JPS6210663B2 - - Google Patents
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- Publication number
- JPS6210663B2 JPS6210663B2 JP51132301A JP13230176A JPS6210663B2 JP S6210663 B2 JPS6210663 B2 JP S6210663B2 JP 51132301 A JP51132301 A JP 51132301A JP 13230176 A JP13230176 A JP 13230176A JP S6210663 B2 JPS6210663 B2 JP S6210663B2
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- JP
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- Prior art keywords
- artificial organ
- container
- artificial
- organ according
- partition wall
- 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.)
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Landscapes
- External Artificial Organs (AREA)
Description
本発明は熱滅菌可能な人工臓器に関する。さら
に詳しくは所望の熱滅菌に供し得る人工臓器、た
とえば熱滅菌中空糸型人工腎臓を提供するもので
ある。
近年、人体の臓器の機能を代行または補助する
人工臓器の発達が著しく、とりわけ人工腎臓、人
工肺臓等が広く普及してきた。人工腎臓は透析に
よる血液中老廃物の処理液への除去と、過剰水の
限外過をもつて生体腎臓能を代行するものであ
る。有効膜面積の割に小型で使い易い中空糸型人
工腎臓が今後の主流機種と見做されている。
中空糸型人工腎臓に代表される人工臓器は、体
外血液循環回路を通じて生体と接続する為に以下
の条件を満足しなければならない。
すなわち、
第1に毒物および発熱物質を含まないこと。
第2に無菌であること。
第3に血液流路中および処理液流路中に漏れ、
閉鎖および滞流が生じないこと。
第4に所期の性能、たとえば老廃物および水の
除去性能を持つこと。
第5に血液流路に血液を置換するに際して洗浄
準備が容易であること。
等である。
従来の人工腎臓はホルマリン、エチレンオキサ
イドガス、または放射線にて滅菌されている。ホ
ルマリン滅菌は1〜5%ホルムアルデヒド水溶液
を人工腎臓に充填して行なうが、滅菌力が強い反
面、その残留毒性が問題とされ、洗浄準備に要す
る生理的食塩水が多く時間がかかるという欠点を
有する。エチレンオキサイドガス滅菌は10〜27%
エチレンオキサイドガス雰囲気下に人工腎臓を置
いて行なうが、エチレンオキサイドおよびその誘
導体の残留毒性、乾燥状態からの洗浄時における
気泡抜および性能の再現性に問題がある。放射線
滅菌は人工腎臓へ0.5〜5Mradのガンマ線を照射
して行ない残留毒性の心配がないが、人工腎臓部
材とりわけ膜の劣化およびガス滅菌に類した洗浄
時の問題がある。
滅菌法としては、他に熱滅菌があり、第9改正
日本薬局方には、高圧蒸気滅菌法として115℃、
30分間:121℃、20分間および126℃、15分間の飽
和水蒸気中での加熱により微生物を殺滅する方法
を規定している。
さらに80〜100℃の水中または流通水蒸気下で
24時間毎に1回30〜60分間ずつ3〜5回の加熱を
行なう間歇滅菌法も規定されている。
熱滅菌は残留毒性がなく、洗浄容易という利点
を有する。
しかしながら、熱滅菌人工腎臓および人工臓器
は現在まで開発されていなかつた。開発が困難な
最大の理由は、人工臓器部材自体が熱滅菌に耐え
得ないことであり、部材の変形、破壊およびシー
ル不良により、血液流路および処理液流路の保全
ができないことである。
第2の理由は性能の熱劣化である。
本発明者は熱滅菌使用の人工臓器を開発すべく
鋭意研究の結果、熱滅菌するに際して、滅菌時に
おける加熱により部材の変形、破壊がなく血液流
路等を保全できる人工臓器を下記する如き手順で
開発し、本発明に到達したものである。
すなわち、第1に人工臓器に用いる各部材とし
て40〜130℃の範囲内で実質的に耐熱性を有する
素材の選択を行なつた。本発明における耐熱性は
実質的なものであり、後述するように文献上の耐
熱性、とくに熱変形温度より高いものである。
第2に実質的に、耐熱性を高めるように静水圧
下で熱滅菌加熱処理を行ない、たとえ部材が軟化
し始めても局部応力がかからないようにし、
第3に各部材間の加熱時の熱膨張による相互作
用を検討し、加熱後の状態で血液流路および処理
液流路のシールが完全に保全される構成を考案し
た。
すなわち、本発明は中空糸、隔壁および容器か
ら構成される中空糸型人工臓器において、該中空
糸、該隔壁および該容器が40〜130℃の範囲で実
質的に耐熱性を有し、該隔壁部材の線膨張係数a
〔1/℃〕が40〜130℃の範囲で、該容器部材の該
係数b〔1/℃〕および温度t〔℃〕の間に次式
の関係を有すること、
(4.13×10-5)e0.00769t≦a≦2b
および該隔壁部材が50〜120℃の範囲で二次転移
しないことを特徴とする熱滅菌使用の人工臓器で
ある。
本発明の人工臓器は第1図に示すように中空糸
1容器2および隔壁3から構成される。なお容器
のうち、血液分配部位4および集合部位5は血液
との適合性により該容器部材と異なる部材を用い
てもよい。第2図の例で、分配および集合部位に
おいて、他部材間の加熱時の熱膨張による相互作
用を著しく受けない場合は、該分配および集合部
材は上記構成条件の適用外である。
本発明の人工臓器において、中空糸はセルロー
ス、セルロースエステル、ポリアクリルニトリ
ル、ポリビニルアルコールおよびポリ芳香族酸ア
ミド、ポリカーボネート、ポリエーテル等を用い
ることができる。いずれの場合も中空糸製膜過程
において剛直な網目構造を形成し、加熱時の膜の
緻密化に対する耐性を強めることが必要である。
換言すれば、膜性能の熱劣化を最小限におさえる
耐熱性を付与することである。セルロース中空糸
に関しては、本発明者等は特開昭50―46921号お
よび特開昭50―70611号においてセルロースエス
テルの熱水処理および高温鹸化再生による真円性
および透過性能の優れた中空糸膜を得る方法を開
示している。この中空糸は製膜過程にて65〜98℃
の熱履歴を受けていて、耐熱性が優れている。他
の高分子中空糸は湿式紡糸により製膜するが、凝
固浴および/または洗浄精練浴を高温にすること
により耐熱性を付与できる。130℃近傍で中空糸
を加熱すると膜性能劣化がみられるが、人工臓器
として所定の性能に組立て得る場合は実質的に耐
熱性を有しているものを使う。耐熱セルロース中
