JPS6246190B2 - - Google Patents
Info
- Publication number
- JPS6246190B2 JPS6246190B2 JP58085093A JP8509383A JPS6246190B2 JP S6246190 B2 JPS6246190 B2 JP S6246190B2 JP 58085093 A JP58085093 A JP 58085093A JP 8509383 A JP8509383 A JP 8509383A JP S6246190 B2 JPS6246190 B2 JP S6246190B2
- Authority
- JP
- Japan
- Prior art keywords
- membrane
- hollow fiber
- semipermeable membrane
- blood processing
- glycerin
- 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.)
- Expired
Links
- 239000012528 membrane Substances 0.000 claims description 93
- 239000012510 hollow fiber Substances 0.000 claims description 41
- 239000008280 blood Substances 0.000 claims description 39
- 210000004369 blood Anatomy 0.000 claims description 39
- 230000001954 sterilising effect Effects 0.000 claims description 26
- 229920002301 cellulose acetate Polymers 0.000 claims description 21
- 230000005855 radiation Effects 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 230000006866 deterioration Effects 0.000 claims description 15
- 230000021736 acetylation Effects 0.000 claims description 13
- 238000006640 acetylation reaction Methods 0.000 claims description 13
- 239000004014 plasticizer Substances 0.000 claims description 12
- 239000011148 porous material Substances 0.000 claims description 7
- 239000000470 constituent Substances 0.000 claims description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 58
- 235000011187 glycerol Nutrition 0.000 description 29
- 230000005251 gamma ray Effects 0.000 description 25
- 238000004659 sterilization and disinfection Methods 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 238000011282 treatment Methods 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 239000000463 material Substances 0.000 description 10
- 230000000704 physical effect Effects 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 7
- 210000003734 kidney Anatomy 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 150000002314 glycerols Chemical class 0.000 description 6
- 230000007423 decrease Effects 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000002510 pyrogen Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 229940105990 diglycerin Drugs 0.000 description 2
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000004388 gamma ray sterilization Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000003206 sterilizing agent Substances 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007705 chemical test Methods 0.000 description 1
- 239000011162 core material Substances 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 239000003779 heat-resistant material Substances 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000002615 hemofiltration Methods 0.000 description 1
- 239000011796 hollow space material Substances 0.000 description 1
