JP2004298354A - Dilation balloon, and balloon catheter equipped with the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a dilation balloon which is excellent in pressure resistance and in which the occurrence of breakage in its peripheral direction is suppressed even when it bursts, a balloon catheter provided with the dilation balloon, and a method for manufacturing the dilation balloon for obtaining the dilation balloon. <P>SOLUTION: In order to manufacturing the dilation balloon 10 from organic polymeric material, the organic polymeric material is biaxially oriented in at least a dilation function part 1, and the orientation state of the polymer chain in the center area 1a of the dilation function part is obtained in order from one end in the direction of the longitudinal axis of the center area to the other end by a wide angle X-ray diffraction method. In this case, the orientation state is controlled so that the difference between the maximum value and the minimum value of the percentage of the polymer chain oriented in the peripheral direction of the dilation function part in the oriented polymer chain may be not larger than 20 points. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【００４０】
拡張用バルーン１０が前述した要件を満たすか否かは、拡張機能部中央域１ａでの長手軸方向の一端から他端にかけて上述の百分率を順次求め、その結果から判断する。このとき、広角Ｘ線回折の測定点は、２ｍｍ以下の間隔で設定することが好ましい。
【００４１】
なお、上述したピークについての半価幅Ｈ°を利用して、拡張機能部１における高分子鎖の配向度Ｆ（％）を、下式（ＩＩ）により求めることができる。拡張機能部１全体における配向度Ｆの最大値と最小値の差は１５％以下であることが好ましく、７％以下であることがより好ましい。また、拡張機能部１全体における好ましい配向度は、前述したとおりである。
【００４２】
【数２】

【００４３】
＜本発明のバルーンカテーテルに係る実施形態＞
図２（Ａ）および図２（Ｂ）は、本発明のバルーンカテーテルに係る一実施形態を概略的に示す。図２（Ａ）は、本実施形態のバルーンカテーテルを真っ直ぐにしたときの状態を概略的に示し、図２（Ｂ）は、図２（Ａ）に示したバルーンカテーテル７０の部分断面を概略的に示す。これらの図に示したバルーンカテーテル７０は、図１（Ａ）および図１（Ｂ）に示した拡張用バルーン１０を用いた血管拡張用バルーンカテーテル（以下、「血管拡張用バルーンカテーテル７０」という。）である。
【００４４】
図示の血管拡張用バルーンカテーテル７０では、拡張用バルーン１０がディスタールシャフト２０の遠位端側に接合され、ディスタールシャフト２０の近位端がプロキシマルシャフト（ハイポチューブ）３０の遠位端に接合され、プロキシマルシャフト３０の近位端がコネクタ４０に接合されている。
【００４５】
拡張用バルーン１０の構造については既に説明したので、ここでは省略する。
ディスタールシャフト２０は、外チューブ２２内に内チューブ２５が配置された２重構造（いわゆる同軸カテーテルチューブ構造）の管状物である。当該ディスタールシャフト２０を構成している外チューブ２２の遠位端に、拡張用バルーン１０の近位端（基端部５）が熱融着、接着等の方法によって気密に接合され、当該外チューブ２２の近位端が、プロキシマルシャフト３０の遠位端に接着等の方法によって気密に接合されている。
【００４６】
外チューブ２２の長さは、血管拡張用バルーンカテーテル７０の用途に応じて適宜選定可能であり、概ね１００〜４００ｍｍの範囲内、好ましくは概ね２００〜３００ｍｍの範囲内で選定される。また、外チューブ２２の外径は、概ね０．５〜５．０ｍｍの範囲内で選定することが好ましく、０．５〜１．０ｍｍの範囲内で選定することが更に好ましい。外チューブ２２の肉厚も適宜選定可能であるが、概ね０．０５〜０．５ｍｍの範囲内で選定することが好ましく、概ね０．１〜０．２ｍｍの範囲内で選定することが更に好ましい。
【００４７】
このような外チューブ２２は、可撓性を有する有機高分子材料で形成されていることが好ましく、その具体例としては、例えばポリエチレン、ポリエチレンテレフタレート、ポリプロピレン、エチレン−プロピレン共重合体、エチレン−酢酸ビニル共重合体、ポリ塩化ビニル、架橋型エチレン−酢酸ビニル共重合体、ポリウレタン、ポリアミド、ポリアミドエラストマー、ポリイミド、ポリイミドエラストマー、シリコーンゴム、天然ゴム等が挙げられる。これらのなかでも、ポリウレタン、ポリエチレン、ポリアミド、ポリイミド等、ショアＡ硬度が５０〜９０程度のものを用いることが特に好ましい。なお、ここでいう「ショアＡ硬度」とは、ＪＩＳ Ｋ−７２１５での規定に基づいて計測される物性値を意味する。
【００４８】
一方、ディスタールシャフト２０を構成している内チューブ２５は、外チューブ２２における近位端側の外周面から当該外チューブ２２内および拡張用バルーン１０内を経て、拡張用バルーン１０の外部にまで達しており、その近位端は熱融着、接着等の方法によって外チューブ２２の外周壁に気密に接合されて、外チューブ２２の外周面に開口している。また、内チューブ２５の遠位端近傍には、拡張用バルーン１０の遠位端（先端部９）が熱融着、接着等の方法によって気密に接合されており、当該内チューブ２５の遠位端が血管拡張用バルーンカテーテル７０の遠位端となっている。内チューブ２５には、血管拡張用バルーンカテーテル７０を血管内に挿入する際に利用されるガイドワイヤ５０が通される。
【００４９】
上記の内チューブ２５は、外チューブ２２と同様の材料によって形成することができるが、外チューブ２２よりも硬質の合成樹脂によって形成することもできる。当該内チューブ２５の外径は、外チューブ２２の内周面との間に隙間が形成されるように、例えば概ね０．３〜３．０ｍｍの範囲内で選定することが好ましく、概ね０．３〜０．８ｍｍの範囲内で選定することが更に好ましい。また、内チューブ２５の内径は、ガイドワイヤ５０を挿入することができる大きさであればよく、例えば概ね０．１〜１．０ｍｍの範囲内で、好ましくは概ね０．２５〜０．６ｍｍの範囲内で選定可能である。
【００５０】
プロキシマルシャフト３０は、継ぎ目のない管状のシャフトであり、例えばオーステナイト系ステンレス鋼やニッケル−チタン合金等の金属材料によって形成される。必要に応じて、外周面上にフッ素樹脂等の固体潤滑剤層（図示せず。）が形成される。
【００５１】
また、図２（Ｂ）に示すように、プロキシマルシャフト３０の遠位端側には、他の部分よりも曲げ剛性の低い低剛性領域３２を形成することが好ましい。図示の例では、プロキシマルシャフト３０の長手方向の一端を、当該一端での端面がプロキシマルシャフト３０の長手軸方向から傾いた面となるように成形することにより、低剛性領域３２が形成されている。プロキシマルシャフト３０の遠位端側に低剛性領域３２を設けることにより、プロキシマルシャフト３０とディスタールシャフト２０との境界部での曲げ剛性の急激な変化が抑制されるので、血管拡張用バルーンカテーテル７０を患者の体内管腔（血管）に挿入する際にディスタールシャフト２０に潰れやキンクが生じることが抑制される。
【００５２】
低剛性領域３２を機械的に保護してその破損を防ぐと共に、ディスタールシャフト２０の内面が低剛性領域３２によって傷つけられるのを防止するために、必要に応じて、低剛性領域３２の周囲を補強チューブ（図示せず。）で被覆することもできる。この補強チューブは、プロキシマルシャフト３０における低剛性領域３２側の開口を閉塞しないようにして被覆する。このとき、低剛性領域３２に対する補強チューブの被覆率は、できるだけ高くすることが好ましい。
【００５３】
