KR20030004582A - Covering composition for drug releasing stent and method of preparing same - Google Patents
Covering composition for drug releasing stent and method of preparing same Download PDFInfo
- Publication number
- KR20030004582A KR20030004582A KR1020010040105A KR20010040105A KR20030004582A KR 20030004582 A KR20030004582 A KR 20030004582A KR 1020010040105 A KR1020010040105 A KR 1020010040105A KR 20010040105 A KR20010040105 A KR 20010040105A KR 20030004582 A KR20030004582 A KR 20030004582A
- Authority
- KR
- South Korea
- Prior art keywords
- drug release
- biologically active
- group
- stent
- crosslinked polymer
- Prior art date
Links
- 229940079593 drug Drugs 0.000 title claims abstract description 64
- 239000003814 drug Substances 0.000 title claims abstract description 64
- 239000000203 mixture Substances 0.000 title claims description 31
- 238000000034 method Methods 0.000 title claims description 22
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 21
- 229920006037 cross link polymer Polymers 0.000 claims abstract description 19
- 239000008199 coating composition Substances 0.000 claims abstract description 16
- 229940088623 biologically active substance Drugs 0.000 claims abstract description 13
- 239000002244 precipitate Substances 0.000 claims abstract description 11
- 230000001225 therapeutic effect Effects 0.000 claims description 19
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 16
- 229960003957 dexamethasone Drugs 0.000 claims description 16
- 229920002635 polyurethane Polymers 0.000 claims description 15
- 239000004814 polyurethane Substances 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 7
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 4
- 229930192392 Mitomycin Natural products 0.000 claims description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
- 229930012538 Paclitaxel Natural products 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 4
- 229960001680 ibuprofen Drugs 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 229960004857 mitomycin Drugs 0.000 claims description 4
- 229960001592 paclitaxel Drugs 0.000 claims description 4
- 229920002401 polyacrylamide Polymers 0.000 claims description 4
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 claims description 4
- 229920006124 polyolefin elastomer Polymers 0.000 claims description 4
- -1 polysiloxane, ethylene vinyl acetate Polymers 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 4
- 229920002943 EPDM rubber Polymers 0.000 claims description 3
- 239000011247 coating layer Substances 0.000 claims description 2
- 229920001971 elastomer Polymers 0.000 claims description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 1
- HQQADJVZYDDRJT-UHFFFAOYSA-N ethene;prop-1-ene Chemical group C=C.CC=C HQQADJVZYDDRJT-UHFFFAOYSA-N 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 16
- 239000000126 substance Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
- 238000000576 coating method Methods 0.000 description 11
- 239000011248 coating agent Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 238000000975 co-precipitation Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 229920006254 polymer film Polymers 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 4
- 239000006184 cosolvent Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229960000103 thrombolytic agent Drugs 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010070716 Intercellular Signaling Peptides and Proteins Proteins 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 239000002318 adhesion promoter Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 229910001285 shape-memory alloy Inorganic materials 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Classifications
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
Abstract
본 발명은 약물 방출 스텐트용 코팅 조성물에 관한 것으로서, 이 코팅 조성물은 생물학적 활성 물질과 수용성 고분자의 공침전물 및 가교 고분자 용액을 포함한다.The present invention relates to a coating composition for drug release stents, the coating composition comprising a co-precipitate of a biologically active substance and a water-soluble polymer and a crosslinked polymer solution.
상술한 바와 같이, 본 발명의 약물 방출 스텐트용 코팅 조성물은 높은 탄력성을 가지고, 약물 방출율을 조절할 수 있다.As described above, the coating composition for drug release stent of the present invention has a high elasticity, it is possible to control the drug release rate.
Description
[산업상 이용 분야][Industrial use]
본 발명은 약물 방출 스텐트용 코팅 조성물, 이의 제조 방법 및 이 조성물로 코팅된 약물 방출 스텐트에 관한 것으로서, 더욱 상세하게는 약물 방출율을 조절할 수 있는 약물 방출 스텐트용 코팅 조성물에 관한 것이다.The present invention relates to a coating composition for drug release stents, a method for preparing the same, and a drug release stent coated with the composition, and more particularly, to a coating composition for drug release stents capable of controlling drug release rates.
[종래 기술][Prior art]
외과적 처치나 이러한 외과적 처치에 관련된 침입성 약제 처치에서, 혈관 또는 관강(lumen)벽 지지물 또는 보강물을 공급하여 재발 협착증을 방지하기 위해 스텐트 장치가 널리 사용되고 있으며, 이밖에도, 치료 촉진 작용 또는 회복 촉진 작용을 위해 식도, 호흡기관, 혈관, 비뇨기관이나 이외에 기타 접근이 어려운 관강에 스텐트 장치를 삽입하거나 팽창시키는 것이 일반적인 치료 형태로 자리잡고 있다.In surgical procedures or invasive pharmaceutical procedures associated with such surgical procedures, stent devices are widely used to supply vascular or lumen wall supports or reinforcements to prevent relapse stenosis, in addition to promoting treatment or recovery. Inserting or dilating a stent device into the esophagus, respiratory tract, blood vessels, urinary system, or other inaccessible lumen for palpation is a common treatment.