空糸の130℃における性能維持率は90〜98%であ
つた。特に、中空糸素材としてはセルロース、ポ
リアクリルニトリルおよびポリ芳香族酸アミド、
たとえばポリアミドベンツヒドラジドイソフタル
アミド等が耐熱性が優れ、中空糸膜としても好ま
しい。
本発明の人工臓器において、容器部材としては
第1表に示すポリカーボネート、ポリ―4―メチ
ルペンテン―1、ポリビニリデンフルオライドお
よびポリアセタールが40〜130℃の範囲で実質的
に耐熱性を有するものである。他にポリスルホ
ン、ポリアリレート等も挙げることができる。比
較として、スチレン・アクリロニトリルコポリマ
ー、ポリメチルメタアクリレート等が実質的に耐
熱性を有しないものである。特に、透明度の高い
ポリカーボネート、ポリ―4―メチルペンテン―
1が血液を処理する人工臓器の部材として好まし
い。
また、ポリカーボネートおよびポリ―4―メチ
ルペンテン―1の40〜130℃における比容を測定
し、これから求めた線膨張係数を第2表に示し
た。これらの測定はASTM D864に準じて高分子
実験学講座7「高分子材料試験法」共立出版
(1961)によつた。
第1図に示す人工臓器装置において、中空糸と
隔壁とのシール、すなわち血液流路のシールは両
者の可撓性と、中空糸の湿潤膨張傾向により加熱
中および加熱後においても保持される。一方、容
器と隔壁とのシールすなわち処理液流路のシール
は加熱時の両者の熱膨張による相互作用により、
大きく影響される。理想的には容器部材と隔壁部
材が同一の熱膨張挙動を示せばよい訳であるが、
第2表に示すように容器の熱膨張係数は温度に依
存し、高温の方が大きい。これと全く同一熱膨張
挙動を示す隔壁部材を見出すことは至難なことで
ある。そこで本発明者らは鋭意研究の結果、下記
の事実を見出し、冒頭の課題を解決するに至つ
た。
第1に40〜130℃の範囲で該隔壁部材の熱膨張
が該容器部材の熱膨張に対し高々2倍で、ほぼ同
程度かむしろ小さいことである。この事実は意外
で、「内側の隔壁の方がより大きく熱膨張して外
側の容器に密着していつた方が両者間のシールが
保てるであろう。」と言う我々の常識に反してい
た。事実は、隔壁部材の熱膨張が容器の熱膨張よ
り大きい場合、加熱時に該隔壁部材が容器から膨
張をおさえるように応力を受け、クリープしてし
まい、降温後クリープした分だけ間隙が空きシー
ルが保たれないという結果を呈した。または容器
が隔壁の膨張により応力を受け破壊するに至つ
た。一方、隔壁部材の熱膨張が容器の熱膨張より
小さい場合は昇温により加熱時に微妙な間隙が空
くとしても、両者とも自由に熱膨張し、そして降
温後再び嵌合してシールを復活し、結果として血
液流路等を保全することができる。
第2には該隔壁部材が25〜130℃で5×10-5〜
1.1×10-4〔1/℃〕程度の線膨張係数以上を有
することで、これ以下だと、容器との係合を維持
し難い。
第3に該隔壁部材が50〜120℃の範囲で二次転
移しないことである。二次転移に際して熱膨張係
数が不連続に変化し、先の2条件を満足できない
場合があり、さらに昇温および降温時に2回の転
移を受けることは、隔壁の寸法再現性に大きな支
障を与える。
しかしながら、二次転移が40〜49℃および121
〜130℃で起るならば、その影響は少なく許容で
き得る。
実施例で隔壁に用いたウレタン樹脂およびエポ
キシ樹脂の比容を測定した。後者は124℃で二次
転移した。これらの樹脂はポリカーボネートおよ
びポリ―4―メチルペンテン―1の容器に対して
上記の3条件を満足する。第2表にこれらの樹脂
の耐熱性および線膨張係数を示すが、これらは40
〜130℃の範囲で実質的に耐熱性を有する。
隔壁部材として用いることのできる素材は高分
子重合体が好ましい。高分子重合体の中では2種
以上の成分、すなわちプレポリマー1種以上およ
び硬化剤等から付加重合により重合および架橋
し、全質量が実質的に変化しない重合体が好まし
い。これは組立において、隔壁をプレポリマー等
を注入して鋳型するに際して副産物が生成しない
こと、および希釈剤ないし溶剤が含有せず、加熱
時に蒸発消失して体積収縮するおそれがないこと
である。
このような重合体としては、ウレタン樹脂およ
びエポキシ樹脂を挙げることができる。ウレタン
樹脂の中では末端がイソシアネートで終るプレポ
リマーと水酸基をもつ脂肪酸とグリセリンのエス
テル等からなるポリオールとを付加重合するポリ
(エステル型ウレタン)が好ましい。
ポリ(エステル型ウレタン)については機械的
強度、硬度および耐熱性が優れている。一方エポ
キシ樹脂は末端がエポキシ基で終るプレポリマー
と末端がアミノ基で終るアミン硬化剤、または酸
無水物硬化剤とを付加重合するものが機械的強
度、硬度および耐熱性の点で優れている。低膨張
の隔壁部材、たとえば無機充填剤入ポリエステル
樹脂(a=3×10-5/℃)を用いたポリカーボネ
ート容器を加熱処理したところ、容器との係合を
維持できず、シール不良となつた。
本発明の如く構成した人工臓器を公知の方法に
より組立て、熱滅菌処理を行ない、熱滅菌人工臓
器を製造することができる。即ち、水または生理
食塩水を充填したタイプおよび充填しないタイプ
について高圧蒸気滅菌を施すことである。本発明
の効果は、熱滅菌加熱により部材の変形、破壊お
よびシール不良等が生ぜず、血液流路および処理
液流路保全ができることである。その結果、中空
糸の耐熱性と相まつて、優れた性能を発現でき
る。総体として、熱滅菌人工臓器は無菌であり、
残留毒性の危険はなく、洗浄準備が容易であり、
人工透折等の治療に寄与すること大である。
本発明の人工臓器とは人工腎臓に限らず、人工
肺臓(酸素供給)、人工肝臓(毒物除去)、および
人工膵臓(血中糖濃度に応じてインシユリンの供
給)等を挙げることができる。また中空糸を用い
ない、たとえば平膜型および吸着型等の人工臓器
においても容器と隔壁がある構成において、本発
明と同様な熱滅菌人工臓器としての改良がなしう
ることは言うまでもない。
The present invention relates to an artificial organ that can be heat sterilized. More specifically, the present invention provides an artificial organ that can be subjected to desired heat sterilization, such as a heat-sterilized hollow fiber artificial kidney. 