JPH034924A - Reproduced cellulose yarn dialysis membrane - Google Patents
Reproduced cellulose yarn dialysis membraneInfo
- Publication number
- JPH034924A JPH034924A JP1134533A JP13453389A JPH034924A JP H034924 A JPH034924 A JP H034924A JP 1134533 A JP1134533 A JP 1134533A JP 13453389 A JP13453389 A JP 13453389A JP H034924 A JPH034924 A JP H034924A
- Authority
- JP
- Japan
- Prior art keywords
- membrane
- dialysis
- regenerated cellulose
- esterification
- dialysis membrane
- 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.)
- Granted
Links
- 239000012528 membrane Substances 0.000 title claims abstract description 81
- 238000000502 dialysis Methods 0.000 title claims abstract description 36
- 239000001913 cellulose Substances 0.000 title abstract description 7
- 229920002678 cellulose Polymers 0.000 title abstract description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 16
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 16
- 210000004369 blood Anatomy 0.000 claims abstract description 12
- 239000008280 blood Substances 0.000 claims abstract description 12
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 239000004627 regenerated cellulose Substances 0.000 claims description 30
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 7
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 abstract description 20
- 238000005886 esterification reaction Methods 0.000 abstract description 13
- 230000032050 esterification Effects 0.000 abstract description 11
- 239000002253 acid Substances 0.000 abstract description 5
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000012429 reaction media Substances 0.000 abstract description 2
- 230000002123 temporal effect Effects 0.000 abstract 1
- 239000012510 hollow fiber Substances 0.000 description 26
- 150000001735 carboxylic acids Chemical class 0.000 description 21
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 7
- 238000004659 sterilization and disinfection Methods 0.000 description 7
- 230000004913 activation Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 210000000265 leukocyte Anatomy 0.000 description 6
- 230000001954 sterilising effect Effects 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- -1 polyethylene Polymers 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- ZURAKLKIKYCUJU-UHFFFAOYSA-N copper;azane Chemical compound N.[Cu+2] ZURAKLKIKYCUJU-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 125000003827 glycol group Chemical group 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 1
- XXDVOJKRZBNPFN-UHFFFAOYSA-N 9-[(e)-diazomethyl]anthracene Chemical compound C1=CC=C2C(C=[N+]=[N-])=C(C=CC=C3)C3=CC2=C1 XXDVOJKRZBNPFN-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 230000012953 feeding on blood of other organism Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 238000004388 gamma ray sterilization Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012414 sterilization procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Artificial Filaments (AREA)
- Chemical Treatment Of Fibers During Manufacturing Processes (AREA)
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Treatments Of Macromolecular Shaped Articles (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野］
本発明は、人工透析療法等に用いられる改良された再生
セルロース系透析膜に関する。更に詳しくは、血液に対
する適合性が改良された再生セルロース系透析膜に関す
る。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an improved regenerated cellulose-based dialysis membrane used in artificial dialysis therapy and the like. More specifically, the present invention relates to a regenerated cellulose-based dialysis membrane with improved compatibility with blood.
人工透析療法に於いて、再生セルロース系透析膜、とり
わけ銅アンモニウム法再生セルロース系透析膜は、広く
用いられ、透析装置や透析技術の進歩と共に、腎不全患
者の延命、社会復帰に大きな役割を果たしている。In artificial dialysis therapy, regenerated cellulose-based dialysis membranes, especially copper ammonium regenerated cellulose-based dialysis membranes, are widely used, and along with advances in dialysis equipment and dialysis technology, they play a major role in prolonging the lives of renal failure patients and reintegrating them into society. There is.
しかしながら、透析療法の進歩にもかかわらず、透析に
伴う種々の問題がまだ未解決で残されている。例えば、
抗凝固剤が長期大量投与され、そのために生じると考え
られる種々の副作用の問題、また、再生セルロース系透
析膜やその他一部の膜で血液透析を行った場合の一過性
の白血球減少や補体成分の活性化の問題等が指摘されて
いる。後者の現象については、臨床症状との関連、或い
は臨床的意義は明らかではないが、再生セルロース系透
析膜の他の優れた性能を損なわず、これらの現象を軽減
することが望まれている。However, despite advances in dialysis therapy, various problems associated with dialysis still remain unsolved. for example,
There are various side effects that may occur due to long-term administration of large doses of anticoagulants, as well as temporary white blood cell reduction and compensation when hemodialysis is performed using regenerated cellulose-based dialysis membranes and some other membranes. Problems such as activation of body components have been pointed out. Regarding the latter phenomenon, although the relationship with clinical symptoms or clinical significance is not clear, it is desired to alleviate these phenomena without impairing the other excellent performance of the regenerated cellulose-based dialysis membrane.
