JP2001503755A - Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用およびデリバリー装置 - Google Patents
Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用およびデリバリー装置Info
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- JP2001503755A JP2001503755A JP52114098A JP52114098A JP2001503755A JP 2001503755 A JP2001503755 A JP 2001503755A JP 52114098 A JP52114098 A JP 52114098A JP 52114098 A JP52114098 A JP 52114098A JP 2001503755 A JP2001503755 A JP 2001503755A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1858—Platelet-derived growth factor [PDGF]
- A61K38/1866—Vascular endothelial growth factor [VEGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/13—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14) with NADH or NADPH as one donor, and incorporation of one atom of oxygen (1.14.13)
- C12Y114/13039—Nitric-oxide synthase (NADPH dependent) (1.14.13.39)
-
- 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
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Vascular Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Peptides Or Proteins (AREA)
- Prostheses (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9622852.3A GB9622852D0 (en) | 1996-11-01 | 1996-11-01 | Treatment of intimal hyperplasma |
| GBGB9709494.0A GB9709494D0 (en) | 1997-05-09 | 1997-05-09 | Delivery device and method |
| GB9717791.9 | 1997-08-21 | ||
| GB9709494.0 | 1997-08-21 | ||
| GBGB9717791.9A GB9717791D0 (en) | 1997-08-21 | 1997-08-21 | Treatment of intimal hyperplasia |
| GB9622852.3 | 1997-08-21 | ||
| PCT/GB1997/003015 WO1998020027A2 (en) | 1996-11-01 | 1997-11-03 | Therapeutic use of an agent that stimulates no or prostacyclin production and delivery device |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008004349A Division JP4783797B2 (ja) | 1996-11-01 | 2008-01-11 | Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用および送達装置 |
| JP2011236266A Division JP2012031196A (ja) | 1996-11-01 | 2011-10-27 | Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用および送達装置 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001503755A true JP2001503755A (ja) | 2001-03-21 |
| JP2001503755A5 JP2001503755A5 (enExample) | 2005-06-16 |
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52114098A Withdrawn JP2001503755A (ja) | 1996-11-01 | 1997-11-03 | Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用およびデリバリー装置 |
| JP2008004349A Expired - Fee Related JP4783797B2 (ja) | 1996-11-01 | 2008-01-11 | Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用および送達装置 |
| JP2011236266A Pending JP2012031196A (ja) | 1996-11-01 | 2011-10-27 | Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用および送達装置 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008004349A Expired - Fee Related JP4783797B2 (ja) | 1996-11-01 | 2008-01-11 | Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用および送達装置 |
| JP2011236266A Pending JP2012031196A (ja) | 1996-11-01 | 2011-10-27 | Ｎｏまたはプロスタサイクリン産生を刺激する薬剤の治療的使用および送達装置 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7320679B2 (enExample) |
| EP (2) | EP1488761A1 (enExample) |
| JP (3) | JP2001503755A (enExample) |
| KR (1) | KR100695590B1 (enExample) |
| AT (1) | ATE287271T1 (enExample) |
| AU (1) | AU729420B2 (enExample) |
| CA (1) | CA2270286C (enExample) |
| DE (1) | DE69732304T2 (enExample) |
| ES (1) | ES2235227T3 (enExample) |
| HU (1) | HU223957B1 (enExample) |
| NO (1) | NO326303B1 (enExample) |
