JP5160015B2 - Separation membrane for water treatment - Google Patents
Separation membrane for water treatment Download PDFInfo
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- JP5160015B2 JP5160015B2 JP2003368531A JP2003368531A JP5160015B2 JP 5160015 B2 JP5160015 B2 JP 5160015B2 JP 2003368531 A JP2003368531 A JP 2003368531A JP 2003368531 A JP2003368531 A JP 2003368531A JP 5160015 B2 JP5160015 B2 JP 5160015B2
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- 239000012528 membrane Substances 0.000 title claims description 103
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims description 61
- 238000011282 treatment Methods 0.000 title claims description 24
- 238000000926 separation method Methods 0.000 title claims description 20
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 17
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 17
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 17
- 239000011550 stock solution Substances 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 11
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- 239000013543 active substance Substances 0.000 description 4
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- 239000002033 PVDF binder Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004695 Polyether sulfone Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229920003278 Udel® P1700 Polymers 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
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- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
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- 229920000768 polyamine Polymers 0.000 description 2
- 229920006393 polyether sulfone Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 2
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- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- ZSZRUEAFVQITHH-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CC(=C)C(=O)OCCOP([O-])(=O)OCC[N+](C)(C)C ZSZRUEAFVQITHH-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 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
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
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Landscapes
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Artificial Filaments (AREA)
Description
本発明は、生体と接触する界面に使用される膜に関する。特に衣料用途、医療用途をはじめ、皮膚と接触する材料の表面に用いる材料や、体液と接触する血液浄化用の医療材、水中の微生物やさびなどを除去する浄水器などの水処理用途などに用いることができる。 The present invention relates to a membrane used for an interface in contact with a living body. Especially for clothing and medical applications, materials used on the surface of materials that come into contact with the skin, blood purification medical materials that come into contact with body fluids, water treatment applications such as water purifiers that remove microorganisms and rust in the water, etc. Can be used.
従来、膜単独では、荷電膜としてスルホン酸基を有したポリマーからなる膜（たとえば特許文献１参照）、製膜後アミドメチル化反応をすることでアミノ基を導入した膜（たとえば特許文献２参照）などが知られている。その他にもアニオン選択吸着性多孔膜とその製造方法（たとえば特許文献３参照）が開示されている。これらの膜では、酸性官能基と塩基性官能基を両方持たせることは考えられておらず、陽性か陰性の荷電を有することで、血中の蛋白質吸着挙動をコントロールする目的に用いられてきた。また、両性荷電を有するものではリン脂質を模した2-メタクリロイルオキシエチルホスホリルコリン（以下、ＭＰＣと略す）を重合したＭＰＣポリマーをコーティングする方法なども知られており（たとえば特許文献４参照）、一つの原液から製膜した例（たとえば特許文献５参照）も開示されているが、膜構造の制御が難しく、所望の分画特性を発現させることは困難であった。また、アミノ酸のような塩基性官能基や酸性官能基を持つモノマーからなる材料についても白血球除去材料で使用した例（例えば特許文献６）も知られているが、溶液中での放射線グラフト重合、プラズマ照射による導入であり、塩基性官能基、酸性官能基の分布が重なりやすく、また孔径が２ミクロン未満の膜に対しては孔が閉塞しやすく適用しにくい。
皮膚や体液などと接する用途に用いる膜において、生体適合性の向上は今や必須要件である。これらの要求を満たす高分子素材の開発はここ２０年ほど行われてきたが、ミクロ相分離構造を有するポリマーに代表されるように、今なお耐滅菌性と低コスト化、高い高次加工性を満たした材料は十分には得られていない。先に記述したＭＰＣポリマーについても、コスト面での改善が要求される。ＭＰＣポリマーでは膜そのものを形成することができないため、既存の構造体にコートするなどの操作が必要になり、この操作によって膜構造が目詰まりを起こし孔径が変化するため、精密な分離膜の設計には不向きな点が多い。 Improving biocompatibility is now an essential requirement for membranes used in contact with skin and body fluids. The development of polymer materials that meet these requirements has been carried out for the past 20 years, but as typified by polymers having a microphase-separated structure, sterilization resistance, low cost, and high-order processability are still present. A material satisfying the above has not been sufficiently obtained. The MPC polymer described above is also required to be improved in cost. Since the MPC polymer cannot form a membrane itself, an operation such as coating an existing structure is required, and this operation causes clogging of the membrane structure and changes the pore size. There are many unsuitable points.