かかる問題や現象に対して、再生セルロース系透析膜の
血液適合性を改良する方法が種々提案されている。例え
ば、膜表面をヘパリン化することにより抗血栓性を付与
する方法が特開昭５１−１９４で提案されているが、充
分な効果が得られず、またコストも割高になるため実用
化されていない。また、各種ポリマーやビタミンを再生
セルロース系透析膜の表面にコーティングする方法も提
案されているが、被膜の安定性や滅菌の方法が限定され
るなどの問題点がある。また、特開昭６１−８１０５に
再生セルロース系透析膜にイソシアネートプレポリマー
を反応させる方法が、特開昭６０−１１８２０３にブリ
ッジ剤を介してポリマー酸を化学的に結合させる方法が
提案されているが、反応物質安定性及び反応工程の？ｌ
ｔさなどの問題がある。さらに、特開昭６１−１１３４
５９にジエチルアミンエチルセルロース等の改変セルロ
ースを用いて製膜した透析膜が提案されているが、血液
凝固を軽減する面での改良は十分とは言えない。In response to such problems and phenomena, various methods have been proposed to improve the blood compatibility of regenerated cellulose-based dialysis membranes. For example, a method of imparting antithrombotic properties by heparinizing the membrane surface was proposed in Japanese Patent Application Laid-Open No. 51-194, but it has not been put to practical use because it is not sufficiently effective and is expensive. do not have. Additionally, methods have been proposed in which the surface of regenerated cellulose-based dialysis membranes is coated with various polymers and vitamins, but these methods have problems such as the stability of the coating and limited sterilization methods. Furthermore, a method of reacting an isocyanate prepolymer with a regenerated cellulose-based dialysis membrane was proposed in JP-A No. 61-8105, and a method of chemically bonding a polymeric acid via a bridging agent was proposed in JP-A-60-118203. But what about reactant stability and reaction process? l
There are problems such as stiffness. Furthermore, JP-A-61-1134
Although a dialysis membrane made using modified cellulose such as diethylamine ethyl cellulose has been proposed in No. 59, the improvement in reducing blood coagulation is not sufficient.
上記のように、再生セルロース膜の血液適合性を向上さ
せる試みには、一長一短がある。そこで本発明の目的は
血液適合性を向上させた、改良された再生セルロース系
透析膜を提供することにある。As mentioned above, attempts to improve the blood compatibility of regenerated cellulose membranes have advantages and disadvantages. Therefore, an object of the present invention is to provide an improved regenerated cellulose-based dialysis membrane with improved blood compatibility.
再生セルロース透析膜を用いた場合生じる補体成分の活
性化や白血球の一過性減少には、膜表面の水酸基が関与
していると考えられている。一方、この膜表面の水酸基
は種々の官能基と反応し分子鎖を結合することができる
。結合した分子鎖が、膜表面上の水酸基をマスキングし
、補体蛋白や血球と水酸基の直接の接触を妨げ、血液に
対する適合性を改良すると考えられる。このような考え
のもとに改良した再生セルロース系透析膜が提案されて
いる。It is thought that the hydroxyl groups on the membrane surface are involved in the activation of complement components and the transient decrease in white blood cells that occur when a regenerated cellulose dialysis membrane is used. On the other hand, the hydroxyl groups on the surface of this membrane can react with various functional groups to bond molecular chains. It is believed that the bound molecular chains mask the hydroxyl groups on the membrane surface, preventing direct contact between the hydroxyl groups and complement proteins and blood cells, and improving compatibility with blood. Based on this idea, improved regenerated cellulose-based dialysis membranes have been proposed.
本発明者らは、改良効果が発現するグラフトｉｔについ
て鋭意研究を重ねた結果、本発明の完成に到った。すな
わち、本発明では、再生セルロース系透析膜において、
少なくとも血液と接触する膜表面に、膜面積１ｒｒｆあ
たり０．１ｍｇ以上゛のポリエチレングライコールジカ
ルボン酸またはポリエチレングライコールモノカルボン
酸のアシル残基がエステル結合によりグラフトしている
ことを特徴とする再生セルロース系透析膜が提供される
。The present inventors have completed the present invention as a result of extensive research into graft IT that exhibits improvement effects. That is, in the present invention, in the regenerated cellulose-based dialysis membrane,
Regenerated cellulose, characterized in that acyl residues of polyethylene glycol dicarboxylic acid or polyethylene glycol monocarboxylic acid in an amount of 0.1 mg or more per 1 rrf of membrane area are grafted through ester bonds at least on the membrane surface that comes into contact with blood. A system dialysis membrane is provided.
本明細書において「グラフト鎖」とは、膜表面に少なく
とも一端が化学結合した分子鎖であり、本発明では、エ
ステル結合しているポリエチレングライコールジカルボ
ン酸またはポリエチレングライコールモノカルボン酸の
アシル残基が相当し、また「グラフト；卯量」とは、エ
ステル結合したポリエチレングライコールジカルボン酸
またはポリエチレングライコールモノカルボン酸の量を
示す。In this specification, the term "graft chain" refers to a molecular chain with at least one end chemically bonded to the membrane surface, and in the present invention, it refers to an acyl residue of polyethylene glycol dicarboxylic acid or polyethylene glycol monocarboxylic acid that has an ester bond. The term "graft amount" refers to the amount of ester-bonded polyethylene glycol dicarboxylic acid or polyethylene glycol monocarboxylic acid.
本発明で使用する「再生セルロース」とは、天然セルロ
ースを一旦化学的に或いは物理的に変化させた後再生し
たものであって、例えば、銅アンモニウム法再生セルロ
ース、ビスコースレーヨン、セルロースエステルを鹸化
したものが含まれるが、透析性能及び長年の実績により
裏付られた高い安全性等から銅アンモニウム法再生セル
ロースが好んで用いられる。The "regenerated cellulose" used in the present invention is natural cellulose that has been chemically or physically changed and then regenerated. However, copper ammonium regenerated cellulose is preferably used due to its dialysis performance and high safety backed by many years of experience.
