JP5726084B2 - 薄型電極アセンブリ - Google Patents
薄型電極アセンブリ Download PDFInfo
- Publication number
- JP5726084B2 JP5726084B2 JP2011535791A JP2011535791A JP5726084B2 JP 5726084 B2 JP5726084 B2 JP 5726084B2 JP 2011535791 A JP2011535791 A JP 2011535791A JP 2011535791 A JP2011535791 A JP 2011535791A JP 5726084 B2 JP5726084 B2 JP 5726084B2
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- electrode
- assembly
- membrane
- conductive
- catheter
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Classifications
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- A61B5/287—Holders for multiple electrodes, e.g. electrode catheters for electrophysiological study [EPS]
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Description
[0080]本明細書で説明する電極装置は、折畳み可能な可撓性電子回路を、比較的剛直かつ容積が大きい電極アセンブリとは対照的に、低侵襲送達のための非常に薄い外形(プロフィール)に組み込む。目標組織に達すると、本明細書で説明する電極装置は、広がって、目標組織と容易に適合可能であり得る非常に表面積の広い電極アセンブリを露出させることができる。
[0081]上述したように、本明細書で説明する装置の電極アセンブリ105は、1または複数の分岐するフレックス回路89を有することができる。後により詳細に説明するように、フレックス回路89は、ベース基板52、導電層96、および誘電体層100を有することができる。更に図1Dを参照すると、フレックス回路89は、複数の導電性遠位分岐部87に分割することができる1または複数の主近位分岐部17(図示せず)を有することができる。各遠位分岐部は複数の導電性トレース16を有することができ、それらは各々、1または複数の導電性パッド59を有している。導電性パッド59は、上に重なっている絶縁誘電体層100の一部が除去されて導電層96が露出することにより形成される、導電性領域を有している。導電性層96の露出部分は、導電性フィルム電極6と接触することができる。導電性パッド59は、広いベース基板層52および絶縁誘電体層100(図示せず)のために大きい表面積を有する導電性トレース16の領域であり得る。導電性トレース16の終端の方法は、本技術分野において既知であるように形成される。これらの表面積が広く大きい領域を、膜により良く付着するために使用することができる。
[0093]1または複数の電極6は、フレックス回路89の導電性トレース16の指定された非絶縁部分、導電性パッド59、および展開式膜34の一部およびフレックス回路89の絶縁部分と接触することができる。電極6は、繰り返し折り畳むことができる薄膜材料であり得、電極6および膜34を低侵襲の送達のために直径が小さくなるように小型化できるようにする。電極6の導電材料の表面積は、それが接触する導電性パッド59と比較して相対的に広く、それにより全体的に広い電極面積が提供される。
[0113]電極アセンブリ105は、フレックス回路89および電極6を結合することができる展開式の可撓性膜34も有している。膜34は、展開されると、電極6の広い表面積を通して目標組織へエネルギを送達することができる。展開された膜34および電極6は、後により詳細に説明するように、広いゾーンまたは部位にわたり種々のパターン、例えば、円周状、曲線状および直線状のパターンで、組織をアブレーションすることができる。電極6およびフレックス回路89により覆われた膜34の全体的な表面積が広いにも関わらず、膜34を、アブレーションされる目標組織に容易に適合可能とし、また、電極アセンブリ105を低侵襲送達のために例えば小さいアクセス導管を通して送達することができるように、小さい直径までコンパクトに折り畳むことができる。