このような補強チューブは、例えばポリエーテルエーテルケトン樹脂によって形成され、プロキシマルシャフト３０の外周面の所定領域上を被覆する。補強チューブの内径は、プロキシマルシャフト３０の外周面の所定領域上を被覆することができるように、プロキシマルシャフト３０の外径に応じて適宜選定される。また、補強チューブの肉厚は、概ね１０〜２００μｍの範囲内で選定することが好ましく、概ね３０〜１００μｍの範囲内で選定することが更に好ましい。補強チューブの引張り強度は２７ＭＰａ以上であることが好ましく、９０ＭＰａ以上であることが更に好ましい。また、その曲げ強度は３４ＭＰａ以上であることが好ましく、１３０ＭＰａ以上であることが更に好ましい。
【００５４】
上述した拡張用バルーン１０の内部空間、ディスタールシャフト２０（内チューブ２５を除く。）の内部空間、および、プロキシマルシャフト３０の内部空間は互いに連なって１つの空間を形成しており、この空間を利用して、プロキシマルシャフト３０の近位端側から拡張用バルーン１０への流体の供給、および拡張用バルーン１０からの流体の排出を行うことができる。
【００５５】
なお、拡張用バルーン１０内における内チューブ２５の外周面には、例えば金、白金、タングステン等の金属材料によって形成された造影リング（図示せず。）を装着することができる。この造影リングを装着することによって、血管拡張用バルーンカテーテル７０を患者の体内に挿入する際に、患者の体内での拡張用バルーン１０の位置をＸ線撮影等により正確に把握することが可能になる。
【００５６】
上述した構成を有する血管拡張用バルーンカテーテル７０の使用にあたっては、まずガイドワイヤ５０が患者の血管内に挿入され、その後、このガイドワイヤ５０の一端側が内チューブ２５の遠位端から当該内チューブ２５内に通される。血管内への血管拡張用バルーンカテーテル７０の挿入は、拡張用バルーン１０が血管の狭窄部に達するまで、ガイドワイヤ５０に沿って拡張用バルーン１０側から血管内に押し込むことによって行われる。
【００５７】
拡張用バルーン１０が血管の狭窄部にまで達したら、拡張用バルーン１０内にプロキシマルシャフト３０の近位端側から流体を注入して当該拡張用バルーン１０を膨らませ、これによって狭窄部を内側から強制的に拡張させる。この後、注入した流体を排出して拡張用バルーン１０を萎ませた後に、血管拡張用バルーンカテーテル７０およびガイドワイヤ５０を血管から抜去する。拡張用バルーン１０によって狭窄部が拡張された後の血管では、血流が回復する。
【００５８】
なお、ディスタールシャフト２０の外周は、血管拡張用バルーンカテーテル７０を血管内に挿入する際の摩擦を低減させるという観点から、潤滑性を有する親水性高分子物質で被覆することが好ましい。拡張用バルーン１０の外周を前記親水性高分子物質で被覆することも可能であるが、血管の狭窄部を拡張する際に当該狭窄部に対して拡張用バルーン１０が滑ることは必ずしも好ましくはない。
【００５９】
上記の親水性高分子物質には、天然高分子系のものと、合成高分子系のものとがある。天然高分子系のものとしては、デンプン系、セルロース系、タンニン・リグニン系、多糖類系、タンパク質系等が例示される。合成高分子系のものとしては、ＰＶＡ系、ポリエチレンオキサイド系、アクリル酸系、無水マレイン酸系、フタル酸系、水溶性ポリエステル、ケトンアルデヒド樹脂、（メタ）アクリルアミド系、ポリアミン系、水溶性ナイロン系等が例示される。
【００６０】
これらのなかでも、セルロース系高分子物質（例えばヒドロキシプロピルセルロース）、ポリエチレンオキサイド系高分子物質（例えばポリエチレングリコール）、無水マレイン酸系高分子物質（例えばメチルビニルエーテル無水マレイン酸共重合体のような無水マレイン酸共重合体）、アクリルアミド系高分子物質（例えばポリジメチルアクリルアミド）は、低摩擦係数の被膜が安定して得られるので、上記の親水性高分子物質として特に好ましい。
【００６１】
＜本発明の拡張用バルーンの製造方法に係る実施形態＞
前述した本発明の拡張用バルーンは、例えば、パリソンをブロー成形し、当該ブロー成形時の条件を特定の条件にすることによって製造することができる。以下、図１（Ａ）および図１（Ｂ）で用いた参照符号を適宜引用しつつ、パリソンを用意する第１工程と、当該パリソンをブロー成形する第２工程とに分けて工程毎に詳述する。
【００６２】
（第１工程）
用意するパリソンは、拡張用バルーン１０の材料として既に説明した有機高分子材料をチューブ状に成形したものである。その成形方法は特に限定されるものではないが、押出し成形法であることが好ましい。パリソンの内径と外径は、ブロー成形によって所定の大きさのブローを得るときに、所望のバルーン膜厚と所望の径方向延伸倍率が得られるように調整される。一般には、その内径は概ね０．１〜１．０ｍｍの範囲内であり、その外径は概ね０．２〜２．０ｍｍの範囲内である。
【００６３】
有機高分子材料の配向度が比較的高い拡張用バルーン１０を得るうえからは、パリソンの水分含有率を０．６質量％以下とすることが好ましく、０．５質量％以下とすることが更に好ましい。この水分含有率の下限は、生産性や生産コスト等を勘案して、例えば０．１質量％程度等、適宜選定可能である。拡張用バルーン１０での有機高分子材料の配向度を比較的高くすることにより、当該拡張用バルーン１０の耐圧性を高め易くなる。有機高分子材料としてポリアミド系エラストマー等を用いる場合、当該有機高分子材料は比較的多くの水分を含有しているので、その水分含有率が上記の範囲内となるように予め真空乾燥等の処理を施すことが好ましい。また、乾燥処理後に吸湿しないように、保存は例えばデシケータ中で行うことが好ましい。
【００６４】
（第２工程）
第２工程では上記のパリソンをブロー成形して拡張用バルーン１０を得る。このとき使用するブロー成形機は、下記（ａ）〜（ｄ）の各条件を満足するものであることが好ましい。
【００６５】
（ａ）加圧源（ボンベ、コンプレッサー）と、当該加圧源に連通するチャンバーと、パリソンが配置される金型とを備えている。
【００６６】
（ｂ）上記チャンバーの内部は、ブロー成形機（金型）にセットされたパリソンの内部空間と連通する。
【００６７】
（ｃ）ブロー成形の前に、チャンバーの内部（パリソンの内部空間を含む。）が上記の加圧源によって所定の圧力にまで加圧され、ブロー成形の直前に、チャンバーと加圧源とが遮断される。
【００６８】
（ｄ）パリソンが径方向へ延伸されるとチャンバーの内圧が低下するので、これをモニターしてパリソンが径方向に延伸された時点を正確に把握することができる。
【００６９】
上記のブロー成形機を用いての拡張用バルーンの作製は、例えば下記（ｉ）〜（ｉＶ）のサブ工程を順次行うことによって実施することができる。
【００７０】
（ｉ）所定長にカットしたパリソンをブロー成形機にセットする。パリソンの長さは、ブロー成形機の構成に応じ、概ね１０〜４０ｃｍの範囲内で適宜選定可能である。
【００７１】
（ｉｉ）加圧源によってチャンバー内を加圧し、パリソンに内圧をかけながら金型温度を上昇させて、当該パリソンを金型内で加熱する。
【００７２】
（ｉｉｉ） 金型温度が目標温度に達したら、パリソンを長手軸方向に延伸する。この延伸は、金型温度（パリソンの温度）とチャンバー内圧力とを所定の値に調整しつつ、パリソンの長手軸方向の両端を固定しているチャックをそのまま前記長手軸方向に沿って外側に移動させることにより、行うことができる。このときの延伸速度は、概ね５０〜１６０ｍｍ／秒の範囲内で適宜選定され、その移動距離は片側当たり概ね５〜６０ｍｍ（全体で１０〜１２０ｍｍ）の範囲内で適宜選定可能である。
【００７３】
チャンバーの内圧と等しい内圧がかかったパリソンが加熱下で長手軸方向に延伸されると、当該パリソンが次第に薄くなり、内圧に耐えられなくなった時点で径方向への膨張（延伸）が始まる。パリソンの径方向の延伸は、長手軸方向の延伸に対して非常に短い時間で完了する（径方向への延伸が長手軸方向の延伸の開始後に始まり、長手軸方向の延伸の終了前に終わる。）。金型温度およびチャンバー内圧力については、後述する。
【００７４】
（ｉｖ）延伸処理後、金型を概ね８５〜１４５℃にまで昇温させ、この温度で概ね１０〜６０秒保持した後に概ね１〜５℃／秒の降温速度で概ね１５〜４０℃にまで急冷する。パリソンの材料が前述したＰＥＢＡＸ７２３３ＳＡ０１である場合、上記の昇温は例えば金型温度が１３５℃となるまで行い、上記急冷の到達温度は３３℃とすることができる。
【００７５】
上記（ｉ）〜（ｉｖ）のサブ工程を順次行うことによって得た拡張用バルーンには、その後にアニール処理を施すことが好ましい。このアニール処理は、大気雰囲気中、概ね３０〜８０℃、概ね０．５〜４８時間の熱処理によって行うことができる。
【００７６】
上述のようにしてパリソンをブロー成形して拡張用バルーンを得る本発明の製造方法は、上記（ｉｉｉ） のサブ工程での金型温度およびチャンバー内圧力それぞれの選定に最大の特徴を有している。
【００７７】
すなわち、上記（ｉｉｉ） のサブ工程では、金型温度（パリソンの温度）とチャンバー内圧力とを調整して、長手軸方向へのパリソンの延伸長が目標延伸長（延伸後の長さと延伸前の長さとの差）の３０〜５０％に達した時点で径方向への膨張（延伸）が開始されるように制御する。
【００７８】