再生セルロースの形状は、平膜または中空糸膜等何れの
形状に成型されたものも用いることができる°が、中空
糸膜が好ましい。例えば、特公昭５０−４０１６８及び
特開昭５９−２０４９１２に開示されているような、膜
厚が数−〜６０卿であり、外径が１０卿〜数百μの真円
形の横断面を有する中空系膜等が用いられる。The regenerated cellulose may be formed into any shape such as a flat membrane or a hollow fiber membrane, but a hollow fiber membrane is preferable. For example, as disclosed in Japanese Patent Publication No. 50-40168 and Japanese Unexamined Patent Publication No. 59-204912, the film thickness is several to sixty centimeters, and the outer diameter is a perfect circular cross section with an outer diameter of ten centimeters to several hundred microns. A hollow membrane or the like is used.
本発明でいうポリエチレングライコールジカルボン酸と
は一般式が、
ＨＯｚＣＣＨｚ （ＯＣＨｚＣ）Ｉｔ）ｎ ０ＣＨ
２ＣＯＺＨ（ｎ＝１〜１５０）
で示される高分子カルボン酸をいい、またポリエチレン
グライコールモノカルボン酸とは一般式が、ＨＯｚＣＧ
Ｈｚ （ＯＣＨｚＣＨｚ）ｎ ０Ｒ（ｎ＝１〜１５
０；
Ｒ＝炭素数が１〜２０の飽和または不飽和炭化水素）
で示される高分子カルボン酸をいう。The polyethylene glycol dicarboxylic acid referred to in the present invention has the general formula: HOzCCHz (OCHzC)It)n 0CH
2COZH (n=1-150) refers to a polymeric carboxylic acid represented by HOzCG.
Hz (OCHzCHz)n 0R (n=1~15
0; R=saturated or unsaturated hydrocarbon having 1 to 20 carbon atoms).
上記高分子カルボン酸の再生セルロース系透析膜の表面
へのグラフトは、膜表面にΔ在する水線基とのエステル
化反応によって行われ、公知の低分子のアルコールと低
分子のカルボン酸またはその酸誘導体との反応が適用で
きる。たとえば、反応を促進させるエステル化触媒とし
て、ジシクロへキシルカルボジイミドと４−ジメチルア
ミノピリジン及び／または４−ピロリジノピリジンとの
混合触媒を用い、これらと高分子カルボン酸またはその
酸誘導体を反応媒体に分散または溶解させた処理液で再
生セルロース系透析膜を処理することにより、エステル
化反応が進み高分子カルボン酸のグラフトが行なわれる
。従って、この処理条件、例えば処理液中のカルボン酸
濃度や触媒濃度、反応時間、及び反応温度等によって、
グラフト量が変動する。Grafting of the above-mentioned polymeric carboxylic acid onto the surface of the regenerated cellulose-based dialysis membrane is carried out by an esterification reaction with the water line group present on the membrane surface. Reactions with acid derivatives are applicable. For example, a mixed catalyst of dicyclohexylcarbodiimide and 4-dimethylaminopyridine and/or 4-pyrrolidinopyridine is used as an esterification catalyst to accelerate the reaction, and these and a polymeric carboxylic acid or its acid derivative are used as the reaction medium. By treating the regenerated cellulose-based dialysis membrane with the dispersed or dissolved treatment liquid, the esterification reaction progresses and grafting of the polymeric carboxylic acid takes place. Therefore, depending on the processing conditions, such as the carboxylic acid concentration and catalyst concentration in the processing solution, reaction time, and reaction temperature,
The amount of grafting varies.
改質した再生セルロース系透析膜をアルカリ水溶液で抽
出すると、エステル結合が加水分解され、膜にグラフト
していた高分子カルボン酸が抽出される。これを分析す
ることにより膜表面上のグラフト量を求めることが出来
る。また、単に付着しているだけの高分子カルボン酸は
水で抽出されるので、改質した再生セルロース系透析膜
表面に付着している高分子カルボン酸の有無は水抽出液
を分析することにより容易に判別できる。When the modified regenerated cellulose-based dialysis membrane is extracted with an aqueous alkaline solution, the ester bonds are hydrolyzed and the polymeric carboxylic acid grafted onto the membrane is extracted. By analyzing this, the amount of grafting on the membrane surface can be determined. In addition, since the polymeric carboxylic acid that is simply attached is extracted with water, the presence or absence of the polymeric carboxylic acid that is attached to the surface of the modified regenerated cellulose dialysis membrane can be determined by analyzing the water extract. Easy to identify.
上述したように、再生セルロース膜での補体成分の活性
化作用や白血球一過性減少には、膜表面の水酸基が関与
する。参考例３に示されるように極微量のグラフト量か
ら膜表面の物理化学的性質、たとえばゼータ電位や親水
性の変化が観察されるが、補体成分の活性化作用の抑制
は不充分である。As mentioned above, the hydroxyl groups on the membrane surface are involved in the activation of complement components and the temporary decrease in white blood cells in the regenerated cellulose membrane. As shown in Reference Example 3, changes in the physicochemical properties of the membrane surface, such as zeta potential and hydrophilicity, are observed from a very small amount of grafting, but the activation effect of complement components is not sufficiently suppressed. .
逆に、グラフト量の多い実施例１５での中空糸膜では、
その親水性は未処理の中空糸と同レベルだが、補体成分
の活性化作用を充分に抑制している。On the contrary, in the hollow fiber membrane of Example 15 with a large amount of grafting,
Its hydrophilicity is on the same level as untreated hollow fibers, but it sufficiently suppresses the activation of complement components.
