JPH04500318A - 高周波経弁軸対称血液ポンプ - Google Patents
高周波経弁軸対称血液ポンプInfo
- Publication number
- JPH04500318A JPH04500318A JP1504824A JP50482489A JPH04500318A JP H04500318 A JPH04500318 A JP H04500318A JP 1504824 A JP1504824 A JP 1504824A JP 50482489 A JP50482489 A JP 50482489A JP H04500318 A JPH04500318 A JP H04500318A
- Authority
- JP
- Japan
- Prior art keywords
- blood
- membrane
- pump
- blood pump
- fluid
- 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.)
- Pending
Links
Classifications
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/80—Constructional details other than related to driving
- A61M60/855—Constructional details other than related to driving of implantable pumps or pumping devices
- A61M60/89—Valves
- A61M60/894—Passive valves, i.e. valves actuated by the blood
- A61M60/896—Passive valves, i.e. valves actuated by the blood having flexible or resilient parts, e.g. flap valves
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/10—Location thereof with respect to the patient's body
- A61M60/122—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body
- A61M60/126—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body implantable via, into, inside, in line, branching on, or around a blood vessel
- A61M60/13—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body implantable via, into, inside, in line, branching on, or around a blood vessel by means of a catheter allowing explantation, e.g. catheter pumps temporarily introduced via the vascular system
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/10—Location thereof with respect to the patient's body
- A61M60/122—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body
- A61M60/126—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body implantable via, into, inside, in line, branching on, or around a blood vessel
- A61M60/135—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body implantable via, into, inside, in line, branching on, or around a blood vessel inside a blood vessel, e.g. using grafting
- A61M60/139—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body implantable via, into, inside, in line, branching on, or around a blood vessel inside a blood vessel, e.g. using grafting inside the aorta, e.g. intra-aortic balloon pumps
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/20—Type thereof
- A61M60/247—Positive displacement blood pumps
- A61M60/253—Positive displacement blood pumps including a displacement member directly acting on the blood
- A61M60/268—Positive displacement blood pumps including a displacement member directly acting on the blood the displacement member being flexible, e.g. membranes, diaphragms or bladders
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/40—Details relating to driving
- A61M60/424—Details relating to driving for positive displacement blood pumps
- A61M60/427—Details relating to driving for positive displacement blood pumps the force acting on the blood contacting member being hydraulic or pneumatic
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/50—Details relating to control
- A61M60/508—Electronic control means, e.g. for feedback regulation
- A61M60/577—High-frequency driving