- 238000007602 hot air drying Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920005749 polyurethane resin Polymers 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Description
＜技術分野＞
本発明は、血液透析、血液濾過などの血液処理
に用いられる、中空繊維半透膜を構成部材とする
血液処理器の放射線滅菌法に関する。
＜従来技術＞
半透膜を用いた医療用血液処理器としては形態
的には、平膜型、コイル型、中空繊維型があり、
効率の優れた中空繊維膜が近年主流を占めるよう
になつてきている。又機能的には透析処理、限外
濾過による、透析型人工腎臓、濾過型人工腎臓、
血漿分離器などがある。これら血液処理器は、血
液を直接、接触させて処理するものであり、従つ
て使用前には各種の滅菌処理がなされ、無菌性を
保持されていなければならない。
従来の滅菌法としては、旧くから使用されてい
るホルマリン水を充填する方法がある。ホルマリ
ンはその強い殺菌力のため、滅菌とという点では
充分であるが、透析前の洗浄による完全除去が難
かしくその残留性が、安全性という面で問題とな
つている。
又、医療用具の滅菌に汎用されるエチレンオキ
サイドガスを用いて血液処理器を乾燥状態で滅菌
する方法があるが、やはり滅菌剤を使用するため
にホルマリンと同様に、微量の滅菌剤の残留が安
全上問題である。
さらに滅菌剤を使用しない滅菌法としては、高
圧蒸気滅菌あるいはγ線照射滅菌法がある。高圧
蒸気滅菌は通常115〜121℃の飽和蒸気雰囲気下で
約20〜30分間処理をするため血液処理器を構成す
る部材類の耐熱性や半透膜の熱劣化について充分
注意する必要がある。現実には、耐熱性素材の選
択、半透膜の熱劣化の小さい、膜素材の限られた
組合せにのみにおいて実用化されている。又γ線
照射滅菌も滅菌剤という化学物質の殺菌力を用い
ない滅菌法であり滅菌剤の残留毒性という心配は
ないが、γ線による素材の分解・劣化が問題とな
る。半透膜の膜素材、膜構造あるいはγ線照射時
における膜の含水率等によつては、γ線照射によ
る半透膜の膜性能等の物性劣化が非常に大きい場
合がある。
即ち、人工腎臓に代表される血液処理器に用い
られる半透膜の素材としては、セルロース膜、セ
ルロースアセテート膜、合成膜糸等が実用化され
ているが、これらの膜素材は滅菌に必要なγ線量
の照射により、半透膜としての基本性能である溶
質透過性や限外濾過性能（除水能）が大巾に減少
し、又機械的物理的性質である強度、伸度等にも
大きな損傷を与えることが知られていた。
かかる問題点を回避するための方策の１つとし
て考え出されたのが、半透膜を水又は水溶液で前
もつて、実質的に含液状態とした後、γ線照射す
ることにより、半透膜の放射線による破壊劣化を
実用範囲内で回避しようとすることである。その
具体的方法としては、血液処理器に水又は水溶液
を充填後、γ線照射するため、血液処理器の最終
製品形態としては、いわゆるウエツトタイプであ
つた。このため血液処理器製造後、γ線照射処理
するまでの輸送、保管期間の間に、血液処理器内
に菌が存在すれば、増殖する可能性が高く最終製
品のパイロジエン発生等の危険性が極めて高かつ
た。
＜発明の目的＞
本発明は以上の技術的背景において成されたも
のであり、その目的とするところは、殺菌剤の残
留がなく安全性の高い優れた血液処理器の滅菌方
法を提供することである。本発明のもう１つの目
的は、セルロース系中空繊維半透膜を構成部材と
する血液処理器を、膜性能を保持したまま、実質
上乾燥状態で安定に放射線滅菌せしめる方法を提
供することである。本発明の他の目的は、パイロ
ジエン発生の危険性がなく、輸送が安易で、凍結
の危険性がない汎用性の高い血液処理器を提供す
ることである。
＜発明の構成＞
本発明者等は、前記の如き背景のもとで、かか
る目的を達成するために、実質的な乾燥状態で放
射線照射可能な中空繊維半透膜の素材の選定し、
膜性能を保持したまま安定に放射線滅菌を行なう
方法について鋭意研究を行なつた。すなわち本発
明者等は、半透膜として汎用されているセルロー
ス膜、セルロースアセテート膜、合成膜等の膜素
材と膜性能保持剤である可塑化剤との組合せを鋭
意研究した結果、意外にも酢化度20％以上のセル
ロースアセテート膜が放射線照射に対して非常に
安定であることを見い出し、本発明に到達した。
即ち本発明は、セルロースアセテートの中空繊
維半透膜を構成部材とする血液処理器を放射線照
射により滅菌するに際し、該セルロースアセテー
ト中空繊維半透膜に酸化度が20％以上であるセル
ロースアセテートを用い、該半透膜の細孔内に実
質的に水を含まない可塑化剤を放射線照射による
該半透膜の劣化を防止し得る範囲で付着せしめ、
且つ該血液処理器内を実質的に乾燥状態とし、該
乾燥状態を保持したままで該半透膜を劣化させな
い範囲の放射線量で放射線照射処理することを特
徴とする血液処理器の滅菌方法である。
以下、本発明についてさらに詳細に説明する。
本願発明いおける血液処理器の構成部材である中
空繊維半透膜は、酢化度が20％以上のセルロース
アセテート膜である。
本発明に言う酢化度とは、セルロースアセテー
トの重量に対するアセチル基の酢酸換算重量百分
率を意味する。
かかる酢化度が20％を境とし、それ未満では、
セルロースアセテート半透膜はセルロース膜の特
性を示し、可塑化剤であるグリセリンを充分付着
せしめても、放射線照射による性能低化、物性劣
化が起るのに対して、酢化度20％以上のセルロー
スアセテート半透膜では、適量の可塑化剤との共
存に於いて、放射線耐性が認められるのである。
本発明において、該セルロースアセテート半透
膜の酢化度が30〜61％の範囲にあれば、放射線耐
性がさらに良好であり、より安定に滅菌処理を行
なうことができる。
また本発明に言う血液処理器の実質的な乾燥状
態とは、該血液処理器内に実質的に水あるいは水
溶液が充填されておらず、且つ中空繊維半透膜が
実質的に乾燥状態にあることを意味する。
ここで言う中空繊維半透膜の実質的な乾燥状態
とは、該半透膜の膜厚部における細孔部分に実質
的に水を保有しないことを意味し、好ましくは実
質的に水を含まない可塑化剤を該細孔内に付着せ
しめること、即ち、該細孔部分の少なくとも１部
がその可塑化剤で満たされていることが望まし
い。
本発明における可塑化剤としては、グリセリン
が好適である。
かかる可塑化剤であるグリセリンの半透膜への
付着量の適正範囲は、半透膜の種類により異な
り、その細孔空孔率の比較的低い透析膜から、空
孔率の高い血漿分離膜まで、その飽和付着量によ
つて決定される。ここで膜厚細孔部分の全部がグ
リセリンで置換・充填された状態が飽和付着であ