2. Description of the Related Art In recent years, artificial organs that substitute or assist the functions of human organs have developed significantly, and in particular, artificial kidneys, artificial lungs, etc. have become widespread. Artificial kidneys replace the functions of living kidneys by removing waste products from the blood into a treatment solution through dialysis and by ultrafiltration of excess water. Hollow fiber artificial kidneys, which are small and easy to use in relation to their effective membrane area, are considered to be the mainstream model in the future. Artificial organs, such as hollow fiber artificial kidneys, must satisfy the following conditions in order to be connected to a living body through an extracorporeal blood circulation circuit. That is, first, it must not contain toxic substances or pyrogens. Second, it must be sterile. Third, leakage into the blood flow path and processing liquid flow path;
No blockages or backlogs will occur. Fourth, it must have the desired performance, such as the ability to remove waste products and water. Fifth, cleaning preparations are easy when replacing blood in the blood flow path. etc. Conventional artificial kidneys are sterilized with formalin, ethylene oxide gas, or radiation. Formalin sterilization is performed by filling an artificial kidney with a 1-5% formaldehyde aqueous solution, but while it has strong sterilizing power, its residual toxicity is a problem, and the disadvantage is that it requires a lot of physiological saline solution to prepare for cleaning, which is time-consuming. . Ethylene oxide gas sterilization is 10-27%
Although the artificial kidney is placed in an ethylene oxide gas atmosphere, there are problems with residual toxicity of ethylene oxide and its derivatives, air bubble removal during cleaning from a dry state, and reproducibility of performance. Radiation sterilization is performed by irradiating the artificial kidney with gamma rays of 0.5 to 5 Mrad, and there is no concern about residual toxicity, but there are problems with deterioration of the artificial kidney components, especially membranes, and cleaning problems similar to gas sterilization. Other sterilization methods include heat sterilization, and the 9th edition of the Japanese Pharmacopoeia states that high-pressure steam sterilization at 115℃,
Specifies a method for killing microorganisms by heating in saturated steam for 30 minutes: 121℃ for 20 minutes and 126℃ for 15 minutes. Furthermore, in water at 80-100℃ or under flowing steam
An intermittent sterilization method in which heating is performed three to five times for 30 to 60 minutes each time every 24 hours is also prescribed. Heat sterilization has the advantage of no residual toxicity and easy cleaning. However, heat-sterilized artificial kidneys and organs have not been developed to date. The main reason why development is difficult is that the artificial organ components themselves cannot withstand heat sterilization, and the blood flow path and treatment liquid flow path cannot be maintained due to deformation, destruction, and poor sealing of the components. The second reason is thermal deterioration of performance. As a result of intensive research to develop an artificial organ that can be heat sterilized, the inventor of the present invention