JPH0773607B2 - 膨張式ステント - Google Patents

膨張式ステント

Info

Publication number
JPH0773607B2
JPH0773607B2 JP3016116A JP1611691A JPH0773607B2 JP H0773607 B2 JPH0773607 B2 JP H0773607B2 JP 3016116 A JP3016116 A JP 3016116A JP 1611691 A JP1611691 A JP 1611691A JP H0773607 B2 JPH0773607 B2 JP H0773607B2
Authority
JP
Japan
Prior art keywords
stent
wall
hollow
hydrophilic material
wall structure
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
JP3016116A
Other languages
English (en)
Other versions
JPH04215768A (ja
Inventor
トーマス・エイ・シルヴェストリーニ
Original Assignee
ハウメディカ・インク
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Filing date
Publication date
Application filed by ハウメディカ・インク filed Critical ハウメディカ・インク
Publication of JPH04215768A publication Critical patent/JPH04215768A/ja
Publication of JPH0773607B2 publication Critical patent/JPH0773607B2/ja
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/88—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure the wire-like elements formed as helical or spiral coils
    • 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
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheets or tubes, e.g. perforated by laser cuts or etched holes
    • 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
    • A61F2002/825—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents having longitudinal struts
    • 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
    • A61F2250/0003—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having an inflatable pocket filled with fluid, e.g. liquid or gas
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1002—Balloon catheters characterised by balloon shape