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/10—Location thereof with respect to the patient's body
- A61M60/122—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body
- A61M60/126—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body implantable via, into, inside, in line, branching on, or around a blood vessel
- A61M60/148—Implantable pumps or pumping devices, i.e. the blood being pumped inside the patient's body implantable via, into, inside, in line, branching on, or around a blood vessel in line with a blood vessel using resection or like techniques, e.g. permanent endovascular heart assist devices
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/20—Type thereof
- A61M60/205—Non-positive displacement blood pumps
- A61M60/211—Non-positive displacement blood pumps using a jet, venturi or entrainment effect for pumping the blood
-
- 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
- A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
- A61M60/40—Details relating to driving
- A61M60/403—Details relating to driving for non-positive displacement blood pumps
- A61M60/408—Details relating to driving for non-positive displacement blood pumps the force acting on the blood contacting member being mechanical, e.g. transmitted by a shaft or cable
- A61M60/411—Details relating to driving for non-positive displacement blood pumps the force acting on the blood contacting member being mechanical, e.g. transmitted by a shaft or cable generated by an electromotor
- A61M60/414—Details relating to driving for non-positive displacement blood pumps the force acting on the blood contacting member being mechanical, e.g. transmitted by a shaft or cable generated by an electromotor transmitted by a rotating cable, e.g. for blood pumps mounted on a catheter
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S128/00—Surgery
- Y10S128/03—Heart-lung
Landscapes
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- Mechanical Engineering (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- External Artificial Organs (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Steroid Compounds (AREA)
- Reciprocating Pumps (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。
Description
【発明の詳細な説明】
高周波経弁軸対称血液ポンプ
発FtAの分野
本発明は、一時的心臓補助装置、特に、心室腔を減圧して拡張期および収縮期の
間、血液流を維持する風船(バルン)型経弁(Transvalvular)血
液ポンプに関するものである。
発明の背景
欧州特許公開公報第0209070号(バラム・ジ。
エイ・シンク)はバルンポンプが心臓の下流の主動脈内に配置され、通常の心拍
の少なくとも3倍の周波数で周期的に膨張および収縮させられる高周波動脈内心
臓支援装置を開示している。拡張期に膨張させられると、シング氏バルンが冠動
脈を介して血液を押圧する。
しかしながら、収縮期には、体が能動的に潅流されている間、冠動脈の抵抗によ
りこの効果は本質的に除かれてしまう。
シング氏バルンは、膨張しても大動脈弁を介して吸引を行なわないので、拡張期
に膨張させられているときに体を能動的に潅流することはない。しかしながら、
心筋の保存を良くするには拡張期に心室腔を減圧すること、すなわち心臓補助装
置を操作することによって大動脈弁を介して吸引することが重要である。
発明の開示
本発明は、収縮および拡張の同期において、交互に、収縮時に大動脈弁を介して
心室腔から血液を抜き取り、膨張時にその血液を体に押し出す空気または油圧操
作弁を有する血管内ポンプを提供することによって従来技術の欠点を克服するも
のである。典型的には、本発明のポンプは、ストロークの大きさによって決まる
が、600〜1.000サイクル/分程度の周波数で作動する。収縮期と拡張期
の同期にポンプを使用できるため、その血液流量は従来技術のポンプよりも40
〜50%増加する。
心室腔を連続的に減圧するので、本発明のポンプは、はとんどの公知のバルンポ
ンプで必要とされるような自然心拍との同期は不必要であり、シング氏ポンプに
好適である。このことは不整脈の場合に決定的に重要であるだけでなく、ポンプ
機構を著しく簡略化し、その操作をより簡単にするとともに信頼性の高いものに
する。また、心電図や大動脈圧の追跡の必要が無いため、緊急事態の際に遅滞な
く心臓補助を開始することができる。