최근 들어 스텐트를 이용한 치료 형태의 효과를 증진하고자 혈전 용해제나 항증식제 등의 약물을 운반할 수 있는 이식 스텐트를 개발하려는 시도가 이루어지고 있다. 그 예로 미국 특허 제 5,092,877 호에는 약물 방출과 관련하여 피복물과 함께 사용할 수 있는 중합체 물질 스텐트가 기재되어 있고, 또한 국제 특허 공개 WO 96/032907호에는 약물 방출용 피복 스텐트가 기술되어 있다.In recent years, attempts have been made to develop implantable stents that can carry drugs such as thrombolytic agents or antiproliferative agents to enhance the effectiveness of therapeutic forms using stents. For example, US Pat. No. 5,092,877 describes polymeric material stents that can be used with coatings in connection with drug release, and International Patent Publication WO 96/032907 describes coating stents for drug release.
이러한 생물학적 활성 치료 물질을 장기간 전달할 수 있도록, 약물을 스텐트에 코팅하는 방법으로는 먼저 생물학적 활성 치료 물질을 고분자 용액에 첨가한 후, 얻어진 혼합물로 스텐트를 코팅한 뒤, 용매를 제거하여 생물학적 활성 치료 물질이 함유된 고분자 막이 스텐트 상에 형성되도록 하는 방법이 연구되었다.In order to provide long-term delivery of such biologically active therapeutic substances, a method of coating a drug on a stent may include first adding a biologically active therapeutic substance to a polymer solution, coating the stent with the obtained mixture, and then removing the solvent to remove the biologically active therapeutic substance. A method for causing this containing polymer film to form on the stent has been studied.
이때, 생물학적 활성 치료 물질로 덱사메타손(dexamethasone)을 사용할 경우, 고분자 용액으로 폴리우레탄 테트라하이드로퓨란 용액을 사용하는데, 덱사메타손을 상기 폴리우레탄 테트라하이드로퓨란 용액에 첨가한 후, 교반하면, 덱사메타손이 고분자 용액에서 낮은 용해도를 나타냄에 따라 잘 섞이지 않게 된다. 또한 폴리우레탄 테트라하이드로퓨란 고분자 용액을 만들기 전에 덱사메타손을 테트하라이드로퓨란 용매에 먼저 용해시키고자 하여도 덱사메타손의 용해도가 낮아 테트라하이드로퓨란에 잘 녹지 않는다. 이 때문에, 테트라하이드로퓨란이 증발 후 고분자 피복에 덱사메타손이 응집되어 덩어리진 형태로 남게 되며, 덩어리진 덱사메타손을 중심으로 균열이 발생되어 높은 탄성도가 요구되는 피복으로 사용할 수 없게 된다. 또한, 덱사메타손의 방출 역시 불균일하게 일어나기 때문에 지속적인 방출효과를 기대할 수 없다.In this case, when dexamethasone (dexamethasone) is used as a biologically active therapeutic substance, a polyurethane tetrahydrofuran solution is used as a polymer solution. Low solubility results in poor mixing. In addition, even when attempting to dissolve dexamethasone in a tetrahydrofuran solvent before the polyurethane tetrahydrofuran polymer solution is made, dexamethasone has low solubility so that it does not dissolve well in tetrahydrofuran. For this reason, dexamethasone aggregates and remains in a lump form after tetrahydrofuran evaporates in a polymer coating, and cracks generate | occur | produce around agglomerated dexamethasone, and it cannot use it as a coating which requires high elasticity. In addition, since the release of dexamethasone also occurs unevenly, a sustained release effect cannot be expected.
본 발명의 목적은 생물학적 활성 치료 물질의 효과적 전달을 위하여 방출율을 조절할 수 있는 약물 방출 스텐트용 코팅 조성물을 제공하는 것이다.It is an object of the present invention to provide a coating composition for drug release stents which can control the release rate for effective delivery of a biologically active therapeutic substance.
본 발명의 다른 목적은 생물학적 활성 치료 물질을 인체에 장기간 전달할 수 있는 약물 방출 스텐트용 코팅 조성물을 제공하는 것이다.Another object of the present invention is to provide a coating composition for drug release stents capable of prolonged delivery of a biologically active therapeutic substance to the human body.
본 발명의 또 다른 목적은 상술한 물성을 갖는 약물 방출 스텐트용 코팅 조성물의 제조 방법을 제공하는 것이다.Still another object of the present invention is to provide a method for preparing a coating composition for drug release stent having the above-described physical properties.