この制御は、金型温度を特定の温度、すなわちパリソンの材料として用いた有機高分子材料の０．４６ＭＰａ加重時における熱変形温度（ＡＳＴＭ Ｄ ６４８による。）と等しくした場合には、パリソンの材料、内径、外径、肉厚等に応じてチャンバーの内圧を２．２〜２．４ＭＰａの範囲内で適宜選定することによって行うことができる。また、金型温度を上記熱変形温度に対して−１０〜＋１０℃の範囲内とし、かつ、チャンバー内の圧力を１．５〜３．５ＭＰａの範囲内とした場合には、パリソンの材料、内径、外径、肉厚等に応じて金型温度を適宜上げ、チャンバー内圧力を適宜下げるか、金型温度を適宜下げ、チャンバー内圧力を適宜上げることで、上記の制御を行うことができる。
【００７９】
パリソンをブロー成形するにあたって上述の制御を行うことにより、前述した本発明の拡張用バルーンを得ることができる。パリソンをブロー成形するにあたって、当該パリソンの長手軸方向への延伸長が目標延伸長の３０％未満であるときに径方向への膨張（延伸）が開始されると、最終的に得られる拡張用バルーンの拡張機能部での高分子鎖の配向状態に大きなムラが生じる。また、パリソンの長手軸方向への延伸長が目標延伸長の５０％を超えてから径方向の膨張（延伸）を開始させようとすると、パリソンの膨張がうまく行われずに成形不良が生じ易くなる。
【００８０】
なお、パリソンのブロー成形によって拡張用バルーンを製造するにあたっては、パリソンの長手軸方向への延伸倍率に対し、パリソンの径方向への延伸倍率を１６０％以下にすることが好ましく、１４０％以下にすることがより好ましく、１２０％以下にすることが更に好ましい。長手軸方向への延伸倍率と径方向への延伸倍率とをこのように選定することにより、拡張機能部中央域において拡張機能部の周方向に配向した高分子鎖の配向状態にムラが少なく、かつ、前記周方向に配向した高分子鎖の割合が比較的低い拡張用バルーンを容易に得ることができる。このような拡張用バルーンでは、前述のように、たとえ破裂した場合でも、拡張機能部の周方向に破断が生じることが抑制される。パリソンの材料がポリアミド系エラストマーである場合には、径方向への延伸倍率を概ね３．５〜５．０倍とし、長手軸方向への延伸倍率を概ね３．０〜４．０倍とすることが好ましい。
【００８１】
なお、本発明でいう「パリソンの径方向の延伸倍率」は、パリソンと当該パリソンから得られた拡張用バルーンでの拡張機能それぞれの断面について、当該断面の面積（ただし、中空領域の断面積を除く。）を互いに面積が等しい内側領域と外側領域とに等分することができる円周の径を求め、これらの径に基づいて求めた値である。また、「パリソンの長手軸方向の延伸倍率」は、得られた拡張用バルーンでの拡張機能部の全長と当該拡張機能部を構成したパリソンの全長とに基づいて求めた値である。
【００８２】
【実施例】
＜実施例１＞
まず、ポリアミド系エラストマー（商品名ＰＥＢＡＸ７２３３ＳＡ０１（アトフィナケミカルズ社製））を押出し成形して、内径０．５１ｍｍ、外径０．９０ｍｍのチューブを得た。上記のポリアミド系エラストマーは、０．４６ＭＰａ加重時における熱変形温度（ＡＳＴＭ Ｄ ６４８による。）が１０６℃の有機高分子材料である。
【００８３】
次に、上記のチューブを長さ３０ｃｍに切断し、８０℃、１時間の条件の下に真空乾燥を行い、その後、デシケータ中に１時間放置して、水分含有率が０．５質量％のパリソンを得た。
【００８４】
このパリソンをブロー成形機にセットし、金型温度１００℃、チャンバー内圧力２．６ＭＰａ、長手軸方向の延伸速度１６０ｍｍ／秒、長手軸方向への延伸長７０ｍｍの条件の下にブロー成形を行った。このとき、長手軸方向への延伸長が目標延伸長（７０ｍｍ）の４０％（２８ｍｍ）に達した時点で、チャンバー内圧力の低下（パリソンの径方向への膨張の開始）が確認された。
【００８５】
次いで、金型温度を１２０℃にまで昇温させ、この温度で１０秒保持した後に３℃／秒の降温速度で３３℃にまで急冷した。これをブロー成形機からオーブンに移し、５５℃、１時間の条件の下にアニール処理を施してから所定長に切断して、目的とする拡張用バルーンを得た。
【００８６】
この拡張用バルーンは、図１（Ａ）および図１（Ｂ）に示した拡張用バルーン１０と同様の形状を有しており、その拡張機能部の長さは１５ｍｍ、第１テーパ部の長さ（テーパ形状に沿った長さを意味する。以下同様。）は３．０ｍｍ、基端部の長さは１．５ｍｍ、第２テーパ部の長さは３．０ｍｍ、先端部の長さは２．０ｍｍ、拡張機能部の膜厚は２２μｍ、拡張機能部を円筒状に変形させたときの外径は３．０ｍｍであり、パリソンの長手軸方向への延伸倍率は３．５倍、径方向への延伸倍率は４．０倍である。
【００８７】
＜実施例２＞
パリソンの内径を０．３９ｍｍ、外径を０．８６ｍｍにすると共に、金型を内部空間形状が異なる他の金型に交換し、更に、パリソンの長手軸方向への延伸長を６０ｍｍにし、他は実施例１と同様にして拡張用バルーンを得た。
【００８８】
この拡張用バルーンでの拡張機能部の長さは１５ｍｍ、第１テーパ部の長さは４．０ｍｍ、基端部の長さは１．５ｍｍ、第２テーパ部の長さは５．０ｍｍ、先端部の長さは２．０ｍｍ、拡張機能部の膜厚は２２μｍ、拡張機能部を円筒状に変形させたときの外径は４．０ｍｍであり、パリソンの長手軸方向への延伸倍率は３．０倍、径方向への延伸倍率は４．７倍である。
【００８９】
なお、本実施例においても、ブロー成形時には、長手軸方向への延伸長が目標延伸長（６０ｍｍ）の４０％（２４ｍｍ）に達した時点でチャンバー内圧力の低下（パリソンの径方向への膨張の開始）が確認された。
【００９０】
＜比較例１＞
ブロー成形時のチャンバー内圧力を３．０ＭＰａとした以外は実施例１と同様にして、実施例１で得た拡張用バルーンと同じ形状および大きさを有する拡張用バルーンを得た。本比較例では、ブロー成形時に、長手軸方向への延伸長が目標延伸長（７０ｍｍ）の２０％（１４ｍｍ）に達した時点でチャンバー内圧力の低下（パリソンの径方向への膨張の開始）が確認された。
【００９１】
＜評価＞
実施例１、実施例２、および比較例１で得られた各拡張用バルーンについて、第２テーパ部の先端部側の端から第１テーパ部の基端部側の端にかけて、当該拡張バルーンの形状に沿って１ｍｍ間隔で高分子鎖の配向度、および、二軸配向している高分子鎖のうちで周方向に配向しているものの百分率（以下、「周方向の配向率」という。）を広角Ｘ線回折法を利用して求めた。また、拡張機能部中央域での長手方向両端においても、同様にして、上記の配向度および周方向の配向率を求めた。これらの結果を図３〜図５に示し、拡張機能部における配向度および拡張機能部中央域における周方向の配向率それぞれについての最大値および最小値を表１に示す。
【００９２】
さらに、実施例１、実施例２、または比較例１と同一条件の下にそれぞれ１００個の拡張用バルーンを作製し、これらの拡張用バルーンについて、図２（Ａ）および図２（Ｂ）に示した血管拡張用カテーテルに適用した状態での耐圧性および安全性を評価した。結果を表２に示す。
【００９３】
なお、耐圧性の評価は、拡張用バルーンに生理食塩水を供給して当該拡張用バルーンを破裂させたときの内圧（平均値）の大小に基づいて相対的に行い、安全性の評価は、拡張機能部の周方向への破断の発生率の大小に基づいて相対的に行った。
【００９４】
【表１】

【００９５】
【表２】

【００９６】
表１、図３〜図５、および表２から明らかなように、拡張機能部中央域での周方向の配向率の最大値と最小値との差が２０ポイント以下である実施例１または実施例２の拡張用バルーンは、耐圧性および安全性ともに相対的に高い。これに対し、上記の差が２０ポイントを超える比較例１の拡張用バルーンは、高分子鎖の配向度は実施例１または実施例２の拡張用バルーンと同程度ではあるものの、耐圧性および安全性が相対的に低い。
【００９７】
【発明の効果】
以上、説明したように、本発明によれば、耐圧性に優れ、破裂したとしても周方向に破断しにくい拡張用バルーンが提供される。したがって、本発明によれば拡張用バルーンを備えた種々のバルーンカテーテルの安全性を高めることができる。
【図面の簡単な説明】
【図１】図１（Ａ）は、本発明の拡張用バルーンに係る一実施形態を概略的に示す側面図であり、図１（Ｂ）は、図１（Ａ）に示した拡張用バルーンの断面構造を示す概略図である。
【図２】図２（Ａ）は、本発明のバルーンカテーテルに係る一実施形態を概略的に示し、図２（Ｂ）は、図２（Ａ）に示したバルーンカテーテルの部分断面を概略的に示す。
【図３】実施例１で得た拡張用バルーンでの高分子鎖の配向状態を示すグラフである。
【図４】実施例２で得た拡張用バルーンでの高分子鎖の配向状態を示すグラフである。
【図５】比較例１で得た拡張用バルーンでの高分子鎖の配向状態を示すグラフである。
【符号の説明】
１ 拡張機能部
１ａ 拡張機能部中央域
３ 第１テーパ部
５ 基端部
７ 第２テーパ部
９ 先端部
１０ 拡張用バルーン
７０ 血管拡張用バルーンカテーテル[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an inflation balloon, a balloon catheter including the inflation balloon, and a method for manufacturing the inflation balloon.