従って、本発明の目的を達成するためには、膜表面の物
理化学的性質の変化よりも、生体反応に関与する膜表面
の水酸基をグラフトした高分子カルボン酸が遮蔽してい
ることが必要である。また、膜表面の物理化学的性質の
変化については、再生セルロース膜の他の特性、例えば
、膜の水濡れ性や物質の透過性等への影響が考えられる
が、実施例１１〜１５に示されるように、グラフトによ
る膜表面の物理化学的性質の変化は、膜の他の特性に影
響するほど大きくない。後述する実施例から明らかに、
本発明の目的を達成するためには、高分子カルボン酸の
グラフト量が膜面積１ｒｒｆあたり０．１ｍｇ以上であ
ることが必要であり、０．２■以上であることが更に好
ましい。Therefore, in order to achieve the purpose of the present invention, it is necessary that the grafted polymeric carboxylic acid shields the hydroxyl groups on the membrane surface that are involved in biological reactions, rather than changing the physicochemical properties of the membrane surface. be. In addition, changes in the physicochemical properties of the membrane surface may have an effect on other properties of the regenerated cellulose membrane, such as the membrane's water wettability and substance permeability, as shown in Examples 11 to 15. As shown, the changes in the physicochemical properties of the membrane surface due to grafting are not large enough to affect other properties of the membrane. It is clear from the examples described below that
In order to achieve the object of the present invention, it is necessary that the amount of grafted polymeric carboxylic acid is 0.1 mg or more per 1 rrf of membrane area, and more preferably 0.2 or more.
治療に使用する前に滅菌操作が必要であるが、本発明の
再生セルロース系透析膜は、各種の滅菌法を利用するこ
とができる。即ち、組み込んだ透析器を、そのまま乾燥
状態で滅菌する、エチレンオキサイドガス滅菌、高圧蒸
気滅菌、及びガンマ−線織面等が利用でき、または組み
込んだ透析器に水または生理食塩水などを充填した後滅
菌する、高圧蒸気滅菌、またはガンマ−線織面などが利
用できる。このような滅菌操作によって、改良された血
液適合性が変化することはない。Although sterilization is required before use for treatment, the regenerated cellulose-based dialysis membrane of the present invention can be sterilized using various sterilization methods. That is, the incorporated dialyzer can be sterilized in a dry state, ethylene oxide gas sterilization, high-pressure steam sterilization, gamma ray sterilization, etc., or the incorporated dialyzer can be sterilized with water or physiological saline. Post-sterilization, high-pressure steam sterilization, or gamma ray woven surface can be used. Such sterilization procedures do not alter the improved hemocompatibility.
次に、実施例により本発明の内容をさらに詳細に述べる
。Next, the content of the present invention will be described in more detail with reference to Examples.
なお以下の実施例中に記載されている測定項目は、各々
次の方法で測定したものである。Note that the measurement items described in the following examples were measured by the following methods.
。（１）補体消費率
約２鵬長に細断した試料中空糸をポリエチレン管に入れ
、これにゲラチンベロナール緩衝液で４倍に希釈したモ
ルモット補体（コープイス・ラボ）２００Ｉｌ！を添加
した。３７°Ｃで１時間攪拌しながらインキュベートし
、上清液の補体価を測定した。. (1) Complement consumption rate A sample hollow fiber cut into approximately 2-length pieces was placed in a polyethylene tube, and guinea-pig complement (Corpus Labs) 200 Il was diluted 4 times with gelatin veronal buffer. was added. The mixture was incubated at 37°C for 1 hour with stirring, and the complement value of the supernatant was measured.
補体価はマイヤー変法：イムノケムストリー（Ｉｍｍｕ
ｎｏｃｈｅｍ ｉｓ ｔｒｙ）第２版、第１３３頁、シ
ー・シー・トーマス（Ｃ０Ｃ１Ｔｈｏｍａｓ）出版者、
１９６１年、参照）によって求めた。即ち、補体の５０
％瀉血価（Ｃ１５０値）を求め、コントロールに対する
補体消費率（％）を算出した。Complement values are determined by Meyer's modified method: Immunochemistry (Immu
nochem is try) 2nd edition, page 133, C0C1 Thomas Publisher,
(1961). That is, 50 of complement
The % phlebotomy value (C150 value) was determined, and the complement consumption rate (%) relative to the control was calculated.
（２）毛細髄管上昇値
試料中空糸を２５°Ｃの水中にほぼ垂直に立てて浸漬さ
せ、毛細管現象による中空糸内部の液面の上昇の値を外
部水面を基準にして測定した。膜表面が親水性であるほ
ど、原理的に毛細管上昇により液面は上昇し、大きな値
を示す。(2) Capillary tube rise value A sample hollow fiber was immersed in water at 25°C in an almost vertical position, and the rise in the liquid level inside the hollow fiber due to capillary action was measured with reference to the external water level. In principle, the more hydrophilic the membrane surface is, the higher the liquid level will be due to capillary rise, and the larger the value will be.