[0133]本明細書で説明する電極アセンブリおよび装置は、容積が小さく薄型で折畳み型とするように最適化する設計および構造を組み込んでいる。本明細書で説明する電極アセンブリおよび装置を、例えば、組織へのエネルギ伝達の低侵襲送達に使用することができる。フレックス回路主リードの装置内における経路等のような、電極装置の構造もまた、装置の小さい容積および薄い外形に寄与することができる。
[0137]上述のように、本明細書で説明する電極アセンブリを、経皮送達用に構成されたカテーテルに取り付けることができる。カテーテルの移動の制御は、一般に、長い管状の構造のために幾分か困難であり得る。移動(運動)に対して十分な制御を提供するために、本明細書に記載するカテーテルを、幾分か剛直であるが、カテーテルが身体を通って正確な位置へ到達することを妨げるほど剛直ではないものとすることができる。更に、カテーテルは、治療されている又は通過している身体の部分に損傷をもたらす可能性があるほど剛直であるべきではない。本明細書で説明するカテーテルを、本技術分野において既知である経皮カテーテルの種々の材料から製造することができ、その材料は、例えば、押出ポリエーテル・ブロック・アミド(PEBAX)、または他の高分子材料、例えば、ポリウレタン、ポリカーボネート、ナイロン、FEP、PTFE、LDPEおよびHDPE、またはそれらの組合せ等を含む。本明細書で説明するカテーテルを、ねじれ剛性を向上させるために、本技術分野において既知であるように、ステンレス鋼の編組やコイル状の層等により補強することができる。金属系およびポリマー系の両方の他の補強材料および構造を使用することができる。カテーテルを、適切な向きに配置するのを容易にするために、例えば湾曲した先端部などのような、所望の形状に成形することも可能である。カテーテルを成形する1つの典型的な方法は、カテーテルの組立て前または組立て後に行うことができる押出成形されたカテーテルの熱再成形によるものである。カテーテルは、解剖学的構造内への導入および追跡中に組織に外傷をもたらすことなく、既知のアクセス点を通って目標組織に達するために、十分な長さと適当な直径とを有する必要がある。
[0143]組織へ付与される過剰なエネルギにより、焦げ付きや凝固などのような二次的損傷がもたらされる可能性がある。逆に、電極が目標組織に十分に並置されないことにより、特に、複雑な3次元形状を有する解剖学的部位においてエネルギが最適に伝達されない結果となる可能性がある。従って、エネルギ伝達の進行を評価すること、および送達されるエネルギを調整および制御することを、特に、装置を取り除く必要なしにできることは、有益なことである。本明細書で説明する装置は、エネルギ伝達をリアルタイムで評価および制御するための他の特徴を有することができる。例えば、本明細書で説明する装置は、後により詳細に説明するように、温度センサ、マッピング電極、潅注(irrigation)機構、視覚化システム、放射線不透過性マーカ、光ファイバ、圧力センサ、熱放散パターン認識ソフトウェア、インピーダンス測定ソフトウェア、固定機構、および他の制御機構を有することができる。
[0145]本明細書で説明する装置は、限定されないが、アブレーション、感知、測定、刺激、および/またはマッピングを含む種々の機能に対して使用することができる1または複数の電極を有することができる。例えば、マッピング電極を使用して、心房細動の治療のためのアブレーションの間および/またはその後に、内因性心臓活動を感知し、伝導ブロック(conduction block)を測定することができる。心房細動が治療される実施形態では、マッピング電極を組み込むことにより、処置中に、別個の装置を導入する必要なしにEKGを測定することができる。上述したものと同じかまたは同様の技法および材料を使用して、種々の電極を堆積(デポジット)させることができる。
[0159]本明細書で説明する電極アセンブリは、目標組織、特に複雑な3次元形状を有する組織との優れた接触を可能にするように適合可能である。本明細書で説明する装置に、電極アセンブリと目標組織との接触を改善する機構を組み込むことができる。実施形態では、バルーン等の支持構造を使用して、目標組織に対して電極アセンブリを押すことができる(図35を参照)。この実施形態では、外面に電極6を有する遠位の相対的に小型の拡張可能電極構造34が、目標組織に対して配置されている。より大型の近位支持構造39が、組織に対して小型の電極構造34を押すことにより、電極構造34の位置決めに役立つことができる。同様に位置決めに役立つように使用することができるガイドワイヤまたは案内ロッド85が示されている。