り、その時のグリセリン量が飽和付着量である。
本発明における可塑化剤の好ましい付着量は、
実質上飽和付着量未満であつて、さらに好ましく
はセルロースアセテート中空繊維の乾燥重量に対
する可塑化剤の重量百分率で表わして、40〜200
％の範囲にある。
該付着量が40％以下では、放射線による膜劣化
を回避することが困難な場合がある。
また飽和付着量以上にグリセリンを付着させる
と過剰のグリセリンは、中空繊維半透膜の中空内
表面又は外表面に液滴状に点在し、中空繊維半透
膜の場合は、内表面のグリセリンが表面張力で凝
集し、中空繊維の中空部空間を部分的に閉塞させ
てしまう。このように飽和付着量以上のグリセリ
ンを付与した中空繊維半透膜は血液処理器に組み
立てた後、人工透析に先だつ通常のプライミング
操作で、生理食塩水等の水溶液を中空繊維の中空
部に通水しても、グリセリンの表面張力のため、
中空繊維束の全てに均一に通すことは、もはや困
難となるためグリセリン付着量の最大値は飽和付
着量以下に抑えることが望ましい。それ故グリセ
リン付着量の好ましい範囲の上限としては、血漿
分離等の最も空孔率の高い膜の場合の飽和付着量
に近い200％があげられる。
本発明において使用される放射線源としては、
60Co、137Cs、などのγ線が好ましく、総照射線
量としては1.5〜5.0Mradの範囲が滅菌安定性か
ら言つて好ましい。照射方法としては通常用いら
れるいかなる方法でもよい。
本発明の滅菌方法が適用できる血液処理器とし
ては、中空繊維半透膜を構成部材とした人工腎臓
あるいは血漿分離器等の血液処理器である。
尚本発明におけるセルロースアセテート中空繊
維半透膜は、前記した要件を満たし血液処理器の
構成部材として使用できるものであればいかなる
ものであつてもよい。更に本発明における血液処
理器を実質的に乾燥状態とする方法としては、い
かなる方法によつてもよい。
また一般に血液処理器の安全性、毒性について
は、血液と直接接触する半透膜が、γ線照射処理
後も無害であることはもちろん、間接的溶出物と
して抽出されるものが毒性を示してもいけない。
このような観点から本発明における血液処理器の
γ線未照射群及びγ線照射群について生物学試
験、溶出物理化学試験の比較検討を実施したが、
その結果両者間で差は認められず、両者とも厚生
省・透析型人工腎臓装置基準（案）に合格した。
さらに一般にはγ線照射により、素材物性は照
射後も経時的に劣化が進行することがあるので、
本発明における血液処理器について１年間のシエ
ルフライフテストを実施したが未照射群と照射群
では有意差はなくともに透析型人工腎臓装置基準
（案）に合格し、経時的にも安定であることを確
認した。この様に本発明の方法によつて得られる
血液処理器は安全性の点でも極めて優れたもので
ある。
＜発明の効果＞
以上詳記した如く、本発明はこれまで成し得な
かつたセルロース系中空繊維半透膜を構成部材と
する血液処理器を実質上乾燥状態で半透膜の特性
を適正に維持したままγ線照射滅菌することを可
能ならしめたものである。
かかる本発明によるγ線滅菌された実質的ドラ
イタイプ血液処理器の出現は、その効果として、
第１にEO滅菌ドライタイプの欠点である殺菌剤
の残留による副作用を解消し、第２にこれまでの
γ線滅菌ウエツトタイプに代つて、パイロジエン
発生の危険性がなく、操作性の優れた、輸送の容
易な、凍結の心配のない、より汎用性の高い血液
処理器の提供を可能にした点にある。
さらに本発明の効果として、毒性のない安全性
に優れた血液処理器を安定に提供し得ることがあ
げられる。
以下に実施例をあげてさらに本発明の説明を行
なうが、本発明はこれらの実施例によつて何ら限
定されるものではない。
実施例 １
セルロースアセテート（平均重合度280、酢化
度60.5％）のフレークス、スルホラン、ジグリセ
リンからなる混合物を、加熱溶融し、２重管ノズ
ルの外環から押出し、内管から芯剤としてN2ガ
スを同時に吐出し、150m／分で巻き取り、内径
205μ、外径255μの中空繊維原膜を得た。この原
膜を70℃の温水浴に連続的に30sec間浸析抽出処
理し続いて、50wt％のグリセリン浴に３分間浸
析後、膜外表面に付着した過剰のグリセリンを圧
空ノズルで除去し、熱風で乾燥し、セルロースア
セテート（酢化度60.5％）の中空繊維半透膜を得
た。乾燥繊維重量に対する重量％で表わしたグリ
セリンの付着量は75％で空孔率から算出した飽和
グリセリン付着量の約95％に相当した。尚付着グ
リセリンは実質上水を含まないものであつた。
この中空繊維半透膜を長さ23cmに切断したもの
を約12000本束ね、ポリスチレンケースに収納
し、両端をポリウレタン樹脂で固定後切断して、
透析器を組立てた。しかる後、通常のポリエチレ
ン製の袋に封入し、カートンケースに梱包した。
この状態で、室温にて総照射線量2.5Mradのγ線
を照射し、滅菌処理をした。その結果、表―１、
及び表―２に示すようにγ線照射群と未照射群と
では、透析器性能、中空糸物性、溶出物、生物学
試験のいずれにおいても、殆んど変化はなく、実
用的な滅菌条件の照射線量に耐え得ることが判明
した。
実施例 ２
セルロースアセテート（平均重合度180、酢化
度55％）のフレークス、ポリエチレングリコール
（平均分子量400）、ジグリセリンからなる混合物
を実施例１と同様に溶融紡糸、抽出処理を施しセ
ルロースアセテート（酢化度55％）の中空繊維半
透膜を得た。グリセリンの付着量は90％で空孔率
から求めた飽和グリセリン付着量95％にほぼ等し
い値であつた。この中空繊維半透膜を用いて実施
例１と同様に透析器を組み立て、γ線照射処理を
実施した。その結果を表―１、及び表―２に示
す。
<Technical Field> The present invention relates to a radiation sterilization method for a blood processing device, which is used for blood processing such as hemodialysis and hemofiltration, and has a hollow fiber semipermeable membrane as a component. <Prior art> Medical blood processing devices using semipermeable membranes include flat membrane types, coil types, and hollow fiber types.