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Description

【発明の詳細な説明】
【０００１】
【産業上の利用分野】本発明は一般に、体腔、たとえば
管（ｄｕｃｔ，ｖｅｓｓｅｌ）を開いた状態に維持する
ために用いられるステント、特に中空の膨張式壁を備え
たステントに関するものである。
【０００２】
【従来の技術】処置を行わない場合には閉じているかま
たは閉塞している体腔、たとえば管を開いた形状に維持
するためにステントを用いることは十分に認められた処
置法である。現在一般に用いられているステントには、
たとえば米国特許第４，６５５，７７１号明細書に記載
される自己膨張式ステント、およびステント内で膨張さ
せるバルーンによりその体腔部位で膨張するステントが
含まれる。いずれの場合もステントは通常は金属製であ
り、従って一般にある程度の剛性および最小の可撓性を
もつ。
【０００３】
【発明が解決しようとする課題】従って本発明の第１の
目的は、挿入に際しては軟質かつ柔軟であり、ただし処
置部位に配置されたのちは適切な程度の剛性および硬質
性を備えうるステントを提供することである。本発明の
他の目的は、少なくとも壁構造の一部が半透膜から製造
された中空の膨張式壁であるステントを提供することで
ある。本発明のさらに他の目的は、中空壁の内部に、液
体を吸収することにより体積が増大して結果的に壁を膨
張させうる親水性材料が配置されたステントを提供する
ことである。本発明のさらに他の目的は、親水性材料と
共に薬物が配置されたステントを提供することである。
これらおよび他の本発明の目的は以下の記載により明ら
かになるであろう。
【０００４】
【課題を解決するための手段】本発明は、少なくともそ
の一部が中空壁である壁構造を含む、体腔内に配置する
ためのステントである。中空壁の内部には、中空壁内へ
液体が導入された際に膨潤し、これにより中空壁を膨張
させる親水性材料が配置され、たとえばこれはゲル状で
あってもよい。内部に親水性材料が配置された中空壁は
半透膜から製造され、これにより配置部位にあるステン
トの周囲組織からの体液は膜を貫通して親水性材料を膨
潤させ、これにより壁を膨張させる。親水性材料と共
に、ステント配置部位において膜を通して放出させるた
めの治療薬が配置されてもよい。本発明のステントを用
いうる体腔の例には、動脈、静脈、尿道および尿管、胆
管、肝管および膵管、気管、食道および腸部分、精管お
よび卵管、耳管ならびに涙管が含まれるが、必ずしもこ
れらに限定されない。ステントの壁構造全体が中空壁で
あってもよく、壁構造に中空部分および非中空部分の両
方、たとえば互いに編組、製織、または巻織されること
により互いに保持された中空繊維および中実繊維が含ま
れてもよい。
【０００５】本発明は、配置したのち膨張させた時点で
は体腔を支持するステントを提供するが、ステントは膨
張していない状態でその部位へ送入することができるの
で、結果的に送入時には小型であるのものを提供し、体
腔内での配置性が向上する。
【０００６】現時点で好ましい本発明の形態を図面に示
す。
【０００７】図１には体腔内に配置するためのチューブ
状ステント１０が示される。ステント１０の壁構造全体
が、中空の膨張式壁１２であり、これはステント１０が
体腔内に配置された際に組織の内生を容易にするために
多数の半径方向開口１６が貫通したバルーン１８からな
る。壁１２は、たとえば当技術分野で既知の半透膜を形
成しうる、かつ適切な膨張圧に耐えうるポリマーから構
成される半透膜から製造される。その例にはポリアミ
ド、ポリエステル、ポリウレタン、およびエチレンビニ
ルアルコールが含まれるが、これらに限定されない。ス
テント１０の中空壁１２の内部には親水性材料３２が配
置される。これは浸透圧希釈により液体を吸収または吸
引しうるものであり、これにより材料３２が与える体積
または圧力が増大する。この親水性材料は浸透圧を生じ
る生体適合性物質のいずれであってもよい。その例には
無機塩類、有機塩類、糖類、多糖類、高分子ヒドロゲル
または両性分子が含まれるが、これらに限定されない。
好ましい材料の１つはヒドロゲル、たとえばポリビニル
アルコールである。
【０００８】使用に際しては、ステント１０をまず膨張
していない状態で、通常の適宜な送入手段、たとえば適
宜なサイズのカテーテル（図示されていない）により、
目的部位に配置する。適量の周囲組織液が壁１２内へ拡
散し、これにより親水性材料３２が膨潤してステント１
０を膨張させ、従ってこれが体腔内壁に突き当たること
により適所に自立滞在しうるのに十分な期間、目的位置
におけるこの配置が送入手段によって維持される。もち
ろん壁１２の製造に用いられる半透膜は、膨張した親水
性材料により内部に形成される圧力による破裂に耐える
のに十分な強度のものでなければならない。最終的に半
径方向開口１６を通して組織の内生が起こる。
【０００９】ステント１０は徐放性ドラッグデリバリー
用具としても使用しうる。特に薬物を親水性材料３２と
共に、別個の成分として、またはそれとブレンドして配
置しうる。こうして薬物は半透膜を通して周囲組織内へ
長期間にわたって放出されるであろう。もちろんこうし
て含有される薬物は適宜な濃度で供給され、目的とする
放出速度を達成するために必要に応じキャリヤーを含ん
でもよい。さらに薬物の分子量は親水性材料のものより
低くすべきである。この種の薬物の一例はピロキシカム
−−フェルデン（Ｆｅｌｄｅｎｅ）として市販される；
ファイザー製、ニューヨーク州ニューヨーク−−であ
り、ステント当たり約２０−５００ｍｇの量で存在す
る。薬物は治療効果を得るためにステント１０からその
のち徐々に放出されるべく、別個の成分であってもよ
く、または親水性材料３２と混合するかもしくはそれに
溶解することにより親水性材料に内包されてもよい。も
ちろん異なるステント用途につき異なる薬物を用いるこ
とができる。この種の薬物の例には心臓血管用の抗トロ
ンビン薬、尿路処置用の石灰沈着防止薬、およびステン
ト処置またはバルーン血管形成術に対する生物反応を抑
制するための抗炎症薬または増殖抑制薬が含まれるが、
