WO2006058479A1 - A stent with impenetrable grooves or blind holes and a method for manufacturing it - Google Patents
A stent with impenetrable grooves or blind holes and a method for manufacturing it Download PDFInfo
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- WO2006058479A1 WO2006058479A1 PCT/CN2005/001773 CN2005001773W WO2006058479A1 WO 2006058479 A1 WO2006058479 A1 WO 2006058479A1 CN 2005001773 W CN2005001773 W CN 2005001773W WO 2006058479 A1 WO2006058479 A1 WO 2006058479A1
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- stent
- main support
- blind hole
- blood vessel
- groove
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
- A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
- A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
- A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/88—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure the wire-like elements formed as helical or spiral coils
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
- A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
- A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
- A61F2002/91508—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other the meander having a difference in amplitude along the band
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
- A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
- A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
- A61F2002/91525—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other within the whole structure different bands showing different meander characteristics, e.g. frequency or amplitude
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
- A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
- A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
- A61F2002/91533—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other characterised by the phase between adjacent bands
- A61F2002/91541—Adjacent bands are arranged out of phase
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
- A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
- A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
- A61F2002/9155—Adjacent bands being connected to each other
- A61F2002/91558—Adjacent bands being connected to each other connected peak to peak
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2230/0002—Two-dimensional shapes, e.g. cross-sections
- A61F2230/0028—Shapes in the form of latin or greek characters
- A61F2230/0054—V-shaped
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
- A61F2250/0068—Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir
Definitions
- Figure 3 is a partial structural schematic view of Embodiment 2 of the stent of the present invention.
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Optics & Photonics (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Physics & Mathematics (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
A stent with impenetrable grooves or blind holes and a method for manufacturing the stent are provided. The stent comprises straight main struts (2) and U-shaped connecting struts for linking the main struts (3). Impenetrable grooves (1) or blind holes are provided on the outer surfaces of the middle parts of the main struts. The grooves or blind holes are coated with therapeutic substances.
Description
一种开有非穿透性槽或盲孔的血管支架及其制作方法 技术领域 Vascular stent with non-penetrating groove or blind hole and manufacturing method thereof
本发明属于医疗器械技术领域， 特别涉及在治疗心血管疾病的手术中， 植入冠 状动脉血管的支架设计。 背景技术 The invention belongs to the technical field of medical instruments, and particularly relates to a stent design for implanting a coronary artery in a surgery for treating cardiovascular diseases. Background technique
在治疗心血管疾病的各种手术中， 经皮球囊腔内冠状动脉成形术 （PTCA)是 近年来迅速发展起来的一项新的治疗手段，它通过从股动脉切入的支架 /球囊导管输 送系统， 本申请人提出一种由直形主支撑条和连接主支撑条的马蹄形连接条构成的 支架， 该支架在医学影像设备的引导下， 与球囊导管一起被送达冠状动脉的病变狭 窄处， 通过球囊的充气扩张， 使支架撑开狭窄的血管， 从而达到治疗的目的。 In various procedures for the treatment of cardiovascular disease, percutaneous balloon endoscopic coronary angioplasty (PTCA) is a new treatment that has developed rapidly in recent years. It passes through a stent/balloon catheter that is cut from the femoral artery. The delivery system, the Applicant proposes a stent consisting of a straight main support strip and a horseshoe-shaped connecting strip connecting the main support strips, which is guided by a medical imaging device and delivered to the coronary artery along with the balloon catheter In the stenosis, through the inflation of the balloon, the stent is opened to a narrow blood vessel for therapeutic purposes.
通常的金属支架在植入冠状动脉后被迅速撑开， 对病变处的血管造成损伤， 并 且由于金属表面直接与血管壁及血液接触， 刺激了人体对异物的排异功能， 金属表 面很快被再生细胞膜包覆， 细胞膜的生长有可能减小甚至阻塞支架扩张形成的新的 血流通道， 造成再狭窄， 研究表明， 支架植入患者的再狭窄率约 30%。 The usual metal stent is rapidly distracted after implantation in the coronary artery, causing damage to the blood vessel in the lesion, and because the metal surface directly contacts the blood vessel wall and blood, stimulating the human body's function of exchanging foreign matter, the metal surface is quickly Regeneration of cell membrane coating, cell membrane growth may reduce or even block the new blood flow channel formed by stent expansion, resulting in restenosis, studies have shown that stent implantation patients with a restenosis rate of about 30%.
