WO2015174711A1 - Stent for blood vessels, having drug-impregnated biodegradable coating film - Google Patents

Stent for blood vessels, having drug-impregnated biodegradable coating film Download PDF

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Publication number
WO2015174711A1
WO2015174711A1 PCT/KR2015/004720 KR2015004720W WO2015174711A1 WO 2015174711 A1 WO2015174711 A1 WO 2015174711A1 KR 2015004720 W KR2015004720 W KR 2015004720W WO 2015174711 A1 WO2015174711 A1 WO 2015174711A1
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Prior art keywords
coating film
drug
stent
biodegradable
drugs
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PCT/KR2015/004720
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French (fr)
Korean (ko)
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권혁문
한종현
김은진
박헌국
장봉석
윤호
김선종
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주식회사 엠아이텍
연세대학교 산학협력단
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Publication of WO2015174711A1 publication Critical patent/WO2015174711A1/en

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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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances

Definitions

  • the present invention relates to a vascular stent having a biodegradable coating film carrying a drug.
  • Vascular disease is a disease in which blood vessels are blocked or narrowed due to ingestion of fatty foods, hyperlipidemia, obesity and smoking, stress and lack of exercise, and diabetes. This causes blood circulation disorders, causing leg swelling and muscle pain, and in severe cases, it may be necessary to cut the site with ischemic ulcers.
  • angioplasty is performed to expand a narrowed blood vessel by inserting a balloon catheter or the like into a blood vessel.
  • angioplasty has a problem that stenosis may occur due to chronic contraction and expansion of neovascularization of the expanded blood vessel and narrowing or clogging of the blood vessel after the procedure.
  • Korean Laid-Open Patent Publication No. 2012-0138974 (announced: 2012.12.27, hereinafter referred to as the prior art) after the angioplasty, by inserting the inside of the blood vessels by supporting the inner wall of the vessel, A stent is proposed to prevent stenosis of blood vessels caused by chronic contraction.
  • the stent of the prior art may cause damage to blood clots and blood vessels in the process of installing at the lesion site, and thus there is a problem in that neovascularization proliferates around the stent and in the stent bore, thereby causing stenosis of blood vessels.
  • An object of the present invention is to provide a stent that is inserted into the lesion to prevent the proliferation of neointima and prevent restenosis of blood vessels.
  • a blood vessel stent having a biodegradable coating film in which a drug is loaded has a plurality of shape memory alloy wires having a plurality of bends connected to each other, and having a hollow cylinder therein.
  • biodegradable polymer polyvinyl alcohol, polyethylene glycol, polylactide, polyglycolide, polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazene, polyanhydride, polyamino acid, cellulose acetate butyl It may be a polymer selected from the group consisting of at least one or two or more copolymers of latex, cellulose triacetate, polyacrylate, polyacrylamide, polyurethane, polysiloxane, polyvinylpyrrolidone.
  • the drug supported on the coating layer is an anticancer agent including paclitaxel series, an immunosuppressive agent including sirolimus and limus series, and an antiplatelet agent including cilostazol. At least one or more of the drugs selected from the group consisting of can be used.
  • the coating film may be formed with a plurality of layers for individually supporting a plurality of different drugs.
  • a blood vessel stent having a biodegradable coating film carrying a drug according to the present invention has the following effects.
  • the drug to inhibit the proliferation of the neointimal membrane is supported on the coating film of the stent, the drug is delivered to the lesion site, thereby preventing the restenosis of blood vessels.
  • the drug is released in the process of decomposing the biodegradable polymer of the coating film, there is an effect that the drug is continuously released.
  • FIG. 1 is a side view showing a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
  • Figure 2 is a cutaway perspective view of a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
  • Figure 3 is a flow chart illustrating a method of manufacturing a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
  • FIG. 1 is a side view showing a stenting for blood vessels having a biodegradable coating film loaded with a drug according to an embodiment of the present invention
  • Figure 2 is a blood vessel having a biodegradable coating film loaded with a drug according to an embodiment of the present invention It is the cutting perspective view of the stent for dragons.
  • the vessel stent 100 having a biodegradable coating film on which the drug is loaded according to an embodiment of the present invention is a stent body 110, a drug ( 124 may include a coating film 120 formed of a biodegradable polymer 122 carrying thereon.
  • the stent body 110 has a plurality of metal wires 112 having a wavy shape along the longitudinal direction are connected in various forms such as a lattice, a mesh, and the like, and may have a cylindrical shape having a hollow in the longitudinal direction.
  • the shape memory alloy wire 112 constituting the stent body 110 may be formed of a material such as nickel-titanium alloy, and thus, the stent body 110 may be expanded or contracted in a circumferential direction at a specific temperature.
  • the stent main body 110 inserted into the lesion part of the blood vessel is expanded in the direction of the blood vessel inner wall to support the blood vessel inner wall, thereby preventing chronic contraction of the blood vessel.
