JP2001129076A - Cuff member for intra-abdominal indwelling catheter - Google Patents
Cuff member for intra-abdominal indwelling catheterInfo
- Publication number
- JP2001129076A JP2001129076A JP31118799A JP31118799A JP2001129076A JP 2001129076 A JP2001129076 A JP 2001129076A JP 31118799 A JP31118799 A JP 31118799A JP 31118799 A JP31118799 A JP 31118799A JP 2001129076 A JP2001129076 A JP 2001129076A
- Authority
- JP
- Japan
- Prior art keywords
- cuff member
- collagen
- catheter
- cuff
- solution
- 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
Abstract
Description
【発明の属する技術分野】本発明は、腹膜透析法におい
て、腹腔内に留置して透析液を注排液するために使用さ
れる腹腔内留置カテーテルに用いるカフ部材に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cuff member used for an intraperitoneal indwelling catheter used for injecting and discharging dialysate in the peritoneal cavity in peritoneal dialysis.
【従来の技術】腹膜透析療法においては、透析液の注入
と排液の排出は腹腔内に留置されている腹腔内留置カテ
ーテルと、このカテーテルに接続される透析液交換シス
テムとにより行われる。この腹腔内留置カテーテルで
は、患者にカテーテルを移植した際に、生体組織がカテ
ーテルを異物認識し生体組織とカテーテルが密着しない
ため表皮がカテーテルに沿って内側に入り込むいわゆる
ダウングロース（Down Growth）が生じ、これが深くな
ると、消毒が行き届かず細菌の感染経路を形成すること
となり、皮膚の炎症やひいては腹膜炎まで引き起こすと
いう問題があった。そこで上記カテーテルの外縁に、生
体適合性に優れた素材からなる感染防止用カフ部材をさ
らに設け、該カフ部材を表皮下に位置させ、生体組織を
カフ部材内に増殖させることによりカテーテルの経皮部
付近の生体組織をカテーテル周辺に密集させ、ダウング
ロースの進行を抑制するようにしたものが提案されてい
る（特開平８−２０６１９３号）。しかし、上記腹腔内
留置カテーテルでは、該カフ部材の密度が低い場合、該
カフ部材を皮下トンネルに設置後、血液、体液、生理食
塩液等の液体を吸収し、該カフ部材の体積が減少し、カ
テーテルの経皮部付近の生体組織をカテーテル周辺に十
分密集させることができず、ダウングロースの進行を抑
制することが困難となる可能性があった。2. Description of the Related Art In peritoneal dialysis therapy, infusion and drainage of dialysate are performed by an intraperitoneal indwelling catheter indwelled in the abdominal cavity and a dialysate exchange system connected to the catheter. In this intraperitoneal indwelling catheter, when the catheter is implanted into a patient, so-called down growth occurs in which the living tissue recognizes the foreign body of the catheter and the living tissue does not adhere to the catheter, so that the epidermis enters inside along the catheter. However, when the depth becomes deeper, disinfection is inadequate, and a bacterial infection route is formed, which causes a problem of causing skin inflammation and eventually peritonitis. Therefore, an infection-preventing cuff member made of a material having excellent biocompatibility is further provided on the outer edge of the catheter, the cuff member is positioned under the epidermis, and the living tissue is allowed to grow in the cuff member. There has been proposed a technique in which the living tissue near the part is concentrated around the catheter to suppress the progress of downgrowth (Japanese Patent Application Laid-Open No. 8-206193). However, in the intraperitoneal indwelling catheter, when the density of the cuff member is low, the cuff member is placed in a subcutaneous tunnel, and then absorbs a liquid such as blood, body fluid, or physiological saline, and the volume of the cuff member decreases. However, the living tissue in the vicinity of the percutaneous portion of the catheter cannot be sufficiently concentrated around the catheter, and it may be difficult to suppress the progress of downgrowth.
【発明が解決しようとする課題】本発明は、上記従来技
術の問題点に鑑みなされたものであり、その目的とする
ところは、腹腔内留置カテーテルを留置した際、カテー
テルの経皮部付近の生体組織をカテーテル周辺に十分密
集させるカフ部材を提供することにある。SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned problems of the prior art, and has as its object to provide a method for indwelling an intraperitoneal indwelling catheter in the vicinity of the percutaneous portion of the catheter. An object of the present invention is to provide a cuff member for sufficiently concentrating living tissue around a catheter.
