JPH0832622B2 - 薬剤投与デバイス - Google Patents

薬剤投与デバイス

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Publication number
JPH0832622B2
JPH0832622B2 JP61191568A JP19156886A JPH0832622B2 JP H0832622 B2 JPH0832622 B2 JP H0832622B2 JP 61191568 A JP61191568 A JP 61191568A JP 19156886 A JP19156886 A JP 19156886A JP H0832622 B2 JPH0832622 B2 JP H0832622B2
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environment
drug
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releasing
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JPS6245520A (ja
Inventor
ジェームス・ビー・エッケンホフ
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アルザ・コ−ポレ−シヨン
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
    • 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
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Nozzles (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Description

【発明の詳細な説明】 （発明の利用分野） 本発明は、薬剤を即時に薬剤受容体環境に供給する手
段を包含する薬剤投与デバイスに関する。この薬剤投与
デバイスは、有用薬剤を予かじめ定められたプログラム
に従つて放出するシステムであり、有用薬剤の有効量が
直ちに放出され、そのあと長期にわたり該薬剤の有効量
を連続放出する。この投与デバイスは、選択された受容
体域に薬剤を即時かつ連続的に放出する投与装置の形態
で製造される。
（従来の技術） 薬剤を調節された速度で長期にわたり正確に投与する
薬剤投与デバイスは、Theeuwesおよびriguchiの米国特
許第3,845,770号および同第3,916,899号ならびにEckenh
offの米国特許第4,350,271号で投与技術分野に知られて
いる。これらの特許に開示された投与デバイスは、薬剤
配合物含有を取り囲む半透過性の壁を有し、薬剤配合物
は（１）浸透活性な溶質または（２）浸透活性な膨潤性
ポリマーの影響下に装置から投与される。これらの投与
デバイスは、溶解性に乏しいものから非常に可溶性なも
のにいたる薬剤を水性の生物流体に放出するのに非常に
効果的である。
前記の投与デバイスは、投与技術分野において顕著か
つ開拓的進歩を示すものであり、無数の薬剤を各種使用
環境に投与するのに有用である。
（発明が解決しようとする問題点） ところで、薬剤放出の機構および装置の有用性を高め
ることにより、これらの投与デバイスが更に改善可能な
ることも見出された。すなわち、初期に生体有効薬剤を
放出すると共に、引続き実質上一定量の薬剤を一定時間
にわたり調節された速度で放出し、それにより、投与デ
バイスから薬剤を放出するためにこれまで頻々必要とさ
れた薬剤放出開始までの時間を実質上無くし、薬剤受容
体への薬剤の即時供給を可能とする投与デバイスを提供
できることが予期されずに知見されたのである。本発明
により可能となつたこの投与デバイスは、初期に独得の
薬剤放出をしたあと、長期にわたり調節された連続的な
放出を行ない、それにより予かじめ選択され内蔵された
薬剤提供最適プログラムに従つて機能するのである。
従つて、前記の提示に照し、本発明の直接の目的は、
初期に有効量の薬剤を放出し、引続き長期間にわたり連
続放出する投与デバイスを提供することにある。
本発明の別の目的は、即時放出用の薬剤を含有する第
一手段と連続放出用の薬剤を含有する第二手段からな
り、それにより使用環境における作動に際し、即時的か