そこで、精密な孔径制御が可能であり、かつ、生体適合性に優れた膜表面を有し、簡便に、低コストで形成される分離膜を目的に鋭意研究した結果、本発明に至った。 Thus, as a result of intensive studies aimed at a separation membrane that can be precisely controlled in pore size and has a membrane surface excellent in biocompatibility and is formed simply and at low cost, the present invention has been achieved.
上記課題を解決するため、本発明は、下記の構成を有する。 In order to solve the above problems, the present invention has the following configuration.
多孔性膜であり、少なくとも、ポリビニルピロリドンと分離膜形成が可能なポリマーと水とを混合したものを製膜原液とし、製膜し、洗浄した段階で、膜表面に残留ポリビニルピロリドンを確保し、その後乾燥させ、熱処理およびまたは放射線処理を施すことで、少なくともカルボキシル基からなる酸性基と１級、２級、３級、４級アミンからなる群より選ばれた１種類以上の塩基性基を自発的に膜表面に形成させ、膜表面に酸性基および塩基性基を持ち、酸性基の密度が５μmol/ｇ以上でかつ塩基性基の密度が３μmol/ｇ以上であり、かつ、膜表面の最大孔径の直径が２ミクロン未満、透水性能が1500ml/hr・kPa・m 2 以上であることを特徴とする水処理用分離膜。 A porous membrane, at least a mixture of polyvinyl pyrrolidone and a polymer capable of forming a separation membrane and water is used as a membrane forming stock solution, and after the membrane is formed and washed, residual polyvinyl pyrrolidone is secured on the membrane surface, Then, it is dried and subjected to heat treatment and / or radiation treatment to spontaneously generate at least one acidic group consisting of carboxyl groups and one or more basic groups selected from the group consisting of primary, secondary, tertiary and quaternary amines. Formed on the membrane surface, has acidic groups and basic groups on the membrane surface, the density of acidic groups is 5 μmol / g or more, the density of basic groups is 3 μmol / g or more, and the maximum on the membrane surface A separation membrane for water treatment characterized by a pore diameter of less than 2 microns and a water permeability of 1500 ml / hr · kPa · m 2 or more .
(2)該酸性基または該塩基性基との反応によりさらに有機物を固定したことを特徴とする(1)項に記載の水処理用分離膜。 ( 2 ) The separation membrane for water treatment according to (1) , wherein an organic substance is further fixed by reaction with the acidic group or the basic group.
(3)膜の形態が中空糸状であることを特徴とする(1)または(2)項に記載の水処理用分離膜。 ( 3 ) The separation membrane for water treatment as described in (1) or (2 ), wherein the membrane is in the form of a hollow fiber.
(4)ポリスルホン系樹脂を含むことを特徴とする(1)〜(3)のいずれかに記載の水処理用分離膜。 ( 4 ) The separation membrane for water treatment according to any one of (1) to ( 3 ), comprising a polysulfone resin.
精密な孔径制御を可能とした分離膜でかつ、生体膜を模倣した表面を簡便に、低コストで形成することを目的とする。 It is an object of the present invention to easily and inexpensively form a separation membrane that enables precise pore size control and that mimics a biological membrane.
以下本発明についてさらに詳細に説明する。 The present invention will be described in further detail below.
本発明は、酸性基および塩基性基を合わせ持つ分離膜を提供するものである。
膜として分離性能を発揮するため、膜表面の孔のうち、最大孔経を有する膜の直径が２ミクロン未満であることが必要である。これ以上の孔径を有するものは、目詰まりを起こす危険はないが、例えば血液浄化などの用途に対し、白血球や、赤血球の除去用途にしか使用することができず、生体膜を模した生体適合性の良さを発揮するに至らない。本発明では２ミクロン未満の孔径を持つため生体膜に近い分離膜を提供することができ、人工腎臓を始め、血漿分離膜など様々な用途への利用が可能となる。
The present invention provides a separation membrane having both an acidic group and a basic group.