【課題を解決するための手段】すなわち、本発明は、腹
腔内に留置される腹腔内留置カテーテルの皮下トンネル
部に用いるカフ部材であって、コラーゲンを主成分と
し、密度が０，０５ｇ／ｃｍ３以上で、湿潤状態での体
積変化率の最大が１００％以上であることを特徴とする
カフ部材である。ここで体積変化率とは下記の式の様に
定義する。 体積変化率(％)＝生理食塩液浸漬後のカフ体積／生理食
塩液浸漬前のカフ体積×１００ 湿潤状態とは前記カフ部材が十分に浸漬する量の生理食
塩液に浸漬した状態とし、生理食塩液浸漬後のカフ体積
の測定は体積変化が定常状態となる８時間後に行う。ま
た、生理食塩液浸漬前のカフ体積の測定は実質的に乾燥
状態で行う。また、本発明は、前記カフ部材がコラーゲ
ンを主材料とする多孔質管状体から形成されていること
を特徴とするカフ部材である。本発明はまた、前記コラ
ーゲンを主材料とする多孔質管状体は線維化コラーゲン
と変性コラーゲンとからなるものであることを特徴とす
る前記カフ部材である。本発明はさらに、カテーテル本
体の外周に沿って軸方向に移動可能であり、前記皮下ト
ンネル部の任意の位置に導入、設置することができるこ
とを特徴とする前記カフ部材である。本発明はさらにま
た、前記カフ部材の両端の外径が異なることを特徴とす
る前記カフ部材である。That is, the present invention relates to a cuff member used for a subcutaneous tunnel portion of an intraperitoneal indwelling catheter which is indwelled in the abdominal cavity, which contains collagen as a main component and has a density of 0.05 g / cm. 3 is a cuff member characterized in that the maximum volume change rate in a wet state is 100% or more. Here, the volume change rate is defined as in the following equation. Volume change rate (%) = cuff volume after immersion in physiological saline / cuff volume before immersion in physiological saline × 100 The wet state refers to a state in which the cuff member is immersed in a sufficient amount of physiological saline to immerse the cuff. The measurement of the cuff volume after immersion in the saline solution is performed 8 hours after the volume change reaches a steady state. The measurement of the cuff volume before immersion in a physiological saline solution is performed in a substantially dry state. Further, the present invention is the cuff member, wherein the cuff member is formed of a porous tubular body containing collagen as a main material. The present invention also provides the cuff member, wherein the collagen-based porous tubular body is made of fibrillar collagen and denatured collagen. The cuff member according to the present invention is further characterized in that the cuff member is movable in the axial direction along the outer periphery of the catheter body and can be introduced and installed at an arbitrary position in the subcutaneous tunnel portion. The present invention is the cuff member, wherein the outer diameters of both ends of the cuff member are different.
【発明の実施形態】カフ部材を構成するコラーゲン多孔
質体は、例えばつぎの方法により製造することができ
る。すなわち、コラーゲン溶液をリン酸緩衝液のような
平衡塩溶液と混合して、３７℃において４時間程度イン
キュベートすることにより、コラーゲンを線維化する。
一方、コラーゲン溶液を加熱することにより、熱変性さ
せ、変性処理する。この場合、コラーゲンの熱変性は、
３７℃前後を境として起こるので、４０〜１００℃の範
囲で熱変性させるが、好ましくは６０〜８０℃がよい。
好適な加熱変性処理は、６０℃で３０分間である。この
ようにして得られた線維化されたコラーゲン溶液と変性
コラーゲン溶液を混合して、管状容器内で凍結乾燥した
後、熱脱水架橋を行うことにより、コラーゲン多孔質体
からなるカフ部材５が得られる。熱脱水による架橋は、
架橋度５０％以上が好ましく、６０〜８０％がより好ま
しい。５０％未満であるとカテーテルの皮下ンネル穿設
の際に、形状が維持できない恐れがあり、架橋度が強す
ぎるとコラーゲンが極度に変性する可能性がある。ま
た、カフ部材５の密度は０．０５g/cm3以上が好まし
く、０．０６〜０．０９g/cm3がより好ましい。カフ部
材５の全長は３．０〜５０ｍｍ程度、好ましくは５．０
〜５０ｍｍ程度がよい。カフ部材５の全長が３．０ｍｍ
以下であるとカテーテル本体の周囲に生体組織を密集さ
せることが難しく、ダウングロースを適度に維持するこ
とが困難であり、全長が５０ｍｍ以上あると外部カフ７
を設置する位置を変更する必要が生じる。また、カフ部
材５は一端がカテーテルの経皮部付近に位置していれ
ば、他端部は外部カフの設置位置までの間にどのような
長さで位置してもよく、例えば全長３．０〜２５ｍｍ程
度のものを複数個、隣接して設置してもよく、所定間隔
だけあけて縦列して設置してもよい。またカフ部分５の
肉厚は、１．０〜４．０ｍｍ程度、好ましくは１．５〜
２．５ｍｍ程度である。肉厚が１．０ｍｍ以下であると
カテーテル本体の周囲に生体組織を密集させることが難
しく、ダウングロースを適度に維持することが困難であ
り、肉厚が４．０ｍｍ以上であると患者にカテーテルを
留置する際に腹壁に与える損傷が大きくなり、創部の治
癒に時間を要することとなる恐れがある。本発明で体積
変化率とは下記の式の様に定義する。 体積変化率(％)＝生理食塩液浸漬後のカフ体積／生理食
塩液浸漬前のカフ体積×１００ 湿潤状態とは前記カフ部材が十分に浸漬する量の生理食
塩液に浸漬した状態とし、生理食塩液浸漬後のカフ体積
の測定は体積変化が定常状態となる８時間後に行う。ま
た、生理食塩液浸漬前のカフ体積の測定は実質的に乾燥
状態で行う。本発明のカフ部材は、湿潤状態での体積変
化率の最大が１００％以上、好ましくは１００〜３００
％である。カフ部材が腹膜皮下に固定された際、体積減
少が小さくカフ部材と腹膜皮下組織が密着し、カテーテ
ルの周辺の生体組織をカテーテルの周囲に十分密集させ
ることができる。特に前記カフ部材は、腹腔内留置カテ
ーテルの皮下トンネル部の延出部側に設けられているた
めカフ部材が表皮下に位置されカテーテルの経皮部付近
の生体組織をカテーテルの周囲に密集させることができ
るので、ダウングロースが深くなるのを防止することが