| PL (1) | PL189744B1 (enExample) |
| PT (1) | PT941116E (enExample) |
| WO (1) | WO1998020027A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502226A (ja) * | 2005-07-22 | 2009-01-29 | アーク・セラピューティックス・リミテッド | ステント |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7423125B2 (en) | 1995-08-01 | 2008-09-09 | Vegenics Limited | Antibodies to VEGF-C |
| US20080305999A1 (en) * | 1996-11-01 | 2008-12-11 | John Francis Martin | Therapeutic use of growth factor, and delivery device, especially for the treatment of intimal hyperplasia |
| EP1019082B2 (en) * | 1997-10-02 | 2008-06-04 | Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften E.V. | Use of a colony stimulating factor (csf) for enhancing collateral growth of collateral arteries and/or other arteries from preexisting arteriolar connections |
| GB9809082D0 (en) | 1998-04-28 | 1998-06-24 | Eurogene Limited | Delivery device |
| JP2002524421A (ja) * | 1998-09-09 | 2002-08-06 | サイオス インコーポレイテッド | 微小血管障害の処置 |
| US6596699B2 (en) | 1998-09-22 | 2003-07-22 | Biosurface Engineering Technologies, Inc. | Nucleic acid coating compositions and methods |
| US6958147B1 (en) | 1998-10-26 | 2005-10-25 | Licentia Ltd | Use of VEGF-C to prevent restenosis |
| FR2792531B1 (fr) * | 1999-04-26 | 2003-01-31 | Aventis Pharma Sa | Utilisation d'adenovirus recombinant defectif comprenant un acide nucleique codant pour un facteur angiogenique pour le traitement de l'hypertension arterielle pulmonaire |
| BR0010034A (pt) * | 1999-04-26 | 2002-01-15 | Aventis Pharma Sa | Utilização de um vetor, processo de preparação de um medicamento útil para a prevenção, a melhoria e/ou o tratamento da hipertensão arterial pulmonar, e, composição farmacêutica |
| IL148826A0 (en) * | 1999-09-23 | 2002-09-12 | An Go Gen Inc | Cell-based gene therapy for the pulmonary system |
| AU782158B2 (en) * | 1999-11-02 | 2005-07-07 | Genentech Inc. | Modulation of eNOS activity and therapeutic uses thereof |
| US7078382B1 (en) | 1999-11-02 | 2006-07-18 | Genentech, Inc. | Modulation of eNOS activity and therapeutic uses thereof |
| SE0000285D0 (sv) * | 1999-12-07 | 2000-01-31 | Mika Lahtinen | Medical implant |
| WO2001062942A2 (en) | 2000-02-25 | 2001-08-30 | Ludwig Institute For Cancer Research | MATERIALS AND METHODS INVOLVING HYBRID VASCULAR ENDOTHELIAL GROWTH FACTOR DNAs AND PROTEINS AND SCREENING METHODS FOR MODULATORS |
| GB0012997D0 (en) * | 2000-05-26 | 2000-07-19 | Eurogene Limited | Gene delivery |
| EP1392837A2 (en) * | 2001-05-29 | 2004-03-03 | Ark Therapeutics Limited | Gene delivery via a baculovirus vector |
| AU2002327219B2 (en) * | 2001-07-06 | 2009-04-23 | Syntach Ag | Anti-arrhythmia devices and methods of use |
| SE0102578L (sv) * | 2001-07-20 | 2003-01-21 | Oeyvind Reitan | Förändring av en stents egenskaper för att förhindra restenos |
| WO2004113384A1 (de) * | 2003-06-18 | 2004-12-29 | Georg-August-Universität Göttingen | Verwendung eines vegf-rezeptorgens oder -genprodukts |
| WO2007022287A2 (en) | 2005-08-15 | 2007-02-22 | Vegenics Limited | Modified vegf and pdgf with improved angiogenic properties |
| EP1984522B1 (en) * | 2006-01-18 | 2010-08-11 | The General Hospital Corporation | Methods of increasing lymphatic function |
| US8721711B2 (en) | 2007-06-20 | 2014-05-13 | Oregon Health & Science University | Graft having microporous membrane for uniform fluid infusion |