Hollow fiber membranes with excellent efficiency have become mainstream in recent years. Functionally, there are dialysis-type artificial kidneys, filtration-type artificial kidneys,
There are plasma separators, etc. These blood processing devices process blood by direct contact with it, and therefore must undergo various sterilization treatments to maintain sterility before use. As a conventional sterilization method, there is a method of filling formalin water, which has been used for a long time. Due to its strong bactericidal power, formalin is sufficient for sterilization, but it is difficult to completely remove by washing before dialysis, and its residual nature poses a safety problem. Another method is to sterilize blood processing equipment in a dry state using ethylene oxide gas, which is commonly used to sterilize medical equipment. This is a safety issue. Further, sterilization methods that do not use sterilizing agents include high-pressure steam sterilization and gamma ray irradiation sterilization. Since high-pressure steam sterilization usually involves processing in a saturated steam atmosphere at 115-121°C for about 20-30 minutes, it is necessary to pay close attention to the heat resistance of the parts that make up the blood processing device and the thermal deterioration of the semipermeable membrane. In reality, it has been put to practical use only in the selection of heat-resistant materials, in which the thermal deterioration of semipermeable membranes is small, and in limited combinations of membrane materials. Furthermore, γ-ray irradiation sterilization is a sterilization method that does not use the sterilizing power of chemical substances called sterilizers, so there is no concern about the residual toxicity of the sterilizer, but there is a problem with the decomposition and deterioration of the material due to γ-rays. Depending on the membrane material of the semipermeable membrane, the membrane structure, the water content of the membrane at the time of γ-ray irradiation, etc., the physical properties of the semi-permeable membrane, such as membrane performance, may deteriorate significantly due to γ-ray irradiation. In other words, cellulose membranes, cellulose acetate membranes, synthetic membrane threads, etc. have been put into practical use as semipermeable membrane materials used in blood processing devices such as artificial kidneys, but these membrane materials do not meet the requirements for sterilization. Due to γ-ray irradiation, the basic performance of a semipermeable membrane, such as solute permeability and ultrafiltration performance (water removal ability), decreases significantly, and mechanical and physical properties such as strength and elongation also decrease. It was known to cause significant damage. One of the measures devised to avoid such problems is to pre-prepare the semi-permeable membrane with water or an aqueous solution to make it substantially liquid-containing, and then irradiate the semi-permeable membrane with gamma rays. The aim is to avoid destructive deterioration of the transparent membrane due to radiation within practical limits. Specifically, the blood processing device is filled with water or an aqueous solution and then irradiated with gamma rays, so the final product form of the blood processing device is a so-called wet type. Therefore, if bacteria are present in the blood processing device during the transportation and storage period after manufacturing the blood processing device and before the gamma ray irradiation treatment, there is a high possibility that bacteria will multiply and there is a risk of generation of pyrogen in the final product. It was extremely expensive. <Objective of the Invention> The present invention has been made against the above technical background, and its object is to provide an excellent method of sterilizing a blood processing device that is highly safe and free of residual sterilizing agents. It is. Another object of the present invention is to provide a method for stably radiation sterilizing a blood processing device having a cellulose-based hollow fiber semipermeable membrane in a substantially dry state while maintaining membrane performance. . Another object of the present invention is to provide a highly versatile blood processing device that is free from the risk of generating pyrogen, is easy to transport, and has no risk of freezing. <Structure of the Invention> Under the above background, in order to achieve the above object, the present inventors selected a material for a hollow fiber semipermeable membrane that can be irradiated with radiation in a substantially dry state,
We have conducted extensive research into methods for stably performing radiation sterilization while maintaining membrane performance. That is, as a result of intensive research into the combination of membrane materials such as cellulose membranes, cellulose acetate membranes, and synthetic membranes, which are commonly used as semipermeable membranes, and plasticizers, which are membrane performance-maintaining agents, the present inventors unexpectedly discovered that The present invention was achieved by discovering that a cellulose acetate film with a degree of acetylation of 20% or more is extremely stable against radiation irradiation. That is, the present invention uses cellulose acetate with an oxidation degree of 20% or more for the cellulose acetate hollow fiber semipermeable membrane when sterilizing a blood processing device having a cellulose acetate hollow fiber semipermeable membrane as a constituent member by radiation irradiation. , adhering a plasticizer that does not substantially contain water into the pores of the semipermeable membrane to the extent that it can prevent deterioration of the semipermeable membrane due to radiation irradiation;
A method for sterilizing a blood processing device, characterized in that the inside of the blood processing device is brought into a substantially dry state, and the inside of the blood processing device is irradiated with radiation at a radiation dose within a range that does not deteriorate the semipermeable membrane while maintaining the dry state. be. The present invention will be explained in more detail below.
The hollow fiber semipermeable membrane, which is a component of the blood treatment device of the present invention, is a cellulose acetate membrane with a degree of acetylation of 20% or more. The degree of acetylation referred to in the present invention means the weight percentage of acetyl groups in terms of acetic acid based on the weight of cellulose acetate. The degree of acetylation is 20%, and if it is less than 20%,
Cellulose acetate semipermeable membranes exhibit the characteristics of cellulose membranes, and even if enough glycerin, which is a plasticizer, is attached, the performance and physical properties deteriorate due to radiation irradiation. Cellulose acetate semipermeable membrane exhibits radiation resistance when coexisting with an appropriate amount of plasticizer. In the present invention, if the degree of acetylation of the cellulose acetate semipermeable membrane is in the range of 30 to 61%, radiation resistance is even better and sterilization can be performed more stably. Furthermore, the substantially dry state of the blood processing device according to the present invention means that the blood processing device is not substantially filled with water or an aqueous solution, and the hollow fiber semipermeable membrane is in a substantially dry state. It means that. The term "substantially dry state of the hollow fiber semipermeable membrane" as used herein means that the pores in the thick part of the semipermeable membrane do not substantially contain water, and preferably contain substantially no water. It is desirable to have a free plasticizer deposited within the pores, ie at least a portion of the pores are filled with the plasticizer. Glycerin is suitable as the plasticizer in the present invention. The appropriate range of the amount of glycerin, which is a plasticizer, attached to semipermeable membranes varies depending on the type of semipermeable membrane, ranging from dialysis membranes with relatively low pore porosity to plasma separation membranes with high porosity. determined by its saturated adhesion amount. Here, the state in which all of the pores in the film thickness are replaced and filled with glycerin is saturated adhesion, and the amount of glycerin at that time is the saturated adhesion amount. The preferred amount of plasticizer in the present invention is:
Substantially less than the saturated coverage, more preferably from 40 to 200 expressed as a weight percentage of the plasticizer relative to the dry weight of the cellulose acetate hollow fibers.