できる。BEST MODE FOR CARRYING OUT THE INVENTION A collagen porous material constituting a cuff member can be produced, for example, by the following method. That is, the collagen solution is mixed with a balanced salt solution such as a phosphate buffer, and incubated at 37 ° C. for about 4 hours to fibrillate the collagen.
On the other hand, the collagen solution is heated to be denatured by heat and denatured. In this case, the thermal denaturation of collagen
Since it occurs around 37 ° C., it is thermally denatured in the range of 40 to 100 ° C., preferably 60 to 80 ° C.
A suitable heat denaturation treatment is at 60 ° C. for 30 minutes. The fibrous collagen solution thus obtained and the denatured collagen solution are mixed, freeze-dried in a tubular container, and then subjected to thermal dehydration crosslinking to obtain a cuff member 5 composed of a collagen porous material. Can be Crosslinking by thermal dehydration
The degree of crosslinking is preferably 50% or more, more preferably 60 to 80%. If it is less than 50%, the shape may not be maintained during subcutaneous tunneling of the catheter, and if the degree of crosslinking is too strong, collagen may be extremely denatured. Further, the density of the cuff member 5 is preferably 0.05 g / cm 3 or more, and more preferably 0.06 to 0.09 g / cm 3 . The total length of the cuff member 5 is about 3.0 to 50 mm, preferably 5.0.
It is preferably about 50 mm. The total length of the cuff member 5 is 3.0 mm
If it is less than the above, it is difficult to concentrate the living tissue around the catheter body, it is difficult to maintain the downgrowth appropriately, and if the total length is 50 mm or more, the external cuff 7
It is necessary to change the position where the camera is installed. In addition, as long as one end of the cuff member 5 is located in the vicinity of the percutaneous portion of the catheter, the other end may be located at any length between the positions where the external cuff is installed. A plurality of devices having a size of about 0 to 25 mm may be provided adjacent to each other, or may be provided in a line at predetermined intervals. The thickness of the cuff portion 5 is about 1.0 to 4.0 mm, preferably 1.5 to 4.0 mm.
It is about 2.5 mm. When the wall thickness is 1.0 mm or less, it is difficult to densely lay the living tissue around the catheter body, and it is difficult to appropriately maintain downgrowth. The injuries to the abdominal wall when placing the incision may increase, and it may take time to heal the wound. In the present invention, the volume change rate is defined as in the following equation. Volume change rate (%) = cuff volume after immersion in physiological saline / cuff volume before immersion in physiological saline × 100 The wet state refers to a state in which the cuff member is immersed in a sufficient amount of physiological saline to be immersed. The measurement of the cuff volume after immersion in the saline solution is performed 8 hours after the volume change reaches a steady state. The measurement of the cuff volume before immersion in a physiological saline solution is performed in a substantially dry state. The cuff member of the present invention has a maximum volume change rate in a wet state of 100% or more, preferably 100 to 300%.
%. When the cuff member is fixed subcutaneously to the peritoneum, the volume decrease is small and the cuff member and the peritoneal subcutaneous tissue come into close contact with each other, and the living tissue around the catheter can be sufficiently concentrated around the catheter. In particular, since the cuff member is provided on the extension side of the subcutaneous tunnel of the intraperitoneal indwelling catheter, the cuff member is located under the epidermis and the living tissue near the percutaneous portion of the catheter is concentrated around the catheter. Therefore, downgrowth can be prevented from becoming deep.