본 발명의 또 다른 목적은 상기 조성물로 코팅되고, 생물학적 활성 치료 물질의 장기간 전달을 위해 최적의 기계적 특성을 갖는 약물 방출 스텐트를 제공하는 것이다.Another object of the present invention is to provide a drug release stent coated with the composition and having optimal mechanical properties for long term delivery of a biologically active therapeutic substance.
도 1은 본 발명의 실시예 1 내지 3 및 비교예 1의 방법으로 제조된 약물 방출 스텐트에 코팅된 폴리우레탄 막의 기계적 성질을 나타내는 그래프.1 is a graph showing the mechanical properties of the polyurethane membrane coated on the drug release stent prepared by the method of Examples 1 to 3 and Comparative Example 1 of the present invention.
도 2는 본 발명의 실시예 1 및 3의 방법으로 제조된 폴리우레탄 막의 약물 방출 형태를 나타낸 그래프.Figure 2 is a graph showing the drug release form of the polyurethane membrane prepared by the method of Examples 1 and 3 of the present invention.
도 3은 본 발명의 스텐트를 개략적으로 나타낸 도면.Figure 3 is a schematic representation of the stent of the present invention.
상기 목적을 달성하기 위하여, 본 발명은 생물학적 활성 물질과 수용성 고분자의 공침전물 및 가교 고분자 용액을 포함하는 약물 방출 스텐트용 코팅 조성물 을 제공한다.In order to achieve the above object, the present invention provides a coating composition for drug release stents comprising a co-precipitate and a crosslinked polymer solution of a biologically active substance and a water-soluble polymer.
본 발명은 또한, 생물학적 활성 물질과 수용성 고분자를 유기 용매에 용해하고, 얻어진 혼합물에서 상기 유기 용매를 제거하여 생물학적 활성 물질과 수용성 고분자의 공침전물을 형성하고, 상기 공침물을 가교 고분자 용액에 첨가하는 약물방출 스텐트용 코팅 조성물의 제조 방법을 제공한다.The present invention also provides a method for dissolving a biologically active substance and a water-soluble polymer in an organic solvent, removing the organic solvent from the obtained mixture to form a co-precipitate of the biologically active substance and a water-soluble polymer, and adding the co-precipitate to a crosslinked polymer solution. Provided is a method for preparing a coating composition for drug release stent.
아울러, 본 발명은 금속 와이어로 형성되는 원통 형상의 본체 및 상기 본체에 코팅되고 생물학적 활성 치료 물질, 수용성 고분자 및 가교 고분자를 포함하는 코팅 층을 포함하는 약물 방출 스텐트를 제공한다.In addition, the present invention provides a drug release stent comprising a cylindrical body formed of metal wire and a coating layer coated on the body and comprising a biologically active therapeutic material, a water soluble polymer and a crosslinked polymer.
이하 본 발명을 더욱 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 약물 방출 스텐트를 제조하기 위하여, 사용되는 코팅 조성물에 관한 것이다. 본 발명의 약물 방출 스텐트는 혈관 또는 관강 이식에 사용되는 탄성 및 자기 팽창성 스텐트로서, 이 스텐트를 코팅하는 상기 코팅 조성물은 생체내 안정성 (biostable) 엘라스토머(elastomer)와 생물학적 활성이 있는 물질(bioactive agent)이 혼합되어 있다.The present invention relates to a coating composition used to prepare a drug release stent. The drug-releasing stent of the present invention is an elastic and self-expanding stent used for vascular or lumen implantation, wherein the coating composition coating the stent is a biostable elastomer and a bioactive agent. Is mixed.
종래에 연구되던 약물 방출 스텐트용 코팅 조성물은 생물학적 활성 치료 물질이, 약물 방출 시스템을 제조하기 위해 사용되는 가교 고분자 용액에 대한 용해도가 낮아 응집이 발생되어 높은 탄성도가 요구되는 스텐트에 사용하기가 힘들었다. 또한 활성 치료 물질의 방출양이 불균일하여 지속적인 효과를 기대할 수 없었다.The coating composition for drug release stents, which has been studied in the past, was difficult to be used in stents where biologically active therapeutic substances had low solubility in crosslinked polymer solutions used to prepare drug release systems, resulting in aggregation due to aggregation. . In addition, the sustained effect could not be expected due to uneven release of active therapeutic substances.
본 발명에서는 이러한 문제를 해결하기 위하여, 일반적인 화학공학 관련 문헌에 기재된 바와 같이 용해도가 떨어지는 약물의 경우 수용성 고분자와 약물을 공용매(cosolvent)에 녹인 후 공용매를 증발시키면 수용성 고분자상에 약물이 나노 크기로 분산되어 용해도가 급격히 증가한다는 원리를 이용하였다. 즉, 본 발명은 수용성 고분자와 공침법(co-precipitation)을 이용하여 활성 치료 물질을나노크기(nano size)로 조절하는 방법을 이용하였다.In the present invention, in order to solve this problem, as described in the general chemical engineering literature, when the solubility drug is insoluble in the cosolvent after dissolving the water-soluble polymer and drug in the cosolvent (cosolvent), the drug is nano- The principle is that the solubility is rapidly increased due to dispersion in size. That is, the present invention uses a method of controlling the active therapeutic substance to nano size using a water-soluble polymer and co-precipitation.