% range. If the amount of adhesion is 40% or less, it may be difficult to avoid film deterioration due to radiation. In addition, when glycerin is deposited in an amount exceeding the saturated amount, the excess glycerin is scattered in the form of droplets on the hollow inner surface or outer surface of the hollow fiber semipermeable membrane. aggregates due to surface tension and partially blocks the hollow space of the hollow fiber. After the hollow fiber semipermeable membrane to which glycerin has been applied in an amount exceeding the saturated adhesion amount is assembled into a blood processing device, an aqueous solution such as physiological saline is passed through the hollow part of the hollow fiber in a normal priming operation prior to artificial dialysis. Even with water, due to the surface tension of glycerin,
It is no longer possible to uniformly pass the glycerin through all the hollow fiber bundles, so it is desirable to keep the maximum amount of glycerin deposited below the saturated amount. Therefore, the upper limit of the preferable range of the glycerin adhesion amount is 200%, which is close to the saturated adhesion amount in the case of a membrane with the highest porosity such as for plasma separation. The radiation source used in the present invention includes:
Gamma rays such as 60Co and 137Cs are preferred, and the total irradiation dose is preferably in the range of 1.5 to 5.0 Mrad from the viewpoint of sterilization stability. Any commonly used irradiation method may be used. A blood processing device to which the sterilization method of the present invention can be applied is a blood processing device such as an artificial kidney or a plasma separator that uses a hollow fiber semipermeable membrane as a component. The cellulose acetate hollow fiber semipermeable membrane in the present invention may be any membrane as long as it satisfies the above requirements and can be used as a component of a blood treatment device. Further, any method may be used to substantially dry the blood processing device of the present invention. Regarding the safety and toxicity of blood processing equipment, in general, the semipermeable membrane that comes into direct contact with blood is harmless even after γ-ray irradiation treatment, and the things extracted as indirect eluates are toxic. Don't do it either.
From this point of view, we conducted a comparative study of biological tests and dissolution physical and chemical tests for the non-γ-ray irradiation group and the γ-ray irradiation group of the blood processing device of the present invention.
As a result, no difference was found between the two, and both passed the Ministry of Health and Welfare's standards for dialysis-type artificial kidney devices (draft). Furthermore, in general, due to gamma ray irradiation, the physical properties of the material may continue to deteriorate over time even after irradiation.
A one-year shelf life test was conducted on the blood processing device of the present invention, and there was no significant difference between the non-irradiated group and the irradiated group, and the device passed the dialysis-type artificial kidney device standards (draft) and is stable over time. It was confirmed. As described above, the blood processing device obtained by the method of the present invention is extremely safe. <Effects of the Invention> As described in detail above, the present invention provides a blood processing device comprising a cellulose-based hollow fiber semipermeable membrane as a component, which has not been achieved hitherto. This makes it possible to sterilize by γ-ray irradiation while maintaining the condition. The advent of the gamma ray sterilized substantially dry type blood processing device according to the present invention has the following effects:
Firstly, it eliminates the side effects caused by residual disinfectant, which is a disadvantage of the EO sterilization dry type.Secondly, it is an easy-to-use product that eliminates the risk of pyrogen generation and is easy to transport, replacing the conventional gamma ray sterilization wet type. This makes it possible to provide a more versatile blood processing device that is easy to use, does not have to worry about freezing, and is more versatile. Another advantage of the present invention is that it is possible to stably provide a blood processing device that is non-toxic and has excellent safety. The present invention will be further explained below with reference to Examples, but the present invention is not limited to these Examples in any way. Example 1 A mixture consisting of cellulose acetate flakes (average degree of polymerization 280, degree of acetylation 60.5%), sulfolane, and diglycerin was heated and melted, extruded from the outer ring of a double tube nozzle, and N was added as a core material from the inner tube. Discharge two gases at the same time, wind up at 150m/min, and
A hollow fiber membrane with an outer diameter of 205μ and an outer diameter of 255μ was obtained. This raw film was subjected to continuous immersion extraction treatment in a 70°C hot water bath for 30 seconds, followed by immersion in a 50 wt% glycerin bath for 3 minutes, and excess glycerin attached to the outer surface of the membrane was removed using a compressed air nozzle. , and dried with hot air to obtain a hollow fiber semipermeable membrane of cellulose acetate (degree of acetylation: 60.5%). The amount of glycerin deposited expressed as a weight % based on the dry fiber weight was 75%, which corresponded to about 95% of the saturated glycerin deposit calculated from the porosity. The attached glycerin was substantially free of water. Approximately 12,000 hollow fiber semipermeable membranes cut into lengths of 23 cm were bundled together, stored in a polystyrene case, fixed at both ends with polyurethane resin, and then cut.
Assembled the dialysis machine. Thereafter, it was sealed in a regular polyethylene bag and packed in a carton case.
In this state, it was sterilized by irradiation with gamma rays at a total dose of 2.5 Mrad at room temperature. As a result, Table 1,
As shown in Table 2, there was almost no change in dialyzer performance, hollow fiber physical properties, eluates, or biological tests between the γ-ray irradiation group and the non-irradiation group, and practical sterilization conditions were observed. It was found that it could withstand irradiation doses of . Example 2 A mixture of cellulose acetate flakes (average degree of polymerization 180, degree of acetylation 55%), polyethylene glycol (average molecular weight 400), and diglycerin was melt-spun and extracted in the same manner as in Example 1 to obtain cellulose acetate ( A hollow fiber semipermeable membrane with a degree of acetylation of 55% was obtained. The adhesion amount of glycerin was 90%, which was approximately equal to the saturated glycerin adhesion amount of 95% determined from the porosity. A dialyzer was assembled using this hollow fiber semipermeable membrane in the same manner as in Example 1, and γ-ray irradiation treatment was performed. The results are shown in Table-1 and Table-2.