In order to exhibit separation performance as a membrane, it is necessary that the diameter of the membrane having the largest pore diameter among the pores on the membrane surface is less than 2 microns. Those with a larger pore size do not risk clogging, but can only be used to remove white blood cells or red blood cells, for example for blood purification, and is biocompatible that mimics biological membranes It does not lead to good sexuality. In the present invention, since it has a pore size of less than 2 microns, it is possible to provide a separation membrane close to a biological membrane, and it can be used for various applications such as an artificial kidney and a plasma separation membrane.
膜には、少なくともカルボキシル基からなる酸性基を含み、さらにリン酸基、スルホン酸基から選ばれる少なくとも１種類の官能基が付加されていることが好適である。塩基性基としてはアミノ基（１級、２級、３級、４級アミンから選ばれる少なくとも１つの官能基）、イミノ基、ウレイド基、アミジノ基、アミノオキシ基などから選ばれた１種類以上の官能基が好適である。 It is preferable that the membrane contains at least an acidic group composed of a carboxyl group and further has at least one functional group selected from a phosphoric acid group and a sulfonic acid group added thereto. As the basic group, at least one selected from an amino group (at least one functional group selected from primary, secondary, tertiary, and quaternary amine), imino group, ureido group, amidino group, aminooxy group, and the like. The functional group is preferred.
官能基の密度は容量滴定によって定量することができる。特に以下で述べる逆滴定法によって測定することが好適である。逆滴定法とは、膜表面で消費された酸または塩基の量を容量滴定する方法である。 The density of functional groups can be quantified by volumetric titration. It is particularly preferable to measure by the back titration method described below. The reverse titration method is a method in which the amount of acid or base consumed on the membrane surface is titrated by volume.
酸性基密度として、５μmol/ｇ以上が好ましく、この官能基を用いて、さらに生理活性物質、ポリマー、モノマーの固定を図るためには、10μmol/ｇ以上が好ましい。 The acid group density is preferably 5 μmol / g or more. In order to further fix physiologically active substances, polymers and monomers using this functional group, 10 μmol / g or more is preferable.
塩基性基密度としても、３μmol/ｇ以上が好ましく、この官能基を用いて、さらに生理活性物質、ポリマー、モノマーの固定を図るためには、10μmol/ｇ以上が好ましく、固定密度を上げるためには25μmol/ｇ以上がさらに好ましい。またこれら２種類の官能基が膜表面に分布することで、血液接触時の生体適合成が向上する。詳細な機構は不明であるが、生体膜表面でのミクロな電化分布を模倣しているためと思われる。これらの目的のため、両官能基ともに５μmol/ｇ以上であることが好ましく、さらに10μmol/ｇ以上であれば、血液適合性が向上しさらに好ましい。 The basic group density is also preferably 3 μmol / g or more. In order to further fix physiologically active substances, polymers, and monomers using this functional group, 10 μmol / g or more is preferable. Is more preferably 25 μmol / g or more. In addition, since these two types of functional groups are distributed on the membrane surface, biosynthetic synthesis at the time of blood contact is improved. The detailed mechanism is unknown, but it seems to mimic the micro electrification distribution on the surface of the biological membrane. For these purposes, both functional groups are preferably 5 μmol / g or more, and more preferably 10 μmol / g or more because blood compatibility is improved.
膜への酸性および塩基性官能基の付与は、以下に掲げる方法により実現できるが、これ以外の方法でもかまわない。 Application of acidic and basic functional groups to the membrane can be realized by the following methods, but other methods may be used.
