Perforation of mm; it is often difficult to deliver the stent to the perforation site when there is severe calcification, severe distortion, or placement into the stent in the proximal section of the perforation. Due to its deliverability Poor, if not released quickly, it is easy to cause cardiac tamponade or even death. 2 Because the coating material ePTFE can not be effectively degraded, it is difficult to completely endothelialize, which may increase the risk of delayed thrombosis. Animal experiments have shown that the endothelium coverage time is longer after placement of the ePTFE stented stent compared to conventional stents. Gercken et al. showed that after placement of stent-grafts, even with conventional antiplatelet therapy (aspirin and dexkeride or clopidogrel) for 1 month, the incidence of stent thrombosis after implantation was as high as 5.7% ( 4/78, mostly occurred 7 to 70 days after surgery), which is much higher than that of bare metal stents by 0.3% to 1.9%. 3 The rate of restenosis after placement of the stent graft was 31.6% higher, and was mostly located at the edge of the stent. The incidence rates at the edge and center of the stent were 29.8% and 8.8%, respectively. There are also expensive (about 24,000 yuan per set), and rely entirely on foreign imports, it is difficult to achieve the problem of regular stocking.
此外,虽然大动脉覆膜支架由单层金属支架和覆膜材料(ePTFE膜、涤纶覆膜及线性聚酯膜)组成,常采用医用非吸收性缝合线机械性地将覆膜缝合于自膨胀式(self-expandable)支架上。由于联接欠紧密,增加了内瘘风险;由于冠状动脉直径较小,采用缝线装载方式后外径会更大,无法满足临床需求;另外,由于支架膨胀时缝线和覆膜材料均需承受较大张力,缝线固定对材料也有极高的要求,一般生物可降解材料根本无法满足要求。In addition, although the aortic stent graft consists of a single-layer metal stent and a coating material (ePTFE membrane, polyester membrane, and linear polyester membrane), the medical non-absorbent suture is often used to mechanically suture the membrane in a self-expanding manner. (self-expandable) on the stand. Due to the tight connection, the risk of internal hemorrhoids is increased; due to the small diameter of the coronary artery, the outer diameter will be larger after the suture loading method, which cannot meet the clinical needs; in addition, the suture and the covering material are both tolerated due to the expansion of the stent. Large tension, suture fixation also has extremely high requirements on materials, and generally biodegradable materials simply cannot meet the requirements.
现阶段,国内覆膜支架产品的研究主要集中于主动脉、颅内动脉及外周动脉。支架梁全层结构采用316L不锈钢、钴基合金、镍钛记忆合金或Conichrome合金等;覆膜材料采用ePTFE膜、涤纶覆膜及线性聚酯膜等。例如,上海微创的
Figure PCTCN2015078198-appb-000001
颅内覆膜支架系统是用于治疗颅内动脉瘤的覆膜支架产品,由钴基合金支架和ePTFE膜组成,总厚度0.13mm;Hercules覆膜支架采用镍钛记忆合金支架和线性聚酯膜;Aegis分叉型大动脉覆膜支架采用Conichrome合金支架和ePTFE膜;有研亿金Grinking主动脉夹层专用支架,采用无梁渐细性支架,涤纶覆膜。但国内在用于处理冠状动脉穿孔的覆膜支架研发方面尚处于空白,在单层金属支架表面制作可控降解覆膜的冠状动脉覆膜支架系统尚待研发。
At this stage, research on domestic stent graft products mainly focuses on the aorta, intracranial arteries and peripheral arteries. The full-layer structure of the support beam is made of 316L stainless steel, cobalt-based alloy, nickel-titanium memory alloy or Conichrome alloy; the coating material is ePTFE film, polyester film and linear polyester film. For example, Shanghai Minimally
Figure PCTCN2015078198-appb-000001
The intracranial stent graft system is a stent graft for the treatment of intracranial aneurysms. It consists of a cobalt-based alloy stent and an ePTFE membrane with a total thickness of 0.13 mm. The Hercules stent graft uses a nickel-titanium memory alloy stent and a linear polyester membrane. The Aegis bifurcated aortic stent graft is made of Conichrome alloy stent and ePTFE membrane; there is a special stent for the Grinking aortic dissection, which adopts a beamless tapered stent and a polyester membrane. However, there is still a gap in the development of stent grafts for the treatment of coronary perforation in China. The coronary artery stent graft system with controlled degradable membrane on the surface of single-layer metal stents has yet to be developed.