【表】【table】
【表】【table】
【表】
実施例 ３〜５
実施例２で得られた中空繊維原膜を表―３に示
す項目のアルカリ溶液組成及び表中に示す濃度の
グリセリン浴で処理し、さらに実施例１と同様の
後処理を行なつて各々飽和グリセリン付着量に近
しい中空繊維半透膜を得た。[Table] Examples 3 to 5 The hollow fiber membrane obtained in Example 2 was treated with a glycerin bath having the alkaline solution composition and concentration shown in Table 3, and then treated in the same manner as in Example 1. Post-treatment was performed to obtain hollow fiber semipermeable membranes each having a coating amount of saturated glycerin.
【表】
この中空繊維半透膜を実施例１と同様に処理し
透析器を組立て、γ線照射処理を行なつた。照射
後の膜物性及び透析器性能を未照射群と比較した
が、表―４に示すように実質的な差は見られなか
つた。又照射後の透析器について膜溶出物試験及
び生物学試験を行ない、実施例２と同様の結果を
得た。γ線照射による変質は認められず毒性に関
する安全性も問題はなかつた。[Table] This hollow fiber semipermeable membrane was treated in the same manner as in Example 1, a dialyzer was assembled, and γ-ray irradiation treatment was performed. The membrane properties and dialyzer performance after irradiation were compared with the non-irradiated group, but as shown in Table 4, no substantial differences were observed. Furthermore, membrane eluate tests and biological tests were conducted on the dialyzer after irradiation, and the same results as in Example 2 were obtained. No deterioration was observed due to γ-ray irradiation, and there were no safety issues regarding toxicity.
【表】
実施例６、７及び比較例１
実施例２で得られた中空繊維半透膜（Ｉ）、及
び実施例５で得られた中空繊維半透膜（）を用
いて透析器を組み立て、γ線照射処理を施した。
照射線量は2.0、3.0、6.0Mradの３水準で実施し
た。その結果を表―５に示す。[Table] Examples 6, 7 and Comparative Example 1 Assembling a dialyzer using the hollow fiber semipermeable membrane (I) obtained in Example 2 and the hollow fiber semipermeable membrane (I) obtained in Example 5 , γ-ray irradiation treatment was performed.
The irradiation dose was carried out at three levels: 2.0, 3.0, and 6.0 Mrad. The results are shown in Table-5.
【表】
透析性能、中空糸物性とも、3.0Mradまでは殆
んど劣化を受けていないが、6.0Mradでは透水
性、強度の損傷が著るしく、実用的な滅菌条件の
照射量は3.0Mrad以下と判定された。
比較例 ２〜４
実施例２で得られた中空繊維原膜を表―６に示
す項目のアルカリ溶液組成及び同表に示す濃度の
グリセリン浴で処理し、さらに実施例１と同様の
後処理を行なつて、各々飽和グリセリン付着量に
近い中空繊維半透膜を得た。なお酢化度の低下に
つれて、膜の親水性基化が増大し、飽和グリセリ
ン付着量も大きくなるため、グリセリン浴の濃度
も高くする必要がある。[Table] Both dialysis performance and hollow fiber physical properties show almost no deterioration up to 3.0 Mrad, but at 6.0 Mrad water permeability and strength are significantly damaged, and the irradiation dose under practical sterilization conditions is 3.0 Mrad. It was determined that: Comparative Examples 2 to 4 The hollow fiber membrane obtained in Example 2 was treated with a glycerin bath having the alkaline solution composition and concentration shown in Table 6, and was further subjected to the same post-treatment as in Example 1. As a result, hollow fiber semipermeable membranes having a coating amount of saturated glycerin close to each other were obtained. Note that as the degree of acetylation decreases, the hydrophilicity of the membrane increases and the amount of saturated glycerin attached increases, so it is necessary to increase the concentration of the glycerin bath.
【表】【table】
【表】
この中空繊維半透膜を、実施例１と同様にして
透析器に組立て、γ線照射による劣化を未照射群
と比較した結果を表―７に示す。[Table] This hollow fiber semipermeable membrane was assembled into a dialyzer in the same manner as in Example 1, and the deterioration due to γ-ray irradiation was compared with the non-irradiated group. Table 7 shows the results.
【表】
この結果より、グリセリンの付着量をほぼ飽和
にしておいても、酢化度が20％未満になるまで、
アルカリで鹸化するともはや膜自体の性質・物性
が変化してしまい。セルロース膜の挙動を示し、
たとえ可塑化剤を飽和付着量まで付着してもγ線
照射で膜劣化が起り、透水性、強度の低下が激し
くなり、極端な場合にはリークの発生が認められ
た。つまり本発明による実用的なγ線照射滅菌の
適用範囲としては、酢化度の下限が20％であると
判定された。
実施例８〜10及び比較例５、６
グリセリン付着量の適正化を検討する目的で、
実施例２で得られた中空繊維原膜を、実施例１と
同様の条件下で連続的に抽出処理をし、続いて表
―８に示す如くグリセリン浴濃度最大50wt％か
ら最小10％までの範囲で変動させて実施例１と同
じ処理を行ない、表―８に示すような付着グリセ
リン量の異なる中空繊維半透膜を得た。グリセリ
ン浴濃度が10％未満の範囲では、続いて行う熱風
乾燥工程で、膜の収縮が発生し、繊維長方向の長
さ斑が大きく連続的に、中空繊維膜を捲取ること
は困難であた。[Table] From this result, even if the amount of glycerin attached is almost saturated, until the degree of acetylation becomes less than 20%,
When saponified with alkali, the properties and physical properties of the membrane itself change. Demonstrates the behavior of cellulose membranes,
Even if the plasticizer was applied to the saturated amount, the film deteriorated due to γ-ray irradiation, resulting in a severe drop in water permeability and strength, and in extreme cases, leakage was observed. In other words, it was determined that the lower limit of the degree of acetylation is 20% for the practical application range of γ-ray sterilization according to the present invention. Examples 8 to 10 and Comparative Examples 5 and 6 For the purpose of examining optimization of the amount of glycerin attached,
The hollow fiber membrane obtained in Example 2 was subjected to continuous extraction treatment under the same conditions as in Example 1, and then extracted in a glycerin bath with a concentration ranging from a maximum of 50 wt% to a minimum of 10% as shown in Table 8. The same treatment as in Example 1 was carried out by varying the amount within the range, and hollow fiber semipermeable membranes having different amounts of attached glycerin as shown in Table 8 were obtained. If the glycerin bath concentration is less than 10%, the membrane will shrink in the subsequent hot air drying process, and the length unevenness in the fiber length direction will be large, making it difficult to continuously wind up the hollow fiber membrane. Ta.