つ連続的に薬剤を放出する投与システムを提供すること
にある。
本発明の更に別なる目的は、第二薬剤供給手段の外部
に位置する薬剤供給用第一担体手段を有し、その第一担
体手段が一度に即時放出する薬剤を含有し、それにより
第二手段に係る放出開始までの時間を実質的に無くすよ
うな投与デバイスを提供することにある。
本発明の更に別なる目的は、即時放出用の薬剤配合物
を収納する最外部材を有し、それにより薬剤配合物にそ
の有用効果を発揮させる、投与デバイス形態で製造され
る投与デバイスを提供することにある。
本発明の更に別なる目的は、初期に薬剤パルスを放出
するための外被を有し、それが引続き一定時間にわたり
調節速度で薬剤を連続放出する動物への薬剤配合物の投
与に適した投与デバイスを提供することにある。
本発明の更に別なる目的は、先行技術の投与デバイス
が薬剤受容体に薬剤を供給しなかつた開始時期に、薬剤
を即時供給し得る投与デバイスを提供可能とすることに
より先行技術を改善することにある。
本発明の更に別なる目的は、製造が容易で安価に使用
でき、且つまた薬剤を即時供給したあと一定時間にわた
り薬剤を一定速度で供給する投与デバイスを提供するこ
とにより、薬剤投与デバイスを改善することである。
本発明は、 （ａ）有用薬剤を使用環境に放出するための第２手段、
前記第２手段は （１）使用環境内でその物理的および化学的状態を維持
し、使用環境に存在する流体の通過に対し透過性である
重合体組成物を少くとも部分的に含有する壁、 （２）コンパートメント （３）前記のコンパートメント内の有用薬剤、および （４）長期にわたり有用薬剤を第２手段から使用環境に
連続的に放出するための壁内の手段、 を有する有用薬剤を使用環境に連続的に放出する第２手
段、ならびに （ｂ）（１）使用環境に有用薬剤配合物を即時に供給す
るため元の物理的および化学的状態を失う壁、前記の壁
が第２手段の一部分を取り巻いており、 （２）第１手段と第２手段の間の内腔、および （３）第１手段により使用環境に即時放出される、前記
内腔内の有用薬剤配合物 を有する、使用環境に有用薬剤を即時供給させる第１手
段 を含む有用薬剤を使用環境に放出するための投与デバイ
スに関する。
本発明のその他の目的、特徴および利点は、以下の図
面を用いた詳細な説明および特許請求の範囲から、当業
者には更に明らかとなるであろう。
図面には尺度を付していないが、本発明の各種実施態
様を示すものであつて以下の通りである。
第１図は、２部分からなる投与デバイス、すなわちは
め込みキヤツプ部分によりはめ込み式に蓋された部分を
有する浸透式投与装置の図である。
第２図は、はめ込みキヤツプ内に即時放出用の薬剤が
存在するはめ込み式にキヤツプで蓋された部分と一定時
間にわたり連続放出する薬剤を含有する浸透式装置を示
す第１図の切開図である。
第３図は、即時放出薬剤を供給するための第一手段を
有し、該第一手段が第二手段上にぴつたりと合うような
一体物として製造されたものであり、第二手段が、第一
手段の薬剤放出後に薬剤を放出するための浸透式装置を
有する投与デバイスの図である。
第４図は、即時放出薬剤を供給する手段が、第３図の
浸透式装置の後端部を取囲み封入するような第３図投与
デバイスの図である。
第５図は、第３図投与デバイスの切開図であつて、即
時放出薬剤供給手段が、即時放出のあと一定時間にわた
り薬剤を連続放出する放出装置と構造的に調和がとれた
ものであることを示している。
第６図は、投与装置をはめ込むためおよび即時使用薬
剤を貯蔵するためのスナツプ止めオーバーキヤツプを有
する第３図投与デバイスの別実施態様の図である。
第７図は、（１）はめ込みキヤツプ部にてはめ込み式
に胴体部を閉した２部分からなるカプセルと、それが定
める内部空間に含まれる（２）遊離薬剤および薬剤投与
装置を組み合せて有する投与デバイスの図である。
第８図は、第７図の投与デバイスの切開図であつて、
２部分から形成されるカプセルと、即時放出用の遊離薬
剤ならびに引続く長期放出に供する投与装置内の薬剤を
示している。
図面および明細書において、類似部分には同じ番号を
付した。これまでの説明および図面の説明にでてきた用
語ならびにそれらの実施態様については、以下の開示で
更に詳細に説明する。
さて、図面につき詳細に説明するが、これらの図面は
本発明が提供する投与デバイスの例示であつて、本発明
を限定すると解されてはならない。投与デバイスの一例
は第１図の数字10で示されるものである。第１図の投与