因此,为提高血管介入治疗并发症的处理水平和有效性,更好的保障介入安全,需要克服支架外形较大、柔顺性与通过性差等缺点,实现覆膜材料的可 控降解,在单层金属支架表面制作可靠支架覆膜,既在支架扩张时保证覆膜的完整性,保障支架与覆膜的一体化,又能有效控制覆膜厚度,确保支架系统具有较小的外径、良好的柔顺性和通过性。这也将进一步提高覆膜支架的应用空间。Therefore, in order to improve the treatment level and effectiveness of vascular interventional treatment complications and better ensure the safety of intervention, it is necessary to overcome the shortcomings of large stent shape, flexibility and poor passage, and realize the material of the coating material. Controlled degradation, making a reliable stent coating on the surface of a single-layer metal stent, ensuring the integrity of the membrane when the stent is expanded, ensuring the integration of the stent and the membrane, and effectively controlling the thickness of the membrane to ensure that the stent system has a smaller Outer diameter, good flexibility and passability. This will further increase the application space of the stent graft.
发明内容Summary of the invention
针对现有技术的不足,本发明的目的在于提供一种生物可降解高分子膜单层金属覆膜支架,解决现有技术中覆膜支架外形较大、柔顺性与通过性差、抗栓性差、内皮化进程长及再狭窄率高的问题。In view of the deficiencies of the prior art, the object of the present invention is to provide a biodegradable polymer film single-layer metal-coated stent, which solves the problems of large shape, flexibility and poor passability, and poor anti-plugging property of the stent graft in the prior art. The problem of long endothelialization and high rate of restenosis.
为实现上述目的,本发明所采用的技术方案是:In order to achieve the above object, the technical solution adopted by the present invention is:
一种生物可降解高分子膜单层金属覆膜支架,包括管状的单层金属支架主体,支架表面的编织层,以及覆盖在所述支架主体外侧的覆膜;其中,所述编织层是在整个支架主体表面,由静电纺丝编织而成的网状结构;所述覆膜通过热压与支架主体焊接为一体。A biodegradable polymer film single-layer metal-coated stent comprises a tubular single-layer metal stent body, a braid layer on the surface of the stent, and a coating covering the outside of the stent body; wherein the braid layer is The entire stent body surface is a mesh structure woven by electrospinning; the film is welded to the stent body by heat pressing.
优选地,所述编织层采用电纺纤维材料。Preferably, the woven layer is an electrospun fibrous material.
优选地,所述覆膜为可降解成膜材料。Preferably, the film is a degradable film forming material.
优选地,所述可降解成膜材料包括聚乳酸、聚羟基乙酸或聚己内酯。Preferably, the degradable film forming material comprises polylactic acid, polyglycolic acid or polycaprolactone.
优选地,所述热压的温度为160℃-240℃。Preferably, the hot pressing temperature is from 160 ° C to 240 ° C.
本发明提供的生物可降解高分子膜单层金属覆膜支架,包括单层管状金属支架主体,静电纺丝编织而成的网状支架表面编织层,以及覆盖在所述支架主体外侧、通过热压与支架主体焊接为一体的覆膜。通过静电纺丝技术编织网格,一方面可作为覆膜的支撑性骨架,又能起到将整个覆膜连为一体的作用。在编织网格的基础上,通过热压成膜技术,可轻易实现在单层金属支架表面覆膜。将静电纺丝与热压成膜技术相结合在单层金属支架表面制作覆膜,既增强了覆膜支架的柔顺性和通过性,又保证了覆膜的拉伸性,确保支架在扩张后覆膜保持良好的完整性。通过热压焊接将膜材料与裸金属支架实现牢固结合,将覆膜 材料与编织层网格材料融为一体,形成一体化、带有骨架的单层覆膜。本发明提供的覆膜支架,具有良好的柔韧性和拉伸性,可以适应不同类型的血管和病变;具有良好的生物相容性和血管相容性,对机体和血管无毒害。The biodegradable polymer film single-layer metal-coated stent provided by the invention comprises a single-layer tubular metal stent body, an electrospun woven mesh stent surface woven layer, and a cover body outside the stent body and through the heat The film is welded to the main body of the stent. The mesh is woven by electrospinning technology, which can be used as a supporting skeleton for the film and as a whole to connect the entire film. On the basis of the woven mesh, the surface of the single-layer metal stent can be easily coated by the hot pressing film forming technology. Combining electrospinning with hot pressing film forming technology to form a film on the surface of a single-layer metal stent, which not only enhances the flexibility and passability of the stent, but also ensures the stretchability of the film, ensuring that the stent is expanded. The film maintains good integrity. The film material is firmly bonded to the bare metal stent by thermocompression bonding, and the film is laminated. The material is integrated with the braided mesh material to form an integrated, single-layered film with a skeleton. The coated stent provided by the invention has good flexibility and stretchability, can adapt to different types of blood vessels and lesions; has good biocompatibility and vascular compatibility, and is non-toxic to the body and blood vessels.