[0177]本明細書で説明する装置は、装置を取り除いたり装置の向きを変える必要なしに、電極アセンブリの操作および再配置に更に役立つことができる、さまざまな構造的エレメントを組み込むことができる。例えば、電極装置は、目標組織またはその近くの適所に固定されるアンカー・カテーテルまたはガイド・エレメントの上を独立して並進可能であり得る。固定具(anchor)は、安定した基準点を提供し、効率的で迅速で制御された再配置装置として作用することができ、電極アセンブリは、例えば、形成されたばかりのアブレーション・パターン領域に接触するように摺動して又は回転して移動することができるようにする。これにより、ユーザは、例えば、完全な貫壁性(trans-mural)アブレーションをもたらさなかった部位において更なるエネルギ伝達を行うことができる。または、ユーザは、例えば、より厚い組織の部位、またはより多くのエネルギ量もしくは数回のエネルギ伝達を必要とする組織の部位において、治療の有効性をマッピングおよび検証することができる。
[0196]本明細書で説明する装置の製造において、さまざまな技法を採用することができる。実施形態では、フレックス回路89を、電極アセンブリ105の全体的に薄い外形に対して最適化するように、構成することができる。フレックス回路89は、フレックス回路89の導電性トレース16のうちの1つを介して電力が供給され得る温度センサ90を有することができる。これにより、膜64上の更なるアセンブリ接合が不要になる。温度センサ90は、マッピング電極51と導電性トレース16を共用することができる。導電性トレース16を共用することにより、より幅の狭いフレックス回路89と電極アセンブリ105の全体的な薄い外形とが可能になる。単一のフレックス回路89は少なくとも2つの分岐部87に分裂でき、そりにより部品の数を低減し、組立てを容易にすることができる。電極6へ電力を供給するために必要なフレックス回路89のすべての分岐部87に分裂するのは、1つのフレックス回路89のみであり得る。フレックス回路分岐部87の遠位端は犠牲タブ102を有することができ、犠牲タブ102は、組立て中にフレックス回路89の分岐部の適切な位置決めを可能にするものである。
[0202]上述のように、本明細書に記載した装置および方法は、心房細動に対する使用に限定されない。以下は単なる例であり、本明細書では他の適応も考慮されることを理解されたい。
〔態様1〕
組織電極アセンブリであって、
患者内で展開可能である拡張可能な適合性の本体を形成するように構成された膜と、
前記膜の表面に配置され、かつ少なくとも1つのベース基板層と、少なくとも1つの絶縁層と、少なくとも1つの平面導電層とを備えるフレキシブル回路と、
前記フレキシブル回路の少なくとも一部と、前記フレキシブル回路により覆われていない前記膜の前記表面の一部とを覆う導電性電極であって、前記患者への当該アセンブリの低侵襲性送達に適している直径を有する送達形態へと、前記膜とともに折畳み可能である、導電性電極と
を備えるアセンブリ。
〔態様2〕
態様1に記載のアセンブリであって、前記ベース層または前記絶縁層が、絶縁材料の基板層を含み、前記平面導電層が、絶縁材料の前記基板層の少なくとも一部を覆う導電材料を含む、アセンブリ。
〔態様3〕
態様2に記載のアセンブリであって、前記絶縁材料が、ポリイミド、ポリエステル、ポリエチレン・テレフタレート、ポリアリルエーテルエーテルケトン、ポリテトラフルオロエチレン、ポリエチレン・ナフタレート、液晶ポリマー、フォトイメジャブル・カバーレイ、薄いエポキシ・ガラス、ポリイミド・ガラス、およびアクリル系接着剤のうちの少なくとも1つを含む群から選択される、アセンブリ。
〔態様4〕
態様2に記載のアセンブリであって、前記導電材料が、銅、金、銀、錫、ニッケル、鋼鉄、キュプロニッケル、およびニッケル・コバルト鉄合金のうちの少なくとも1つを含む群から選択される、アセンブリ。
〔態様5〕
態様2に記載のアセンブリであって、前記導電層が、絶縁材料の誘電体層により少なくとも部分的に更に覆われる、アセンブリ。
〔態様6〕
態様5に記載のアセンブリであって、前記フレキシブル回路が、1または複数の導電性トレースを有する少なくとも2つの分岐部へと分裂する主リードを備える、アセンブリ。
〔態様7〕
態様6に記載のアセンブリであって、それぞれの前記導電性トレースが、前記絶縁材料の誘電体層により覆われていない露出した導電性層の領域を含む導電性パッドを備える、アセンブリ。
〔態様8〕
態様7に記載のアセンブリであって、前記導電性パッドの下にある前記絶縁材料の基板層の領域が、前記導電性トレースの下にある前記絶縁材料の基板層の領域と比較して広くされた幅を有する、アセンブリ。