酸性基、塩基性基を導入するための添加剤としては、例えばポリリン酸のような酸性基を持つポリマーと、ポリアミンのような塩基性基を持つポリマー、すなわちイオン性基を持つポリマーの混合や、環状アミドを持つポリビニルピロリドンおよびその誘導体の混合が考えられる。製糸原液を調製する際にイオン性ポリマーと混合する方法ではポリリン酸やポリアクリル酸などの酸性基を持つポリマーとポリエチレンイミンのようなポリアミンとの混合が考えられるが、この場合は原液を均一に溶解することが難しい場合があり、より好ましくは後者のポリビニルピロリドンおよびその誘導体と分離膜形成が可能なポリマーとの混合を行う。ポリビニルピロリドンはいろいろなエンジニアリングプラスチック、例えば、ポリスルホン、ポリエーテルスルホン、ポリメチルメタクリレート（以下、ＰＭＭＡと略す）、ポリビニリデンフルオリドなどのフッ素性樹脂などと相溶性が良く、原液粘度を上げることができるために紡糸原液としてこの組み合わせは好適に用いることができる。ポリビニルピロリドンとして分子量は種々のものを用いることが可能であるが、Ｋ９０，Ｋ６０，Ｋ３０，Ｋ１５など市販されているものを使うと簡便である。これらの混合や、上記以外の分子量領域のものを重合して用いても良いが、分子量が高いほど原液としては使用しやすい。このため、Ｋ９０を用いるのがより好ましい。溶媒としてはジメチルアセトアミド（以下ＤＭＡｃと略す）やN-メチルピロリドンのような高沸点極性溶媒が好ましいが、均一に溶解できることができればその他の組み合わせでも使用可能である。膜を構成するポリマーとしては、ポリスルホン、ポリエーテルスルホン、PMMA、ポリビニリデンフルオリドなどのフッ素性樹脂が好適に用いられるが、下記製造法での後処理に耐えるポリマー、すなわち、放射線処理または７０℃以上で膜構造が変化しない素材であればこれらに限らない。 Examples of additives for introducing acidic groups and basic groups include a mixture of a polymer having an acidic group such as polyphosphoric acid and a polymer having a basic group such as polyamine, that is, a polymer having an ionic group. Further, a mixture of polyvinylpyrrolidone having a cyclic amide and a derivative thereof is conceivable. In the method of mixing with an ionic polymer when preparing the yarn stock solution, mixing of a polymer having an acidic group such as polyphosphoric acid or polyacrylic acid with a polyamine such as polyethyleneimine is possible. In some cases, it is difficult to dissolve, and the latter polyvinyl pyrrolidone and its derivatives are mixed with a polymer capable of forming a separation membrane. Polyvinylpyrrolidone has good compatibility with various engineering plastics, for example, fluorine resins such as polysulfone, polyethersulfone, polymethyl methacrylate (hereinafter abbreviated as PMMA) and polyvinylidene fluoride, and can increase the viscosity of the stock solution. Therefore, this combination can be suitably used as a spinning dope. Polyvinyl pyrrolidone having various molecular weights can be used, but it is convenient to use commercially available products such as K90, K60, K30, K15. A mixture thereof or a polymer having a molecular weight other than those described above may be polymerized and used. For this reason, it is more preferable to use K90. The solvent is preferably a high-boiling polar solvent such as dimethylacetamide (hereinafter abbreviated as DMAc) or N-methylpyrrolidone, but other combinations can be used as long as they can be dissolved uniformly. As the polymer constituting the membrane, a fluororesin such as polysulfone, polyethersulfone, PMMA, and polyvinylidene fluoride is preferably used. However, a polymer that can withstand post-treatment in the following production method, that is, radiation treatment or 70 ° C. The material is not limited to the above as long as the film structure does not change.