（３）ゼータ電位
試料中空糸の片側から１ミリモル／リッターの塩化カリ
ウム溶液を圧力（Ｐ）をかけて流通させ、その際中空糸
の両端に生じる電位差（Ｅ）を白金電極により測定する
。圧力変化（ΔＰ）に対応する電位差変化（ΔＥ）を求
め、次式からゼータ電位を算出した。(3) Zeta potential sample A 1 mmol/liter potassium chloride solution is passed through one side of the hollow fiber under pressure (P), and the potential difference (E) generated at both ends of the hollow fiber is measured using a platinum electrode. The potential difference change (ΔE) corresponding to the pressure change (ΔP) was determined, and the zeta potential was calculated from the following equation.
但し、η、に、Ｄは、それぞれ塩化カリウム溶液の粘度
、比電気伝導度、誘導率を示す。However, η, and D represent the viscosity, specific electrical conductivity, and dielectric constant of the potassium chloride solution, respectively.
（４）グラフト量
試料中空糸を細断し、三角フラスコに入れ、これに水を
加え、３７°Ｃで１時間振盪し、付着の高分子カルボン
酸を水抽出した。この水抽出液を半分だけ分離後、試料
中空糸の三角フラスコにさらに水酸化ナトリウム水溶液
を加え、５０°Ｃで２時間振盪した。このようにして得
られたアルカリ抽出液を分離し塩酸で中和した。水抽出
液及びアルカリ抽出液をそれぞれ凍結乾燥した後、残渣
を１゜４−ジオキサンに再溶解し、９−アンスリルジア
ゾメタン（フナコシ薬品製）を添加して反応させ、蛍光
検出器を備えた高速液体クロマトグラフィにより分析し
た。(4) Amount of Graft Sample The hollow fiber was cut into pieces, placed in an Erlenmeyer flask, water was added thereto, and the mixture was shaken at 37°C for 1 hour to extract the attached polymeric carboxylic acid with water. After separating only half of this water extract, an aqueous sodium hydroxide solution was further added to the sample hollow fiber Erlenmeyer flask, and the mixture was shaken at 50°C for 2 hours. The alkaline extract thus obtained was separated and neutralized with hydrochloric acid. After freeze-drying the aqueous extract and alkaline extract, the residue was redissolved in 1°4-dioxane, and 9-anthryldiazomethane (manufactured by Funakoshi Pharmaceutical Co., Ltd.) was added for reaction. Analyzed by liquid chromatography.
アルカリ抽出液の分析値から水抽出液の分析値差引いて
、高分子カルボン酸のグラフト量を算出した。The amount of grafted polymeric carboxylic acid was calculated by subtracting the analytical value of the aqueous extract from the analytical value of the alkaline extract.
実施例１
再生セルロース中空糸膜（内径１８０−１膜厚１１ｊ１
ｍ、長さ２４ｃｍ）の束（本数約９．０００本）を、上
下にノズルを装備したステンレス管に充填した。Example 1 Regenerated cellulose hollow fiber membrane (inner diameter 180-1 membrane thickness 11j1
24 cm in length) (approximately 9,000 pieces) was filled into a stainless steel tube equipped with nozzles on the top and bottom.
また内容が１０００ｍのフラスコ内に、ポリエチレング
ライコール部の平均分子量が２００のポリエチレングラ
イコールジカルボン酸０．１６ｇ、４−ジメチルアミノ
ピリジン（以下、ｒ ＤＭＡＰ Ｊという）０．０２ｇ
、ジシクロへキシルカルボジイミド（以下、ｒＤＣＣＪ
という）０．１５ｇ及び１．１．２−１−ジクロロ−１
，２，２−１−リフルオロエタン−アセトン混合溶媒（
アセトン１２．５ｗｔ％）７００＋＋ｊ！を加え、処理
液を調合した。この処理液をチューブポンプを用い、下
部ノズルからステンレス管に導入し、上部ノズルからの
流出液をフラスコに戻す方式で、２０分循環した。この
際ステンレス管とフラスコは、水浴中にいれ、処理液の
液温が３５°Ｃを保つようにした。Additionally, in a flask with a capacity of 1000 m, 0.16 g of polyethylene glycol dicarboxylic acid whose polyethylene glycol moiety has an average molecular weight of 200, and 0.02 g of 4-dimethylaminopyridine (hereinafter referred to as rDMAP J)
, dicyclohexylcarbodiimide (rDCCJ)
) 0.15 g and 1.1.2-1-dichloro-1
,2,2-1-lifluoroethane-acetone mixed solvent (
Acetone 12.5wt%) 700++j! was added to prepare a treatment solution. This treated liquid was introduced into the stainless steel tube from the lower nozzle using a tube pump, and the effluent from the upper nozzle was returned to the flask for 20 minutes of circulation. At this time, the stainless steel tube and flask were placed in a water bath to maintain the temperature of the treatment solution at 35°C.
処理後の中空糸膜束をメチルアルコール中に一昼夜浸漬
した後、室温で減圧乾燥することによって改良された中
空糸膜を得た。The treated hollow fiber membrane bundle was immersed in methyl alcohol for a day and night, and then dried under reduced pressure at room temperature to obtain an improved hollow fiber membrane.
エステル化処理を行った中空糸膜について、グラフト量
及び補体消費率の測定を実施した。結果を第１表に示す
。The amount of grafting and the complement consumption rate were measured for the hollow fiber membranes subjected to the esterification treatment. The results are shown in Table 1.