본 발명의 약물 방출 스텐트용 코팅 조성물의 제조 방법은, 먼저 생물학적 활성 치료 물질과 수용성 고분자를 유기 용매에 용해한다. 이때, 생물학적 활성 치료 물질과 수용성 고분자는 동일한 양으로 사용하며, 최소 0 중량%보다 크고, 최대 20 중량% 이하의 양으로 사용하며, 유기 용매는 60 중량% 이상, 100 중량% 미만으로 사용한다. 생물학적 활성 치료 물질과 수용성 고분자의 사용량이 20 중량%를 초과하는 경우 생물학적 활성 물질과 수용성 고분자의 공침화합물이 형성되지 않고, 분해되어 단순한 혼합물이 형성되어 바람직하지 않다. 상기 생물학적 활성 치료 물질로는 항혈전제, 항응고제, 항혈소판제, 혈전용해제, 항증식제, 항염증제; 과형성, 특히 재발협착증 억제시약, 평활근 세포 억제제, 항생제, 성장 인자, 성장 인자 억제제, 세포 부착 억제제, 세포 부착 촉진제; 및 내피 세포 재생을 비롯한 건강한 네오혈관내막(neointimal) 조직 형성을 증가시킬 수 있는 약물을 사용할 수 있으며, 대표적인 예로 덱사메타손(dexamethasone), 파클리탁셀(paclitaxel), 미토마이신(mitomycin) 또는 이부프로펜(ibuprofen)을 사용할 수 있다. 상기 수용성 고분자로는 폴리비닐피롤리돈, 폴리에틸렌 옥사이드, 하이드록시프로필 메틸 셀루로즈, 폴리비닐알콜, 폴리아크릴아미드, 폴리히드록시에틸메타아크릴레이트 또는 이들의 혼합물을 사용할 수 있다. 상기 유기 용매로는 에탄올과 같은 인체에 무해한 알콜은 어떠한 것도 사용할 수 있다.The method for producing a coating composition for drug release stent of the present invention first dissolves a biologically active therapeutic substance and a water-soluble polymer in an organic solvent. At this time, the biologically active therapeutic substance and the water-soluble polymer are used in the same amount, greater than at least 0% by weight, up to 20% by weight or less, and organic solvents are used in more than 60% by weight, less than 100% by weight. When the amount of the biologically active therapeutic substance and the water-soluble polymer is more than 20% by weight, the coprecipitation compound of the biologically active substance and the water-soluble polymer is not formed, but is decomposed to form a simple mixture, which is not preferable. The biologically active therapeutic substances include anti-thrombotic agents, anticoagulants, antiplatelet agents, thrombolytic agents, antiproliferative agents, anti-inflammatory agents; Hyperplasia, in particular reagents for restenosis, smooth muscle cell inhibitors, antibiotics, growth factors, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters; And drugs capable of increasing healthy neointimal tissue formation, including endothelial cell regeneration, and representative examples thereof include dexamethasone, paclitaxel, mitomycin, or ibuprofen. Can be. As the water-soluble polymer, polyvinylpyrrolidone, polyethylene oxide, hydroxypropyl methyl cellulose, polyvinyl alcohol, polyacrylamide, polyhydroxyethyl methacrylate or a mixture thereof may be used. The organic solvent may be any alcohol that is harmless to the human body, such as ethanol.
이어서, 상기 혼합물에서 유기 용매를 제거하여 생물학적 활성 물질과 수용성 고분자의 공침전물을 형성한다. 이 공침전물에서, 생물학적 활성 물질은 수용성 고분자에 균일하게 분산되어 있다.Subsequently, the organic solvent is removed from the mixture to form a co-precipitate of the biologically active substance and the water-soluble polymer. In this coprecipitation, the biologically active substance is uniformly dispersed in the water soluble polymer.