为了防止再狭窄的发生， 一些含有阻止血管细胞膜生长药物的涂层被涂覆在支 架的表面。 由于支架在送达血管狭窄处之后被球囊撑开， 形状有很大的改变， 特别 是一些曲率较大的连接条的弯曲处， 形状的改变也很大， 很容易使涂覆在此处的药 物涂层发生脱落。 脱落的涂层块随血流运动， 很可能形成血栓， 造成新的危害。 发明内容 In order to prevent the occurrence of restenosis, some coatings containing drugs that block the growth of vascular cell membranes are coated on the surface of the stent. Since the stent is stretched by the balloon after being delivered to the stenosis of the blood vessel, the shape is greatly changed, especially the curvature of the connecting strip with a large curvature, and the shape changes greatly, so it is easy to apply it here. The drug coating peeled off. The detached coating block moves with the bloodstream and is likely to form a thrombus, causing new hazards. Summary of the invention
本发明的目的是为克服已有技术的不足之处， 提出一种开有非穿透性槽或盲孔 的血管支架， 可改善药物涂层在支架上的附着能力， 延'长药物的释放时间。 The object of the present invention is to overcome the deficiencies of the prior art, and to provide a blood vessel stent with a non-penetrating groove or a blind hole, which can improve the adhesion of the drug coating on the stent and prolong the release of the drug. time.
本发明的另一目的是提出上述具有非穿透性槽或盲孔支架的加工方法。具有操 作简单易行的特点。 Another object of the present invention is to provide a method of processing described above having a non-penetrating groove or blind hole holder. It is easy to operate.
本发明提出的幵有非穿透性槽或盲孔的血管支架， 由直形主支撑条和连接主支 撑条的马蹄形连接条构成， 所述主支撑条的外表面开有非穿透性的槽或打有多个盲 孔， 在该槽或孔中嵌入药物涂层。 The blood vessel stent with non-penetrating groove or blind hole proposed by the invention is composed of a straight main supporting strip and a horseshoe-shaped connecting strip connecting the main supporting strip, and the outer surface of the main supporting strip is non-penetrating The slot or punch has a plurality of blind holes in which the drug coating is embedded.
进一步， 本发明提出的开有非穿透性槽或盲孔的血管支架， 所述的槽或盲孔中
嵌入的药物涂层含有三氧化二砷（AS203)， 这种药物能促进损伤后的血管平滑肌细 胞凋亡， 从而降低损伤后血管再狭窄的可能性。 Further, the invention provides a blood vessel stent with a non-penetrating groove or a blind hole, in the groove or the blind hole The embedded drug coating contains arsenic trioxide (AS 2 0 3 ), which promotes apoptosis of vascular smooth muscle cells after injury, thereby reducing the likelihood of restenosis after injury.
本发明提出制备上述血管支架的一种方法， 包括以下步骤： The invention proposes a method for preparing the above blood vessel stent, comprising the following steps:
1 )制备 （可采用已知方法）或直接选用带有主支撑条及连接条的成型支架； 1) preparation (known methods can be used) or directly using a shaped support with a main support strip and a connecting strip;
2)采用激光加工、 电子束加工或化学刻蚀方法， 在该成型支架的主支撑条上 开非穿透性的槽或打盲孔； 2) using a laser processing, electron beam processing or chemical etching method to open a non-penetrating groove or blind hole on the main support strip of the forming bracket;
3)在所述槽或盲孔中涂覆药物涂层 （具体可采用已知方法制备)。 3) Applying a drug coating (specifically prepared by known methods) in the trough or blind hole.
本发明的特点是使药物涂层可嵌入到槽或孔中。 槽或孔位于支撑条的中部， 其 深度不应影响条的支撑力。 由于处在主支撑条上而不是连接条上， 这些槽或孔在支 架被压缩或撑开时基本上不发生变形， 或者变形极小， 避免了涂层与支架金属表面 之间的相对移动， 从根本上解决了涂层脱落的问题， 改善了药物在支架上的附着能 力。 又由于药物涂层被镶嵌在槽或孔中， 其被血液冲蚀或被血管壁磨蚀的几率也很 小， 涂层的厚度可适当增加， 从而延长了药物的释放时间。 A feature of the invention is that the drug coating can be embedded in a trough or well. The groove or hole is located in the middle of the support strip and its depth should not affect the support force of the strip. Due to being on the main support strip rather than the tie strips, the grooves or holes are substantially free of deformation when the support is compressed or expanded, or the deformation is minimal, thereby avoiding relative movement between the coating and the metal surface of the support, The problem of peeling off the coating is fundamentally solved, and the adhesion ability of the drug on the stent is improved. Moreover, since the drug coating is embedded in the groove or the hole, the probability of being abraded by the blood or abraded by the blood vessel wall is also small, and the thickness of the coating layer can be appropriately increased, thereby prolonging the release time of the drug.