デバイス10は、投与装置11とキヤツプ部材12の２部分か
らなる。キヤツプ部材12は、投与装置11の一部に滑りこ
み、取りはずせる形でそれにはまり込み且つそれを被う
ように製られている。
第２図は、投与システム10を構成する構造部材を説明
するため、投与装置11とキヤツプ12を有する図１の投与
デバイス10を切り開いた図である。図２では、投与装置
11は浸透式分与装置であり、コンパートメント14を取り
巻く壁13と浸透性通路15を有する。壁12は、全面的もし
くは少くともその一部が、外部流体の通過に対し透過性
であり、コンパートメント14内に存在する薬剤配合物16
に対しては実質上不透過性であるような非毒性重合体組
成物で形成されている。壁13を形成する重合体組成物は
不活性であり、その物理的・化学的状態を維持して浸透
式投与装置11の投与寿命を延長させる。壁13を形成する
ための代表的材料には、浸透膜および逆浸透膜として知
られる半透過性重合体がある。これらの重合体材料には
セルロースエステル、セルロースエーテル、セルロース
エステル−エーテル、セルロースアシレート、セルロー
スジアシレートおよびセルローストリアシレートが含ま
れる。
装置10のコンパートメント14は有用薬剤配合物16を含
有する。薬剤配合物16は、一実施態様では、外部流体に
可溶であり、かつ、半透過性壁13を横切つて外部流体に
対し浸透圧勾配を示す適切な薬剤16を含有することがで
き、あるいは外部流体における薬剤16の溶解度に限界が
ある際の別の実施態様では、外部流体に可溶かつ壁13を
横切つて外部流体に対し浸透圧勾配を示す浸透剤と混合
することができる。
キヤツプ部材12は、有用薬剤配合物19を含有するため
の内部空間を取巻き、それを定める壁17を有する。薬剤
配合物19は、使用環境への即時放出に供せられる。壁17
は、一好適実施態様では、親水性であつて、水性液また
は生体流体中で加水分解乃至溶解する非毒性の壁形成材
料で形成される。壁17のこの性質は、その元の状態を失
なわせ、キヤツプ部材17から薬剤配合物19を直ちに使用
環境に放出させる。壁17を形成するための代表的材料に
はゼラチンがあり、更に詳しくは15乃至30ミリポイズの
粘度および150グラムまでのブルーム強度（bloomstreng
th）を有するゼラチン、160乃至250のブルーム値を有す
るゼラチン、30,000乃至300,000なる範囲の分子量を有
するペクチン、プロラミンとして入手できるゼイン（ze
in）およびその類似物が含まれる。
作動時には、投与デバイス10は、使用環境での順次作
動により有用薬剤を即時かつそのあと連続的に放出す
る。すなわち、キヤツプ部材12は、使用環境の流体の存
在下で溶解し、薬剤配合物19を即時に使用環境に放出す
る。この第一作動は投与装置11の全体を使用環境に露出
させる。それに付随して投与装置11は、壁13の透過率と
壁13を横切る浸透圧勾配で定められる速度で、浸透平衡
に向う流体を半透過性壁13を経てコンパートメント14に
吸収する。吸収された流体は、活性薬剤16を含有する溶
液あるいは活性薬剤を懸濁状態で含有する浸透剤の溶液
を連続的に形成し、この溶液または懸濁体はいずれの場
合も、投与装置11の作動により通路15を経て水力学的に
投与される。投与デバイス10は、キヤツプ部材12と投与
装置11の協同作用により、薬剤配合物を使用環境に即時
供給すると共に、そのあと一定時間にわたり連続的に供
給する。
第３図および第４図は、共に本発明が提供する別の投
与デバイス10を示すものである。第３図および第４図の
投与デバイス10は、温血動物とくに反すう動物への有用
薬剤の投与に適した形状ならびに寸法の長い円筒状の投
与デバイス10に関する。第３図の投与デバイス10は、胴
体部21、前端部22、後端部23およびキヤツプ部材24で取
巻かれ、それで保護される前端部22部分を有する投与装
置20を包含する。第４図は、胴体部21、前端部22、後端
部23および後部キヤツプ16で取り巻かれた後端部分を有
する投与装置20を示すものである。第３図および第４図
の投与装置20には共に、投与装置20の外部を投与装置20
の内部に連結する、通路27が付与されている。
第５図は、第３図の投与デバイス10の切開図である。
投与デバイス10は、投与装置20とキヤツプ24からなる。
投与装置20は29で切り開かれており、キヤツプ24は31で
切り開かれている。投与装置20は胴体部21、前端部22、