〔態様9〕
態様8に記載のアセンブリであって、前記導電性パッドの下にある前記絶縁材料の基板層の前記領域が、前記フレキシブル回路と前記膜とのより優れた付着を可能にするように1または複数の穴を更に備える、アセンブリ。
〔態様10〕
態様6に記載のアセンブリであって、少なくとも1つの導電性トレースが少なくとも2つの導電性パッドを備える、アセンブリ。
〔態様11〕
態様1に記載のアセンブリであって、前記導電性電極により覆われている前記フレキシブル回路の前記部分は前記導電性パッドを含む、アセンブリ。
〔態様12〕
態様11に記載のアセンブリであって、前記導電性電極が、前記導電性パッドの表面積よりも広い表面積を有する、アセンブリ。
〔態様13〕
態様1に記載のアセンブリであって、前記導電性電極が、エネルギ供給される組織へ直接に接触する、アセンブリ。
〔態様14〕
態様1に記載のアセンブリであって、前記導電性電極が、導電性インク、光学インク、ポリマー系インク、銀フレーク接着剤、金、およびプラチナのうちの少なくとも1つを含む群から選択される材料を含む、アセンブリ。
〔態様15〕
態様1に記載のアセンブリであって、前記導電性電極が、印刷、塗装、噴霧、はんだ付け、接着、真空蒸着、およびポジ型材料堆積のうちの少なくとも1つを含む群から選択された技法により堆積されている、アセンブリ。
〔態様16〕
態様1に記載のアセンブリであって、前記導電性電極が膜の適合性を変えない、アセンブリ。
〔態様17〕
態様1に記載のアセンブリであって、前記導電性電極が、単極無線周波数、双極無線周波数、マイクロ波、高電圧、およびエレクトロポレーションのうちの少なくとも1つを含む群から選択されるエネルギを放出する、アセンブリ。
〔態様18〕
態様1に記載のアセンブリであって、1つより多いフレキシブル回路を更に備える、アセンブリ。
〔態様19〕
態様1に記載のアセンブリであって、少なくとも5つのフレキシブル回路を備え、それぞれの前記フレキシブル回路が、1または複数の導電トレースを有する少なくとも2つの分岐部へと分裂し、それぞれの前記導電性トレースが少なくとも1つの導電性電極へ電力を供給する、アセンブリ。
〔態様20〕
態様19に記載のアセンブリであって、前記導電性電極が個々に制御される、アセンブリ。
〔態様21〕
態様1に記載のアセンブリであって、前記フレキシブル回路に取り付けられ、かつ導電性フィルム電極に隣接して配置される少なくとも1つの温度センサを更に備える、アセンブリ。
〔態様22〕
態様21に記載のアセンブリであって、前記温度センサが、導電性トレースを前記導電性電極と共用する、アセンブリ。
〔態様23〕
態様21に記載のアセンブリであって、導電性電極に隣接して配置される前記温度センサが、前記導電性電極から約1mm未満離れている、アセンブリ。
〔態様24〕
態様21に記載のアセンブリであって、前記温度センサが、表面実装サーミスタ、熱電対、プラチナ抵抗温度計、または抵抗温度検出器を含む、アセンブリ。
〔態様25〕
態様1に記載のアセンブリであって、前記拡張可能な適合性の本体が自己拡張型である、アセンブリ。
〔態様26〕
態様1に記載のアセンブリであって、前記膜の前記拡張可能な適合性の本体が液密である、アセンブリ。
〔態様27〕
態様1に記載のアセンブリであって、前記膜の前記拡張可能な適合性の本体が織られたものである、アセンブリ。
〔態様28〕
態様1に記載のアセンブリであって、前記拡張可能な適合性の本体が、管状、球状、トロイド状、円錐状、分岐状、又状、テーパ状、および非対称状の形状を含む群から選択される形状を有する、アセンブリ。
〔態様29〕
態様1に記載のアセンブリであって、前記膜が、ポリ塩化ビニル、ポリエチレン、架橋ポリエチレン、ポリオレフィン、ポリオレフィン・コポリマー、ポリエチレン・テレフタレート、ナイロン、ポリマー・ブレンド、ポリエステル、ポリイミド、ポリアミド、ポリウレタン、シリコーン、ラテックス、マイラー・エラストマー、およびポリジメチルシロキサンのうちの少なくとも1つを含む群から選択された材料を含む、アセンブリ。
〔態様30〕
態様1に記載のアセンブリであって、前記膜が、低侵襲の送達のために構成されたカテーテルの遠位端に結合される、アセンブリ。
〔態様31〕
態様30に記載のアセンブリであって、前記送達の構成は、前記膜が前記カテーテルの前記遠位端に対して遠位へ折り畳まれることと、前記導電性電極がそれ自体の上に折り畳まれることとを含む、アセンブリ。
〔態様32〕
態様30に記載のアセンブリであって、前記フレキシブル回路が、1または複数の導電性トレースを有する少なくとも2つの分岐部へと分裂する主リードを備え、前記主リードが、前記カテーテルの内径を通され、前記膜の近位領域で前記カテーテル内径から出る、アセンブリ。