has developed an artificial organ that can maintain the blood flow path without deforming or destroying the parts due to heat during sterilization. The present invention was achieved through the development of this method. That is, firstly, materials that are substantially heat resistant within the range of 40 to 130° C. were selected for each member used in the artificial organ. The heat resistance in the present invention is substantial, and as described later, it is higher than the heat resistance in the literature, especially the heat distortion temperature. Second, heat sterilization heat treatment is performed under hydrostatic pressure to substantially increase heat resistance, so that local stress is not applied even if the component begins to soften; and third, thermal expansion during heating between each component. After considering the interaction between the two, we devised a configuration that completely maintains the seals of the blood flow path and processing liquid flow path after heating. That is, the present invention provides a hollow fiber type artificial organ composed of a hollow fiber, a partition wall, and a container, wherein the hollow fiber, the partition wall, and the container have substantially heat resistance in the range of 40 to 130°C; Linear expansion coefficient a of the member
[1/°C] is in the range of 40 to 130°C, and the coefficient b [1/°C] and temperature t [°C] of the container member have the following relationship: (4.13×10 -5 ) The present invention is an artificial organ for use in heat sterilization, characterized in that e 0 . The artificial organ of the present invention is composed of a hollow fiber 1 container 2 and a partition wall 3 as shown in FIG. Note that in the container, the blood distribution part 4 and the collection part 5 may be made of different members from the container member depending on their compatibility with blood. In the example of FIG. 2, if the distribution and gathering parts are not significantly affected by the interaction between other members due to thermal expansion during heating, the above configuration conditions do not apply to the distribution and gathering parts. In the artificial organ of the present invention, the hollow fibers can be made of cellulose, cellulose ester, polyacrylonitrile, polyvinyl alcohol, polyaromatic acid amide, polycarbonate, polyether, or the like. In either case, it is necessary to form a rigid network structure in the hollow fiber membrane forming process to strengthen the membrane's resistance to densification during heating.
In other words, it is to provide heat resistance that minimizes thermal deterioration of membrane performance. Regarding cellulose hollow fibers, the present inventors have developed hollow fiber membranes with excellent circularity and permeability through hydrothermal treatment and high-temperature saponification regeneration of cellulose ester in Japanese Patent Application Laid-open Nos. 50-46921 and 1977-70611. discloses how to obtain it. This hollow fiber is heated at 65 to 98℃ during the membrane forming process.