상기 공침전물을 가교 고분자 용액과 혼합하여 약물 방출 스텐트용 약물 방출 조성물을 제조한다. 제조된 약물 방출 조성물에는 생물학적 활성 물질이 완전히 용해되어 있다. 상기 공침전물과 가교 고분자 용액의 혼합 비율은 0.01 내지 30 대 70 내지 99.99 중량%로 한다. 공침전물의 양이 0.01 중량% 미만일 경우에는 약물 활성이 나타나지 않으며, 30 중량%를 초과하는 경우에는, 공침전물이 가교 고분자 용액에 완전히 용해되지 않고 침전될 수 있어 바람직하지 않다. 상기 가교 고분자 용액은 폴리우레탄, 폴리실록산(실리콘), 에틸렌 비닐 아세테이트, 폴리올레핀 고무, 에틸렌-프로필렌 디엔 모노머 고무 또는 이들의 혼합물의 가교 고분자를 테트라하이드로퓨란, 디메틸아세트아마이드, 디메틸설폭사이드 또는 디메틸포름알데하이드의 유기 용매에 용해시켜 제조한다. 상기 가교 고분자 용액의 농도는 3 내지 30%가 바람직하다. 상기 가교 고분자 용액의 농도가 3% 미만일 경우에는 고분자막의 형성이 어려우며, 30%를 초과하는 경우에는 탄성을 지닌 고분자막의 형성에 제약을 받는다.The co-precipitate is mixed with a crosslinked polymer solution to prepare a drug release composition for drug release stent. The biologically active substance is completely dissolved in the prepared drug release composition. The mixing ratio of the co-precipitate and the crosslinked polymer solution is 0.01 to 30 to 70 to 99.99% by weight. If the amount of the coprecipitate is less than 0.01% by weight, no drug activity is observed. If the amount of the coprecipitate is greater than 30%, the coprecipitate may be precipitated without being completely dissolved in the crosslinked polymer solution. The crosslinked polymer solution may be a crosslinked polymer of polyurethane, polysiloxane (silicone), ethylene vinyl acetate, polyolefin rubber, ethylene-propylene diene monomer rubber, or mixtures thereof. It is prepared by dissolving in an organic solvent. The concentration of the crosslinked polymer solution is preferably 3 to 30%. If the concentration of the crosslinked polymer solution is less than 3%, it is difficult to form the polymer film, and if it exceeds 30%, the formation of the polymer film having elasticity is restricted.
이하에서는 본 발명에 따라 제조된 약물 조성물을 이용하여 스텐트를 제조하는 방법에 대하여 설명한다.Hereinafter, a method for preparing a stent using the drug composition prepared according to the present invention will be described.
먼저, 형상기억합금이나 스텐인레스 강과 같은 탄성이 높고 내식성이 우수한 금속와이어를 사용하여 스텐트 본체를 제작한다. 스텐트 본체는 다양한 형태로 제작될 수 있으며, 일반적으로 원통 형상으로 제조된다. 이러한 여러 가지 스텐트 본체의 형태 중에서 하나의 예를 도 3에 나타내었다. 이하에는 도 3에 나타난 스텐트 본체의 구조에 대하여 보다 간략히 설명한다.First, a stent body is manufactured using metal wires having high elasticity and corrosion resistance such as shape memory alloys or stainless steels. The stent body can be manufactured in various forms and is generally manufactured in a cylindrical shape. An example of one of these various stent bodies is shown in FIG. 3. Hereinafter, the structure of the stent main body shown in FIG. 3 will be described more briefly.
스텐트 본체는 크게 원통부(1)와 이동 방지부(5)로 이루어져 있다. 상기 원통부(1)는 일정한 내경을 갖고, 다수개의 금속 와이어가 나선형으로 엮어져 있다. 상기 이동 방지부(5)는 상기 원통부(1) 보다 큰 내경을 가지며 다수의 금속 와이어가 지그재그 형태로 연결되어 구부러진 원주 구조를 이룬다. 물론, 본 발명에서 사용가능한 스텐트 본체가 이러한 형상에 한정되는 것은 아니며, 원통부로만 이루어진 스텐트 본체를 사용할 수도 있고, 원통부가 지그재그 형태로 구부러져 있는 형태 등 일반적인 스텐트 본체는 모두 사용할 수 있다.The stent body is largely composed of a cylindrical portion (1) and the movement preventing portion (5). The cylindrical portion 1 has a constant inner diameter, and a plurality of metal wires are woven in a spiral manner. The movement preventing part 5 has an inner diameter larger than that of the cylindrical part 1, and a plurality of metal wires are connected in a zigzag form to form a bent cylindrical structure. Of course, the stent main body usable in the present invention is not limited to this shape, and a stent main body consisting of only a cylindrical part may be used, and a general stent main body such as a cylindrical part bent in a zigzag shape may be used.
이상 설명한 바와 같이 제작된 스텐트 본체에 본 발명에 의하여 제조된 약물 방출 조성물을 코팅한다.The drug release composition prepared according to the present invention is coated on the stent body manufactured as described above.
약물 방출 조성물을 스텐트 본체에 코팅하는 방법으로는 스텐트 본체를 액상의 약물 조성물에 담그었다가 꺼내는 침적법이나 액상의 약물 조성물을 스텐트 본체에 분사하는 분사법을 사용할 수 있다.As a method of coating the drug release composition on the stent body, a deposition method in which the stent body is immersed in a liquid drug composition and then taken out, or a spraying method of spraying the liquid drug composition on the stent body may be used.