【実施例】（実施例１）密度０．０２５g/cm3、０．０
４g/cm3、０．０８g/cm3のコラーゲンを主材料とする多
孔質管状体よりなるカフ部材を作製し、これらのカフ部
材が十分に浸漬する量の生理食塩液に浸漬した。８時間
後、カフ部材の体積を測定し、生理食塩液浸漬前のカフ
部材の体積を１００として比較した。結果を表１に示
す。EXAMPLES (Example 1) Density 0.025 g / cm 3 , 0.0
A cuff member made of a porous tubular body mainly composed of 4 g / cm 3 and 0.08 g / cm 3 collagen was prepared and immersed in a physiological saline solution in an amount sufficient to immerse these cuff members. Eight hours later, the volume of the cuff member was measured, and the volume of the cuff member before immersion in the physiological saline solution was compared with 100. Table 1 shows the results.
【表１】 （実施例２）密度０．０２５g/cm3、０．０４g/cm3、
０．０８g/cm3のコラーゲンを主材料とする多孔質管状
体よりなるカフ部材を作製し、これらのカフ部材を設置
したシリコーンチューブとカフ部材を設置していないシ
リコーンチューブを用いて評価実験を行った。ラットの
背部にメスを入れ、カフ部材を設置したシリコーンチュ
ーブとカフ部材を設置していないシリコーンチューブを
皮下に移植し、２、４、１２週間後、チューブ周辺組織
を評価した。チューブを移植して２週間後、カフ部材を
設置していないチューブ界面では高い炎症反応が認めら
れた。カフ部材を設置したチューブ界面ではカフ部材を
設置していないチューブ界面と比較し、炎症反応が抑制
されていたが、密度０．０２５g/cm3および０．０４g/c
m3のカフ部材については比較的高い炎症反応がみられ
た。更に密度が高い０．０８g/cm3カフ部材は、炎症反
応は低く、２週間以降も低く推移した。また、カフ部材
を設置することにより２週間以降、カフ部材自身が良く
褶曲した太いコラーゲン束とその間隙に侵入した線維芽
細胞と毛細血管等よりなる真皮様組織に置換されてお
り、更にカフ部材の密度が高い程、真皮様組織も増加し
た。 （実施例３） 線維化コラーゲンの生成 アテロコラーゲン粉末を４℃の温度下でｐＨ３．０の希
塩酸に溶解して０．３〜０．４w/v％に調整した。この
溶液を０．８μｍ及び０．２μｍの直径の空孔を有する
２種類のフィルターに順次通して濾過滅菌した後に、４
℃に維持しつつ攪拌しながら、ｐＨ７．０のリン酸緩衝
液を加え、最終濃度が０．１〜０．１５w/v％のアテロ
コラーゲン（３０mmol/Ｌリン酸２ナトリウム、１００m
mol/L塩化ナトリウム）であるコラーゲン溶液とした。
次いで、３７℃の恒温槽内に４時間放置し、線維化アテ
ロコラーゲン（ＦＣ）溶液を調整した。そして、このＦ
Ｃ溶液を無菌条件下で遠心操作による濃縮を行って、濃
度を８．０w/v％に調整した。 変性コラーゲンの生成 一方、上述のフィルターを順次通過させた０．３〜０．
４w/v％のアテロコラーゲン溶液を凍結乾燥し、再び無
菌の蒸留水に８．０w/v％となるよう再溶解した。この
溶液を６０℃の恒温槽内に３０分間放置して熱変性を生
じせしめ変性アテロコラーゲン（ＨＡＣ）溶液とした。
そして、このＨＡＣ溶液を３７℃の温度下で０．４５μ
ｍの直径の空孔を有するフィルターを通して濾過した。 コラーゲン多孔質体の生成 このようにして得られたＦＣ溶液とＨＡＣ溶液を９：１
の割合で混合し、全長４０ｍｍ、内径４．３ｍｍ、外径
８．３ｍｍの管状容器に流し込み、凍結乾燥を行った。
得られた内径４．３ｍｍ、肉厚２．０ｍｍコラーゲン多
孔質管状体を全長１０ｍｍに切断した。さらにこのコラ
ーゲン多孔質管状体を０．０５Ｔｏｒｒ未満の真空下、
１１０℃の温度下で１．２５時間熱脱水架橋を行い、カ
フ部材を得た。 （実施例４） 線維化コラーゲンの生成 アテロコラーゲン粉末を４℃の温度下でｐＨ３．０の希
塩酸に溶解して０．３〜０．４w/v％に調整した。この
溶液を０．８μｍ及び０．２μｍの直径の空孔を有する
２種類のフィルターに順次通して濾過滅菌した後に、４
℃に維持しつつ攪拌しながら、ｐＨ７．０のリン酸緩衝
液を加え、最終濃度が０．１〜０．１５w/v％のアテロ
コラーゲン（３０mmol/Ｌリン酸２ナトリウム、１００m
mol/L塩化ナトリウム）であるコラーゲン溶液とした。
次いで、３７℃の恒温槽内に４時間放置し、線維化アテ
ロコラーゲン（ＦＣ）溶液を調整した。そして、このＦ
Ｃ溶液を無菌条件下で遠心操作による濃縮を行って、濃
度を４．０w/v％に調整した。 変性コラーゲンの生成 一方、上述のフィルターを順次通過させた０．３〜０．
４w/v％のアテロコラーゲン溶液を凍結乾燥し、再び無
菌の蒸留水に４．０w/v％となるよう再溶解した。この
溶液を６０℃の恒温槽内に３０分間放置して熱変性を生
じせしめ変性アテロコラーゲン（ＨＡＣ）溶液とした。
そして、このＨＡＣ溶液を３７℃の温度下で０．４５μ