〔態様33〕
態様32に記載のアセンブリであって、前記フレキシブル回路の前記主リードが、前記膜の内径を通され、前記膜の遠位領域で前記膜内径から出る、アセンブリ。
Claims (32)
- 組織電極アセンブリ(105)であって、
患者内で展開可能である拡張可能な適合性の本体を形成するように構成された膜(34)と、
前記膜(34)の表面に配置され、かつ少なくとも1つのベース基板層(52)と、少なくとも1つの絶縁層(100)と、少なくとも1つの平面導電層(96)とを備えるフレキシブル回路(89)と、
ポリマー系インクを含み、前記フレキシブル回路(89)の少なくとも一部と、前記フレキシブル回路(89)により覆われていない前記膜(34)の前記表面の一部とを覆う導電性電極(6)であって、前記患者への当該アセンブリ(105)の低侵襲性送達に適している直径を有する送達形態へと、前記膜(34)とともに折畳み可能である、導電性電極(6)と
を備えるアセンブリ。 - 請求項1に記載のアセンブリであって、前記ベース層または前記絶縁層が、絶縁材料の基板層を含み、前記平面導電層が、絶縁材料の前記基板層の少なくとも一部を覆う導電材料を含む、アセンブリ。
- 請求項2に記載のアセンブリであって、前記絶縁材料が、ポリイミド、ポリエステル、ポリエチレン・テレフタレート、ポリアリルエーテルエーテルケトン、ポリテトラフルオロエチレン、ポリエチレン・ナフタレート、液晶ポリマー、フォトイメジャブル・カバーレイ、薄いエポキシ・ガラス、ポリイミド・ガラス、およびアクリル系接着剤のうちの少なくとも1つを含む群から選択される、アセンブリ。
- 請求項2に記載のアセンブリであって、前記導電材料が、銅、金、銀、錫、ニッケル、鋼鉄、キュプロニッケル、およびニッケル・コバルト鉄合金のうちの少なくとも1つを含む群から選択される、アセンブリ。
- 請求項2に記載のアセンブリであって、前記導電層が、絶縁材料の誘電体層により少なくとも部分的に更に覆われる、アセンブリ。
- 請求項5に記載のアセンブリであって、前記フレキシブル回路が、1または複数の導電性トレースを有する少なくとも2つの分岐部へと分裂する主リードを備える、アセンブリ。
- 請求項6に記載のアセンブリであって、それぞれの前記導電性トレースが、前記絶縁材料の誘電体層により覆われていない露出した導電性層の領域を含む導電性パッドを備える、アセンブリ。
- 請求項7に記載のアセンブリであって、前記導電性パッドの下にある前記絶縁材料の基板層の領域が、前記導電性トレースの下にある前記絶縁材料の基板層の領域と比較して広くされた幅を有する、アセンブリ。
- 請求項8に記載のアセンブリであって、前記導電性パッドの下にある前記絶縁材料の基板層の前記領域が、前記フレキシブル回路と前記膜とのより優れた付着を可能にするように1または複数の穴を更に備える、アセンブリ。
- 請求項6に記載のアセンブリであって、少なくとも1つの導電性トレースが少なくとも2つの導電性パッドを備える、アセンブリ。
- 請求項1に記載のアセンブリであって、前記導電性電極により覆われている前記フレキシブル回路の前記部分は導電性パッドを含む、アセンブリ。
- 請求項11に記載のアセンブリであって、前記導電性電極が、前記導電性パッドの表面積よりも広い表面積を有する、アセンブリ。
- 請求項1に記載のアセンブリであって、前記導電性電極が、エネルギ供給される組織へ直接に接触する、アセンブリ。
- 請求項1に記載のアセンブリであって、前記導電性電極が、印刷、塗装、噴霧、はんだ付け、接着、真空蒸着、およびポジ型材料堆積のうちの少なくとも1つを含む群から選択された技法により堆積されている、アセンブリ。
- 請求項1に記載のアセンブリであって、前記導電性電極が膜の適合性を変えない、アセンブリ。
- 請求項1に記載のアセンブリであって、前記導電性電極が、単極無線周波数、双極無線周波数、マイクロ波、高電圧、およびエレクトロポレーションのうちの少なくとも1つを含む群から選択されるエネルギを放出する、アセンブリ。
- 請求項1に記載のアセンブリであって、1つより多いフレキシブル回路を更に備える、アセンブリ。
- 請求項1に記載のアセンブリであって、少なくとも5つのフレキシブル回路を備え、それぞれの前記フレキシブル回路が、1または複数の導電トレースを有する少なくとも2つの分岐部へと分裂し、それぞれの前記導電性トレースが少なくとも1つの導電性電極へ電力を供給する、アセンブリ。
- 請求項18に記載のアセンブリであって、前記導電性電極が個々に制御される、アセンブリ。