| US8808255B2 (en) | 2007-12-14 | 2014-08-19 | Oregon Health & Science University | Drug delivery cuff |
| DE102008002396A1 (de) | 2008-06-12 | 2009-12-17 | Biotronik Vi Patent Ag | Implantierbares Wirkstoffreservoir und Vorrichtung mit einem implantierbaren Wirkstoffreservoir |
| EP2814513B1 (en) * | 2012-02-14 | 2017-12-20 | The Regents of The University of California | Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions |
| KR102041381B1 (ko) | 2012-03-12 | 2019-11-27 | 젬백스 에이에스 | 능동적인 면역치료법을 이용한 비-소세포성 폐암의 치료 |
| AU2013296611B2 (en) | 2012-08-01 | 2017-11-23 | United Therapeutics Corporation | Treatment of pulmonary arterial hypertension with mesenchymal stem cells |
| EP2943069B1 (en) | 2013-01-09 | 2018-08-15 | United Therapeutics Corporation | Treatment of vasculopathy with prostacyclin and mesenchymal stem cells |
| IL266175B2 (en) | 2016-10-24 | 2024-01-01 | United Therapeutics Corp | Enhancement of msc immunomodulatory properties by treprostinil |
| IT201900012537A1 (it) * | 2019-07-22 | 2021-01-22 | Milano Politecnico | Dispositivo di condizionamento per condizionare un tratto esposto di un vaso sanguigno e metodo |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3797485A (en) * | 1971-03-26 | 1974-03-19 | Alza Corp | Novel drug delivery device for administering drug into blood circulation in blood vessel |
| WO1994023668A1 (en) * | 1993-04-14 | 1994-10-27 | Emory University | A device for local drug delivery and methods for using the same |
| WO1994028721A1 (en) * | 1993-06-11 | 1994-12-22 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of vascular degenerative diseases by modulation of endogenous nitric oxide production or activity |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56122317A (en) * | 1980-02-29 | 1981-09-25 | Koken:Kk | Drug transporting material and its preparation |
| US5201728A (en) * | 1991-05-03 | 1993-04-13 | Giampapa Vincent C | Subcutaneous implantable multiple-agent delivery system |
| US5326568A (en) * | 1991-05-03 | 1994-07-05 | Giampapa Vincent C | Method of tissue-specific delivery |
| US5653744A (en) * | 1995-04-27 | 1997-08-05 | Khouri Biomedical Research, Inc. | Device and method for vascular anastomosis |
| US5830879A (en) * | 1995-10-02 | 1998-11-03 | St. Elizabeth's Medical Center Of Boston, Inc. | Treatment of vascular injury using vascular endothelial growth factor |
-
1997
- 1997-11-03 ES ES97910563T patent/ES2235227T3/es not_active Expired - Lifetime
- 1997-11-03 JP JP52114098A patent/JP2001503755A/ja not_active Withdrawn
- 1997-11-03 HU HU9902867A patent/HU223957B1/hu not_active IP Right Cessation
- 1997-11-03 AU AU47906/97A patent/AU729420B2/en not_active Ceased
- 1997-11-03 CA CA002270286A patent/CA2270286C/en not_active Expired - Fee Related
- 1997-11-03 DE DE69732304T patent/DE69732304T2/de not_active Expired - Lifetime
- 1997-11-03 PL PL97333272A patent/PL189744B1/pl not_active IP Right Cessation
- 1997-11-03 PT PT97910563T patent/PT941116E/pt unknown
- 1997-11-03 KR KR1019997003881A patent/KR100695590B1/ko not_active Expired - Fee Related
- 1997-11-03 EP EP04021613A patent/EP1488761A1/en not_active Withdrawn
- 1997-11-03 WO PCT/GB1997/003015 patent/WO1998020027A2/en not_active Ceased
- 1997-11-03 EP EP97910563A patent/EP0941116B1/en not_active Expired - Lifetime
- 1997-11-03 AT AT97910563T patent/ATE287271T1/de active
-