ｍの直径の空孔を有するフィルターを通して濾過した。 コラーゲン多孔質体の生成 このようにして得られたＦＣ溶液とＨＡＣ溶液を９：１
の割合で混合し、全長４０ｍｍ、内径４．３ｍｍ、外径
１０．３ｍｍの管状容器に流し込み、凍結乾燥を行っ
た。得られた内径４．３ｍｍ、肉厚３．０ｍｍコラーゲ
ン多孔質管状体を全長１０ｍｍに切断した。次いでこの
管状体の内径を保持した状態で外周部から軸方向に対し
垂直に圧縮し、内径４．３ｍｍ、肉厚２．０ｍｍのコラ
ーゲン多孔質管状体を得た。さらにこのコラーゲン多孔
質管状体を０．０５Ｔｏｒｒ未満の真空下、１１０℃の
温度下で３時間熱脱水架橋を行い、カフ部材を得た。 （実施例５）実施例１で得られた濃度８．０w/v％のコ
ラーゲン溶液を用いた全長１０ｍｍ、内径４．３ｍｍ、
肉厚２．０ｍｍのコラーゲン多孔質管状体よりなるカフ
部材、実施例２で得られた濃度４．０w/v％のコラーゲ
ン溶液を用い、圧縮による体積減少を行った全長１０ｍ
ｍ、内径４．３ｍｍ、肉厚２．０ｍｍのコラーゲン多孔
質管状体よりなるカフ部材及び、濃度４．０w/v％のコ
ラーゲン溶液を用い、圧縮による体積減少を行っていな
い全長１０ｍｍ、内径４．３ｍｍ、肉厚２．０ｍｍのコ
ラーゲン多孔質管状体よりなるカフ部材をそれぞれのカ
フ部材が十分に浸漬する量の生理食塩液に浸漬した。８
時間後、カフ部材の体積を測定し、生理食塩液浸漬前の
カフ部材の体積を１００vol％として比較した。結果を
表２に示す。[Table 1] (Example 2) Density 0.025 g / cm 3 , 0.04 g / cm 3 ,
A cuff member made of a porous tubular body containing 0.08 g / cm 3 of collagen as a main material was prepared, and an evaluation experiment was performed using a silicone tube having the cuff member and a silicone tube having no cuff member. went. A scalpel was placed in the back of the rat, and a silicone tube provided with a cuff member and a silicone tube not provided with a cuff member were implanted subcutaneously. After 2, 4, and 12 weeks, the tissue around the tube was evaluated. Two weeks after the tube was implanted, a high inflammatory reaction was observed at the tube interface where the cuff member was not installed. The inflammatory reaction was suppressed at the tube interface where the cuff member was installed, compared to the tube interface where the cuff member was not installed, but the density was 0.025 g / cm 3 and 0.04 g / c.
higher inflammatory response was observed for the cuff member m 3. Further, the 0.08 g / cm 3 cuff member having a higher density had a low inflammatory response and remained low even after 2 weeks. Further, by installing the cuff member, after 2 weeks, the cuff member itself has been replaced by a well-folded thick collagen bundle and a dermis-like tissue consisting of fibroblasts and capillaries that have invaded the gap. The higher the density of, the more dermis-like tissue increased. (Example 3) Production of fibrillated collagen Atelocollagen powder was dissolved in dilute hydrochloric acid having a pH of 3.0 at a temperature of 4 ° C and adjusted to 0.3 to 0.4 w / v%. The solution was sterilized by passing it through two types of filters having pores of 0.8 μm and 0.2 μm in diameter, and then filtered.