이러한 코팅 방법 이외에도 약리학적으로 허용가능한 코팅 공정을 모두 사용할 수 있다.In addition to these coating methods, any pharmacologically acceptable coating process can be used.
이어서, 약물 방출 조성물이 코팅된 스텐트를 건조하여, 약물 방출 조성물에서 용매를 제거한다. 스텐트를 건조하고 나면 스텐트의 표면에는 투명한 고분자 막이 형성된다. 제조된 스텐트 본체를 피복하고 있는 피복물에는 생물학적 활성 치료 물질이 나노 크기로 완전히 분산되어 있다. 즉, 금속 와이어로 이루어진 스텐트 본체 전체가 고분자로 피복되므로, 금속 와이어 부분이 생체학적 활성 치료물질을 포함하는 고분자 막으로 형성된다.The stent coated with the drug release composition is then dried to remove the solvent from the drug release composition. After the stent is dried, a transparent polymer film is formed on the surface of the stent. The coating covering the manufactured stent body is completely dispersed in nano size biologically active therapeutic substances. That is, since the entire stent body made of metal wire is covered with a polymer, the metal wire portion is formed of a polymer film containing a biologically active therapeutic material.
이하 본 발명의 바람직한 실시예 및 비교예를 기재한다. 그러나 하기한 실시예는 본 발명의 바람직한 일 실시예일 뿐 본 발명이 하기한 실시예에 한정되는 것은 아니다.Hereinafter, preferred examples and comparative examples of the present invention are described. However, the following examples are only one preferred embodiment of the present invention and the present invention is not limited to the following examples.
(실시예 1)(Example 1)
중량 평균 분자량이 4,000인 폴리비닐피롤리돈 13 중량%와 덱사메타손 13 중량%를 에탄올 74 중량%에 완전히 용해한 후, 이 용액에서 에탄올을 증발시켜 폴리비닐피롤리돈과 덱사메타손의 공침물을 제조하였다. 이 공침물 26 중량%를 12% 농도의 폴리우레탄 테트라하이드로퓨란 용액 74 중량%에 첨가하여 약물 방출 조성물을 제조하였다. 이때, 약물 방출 조성물에 함유된 덱사메타손의 함량은 13 중량%였다.After dissolving 13% by weight of polyvinylpyrrolidone having a weight average molecular weight of 4,000 and 13% by weight of dexamethasone in 74% by weight of ethanol, ethanol was evaporated from this solution to prepare a co-precipitate of polyvinylpyrrolidone and dexamethasone. A drug release composition was prepared by adding 26 wt% of this coprecipitate to 74 wt% of a 12% concentration of polyurethane tetrahydrofuran solution. At this time, the content of dexamethasone contained in the drug release composition was 13% by weight.
상기 약물 방출 조성물로 스텐트를 분무 코팅하여 약물 방출 스텐트를 제조하였다.The drug release stent was prepared by spray coating the stent with the drug release composition.
(실시예 2)(Example 2)
중량 평균 분자량이 50,000인 폴리비닐피롤리돈을 사용한 것을 제외하고는 상기 실시예 1과 동일하게 실시하였다.The same procedure as in Example 1 was carried out except that polyvinylpyrrolidone having a weight average molecular weight of 50,000 was used.
(실시예 3)(Example 3)
중량 평균 분자량이 800,000인 폴리비닐피롤리돈을 사용한 것을 제외하고는 상기 실시예 1과 동일하게 실시하였다.The same procedure as in Example 1 was carried out except that polyvinylpyrrolidone having a weight average molecular weight of 800,000 was used.
(비교예 1)(Comparative Example 1)
덱사메타손을 폴리우레탄 테트라하이드로퓨란 용액에 첨가하여 약물 방출 조성물을 제조하였다. 이때, 약물 방출 조성물에 함유된 덱사메타손의 함량은 13 중량%로 하였다.Dexamethasone was added to the polyurethane tetrahydrofuran solution to prepare a drug release composition. At this time, the content of dexamethasone contained in the drug release composition was 13% by weight.
상기 약물 방출 조성물로 스텐트를 코팅하여 약물 방출 스텐트를 제조하였다.The stent was coated with the drug release composition to prepare a drug release stent.
상기 실시예 1 내지 3과 비교예 1의 방법으로 제조된 약물 방출 스텐트에서 제조된 폴리우레탄 막의 기계적 성질을 측정하여, 그 결과를 도 1에 나타내었다. 도 1에서 보면, 실시예 1 내지 3의 폴리우레탄 막이 비교예 1의 폴리우레탄 막에 비하여 우수한 탄성력을 나타냄을 알 수 있다. 도 1을 보면, 공침시에 사용된 폴리비닐피롤리돈의 분자량이 증가할수록 탄성력이 증가하였음을 알 수 있다.The mechanical properties of the polyurethane membrane prepared from the drug release stent prepared by the method of Examples 1 to 3 and Comparative Example 1 were measured, and the results are shown in FIG. 1, it can be seen that the polyurethane membranes of Examples 1 to 3 exhibited excellent elastic force as compared to the polyurethane membrane of Comparative Example 1. 1, it can be seen that the elastic force increased as the molecular weight of the polyvinylpyrrolidone used during coprecipitation increased.