  • the coating film 120 may be formed by wrapping the stent body 110 using a method such as dipping, ultrasonic spraying, and electrospinning.
  • the coating film 120 may be composed of a biodegradable polymer 122, which is biodegradable and converted into water or carbon dioxide, and a drug 124 supported on the biodegradable polymer 122 to inhibit the neointimal proliferation of the lesion site. .
  • the biodegradable polymer 122 is polyvinyl alcohol, polyethylene glycol, polylactide, polyglycolide, polylactide copolymer, polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazene, polyanhydride, poly At least one selected from the group consisting of amino acids, cellulose acetate butyrate, cellulose triacetate, polyacrylate, polyacrylamide, polyurethane, polysiloxane, polyvinylpyrrolidone or two or more copolymers may be applied. It doesn't work.
  • the biodegradable polymer 122 may have a different distribution depending on the type and composition ratio of the composition.
  • the drug 124 is a drug selected from the group consisting of an anticancer agent including a Paclitaxel family, an immunosuppressant including a family of Sirolimus and Limus, and an antiplatelet agent including Cilostazol. At least one of the above may be used, but is not limited thereto, and various drugs 124 may be used depending on the symptoms of the lesion.
  • the drug 124 may be gradually released by being exposed to the outside in the process of decomposing the biodegradable polymer 122.
  • the coating film 120 is formed surrounding the stent body 110, when the blood vessel stent 100 having the biodegradable coating film on which the drug is loaded is expanded in the direction of the blood vessel inner wall to support the inner wall, the coating film 120 The drug 124 can be delivered directly to the lesion site by being in close contact with the blood vessel inner wall.
  • the blood vessel stent 100 having a biodegradable coating film loaded with a drug inserted into the lesion site is expanded in the direction of the blood vessel wall to support the blood vessel inner wall, thereby preventing chronic contraction of the blood vessel, and the coating membrane 120 is the blood vessel inner wall. It can be in close contact.
  • the drug 124 exposed to the outside in the process of decomposing the biodegradable polymer 122 is directly delivered to the lesion site, it is possible to suppress the proliferation of the neo-intima.
  • the coating film 120 may be formed of a plurality of layers supporting each drug individually, in order to sequentially release a plurality of different drugs in the lesion area, each layer is a kind and release of the drug 124 supporting
  • the composition and composition ratio of the biodegradable polymer 122 may vary depending on the period.
  • the vessel stent 100 having a biodegradable coating film on which the drug is loaded may be a vessel stent inserted into a blood vessel lesion to treat a vascular disease.
  • Figure 3 is a flow chart showing the manufacturing process of a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
  • a method for forming the coating film 120 on the stent body 110 there are immersion method, ultrasonic spray method, electrospinning method and the like.
  • the method of forming the coating film 120 on the stent body 110 will be described in the electrospinning method using an electrospinning device.
  • a step of preparing the stent main body 110 is performed to evenly form the coating film 120 on the stent main body 110 (S100).
  • the stent body 110 may be manufactured by winding a metal wire 112 of a nitinol material having a diameter of about 50 to 150 microns in a net form on a jig for manufacturing a stent, and then performing heat treatment, and laser cutting. It can be produced by cutting the metal in the form of a tube in a manner.
  • the stent main body 110 may be manufactured by 3D printing.
  • the stent body 110 is inserted into and fixed to a roller-type collector provided in the electrospinning apparatus.
  • the coating solution loaded in the electrospinning apparatus may be prepared by varying the composition and composition ratio of the biodegradable polymer 122 according to the type and release period of the drug 124.
  • the coating solution loaded in the electrospinning apparatus is discharged in the collector direction to form the coating film 120 on the stent main body 110 fixed to the collector (S300).
  • the collector on which the stent main body 110 is fixed may be evenly applied to the stent main body 110 by rotating in the length axis of the stent main body 110.
  • a coating solution may be prepared in which the biodegradable polymer 122 is mixed according to the type and release period.
  • the order of the coating solution loaded and discharged in the electrospinning apparatus may be determined in the order of release of the drug 124.
  • the stent main body 110 to which the coating solution is adsorbed is placed in a vacuum dryer and dried at 70 ° C. for 24 hours, thereby obtaining a blood vessel stent 100 having a biodegradable coating film in which the drug having the coating film 120 is supported. Will be.
  • the present invention supports a drug that inhibits the proliferation of neointima in a coating film made of a biodegradable polymer, thereby controlling the release period of the drug supported on the coating film according to the composition and composition ratio of the biodegradable polymer, and release from the coating film
  • the drug is continuously delivered to the lesion site, thereby providing a stent for blood vessels having a biodegradable coating film containing a drug that inhibits proliferation of neointima and prevents restenosis of blood vessels.