この原液を用いて、膜すなわち分離膜を製造するが、その形状は平膜であっても、中空糸膜であってもかまわない。中空糸膜を製造する場合には、透水性の小さい1500ml/hr・kPa・m2程度の膜を作るには、注入液としてＤＭＡｃと水が55/45程度の混合液を用いて紡糸が可能である。それ以上の透水性を求めるには、例えばこの比を95/5程度に迄高めれば75000ml/hr・kPa・m2程度の膜を作ることも可能である。こうしてできた膜に例えば以下に述べる後処理をすることによって、酸性基、塩基性基の両方を膜表面に付与することができる。まず水洗し、より好ましくは沸騰水中で洗浄し、付着ポリビニルピロリドンの量を調節する。５時間以上洗浄するとポリビニルピロリドンの残存量が少なすぎ、酸性基、塩基性基を所望の密度で膜表面に付与することはできない。４時間以下がより好ましく、２時間程度であれば表面官能基量は十分であり、生理活性物質等の担持も可能となる。このあと、膜を透過させて洗浄し、その後乾燥させ、酸素存在下で、70℃以上の膜素材が溶融しない温度で熱処理を施すこと、およびまたは、ラジカルスカベンジャーの非存在下放射線処理を施すこと等によって達成される。膜を塩基性に保つことは不要である。処理時間は２時間程度から可能であるが、処理時間が長いほど表面官能基密度は高くなる。処理温度は使用した膜構造構成ポリマーのガラス転位温度以下が好ましい。温度が高くなるほど表面官能基密度は高くなる。温度および時間の組み合わせで、表面官能基密度は調整が可能である。これらの処理によって、カルボキシル基およびアミノ基が自発的に膜表面に形成される。ポリリン酸や硫酸共存下で上記後処理をおこなうことでリン酸基やスルホン酸基の導入も可能である。 A membrane, that is, a separation membrane is produced using this stock solution, but the shape may be a flat membrane or a hollow fiber membrane. When manufacturing hollow fiber membranes, spinning with a mixture of DMAc and water of about 55/45 is possible as an injection solution to produce a membrane with a low water permeability of about 1500 ml / hr · kPa · m 2. It is. In order to obtain higher water permeability, for example, if this ratio is increased to about 95/5, a film of about 75000 ml / hr · kPa · m 2 can be formed. By subjecting the film thus formed to post-treatment described below, for example, both acidic groups and basic groups can be imparted to the film surface. First, it is washed with water, more preferably with boiling water, and the amount of adhered polyvinylpyrrolidone is adjusted. When washed for 5 hours or more, the residual amount of polyvinyl pyrrolidone is too small, and acidic groups and basic groups cannot be imparted to the film surface at a desired density. 4 hours or less is more preferable, and if it is about 2 hours, the amount of surface functional groups is sufficient, and it is possible to carry a physiologically active substance or the like. After this, the membrane is permeated and washed, then dried, and heat-treated in the presence of oxygen at a temperature at which the film material of 70 ° C. or higher does not melt, or radiation treatment in the absence of a radical scavenger. Achieved by etc. It is not necessary to keep the membrane basic. The treatment time can be from about 2 hours, but the longer the treatment time, the higher the surface functional group density. The treatment temperature is preferably equal to or lower than the glass transition temperature of the film structure constituting polymer used. The higher the temperature, the higher the surface functional group density. The surface functional group density can be adjusted by a combination of temperature and time. By these treatments, carboxyl groups and amino groups are spontaneously formed on the film surface. Phosphoric acid groups and sulfonic acid groups can be introduced by performing the above-mentioned post-treatment in the presence of polyphosphoric acid or sulfuric acid.
酸性基の密度が５μｍｏｌ／ｇ以上で、塩基性基の密度が３μｍｏｌ／ｇ以上とするためには、上述のとおり、水洗時間を５時間以下にして残存ポリビニルピロリドンを確保し、その後乾燥させ、酸素存在下で、70℃以上の膜素材が溶融しない温度で熱処理を施すこと、およびまたは、ラジカルスカベンジャーの非存在下放射線処理を施すこと等によって達成される。 さらに高密度にするためには熱処理温度を高めたり、放射線照射量を高めればよい。 In order to set the density of acidic groups to 5 μmol / g or more and the density of basic groups to 3 μmol / g or more, as described above, the washing time is set to 5 hours or less to ensure the remaining polyvinylpyrrolidone, and then dried. This is achieved by performing heat treatment at a temperature at which the film material of 70 ° C. or higher does not melt in the presence of oxygen, or by performing radiation treatment in the absence of a radical scavenger. In order to achieve a higher density, the heat treatment temperature may be increased or the radiation dose may be increased.
膜表面の酸性基および／または塩基性基に有機物を固定するためには、これら官能基と、タンパク質やその他生理活性物質などのカルボキシル基およびまたはアミノ基との縮合反応をすることによって可能である。 In order to fix organic substances to the acidic group and / or basic group on the membrane surface, it is possible to perform a condensation reaction between these functional groups and carboxyl groups and / or amino groups of proteins and other physiologically active substances. .