実施例２〜５
高分子カルボン酸としてポリエチレングライコール部の
平均分子量が２００のポリエチレングライコールジカル
ボン酸を用い、下記の条件で処理液を調合した。実施例
１と同様にしてエステル化処理を行ない、改良された中
空糸膜を得た。Examples 2 to 5 A treatment liquid was prepared under the following conditions using polyethylene glycol dicarboxylic acid having an average molecular weight of 200 in the polyethylene glycol portion as the polymeric carboxylic acid. Esterification treatment was carried out in the same manner as in Example 1 to obtain an improved hollow fiber membrane.
高分子カルボン酸 ＤＭＡＰ ［）ＣＣ実施例２
０．２０ ｇ ０．０３ ｇ ０．２３
ｇ実施例３ ０．３１ ｇ ０．０５
ｇ ０．３０ ｇ実施例４ ０．４５ ｇ
０．０６ ｇ ０．４３ ｇ実施例５ ０．
６３ ｇ ０．０８ ｇ ０．６０ ｇ得ら
れたそれぞれの中空糸膜について、グラフト量及び補体
消費率の測定を実施した。結果を第１表に示す。Polymeric carboxylic acid DMAP [)CC Example 2
0.20 g 0.03 g 0.23
g Example 3 0.31 g 0.05
g 0.30 g Example 4 0.45 g
0.06 g 0.43 g Example 5 0.
63 g 0.08 g 0.60 g The graft amount and complement consumption rate were measured for each of the obtained hollow fiber membranes. The results are shown in Table 1.
参考例１
高分子カルボン酸、ＤＭＡＰ、及びＤＣＣの濃度をそれ
ぞれ実施例１の１／３にして処理液を調合した。実施例
１と同様にしてエステル化処理を行ない、得られた中空
糸膜についてグラフ）！及び補体消費率の測定を実施し
た。結果を第１表に示す。Reference Example 1 A treatment solution was prepared in which the concentrations of polymeric carboxylic acid, DMAP, and DCC were set to ⅓ of those in Example 1. A graph of the hollow fiber membrane obtained by performing the esterification treatment in the same manner as in Example 1)! and complement consumption rate measurements were performed. The results are shown in Table 1.
以下余白
以下余白
第 １ 表
実施例１ ０．１
実施例２０．２
実施例３１．１
実施例４１．５
実施例５２．６
参考例１ ０．１以下
実施例６〜ｌＯ
高分子カルボン酸としてポリエチレングライコール部の
平均分子量が１０００のメトキシポリエチレングライコ
−・ルカルボン酸を、また、溶媒としてトルエンを用い
て、下記の条件で処理液を調合した。実施例１と同様に
してエステル化処理を行ない、改良された中空糸膜を得
た。Below margins Below margins 1 Table Example 1 0.1 Example 20.2 Example 31.1 Example 41.5 Example 52.6 Reference example 1 0.1 or less Examples 6 to lO As a polymeric carboxylic acid A treatment solution was prepared under the following conditions using methoxypolyethylene glycol carboxylic acid whose polyethylene glycol moiety has an average molecular weight of 1000 and toluene as a solvent. Esterification treatment was carried out in the same manner as in Example 1 to obtain an improved hollow fiber membrane.
高分子カルボン酸 ＤＭＡＰ ＤＣＣ実施例６
０．８８ ｇ ０．０２ ｇ ０．２０
ｇ実施例７ １．７８ｇ ０．０４ｇ
０．４４ｇ実施例８ ３．５０ ｇ ０．
０８ ｇ ０．８４ ｇ実施例９ ７．００ ｇ
０．１５ ｇ １．７２ ｇ実施例１０
１４．１ｇ ０．３０ｇ ３．３９ｇ得
られたそれぞれの中空糸膜について、グラフト量及び補
体消費率の測定を実施した。結果を第２表に示す。Polymeric carboxylic acid DMAP DCC Example 6
0.88 g 0.02 g 0.20
gExample 7 1.78g 0.04g
0.44g Example 8 3.50g 0.
08 g 0.84 g Example 9 7.00 g
0.15 g 1.72 g Example 10
14.1g 0.30g 3.39gThe graft amount and complement consumption rate were measured for each of the obtained hollow fiber membranes. The results are shown in Table 2.
参考例２
高分子カルボン酸、ＤＭＡＰ、及びＤＣＣの濃度をそれ
ぞれ実施例６の１／３にして処理液を調合した。実施例
１と同様にしてエステル化処理を行ない、得られた中空
糸膜についてグラフト量及び補体消費率の測定を実施し
た。結果を第２表に示す。Reference Example 2 A treatment solution was prepared in which the concentrations of polymeric carboxylic acid, DMAP, and DCC were set to ⅓ of those in Example 6. The esterification treatment was carried out in the same manner as in Example 1, and the graft amount and complement consumption rate of the obtained hollow fiber membrane were measured. The results are shown in Table 2.
第２表
実施例６ ０．１ ２７実施例７
０．３ １９実施例８ １．
０ １７実施例９ １．５
１５実施例１０． ．２．．５
１５参考例２ ０．１以下 ４０実施
例１１−１５
高分子カルボン酸としてアルコキシポリエチレングライ
コールモノカルボン酸（ＨＯ，ＣＣｌ１．− （ＯＣＩ
Ｉ□Ｃ１１□）。Table 2 Example 6 0.1 27 Example 7
0.3 19 Example 8 1.
0 17 Example 9 1.5
15 Example 10. ．． 2. ．． 5
15 Reference Example 2 0.1 or less 40 Examples 11-15 Alkoxypolyethylene glycol monocarboxylic acid (HO, CCl1.- (OCI
I□C11□).