[0002]
[Prior art]
In recent years, for stenosis or occlusion that has occurred in a body lumen such as a blood vessel, for example, as described in Patent Document 1, percutaneous transluminal coronary angioplasty (PTCA), percutaneous transluminal angioplasty 2. Description of the Related Art A therapeutic method such as surgery (PTA) has been widely applied in which a catheter (balloon catheter) having an expansion balloon is forcibly expanded from the inside of a body lumen to recover blood flow and the like. In this treatment method, the balloon catheter is inserted into a body lumen, and the stenosis or occlusion is forcibly expanded by inflating the dilatation balloon in the stenosis or occlusion. Thereafter, the balloon catheter is withdrawn after deflating the dilatation balloon.
[0003]
By the way, when the above-mentioned treatment method is applied to, for example, a stenotic part of a blood vessel in which calcification has progressed, it is necessary to apply a high internal pressure to the dilatation balloon when expanding the dilatation balloon. At this time, the rupture of the dilatation balloon has a serious adverse effect on the patient. Therefore, high pressure resistance is required for the dilatation balloon.
[0004]
As a method of obtaining a balloon having excellent pressure resistance, for example, as described in Patent Document 1, a method of adjusting the crystallinity of an organic polymer material used as a material of an expansion balloon to 10 to 40% is known. Have been.
[0005]
[Patent Document 1]
JP-A-2000-271209
[0006]
[Problems to be solved by the invention]
However, even an expansion balloon manufactured by adjusting the degree of crystallinity of the polymer material to 10 to 40% may be ruptured when a high internal pressure is applied. May cause breakage.
[0007]
When a break occurs in the circumferential direction of the dilatation balloon, the distal end fragment of the dilatation balloon is in a state of being joined only to the distal end end of the balloon catheter. As a result, there is a risk that when the balloon catheter is withdrawn from the patient, the fragments fall off the balloon catheter and remain in the blood vessels. If fragments of the balloon remain in the blood vessel, they will interfere with blood flow. In addition, a surgical operation is required to remove the fragment, which results in a great burden on the patient.
[0008]
Therefore, the present invention can provide an expansion balloon which is excellent in pressure resistance and suppresses the occurrence of circumferential rupture even when ruptured, a balloon catheter including the expansion balloon, and the above-described expansion balloon. An object of the present invention is to provide a method for manufacturing an inflation balloon.
[0009]
[Means for Solving the Problems]
The present inventors diligently studied the relationship between the material of the inflation balloon and the direction of the rupture that occurs when the inflation balloon ruptures, and found that the polymer chains in the inflation balloon made of an organic polymer material By controlling the orientation state of the inflatable balloon to a specific state, it was found that even when the inflation balloon ruptured, it was possible to suppress the occurrence of rupture in the circumferential direction, and completed the present invention.
[0010]
Thus, according to the first aspect of the present invention, an extended function portion capable of expanding its diameter and deforming into a cylindrical shape is connected to one end of the extended function portion directly or via the first tapered portion. A straight body-shaped base end, and a straight body-shaped tip end connected directly or via a second tapered portion to the other end of the extension function part; the extension function part, the base end part, and An expansion balloon having the tip portion integrally formed from one organic polymer material, wherein the organic polymer material in at least the expansion function portion includes a biaxially oriented polymer chain; When the orientation state of the polymer chains in the central region was sequentially determined by a wide-angle X-ray diffraction method from one end to the other end in the longitudinal axis direction of the central region of the extended function portion, the biaxially oriented polymer chains were Orientation in the circumferential direction when the extended function part is deformed into a cylindrical shape Expanded balloon difference between the maximum value and the minimum value of the percentage of polymer chains is less than 20 points there are provided.
[0011]
Preferably, the maximum value of the percentage is 80% or less.
[0012]
The organic polymer material is preferably a polyamide elastomer.
[0013]
The balloon for expansion of the present invention is preferably formed by blow molding a parison having a water content of 0.6% by mass or less.
[0014]
According to a second aspect of the present invention, there is provided a balloon catheter including the above-described dilatation balloon of the present invention.
[0015]
According to a third aspect of the present invention, there is provided a first step of preparing a parison formed of an organic polymer material capable of orienting a polymer chain; An extended function part that can be expanded in the radial direction to expand the diameter to be deformed into a cylindrical shape, and a straight body base end connected directly to one end of the extended function part or via a first taper part And a second step of obtaining a balloon having a straight body-shaped tip end directly or via a second tapered portion to the other end of the expansion function section, a method for manufacturing an expansion balloon, In the second step, there is provided a method for producing an inflation balloon, in which the radial expansion is started when the stretch length of the parison in the longitudinal axis direction reaches 30 to 50% of a target stretch length. Is done.
[0016]
The stretching ratio in the radial direction in the second step is preferably not more than 160% of the stretching ratio in the longitudinal axis direction.
[0017]
The parison prepared in the first step preferably has a water content of 0.6% by mass or less.
[0018]
Further, the parison prepared in the first step is preferably formed of a polyamide elastomer.
[0019]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
[0020]
<Embodiment of balloon for expansion of the present invention>
FIG. 1A is a side view schematically showing an embodiment of the expansion balloon of the present invention, and FIG. 1B is a cross-sectional structure of the expansion balloon 10 shown in FIG. FIG.
[0021]
The dilatation balloon 10 shown in these figures is, for example, near the distal end of a balloon catheter such as a PTCA (percutaneous transluminal coronary angioplasty) balloon catheter and a PTA (percutaneous transluminal angioplasty) balloon catheter. And is used to forcibly expand a stenosis or an obstruction generated in a body lumen such as a blood vessel from the inside of the body lumen.
[0022]
In order to forcibly expand a stenosis part or a closed part from the inside, the expansion balloon 10 has an expansion function part 1 that can be expanded in diameter and deformed into a cylindrical shape. A straight base portion 5 is connected to one end of the extended function portion 1 via a first tapered portion 3, and a second tapered portion 7 is connected to the other end thereof. A straight body-shaped tip portion 9 is continuous. The diameter of each of the first tapered portion 3 and the second tapered portion 7 gradually decreases as the distance from the extended function portion 1 increases. The first taper 3 and the second taper 7 can be omitted. However, in order to obtain a practical balloon for expansion, it is necessary to provide the first taper 3 and the second taper 7. preferable.
[0023]
For example, when the expansion balloon 10 is used as an expansion balloon of a PTCA balloon catheter, the length of the expansion function section 1 in the longitudinal direction is generally in a range of 5 to 30 mm, and the film thickness thereof is generally in a range of 2 to 50 μm. It is preferable to select appropriately within the range. Further, when the internal pressure of the expansion balloon 10 is increased to deform the expansion function portion 1 into a cylindrical shape, the outer diameter of the expansion function portion 1 is preferably selected within a range of approximately 1 to 6 mm. 1 (A) and 1 (B) each schematically show a shape when the internal pressure of the inflation balloon 10 is increased to deform the expansion function unit 1 into a cylindrical shape.