これらに限定されない。
【００１０】ステント１０は、各々チューブ状にした２
枚の膜を同心円状に重ねて、これにより外側膜の内面と
内側膜の外面に囲まれた中空部を有する中空構造体を構
成することによって製造することができる。２枚の膜の
間にゲルを導入したのち当技術分野で既知の膜シール法
によりステント１０の末端をシールし、同時に半径方向
開口１６を切り取り、シールする。
【００１１】図２は体腔内に配置するためのチューブ状
ステント２０の第２形態を示す。ステント２０の壁構造
全体が編組された多数の中空繊維２６からなる中空の膨
張式壁２４である。実質的に壁構造全体が図２に示すよ
うに編組された多数の中空繊維２６からなっていてもよ
いが、図３に示すチューブ状ステント４０のように壁４
４の一部のみが中空繊維２６からなる構造であってもよ
い。この場合ステント４０の中空繊維２６は中実繊維２
８と編組されている。ステント２０、４０が体腔内の適
所に配置された際に組織の内生を容易にすべく、多数の
半径方向開口２９ががそれぞれの壁２４、４４を貫通し
て伸びる。図１に示すステント１０のバルーン１８と同
様にステント２０、４０の中空繊維２６は、たとえば当
技術分野で既知の半透膜を形成しうるポリマーから構成
される半透膜から製造される。その例にはポリアミド、
ポリエステル、ポリウレタン、およびエチレンビニルア
ルコールが含まれるが、これらに限定されない。先に図
１に関して述べたように、中空繊維２６の内部には親水
性材料が配置される。これは液体を吸収しうるものであ
り、これによりこの材料の体積が増大し、繊維２６を膨
張させる。同様に先に述べたように、親水性材料は繊維
２６の半透膜を通して周囲組織内へ長期間にわたって放
出される薬物を内包しうる。
【００１２】ステント２０、４０は先に図１に関して述
べたように、体腔内の目的部位に配置される。同様に、
適量の周囲組織液が繊維２６内へ拡散し、これにより親
水性材料が膨潤してステント２０、４０を膨張させ、従
ってこれが体腔内壁に突き当たることにより適所に自立
滞在しうるのに十分な期間、目的位置におけるこの配置
が送入手段によって維持される。もちろん中空繊維２６
の製造に用いられる半透膜は、膨張した親水性材料によ
り内部に形成される圧力による破裂に耐えるのに十分な
強度のものでなければならない。半径方向開口２９を通
して組織の内生が起こる。
【００１３】ここに記載するステント２０を構成する１
方法は、当技術分野で既知の溶剤キャスチング法の採用
である。たとえばポリマー溶液がダイの一部から送り出
されて中空壁を形成する適宜な形状のダイを設置する。
同時に親水性材料、たとえばゲルをダイの他の部分から
ポリマー溶液の中心へ送り出す。ポリマーおよびゲルが
この種の溶剤キャスチングに際して設置される凝固浴に
達した時点で、この構造体が硬化するのに伴いゲルはポ
リマーで囲まれる。あるいはもちろん、繊維末端をシー
ルしたのち繊維の長さ内へゲルを加圧下に添加すること
もできる。
【００１４】図４は壁構造全体が中空壁５２であるステ
ント５０を示す。特にステント５０は、図示したように
膨張した状態ではらせん形状をもつが、体腔内の部位へ
は膨張していない直線形状で送り込むことができるバル
ーン５４からなる中空の膨張式壁５２を含む。図１−３
に示すステントと同様にステント５０の壁５２は、たと
えば当技術分野で既知の半透膜を形成しうるポリマーか
ら構成される半透膜から製造される。その例には同様に
ポリアミド、ポリエステル、ポリウレタン、およびエチ
レンビニルアルコールが含まれるが、これらに限定され
ない。先に図１に関して述べたように、壁５２の内部に
は親水性材料が配置される。これは液体を吸収しうるも
のであり、これによりこの材料の体積が増大し、膨張を
達成する。壁５２の少なくとも一部を繊維強化材５６、
たとえばポリエステル、ナイロンまたはポリプロピレ
ン、好ましくはポリエステルで強化することもできる。
製造中に壁５２に強化材５６を付与する１手段は、構造
体の周りに繊維を編組し、次いで半透膜のオーバーコー
トを施すものである。この種の強化材はもちろんステン
ト５０にいっそう大きな強度を付与する。
【００１５】中空壁５２の内部には親水性材料が配置さ
れ、ステント５０は先に図１−３に関して述べたよう
に、体腔内の目的部位に配置される。同様に、適量の周
囲組織液が壁５２内へ拡散し、これにより親水性材料が
膨潤してステント５０を膨張させ、従ってこれがそのら
せん形状を確保し、体腔内壁に突き当たることにより適
所に自立滞在しうるのに十分な期間、目的位置における
この配置が送入手段によって維持される。もちろん膨張
式壁５２の製造に用いられる半透膜は、膨張した親水性
材料により内部に形成される圧力による破裂に耐えるの
に十分な強度のものでなければならない。
【００１６】図４に示すステント５０も徐放性ドラッグ
デリバリー用具として使用しうる。特に薬物を壁５２内
に上記親水性材料と共に配置することができ、薬物は半
透膜の壁構造を通して周囲組織内へ長期間にわたって放
出される。
【００１７】本発明の一例となる、現時点で好ましい形
態につき詳述したが、本発明の概念は他の各種形態およ
び用途が可能であり、特許請求の範囲の記載は先行技術
により制限されない限りこれらの概念を包含すると解す
べきである。
【図面の簡単な説明】
【図１】壁構造全体が膨張式バルーンからなる中空壁で
あるチューブ状ステントの、一部断面を含む透視図であ
る。
【図２】壁構造全体が編組された膨張性繊維からなる中
空壁である第２形態のチューブ状ステントの、一部断面
を含む立面図である。
【図３】壁構造が膨張性繊維の中空壁部分および中実繊
維の中実壁部分からなり、中空繊維および中実繊維の双
方が互いに編組された第３形態のチューブ状ステント
の、一部断面を含む立面図である。
【図４】壁構造全体が膨張式らせんからなる第４形態の
ステントの、一部断面を含む透視図である。
【符号の説明】
１０，２０，４０，５０ ステント １２，２４，，４４，５２ 膨張式壁 １６，２９ 開口 １８，５４ バルーン ２６ 中空繊維 ２８ 中実繊維 ３２ 親水性材料 ５６ 強化材