Abstract

A stent for blood vessels, comprising a drug-impregnated biodegradable coating film, according to one embodiment of the present invention, comprises: a cylindrical stent main body in which a plurality of shape memory alloy wires having a plurality of bents are cross-connected, and having a cavity therein; and a coating film formed such that the stent main body is encompassed with a biodegradable polymer, wherein the coating film can be impregnated with a drug for inhibiting restenosis caused by neointimal hyperplasia of a lesion region. According to the present invention, a drug for inhibiting neointimal hyperplasia is impregnated in a coating film formed such that a stent is encompassed, and formed from a biodegradable polymer, and thus there are effects of preventing the restenosis of blood vessels by continuously delivering a drug to a lesion region during the degradation of a biodegradable polymer, and enabling the control of a drug release period according to the composition of a biodegradable polymer and the composition ratio thereof.

Description

약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트Vessel Stents with Biodegradable Coatings on Drugs
본 발명은 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트에 관한 것이다.The present invention relates to a vascular stent having a biodegradable coating film carrying a drug.
혈관질환은 기름진 음식의 섭취, 고지혈증, 비만과 흡연, 스트레스 및 운동부족, 당뇨병 등의 원인으로 인해, 혈관이 막히거나 좁아져 있는 질환을 말한다. 이로 인해 혈액순환장애가 발생하여, 다리가 저리는 현상 및 근육통증이 유발되기도 하며, 심할 경우에는 허혈성 궤양으로 해당 부위를 절단해야할 수도 있다.Vascular disease is a disease in which blood vessels are blocked or narrowed due to ingestion of fatty foods, hyperlipidemia, obesity and smoking, stress and lack of exercise, and diabetes. This causes blood circulation disorders, causing leg swelling and muscle pain, and in severe cases, it may be necessary to cut the site with ischemic ulcers.
따라서, 이러한 혈관질환을 치료하기 위해 풍선 카테터 등의 기구를 혈관에 삽입하여 좁아져 있는 혈관을 확장시키는 혈관성형술이 시행되고 있다.Therefore, in order to treat such vascular diseases, angioplasty is performed to expand a narrowed blood vessel by inserting a balloon catheter or the like into a blood vessel.
하지만, 이러한 혈관성형술은 확장된 혈관의 만성수축 및 신생내막 증식으로 인해 시술 이후 혈관이 다시 좁아지거나 막히는 재협착이 발생할 수 있는 문제점이 있다.However, such angioplasty has a problem that stenosis may occur due to chronic contraction and expansion of neovascularization of the expanded blood vessel and narrowing or clogging of the blood vessel after the procedure.
이러한 문제점을 해결하기 위해, 대한민국 공개특허공보 공개번호 제2012-0138974호 (공고일 : 2012.12.27, 이하, 종래기술이라 칭함)에서는 혈관성형술 이후, 혈관 내부에 삽입 설치하여 혈관 내벽을 지지함으로써, 혈관의 만성수축으로 인해 발생되는 혈관의 재협착을 방지하는 스텐트를 제시하였다.In order to solve this problem, Korean Laid-Open Patent Publication No. 2012-0138974 (announced: 2012.12.27, hereinafter referred to as the prior art) after the angioplasty, by inserting the inside of the blood vessels by supporting the inner wall of the vessel, A stent is proposed to prevent stenosis of blood vessels caused by chronic contraction.
*하지만, 종래기술의 스텐트는 병변부위에 설치하는 과정에서 혈전 및 혈관의 손상이 유발될 수 있으며, 그로 인해 스텐트 주위와 스텐트 내경 안에 신생내막이 증식함으로써 혈관의 재협착이 발생되는 문제점이 있다.* However, the stent of the prior art may cause damage to blood clots and blood vessels in the process of installing at the lesion site, and thus there is a problem in that neovascularization proliferates around the stent and in the stent bore, thereby causing stenosis of blood vessels.
본 발명은 상술한 문제점을 해결하기 위한 것으로, 병변부위에 삽입 설치되어 신생내막의 증식을 억제하여 혈관의 재협착을 방지하는 스텐트를 제공하는데 그 목적이 있다.An object of the present invention is to provide a stent that is inserted into the lesion to prevent the proliferation of neointima and prevent restenosis of blood vessels.
이러한 목적을 달성하기 위하여 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트는 다수의 굴곡이 형성된 복수개의 형상기억합금 와이어가 상호 교차 연결되며, 내부에 중공을 가지는 원통 형상의 스텐트 본체; 및 생분해성 고분자가 상기 스텐트 본체를 감싸며 형성되는 코팅막;을 포함하며, 상기 코팅막은 병변부위의 혈관 신생내막 증식에 의한 혈관의 재협착을 억제하기 위한 약물이 담지될 수 있다.In order to achieve this object, a blood vessel stent having a biodegradable coating film in which a drug is loaded according to an embodiment of the present invention has a plurality of shape memory alloy wires having a plurality of bends connected to each other, and having a hollow cylinder therein. A stent body in shape; And a coating film in which a biodegradable polymer surrounds the stent body, wherein the coating film may be loaded with a drug for inhibiting stenosis of blood vessels due to neovascularization of the lesion.