[0024]
When the inflation balloon 10 is used, for example, the proximal end portion 5 is joined to the distal end of the outer tube of a distal shaft having a so-called coaxial catheter tube structure, and the vicinity of the distal end of the inner tube of the distal shaft. The distal end 9 is joined to the end. At this time, the distal end portion 9 side of the dilatation balloon 10 is closed by joining with the inner tube. In this state, when a predetermined amount of fluid (gas or liquid) is supplied into the expansion balloon 10 through a gap between the outer tube and the inner tube of the distal shaft, the internal pressure of the expansion balloon 10 increases. The extended function unit 1 is deformed into a cylindrical shape as shown in FIGS. 1 (A) and 1 (B).
[0025]
Such an expansion balloon 10 is made of various organic polymer materials capable of orienting a polymer chain, for example, polyolefin, polyamide, polyurethane, polyester, polyolefin elastomer, polyamide elastomer, polyurethane elastomer, polyester elastomer. It can be manufactured using an elastomer or the like. Among the above materials, those which can be blow-molded are preferable, and from the viewpoint of obtaining an expansion balloon 10 having excellent pressure resistance and flexibility by the blow-molding, it is particularly preferable to use a polyamide elastomer.
[0026]
As the polyamide-based elastomer, a block copolymer having polyamide as a hard segment and polyether as a soft segment is preferable. Examples of the polyamide constituting the hard segment include polyamide 6 (nylon 6), polyamide 6.6 (nylon 66), polyamide 610 (nylon 6/10), polyamide 6-1 (nylon 6/12), and polyamide. 11 (nylon 11), polyamide 12 (nylon 12) and the like can be used, but polyamide 12 is particularly preferred. On the other hand, as the polyether constituting the soft segment, polyethylene glycol, polypropylene glycol, polytetramethylene glycol and the like can be used, and polytetramethylene glycol is particularly preferable.
[0027]
When a polyamide-based elastomer is used as the material of the balloon for expansion 10, its hardness can be appropriately selected according to the use of the balloon for expansion 10, and the Shore D hardness based on JIS K 7215 is 55 to 85, particularly Those having 60 to 75 are preferred. Such a polyamide-based elastomer is available, for example, under the trade name PEBAX7233SA01 (manufactured by Atofina Chemicals).
[0028]
In the dilatation balloon 10 that can be manufactured using the above-described organic polymer material, at least in the dilation function part 1, when the polymer chain of the organic polymer material deforms the dilation function part 1 into a cylindrical shape. Are biaxially oriented in a circumferential direction (hereinafter, simply referred to as a “peripheral direction of the extended function part”) and a longitudinal axis direction. The degree of orientation of the polymer chains in the extended function unit 1 varies depending on the material used, the molding method, the molding conditions, and the like, but is preferably in the range of about 50 to 65%, and is preferably in the range of about 53 to 60%. More preferably, it is within the range. The method for measuring the degree of orientation will be described later.
[0029]
In addition, in the balloon for expansion 10, when the orientation state of the polymer chains in the central region 1 a of the expansion function part is sequentially obtained from one end to the other end of the central region 1 a by the wide-angle X-ray diffraction method, The percentage of the polymer chains oriented in the circumferential direction of the extended functional unit 1 in the chains satisfies the following requirements.
[0030]
That is, the difference between the maximum value and the minimum value of the percentage is 20 points or less, more preferably 15 points or less, and further preferably 10 points or less.
[0031]
Here, the “central area of the extended function part” in the present invention is an area defined by two planes whose normal lines are the longitudinal axes of the extended function part when the extended function part is deformed into a cylindrical shape. In this case, the geometric center overlaps the geometric center of the extension unit, and the distance between the two planes corresponds to 80% of the length of the extension unit in the longitudinal axis direction.
[0032]
The rupture (particularly, circumferential rupture) of the dilatation balloon 10 occurs when stress is concentrated on a portion having low strength when a high internal pressure is applied to the dilation function portion 1. Particularly, due to the structure of the dilatation balloon 10, if stress is concentrated at a position relatively distant from the first taper portion 3 or the second taper portion 7 in the dilatation function portion 1, circumferential breakage is likely to occur.
[0033]
In the balloon for expansion 10 satisfying the above requirements, since the orientation state of the polymer chains in the central region 1a of the expansion function portion has little unevenness, stress concentration hardly occurs even when a high internal pressure is applied to the expansion function portion 1. As a result, the pressure resistance of the inflation balloon 10 is increased, and rupture is less likely to occur. Moreover, even if it ruptures, the occurrence of breakage of the extension function unit 1 in the circumferential direction is suppressed. Therefore, it is possible to obtain a highly safe dilatation balloon and a catheter including the dilatation balloon.
[0034]
From the viewpoint of increasing the pressure resistance of the dilatation balloon 10 and suppressing breakage in the circumferential direction even if the dilatation balloon 10 ruptures, the maximum value of the percentage in the dilatation function part central region 1a is preferably 80% or less, and 50% or less. %, More preferably 40% or less.
[0035]
By producing the expansion balloon 10 by blow molding, the polymer chains can be biaxially oriented, and the orientation state of the polymer chains in the central region 1a of the expansion function portion can be determined by selecting the conditions during blow molding. It is possible to control. Details of the conditions at the time of blow molding will be described later.
[0036]
The percentage of the polymer chains oriented in the circumferential direction can be determined by using a wide-angle X-ray diffraction method, for example, as follows.
[0037]
First, the balloon for expansion 10 is fixed to a fiber sample table, an X-ray spectrum is obtained by a wide-angle X-ray diffractometer, and a peak based on the orientation of the polymer chain is selected based on the X-ray spectrum. For example, when a polyamide-based elastomer whose hard segment is made of polyamide 12 is used as the material of the balloon 10 for expansion, the above peak appears at a scattering angle 2θ of around 6 °.
[0038]
Next, with respect to the scattering angle showing the above peak, X-ray diffraction intensity measurement at 0 ° to 360 ° in the azimuthal direction is performed to obtain an intensity distribution. Then, the background intensity is subtracted from the data of the intensity distribution, and the integrated intensity (S1) of the peak due to the polymer chain oriented in the circumferential direction of the extended function unit 1 and the integrated intensity of the peak in the longitudinal axis direction of the extended function unit 1 are obtained. And the integrated intensity (S2) of the peak due to the high molecular chain. By calculating these integrated intensities S1 and S2, the percentage of the polymer chains that are oriented in the circumferential direction of the extended function part 1 among the polymer chains that are biaxially oriented at a certain measurement point is expressed by the following equation. It can be calculated by (I).
[0039]
(Equation 1)

[0040]
Whether or not the expansion balloon 10 satisfies the above-described requirements is determined in order from the one end to the other end in the longitudinal axis direction in the central region 1a of the expansion function part, and is determined from the result. At this time, it is preferable that the measurement points of the wide-angle X-ray diffraction are set at intervals of 2 mm or less.
[0041]
In addition, the orientation degree F (%) of the polymer chain in the extended function part 1 can be obtained by the following equation (II) using the half width H ° of the peak described above. The difference between the maximum value and the minimum value of the degree of orientation F in the entire extended function unit 1 is preferably 15% or less, and more preferably 7% or less. The preferred orientation degree in the entire extended function unit 1 is as described above.
[0042]
(Equation 2)

[0043]
<Embodiment of balloon catheter of the present invention>
2 (A) and 2 (B) schematically show one embodiment of the balloon catheter of the present invention. FIG. 2A schematically shows a state in which the balloon catheter of the present embodiment is straightened, and FIG. 2B schematically shows a partial cross section of the balloon catheter 70 shown in FIG. Shown in The balloon catheter 70 shown in these figures is a vascular dilatation balloon catheter using the dilatation balloon 10 shown in FIGS. 1A and 1B (hereinafter, referred to as a “vascular dilation balloon catheter 70”). ).
[0044]
In the illustrated vascular dilatation balloon catheter 70, the dilation balloon 10 is joined to the distal end side of the distal shaft 20, and the proximal end of the distal shaft 20 is connected to the distal end of the proximal shaft (hypotube) 30. The proximal end of the proximal shaft 30 is joined to the connector 40.
[0045]
Since the structure of the dilatation balloon 10 has already been described, it is omitted here.