또한, 실시예 1 및 3의 방법으로 제조된 폴리우레탄 막의 약물 방출 실험을 실시하여 그 결과를 도 2에 나타내었다. 약물 방출 실험은 실시예 1 및 3의 방법으로 제조된 폴리우레탄 막 500㎎을 pH 7.4 완충 용액 50㎖에 함침시킨 후, 일정 시간을 유지한 뒤, 여기에서 완충 용액 50㎖를 채취하고, 채취된 완충 용액 중에서 20㎖를 고성능 크로마토그래피(HPLC)로 분석하여 그 약물 방출량을 측정하여 실시하였다. 이어서, 새로운 완충 용액 50㎖를 다시 첨가하여 동일한 방법으로 다시 일정 시간 후의 약물 방출량을 측정하였다. 도 2에 나타낸 결과를 보면, 실시예 1 및 3의 경우 모두 시간에 비례하여 약물 방출량이 증가되었으며, 또한 공침시에 사용된 폴리비닐피롤리돈의 분자량에 따라 약물 방출 형태를 조절할 수 있음을 알 수 있다.In addition, the drug release experiment of the polyurethane membrane prepared by the method of Examples 1 and 3 was carried out and the results are shown in FIG. The drug release experiment was performed by impregnating 500 mg of the polyurethane membrane prepared by the method of Examples 1 and 3 in 50 ml of pH 7.4 buffer solution, and then maintaining a predetermined time, and then extracting 50 ml of the buffer solution from the sample. 20 ml in a buffer solution was analyzed by high performance chromatography (HPLC) to measure the drug release. Subsequently, 50 ml of fresh buffer solution was added again to measure the amount of drug release after a certain time by the same method. In the results shown in Figure 2, it was found that in the case of Examples 1 and 3, the amount of drug release was increased in proportion to time, and also the drug release form could be controlled according to the molecular weight of polyvinylpyrrolidone used at the time of coprecipitation. Can be.
상술한 바와 같이, 본 발명의 스텐트용 약물 방출 조성물은 높은 탄력성을 가지며, 약물 방출율을 조절할 수 있다.As described above, the drug release composition for stent of the present invention has a high elasticity, it is possible to control the drug release rate.
Claims (12)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2001-0040105A KR100439156B1 (en) | 2001-07-05 | 2001-07-05 | Covering composition for drug releasing stent and method of preparing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2001-0040105A KR100439156B1 (en) | 2001-07-05 | 2001-07-05 | Covering composition for drug releasing stent and method of preparing same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20030004582A true KR20030004582A (en) | 2003-01-15 |
| KR100439156B1 KR100439156B1 (en) | 2004-07-05 |
Family
ID=27713583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2001-0040105A KR100439156B1 (en) | 2001-07-05 | 2001-07-05 | Covering composition for drug releasing stent and method of preparing same |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR100439156B1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100455343B1 (en) * | 2001-08-29 | 2004-11-12 | 학교법인 인하학원 | Covering composition for drug releasing stent and drug releasing stent manufactured using same |
| WO2005011533A1 (en) * | 2003-07-29 | 2005-02-10 | Taewoong Medical Co.,Ltd | Self-expandable stent |
| KR100916750B1 (en) * | 2007-10-12 | 2009-09-14 | (주) 태웅메디칼 | Manufacturing method of coating agent for drug release stent and coating agent for drug release stent |
| US20110190876A1 (en) * | 2004-03-31 | 2011-08-04 | Zhao Jonathon Z | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
| US20120157580A1 (en) * | 2009-08-31 | 2012-06-21 | Hiroyuki Yoshino | Coating composition |
| KR20150061949A (en) | 2013-11-28 | 2015-06-05 | 가톨릭대학교 산학협력단 | Coating composition for drug releasing stent comprising penetration enhancer and drug releasing stent coated the thereof |
| US11207267B2 (en) * | 2019-10-02 | 2021-12-28 | Segal Innovations LLC | Bio-adhesive dissolving compounds and device |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100904207B1 (en) | 2007-06-01 | 2009-06-25 | (주) 태웅메디칼 | Drug release coating for stents, preparation method thereof and drug release stent coated with the coating |
| AU2008202283B2 (en) | 2007-06-01 | 2011-01-20 | Kyong-Min Shin | Coating agent for drug releasing stent, preparation method thereof and drug releasing stent coated therewith |
| KR102033955B1 (en) | 2018-02-08 | 2019-10-18 | 박영준 | Processing Apparatus and Method of Multi-Layer Film |
| KR102068050B1 (en) | 2019-09-25 | 2020-01-20 | 박영준 | Medical Dressing Patch and Methods of the same |
| KR102311714B1 (en) | 2019-11-13 | 2021-10-12 | 박영준 | Apparatus For Medical Dressing Patch |
| KR20210097069A (en) | 2021-07-19 | 2021-08-06 | 박영준 | Medical Dressing Patch and Methods of the same |
| KR20230146289A (en) | 2022-04-12 | 2023-10-19 | 주식회사 큐아 | Medical Dressing Band and Methods of the same |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5464650A (en) * | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