그리고, 상기 생분해성 고분자는, 폴리비닐알코올, 폴리에틸렌글리콜, 폴리락타이드, 폴리글리콜라이드, 폴리에틸렌 옥사이드, 폴리디옥사논, 폴리카프로락톤, 폴리포스파젠, 폴리안하이드라이드, 폴리아미노산, 셀룰로오스 아세테이트 부틸레이트, 셀룰로오스 트리아세테이트, 폴리아클릴레이트, 폴리아크릴아미드, 폴리우레탄, 폴리실록산, 폴리비닐피롤리돈 중 적어도 어느 하나 또는 둘 이상의 공중합체로 이루어진 군으로부터 선택된 고분자일 수 있다.In addition, the biodegradable polymer, polyvinyl alcohol, polyethylene glycol, polylactide, polyglycolide, polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazene, polyanhydride, polyamino acid, cellulose acetate butyl It may be a polymer selected from the group consisting of at least one or two or more copolymers of latex, cellulose triacetate, polyacrylate, polyacrylamide, polyurethane, polysiloxane, polyvinylpyrrolidone.
또한, 상기 코팅 층에 담지되는 약물은 파클리탁셀(Paclitaxel) 계열을 포함하는 항암제, 시롤리무스(Sirolimus) 및 리무스(Limus) 계열을 포함하는 면역억제제 및 실로스타졸(Cilostazol)을 포함하는 항혈소판제로 이루어진 군으로부터 선택된 약물 중 적어도 하나 이상이 사용될 수 있다.In addition, the drug supported on the coating layer is an anticancer agent including paclitaxel series, an immunosuppressive agent including sirolimus and limus series, and an antiplatelet agent including cilostazol. At least one or more of the drugs selected from the group consisting of can be used.
아울러, 상기 코팅막은 복수의 상이한 약물을 개별적으로 담지하기 위한 복수의 층이 형성될 수 있다.In addition, the coating film may be formed with a plurality of layers for individually supporting a plurality of different drugs.
본 발명에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트는, 다음과 같은 효과가 있다.A blood vessel stent having a biodegradable coating film carrying a drug according to the present invention has the following effects.
첫째, 스텐트의 코팅막에 신생내막의 증식을 억제하는 약물을 담지하여, 병변부위에 약물을 전달함으로써, 혈관의 재협착을 방지하는 효과가 있다.First, the drug to inhibit the proliferation of the neointimal membrane is supported on the coating film of the stent, the drug is delivered to the lesion site, thereby preventing the restenosis of blood vessels.
둘째, 생분해성 고분자 조성물 및 조성 비율에 따라, 생분해성 고분자에 담지되는 약물의 방출기간을 조절할 수 있는 효과가 있다.Second, according to the biodegradable polymer composition and composition ratio, there is an effect that can control the release period of the drug supported on the biodegradable polymer.
셋째, 코팅막의 생분해성 고분자가 분해되는 과정에서 약물이 방출됨으로써, 약물이 지속적으로 방출되는 효과가 있다.Third, the drug is released in the process of decomposing the biodegradable polymer of the coating film, there is an effect that the drug is continuously released.
도1은 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트를 도시한 측면도이다.1 is a side view showing a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
도2는 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트의 절단 사시도이다.Figure 2 is a cutaway perspective view of a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
도3은 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트의 제조방법을 나타낸 순서도이다.Figure 3 is a flow chart illustrating a method of manufacturing a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
본 발명의 바람직한 실시예에 대하여 첨부된 도면을 참조하여 더 구체적으로 설명하되, 이미 주지되어진 기술적 부분에 대해서는 설명의 간결함을 위해 생략하거나 압축하기로 한다.DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described in more detail with reference to the accompanying drawings, and the well-known technical parts will be omitted or compressed for brevity of description.
<스텐트의 구성><Configuration of the stent>
도1은 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트를 도시한 측면도이며, 도2는 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트의 절단 사시도이다.1 is a side view showing a stenting for blood vessels having a biodegradable coating film loaded with a drug according to an embodiment of the present invention, Figure 2 is a blood vessel having a biodegradable coating film loaded with a drug according to an embodiment of the present invention It is the cutting perspective view of the stent for dragons.
도1 내지는 도2를 참조하면, 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트(100)는 형상기억합금 와이어(112)로 구성된 스텐트 본체(110), 약물(124)를 담지한 생분해성 고분자(122)로 형성된 코팅막(120)을 포함할 수 있다.1 to 2, the vessel stent 100 having a biodegradable coating film on which the drug is loaded according to an embodiment of the present invention is a stent body 110, a drug ( 124 may include a coating film 120 formed of a biodegradable polymer 122 carrying thereon.