- 請求項1に記載のアセンブリであって、前記フレキシブル回路に取り付けられ、かつ導電性フィルム電極に隣接して配置される少なくとも1つの温度センサを更に備える、アセンブリ。
- 請求項20に記載のアセンブリであって、前記温度センサが、導電性トレースを前記導電性電極と共用する、アセンブリ。
- 請求項20に記載のアセンブリであって、導電性電極に隣接して配置される前記温度センサが、前記導電性電極から1mm未満離れている、アセンブリ。
- 請求項20に記載のアセンブリであって、前記温度センサが、表面実装サーミスタ、熱電対、プラチナ抵抗温度計、または抵抗温度検出器を含む、アセンブリ。
- 請求項1に記載のアセンブリであって、前記拡張可能な適合性の本体が自己拡張型である、アセンブリ。
- 請求項1に記載のアセンブリであって、前記膜の前記拡張可能な適合性の本体が液密である、アセンブリ。
- 請求項1に記載のアセンブリであって、前記膜の前記拡張可能な適合性の本体が織られたものである、アセンブリ。
- 請求項1に記載のアセンブリであって、前記拡張可能な適合性の本体が、管状、球状、トロイド状、円錐状、分岐状、又状、テーパ状、および非対称状の形状を含む群から選択される形状を有する、アセンブリ。
- 請求項1に記載のアセンブリであって、前記膜が、ポリ塩化ビニル、ポリエチレン、架橋ポリエチレン、ポリオレフィン、ポリオレフィン・コポリマー、ポリエチレン・テレフタレート、ナイロン、ポリマー・ブレンド、ポリエステル、ポリイミド、ポリアミド、ポリウレタン、シリコーン、ラテックス、マイラー・エラストマー、およびポリジメチルシロキサンのうちの少なくとも1つを含む群から選択された材料を含む、アセンブリ。
- 請求項1に記載のアセンブリであって、前記膜が、低侵襲の送達のために構成されたカテーテルの遠位端に結合される、アセンブリ。
- 請求項29に記載のアセンブリであって、前記送達の構成は、前記膜が前記カテーテルの前記遠位端に対して遠位へ折り畳まれることと、前記導電性電極がそれ自体の上に折り畳まれることとを含む、アセンブリ。
- 請求項29に記載のアセンブリであって、前記フレキシブル回路が、1または複数の導電性トレースを有する少なくとも2つの分岐部へと分裂する主リードを備え、前記主リードが、前記カテーテルの内径を通され、前記膜の近位領域で前記カテーテル内径から出る、アセンブリ。
- 請求項31に記載のアセンブリであって、前記フレキシブル回路の前記主リードが、前記膜の内径を通され、前記膜の遠位領域で前記膜内径から出る、アセンブリ。
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AU2009314159B2 (en) | 2016-04-14 |
JP6622354B2 (ja) | 2019-12-18 |
US20100204560A1 (en) | 2010-08-12 |
JP2017136386A (ja) | 2017-08-10 |
JP6345823B2 (ja) | 2018-06-20 |
CN104068933B (zh) | 2017-03-15 |
JP2018153671A (ja) | 2018-10-04 |
AU2016204855B2 (en) | 2018-05-24 |
US8295902B2 (en) | 2012-10-23 |
CN104068933A (zh) | 2014-10-01 |
ES2615826T3 (es) | 2017-06-08 |
CN102271607B (zh) | 2014-03-19 |
EP2370015B1 (en) | 2016-12-21 |
JP6105663B2 (ja) | 2017-03-29 |
JP2015154946A (ja) | 2015-08-27 |
CA2743140A1 (en) | 2010-05-20 |
EP3173043A1 (en) | 2017-05-31 |
CN102271607A (zh) | 2011-12-07 |
EP2370015A1 (en) | 2011-10-05 |
AU2009314159A1 (en) | 2010-05-20 |
JP2012508083A (ja) | 2012-04-05 |
WO2010056771A1 (en) | 2010-05-20 |
PL2370015T3 (pl) | 2017-07-31 |
AU2016204855A1 (en) | 2016-08-04 |
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