It has undergone a thermal history of Other polymer hollow fibers are formed by wet spinning, but heat resistance can be imparted by raising the temperature of the coagulation bath and/or washing and scouring bath. When hollow fibers are heated to around 130°C, membrane performance deteriorates, but if it can be assembled to the desired performance as an artificial organ, use one that is substantially heat resistant. The performance retention rate of the heat-resistant cellulose hollow fibers at 130°C was 90-98%. In particular, hollow fiber materials such as cellulose, polyacrylonitrile and polyaromatic acid amide,
For example, polyamide benzhydrazide isophthalamide has excellent heat resistance and is preferred as a hollow fiber membrane. In the artificial organ of the present invention, the container members include polycarbonate, poly-4-methylpentene-1, polyvinylidene fluoride, and polyacetal shown in Table 1, which have substantial heat resistance in the range of 40 to 130°C. be. Other examples include polysulfone and polyarylate. For comparison, styrene/acrylonitrile copolymer, polymethyl methacrylate, etc. have substantially no heat resistance. In particular, highly transparent polycarbonate, poly-4-methylpentene
1 is preferable as a member of an artificial organ that processes blood. Further, the specific volumes of polycarbonate and poly-4-methylpentene-1 at 40 to 130°C were measured, and the coefficients of linear expansion determined therefrom are shown in Table 2. These measurements were carried out in accordance with ASTM D864 according to Polymer Experimental Science Course 7, "Polymer Materials Testing Methods", Kyoritsu Shuppan (1961). In the artificial organ device shown in FIG. 1, the seal between the hollow fiber and the septum, ie, the seal of the blood flow path, is maintained during and after heating due to the flexibility of both and the tendency of the hollow fiber to expand due to moisture. On the other hand, the seal between the container and the partition wall, that is, the seal of the processing liquid flow path, is caused by interaction due to thermal expansion between the two during heating.
greatly affected. Ideally, the container member and the partition wall member should exhibit the same thermal expansion behavior, but
As shown in Table 2, the coefficient of thermal expansion of the container depends on the temperature, and is larger at higher temperatures. It is extremely difficult to find a partition wall member that exhibits exactly the same thermal expansion behavior. As a result of intensive research, the present inventors discovered the following facts and came to solve the problem mentioned above. First, in the range of 40 to 130°C, the thermal expansion of the partition member is at most twice the thermal expansion of the container member, and is approximately the same or even smaller. This fact was surprising and went against our common sense that ``If the inner partition wall expands more thermally and comes into close contact with the outer container, the seal between the two will be better maintained.'' The fact is that if the thermal expansion of the partition wall member is larger than that of the container, the partition wall member will receive stress from the container during heating to suppress the expansion, and will creep, and after the temperature cools down, a gap will be created by the amount of creep, and the seal will fail. The result was that it was not maintained. Alternatively, the container was subjected to stress due to the expansion of the partition wall, leading to its destruction. On the other hand, if the thermal expansion of the partition wall member is smaller than that of the container, even if a slight gap is created during heating due to temperature rise, both will thermally expand freely, and after the temperature cools down, they will fit again and restore the seal. As a result, the blood flow path etc. can be maintained. Secondly, the partition wall member has a temperature of 5×10 -5 to 25 to 130°C.
It has a linear expansion coefficient of about 1.1×10 -4 [1/°C] or more; if it is less than this, it is difficult to maintain engagement with the container. Thirdly, the partition wall member does not undergo secondary transition in the temperature range of 50 to 120°C. During the secondary transition, the coefficient of thermal expansion changes discontinuously, and the above two conditions may not be satisfied.Furthermore, undergoing the transition twice when the temperature is raised and lowered greatly impedes the dimensional reproducibility of the partition wall. . However, the secondary transition occurs at 40–49 °C and 121 °C.
If it occurs at ~130°C, the effect is small and can be tolerated. The specific volumes of the urethane resin and epoxy resin used for the partition walls in the examples were measured. The latter underwent a secondary transition at 124°C. These resins satisfy the above three conditions for polycarbonate and poly-4-methylpentene-1 containers. Table 2 shows the heat resistance and linear expansion coefficient of these resins, which are 40
Substantially heat resistant in the range of ~130°C. The material that can be used as the partition member is preferably a high molecular weight polymer. Among high-molecular polymers, preferred are polymers that are polymerized and crosslinked by addition polymerization from two or more components, ie, one or more prepolymers, a curing agent, etc., and whose total mass does not substantially change. This is because no by-products are generated when the partition wall is injected with a prepolymer or the like and molded during assembly, and because it does not contain a diluent or solvent, there is no risk of volumetric shrinkage due to evaporation during heating. Such polymers include urethane resins and epoxy resins. Among urethane resins, poly(ester type urethane) is preferable, which is obtained by addition polymerizing a prepolymer whose terminal end is an isocyanate, a polyol consisting of a fatty acid having a hydroxyl group, and an ester of glycerin, or the like. Poly(ester urethane) has excellent mechanical strength, hardness and heat resistance. On the other hand, epoxy resins that are produced by addition polymerization of a prepolymer whose terminal end is an epoxy group and an amine curing agent or an acid anhydride curing agent whose terminal end is an amino group are superior in terms of mechanical strength, hardness, and heat resistance. . When we heat-treated a polycarbonate container using a low-expansion partition member, such as a polyester resin containing an inorganic filler (a = 3 x 10 -5 /°C), we were unable to maintain engagement with the container, resulting in a seal failure. . A heat-sterilized artificial organ can be manufactured by assembling the artificial organ constructed as in the present invention by a known method and performing heat sterilization treatment. That is, high-pressure steam sterilization is applied to types filled with water or physiological saline and types not filled. The effect of the present invention is that the heat sterilization heating does not cause deformation, destruction, or seal failure of members, and the blood flow path and processing liquid flow path can be maintained. As a result, combined with the heat resistance of the hollow fibers, excellent performance can be achieved. Overall, heat-sterilized artificial organs are sterile;
There is no risk of residual toxicity, easy preparation for cleaning,
This will greatly contribute to treatments such as artificial fluoroscopy. The artificial organ of the present invention is not limited to an artificial kidney, but may include an artificial lung (oxygen supply), an artificial liver (poison removal), an artificial pancreas (insulin supply according to blood sugar concentration), and the like. It goes without saying that even in artificial organs that do not use hollow fibers, such as flat membrane type and adsorption type, which have a container and a partition, improvements as heat sterilized artificial organs similar to the present invention can be made.