스텐트 본체(110)는 길이 방향을 따라 물결모양을 가지는 복수개의 금속 와이어(112)가 격자형, 메쉬형 등의 다양한 형태로 연결되며, 길이 방향으로 중공을 가지는 원통 형상일 수 있다.The stent body 110 has a plurality of metal wires 112 having a wavy shape along the longitudinal direction are connected in various forms such as a lattice, a mesh, and the like, and may have a cylindrical shape having a hollow in the longitudinal direction.
그리고, 스텐트 본체(110)를 구성하는 형상기억합금 와이어(112)는 니켈-티타늄 함금과 같은 소재가 사용되어, 특정 온도에서 스텐트 본체(110)는 둘레 방향으로 팽창 또는 수축될 수 있다.The shape memory alloy wire 112 constituting the stent body 110 may be formed of a material such as nickel-titanium alloy, and thus, the stent body 110 may be expanded or contracted in a circumferential direction at a specific temperature.
여기서, 혈관의 병변부위에 삽입 설치되는 스텐트 본체(110)는 혈관 내벽 방향으로 팽창되어 혈관 내벽을 지지함으로써, 혈관의 만성수축을 방지할 수 있다.Here, the stent main body 110 inserted into the lesion part of the blood vessel is expanded in the direction of the blood vessel inner wall to support the blood vessel inner wall, thereby preventing chronic contraction of the blood vessel.
코팅막(120)은 침지방식, 초음파 스프레이방식 및 전기방사 방식 등의 방법을 이용하여 스텐트 본체(110)를 감싸며 형성될 수 있다.The coating film 120 may be formed by wrapping the stent body 110 using a method such as dipping, ultrasonic spraying, and electrospinning.
또한, 코팅막(120)은 생분해되어 물 또는 이산화탄소 등으로 변환되는 생분해성 고분자(122) 및 생분해성 고분자(122)에 담지되어 병변부위의 신생내막 증식을 억제하는 약물(124)로 구성될 수 있다.In addition, the coating film 120 may be composed of a biodegradable polymer 122, which is biodegradable and converted into water or carbon dioxide, and a drug 124 supported on the biodegradable polymer 122 to inhibit the neointimal proliferation of the lesion site. .
생분해성 고분자(122)는 폴리비닐알코올, 폴리에틸렌글리콜, 폴리락타이드, 폴리글리콜라이드, 폴리락타이드 공중합체, 폴리에틸렌 옥사이드, 폴리디옥사논, 폴리카프로락톤, 폴리포스파젠, 폴리안하이드라이드, 폴리아미노산, 셀룰로오스 아세테이트 부틸레이트, 셀룰로오스 트리아세테이트, 폴리아클릴레이트, 폴리아크릴아미드, 폴리우레탄, 폴리실록산, 폴리비닐피롤리돈 중 적어도 하나 또는 둘 이상의 공중합체로 이루어진 군으로부터 선택되어 적용될 수 있으나, 이에 한정되지 않는다.The biodegradable polymer 122 is polyvinyl alcohol, polyethylene glycol, polylactide, polyglycolide, polylactide copolymer, polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazene, polyanhydride, poly At least one selected from the group consisting of amino acids, cellulose acetate butyrate, cellulose triacetate, polyacrylate, polyacrylamide, polyurethane, polysiloxane, polyvinylpyrrolidone or two or more copolymers may be applied. It doesn't work.
여기서, 생분해성 고분자(122)는 조성물의 종류 및 조성 비율에 따라 각기 다른 분해주기를 가질 수 있다.Here, the biodegradable polymer 122 may have a different distribution depending on the type and composition ratio of the composition.
약물(124)은 파클리탁셀(Paclitaxel)계열을 포함하는 항암제, 시롤리무스(Sirolimus) 및 리무스(Limus) 계열을 포함하는 면역억제제 및 실로스타졸(Cilostazol)을 포함하는 항혈소판제로 이루어진 군으로부터 선택된 약물 중 적어도 하나 이상이 사용될 수 있으나, 이에 한정되지 않고, 병변부위의 증상에 따라 다양한 약물(124)이 사용될 수 있다.The drug 124 is a drug selected from the group consisting of an anticancer agent including a Paclitaxel family, an immunosuppressant including a family of Sirolimus and Limus, and an antiplatelet agent including Cilostazol. At least one of the above may be used, but is not limited thereto, and various drugs 124 may be used depending on the symptoms of the lesion.
그리고, 약물(124)은 생분해성 고분자(122)가 분해되는 과정에서 외부로 노출됨으로써, 서서히 방출될 수 있다.In addition, the drug 124 may be gradually released by being exposed to the outside in the process of decomposing the biodegradable polymer 122.