发明人的研究进一步表明， 当所述的药物涂层含有三氧化二砷时， 本发明的血 管支架植入血管后发生再狭窄的几率进一步降低， 可低至 5%以下。 所述的药物涂 层均可采用现有技术中的药物涂层， 只是其中的活性成分选用三氧化二砷， 每个支 架三氧化二砷的剂量范围是： 10~80μ 发明人通过三十多例动物试验发现， 三氧 化二砷对新西兰白兔左颈动脉、骼动脉的球囊损伤后的血管平滑肌细胞的凋亡有促 进作用， 也可诱导大鼠胸主动脉损伤的血管平滑肌细胞凋亡。 三氧化二砷有剧毒， 不宜进行全身系统的用药。 目前应用的全身系统的药物在局部血管损伤处的药物浓 度极低， 一般在 S^m kg-1^以下， 这个剂量是安全的。三氧化二砷在血管局部损 伤处的释放曲线 （如图 6所示）表明局部组织药物浓度高， 而系统机体的药物浓度 低， 因而含有剧毒三氧化二砷的药物涂层不会对系统机体产生影响。 缓慢释放的剧 毒三氧化而砷， 不仅可以对损伤的血管平滑肌细胞的增生起到很好的抑制作用， 并 且可以杀死附着在血管支架表面的细胞， 抑制细胞膜在血管支架表面的生长， 从而 降低冠状动脉介入治疗的再狭窄率。 The inventors' research further indicates that when the drug coating contains arsenic trioxide, the probability of restenosis after implantation of the blood vessel stent of the present invention is further reduced to less than 5%. The drug coating can use the prior art drug coating, except that the active ingredient is arsenic trioxide, and the dosage range of each arsenic trioxide is: 10~80μ. The inventors discovered through more than 30 animal experiments, arsenic trioxide. It can promote the apoptosis of vascular smooth muscle cells after balloon injury of the left carotid artery and iliac artery in New Zealand white rabbits, and also induce the apoptosis of vascular smooth muscle cells injured by thoracic aorta in rats. Arsenic trioxide is highly toxic and should not be administered systemically. The currently applied systemic system of drugs has a very low drug concentration at local vascular lesions, typically below S^m kg- 1 ^, which is safe. The release profile of arsenic trioxide in the local lesion of the blood vessel (as shown in Fig. 6) indicates that the local tissue drug concentration is high, and the drug concentration of the system body is low, so the drug coating containing the highly toxic arsenic trioxide does not affect the system body. The slow release of highly toxic trioxide and arsenic can not only inhibit the proliferation of damaged vascular smooth muscle cells, but also kill cells attached to the surface of the vascular stent, inhibiting the growth of the cell membrane on the surface of the vascular stent. Reduce the rate of restenosis in coronary interventions.
本发明的有益效果是： 改善药物涂层在支架上的附着能力， 延长药物的释放时 间， 降低了支架植入后的再狭窄率。 附图说明
图 l是本发明的支架的平面展开图。 - 图 2是本发明的支架的实施例 1局部结构示意图。 The beneficial effects of the invention are: improving the adhesion ability of the drug coating on the stent, prolonging the release time of the drug, and reducing the restenosis rate after the stent is implanted. DRAWINGS Figure 1 is a plan development view of the stent of the present invention. - Figure 2 is a partial structural schematic view of Embodiment 1 of the stent of the present invention.
图 3是本发明的支架的实施例 2局部结构示意图。 Figure 3 is a partial structural schematic view of Embodiment 2 of the stent of the present invention.
图 4是本发明的支架的实施例 3局部结构示意图。 Fig. 4 is a partial structural view showing a third embodiment of the stent of the present invention.
图 5是本发明的支架的实施例 4局部结构示意图。 Fig. 5 is a partial structural schematic view of a fourth embodiment of the stent of the present invention.