While maintaining the temperature and stirring, a pH 7.0 phosphate buffer solution was added, and a final concentration of 0.1 to 0.15 w / v% atelocollagen (30 mmol / L disodium phosphate, 100 mM) was added.
mol / L sodium chloride).
Then, it was left in a thermostat at 37 ° C. for 4 hours to prepare a fibrillated atelocollagen (FC) solution. And this F
The solution C was concentrated by centrifugation under aseptic conditions to adjust the concentration to 8.0 w / v%. Production of denatured collagen On the other hand, 0.3 to 0.
The 4 w / v% atelocollagen solution was freeze-dried and redissolved again in sterile distilled water to 8.0 w / v%. This solution was allowed to stand in a thermostat at 60 ° C. for 30 minutes to cause heat denaturation to obtain a denatured atelocollagen (HAC) solution.
Then, the HAC solution was added at a temperature of 37 ° C. to 0.45 μm.
Filtered through a filter having pores of m diameter. Formation of Collagen Porous Material The FC solution and HAC solution thus obtained were mixed at a ratio of 9: 1.
, And poured into a tubular container having a total length of 40 mm, an inner diameter of 4.3 mm, and an outer diameter of 8.3 mm, and freeze-dried.
The obtained collagen porous tubular body having an inner diameter of 4.3 mm and a thickness of 2.0 mm was cut into a total length of 10 mm. Further, the collagen porous tubular body is placed under a vacuum of less than 0.05 Torr,
Thermal dehydration crosslinking was performed at 110 ° C. for 1.25 hours to obtain a cuff member. (Example 4) Production of fibrillated collagen Atelocollagen powder was dissolved in dilute hydrochloric acid at pH 3.0 at a temperature of 4 ° C to adjust to 0.3 to 0.4 w / v%. The solution was sterilized by passing it through two types of filters having pores of 0.8 μm and 0.2 μm in diameter, and then filtered.
While maintaining the temperature and stirring, a pH 7.0 phosphate buffer solution was added, and a final concentration of 0.1 to 0.15 w / v% atelocollagen (30 mmol / L disodium phosphate, 100 mM) was added.
mol / L sodium chloride).
Then, it was left in a thermostat at 37 ° C. for 4 hours to prepare a fibrillated atelocollagen (FC) solution. And this F
The solution C was concentrated by centrifugation under aseptic conditions to adjust the concentration to 4.0 w / v%. Production of denatured collagen On the other hand, 0.3 to 0.
The 4 w / v% atelocollagen solution was freeze-dried and redissolved again in sterile distilled water to 4.0 w / v%. This solution was allowed to stand in a thermostat at 60 ° C. for 30 minutes to cause heat denaturation to obtain a denatured atelocollagen (HAC) solution.
Then, the HAC solution was added at a temperature of 37 ° C. to 0.45 μm.
Filtered through a filter having pores of m diameter. Formation of Collagen Porous Material The FC solution and HAC solution thus obtained were mixed at a ratio of 9: 1.
, And poured into a tubular container having a total length of 40 mm, an inner diameter of 4.3 mm, and an outer diameter of 10.3 mm, and freeze-dried. The obtained collagen porous tubular body having an inner diameter of 4.3 mm and a thickness of 3.0 mm was cut to a total length of 10 mm. Next, while maintaining the inner diameter of the tubular body, it was compressed perpendicularly to the axial direction from the outer peripheral portion to obtain a collagen porous tubular body having an inner diameter of 4.3 mm and a wall thickness of 2.0 mm. Further, the collagen porous tubular body was subjected to thermal dehydration crosslinking under a vacuum of less than 0.05 Torr at a temperature of 110 ° C. for 3 hours to obtain a cuff member. (Example 5) Using the collagen solution having a concentration of 8.0 w / v% obtained in Example 1, a total length of 10 mm, an inner diameter of 4.3 mm,
Using a cuff member made of a collagen porous tubular body having a thickness of 2.0 mm and the collagen solution having a concentration of 4.0 w / v% obtained in Example 2, the volume was reduced by compression to a total length of 10 m.
m, a cuff member composed of a collagen porous tubular body having an inner diameter of 4.3 mm and a wall thickness of 2.0 mm, and a collagen solution having a concentration of 4.0 w / v%. A cuff member made of a collagen porous tubular body having a thickness of 0.3 mm and a thickness of 2.0 mm was immersed in a physiological saline solution in such an amount that each cuff member was sufficiently immersed. 8
After a period of time, the volume of the cuff member was measured, and the volume of the cuff member before immersion in the physiological saline solution was compared with 100 vol%. Table 2 shows the results.