後端部23および通路27からなる。投与装置20は、コンパ
ートメント30を取巻き、それを定める壁28を更に有す
る。壁28は、この好適実施態様では、外部流体の通過に
対し実質上透過性であり、コンパートメント30内に存在
する有用薬剤その他の成分の通過に対しては実質上非透
過性の半透過性壁形成組成物で形成されている。コンパ
ートメント30は多数の線で示される熱応答性感熱性組成
物33を更に含有し、この熱応答性感熱性組成物は点で示
される有用薬剤32を含有する。コンパートメント30は更
に膨脹性駆動手段34を含有し、これは熱応答性組成物33
と接触した層状配列物である。熱応答性組成物と膨脹性
部材は、共にコンパートメント30の内部形状に対応する
形状を有する。コンパートメント30は、感熱性組成物33
と接触する高密部材35すなわち高密度化材をも含有し、
図示の実施態様では膨脹部材34から離れた位置にある。
通路36は投与装置20から有用薬剤配合物32を放出するた
め、高密部材35を通して伸長している。
膨脹性組成物34はヒドロゲル組成物から製造される。
ヒドロゲルは非架橋型あるいは必要に応じて架橋された
ものでもよく、流体を吸収して拡大状態に膨潤乃至膨脹
する能力を有する。ヒドロゲルは重合体組成物であり、
膨潤乃至膨脹して２乃至50倍の体積増加を示す。本発明
の目的に有用なヒドロゲルには、ポリ（メタクリル酸ヒ
ドロキシアルキル）、ポリ（酸化エチレン）、寒天およ
びその類似物が包含される。熱応答性組成物33は、この
好適実施態様では、室温の21℃およびその数度の範囲内
の温度で固体様性質を示し、哺乳動物体温の37℃および
その数度の範囲内の温度、通常35乃至42℃で熱を吸収し
て融解する能力を示す感熱性の疎水性または親水性材料
で形成される。熱応答性組成物は熱に応答して投与可能
な状態になり、その中に分散された薬剤組成物33の担体
として機能する。代表的な熱応答性組成物はカカオ脂、
水素化植物油、飽和植物脂肪酸のトリグリセリドおよび
その類似物である。高密部材35は、反すう動物の第一胃
網状袋に投与装置20を保持するため投与装置20内に使用
される。一般に高密部材35は約１乃至８の密度を有し、
鉄、酸化鉄で被覆された鉄小球、ステンレス鋼およびそ
の類似物で形成される。
投与装置20の前端部22上に位置するキヤツプ24は、薬
剤受入れ空間38を取り巻いてそれを形成する壁37を有す
る。空間38は、キヤツプ24の内表面と投与装置20の外表
面で形成される。空間38は有用薬剤配合物39を含有す
る。有用薬剤配合物39は、投与デバイス10が使用動物に
入つた際に、即時放出用に供せられる。即時放出のため
キヤツプ内に収納される有用薬剤および調節連続放出の
ために投与装置内に収納される有用薬剤には、医薬品、
栄養剤、ビタミン類、食品補足剤、抗腸内寄生虫薬、抗
寄生体薬、抗伝染病薬およびその類似物が包含される。
有用薬剤の代表例には、イベルメクチン（ivermecti
n）、フエンベンダゾール（fenbendazole）、ピランテ
ル（pirantel）およびその類似物が含まれる。即時放出
に供される有用薬剤の量は約75ng乃至5gであり、調節連
続放出に供される有用薬剤の量は約250mg乃至25gあるい
はそれ以上である。
第５図の投与デバイス10は、動物内での作動時に、熱
力学作用と動力学的作用が一体となつた組合せ作用によ
り有用薬剤を使用流体環境に放出する。すなわち、投与
デバイス10が胃腸管に入つた作動時に、キヤツプ24は溶
解し、動物が急速使用するための有用薬剤配合物39を直
ちに供給する。キヤツプ24が溶解して配合物39を放出す
ると同時に、投与装置20は有用薬剤配合物32を連続投与
できる状態になる。この作動時に、感熱性組成物33は動
物とくにその第一胃の温度に応答してエネルギーを吸収
・融解し、通路36および27を経て第一胃に放出するため
の流動性または半ペースト状の放出可能な組成物を形成
する。組成物33が熱エネルギーを吸収・融解するにつれ
て、外部流体が外部半透過性壁28を通して、浸透平衡に
向う状態にある膨脹性親水性層状部材34に吸収され、連
続的にヒドロゲル層34を膨脹させる。層34は、一好適実
施態様においては、感熱性組成物33と膨脹性層34が定め
る界面40でもとのままの非混和性境界を維持しながら膨
脹する。層34の膨脹および膨潤は層34の容積を増大さ
せ、同時に層34は有用薬剤組成物33に向つて膨脹し、通