【表】【table】
【表】
(注1) 桜内雄二郎著「プラスチツク材料読
本」工業調査会(1973),ASTM D696
(注2) 実測値 ASTM D864
(注3) 耐熱性 88―121℃
(注4) 耐熱性 121―149℃
以下実施例および比較例を挙げ本発明をより詳
細に説明する。
実施例 1
第2図右半に示すような構成の中空糸型人工臓
器を、耐熱セルロース中空糸(内径250μ、膜厚
30μ)を10000本集束し、ポリカーボネート〔パ
ンライト(登録商標)L―1250〕製容器内に収納
し、両端をポリ(エステル型ウレタン)樹脂〔ハ
イゾル(Hysol)(登録商標)ES4003〕に埋め込
み隔壁を鋳型し、血液分配、集合板を取付け、除
菌気流下で組立た。
血液室および透析処理液室に蒸留水を充填し水
の熱膨張を緩衝する手段を講じて静水圧下で所定
の熱滅菌処理を行なつた。
第3表に示すごとく、本発明の人工臓器は外観
およびシール性が良好で、中空糸のリークもな
く、性能が優れたものであつた。無菌試験の結果
はすべてマイナスであり、生物学試験も合格し、
人工腎臓として臨床に供し得るものであつた。
さらに、50個の製品につき同様な熱滅菌を行な
い、中空糸のリークの発生の有無をみたがリーク
発生品は皆無であつた。[Table] (Note 1) Yujiro Sakurauchi, “Plastic Material Reader” Kogyo Kenkyukai (1973), ASTM D696 (Note 2) Actual value ASTM D864 (Note 3) Heat resistance 88-121℃ (Note 4) Heat resistance 121 -149°C The present invention will be explained in more detail with reference to Examples and Comparative Examples. Example 1 A hollow fiber type artificial organ having the structure shown in the right half of Fig.
30μ) and stored in a container made of polycarbonate [Panlite (registered trademark) L-1250], and both ends were embedded in poly(ester-type urethane) resin [Hysol (registered trademark) ES4003] with a partition wall. A mold was made, blood distribution and collection plates were attached, and the assembly was carried out under a sterilizing air stream. A predetermined heat sterilization process was performed under hydrostatic pressure by filling the blood chamber and the dialysate chamber with distilled water to buffer the thermal expansion of the water. As shown in Table 3, the artificial organ of the present invention had good appearance and sealing performance, no leakage from the hollow fibers, and excellent performance. All sterility test results were negative, and the biological test was also passed.
The device could be used clinically as an artificial kidney. Furthermore, 50 products were subjected to similar heat sterilization to check for leakage from the hollow fibers, but no leakage occurred.