【表】
この中空繊維半透膜を実施例１と同様にして透
析器を組立て、γ線照射処理を行つた。照射後の
透析器について、膜物性の測定及び溶出物試験を
行つた結果、実施例２とほぼ同様であつた。しか
し、透析性能に関してはグリセリンの付着量の減
少と共に、劣化の傾向が認められた。性能結果を
表―９に示す。[Table] A dialyzer was assembled using this hollow fiber semipermeable membrane in the same manner as in Example 1, and γ-ray irradiation treatment was performed. After irradiation, the dialyzer was measured for membrane properties and tested for eluates, and the results were almost the same as in Example 2. However, regarding the dialysis performance, a tendency towards deterioration was observed along with a decrease in the amount of glycerin attached. The performance results are shown in Table 9.
【表】
表―９より明らかなようにグリセリン付着量40
％以上では性能が保持されているのに対して、22
％以下では、特に透水性の低下傾向にあり、透析
器としての基本性能からはずれる。すなわち、実
用的なγ線照射による滅菌に耐えるためには、グ
リセリン付着量として40％以上必要であることが
判つた。
実施例 11
セルロースアセテートより成る血漿分離用中空
繊維膜に空孔率より求めた飽和グリセリン付着量
の約90％に相当する付着量200％のグリセリンを
付着させた。この分離膜を用いて、実施例１と同
様にして、分離器を組立て、γ線照射滅菌した。
照射による性能、物性の劣化は殆んどなく、γ線
による損傷は受けていなかつた。
実施例 12
γ線照射による半透膜の劣化、素材の分解の進
行は素材によつて異なり、照射直後も継続して進
行する場合があることが知られており、本発明に
よるジアセテート膜のγ線照射後の経時劣化の有
無を確認検討した。
実施例２で組立てた透析器をγ線照射滅菌し密
封のまま、室温にて、６ケ月間及び12ケ月間保管
後透析性能、膜物性、溶出物試験及び生物学試験
を実施したが、実施例２と全く差は認められず厚
生省透析型人工腎臓装置基準（案）に合格した。
つまり、経時的な変質はなく、本発明の効果が
持続されていることを確認した。[Table] As is clear from Table 9, the amount of glycerin attached is 40
Performance is maintained above 22%.
% or less, the water permeability tends to decrease, and the basic performance as a dialyzer is lost. In other words, it was found that in order to withstand practical sterilization by γ-ray irradiation, a glycerin adhesion amount of 40% or more is required. Example 11 A 200% amount of glycerin was deposited on a hollow fiber membrane for plasma separation made of cellulose acetate, which corresponds to about 90% of the amount of saturated glycerin deposited as determined from the porosity. Using this separation membrane, a separator was assembled in the same manner as in Example 1, and sterilized by γ-ray irradiation.
There was almost no deterioration in performance or physical properties due to irradiation, and there was no damage caused by gamma rays. Example 12 It is known that the deterioration of semipermeable membranes and the progress of decomposition of materials due to γ-ray irradiation differ depending on the material and may continue to progress even immediately after irradiation. We investigated whether there was any deterioration over time after γ-ray irradiation. The dialyzer assembled in Example 2 was sterilized by γ-ray irradiation and kept sealed at room temperature for 6 months and 12 months, after which dialysis performance, membrane properties, eluate tests, and biological tests were conducted. No difference was observed from Example 2, and it passed the Ministry of Health and Welfare's standards for dialysis-type artificial kidney devices (draft). In other words, there was no deterioration over time, confirming that the effects of the present invention were sustained.