1999
- 1999-04-30 NO NO19992106A patent/NO326303B1/no not_active IP Right Cessation
-
2003
- 2003-02-19 US US10/370,291 patent/US7320679B2/en not_active Expired - Fee Related
-
2008
- 2008-01-11 JP JP2008004349A patent/JP4783797B2/ja not_active Expired - Fee Related
-
2011
- 2011-10-27 JP JP2011236266A patent/JP2012031196A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3797485A (en) * | 1971-03-26 | 1974-03-19 | Alza Corp | Novel drug delivery device for administering drug into blood circulation in blood vessel |
| WO1994023668A1 (en) * | 1993-04-14 | 1994-10-27 | Emory University | A device for local drug delivery and methods for using the same |
| WO1994028721A1 (en) * | 1993-06-11 | 1994-12-22 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of vascular degenerative diseases by modulation of endogenous nitric oxide production or activity |
Non-Patent Citations (5)
| Title |
|---|
| JPN4007020786, ＡＳＡＨＡＲＡ， Ｔ．， ｅｔ ａｌ．, "Ｌｏｃａｌ Ｄｅｌｉｖｅｒｙ ｏｆ Ｖａｓｃｕｌａｒ Ｅｎｄｏｔｈｅｌｉａｌ Ｇｒｏｗｔｈ Ｆａｃｔｏｒ Ａｃｃｅｌｅｒａｔｅｓ Ｒｅｅｎｄｏｔｈｅｌｉａｌｉｚａｔｉｏｎ ａｎｄ Ａｔｔｅｎｕａｔｅｓ", Ｃｉｒｃｕｌａｔｉｏｎ, 19950601, Ｖｏｌ．９１， Ｎｏ．１１, ｐ．２７９３−２８０１, US * |
| JPN4007020787, ＢＵＲＫＥ， Ｐ．Ａ．， ｅｔ ａｌ．, "ＶＡＳＣＵＬＡＲ ＥＮＤＯＴＨＥＬＩＡＬ ＧＲＯＷＴＨＦＡＣＴＯＲ ＣＡＵＳＥＳ ＥＮＤＯＴＨＥＬＩＡＬ ＰＲＯＬＩＦＥＲＡＴＩＯＮ ＡＦＴＥＲ ＶＡＳＣＵＬＡＲ ＩＮＪＵＲＹ", Ｂｉｏｃｈｅｍｉｃａｌ ａｎｄ Ｂｉｏｐｈｙｓｉｃａｌ Ｒｅｓｅａｒｃｈ Ｃｏｍｍｕｎｉｃａｔｉｏｎｓ, 19950206, Ｖｏｌ．２０７， Ｎｏ．１, ｐ．３４８−３５４, US * |
| JPN6008039621, ＶＯＮ ＤＥＲ ＬＥＹＥＮ， Ｈ．Ｅ．， ｅｔ ａｌ．, "Ｇｅｎｅ ｔｈｅｒａｐｙ ｉｎｈｉｂｉｔｉｎｇ ｎｅｏｉｎｔｉｍａｌ ｖａｓｃｕｌａｒ ｌｅｓｉｏｎ： Ｉｎ ｖｉｖｏ ｔｒａｎｓｆｅｒ ｏｆ ｅｎｄｏｔｈｅｌｉａｌ ｃｅｌｌ ｎｉｔｒｉｃ ｏｘｉｄ", Ｐｒｏｃｅｅｄｉｎｇｓ ｏｆ ｔｈｅ Ｎａｔｉｏｎａｌ Ａｃａｄｅｍｙ ｏｆ Ｓｃｉｅｎｃｅｓ ｏｆ ｔｈｅ Ｕｎｉｔｅｄ Ｓｔａｔｅｓ ｏｆ Ａｍｅｒｉｃａ, 199502, Ｖｏｌ．９２, ｐ．１１３７−１１４１, US, Ｎａｔｉｏｎａｌ Ａｃａｄｅｍｙ ｏｆ Ｓｃｉｅｎｃｅｓ；Ｗａｓｈｉｎｇｔｏｎ * |
| JPN6008039625, ＢＯＯＴＨ， Ｒ．Ｆ．Ｇ．， ｅｔ ａｌ．, "Ｒａｐｉｄ ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ａｔｈｅｒｏｓｃｌｅｒｏｔｉｃ ｌｅｓｉｏｎｓ ｉｎ ｔｈｅ ｒａｂｂｉｔ ｃａｒｏｔｉｄ ａｒｔｅｒｙ ｉｎｄｕｃｅｄ ｂｙ ｐｅｒｉｖａｓｃｕｌａｒ ｍａ", Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ, 1989, Ｖｏｌ．７６, ｐ．２５７−２６８ * |
| JPN6008039626, ＬＡＩＴＩＮＥＮ， Ｍ．， ｅｔ ａｌ．, "Ｌｏｃａｌ Ａｄｖｅｎｔｉｔｉａｌ ＶＥＧＦ ｇｅｎｅ Ｔｒａｎｓｆｅｒ Ｒｅｄｕｃｅｓ Ｎｅｏｉｎｔｉｍａ Ｆｏｒｍａｔｉｏｎ ｉｎ Ｒａｂｂｉｔ Ｃａｒｏｔｉｄ Ａｒｔｅｒｉｅｓ", ＣＩＲＣＵＬＡＴＩＯＮ, 1996, Ｖｏｌ．９４， Ｎｏ．８ ＳＵＰＰＬ．, ｐ．Ｉ−６３７ * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502226A (ja) * | 2005-07-22 | 2009-01-29 | アーク・セラピューティックス・リミテッド | ステント |
Also Published As
| Publication number | Publication date |
|---|---|
| US7320679B2 (en) | 2008-01-22 |
| NO992106L (no) | 1999-06-30 |
| HK1108845A1 (zh) | 2008-05-23 |
| KR100695590B1 (ko) | 2007-03-14 |
| EP0941116A2 (en) | 1999-09-15 |
| DE69732304T2 (de) | 2005-06-02 |
| AU4790697A (en) | 1998-05-29 |
| PT941116E (pt) | 2005-05-31 |
| HU223957B1 (hu) | 2005-03-29 |
| US20030225020A1 (en) | 2003-12-04 |
| JP4783797B2 (ja) | 2011-09-28 |
| AU729420B2 (en) | 2001-02-01 |
| JP2012031196A (ja) | 2012-02-16 |
| NO992106D0 (no) | 1999-04-30 |
| KR20000052999A (ko) | 2000-08-25 |
| WO1998020027A3 (en) | 1998-10-08 |
| WO1998020027A2 (en) | 1998-05-14 |
| CA2270286A1 (en) | 1998-05-14 |
| NO326303B1 (no) | 2008-11-03 |
| CA2270286C (en) | 2009-03-03 |
| ES2235227T3 (es) | 2005-07-01 |
| EP0941116B1 (en) | 2005-01-19 |
| DE69732304D1 (de) | 2005-02-24 |
| PL333272A1 (en) | 1999-11-22 |
| ATE287271T1 (de) | 2005-02-15 |
| EP1488761A1 (en) | 2004-12-22 |
| HUP9902867A3 (en) | 2001-12-28 |
| JP2008155036A (ja) | 2008-07-10 |
| PL189744B1 (pl) | 2005-09-30 |
| HUP9902867A2 (hu) | 1999-12-28 |
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