【表２】 （実施例６）実施例３で得られた濃度８．０w/v％のコ
ラーゲン溶液を用いた全長１０ｍｍ、内径４．３ｍｍ、
肉厚２．０ｍｍのコラーゲン多孔質管状体よりなるカフ
部材、実施例２で得られた濃度４．０w/v％のコラーゲ
ン溶液を用い、圧縮による体積減少を行った全長１０ｍ
ｍ、内径４．３ｍｍ、肉厚２．０ｍｍのコラーゲン多孔
質管状体よりなるカフ部材及び濃度４．０w/v％のコラ
ーゲン溶液を用い、圧縮による体積減少を行っていない
全長１０ｍｍ、内径４．３ｍｍ、肉厚２．０ｍｍコラー
ゲン多孔質管状体よりなるカフ部材を設置したシリコー
ンチューブとカフ部材を設置していないシリコーンチュ
ーブを用いて評価実験を行った。ラットの背部にメスを
入れ、カフ部材を設置したシリコーンチューブとカフ部
材を設置していないシリコーンチューブを皮下に移植
し、２、４、１２週間後、チューブ周辺組織を評価し
た。チューブを移植して２週間後、カフ部材を設置して
いないチューブ界面では高い炎症反応が認められた。カ
フ部材を設置したチューブ界面ではカフ部材を設置して
いないチューブ界面と比較し、炎症反応が抑制されてい
たが、濃度４．０w/v％のコラーゲン溶液を用い、圧縮
による体積減少を行っていないカフ部材については比較
的高い炎症反応がみられた。濃度８．０w/v％のコラー
ゲン溶液を用いたカフ部材および濃度４．０w/v％のコ
ラーゲン溶液を用い、圧縮による体積減少を行ったカフ
部材については、炎症反応は低く、２週間以降も低く推
移した。また、カフ部材を設置することにより２週間以
降、カフ部材自身が良く褶曲した太いコラーゲン束とそ
の間隙に侵入した線維芽細胞と毛細血管等よりなる真皮
様組織に置換されており、更に濃度８．０w/v％のコラ
ーゲン溶液を用いる、あるいは濃度４．０w/v％のコラ
ーゲン溶液を用い圧縮による体積減少を行うことにより
密度を向上させると真皮様組織も増加した。[Table 2] (Example 6) Using the collagen solution having a concentration of 8.0 w / v% obtained in Example 3, a total length of 10 mm, an inner diameter of 4.3 mm,
Using a cuff member made of a collagen porous tubular body having a thickness of 2.0 mm and the collagen solution having a concentration of 4.0 w / v% obtained in Example 2, the volume was reduced by compression to a total length of 10 m.
A cuff member made of a collagen porous tubular body having a diameter of 4.3 m and an inner diameter of 4.3 mm and a wall thickness of 2.0 mm and a collagen solution having a concentration of 4.0 w / v% were used. An evaluation experiment was carried out using a silicone tube provided with a cuff member made of a 3 mm, 2.0 mm thick collagen porous tubular body and a silicone tube not provided with a cuff member. A scalpel was placed in the back of the rat, and a silicone tube with a cuff member and a silicone tube without a cuff member were implanted subcutaneously. After 2, 4, and 12 weeks, tissues around the tube were evaluated. Two weeks after the tube was implanted, a high inflammatory reaction was observed at the tube interface where the cuff member was not installed. Although the inflammatory reaction was suppressed at the tube interface where the cuff member was installed compared to the tube interface where the cuff member was not installed, the volume was reduced by compression using a collagen solution having a concentration of 4.0 w / v%. A relatively high inflammatory response was seen for the unfilled cuff members. Regarding the cuff member using a collagen solution having a concentration of 8.0 w / v% and the cuff member using a collagen solution having a concentration of 4.0 w / v% and reducing the volume by compression, the inflammatory reaction was low and even after 2 weeks. It remained low. By installing the cuff member, after 2 weeks, the cuff member itself has been replaced by a well-folded thick collagen bundle and a dermis-like tissue consisting of fibroblasts and capillaries that have penetrated into the gap, and a concentration of 8%. The dermis-like tissue also increased when the density was improved by using a collagen solution at a concentration of 4.0 w / v% or reducing the volume by compression using a collagen solution having a concentration of 4.0 w / v%.