０−ＣｌＪｚｙ）を、また、を容媒として１，１．２−
トリクロロ−１，２，２−）リフルオロエタン−ジクロ
ロメタン混合溶媒（ジクロロメタン５ｗｔ％）を用い、
下記の条件で処理液を調合した。実施例１と同様にして
エステル化処理を行ない、改良さ高分子カルボン酸 Ｄ
ＭＡＰ ＤＣＣ実施例１１ ０．２８ｇ
０．０１ｇ ０．１３ｇ実施例１２ ０．５
４ｇ ０．０２ｇ ０．２４ｇ実施例１３
１．２０ｇ ０．０５ｇ ０．５４ｇ実
施例１４ ２．０８ｇ ０．０９ｇ ０
．９４ｇ実施例１５ ４．４９ｇ Ｏ，１
９ｇ ２．０２ｇ得られたそれぞれの中空糸膜につい
て、毛細管上昇、ゼータ電位、グラフト量及び°補体消
費率の測定を実施した。結果を第３表に示す。0-ClJzy) and 1,1.2-
Using a trichloro-1,2,2-)lifluoroethane-dichloromethane mixed solvent (dichloromethane 5 wt%),
A treatment solution was prepared under the following conditions. Esterification treatment was carried out in the same manner as in Example 1 to obtain improved polymeric carboxylic acid D.
MAP DCC Example 11 0.28g
0.01g 0.13gExample 12 0.5
4g 0.02g 0.24gExample 13
1.20g 0.05g 0.54gExample 14 2.08g 0.09g 0
．． 94g Example 15 4.49g O,1
Capillary rise, zeta potential, graft amount, and complement consumption rate were measured for each of the hollow fiber membranes obtained. The results are shown in Table 3.
参考例３
高分子カルボン酸、ＤＭＡＰ、及びＤＣＣの濃度をそれ
ぞれ実施例１１の１／３にして処理液を調合し、実施例
１と同様にしてエステル化処理を行なった。得られた中
空糸膜及び未処理中空糸について毛細管上昇、ゼータ電
位、グラフ）！及び補体消費率の測定を実施した。結果
を第３表に示すが、毛細管上昇では、変化が見られるが
、補体の活性化の抑制は不充分であった。Reference Example 3 A treatment solution was prepared in which the concentrations of polymeric carboxylic acid, DMAP, and DCC were set to ⅓ of those in Example 11, and esterification treatment was performed in the same manner as in Example 1. Capillary rise, zeta potential, graph) for the obtained hollow fiber membrane and untreated hollow fiber! and complement consumption rate measurements were performed. The results are shown in Table 3. Although changes were observed in capillary rise, suppression of complement activation was insufficient.
第３表
実施例１１ ０．１ ２７ ６９実
施例１２ ０．２ １８ ６６実施
例１３ ．０．９ １７ ６８実施例
１４ １．４ １７ ６５実施例１
５ ２．４ １４ ３６参考例３
０．１以下 ４４６Ｂ未処理 ０．０
５５ ３５
−１．５
−１．５
１．６
１．９
２．１
１．３
−１．２
実施例１６
実施例１，３，７．−９．１１，１２，１５、及び未処
理の再生セルロース中空糸膜を透析器に組込み、それぞ
れ犬による体外循環を行った。犬は体重約１０ｋｇのピ
ーグル大を用い、頚部に造設したシャントから１００Ｊ
／＋＋＋ｉｎの血流をとって透析器血液側に流した。な
お体外循環に先だって、生理食塩水で透析器内を洗浄し
た後、ヘパリン６、０００Ｕ／Ｌ含有の生理食塩水で透
析器及び血液回路内を充填し、その後血液を流した。透
析器入口部で血液を採取し白血球数を測定した。透析直
前の白血球数を１００とした時、透析後１５分及び３０
分の値を第４表に示した。Table 3 Example 11 0.1 27 69 Example 12 0.2 18 66 Example 13. 0.9 17 68 Example 14 1.4 17 65 Example 1
5 2.4 14 36 Reference example 3
0.1 or less 446B untreated 0.0
55 35 -1.5 -1.5 1.6 1.9 2.1 1.3 -1.2 Example 16 Examples 1, 3, 7. -9.11, 12, 15, and untreated regenerated cellulose hollow fiber membranes were installed in a dialyzer, and extracorporeal circulation was performed using a dog. A peagle-sized dog weighing approximately 10 kg was used, and 100 J was administered through a shunt placed in the neck.
/+++in blood flow was taken and sent to the blood side of the dialyzer. Prior to extracorporeal circulation, the inside of the dialyzer was washed with physiological saline, and then the inside of the dialyzer and blood circuit were filled with physiological saline containing 6,000 U/L of heparin, and then blood was allowed to flow. Blood was collected at the inlet of the dialyzer and the number of white blood cells was measured. When the white blood cell count immediately before dialysis is 100, 15 minutes and 30 minutes after dialysis.
The minute values are shown in Table 4.