The distal shaft 20 is a tubular member having a double structure (a so-called coaxial catheter tube structure) in which the inner tube 25 is disposed inside the outer tube 22. The proximal end (proximal end 5) of the inflation balloon 10 is hermetically joined to the distal end of the outer tube 22 constituting the distal shaft 20 by a method such as heat fusion or adhesion. The proximal end of the tube 22 is hermetically bonded to the distal end of the proximal shaft 30 by a method such as bonding.
[0046]
The length of the outer tube 22 can be appropriately selected depending on the use of the vascular dilatation balloon catheter 70, and is selected within a range of approximately 100 to 400 mm, preferably within a range of approximately 200 to 300 mm. Further, the outer diameter of the outer tube 22 is preferably selected within a range of about 0.5 to 5.0 mm, and more preferably within a range of 0.5 to 1.0 mm. The thickness of the outer tube 22 can also be appropriately selected, but is preferably selected within a range of about 0.05 to 0.5 mm, more preferably within a range of about 0.1 to 0.2 mm. .
[0047]
The outer tube 22 is preferably formed of a flexible organic polymer material, and specific examples thereof include polyethylene, polyethylene terephthalate, polypropylene, ethylene-propylene copolymer, and ethylene-acetic acid. Examples include vinyl copolymer, polyvinyl chloride, cross-linked ethylene-vinyl acetate copolymer, polyurethane, polyamide, polyamide elastomer, polyimide, polyimide elastomer, silicone rubber, and natural rubber. Among these, it is particularly preferable to use polyurethane, polyethylene, polyamide, polyimide and the like having a Shore A hardness of about 50 to 90. Here, the “Shore A hardness” means a physical property value measured based on the provisions of JIS K-7215.
[0048]
On the other hand, the inner tube 25 constituting the distal shaft 20 extends from the outer peripheral surface on the proximal end side of the outer tube 22 to the outside of the inflation balloon 10 via the inside of the outer tube 22 and the inflation balloon 10. The proximal end of the outer tube 22 is hermetically joined to the outer peripheral wall of the outer tube 22 by a method such as heat fusion or adhesion, and is opened to the outer peripheral surface of the outer tube 22. Further, near the distal end of the inner tube 25, the distal end (tip portion 9) of the dilatation balloon 10 is hermetically joined by a method such as heat fusion or adhesion. The end is the distal end of the vascular dilatation balloon catheter 70. A guide wire 50 used for inserting the vascular dilatation balloon catheter 70 into a blood vessel is passed through the inner tube 25.
[0049]
The inner tube 25 can be formed of the same material as the outer tube 22, but can also be formed of a synthetic resin harder than the outer tube 22. The outer diameter of the inner tube 25 is preferably selected within a range of, for example, approximately 0.3 to 3.0 mm so that a gap is formed between the inner tube 25 and the inner peripheral surface of the outer tube 22. More preferably, it is selected within the range of 3 to 0.8 mm. The inner diameter of the inner tube 25 may be any size as long as the guide wire 50 can be inserted into the inner tube 25. For example, the inner diameter is within a range of about 0.1 to 1.0 mm, preferably about 0.25 to 0.6 mm. It can be selected within the range.
[0050]
The proximal shaft 30 is a seamless tubular shaft, and is formed of a metal material such as austenitic stainless steel or a nickel-titanium alloy. If necessary, a solid lubricant layer (not shown) such as a fluororesin is formed on the outer peripheral surface.
[0051]
Further, as shown in FIG. 2 (B), it is preferable to form a low rigidity region 32 having lower bending rigidity than other parts on the distal end side of the proximal shaft 30. In the illustrated example, the low-rigidity region 32 is formed by molding one end of the proximal shaft 30 in the longitudinal direction such that the end surface at the one end is a surface inclined from the longitudinal axis direction of the proximal shaft 30. ing. By providing the low rigidity region 32 on the distal end side of the proximal shaft 30, a sudden change in bending rigidity at the boundary between the proximal shaft 30 and the distal shaft 20 is suppressed. When the catheter 70 is inserted into a body lumen (blood vessel) of a patient, crushing and kink of the distal shaft 20 are suppressed.
[0052]
In order to protect the low-rigidity region 32 mechanically to prevent its breakage, and to prevent the inner surface of the distal shaft 20 from being damaged by the low-rigidity region 32, the periphery of the low-rigidity region 32 may be changed as necessary. It can also be covered with a reinforcing tube (not shown). The reinforcing tube covers the opening of the proximal shaft 30 on the low rigidity region 32 side so as not to be closed. At this time, it is preferable that the coverage ratio of the reinforcing tube to the low-rigidity region 32 be as high as possible.
[0053]
Such a reinforcing tube is formed of, for example, a polyetheretherketone resin, and covers a predetermined region on the outer peripheral surface of the proximal shaft 30. The inner diameter of the reinforcing tube is appropriately selected according to the outer diameter of the proximal shaft 30 so that a predetermined region of the outer peripheral surface of the proximal shaft 30 can be covered. The thickness of the reinforcing tube is preferably selected within a range of about 10 to 200 μm, and more preferably within a range of about 30 to 100 μm. The tensile strength of the reinforcing tube is preferably at least 27 MPa, more preferably at least 90 MPa. The bending strength is preferably at least 34 MPa, more preferably at least 130 MPa.
[0054]
The internal space of the above-described balloon for expansion 10, the internal space of the distal shaft 20 (excluding the inner tube 25), and the internal space of the proximal shaft 30 are connected to each other to form one space. The fluid can be supplied to the inflation balloon 10 from the proximal end side of the proximal shaft 30 and the fluid can be discharged from the inflation balloon 10 by using the.
[0055]
Note that a contrast ring (not shown) made of a metal material such as gold, platinum, or tungsten can be attached to the outer peripheral surface of the inner tube 25 in the expansion balloon 10. By attaching the contrast ring, when the vascular dilatation balloon catheter 70 is inserted into the patient's body, the position of the dilatation balloon 10 in the patient's body can be accurately grasped by X-ray photography or the like. Become.
[0056]
In using the vascular dilatation balloon catheter 70 having the above-described configuration, first, the guide wire 50 is inserted into a patient's blood vessel, and then one end of the guide wire 50 is inserted from the distal end of the inner tube 25 to the inner tube 25. Passed through. The insertion of the vascular dilatation balloon catheter 70 into the blood vessel is performed by pushing the dilatation balloon 10 from the dilatation balloon 10 side along the guide wire 50 into the blood vessel until the dilatation balloon 10 reaches the stenosis of the blood vessel.
[0057]
When the dilatation balloon 10 reaches the stenosis part of the blood vessel, fluid is injected into the dilation balloon 10 from the proximal end side of the proximal shaft 30 to inflate the dilatation balloon 10, whereby the stenosis part is inflated from inside. Force expansion. Thereafter, the infused fluid is discharged to deflate the dilatation balloon 10, and then the vascular dilatation balloon catheter 70 and the guide wire 50 are removed from the blood vessel. In a blood vessel after the stenosis is expanded by the expansion balloon 10, blood flow is restored.
[0058]
The outer periphery of the distal shaft 20 is preferably coated with a hydrophilic polymer having lubricity from the viewpoint of reducing friction when the vascular dilatation balloon catheter 70 is inserted into a blood vessel. It is possible to coat the outer periphery of the dilatation balloon 10 with the hydrophilic polymer substance, but it is not always preferable that the dilatation balloon 10 slide on the stenosis part when dilating the stenosis part of the blood vessel. .
[0059]
The hydrophilic polymer substance includes a natural polymer-based substance and a synthetic polymer-based substance. Examples of natural polymers include starch, cellulose, tannin / lignin, polysaccharide, and protein. Synthetic polymers include PVA, polyethylene oxide, acrylic acid, maleic anhydride, phthalic acid, water-soluble polyester, ketone aldehyde resin, (meth) acrylamide, polyamine, and water-soluble nylon. Etc. are exemplified.
[0060]
Among these, cellulose-based polymer substances (for example, hydroxypropyl cellulose), polyethylene oxide-based polymer substances (for example, polyethylene glycol), and maleic anhydride-based polymer substances (for example, methyl vinyl ether and maleic anhydride copolymer such as maleic anhydride copolymer). Maleic acid copolymer) and acrylamide-based polymer substances (for example, polydimethylacrylamide) are particularly preferable as the above-mentioned hydrophilic polymer substances because a film having a low coefficient of friction can be stably obtained.
[0061]
<Embodiment of the method for manufacturing an expansion balloon of the present invention>
The above-described balloon for expansion according to the present invention can be manufactured, for example, by blow-molding a parison and setting the conditions during the blow-molding to specific conditions. Hereinafter, the first step of preparing the parison and the second step of blow-molding the parison will be described in detail with reference to the reference numerals used in FIGS. 1 (A) and 1 (B). I will describe.