本発明のポンプは物理的には細長く堅い、両端の開いた胴体からなり、大動脈内
に配置される。胴体の取り入れ端部は大動脈弁を通って延び心室腔内に取り入れ
口を有する取り入れカニユーレに密封裡に結合されている。胴体の取り入れ端部
および流出端部は血液を体の潅流の方向にのみ流すことを許す可視性の一方弁に
よって閉じられている。
胴体とほぼ同じ広がりを持つ可視性の弾力性膜が胴体壁の内側に載置されて胴体
の両端の周縁に沿って該内側に密封裡に取付けられている。体外にあるポンプ装
置まで経皮的に延びている適当な導管が配置されており、気体または液体作動流
体を胴体壁と膜との間の空間に導入したり、そこから排出したりする。
作動流体が導入および排出されるにつれて、膜は一方弁同士の間の膜の内表面に
よって規定されるポンプ室の容積を交互に減少したり増大したりする。この動作
によlり入れカニユーレおよび取り入れ弁を介して心室腔から血液を抜き取り、
この血液を流出弁を介して大動脈に押し出す。
本発明のポンプの上記の軸対称構造にはさらに別の利点がある。従来技術のバル
ンポンプは本来的にそれが位置する血管の直径まで膨張するので、それらが収縮
期に1秒間光たり10回も血液流を閉塞する。しかしながら、収縮期の閉塞は溶
血を生じる。さらに、従来技術のポンプにより引き起こされる大動脈弁の高周波
での引っ張りは大動脈弁を損傷することがある。
本発明のポンプでは、胴体の直径が大動脈よりも小さいため血液がその周りを流
れることができることと、可視性の膜を該層が膨張期に胴体を通る通路を閉塞す
る手前で停止するように操作することとにより閉塞が防止される。大動脈弁に対
する高周波での引っ張りは全て取り入れカニユーレの経弁配置によって回避され
る。
従って、本発明の目的は、収縮期と拡張期の同期において心室腔を減圧すること
のできる心臓補助用高周波血液ポンプを提供することである。
本発明の別の目的は、自然の心拍に同期させる必要のない心臓補助用高周波ポン
プ提供することである。
本発明のさらに別の目的は、配置されている血管を収縮期に閉塞することがなく
、大動脈弁に高周波ストレスをかけることのない心臓補助用高周波血液ポンプを
提供することである。
図面の簡単な説明
第1図は、ヒトの心臓および大動脈の一部分を示す概略図であり、本発明の装置
の配置を示すものである。
第2図は、本発明のポンプの軸方向断面図である。
第3図ji、排出に続く第2図のポンプの要素の位置を説明する概略図である。
第4図は、膨張に続く第2図のポンプの要素の位置を説明する概略図である。
発明を実施するための最良の形悪
第1図は本発明の一時的な心臓補助における使用を説明するものである。高周波
ポンプlOは取り入れカニユーレを備えており、公知の手段により経皮的に例え
ば大腿動脈(図示せず)に挿入され、次いで、大腿動脈を通って、カニユーレ1
2の遠位端が大動脈弁16を通って心臓20の心室腔18内に侵入するまで、大
動脈内に押し込まれる。
取り入れカニユーレ12は任意の適当な構成、例えば本発明者らの同時係属米国
特許出願第129.713号(1987年12月7日出願)に示されるものであ
ってもよい。カニユーレ12は密封裡にポンプ10の取り入れ端部に取付けられ
ており、かつポンプ10の操作の間は心室腔18−に位置する取り入れ開口部を
その遠位端に有する。
作動流体供給ルーメン24がポンプ10から大動脈、大腿動脈および経皮挿入点
を通って、交互にルーメン24に作動流体を注入しルーメン24からこれを排出
する適当な体外制御袋1(図示せず)まで延びてい乙。
作動流体は気体状でも液状でもよく、ヘリウムがその化学的物理的性質から好ま
しい。ルーメン24の加圧と排出の交代速度はポンプ10の各ストロークに移動
する血液の体積によって決まる。典型的には、5’ccのストロークに対して、
周波数は約600サイクル/分であり、3ccのストロークに対して、周波数は
約1.000サイクル/分である。
第2図はポンプ10の内部構造をいくぶん図式的に示すものである。堅い、生体
適合性プラスチック材料製の円筒状胴体26がポンプ10のハウジングを形成し
ている。円筒状の可視性・弾力性膜28が胴体26の内壁にその取り入れ端部3
0および流出端部32において円周状に密封裡に取付けられている。胴体26の
壁の充填空間34は、ルーメン24と、膜28を胴体26の内壁から分離してい
る空間38との間に作動流体を運搬する。
一方取り入れ弁40と一方流出弁42が、胴体26の内壁にその取り入れ端部3
0および流出端部32において円周状に密封裡に取付けられている。弁40.4
2は好ましくは天然の大動脈弁16と同様の構造(第1図)をしており、矢印4
4.46の方向しこ胴体26を通って血液が自由に流れるのを許容するよう(こ
配向するが、胴体26を通って逆方向シこ流れる血液流をすべて阻止する。
ポンプlOの操作は第3図および第4図しこ概略的に説明されている。作動流体
が空間38力1ら矢印50(第3図)で示すように排出されると、膜28カで胴
体26の膜に向かって引っ張られポンプ室52を拡張してその中に血液を心室腔
18(第1図)からカニユーレ12と血液流(矢印54)&こよって開力1れた
取り入れ弁42とを通って引き込む。流出弁42(よ室52の拡張によって生じ
た背圧によって閉じられて血液力(体の方向から室52内に引き込まれるのを防
止する。
加圧作動流体が矢印56(第4図)で示すよう番二空間38に導入されると、膜
28が室52の容積を減少させるように動作して室52から血液力τ今度1′1
開し)ている流出弁42を通って体に開力)って(矢印58)追い出される。溶
血を防止するために、膜28の運動(よ、室52を通る血液流を決して閉塞しな
し1ようしこ、IIJ限されている。
収縮期の自然血圧が十分高し)なら!f、取り入れ弁40および流出弁42はポ
ンプ操作サイクJしを通してずつと、ともにある程度間νまたままで室52を通
って体に向かって追加の血液を運搬するようにしてもより1゜カニユーレ12の
取り入れ口22が心室腔18内に位置している限り、ポンプ10の作動は大動脈
弁の自然作動にに影響しないが、それでも脈動吸引を能えて収縮期と拡張期との
雨期に心室腔18を減圧する。このことは心筋の良好な保存のためには重要であ
り、さらに、冠状シクル中ポンプを連続的に作動させると、従来技術の心臓補助
装置に比べて唾液流量が著しく増加する。
FIG、 3
FIG、 4
国際調査報告
Claims (6)
- (1)a)血管に通せる寸法の、実質的に円筒状の、堅い胴体であって、取り入 れ端部と流出端部とを有する胴体、 b)心臓の弁を通して心室腔内に挿入するためのカニューレであって、その近位 端において、該胴体の内部と流体連絡している該取り入れ端部に密封裡に接合さ れるとともに、その遠位端において、取り入れ口を有するカニューレ、 c)交互に、血液を該胴体の内部に引き入れ、かつ該胴体から追い出すための該 胴体内の流体作動ポンプ手段、および d)該カニューレから該流出端の方向のみに血液が該胴体に対して流入し、かつ 該胴体から流出するのを許容するための該胴体の各端部におけるパルプ手段、 を備えて成る高周波経弁軸対称血液ポンプ。