여기서, 코팅막(120)은 스텐트 본체(110)를 감싸며 형성되기 때문에, 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트(100)가 혈관 내벽 방향으로 팽창되어 내벽을 지지할 때, 코팅막(120)이 혈관 내벽에 밀착됨으로써 약물(124)이 병변부위에 직접 전달될 수 있다.Here, since the coating film 120 is formed surrounding the stent body 110, when the blood vessel stent 100 having the biodegradable coating film on which the drug is loaded is expanded in the direction of the blood vessel inner wall to support the inner wall, the coating film 120 The drug 124 can be delivered directly to the lesion site by being in close contact with the blood vessel inner wall.
즉, 병변부위에 삽입 설치되는 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트(100)는 혈관 내벽 방향으로 팽창되어 혈관 내벽을 지지함으로써 혈관의 만성수축을 방지하며, 코팅막(120)이 혈관 내벽에 밀착될 수 있다. That is, the blood vessel stent 100 having a biodegradable coating film loaded with a drug inserted into the lesion site is expanded in the direction of the blood vessel wall to support the blood vessel inner wall, thereby preventing chronic contraction of the blood vessel, and the coating membrane 120 is the blood vessel inner wall. It can be in close contact.
이때, 생분해성 고분자(122)가 분해되는 과정에서 외부로 노출되는 약물(124)이 병변부위에 직접 전달됨으로써, 신생내막의 증식을 억제할 수 있게 된다.At this time, the drug 124 exposed to the outside in the process of decomposing the biodegradable polymer 122 is directly delivered to the lesion site, it is possible to suppress the proliferation of the neo-intima.
또한, 코팅막(120)은 병변부위에 상이한 복수의 약물을 순차적으로 방출하기 위해, 각 약물을 개별적으로 담지하는 복수의 층으로 형성될 수 있으며, 각 층은 담지하는 약물(124)의 종류 및 방출기간에 따라 생분해성 고분자(122)의 조성물 및 조성 비율이 달라질 수 있다.In addition, the coating film 120 may be formed of a plurality of layers supporting each drug individually, in order to sequentially release a plurality of different drugs in the lesion area, each layer is a kind and release of the drug 124 supporting The composition and composition ratio of the biodegradable polymer 122 may vary depending on the period.
여기서, 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트(100)는 혈관질환을 치료하기 위해 혈관의 병변부위에 삽입 설치되는 혈관용 스텐트일 수 있다.Here, the vessel stent 100 having a biodegradable coating film on which the drug is loaded may be a vessel stent inserted into a blood vessel lesion to treat a vascular disease.
<스텐트의 제조방법><Method of manufacturing stent>
도3은 본 발명의 일실시예에 따른 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트의 제조과정을 나타낸 순서도이다.Figure 3 is a flow chart showing the manufacturing process of a blood vessel stent having a biodegradable coating film loaded with a drug according to an embodiment of the present invention.
스텐트 본체(110)에 코팅막(120)을 형성시키기 위한 방법 으로는 침지방식, 초음파 스프레이 방식, 전기방사 방식 등이 있다.As a method for forming the coating film 120 on the stent body 110, there are immersion method, ultrasonic spray method, electrospinning method and the like.
이하에서는, 스텐트 본체(110)에 코팅막(120)을 형성하는 방법으로 전기방사장치를 이용한 전기방사 방식에 한해서 설명하도록 한다.Hereinafter, the method of forming the coating film 120 on the stent body 110 will be described in the electrospinning method using an electrospinning device.
스텐트 본체 준비단계Stent Body Preparation Step (S100) (S100)
스텐트 본체(110)에 코팅막(120)이 고르게 형성될 수 있도록 스텐트 본체(110)를 준비하는 단계가 이루어진다.(S100)A step of preparing the stent main body 110 is performed to evenly form the coating film 120 on the stent main body 110 (S100).
스텐트 본체(110)는 직경이 50 내지 150 미크론(micron) 정도인 니틴올 재질의 금속 와이어(112)를 스텐트 제조용 지그 위에 그물형태로 감은 뒤 열처리를 하여 제조될 수 있으며, 레이저커팅(Laser cutting) 방식을 통해 튜브 형태의 금속을 절단 가공함으로써 제조될 수 있다. The stent body 110 may be manufactured by winding a metal wire 112 of a nitinol material having a diameter of about 50 to 150 microns in a net form on a jig for manufacturing a stent, and then performing heat treatment, and laser cutting. It can be produced by cutting the metal in the form of a tube in a manner.
또한, 스텐트 본체(110)가 금속이 아닌 폴리머 등의 재질로 이루어질 경우엔 3D 프린팅(3D Printing) 방식을 통해 성형 제조될 수 있다.In addition, when the stent body 110 is made of a material such as a polymer rather than a metal, the stent main body 110 may be manufactured by 3D printing.