图 6为药物涂层含有三氧化二砷的本发明的支架在动物体内时间一组织药物浓 度曲线图。 具体实施方式 Figure 6 is a graph showing the time-to-tissue drug concentration of the stent of the present invention containing arsenic trioxide in an animal body. detailed description
下面结合附图和实施例对本发明作进一步说明。 The invention will now be further described with reference to the accompanying drawings and embodiments.
本发明的支架结构如图 1所示， 由直形主支撑条 2和连接主支撑条的马蹄形连 接条 3构成， 主支撑条 2中部的外表面开有非穿透性的槽 1 (或打有多个盲孔)，在 该槽或孔中可嵌入药物涂层 （图中未示出）。 The bracket structure of the present invention is composed of a straight main support strip 2 and a horseshoe-shaped connecting strip 3 connecting the main support strips. The outer surface of the central portion of the main support strip 2 is provided with a non-penetrating groove 1 (or There are a plurality of blind holes) in which a drug coating (not shown) can be embedded.
本发明的支架的制备方法， 包括以下步骤： The preparation method of the stent of the invention comprises the following steps:
1 )制备 （可采用已知方法）或直接选用带有主支撑条及连接条的成型支架； 1) preparation (known methods can be used) or directly using a shaped support with a main support strip and a connecting strip;
2) 采用激光加工、 电子束加工或化学刻蚀方法， 在成型支架的主支撑条上开 非穿透性的槽或打盲孔； 2) using a laser processing, electron beam processing or chemical etching method to open a non-penetrating groove or blind hole on the main support strip of the molded bracket;
3)在所述槽或盲孔中涂覆药物涂层 （具体采用已知方法制备）。 3) Applying a drug coating (specifically prepared by known methods) in the trough or blind hole.
本发明的实施例 1的结构如图 2所示， 图 2是支架的局部示意图， 在本实施例 中， 主支撑条 2宽度为 0.09mm， 厚度为 0.09mm。利用化学刻蚀技术制作出宽度为 0.03mm,长度为 0.40〜1.90mm (根据不同的主支撑条的长度而定），深度为 0.02mm 的非穿透性直槽 1，直槽 1中嵌入的药物涂层的三氧化二砷含量为 10〜80μβ/个。化 学刻蚀的具体方法为： 首先在支架表面涂一层耐蚀涂料（本实施例采用丁基橡胶)， 用激光束（本实施例釆用的激光功率密度为 103~104W/cm2)烧蚀掉支架主支撑条上 将要刻槽或打孔处的耐蚀涂料， 然后将支架置于腐蚀液中进行刻蚀。 The structure of Embodiment 1 of the present invention is shown in Fig. 2. Fig. 2 is a partial schematic view of the bracket. In this embodiment, the main support strip 2 has a width of 0.09 mm and a thickness of 0.09 mm. A non-penetrating straight groove 1 having a width of 0.03 mm, a length of 0.40 to 1.90 mm (depending on the length of different main support bars), a depth of 0.02 mm, and a straight groove 1 embedded therein is formed by a chemical etching technique. The arsenic trioxide content of the drug coating is 10 to 80 μ β /piece. The specific method of chemical etching is as follows: Firstly, a corrosion-resistant coating is applied on the surface of the stent (the butyl rubber is used in this embodiment), and a laser beam is used. (The laser power density used in this embodiment is 10 3 to 10 4 W/cm. 2 ) Absorb the corrosion-resistant coating on the main support strip of the bracket that will be grooved or punched, and then place the bracket in the etching solution for etching.
本发明的实施例 2的结构如图 3所示， 图 3是支架的局部示意图， 在本实施例 中， 主支撑条 2 宽度为 0.10mm, 厚度为 0.10rnm。 利用激光技术制作出直径为 0.03mm, 深度为 0.02mm的呈直线排列的盲孔 4, 盲孔 4中嵌入的药物涂层的三氧 化二砷含量为 10〜80μ§/个。 激光加工的具体方法为： 釆用波长为 1.06μπι、 光斑直 径为 30〜40μιη、 激光功率密度为 107~10sW/cm2的脉冲激光束， 在所述主支撑条上
开非穿透性的槽或打盲孔。 The structure of Embodiment 2 of the present invention is shown in Fig. 3. Fig. 3 is a partial schematic view of the bracket. In this embodiment, the main support strip 2 has a width of 0.10 mm and a thickness of 0.10 rnm. A linear blind hole 4 having a diameter of 0.03 mm and a depth of 0.02 mm was produced by laser technology, and the arsenic trioxide content of the drug coating embedded in the blind hole 4 was 10 to 80 μ § / piece. The specific method of laser processing is as follows: a pulsed laser beam having a wavelength of 1.06 μm, a spot diameter of 30 to 40 μm, and a laser power density of 10 7 to 10 s W/cm 2 is used on the main support bar. Open non-penetrating grooves or blind holes.