附图说明DRAWINGS
图1为本发明生物可降解高分子膜单层金属覆膜支架的支架主体示意图;1 is a schematic view of a stent body of a biodegradable polymer membrane single-layer metal stent according to the present invention;
图2为本发明生物可降解高分子膜单层金属覆膜支架的支架表面的编制层示意图;2 is a schematic view showing a layer of a stent surface of a biodegradable polymer film single-layer metal stent graft of the present invention;
图3为本发明生物可降解高分子膜单层金属覆膜支架的支架主体的整体示意图。3 is a schematic overall view of a stent body of a biodegradable polymer membrane single-layer metal stent graft of the present invention.
具体实施方式detailed description
以下结合附图对本发明的技术方案作进一步描述。The technical solutions of the present invention are further described below with reference to the accompanying drawings.
如图1-3所示,一种生物可降解高分子膜单层金属覆膜支架,包括管状的单层金属支架主体1,支架表面的编织层2,以及覆盖在所述支架主体1外侧的覆膜3;其中,所述编织层2是在整个支架主体1表面,由静电纺丝编织而成的网状结构;所述覆膜3通过热压与支架主体焊接为一体。As shown in FIG. 1-3, a biodegradable polymer film single-layer metal-coated stent comprises a tubular single-layer metal stent body 1, a braided layer 2 on the surface of the stent, and a cover on the outside of the stent body 1. The film 3; wherein the woven layer 2 is a mesh structure woven by electrospinning on the entire surface of the stent body 1, and the film 3 is integrally welded to the stent body by hot pressing.
将静电纺丝与热压成膜相结合在单层金属支架表面制作覆膜3,既增强了覆膜支架的柔顺性和通过性,又保证了覆膜3的拉伸性,确保支架在扩张后覆膜3保持良好的完整性。以可降解的成膜材料作为覆膜3,生物可控降解,在置入覆膜支架数月、血管损伤修复后,覆膜材料能完全降解,降低了支架血栓和再狭窄发生率。其中,通过电纺丝技术制作编织层2,可直接得到管网状支架;还能将生物相容性、抗凝血性以及细胞吸附性好的材料喷涂到管状支架的表面,从而使覆膜支架的表面性能得到明显的改善。Combining electrospinning with hot-pressing film forming a film 3 on the surface of a single-layer metal stent not only enhances the flexibility and passability of the stent, but also ensures the stretchability of the film 3, ensuring that the stent is expanding. The rear film 3 maintains good integrity. The biodegradable film-forming material is used as the film 3, and the film can be completely degraded after the stent is placed for several months and the vascular injury is repaired, which reduces the incidence of stent thrombosis and restenosis. Among them, the braided layer 2 can be directly obtained by electrospinning technology, and the tube mesh stent can be directly obtained; the biocompatible, anticoagulant and cell adsorbing materials can also be sprayed onto the surface of the tubular stent, thereby making the stent graft The surface properties are significantly improved.
所述编织层2采用电纺纤维材料。所述电纺纤维通常具有纳米级直径,比表面积大,而且均一性高,还具有轻质高强耐拉伸的特性。接收电纺丝,得到 纤维交错编织成的无纺布。这种无纺布在微观结构上既可以是纤维的取向排列,也可以是按照一定规律编织成的网状结构。纤维的密集程度和直径的大小决定了无纺布中孔的大小和孔隙率的高低。电纺纤维的这些结构特点使得材料不仅具有一定的力学性能,而且具有很好的生物仿生性,使得本发明单层金属覆膜支架满足其对细胞黏附性和膜渗透传质作用的要求。The woven layer 2 is made of an electrospun fiber material. The electrospun fibers generally have a nanometer diameter, a large specific surface area, and high uniformity, and also have the characteristics of light weight, high strength and tensile strength. Receiving electrospinning, getting A non-woven fabric in which fibers are interlaced. The non-woven fabric may be in the form of orientation of fibers or a network structure woven according to a certain rule. The density of the fibers and the size of the diameter determine the size and porosity of the pores in the nonwoven. These structural characteristics of the electrospun fiber make the material not only have certain mechanical properties, but also have good biomimetic properties, so that the single-layer metal-coated stent of the present invention satisfies the requirements for cell adhesion and membrane permeation and mass transfer.
所述覆膜3为可降解成膜材料。以可降解的成膜材料作为覆膜3,在生物体内可控的分解,参与人体的新陈代谢,并最终排出体外;生物可控降解,在置入覆膜支架数月、血管损伤修复后,覆膜材料能完全降解,降低了支架血栓和再狭窄发生率。The film 3 is a degradable film forming material. The degradable film-forming material is used as the film 3, which can be controlled and decomposed in the living body, participate in the metabolism of the human body, and finally excreted in the body; bio-controlled degradation, after being placed into the stent for several months, repairing the vascular injury, covering The membrane material is completely degraded, reducing the incidence of stent thrombosis and restenosis.