【発明の効果】以上説明したように、本発明のカフ部材
は、線維芽細胞が浸潤し、自己のコラーゲンが生成され
生体組織に置換される。これにより、カテーテルの周辺
の生体組織をカテーテルの周囲に十分密集させることが
できる。特にカフ部材が表皮下に位置されカテーテルの
経皮部付近の生体組織をカテーテルの周囲に密集させる
ことができるので、ダウングロースが深くなるのを防止
することができる。また、コラーゲンを主材料とするカ
フ部材に線維芽細胞が浸潤し、自己のコラーゲンが生成
され生体組織に置換させることができる。さらに早期に
生体組織のカテーテル本体への密集を達成するものであ
る。本発明はさらに、カテーテル本体の外周に沿って軸
方向に移動可能であり、前記皮下トンネル部の任意の位
置に導入、設置することができることを特徴とする前記
カフ部材である。これにより、カテーテルの皮下トンネ
ル穿刺の際に、カフ部材を装着し、カテーテル中間部延
出側体内の任意の位置に設置することが可能である。本
発明のカフ部材は腹腔内留置カテーテル留置手術の際、
カフ部材の装着されたカテーテルを皮下トンネルに通す
ときに、より抵抗を受けずに作業を行うことができる。As described above, the cuff member of the present invention is infiltrated by fibroblasts, generates its own collagen, and is replaced by living tissue. Thereby, the living tissue around the catheter can be sufficiently densely packed around the catheter. In particular, since the cuff member is located under the epidermis and the living tissue near the percutaneous portion of the catheter can be concentrated around the catheter, it is possible to prevent downgrowth from becoming deep. In addition, fibroblasts infiltrate the cuff member mainly composed of collagen, and self-collagen is generated and can be replaced with living tissue. Further, it is possible to achieve the concentration of the living tissue on the catheter body earlier. The cuff member according to the present invention is further characterized in that the cuff member is movable in the axial direction along the outer periphery of the catheter body and can be introduced and installed at an arbitrary position in the subcutaneous tunnel portion. Thus, when the catheter is punctured in the subcutaneous tunnel, it is possible to attach the cuff member and to install the cuff member at an arbitrary position in the catheter intermediate portion extension side body. The cuff member of the present invention, in the case of indwelling catheter indwelling abdominal cavity,
When the catheter with the cuff member is passed through the subcutaneous tunnel, the operation can be performed with less resistance.
───────────────────────────────────────────────────── フロントページの続き Ｆターム(参考） 4C077 AA06 BB01 CC09 DD22 FF04 KK09 PP05 4C081 AC08 AC09 AC15 BA13 BA14 BB01 BB04 BB07 BC02 CB041 CC04 CD121 CD131 DA03 DA12 EA02 EA03 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C077 AA06 BB01 CC09 DD22 FF04 KK09 PP05 4C081 AC08 AC09 AC15 BA13 BA14 BB01 BB04 BB07 BC02 CB041 CC04 CD121 CD131 DA03 DA12 EA02 EA03
Claims (2)
の皮下トンネル部に用いるカフ部材であって、コラーゲ
ンを主成分とし、密度が０，０５ｇ／ｃｍ３以上で、湿
潤状態での体積変化率の最大が１００％以上であること
を特徴とするカフ部材。1. A cuff member for use in a subcutaneous tunnel of an intraperitoneal indwelling catheter, comprising collagen as a main component, a density of 0.05 g / cm 3 or more, and a volume change in a wet state. A cuff member having a maximum rate of 100% or more.
特徴とする請求項１記載のカフ部材2. The cuff member according to claim 1, wherein the outer diameters of both ends of the cuff member are different.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31118799A JP2001129076A (en) | 1999-11-01 | 1999-11-01 | Cuff member for intra-abdominal indwelling catheter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31118799A JP2001129076A (en) | 1999-11-01 | 1999-11-01 | Cuff member for intra-abdominal indwelling catheter |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001129076A true JP2001129076A (en) | 2001-05-15 |
Family
ID=18014150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP31118799A Pending JP2001129076A (en) | 1999-11-01 | 1999-11-01 | Cuff member for intra-abdominal indwelling catheter |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2001129076A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003082366A1 (en) * | 2002-03-28 | 2003-10-09 | Japan As Represented By President Of National Cardiovascular Center | Tissue engineering scaffold material, aritficial vessel, cuff member and coating for implants |
| WO2005084742A1 (en) * | 2004-03-08 | 2005-09-15 | Japan As Represented By President Of National Cardiovascular Center | Cuff member |
-
1999
- 1999-11-01 JP JP31118799A patent/JP2001129076A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003082366A1 (en) * | 2002-03-28 | 2003-10-09 | Japan As Represented By President Of National Cardiovascular Center | Tissue engineering scaffold material, aritficial vessel, cuff member and coating for implants |
| WO2005084742A1 (en) * | 2004-03-08 | 2005-09-15 | Japan As Represented By President Of National Cardiovascular Center | Cuff member |
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