Claims (12)

    【特許請求の範囲】
  1. 【請求項１】 体腔内に配置するためのステントであっ
    て、 ａ）該ステントは壁構造体からなり； ｂ）該壁構造体の少なくとも一部が、閉じた中空を有す
    る半透膜の壁でできており； ｃ）該壁の中空部には、液体を吸収することにより体積
    が増大しうる親水性材料が配置されており；そして ｄ）該壁構造体はステントの半径方向に貫通した複数の
    開口を有している、ステント。
  2. 【請求項２】 親水性材料がゲルである、請求項１に記
    載のステント。
  3. 【請求項３】 形状がチューブである、請求項１に記載
    のステント。
  4. 【請求項４】 バルーン型である、請求項３に記載のス
    テント。
  5. 【請求項５】 親水性材料と共に薬剤が配置された、請
    求項１に記載のステント。
  6. 【請求項６】 体腔内に配置するためのステントであっ
    て、 ａ）該ステントは壁構造体からなり； ｂ）該壁構造体の少なくとも一部が、複数の中空繊維が
    互いに編織、製織または巻織されて一体に保持されるこ
    とによって構成されており； ｃ）該中空繊維は閉じた中空を有する半透膜からできて
    おり；そして ｄ）該中空繊維の中空部には、液体を吸収することによ
    り体積が増大しうる親水性材料が配置されている、 ステント。
  7. 【請求項７】 親水性材料がゲルである、請求項６に記
    載のステント。
  8. 【請求項８】 親水性材料と共に薬剤が配置された、請
    求項６に記載のステント。
  9. 【請求項９】 体腔内に配置するためのステントであっ
    て、 ａ）該ステントは壁構造体からなり； ｂ）該壁構造体の少なくとも一部が、閉じた中空を有す
    る半透膜の壁でできており； ｃ）該壁の中空部には、液体を吸収することにより体積
    が増大しうる親水性材料が配置されており；そして ｄ）膨張した際に該壁構造体がらせん型となる、 ステント。
  10. 【請求項１０】 親水性材料と共に薬剤が配置された、
    請求項９に記載のステント。
  11. 【請求項１１】 中空壁の少なくとも一部が強化されて
    いる、請求項９に記載のステント。
  12. 【請求項１２】 バルーン型である、請求項９に記載の
    ステント。
JP3016116A 1990-02-08 1991-02-07 膨張式ステント Expired - Fee Related JPH0773607B2 (ja)

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Application Number Priority Date Filing Date Title
US47726490A 1990-02-08 1990-02-08
US477264 1990-02-08

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Publication Number Publication Date
JPH04215768A JPH04215768A (ja) 1992-08-06
JPH0773607B2 true JPH0773607B2 (ja) 1995-08-09

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US (1) US5234456A (ja)
EP (1) EP0441516B1 (ja)
JP (1) JPH0773607B2 (ja)
AT (1) ATE120377T1 (ja)
AU (1) AU621780B2 (ja)
CA (1) CA2035853C (ja)
DE (2) DE69108423T2 (ja)
DK (1) DK0441516T3 (ja)
ES (1) ES2071207T3 (ja)
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IE65798B1 (en) 1995-11-15
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DE9101344U1 (de) 1991-06-06
US5234456A (en) 1993-08-10
ES2071207T3 (es) 1995-06-16
ATE120377T1 (de) 1995-04-15
DE69108423T2 (de) 1995-07-27
DK0441516T3 (da) 1995-06-12
JPH04215768A (ja) 1992-08-06
AU621780B2 (en) 1992-03-19
EP0441516A3 (en) 1992-08-05
CA2035853C (en) 1995-02-07
EP0441516B1 (en) 1995-03-29
EP0441516A2 (en) 1991-08-14
AU7088791A (en) 1991-08-29

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