여기서, 스텐트 본체(110)의 표면에 붙어있는 이물질을 제거하기 위해 초음파세척기에 에탄올 및 증류수 혼합용매를 사용하여 1시간 동안 세척하고 50~70℃의 열풍 건조기에서 12~24시간동안 건조시킨 뒤, 전기방사장치에 마련된 롤러 형태의 콜렉터에 스텐트 본체(110)를 삽입 고정시킨다.Here, after washing for 1 hour using a mixed solvent of ethanol and distilled water in an ultrasonic cleaner to remove the foreign matter adhering to the surface of the stent body 110 and dried for 12 to 24 hours in a hot air dryer of 50 ~ 70 ℃, The stent body 110 is inserted into and fixed to a roller-type collector provided in the electrospinning apparatus.
코팅 용액 준비단계Coating Solution Preparation Step (S200) (S200)
이후, 생분해성 고분자(122)와 약물(124)을 혼합한 코팅용액을 전기방사장치에 장전하는 단계가 이루어진다.(S200)Thereafter, the step of loading the coating solution mixed with the biodegradable polymer 122 and the drug 124 to the electrospinning apparatus is made (S200).
여기서, 전기방사 장치에 장전되는 코팅용액은, 약물(124)의 종류 및 방출기간에 따라, 생분해성 고분자(122)의 조성물 및 조성 비율을 달리하여 준비될 수 있다.Here, the coating solution loaded in the electrospinning apparatus may be prepared by varying the composition and composition ratio of the biodegradable polymer 122 according to the type and release period of the drug 124.
코팅막 형성단계Coating film forming step (S300) (S300)
이어서, 전기방사장치에 장전된 코팅용액이 콜렉터 방향으로 토출되어 콜렉터에 고정된 스텐트 본체(110)에 코팅막(120)이 형성되는 단계가 이루어진다.(S300)Subsequently, the coating solution loaded in the electrospinning apparatus is discharged in the collector direction to form the coating film 120 on the stent main body 110 fixed to the collector (S300).
이때, 스텐트 본체(110)가 고정된 콜렉터는 스텐트 본체(110)의 길이축으로 회전함으로써, 스텐트 본체(110)에 코팅용액이 골고루 도포될 수 있다.At this time, the collector on which the stent main body 110 is fixed may be evenly applied to the stent main body 110 by rotating in the length axis of the stent main body 110.
만약, 병변부위에 상이한 복수의 약물을 순차적으로 방출하기 위해, 각 약물을 개별적으로 담지하는 복수의 코팅막을 형성하려 할 때, S200단계에서 각 층에 담지하는 약물(124)과 각 약물(124)의 종류 및 방출기간에 따른 생분해성 고분자(122)를 혼합한 코팅용액이 준비될 수 있다.If, in order to form a plurality of coating films supporting each drug individually, in order to sequentially release a plurality of different drugs on the lesion site, the drug 124 and each drug 124 supported on each layer in step S200 A coating solution may be prepared in which the biodegradable polymer 122 is mixed according to the type and release period.
여기서, 약물(124)의 방출 순서에 전기방사장치에 장전 및 토출되는 코팅용액의 순서가 정해질 수 있다.Here, the order of the coating solution loaded and discharged in the electrospinning apparatus may be determined in the order of release of the drug 124.
이후, 코팅용액이 흡착된 스텐트 본체(110)를 진공 건조기에 넣어 70℃에서 24시간동안 건조시킴으로써, 코팅막(120)을 가지는 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트(100)를 얻을 수 있게 된다.Thereafter, the stent main body 110 to which the coating solution is adsorbed is placed in a vacuum dryer and dried at 70 ° C. for 24 hours, thereby obtaining a blood vessel stent 100 having a biodegradable coating film in which the drug having the coating film 120 is supported. Will be.
결국, 본 발명은 생분해성 고분자로 이루어진 코팅막에 신생내막의 증식을 억제하는 약물을 담지하여, 생분해성 고분자의 조성물 및 조성 비율에 따라 코팅막에 담지되는 약물의 방출기간을 조절할 수 있고, 코팅막에서 방출되는 약물이 병변부위에 지속적으로 전달됨으로써, 신생내막의 증식을 억제하여 혈관의 재협착을 방지하는 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트를 제공한다.As a result, the present invention supports a drug that inhibits the proliferation of neointima in a coating film made of a biodegradable polymer, thereby controlling the release period of the drug supported on the coating film according to the composition and composition ratio of the biodegradable polymer, and release from the coating film The drug is continuously delivered to the lesion site, thereby providing a stent for blood vessels having a biodegradable coating film containing a drug that inhibits proliferation of neointima and prevents restenosis of blood vessels.
위에서 설명한 바와 같이 본 발명에 대한 구체적인 설명은 첨부된 도면을 참조한 실시예에 의해서 이루어졌지만, 상술한 실시예는 본 발명의 바람직한 예를 들어 설명하였을 뿐이기 때문에, 본 발명이 상기의 실시예에만 국한되는 것으로 이해되어져서는 아니 되며, 본 발명의 권리범위는 후술하는 청구범위 및 그 등가개념으로 이해되어져야 할 것이다.As described above, the detailed description of the present invention has been made by the embodiments with reference to the accompanying drawings. However, since the above-described embodiments have only been described with reference to preferred examples of the present invention, the present invention is limited to the above embodiments. It should not be understood that the scope of the present invention is to be understood by the claims and equivalent concepts described below.