- (2)前記胴体が作動流体を体の外部に対して搬出し外部から搬入するための手 段を有し、前記ポンプ手段が、 i)前記胴体に円周状に密封裡に取付けられた実質的に円筒状の、可橈性の膜で あって、該胴体の壁と当該膜との間に空間を規定する膜、およびii)交互に作 動流体を該空間に対して導入および排出して交互に該膜が該膜の内表面と前記バ ルブ手段とによって規定された容積を減少または増大させるための手段、 を備えて成ることを特徴とする請求の範囲第1項に記載の血液ポンプ。
- (3)前記作動流体が気体であることを特徴とする請求の範囲第2項に記載の血 液ポンプ。
- (4)前記作動流体がヘリウムであることを特徴とする請求の範囲第3項に記載 の血液ポンプ。
- (5)前記膜の運動が前記パルプ手段同士の間の流体流路の閉塞を防止するよう に制限されていることを特徴とする請求の範囲第2項に記載の血液ポンプ。
- (6)前記ポンプ手段の交代周波数が実質的に600〜1、000サイクル/分 であることを特徴とする請求の範囲第1項に記載の血液ポンプ。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US189,527 | 1988-05-03 | ||
| US07/189,527 US4906229A (en) | 1988-05-03 | 1988-05-03 | High-frequency transvalvular axisymmetric blood pump |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04500318A true JPH04500318A (ja) | 1992-01-23 |
Family
ID=22697710
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1504824A Pending JPH04500318A (ja) | 1988-05-03 | 1989-04-17 | 高周波経弁軸対称血液ポンプ |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US4906229A (ja) |
| EP (1) | EP0415949B1 (ja) |
| JP (1) | JPH04500318A (ja) |
| AT (1) | ATE119400T1 (ja) |
| AU (1) | AU625556B2 (ja) |
| BR (1) | BR8907417A (ja) |
| CA (1) | CA1328790C (ja) |
| DE (1) | DE68921627T2 (ja) |
| WO (1) | WO1989010763A1 (ja) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3099260A (en) * | 1960-02-09 | 1963-07-30 | Davol Rubber Co | Heart pump apparatus |
| SU400331A1 (ja) * | 1971-07-06 | 1973-10-01 | ||
| US4080958A (en) * | 1976-02-27 | 1978-03-28 | Datascope Corporation | Apparatus for aiding and improving the blood flow in patients |
| US4250872A (en) * | 1978-05-25 | 1981-02-17 | Yehuda Tamari | Blood pulsating and/or pumping device |
| US4465063A (en) * | 1982-05-25 | 1984-08-14 | University Of Utah | Cardiac flow measurement system and method |
| US4625712A (en) * | 1983-09-28 | 1986-12-02 | Nimbus, Inc. | High-capacity intravascular blood pump utilizing percutaneous access |
| EP0209070A3 (en) * | 1985-07-15 | 1988-07-20 | ABIOMED, INC. ( a Delaware Corporation) | High frequency intra-arterial cardiac support system |
-
1988
- 1988-05-03 US US07/189,527 patent/US4906229A/en not_active Expired - Lifetime
-
1989
- 1989-04-17 DE DE68921627T patent/DE68921627T2/de not_active Expired - Fee Related
- 1989-04-17 WO PCT/US1989/001645 patent/WO1989010763A1/en not_active Ceased
- 1989-04-17 BR BR898907417A patent/BR8907417A/pt not_active IP Right Cessation
- 1989-04-17 AT AT89904906T patent/ATE119400T1/de not_active IP Right Cessation
- 1989-04-17 JP JP1504824A patent/JPH04500318A/ja active Pending
- 1989-04-17 EP EP89904906A patent/EP0415949B1/en not_active Expired - Lifetime
- 1989-04-17 AU AU34302/89A patent/AU625556B2/en not_active Ceased
- 1989-04-24 CA CA000597614A patent/CA1328790C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU3430289A (en) | 1989-11-29 |
| AU625556B2 (en) | 1992-07-16 |
| WO1989010763A1 (en) | 1989-11-16 |
| ATE119400T1 (de) | 1995-03-15 |
| CA1328790C (en) | 1994-04-26 |
| DE68921627T2 (de) | 1995-07-06 |
| US4906229A (en) | 1990-03-06 |
| BR8907417A (pt) | 1991-04-02 |
| EP0415949A1 (en) | 1991-03-13 |
| DE68921627D1 (en) | 1995-04-13 |
| EP0415949B1 (en) | 1995-03-08 |
| EP0415949A4 (en) | 1991-07-03 |
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