路を経て有用薬剤を投与装置20の外部へと追いたてる。
投与装置20が作動すると、通常１日乃至６ヶ月の長期間
にわたり調節された速度で有用薬剤の供給が可能とな
る。すなわち、投与デバイス10は組合せ作動により、有
用薬剤を即時かつ連続的に使用環境に供給する。
第６図は、本発明が提供する別の投与デバイス10を示
すものである。投与デバイス10は、キヤツプ42で覆れた
投与装置41を有する。投与装置41は、第３図乃至第５図
に示した投与装置に類似したものである。第６図では、
投与装置41の一部はキヤツプ42で囲まれ、光で位置ぎめ
してレーザーで穿孔された通路43を有する。キヤツプ42
は即時供給薬剤44を取り囲んでいる。投与装置41は、そ
の胴体部周囲の切れ込みである雌型のスナツプ嵌合受け
部材45も有する。このスナツプ嵌合切れ込みは任意の幾
何学的形で取り巻くことができる。図示実施態様のスナ
ツプ嵌合45は円形の切れ込みである。キヤツプ42は切れ
込みまたは表面くぼみである雄型スナツプ嵌合部材46で
あり、キヤツプ42の周囲に伸長している。スナツプ嵌合
45および46は、投与装置41上にキヤツプ42を配置させる
ため、および投与装置からキヤツプ42を取り外すための
対応嵌合形状を有する。
第７図は、本発明が提供する別の実施態様を示すもの
である。第７図は、胴体50aおよびそれとはめ込み式に
接合されるぴつたり合つたキヤツプ50bからなる内腔51
を定める２部分から形成され、投与装置52を含有する外
側カプセル50を有する投与デバイス10を示す。必要に応
じ、カプセル50は、投与装置含有空間を取り巻く壁の一
体カプセルとすることもできる。第８図は、第７図の投
与デバイス10の切開図である。第８図では、投与デバイ
ス10は、カプセルキヤツプ50a、カプセルキヤツプ50b、
有用薬剤配合物53を含有する内部空間51、および内部の
投与装置52を有する。投与装置52は、半透過性壁54、コ
ンパートメント55、有用薬剤56、膨脹性部材57および予
かじめ定められた通路58を有する。投与デバイス10は、
前の投与デバイスで説明した有用薬剤を放出する。
本発明の新規な投与デバイスは、使用環境に有用薬剤
配合物を即時供給すると共に、そのあと連続的に供給す
る。好適実施態様につき本発明の諸特徴を説明・指摘し
てきたが、本発明の精神から逸脱することなく、図示な
らびに説明してきた分与システムに対し各種の変更、付
加および省略が可能なことは、当業者の理解するところ
であろう。
【図面の簡単な説明】
第１図は２部分からなる投与デバイスの図である。 第２図は第１図の切開図である。 第３図は薬剤を即時放出する第一手段と長期に放出する
第二手段からなる投与デバイスの図である。 第４図は、薬剤の即時放出手段が、第３図の後端部を取
囲み封入する第３図の投与デバイスの図である。 第５図は、第３図の投与デバイスの切開図である。 第６図は、スナツプ止めオーバーキヤツプを有する別の
実施態様の図である。 第７図は、遊離薬剤と薬剤分を装置をカプセル内に含む
投与デバイスの図である。 第８図は、第７図の投与デバイスの切開図である。

Claims (6)

    【特許請求の範囲】
  1. 【請求項１】（ａ）有用薬剤を使用環境に放出するため
    の第２手段、前記第２手段は （１）使用環境内でその物理的および化学的状態を維持
    し、使用環境に存在する流体の通過に対し透過性である
    重合体組成物を少くとも部分的に含有する壁、 （２）コンパートメント （３）前記のコンパートメント内の有用薬剤、および （４）長期にわたり有用薬剤を第２手段から使用環境に
    連続的に放出するための壁内の手段、 を有する有用薬剤を使用環境に連続的に放出する第２手
    段、ならびに （ｂ）（１）使用環境に有用薬剤配合物を即時に供給す
    るため元の物理的および化学的状態を失う壁、前記の壁
    が第２手段の一部分を取り巻いており、 （２）第１手段と第２手段の間の内腔、および （３）第１手段により使用環境に即時放出される、前記
    内腔内の有用薬剤配合物 を有する、使用環境に有用薬剤を即時供給させる第１手
    段 を含む有用薬剤を使用環境に放出するための投与デバイ
    ス。
  2. 【請求項２】コンパートメント内の有用薬剤配合物が、
    外部流体に対し、半透過性壁を横切る浸透圧勾配を示
    し、壁を通して流体を吸収し、かつ、有用薬剤を使用環
    境に放出する手段を通して浸透的に放出される特許請求