[0062]
(First step)
The parison to be prepared is formed by shaping the organic polymer material described above as the material of the inflation balloon 10 into a tubular shape. The molding method is not particularly limited, but is preferably an extrusion molding method. The inner diameter and outer diameter of the parison are adjusted so that a desired balloon film thickness and a desired radial stretching ratio can be obtained when a blow of a predetermined size is obtained by blow molding. Generally, its inner diameter is generally in the range of 0.1-1.0 mm and its outer diameter is generally in the range of 0.2-2.0 mm.
[0063]
In order to obtain the expansion balloon 10 having a relatively high degree of orientation of the organic polymer material, the water content of the parison is preferably set to 0.6% by mass or less, more preferably 0.5% by mass or less. preferable. The lower limit of the water content can be appropriately selected, for example, about 0.1% by mass in consideration of productivity, production cost, and the like. By relatively increasing the degree of orientation of the organic polymer material in the expansion balloon 10, the pressure resistance of the expansion balloon 10 can be easily increased. When a polyamide-based elastomer or the like is used as the organic polymer material, since the organic polymer material contains a relatively large amount of water, treatment such as vacuum drying is performed in advance so that the water content is within the above range. Is preferably applied. Further, it is preferable that the preservation is performed, for example, in a desiccator so as not to absorb moisture after the drying treatment.
[0064]
(2nd process)
In the second step, the above-mentioned parison is blow-molded to obtain the dilatation balloon 10. The blow molding machine used at this time preferably satisfies the following conditions (a) to (d).
[0065]
(A) A pressure source (cylinder, compressor), a chamber communicating with the pressure source, and a mold in which a parison is arranged are provided.
[0066]
(B) The inside of the chamber communicates with the inner space of the parison set in the blow molding machine (die).
[0067]
(C) Before the blow molding, the inside of the chamber (including the inner space of the parison) is pressurized to a predetermined pressure by the pressurizing source, and immediately before the blow molding, the chamber and the pressurizing source are connected. Be cut off.
[0068]
(D) Since the internal pressure of the chamber decreases when the parison is stretched in the radial direction, the time at which the parison is stretched in the radial direction can be accurately monitored by monitoring this.
[0069]
The production of the balloon for expansion using the blow molding machine described above can be performed, for example, by sequentially performing the following sub-steps (i) to (iV).
[0070]
(I) The parison cut to a predetermined length is set in a blow molding machine. The length of the parison can be appropriately selected within a range of approximately 10 to 40 cm according to the configuration of the blow molding machine.
[0071]
(Ii) The inside of the chamber is pressurized by a pressurizing source, the mold temperature is raised while applying an internal pressure to the parison, and the parison is heated in the mold.
[0072]
(Iii) When the mold temperature reaches the target temperature, the parison is stretched in the longitudinal axis direction. This stretching is performed by adjusting the mold temperature (the temperature of the parison) and the pressure in the chamber to predetermined values, and holding the chucks, which fix both ends of the parison in the longitudinal axis direction, outwardly along the longitudinal axis. It can be done by moving it. The stretching speed at this time is appropriately selected within a range of approximately 50 to 160 mm / sec, and the moving distance thereof can be appropriately selected within a range of approximately 5 to 60 mm per side (10 to 120 mm in total).
[0073]
When the parison to which the internal pressure equal to the internal pressure of the chamber is applied is stretched in the longitudinal direction under heating, the parison gradually becomes thinner, and when the parison cannot withstand the internal pressure, expansion (stretching) in the radial direction starts. The radial stretching of the parison is completed in a very short time relative to the longitudinal stretching (the radial stretching starts after the start of the longitudinal stretching and ends before the end of the longitudinal stretching. .). The mold temperature and the pressure in the chamber will be described later.
[0074]
(Iv) After the stretching treatment, the temperature of the mold is raised to approximately 85 to 145 ° C, and after maintaining at this temperature for approximately 10 to 60 seconds, the temperature is reduced to approximately 15 to 40 ° C at a temperature reduction rate of approximately 1 to 5 ° C / second. Quench quickly. When the material of the parison is the above-mentioned PEBAX7233SA01, the above-mentioned temperature rise is performed, for example, until the mold temperature reaches 135 ° C., and the ultimate temperature of the rapid cooling can be 33 ° C.
[0075]
It is preferable that the expanding balloon obtained by sequentially performing the sub-steps (i) to (iv) be subjected to an annealing treatment thereafter. This annealing treatment can be performed by heat treatment in an air atmosphere at about 30 to 80 ° C. for about 0.5 to 48 hours.
[0076]
The manufacturing method of the present invention for obtaining an inflation balloon by blow-molding a parison as described above has the greatest features in selecting the mold temperature and the chamber pressure in the sub-step (iii). I have.
[0077]
In other words, in the sub-step (iii), the mold temperature (the temperature of the parison) and the pressure in the chamber are adjusted so that the stretch length of the parison in the longitudinal axis direction becomes the target stretch length (the length after stretching and the length before stretching). Is controlled so that the expansion (stretching) in the radial direction is started at the time when the difference reaches 30 to 50% of the length (difference from the length).
[0078]
This control is performed when the mold temperature is set equal to the specific temperature, that is, the heat distortion temperature (according to ASTM D 648) of the organic polymer material used as the parison material under a load of 0.46 MPa (according to ASTM D648). , Inner diameter, outer diameter, wall thickness, etc., by appropriately selecting the internal pressure of the chamber within the range of 2.2 to 2.4 MPa. When the mold temperature is in the range of −10 to + 10 ° C. with respect to the above-mentioned heat deformation temperature and the pressure in the chamber is in the range of 1.5 to 3.5 MPa, the parison material, The above control can be performed by appropriately increasing the mold temperature and appropriately reducing the chamber pressure according to the inner diameter, outer diameter, wall thickness, or the like, or appropriately reducing the mold temperature and appropriately increasing the chamber pressure. .
[0079]
By performing the above-described control in blow molding the parison, the above-described expansion balloon of the present invention can be obtained. In the blow molding of the parison, when expansion (stretching) in the radial direction is started when the stretch length in the longitudinal axis direction of the parison is less than 30% of the target stretch length, the finally obtained expansion Large unevenness occurs in the orientation state of the polymer chains in the expansion function part of the balloon. Further, if the expansion of the parison in the longitudinal axis direction exceeds 50% of the target stretching length and then the expansion (extension) in the radial direction is started, the expansion of the parison is not performed properly, and molding defects easily occur. .
[0080]
In producing an expansion balloon by blow molding of a parison, the stretching ratio in the radial direction of the parison is preferably 160% or less, more preferably 140% or less, with respect to the stretching ratio in the longitudinal axis direction of the parison. More preferably, it is more preferably 120% or less. By selecting the stretching ratio in the longitudinal axis direction and the stretching ratio in the radial direction in this way, the orientation state of the polymer chains oriented in the circumferential direction of the extended function portion in the central region of the extended function portion has less unevenness, In addition, an expansion balloon having a relatively low ratio of the polymer chains oriented in the circumferential direction can be easily obtained. In such an expansion balloon, as described above, even if it ruptures, the occurrence of breakage in the circumferential direction of the expansion function portion is suppressed. When the parison material is a polyamide-based elastomer, the stretching ratio in the radial direction is approximately 3.5 to 5.0 times, and the stretching ratio in the longitudinal axis direction is approximately 3.0 to 4.0 times. Is preferred.
[0081]
In the present invention, the “radial stretching ratio of the parison” refers to the area of the cross-section (however, the cross-sectional area of the hollow region is the cross-sectional area of the parison and the cross-section of the expansion function of the expansion balloon obtained from the parison) Excluding) is determined based on the diameters of the circumferences that can be equally divided into an inner region and an outer region having the same area. Further, the “stretching ratio in the longitudinal direction of the parison” is a value obtained based on the total length of the expansion function portion of the obtained expansion balloon and the total length of the parison constituting the expansion function portion.
[0082]
【Example】
<Example 1>
First, a polyamide-based elastomer (trade name: PEBAX7233SA01 (manufactured by Atfina Chemicals)) was extruded to obtain a tube having an inner diameter of 0.51 mm and an outer diameter of 0.90 mm. The above polyamide-based elastomer is an organic polymer material having a heat distortion temperature (according to ASTM D648) of 106 ° C. under a load of 0.46 MPa.
[0083]
Next, the above tube was cut into a length of 30 cm, vacuum dried at 80 ° C. for 1 hour, and then left in a desiccator for 1 hour to obtain a water content of 0.5% by mass. I got a parison.