本发明的实施例 3的结构如图 4所示， 图 4是支架的局部示意图， 在本实施例 中， 主支撑条 2宽度为 0.11mm, 厚度为 0.10mm。 利用高能电子束制作出宽度为 0.04mm, 端点直线距离为 0.40〜1.90mm (根据不同的主支撑条的长度而定）， 深度 为 0.018mm的折线（或曲线）型非穿透性槽 5, 槽 5中嵌入的药物涂层的三氧化二 砷含量为 10〜80μδ/个。 电子束加工的具体方法为： 将所述支架放在真空室中， 抽 真空至 10'3〜10_4Pa，电流 5〜8mA，通过磁聚集系统将电子束汇聚成直径 30〜40μιη 的斑， 使功率密度达到 107W/cm2后， 在该支架的支撑条上开非穿透性的槽或打盲 孔。 The structure of Embodiment 3 of the present invention is shown in Fig. 4. Fig. 4 is a partial schematic view of the bracket. In the present embodiment, the main support strip 2 has a width of 0.11 mm and a thickness of 0.10 mm. A high-energy electron beam is used to produce a polygonal (or curved) non-penetrating groove 5 having a width of 0.04 mm, an end straight line distance of 0.40 to 1.90 mm (depending on the length of different main support bars), and a depth of 0.018 mm. The drug coating embedded in the tank 5 has a arsenic trioxide content of 10 to 80 μ δ /piece. The specific method of electron beam processing is as follows: placing the holder in a vacuum chamber, evacuating to 10' 3 ～10 _ 4 Pa, current 5 to 8 mA, and concentrating the electron beams into spots having a diameter of 30 to 40 μm through a magnetic aggregation system. After the power density reached 10 7 W/cm 2 , non-penetrating grooves or blind holes were opened on the support strip of the stent.
本发明的实施例 4的结构如图 5所示， 图 5是支架的局部示意图， 在本实施例 中， 主支撑条 2宽度为 0.12min， 厚度为 0.12mm。 利用激光技术制作（具体方法同 实施例 2) 出直径为 0.04mm， 深度为 0.02mm的呈不规则分布的盲孔 6。 盲孔 4中 嵌入的药物涂层的三氧化二砷含量为 10〜80μ§/个。
The structure of Embodiment 4 of the present invention is shown in Fig. 5. Fig. 5 is a partial schematic view of the bracket. In the present embodiment, the main support strip 2 has a width of 0.12 min and a thickness of 0.12 mm. It was produced by laser technology (the specific method is the same as in Example 2). The blind holes 6 having an irregular diameter of 0.04 mm and a depth of 0.02 mm were formed. The arsenic trioxide content of the drug coating embedded in the blind hole 4 is 10 to 80 μ § / piece.
Claims
1. 一种开有非穿透性槽或盲孔的血管支架， 由直形主支撑条和连接主支撑条 的马蹄形连接条构成， 其特征在于， 所述主支撑条的外表面开有非穿透性的槽或打 有多个盲孔， 在该槽或孔中嵌入药物涂层。 A blood vessel stent having a non-penetrating groove or a blind hole, comprising a straight main support strip and a horseshoe-shaped connecting strip connecting the main support strip, wherein the outer surface of the main support strip is open A penetrating groove or a plurality of blind holes in which a drug coating is embedded.
2. 如权利要求 1所述的血管支架， 其特征在于， 所述槽是直线型、 折线型或 曲线型。 The blood vessel stent according to claim 1, wherein the groove is a linear type, a polygonal line type or a curved type.
3. 如权利要求 1所述的血管支架， 其特征在于， 所述盲孔的排列呈直线式， 呈曲折式， 或其他不规则的分布形式。 3. The blood vessel stent according to claim 1, wherein the blind holes are arranged in a straight line, in a meandering manner, or in other irregularly distributed forms.