Claims (1)
成部材とする血液処理器を放射線照射により滅菌
するに際し、該セルロースアセテート中空繊維半
透膜に酢化度が20％以上であるセルロースアセテ
ートを用い、該半透膜の細孔内に実質的に水を含
まない可塑化剤を放射線照射による該半透膜の劣
化を防止し得る範囲で付着せしめ、且つ該血液処
理器内を実質的に乾燥状態とし、該乾燥状態を保
持したままで該半透膜を劣化させない範囲の照射
線量で放射線照射処理することを特徴とする血液
処理器の滅菌方法。1. When sterilizing a blood processing device having a cellulose acetate hollow fiber semipermeable membrane as a constituent member by radiation irradiation, use cellulose acetate with an acetylation degree of 20% or more for the cellulose acetate hollow fiber semipermeable membrane, and adhering a substantially water-free plasticizer to the pores of the permeable membrane to the extent that it can prevent deterioration of the semipermeable membrane due to radiation irradiation, and keeping the inside of the blood processing device in a substantially dry state; A method for sterilizing a blood processing device, characterized in that the semipermeable membrane is irradiated with radiation at a dose that does not deteriorate the semipermeable membrane while maintaining the dry state.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58085093A JPS59211459A (en) | 1983-05-17 | 1983-05-17 | Pasturization of blood treating device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58085093A JPS59211459A (en) | 1983-05-17 | 1983-05-17 | Pasturization of blood treating device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59211459A JPS59211459A (en) | 1984-11-30 |
| JPS6246190B2 true JPS6246190B2 (en) | 1987-10-01 |
Family
ID=13848987
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58085093A Granted JPS59211459A (en) | 1983-05-17 | 1983-05-17 | Pasturization of blood treating device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59211459A (en) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63111878A (en) * | 1986-10-30 | 1988-05-17 | 日機装株式会社 | Sterilization of semipermeable membrane module |
| JPH0288074A (en) * | 1988-09-27 | 1990-03-28 | Teijin Ltd | Manufacture of blood treating device |
| US8527026B2 (en) | 1997-03-04 | 2013-09-03 | Dexcom, Inc. | Device and method for determining analyte levels |
| US6001067A (en) | 1997-03-04 | 1999-12-14 | Shults; Mark C. | Device and method for determining analyte levels |
| JP2001205057A (en) * | 2000-01-27 | 2001-07-31 | Toyobo Co Ltd | Hollow fiber membrane |
| US20030032874A1 (en) | 2001-07-27 | 2003-02-13 | Dexcom, Inc. | Sensor head for use with implantable devices |
| US7613491B2 (en) | 2002-05-22 | 2009-11-03 | Dexcom, Inc. | Silicone based membranes for use in implantable glucose sensors |
| EP1648298A4 (en) | 2003-07-25 | 2010-01-13 | Dexcom Inc | Oxygen enhancing membrane systems for implantable devices |
| US7920906B2 (en) | 2005-03-10 | 2011-04-05 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
| US9247900B2 (en) | 2004-07-13 | 2016-02-02 | Dexcom, Inc. | Analyte sensor |
| US7654956B2 (en) | 2004-07-13 | 2010-02-02 | Dexcom, Inc. | Transcutaneous analyte sensor |
| US8744546B2 (en) | 2005-05-05 | 2014-06-03 | Dexcom, Inc. | Cellulosic-based resistance domain for an analyte sensor |
| WO2006110193A2 (en) * | 2005-04-08 | 2006-10-19 | Dexcom, Inc. | Cellulosic-based interference domain for an analyte sensor |
| US11730407B2 (en) | 2008-03-28 | 2023-08-22 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
| US8682408B2 (en) | 2008-03-28 | 2014-03-25 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
| US8583204B2 (en) | 2008-03-28 | 2013-11-12 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
| EP2326944B1 (en) | 2008-09-19 | 2020-08-19 | Dexcom, Inc. | Particle-containing membrane and particulate electrode for analyte sensors |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5285525A (en) * | 1975-12-29 | 1977-07-15 | Nippon Zeon Co Ltd | Production of hollow fibers |
| JPS5399695A (en) * | 1977-02-14 | 1978-08-31 | Teijin Ltd | Method of making aseptic artificial viscus |
| JPS5438927A (en) * | 1977-08-31 | 1979-03-24 | Senko Med Instr Mfg | Treating of hollow yarn |
| JPS5442420A (en) * | 1977-07-05 | 1979-04-04 | Cordis Dow Corp | Improved cellulose acetate hollow fiber and production thereof |
| JPS5523620A (en) * | 1978-08-05 | 1980-02-20 | Nippon Columbia Co Ltd | Headphone receiver |
| JPS5547860A (en) * | 1978-10-03 | 1980-04-05 | Nippon Zeon Co | Germmkilling process |
| JPS56112507A (en) * | 1980-02-05 | 1981-09-04 | Mitsubishi Rayon Co Ltd | Preparation of hollow fiber from cellulosic derivative |
| JPS5738283A (en) * | 1980-08-19 | 1982-03-02 | Fujitec Kk | Method of installation of elevator for construction |
| JPS57133211A (en) * | 1981-02-09 | 1982-08-17 | Toyobo Co Ltd | Production of hollow fiber of cellulose ester |
| JPS59192373A (en) * | 1983-04-18 | 1984-10-31 | 東洋紡績株式会社 | Pasturization of osmosis apparatus |
| JPS6246190A (en) * | 1985-08-26 | 1987-02-28 | 石川島播磨重工業株式会社 | Hot isotropic pressure press device |
-
1983
- 1983-05-17 JP JP58085093A patent/JPS59211459A/en active Granted
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5285525A (en) * | 1975-12-29 | 1977-07-15 | Nippon Zeon Co Ltd | Production of hollow fibers |
| JPS5399695A (en) * | 1977-02-14 | 1978-08-31 | Teijin Ltd | Method of making aseptic artificial viscus |
| JPS5442420A (en) * | 1977-07-05 | 1979-04-04 | Cordis Dow Corp | Improved cellulose acetate hollow fiber and production thereof |
| JPS5438927A (en) * | 1977-08-31 | 1979-03-24 | Senko Med Instr Mfg | Treating of hollow yarn |
| JPS5523620A (en) * | 1978-08-05 | 1980-02-20 | Nippon Columbia Co Ltd | Headphone receiver |
| JPS5547860A (en) * | 1978-10-03 | 1980-04-05 | Nippon Zeon Co | Germmkilling process |
| JPS56112507A (en) * | 1980-02-05 | 1981-09-04 | Mitsubishi Rayon Co Ltd | Preparation of hollow fiber from cellulosic derivative |
| JPS5738283A (en) * | 1980-08-19 | 1982-03-02 | Fujitec Kk | Method of installation of elevator for construction |
| JPS57133211A (en) * | 1981-02-09 | 1982-08-17 | Toyobo Co Ltd | Production of hollow fiber of cellulose ester |
| JPS59192373A (en) * | 1983-04-18 | 1984-10-31 | 東洋紡績株式会社 | Pasturization of osmosis apparatus |
| JPS6246190A (en) * | 1985-08-26 | 1987-02-28 | 石川島播磨重工業株式会社 | Hot isotropic pressure press device |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59211459A (en) | 1984-11-30 |
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