透水性については、血液浄化や水処理用途などで高い方が好ましいが、本発明においては２ミクロン未満の孔径で1500ml/hr・kPa・m2以上の透水性を有する膜を作ることが可能である。 The water permeability is preferably higher for blood purification and water treatment applications, but in the present invention, it is possible to produce a membrane having a water permeability of 1500 ml / hr · kPa · m 2 or more with a pore diameter of less than 2 microns. is there.
本発明により得られた分離膜は、皮膚と接触するガーゼや創傷被服材の表面に用いる材料や体液と接触する血液浄化用の医療材、水中のさびや微生物を除去する浄水器などの水処理用途 などとして好適に用いられる。 The separation membrane obtained by the present invention is a water treatment such as a gauze that comes into contact with the skin, a material used for the surface of a wound dressing material, a blood purification medical material that comes into contact with a body fluid, a water purifier that removes rust and microorganisms in water. It is suitably used for applications.
以下、実施例によってさらに詳細に説明する。 Hereinafter, it demonstrates still in detail according to an Example.
用いた測定法は以下の通りである。
（１）逆滴定法
膜を乾燥させ、１ｇ用意する。測定は２３℃室温下で行った。測定を３回繰り返し、その平均値を採用した。
The measurement method used is as follows.
(1) Back titration method The membrane is dried to prepare 1 g. The measurement was performed at room temperature at 23 ° C. The measurement was repeated three times and the average value was adopted.
酸性基の定量用のものは、あらかじめ1/10mol濃度のHCl水溶液（容量分析用）10mlで15min以上浸漬し、Na塩などを除く。その膜を、超純水で十分洗浄し、洗浄後の水が中性（pHが７±1）になったのを確認し、凍結乾燥させる。得られた膜を、1/100mol濃度のNaOH水溶液（容量分析用）100ml中に１hr振盪浸漬し、そのうちの30mlを取り出し、1/100mol濃度のHCl水溶液（容量分析用）を用いて容量分析を行う。先に用いた1/100mol濃度のNaOH水溶液（容量分析用）30mlを同様に容量滴定し（コントロール）、中和に使用した1/100mol濃度のHCl水溶液（容量分析用）量の差から、膜に付着した酸性基の濃度を計算で求める。 For quantification of acidic groups, immerse in advance with 10 ml of 1/10 mol HCl aqueous solution (for volumetric analysis) for 15 min or longer to remove Na salts. The membrane is thoroughly washed with ultrapure water, and it is confirmed that the water after washing has become neutral (pH is 7 ± 1) and freeze-dried. The obtained membrane was shaken and immersed in 100 ml of 1/100 mol NaOH aqueous solution (for volumetric analysis) for 1 hour, 30 ml of which was taken out, and volumetric analysis was performed using 1/100 mol HCl aqueous solution (for volumetric analysis). Do. The volume of 1/100 mol NaOH aqueous solution (for volumetric analysis) 30 ml used before was titrated in the same manner (control), and the difference in the amount of 1/100 mol HCl aqueous solution (for volumetric analysis) used for neutralization The concentration of acidic groups attached to the surface is calculated.