    の範囲第１項に記載の有用薬剤の使用環境に放出するた
    めの投与デバイス。
  3. 【請求項３】壁を通してコンパートメントに摂取された
    流体を吸収して膨脹し、有用薬剤配合物を通路を通して
    使用環境に移動させる膨脹性部材をコンパートメントが
    含有する特許請求の範囲第１項に記載の有用薬剤の使用
    環境に放出するための投与デバイス。
  4. 【請求項４】有用薬剤配合物が、室温では固体であっ
    て、使用環境温度では通路を通して投与可能となる熱応
    答性担体を含有する特許請求の範囲第１項に記載の有用
    薬剤配合物を使用環境に放出するための投与デバイス。
  5. 【請求項５】コンパートメントが、投与デバイスを使用
    環境に保持するために１を超える比重の高密部材を含有
    する特許請求の範囲第１項に記載の有用薬剤配合物を使
    用環境に放出するための投与デバイス。
  6. 【請求項６】第１手段の壁が、第２手段を取り巻いてそ
    れを囲んでいる特許請求の範囲第１項に記載の有用薬剤
    配合物を使用環境に放出するための投与デバイス。
JP61191568A 1985-08-16 1986-08-15 薬剤投与デバイス Expired - Lifetime JPH0832622B2 (ja)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US766454 1985-08-16
US06/766,454 US4643731A (en) 1985-08-16 1985-08-16 Means for providing instant agent from agent dispensing system

Publications (2)

Publication Number Publication Date
JPS6245520A JPS6245520A (ja) 1987-02-27
JPH0832622B2 true JPH0832622B2 (ja) 1996-03-29

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JP (1) JPH0832622B2 (ja)
AU (1) AU588902B2 (ja)
BE (1) BE905282A (ja)
BR (1) BR8603913A (ja)
CA (1) CA1265404A (ja)
DE (1) DE3627618A1 (ja)
ES (1) ES2001080A6 (ja)
FR (1) FR2586187B1 (ja)
GB (1) GB2179251B (ja)
IT (2) IT1195824B (ja)
NL (1) NL8602022A (ja)
NZ (1) NZ216865A (ja)
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Also Published As

Publication number Publication date
BR8603913A (pt) 1987-11-17
IT1195824B (it) 1988-10-27
ES2001080A6 (es) 1988-04-16
ZA866130B (en) 1987-03-25
FR2586187A1 (fr) 1987-02-20
NZ216865A (en) 1989-07-27
DE3627618A1 (de) 1987-02-26
CA1265404A (en) 1990-02-06
AU6113686A (en) 1987-02-19
GB2179251A (en) 1987-03-04
IT8667659A0 (it) 1986-08-13
GB8618023D0 (en) 1986-08-28
GB2179251B (en) 1989-08-02
AU588902B2 (en) 1989-09-28
FR2586187B1 (fr) 1990-08-10
US4643731A (en) 1987-02-17
NL8602022A (nl) 1987-03-16
JPS6245520A (ja) 1987-02-27
BE905282A (fr) 1986-12-01
IT8653757V0 (it) 1986-08-13

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