【表】
実施例 2
第2図右半に示すような構成の中空糸型人工臓
器を、耐熱ポリアクリルニトリル中空糸(内径
450μ、膜厚75μ)を5000本集束し、ポリカーボ
ネート製容器内に収納し、実施例1と同様にエポ
キシ樹脂〔主剤:三井鐘紡エポキシR―130、硬
化剤:UCC ZZL―0803;混合比6C:40〕にて隔
壁を鋳型し組立た。
実施例1と同様な充填、熱滅菌処理を行い、外
観、シール性、中空糸リーク、性能および無菌試
験においてすべて合格であつた。
比較例 1
第1図に示すような人工臓器試作品を、耐熱セ
ルロース中空糸を8000本集束し、不錆鋼線膨張係
数1×10-5/℃)製の容器およびパイレツク硝子
(線膨張係数0.3×10-5/℃)製の容器内に収納
し、実施例1、2に用いた樹脂にて隔壁を鋳型し
4組合せ各3個試作した。実施例1と同様な充
填、熱滅菌処理を行なつたところ、全部の試作品
の内7個がシール不良であつた。
実施例 3
ポリ―4―メチルペンテン―1〔TPX(登録
商標)〕製容器内に実施例1と容器以外、すべて
同じ条件で製品を20個組立た。熱滅菌後の外観、
シール性、性能および無菌試験においてすべて合
格であつた。中空糸のリークの発生は20個中皆無
であつた。
実施例 4
第1図に示すような構成の人工臓器試作品をポ
リ―4―メチルペンテン―1製容器内にエポキシ
樹脂隔壁を鋳型して組立た。熱滅菌処理を行ない
シールを確認したが漏れはなかつた。
実施例 5
実施例1と同様に中空糸型人工腎臓を組立てる
に際し、ポリエステル型ウレタンとして、プレポ
リマーにボライト689(Vorite:登録商標)及び
ポリオールにポリシン(Polycin)936を使用し
て、隔壁を鋳型した。このポリウレタンの線熱膨
張係数は2.5×10-4/℃であつた。人工臓器に生
理食塩液を充填したタイプ及びこの液を充填しな
いタイプの両者について高圧蒸気による熱滅菌処
理を施した。両者の人工臓器とも中空糸と隔壁、
隔壁と容器とのシール性は良好であつた。[Table] Example 2 A hollow fiber artificial organ having the structure shown in the right half of Figure 2 was fabricated using heat-resistant polyacrylonitrile hollow fibers (inner diameter
450μ, film thickness 75μ), and stored in a polycarbonate container, and in the same manner as in Example 1, epoxy resin [base material: Mitsui Kanebo Epoxy R-130, curing agent: UCC ZZL-0803; mixing ratio 6C: 40], the bulkhead was molded and assembled. Filling and heat sterilization were performed in the same manner as in Example 1, and the appearance, sealing performance, hollow fiber leakage, performance, and sterility tests all passed. Comparative Example 1 An artificial organ prototype as shown in Figure 1 was made by bundling 8000 heat-resistant cellulose hollow fibers into a container made of rust-free steel (linear expansion coefficient 1 x 10 -5 /℃) and Pyrex glass (linear expansion coefficient 0.3×10 −5 /° C.), partition walls were molded using the resin used in Examples 1 and 2, and three prototypes of each of four combinations were fabricated. When filling and heat sterilization were performed in the same manner as in Example 1, seven of the prototypes had poor sealing. Example 3 Twenty products were assembled in a container made of poly-4-methylpentene-1 [TPX (registered trademark)] under the same conditions as in Example 1 except for the container. Appearance after heat sterilization,
It passed all sealability, performance, and sterility tests. There were no leaks from the hollow fibers out of 20. Example 4 An artificial organ prototype having the configuration shown in FIG. 1 was assembled by molding an epoxy resin partition wall inside a container made of poly-4-methylpentene-1. I performed heat sterilization and checked the seal, but no leakage was found. Example 5 When assembling a hollow fiber artificial kidney in the same manner as in Example 1, the septum was molded using Vorite 689 (registered trademark) as the prepolymer and Polycin 936 as the polyol as the polyester urethane. did. The linear thermal expansion coefficient of this polyurethane was 2.5×10 −4 /°C. Heat sterilization treatment using high-pressure steam was applied to both types of artificial organs filled with physiological saline and types not filled with this liquid. Both artificial organs have hollow fibers and septa,
The sealing property between the partition wall and the container was good.
第1図および第2図は本発明の実施態様の縦断
面図である。第2図において右半分と左半分とは
異なつた態様を示してある。各図中の1〜9は
各々次のものを表わす。
1……中空糸、2……容器、3……隔壁、4…
…血液分配(または集合)部位、5……血液集合
(または分配)部位、6……血液導管、7……処
理液(または処理流体)導管、8……血液室、9
……処理液(または処理流体)室。
1 and 2 are longitudinal sectional views of an embodiment of the invention. In FIG. 2, the right half and left half show different aspects. 1 to 9 in each figure represent the following, respectively. 1... Hollow fiber, 2... Container, 3... Partition wall, 4...
... blood distribution (or collection) site, 5 ... blood collection (or distribution) site, 6 ... blood conduit, 7 ... processing liquid (or processing fluid) conduit, 8 ... blood chamber, 9
...Processing liquid (or processing fluid) chamber.