同様に塩基性基の定量用のものは、あらかじめ1/10mol濃度のNaOH水溶液（容量分析用）10mlで15min以上浸漬し、例えばHCl塩などを除く。その膜を、超純水で十分洗浄し、洗浄液が中性（pHが７±1）になったのを確認し、乾燥させる。得られた膜を、1/100mol濃度のHCl水溶液（容量分析用）100ml中に１hr振盪浸漬し、そのうちの30mlを取り出し、1/100mol濃度のNaOH水溶液（容量分析用）を用いて容量分析を行う。先に用いた1/100mol濃度のHCl水溶液（容量分析用）30mlを同様に容量滴定し（コントロール）、中和に使用した1/100mol濃度のNaOH水溶液（容量分析用）量の差から、膜に付着した酸性基の濃度を計算で求める。 Similarly, those for quantifying basic groups are preliminarily immersed in 10 ml of 1/10 mol NaOH aqueous solution (for volumetric analysis) for 15 min or longer to remove, for example, HCl salts. The membrane is thoroughly washed with ultrapure water, and it is confirmed that the washing solution is neutral (pH is 7 ± 1) and dried. The obtained film was immersed in 100 ml of 1/100 mol HCl aqueous solution (for volumetric analysis) for 1 hr with shaking, 30 ml of which was taken out, and volumetric analysis was performed using 1/100 mol NaOH aqueous solution (for volumetric analysis). Do. 30 ml of the 1/100 mol HCl aqueous solution (for volumetric analysis) used previously was volume titrated in the same manner (control), and the membrane was determined from the difference in the amount of 1/100 mol NaOH aqueous solution (for volumetric analysis) used for neutralization. The concentration of acidic groups attached to the surface is calculated.
膜１ｇ当たりの酸性基、塩基性基の官能基密度は以下の式１で計算した。 The functional group density of acidic groups and basic groups per gram of membrane was calculated by the following formula 1.
官能基密度（μmol/ｇ）=33.3×（サンプルの中和に必要な液量（ml）-コントロール 液量（ml）） 式１
（２）透水性能の測定
中空糸両端部を封止したガラス管ミニモジュール（本数３６本：有効長１０ｃｍ）の中空糸内側に水圧１００ｍｍＨｇをかけ、外側へ流出してくる単位時間当たりの濾過量を測定した。
Functional group density (μmol / g) = 33.3 × (volume required for sample neutralization (ml) −control volume (ml)) Formula 1
(2) Measurement of water permeation performance A water pressure of 100 mmHg is applied to the inside of the hollow fiber of a glass tube mini-module (36 pieces: effective length 10 cm) sealed at both ends of the hollow fiber, and the amount of filtration per unit time flowing out to the outside Was measured.
透水性能は下記の式２で算出した。 The water permeability was calculated by the following formula 2.
透水性能（ml/hr・kPa・m2）＝濾過水量（ml）÷流出時間（hr）÷圧力差（kPa）÷中空糸膜内表面面積(m2) 式２
（３）アルブミン透過率の測定
血液槽に温度３７℃で保温したヘマトクリット３０％、総蛋白量６．５ｇ／ｄｌの牛血（ヘパリン処理血）を用いて、中空糸内側にポンプで２００ｍｌ／ｍｉｎで送った。その際、モジュール出口側の圧力を調整して、濾過量がモジュール面積１ｍ2当たり２０ｍｌ／ｍｉｎ（すなわち１．６ｍ2では３２ｍｌ／ｍｉｎ）かかるようにし、濾液、出口血液は血液槽に戻した。環流開始後１時間後に中空糸側入り口、出口の血液、濾液をサンプリングし、血液は遠心分離により血清に分離した後、商品名Ａ／Ｇ Ｂ−テストワコーアルブミン発色試薬（和光純薬）のＢＣＧ（ブロムクレゾールグリーン）法キットによって分析し、その濃度からアルブミン透過率（％）を算出した。また、濾液の濃度算出に当たって、アルブミンの検量線については、良好な感度を得るため、低濃度での検量線を作成する目的で、キット付属の血清アルブミンを適宜、希釈して作成した。
Permeability (ml / hr · kPa · m 2 ) = Filtration water volume (ml) ÷ Outflow time (hr) ÷ Pressure difference (kPa) ÷ Hollow fiber membrane surface area (m 2 ) Equation 2
(3) Measurement of albumin permeability Using bovine blood (heparin-treated blood) having a hematocrit of 30% and a total protein content of 6.5 g / dl kept at 37 ° C. in a blood tank, the inner side of the hollow fiber is pumped at 200 ml / min. Sent by. At that time, the pressure on the module outlet side was adjusted so that the filtration amount was 20 ml / min per 1 m 2 of module area (that is, 32 ml / min for 1.6 m 2 ), and the filtrate and outlet blood were returned to the blood tank. One hour after the start of recirculation, the blood and filtrate at the inlet and outlet of the hollow fiber were sampled. The blood was separated into serum by centrifugation, and then BCG of the trade name A / GB B-Test Wako albumin coloring reagent (Wako Pure Chemical Industries) (Bromcresol green) was analyzed by a method kit, and albumin permeability (%) was calculated from the concentration. In calculating the concentration of the filtrate, an albumin calibration curve was prepared by appropriately diluting the serum albumin attached to the kit for the purpose of creating a calibration curve at a low concentration in order to obtain good sensitivity.