中空糸膜 １
実施例１
実施例３
実施例７
実施例９
実施例１１
実施例１２
実施例１５
未処理
第４表
５分値 ３０分値
６６５
０８４
３８８
２９２
２６８
１９２
５９２
３４０
〔発明の効果〕
高分子カルボン酸が膜面積１ｒＴｒあたり０．１ｍｇ以
上グラフトしている本発明の再生セルロース膜は、次の
ような顕著な効果を奏する。Hollow fiber membrane 1 Example 1 Example 3 Example 7 Example 9 Example 11 Example 12 Example 15 Untreated Table 4 5 minute value 30 minute value 665 084 388 292 268 192 592 340 [Effect of the invention] High The regenerated cellulose membrane of the present invention, in which molecular carboxylic acid is grafted in an amount of 0.1 mg or more per 1 rTr of membrane area, has the following remarkable effects.
イ、 第１．２．３表に示されるように、補体成分の活
性化作用が抑制される。B. As shown in Table 1.2.3, the activation effect of complement components is suppressed.
Ｕ、 第４表に示されるように、白血球一過性減少が大
幅に軽減される。U. As shown in Table 4, the transient decrease in leukocytes is significantly reduced.
ハ、 製造が容易であり、用いた試薬等を除去すること
も容易であるので、経済的で安全性の高い透析膜である
。C. It is an economical and highly safe dialysis membrane because it is easy to manufacture and the reagents used are easy to remove.
Claims (1)
と接触する膜表面に、膜面積１ｍ＾２あたり０．１ｍｇ
以上のポリエチレングライコールジカルボン酸またはポ
リエチレングライコールモノカルボン酸のアシル残基が
エステル結合によりグラフトしていることを特徴とする
再生セルロース系透析膜。1. In regenerated cellulose-based dialysis membranes, at least on the membrane surface that comes into contact with blood, 0.1 mg per 1 m^2 of membrane area.
A regenerated cellulose-based dialysis membrane characterized in that the acyl residues of the above polyethylene glycol dicarboxylic acid or polyethylene glycol monocarboxylic acid are grafted through ester bonds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1134533A JPH034924A (en) | 1989-05-30 | 1989-05-30 | Reproduced cellulose yarn dialysis membrane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1134533A JPH034924A (en) | 1989-05-30 | 1989-05-30 | Reproduced cellulose yarn dialysis membrane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH034924A true JPH034924A (en) | 1991-01-10 |
| JPH0556175B2 JPH0556175B2 (en) | 1993-08-18 |
Family
ID=15130543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1134533A Granted JPH034924A (en) | 1989-05-30 | 1989-05-30 | Reproduced cellulose yarn dialysis membrane |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH034924A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE112016000556B4 (en) | 2015-01-29 | 2021-11-11 | The Yokohama Rubber Co., Ltd. | tire |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105056772B (en) * | 2015-09-18 | 2017-05-31 | 淮阴师范学院 | The preparation method of polyvinyl alcohol/recessed native poly ion liquid catalytic esterification composite membrane |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63238869A (en) * | 1986-11-07 | 1988-10-04 | 筏 義人 | Blood compatible cellulosic dialytic membrane and its production |
-
1989
- 1989-05-30 JP JP1134533A patent/JPH034924A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63238869A (en) * | 1986-11-07 | 1988-10-04 | 筏 義人 | Blood compatible cellulosic dialytic membrane and its production |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE112016000556B4 (en) | 2015-01-29 | 2021-11-11 | The Yokohama Rubber Co., Ltd. | tire |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0556175B2 (en) | 1993-08-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0266795B2 (en) | Improved regenerated cellulose membrane and process for preparation thereof | |
| CA1326418C (en) | Extracorporeal blood de-heparinization system | |
| US4008047A (en) | Blood compatible polymers for blood oxygenation devices | |
| EP0641226A1 (en) | Polymeric coating. | |
| JP3899128B2 (en) | Apparatus and method for biospecific removal of heparin | |
| SE436242B (en) | BIO-COMPATIBLE POLYMER MATERIAL AND PROCEDURE FOR ITS PREPARATION | |
| EP0404683A2 (en) | Medical material, process for its production, and medical device using the medical material | |
| JPH04314453A (en) | Medical material, medical apparatus and manufacture of medical material | |
| US4882106A (en) | Methods of manufacturing nucleophilic material modified for improved biocompatibility | |
| KR970007243B1 (en) | Water-soluble cellulose derivatives and biocompatible material | |
| JPH034924A (en) | Reproduced cellulose yarn dialysis membrane | |
| JPH022848A (en) | Improved regenerated cellulose membrane and its production | |
| CN109647227A (en) | A kind of filter membrane and preparation method thereof removing low-density lipoprotein | |
| DE10135277C2 (en) | Defoaming agent, device with a surface coated with the defoaming agent and use of such a device | |
| US5073265A (en) | Methods of manufacturing nucleophilic material modified for improved biocompatibility | |
| JP2904286B2 (en) | Dialysis membrane for hemodialysis | |
| CA1188222A (en) | Agents for improvement of peripheral blood flow | |
| JPH0611318B2 (en) | Hemophilic cellulose-based dialysis membrane and method for producing the same | |
| JP3108453B2 (en) | Anticoagulant materials and medical devices | |
| JP4453395B2 (en) | Use of extracorporeal circulation column suitable for cancer treatment | |
| JP2754203B2 (en) | Sterilization method for body fluid treatment device and sterilized body fluid treatment device | |
| CA1312430C (en) | Methods of manufacturing nucleophilic material modified for improved biocompatibility | |
| JPS6121243B2 (en) | ||
| JPH0470047B2 (en) | ||
| JP2929541B2 (en) | Medical material and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| LAPS | Cancellation because of no payment of annual fees |