| US5824048A (en) * | 1993-04-26 | 1998-10-20 | Medtronic, Inc. | Method for delivering a therapeutic substance to a body lumen |
| CA2216943C (en) * | 1995-04-19 | 2003-06-17 | Schneider (Usa) Inc. | Drug release coated stent |
| KR20010015631A (en) * | 1997-09-26 | 2001-02-26 | 스티븐 사브로트스키 | Bioadhesive compositions and methods for topical administration of active agents |
| US6168619B1 (en) * | 1998-10-16 | 2001-01-02 | Quanam Medical Corporation | Intravascular stent having a coaxial polymer member and end sleeves |
-
2001
- 2001-07-05 KR KR10-2001-0040105A patent/KR100439156B1/en not_active IP Right Cessation
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100455343B1 (en) * | 2001-08-29 | 2004-11-12 | 학교법인 인하학원 | Covering composition for drug releasing stent and drug releasing stent manufactured using same |
| WO2005011533A1 (en) * | 2003-07-29 | 2005-02-10 | Taewoong Medical Co.,Ltd | Self-expandable stent |
| US20110190876A1 (en) * | 2004-03-31 | 2011-08-04 | Zhao Jonathon Z | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
| US8557272B2 (en) * | 2004-03-31 | 2013-10-15 | Cordis Corporation | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
| KR100916750B1 (en) * | 2007-10-12 | 2009-09-14 | (주) 태웅메디칼 | Manufacturing method of coating agent for drug release stent and coating agent for drug release stent |
| CN104984463A (en) * | 2008-03-31 | 2015-10-21 | 科迪斯公司 | Device for local and/or regional delivery employing liquid formulations of therapeutic agents |
| US20120157580A1 (en) * | 2009-08-31 | 2012-06-21 | Hiroyuki Yoshino | Coating composition |
| KR20150061949A (en) | 2013-11-28 | 2015-06-05 | 가톨릭대학교 산학협력단 | Coating composition for drug releasing stent comprising penetration enhancer and drug releasing stent coated the thereof |
| US11207267B2 (en) * | 2019-10-02 | 2021-12-28 | Segal Innovations LLC | Bio-adhesive dissolving compounds and device |
Also Published As
| Publication number | Publication date |
|---|---|
| KR100439156B1 (en) | 2004-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100439156B1 (en) | Covering composition for drug releasing stent and method of preparing same | |
| US7097850B2 (en) | Bioactive agent release coating and controlled humidity method | |
| JP3954616B2 (en) | Method and system for providing a bioactive agent release coating | |
| CN101869514B (en) | Controlled drug-release composition and drug-releasable medical device | |
| CN101199873B (en) | Medicament elution instrument nanometer class colon washer machineole drug releasing structure and preparing method thereof | |
| EP2265316B1 (en) | Triggered drug release | |
| EP1551469B1 (en) | Bioactive agent release coating with aromatic poly(meth)acrylates | |
| JP2004230381A (en) | Coating method for medical care equipment | |
| JP2003503153A (en) | Stent coating | |
| JPWO2014163091A1 (en) | Drug coat layer | |
| CN101474455B (en) | Nano micropore structure medicament eluting instrument capable of storing and releasing various kinds of medicament and preparation method | |
| KR100455343B1 (en) | Covering composition for drug releasing stent and drug releasing stent manufactured using same | |
| JP2006051364A (en) | Kit for applying medicinal coating to medical device in operating room | |
| CN101309706A (en) | Drug release controlled composition and drug releasing medical device | |
| EP2801379B1 (en) | Coating composition and medical device | |
| JP4456322B2 (en) | Stent | |
| US20200254152A1 (en) | Coating system for medical devices | |
| JP2005132737A (en) | Embedding type preparation medicine-holding carrier |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 20010705 |
|
| PA0201 | Request for examination | ||
| PG1501 | Laying open of application | ||
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 20030528 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20031126 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20040324 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20040625 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20040628 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| FPAY | Annual fee payment |
Payment date: 20070626 Year of fee payment: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20070626 Start annual number: 4 End annual number: 4 |
|
| LAPS | Lapse due to unpaid annual fee | ||
| PC1903 | Unpaid annual fee |
Termination category: Default of registration fee Termination date: 20090509 |