可降解成膜材料包括聚己内酯。所述可降解成膜材料包括聚乳酸(PLA)、聚羟基乙酸或聚己内酯(PCL)等可降解高分子材料。PCL为半结晶性高分子,极易与其他高分子共混;PCL作为脂肪族聚酯类高分子,生物相容性良好,可降解及速率可控,有一定的孔隙及机械强度,具有较高韧性。本发明利用PCL制备单层金属覆膜支架的覆膜,使得单层金属覆膜支架具有可控降解特性、柔韧性和良好拉伸性,既能有效封堵动脉破口,又能在血管破口完全修复后实现覆膜完全降解,从而有效降低支架血栓和再狭窄的发生率。Degradable film forming materials include polycaprolactone. The degradable film-forming material includes a degradable polymer material such as polylactic acid (PLA), polyglycolic acid or polycaprolactone (PCL). PCL is a semi-crystalline polymer, which is easily blended with other polymers. PCL is an aliphatic polyester polymer with good biocompatibility, degradable and controllable, and has certain pore and mechanical strength. High toughness. The invention utilizes PCL to prepare a film of a single-layer metal-coated stent, so that the single-layer metal-coated stent has controllable degradation characteristics, flexibility and good stretchability, and can effectively block the arterial fracture and break the blood vessel. After the mouth is completely repaired, the complete degradation of the membrane is achieved, thereby effectively reducing the incidence of stent thrombosis and restenosis.
所述热压的温度为160℃-240℃,确保膜与支架之间的复合强度,同时保证膜的微观结构不受到破坏,增强复合后的支架整体强度。The hot pressing temperature is 160 ° C - 240 ° C, ensuring the composite strength between the film and the stent, while ensuring that the microstructure of the film is not damaged, and enhancing the overall strength of the composite after the composite.
在以上的描述中阐述了很多具体细节以便于充分理解本发明。但是以上描述仅是本发明的较佳实施例而已,本发明能够以很多不同于在此描述的其它方式来实施,因此本发明不受上面公开的具体实施的限制。同时任何熟悉本领域技术人员在不脱离本发明技术方案范围情况下,都可利用上述揭示的方法和技术内容对本发明技术方案做出许多可能的变动和修饰,或修改为等同变化的等效实施例。凡是未脱离本发明技术方案的内容,依据本发明的技术实质对以上实施例所做的任何简单修改、等同变化及修饰,均仍属于本发明技术方案保护的范围内。 Numerous specific details are set forth in the above description in order to provide a thorough understanding of the invention. However, the above description is only a preferred embodiment of the present invention, and the present invention can be implemented in many other ways than those described herein, and thus the present invention is not limited by the specific embodiments disclosed above. At the same time, any person skilled in the art can make many possible changes and modifications to the technical solutions of the present invention by using the methods and technical contents disclosed above, or modify the equivalent implementation of equivalent changes without departing from the scope of the technical solutions of the present invention. example. Any simple modifications, equivalent changes, and modifications made to the above embodiments in accordance with the technical spirit of the present invention are still within the scope of the technical solutions of the present invention.

Claims (5)

  1. 一种生物可降解高分子膜单层金属覆膜支架,其特征在于,包括管状的单层金属支架主体,支架表面的编织层,以及覆盖在所述支架主体外侧的覆膜;其中,所述编织层是在整个支架主体表面,由静电纺丝编织而成的网状结构;所述覆膜通过热压与支架主体焊接为一体。A biodegradable polymer film single-layer metal-coated stent, comprising: a tubular single-layer metal stent body, a braid layer on the surface of the stent, and a coating covering the outside of the stent body; wherein The woven layer is a mesh structure woven by electrospinning on the entire surface of the stent body; the film is welded to the body of the stent by heat pressing.
  2. 根据权利要求1所述的覆膜支架,其特征在于,所述编织层采用电纺纤维材料。The stent graft of claim 1 wherein said woven layer is of an electrospun fibrous material.
  3. 根据权利要求1所述的覆膜支架,其特征在于,所述覆膜为可降解成膜材料。The stent graft according to claim 1, wherein the coating is a degradable film-forming material.
  4. 根据权利要求3所述的覆膜支架,其特征在于,所述可降解成膜材料包括聚乳酸、聚羟基乙酸或聚己内酯。The stent graft of claim 3 wherein said degradable film forming material comprises polylactic acid, polyglycolic acid or polycaprolactone.
  5. 根据权利要求1所述的覆膜支架,其特征在于,所述热压的温度为160℃-240℃。 The stent graft according to claim 1, wherein the hot pressing temperature is from 160 ° C to 240 ° C.
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