(부호의 설명)(Explanation of the sign)
100 : 약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트100: Vessel stent having a biodegradable coating film loaded with drugs
110 : 스텐트 본체110: stent body
112 : 형상기억합금 와이어112: shape memory alloy wire
120 : 코팅막120: coating film
122 : 생분해성 고분자122: biodegradable polymer
124 : 약물124: Drugs

Claims (4)

  1. 다수의 굴곡이 형성된 복수개의 형상기억합급 와이어가 상호 교차 연결되며, 내부에 중공을 가지는 원통 형상의 스텐트 본체; 및A plurality of shape memory alloy wires having a plurality of bends cross-connected to each other and having a hollow cylindrical stent body therein; And
    생분해성 고분자가 상기 스텐트 본체를 감싸며 형성되는 코팅막;을 포함하며,It includes; biodegradable polymer coating film formed to surround the stent body,
    상기 코팅막은 병변부위의 혈관 신생내막 증식에 대한 재협착을 억제하기 위한 약물이 담지되는 것을 특징으로 하는The coating film is characterized in that the drug for inhibiting restenosis to the neovascularization proliferation of the lesion site is supported
    약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트.A vessel stent having a biodegradable coating film loaded with drugs.
  2. 제1항에 있어서,The method of claim 1,
    상기 생분해성 고분자는, 폴리비닐알코올, 폴리에틸렌글리콜, 폴리락타이드, 폴리글리콜라이드, 폴리에틸렌 옥사이드, 폴리디옥사논, 폴리카프로락톤, 폴리포스파젠, 폴리안하이드라이드, 폴리아미노산, 셀룰로오스 아세테이트 부틸레이트, 셀룰로오스 트리아세테이트, 폴리아클릴레이트, 폴리아크릴아미드, 폴리우레탄, 폴리실록산, 폴리비닐피롤리돈 중 적어도 어느 하나 또는 둘 이상의 공중합체로 이루어진 군으로부터 선택된 고분자인 것을 특징으로 하는The biodegradable polymer, polyvinyl alcohol, polyethylene glycol, polylactide, polyglycolide, polyethylene oxide, polydioxanone, polycaprolactone, polyphosphazene, polyanhydride, polyamino acid, cellulose acetate butylate, It is a polymer selected from the group consisting of at least one or two or more copolymers of cellulose triacetate, polyacrylate, polyacrylamide, polyurethane, polysiloxane, polyvinylpyrrolidone
    약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트.A vessel stent having a biodegradable coating film loaded with drugs.
  3. 제1항에 있어서,The method of claim 1,
    상기 약물은, 파클리탁셀(Paclitaxel) 계열을 포함하는 항암제, 시롤리무스(Sirolimus) 및 리무스(Limus) 계열을 포함하는 면역억제제 및 실로스타졸(Cilostazol)을 포함하는 항혈소판제로 이루어진 군으로부터 선택된 약물 중 적어도 어느 하나 이상이 사용되는 것을 특징으로 하는The drug is selected from the group consisting of an anticancer agent including the Paclitaxel family, an immunosuppressive agent including the Sirolimus family and the Limus family, and an antiplatelet agent including Cilostazol. Characterized in that at least one or more is used
    약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트.A vessel stent having a biodegradable coating film loaded with drugs.
  4. 제1항에 있어서,The method of claim 1,
    상기 코팅막은 복수의 상이한 약물을 개별적으로 담지하기 위한 복수의 층이 형성되는 것을 특징으로 하는The coating film is characterized in that a plurality of layers for separately supporting a plurality of different drugs are formed
    약물이 담지된 생분해성 코팅막을 가지는 혈관용 스텐트.A vessel stent having a biodegradable coating film loaded with drugs.
PCT/KR2015/004720 2014-05-13 2015-05-12 Stent for blood vessels, having drug-impregnated biodegradable coating film WO2015174711A1 (en)

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KR10-2014-0057091 2014-05-13
KR1020140057091A KR20150130049A (en) 2014-05-13 2014-05-13 Biodegradable polymer coated vascular stent for drug eluting

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KR101905687B1 (en) * 2017-01-17 2018-10-11 포항공과대학교 산학협력단 Stent Having Multiple Layer Structure and Its Manufacturing Method
KR102648316B1 (en) * 2020-06-12 2024-03-15 연세대학교 산학협력단 Drug delivery stent and manufacturing method of the same
WO2021251712A1 (en) * 2020-06-12 2021-12-16 연세대학교 산학협력단 Stent for drug delivery and manufacturing method therefor

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