[0084]
The parison is set in a blow molding machine, and blow molding is performed under the conditions of a mold temperature of 100 ° C., a chamber pressure of 2.6 MPa, a stretching speed in the longitudinal axis direction of 160 mm / sec, and a stretching length of 70 mm in the longitudinal axis direction. Was. At this time, when the stretching length in the longitudinal axis direction reached 40% (28 mm) of the target stretching length (70 mm), a decrease in the pressure in the chamber (start of expansion of the parison in the radial direction) was confirmed.
[0085]
Next, the mold temperature was raised to 120 ° C., and the temperature was maintained at this temperature for 10 seconds, followed by quenching to 33 ° C. at a rate of 3 ° C./sec. This was transferred from a blow molding machine to an oven, annealed at 55 ° C. for 1 hour, and then cut into a predetermined length to obtain a target balloon for expansion.
[0086]
This inflation balloon has the same shape as the inflation balloon 10 shown in FIGS. 1A and 1B, the length of the inflation function portion is 15 mm, and the length of the first taper portion is 15 mm. (Meaning the length along the taper shape; the same applies hereinafter) is 3.0 mm, the length of the base end portion is 1.5 mm, the length of the second taper portion is 3.0 mm, and the length of the tip end portion is Is 2.0 mm, the film thickness of the extended function part is 22 μm, the outer diameter when the extended function part is deformed into a cylindrical shape is 3.0 mm, the stretching ratio in the longitudinal direction of the parison is 3.5 times, The stretching ratio in the radial direction is 4.0 times.
[0087]
<Example 2>
The inner diameter of the parison is 0.39 mm, the outer diameter is 0.86 mm, the mold is replaced with another mold having a different internal space shape, and the extension length of the parison in the longitudinal axis direction is 60 mm. Was obtained in the same manner as in Example 1.
[0088]
The length of the expansion function part in this balloon for expansion is 15 mm, the length of the first taper part is 4.0 mm, the length of the base end part is 1.5 mm, the length of the second taper part is 5.0 mm, The length of the tip portion is 2.0 mm, the film thickness of the extended function portion is 22 μm, the outer diameter when the extended function portion is deformed into a cylindrical shape is 4.0 mm, and the stretching ratio of the parison in the longitudinal axis direction is 3.0 times, and the stretching ratio in the radial direction is 4.7 times.
[0089]
Also in this embodiment, at the time of blow molding, when the stretching length in the longitudinal axis direction reaches 40% (24 mm) of the target stretching length (60 mm), the pressure in the chamber decreases (the parison expands in the radial direction). Start) was confirmed.
[0090]
<Comparative Example 1>
An inflation balloon having the same shape and size as the inflation balloon obtained in Example 1 was obtained in the same manner as in Example 1 except that the pressure in the chamber during blow molding was set to 3.0 MPa. In this comparative example, when the stretch length in the longitudinal axis direction reaches 20% (14 mm) of the target stretch length (70 mm) during blow molding, the pressure in the chamber decreases (the parison starts to expand in the radial direction). Was confirmed.
[0091]
<Evaluation>
For each of the dilatation balloons obtained in Example 1, Example 2, and Comparative Example 1, from the end on the distal end side of the second tapered portion to the end on the proximal end side of the first tapered portion, The degree of orientation of the polymer chains at 1 mm intervals along the shape, and the percentage of the biaxially oriented polymer chains that are oriented in the circumferential direction (hereinafter, referred to as “peripheral orientation rate”). Was determined using a wide-angle X-ray diffraction method. In addition, the above-mentioned degree of orientation and the degree of orientation in the circumferential direction were similarly obtained at both ends in the longitudinal direction in the central region of the extended function part. These results are shown in FIGS. 3 to 5. Table 1 shows the maximum value and the minimum value of the degree of orientation in the extended function portion and the orientation ratio in the circumferential direction in the central region of the extended function portion.
[0092]
Further, under the same conditions as in Example 1, Example 2, or Comparative Example 1, 100 inflation balloons were produced, and these inflation balloons were shown in FIGS. 2 (A) and 2 (B). The pressure resistance and safety when applied to the indicated vascular dilatation catheter were evaluated. Table 2 shows the results.
[0093]
The evaluation of the pressure resistance is relatively performed based on the magnitude of the internal pressure (average value) when a physiological saline solution is supplied to the inflation balloon and the inflation balloon is ruptured. It was relatively performed based on the magnitude of the rate of occurrence of breakage in the circumferential direction of the extended function part.
[0094]
[Table 1]

[0095]
[Table 2]

[0096]
As is clear from Table 1, FIGS. 3 to 5 and Table 2, Example 1 or Example in which the difference between the maximum value and the minimum value of the circumferential orientation ratio in the central region of the extended function part is 20 points or less. The dilatation balloon of Example 2 has relatively high pressure resistance and safety. On the other hand, the expansion balloon of Comparative Example 1 in which the difference exceeds 20 points has the same degree of orientation of the polymer chains as the expansion balloon of Example 1 or 2, but has pressure resistance and safety. Sex is relatively low.
[0097]
【The invention's effect】
As described above, according to the present invention, there is provided an inflation balloon which has excellent pressure resistance and is less likely to be broken in the circumferential direction even when ruptured. Therefore, according to the present invention, the safety of various balloon catheters having the dilatation balloon can be enhanced.
[Brief description of the drawings]
FIG. 1 (A) is a side view schematically showing an embodiment of an expansion balloon of the present invention, and FIG. 1 (B) is an expansion balloon shown in FIG. 1 (A). It is the schematic which shows the cross-section structure of.
FIG. 2 (A) schematically shows an embodiment of the balloon catheter of the present invention, and FIG. 2 (B) schematically shows a partial cross section of the balloon catheter shown in FIG. 2 (A). Shown in
FIG. 3 is a graph showing an orientation state of a polymer chain in the dilatation balloon obtained in Example 1.
FIG. 4 is a graph showing the orientation of polymer chains in the dilatation balloon obtained in Example 2.
FIG. 5 is a graph showing the orientation of polymer chains in the dilatation balloon obtained in Comparative Example 1.
[Explanation of symbols]
1 Extended function section
1a Central area of extended function section
3 First taper
5 Base end
7 2nd taper part
9 Tip
10 balloon for expansion
70 Balloon catheter for vasodilation

Claims (9)

An extension function portion capable of expanding its diameter to be deformed into a cylindrical shape, a straight body base end portion directly connected to one end of the extension function portion or via a first taper portion, and the extension function portion And a straight body-shaped tip end connected directly or via a second taper portion, wherein the extended function portion, the base end portion, and the tip end are integrally formed from one organic polymer material. A shaped expansion balloon,
At least the organic polymer material in the extended function part includes a biaxially oriented polymer chain, and the orientation state of the polymer chain in the central area of the extended function part is changed at one end in the longitudinal axis direction of the central area of the extended function part. From the other end to the other end, when sequentially obtained by the wide-angle X-ray diffraction method, among the biaxially oriented polymer chains, the polymer chains that are oriented in the circumferential direction when the extended function portion is deformed into a cylindrical shape. The difference between the maximum and minimum percentages is less than or equal to 20 points. The dilatation balloon according to claim 1, wherein the maximum value of the percentage is 80% or less. The expansion balloon according to claim 1 or 2, wherein the organic polymer material is a polyamide elastomer. The expansion balloon according to any one of claims 1 to 3, wherein the balloon is formed by blow molding a parison having a water content of 0.6% by mass or less. A balloon catheter comprising the dilatation balloon according to claim 1. A first step of preparing a parison formed of an organic polymer material capable of orienting a polymer chain, and stretching the parison in a longitudinal direction and a radial direction by blow molding to expand a diameter of the cylinder. An extended function part capable of being deformed into a shape, a straight body-shaped base end part directly connected to one end of the extended function part or via a first tapered part, and directly or A second step of obtaining a balloon having a straight body-shaped tip portion connected via a second tapered portion, the method comprising:
In the second step, a method for manufacturing an inflation balloon in which the radial stretching is started when the stretch length of the parison in the longitudinal axis direction reaches 30 to 50% of a target stretch length. The method for producing an inflation balloon according to claim 6, wherein the stretching ratio in the radial direction in the second step is 160% or less of the stretching ratio in the longitudinal axis direction. 8. The method for producing an inflation balloon according to claim 6, wherein the water content of the parison prepared in the first step is 0.6% by mass or less. The method for manufacturing an inflation balloon according to any one of claims 6 to 8, wherein the parison prepared in the first step is formed of a polyamide elastomer.

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