Claims (1)
糸型人工臓器において、該中空糸、該隔壁および
該容器が40〜130℃の範囲で実質的に耐熱性を有
し、該隔壁部材の線膨張係数a〔1/℃〕が40〜
130℃の範囲で該容器部材の該係数b〔1/℃〕
および温度t〔℃〕との間に次式の関係を有する
こと、 (4.13×10-5)e0.00769t≦a≦2b および該隔壁部材が50〜120℃の範囲で二次転移
しないことを特徴とする熱滅菌使用の人工臓器。 2 中空糸がセルロースである特許請求の範囲第
1項記載の人工臓器。 3 中空糸がポリアクリルニトリルである特許請
求の範囲第1項記載の人工臓器。 4 容器部材がポリカーボネートである特許請求
の範囲第1項記載の人工臓器。 5 容器部材がポリ―4―メチルペンテン―1で
ある特許請求の範囲第1項記載の人工臓器。 6 隔壁部材が高分子重合体である特許請求の範
囲第1項記載の人工臓器。 7 高分子重合体が2種以上の成分から付加重合
により重合および架橋し全質量が実質的に変化し
ない重合体である特許請求の範囲第6項記載の人
工臓器。 8 高分子重合体がウレタン樹脂である特許請求
の範囲第7項記載の人工臓器。 9 ウレタン樹脂がポリ(エステル型ウレタン)
である特許請求の範囲第8項記載の人工臓器。 10 高分子重合体がエポキシ樹脂である特許請
求の範囲第7項記載の人工臓器。[Claims] 1. A hollow fiber type artificial organ composed of a hollow fiber, a partition wall, and a container, wherein the hollow fiber, the partition wall, and the container have substantially heat resistance in the range of 40 to 130°C; The linear expansion coefficient a [1/℃] of the partition wall member is 40~
The coefficient b [1/°C] of the container member in the range of 130°C
and temperature t [°C], (4.13×10 -5 ) e 0 . An artificial organ that uses heat sterilization. 2. The artificial organ according to claim 1, wherein the hollow fibers are cellulose. 3. The artificial organ according to claim 1, wherein the hollow fibers are polyacrylonitrile. 4. The artificial organ according to claim 1, wherein the container member is made of polycarbonate. 5. The artificial organ according to claim 1, wherein the container member is poly-4-methylpentene-1. 6. The artificial organ according to claim 1, wherein the partition member is made of a high molecular weight polymer. 7. The artificial organ according to claim 6, wherein the high molecular weight polymer is a polymer that is polymerized and crosslinked by addition polymerization from two or more components and whose total mass does not substantially change. 8. The artificial organ according to claim 7, wherein the high molecular weight polymer is a urethane resin. 9 Urethane resin is poly(ester type urethane)
The artificial organ according to claim 8. 10. The artificial organ according to claim 7, wherein the high molecular weight polymer is an epoxy resin.
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP13230176A JPS5358194A (en) | 1976-11-05 | 1976-11-05 | Thermally sterilizing artificial organ |
US05/847,619 US4176156A (en) | 1976-11-05 | 1977-11-01 | Method for heat-sterilizing artificial kidneys |
GB46049/77A GB1575377A (en) | 1976-11-05 | 1977-11-04 | Method for heat-sterilizing artificial kidneys |
DE2749516A DE2749516C2 (en) | 1976-11-05 | 1977-11-04 | Process for heat sterilization of artificial kidneys |
FR7733367A FR2369846A1 (en) | 1976-11-05 | 1977-11-07 | PROCESS FOR STERILIZING ARTIFICIAL KIDNEYS BY HEAT |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP13230176A JPS5358194A (en) | 1976-11-05 | 1976-11-05 | Thermally sterilizing artificial organ |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5358194A JPS5358194A (en) | 1978-05-25 |
JPS6210663B2 true JPS6210663B2 (en) | 1987-03-07 |
Family
ID=15078086
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP13230176A Granted JPS5358194A (en) | 1976-11-05 | 1976-11-05 | Thermally sterilizing artificial organ |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5358194A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0329849A (en) * | 1989-06-28 | 1991-02-07 | Sumitomo Metal Ind Ltd | Method and apparatus for supplying contact medium for ultrasonic flaw detection |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5348395A (en) * | 1976-10-15 | 1978-05-01 | Terumo Corp | Method of sterilizing hollow yarn substance moving device |
-
1976
- 1976-11-05 JP JP13230176A patent/JPS5358194A/en active Granted
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5348395A (en) * | 1976-10-15 | 1978-05-01 | Terumo Corp | Method of sterilizing hollow yarn substance moving device |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0329849A (en) * | 1989-06-28 | 1991-02-07 | Sumitomo Metal Ind Ltd | Method and apparatus for supplying contact medium for ultrasonic flaw detection |
Also Published As
Publication number | Publication date |
---|---|
JPS5358194A (en) | 1978-05-25 |
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