4. 如权利要求 1或 2所述的血管支架， 其特征在于， 所述槽的深度为 0.018〜 0.02mm, 槽的宽度为 0.03〜0.04mm。 The blood vessel stent according to claim 1 or 2, wherein the groove has a depth of 0.018 to 0.02 mm and a groove width of 0.03 to 0.04 mm.
5.如权利要求 1或 3所述的血管支架，其特征在于，所述盲孔的深度为 0.018〜 0.02mm, 盲孔的直径为 0.03〜0.04mm。 The blood vessel stent according to claim 1 or 3, wherein the blind hole has a depth of 0.018 to 0.02 mm, and the blind hole has a diameter of 0.03 to 0.04 mm.
6. 如权利要求 1或 2或 3所述的血管支架， 其特征在于， 所述的药物涂层含 有三氧化二砷。 The blood vessel stent according to claim 1 or 2 or 3, wherein the drug coating layer contains arsenic trioxide.
7. 一种开有非穿透性槽或盲孔的血管支架的制备方法， 包括以下步骤： 7. A method of preparing a vascular stent having a non-penetrating groove or a blind hole, comprising the steps of:
1 )制备或直接选用带有主支撑条及连接条的成型支架； 1) preparing or directly selecting a forming bracket with a main support bar and a connecting strip;
2)釆用激光加工、 电子束加工或化学刻蚀方式在所述主支撑条上开非穿透性 的槽或打盲孔； 2) using a laser processing, electron beam processing or chemical etching to open non-penetrating grooves or blind holes in the main support strip;
3 )在所述槽或盲孔中涂覆药物涂层。 3) Applying a drug coating in the trough or blind hole.
8. 如权利要求 7所述的方法， 其特征在于， 所述步骤 2)中釆用激光加工方法 为： 采用波长为 1.06μηι、 光斑直径为 30〜40μιη、 激光功率密度为 107~108W/cm2 的脉冲激光束， 在所述主支撑条上开非穿透性的槽或打盲孔。 8. The method according to claim 7, wherein the laser processing method in the step 2) is: using a wavelength of 1.06 μηι, a spot diameter of 30 to 40 μm, and a laser power density of 10 7 to 10 8 . A pulsed laser beam of W/cm 2 is used to open a non-penetrating groove or blind hole on the main support bar.
9. 如权利要求 7所述的方法， 其特征在于， 所述步骤 2)采用电子束加工方法 为： 将所述支架放在真空室中， 抽真空至 l(T3〜10_4Pa， 电流 5〜8mA， 通过磁聚集 系统将电子束汇聚成直径为 30〜40μπι的斑， 使功率密度达到 107W/cm2， 在该支架 的支撑条上开非穿透性的槽或打盲孔。 9. The method according to claim 7, wherein the step 2) adopts an electron beam processing method: placing the holder in a vacuum chamber and evacuating to 1 (T 3 ～10 _ 4 Pa, current) 5~8mA, the electron beam is condensed into a spot with a diameter of 30~40μππ by a magnetic focusing system, so that the power density reaches 10 7 W/cm 2 , and a non-penetrating groove or blind hole is opened on the support strip of the bracket. .
10. 如权利要求 7所述的方法， 其特征在于， 所述步骤 2) 中釆用化学刻蚀方 法为： 首先在支架表面涂一层耐蚀涂料， 用激光束烧蚀掉支架主支撑条上将要刻槽 或打孔处的耐蚀涂料， 然后将支架置于腐蚀液中进行刻蚀。
10. The method according to claim 7, wherein the step 2) is performed by chemical etching: first coating a surface of the stent with a corrosion resistant coating, and abrading the main support strip with a laser beam. The corrosion-resistant coating is to be grooved or punched, and then the stent is placed in an etching solution for etching.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410096617 CN1605366A (en) | 2004-12-03 | 2004-12-03 | Vascular stent mounted with non penetrable slot or blind hole and its preparing method |
| CN200410096617.4 | 2004-12-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2006058479A1 true WO2006058479A1 (en) | 2006-06-08 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2005/001773 WO2006058479A1 (en) | 2004-12-03 | 2005-10-27 | A stent with impenetrable grooves or blind holes and a method for manufacturing it |
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| CN (1) | CN1605366A (en) |
| WO (1) | WO2006058479A1 (en) |
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| US9089446B2 (en) | 2008-11-04 | 2015-07-28 | Shanghai Microport Medical (Group) Co., Ltd. | Coronary artery vascular stent with medicine carrying slots |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1605366A (en) | 2005-04-13 |
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