アルブミン透過率（％）=100×２×濾液中アルブミン濃度÷（モジュール入り口アルブミン濃度+モジュール出口アルブミン濃度） 式３
（４）表面孔径の測定
中空糸膜に凍結乾燥処理を施す。これを試料として走査型電子顕微鏡観察を行う。ランダムに１０視野（1000倍）観察し、孔径の大きい部分についてさらに倍率を上げて測定精度を上げて観察し、長径と短径の平均値を最大孔径とする。この最大孔径を１視野あたり３点計測する。都合３０点の測定の平均値を持ってこの膜の最大孔径とする。膜の表裏又は内外表面の両面について実施し、最大孔径の小さい面の最大孔径が実質的物質透過を規定するため、この値を採用する。
（実施例１）
ポリスルホン（アモコ社 Ｕｄｅｌ−Ｐ３５００）8部、（アモコ社 Ｕｄｅｌ−Ｐ１７００）8部、ポリビニルピロリドン（インターナショナルスペシャルプロダクツ社；以下ＩＳＰ社と略す） Ｋ３０ ４部、ポリビニルピロリドン（ＩＳＰ社Ｋ９０）２部をジメチルアセトアミド７７部、水１部を加熱溶解し、製膜原液とした。
Albumin permeability (%) = 100 × 2 × albumin concentration in filtrate ÷ (module inlet albumin concentration + module outlet albumin concentration) Equation 3
(4) Measurement of surface pore diameter The hollow fiber membrane is freeze-dried. This is used as a sample for observation with a scanning electron microscope. Observe 10 fields of view (1000 times) at random, and further increase the magnification of the portion with a large pore diameter and increase the measurement accuracy, and the average value of the major and minor diameters is taken as the maximum pore diameter. This maximum pore size is measured at three points per field of view. The average value of the measurement at 30 points is taken as the maximum pore size of this membrane. It is carried out on both the front and back surfaces of the membrane or both the inner and outer surfaces, and this value is adopted because the maximum pore size of the surface having a small maximum pore size defines the substantial material permeation.
Example 1
Polysulfone (Amoco Corporation Udel-P3500) 8 parts, (Amoco Corporation Udel-P1700) 8 parts, Polyvinylpyrrolidone (International Special Products Co .; hereinafter abbreviated as ISP) K30 4 parts, Polyvinylpyrrolidone (ISP K90) 2 parts 77 parts of acetamide and 1 part of water were dissolved by heating to obtain a stock solution.
原液粘度は５０℃で1．2Pa・secであった。この原液を温度５０℃の紡糸口金部へ送り、外径０．３５ｍｍ、内径０．２５ｍｍの２重スリット管から芯液としてジメチルアセトアミド６０部、水４０部からなる溶液を吐出させ、中空糸状を形成させた後、温度３０℃、露点２８℃で調湿し、１０ミクロン以下のドライミストを加えた２５０ｍｍのドライゾーン雰囲気を経て、ジメチルアセトアミド２０重量％、水８０重量％からなる温度４０℃の凝固浴を通過させ、８０℃15分の水洗工程を通過させ、巻き取り束とした。中空糸内径は200μｍ、膜厚40μｍである。この束を100℃で2時間水洗した後、１００℃で２時間乾燥後、１７０℃の熱処理工程でさらに３．５時間処理し、膜面積１．６ｍ2になるように、ケースに充填し、ポッティングし、端部を両面開口させて、血液浄化モジュールとした。この後乾燥状態で、γ線照射（２５ＫＧｙ）を行ない滅菌し実施例１の膜を得た。 The viscosity of the stock solution was 1.2 Pa · sec at 50 ° C. This stock solution is sent to a spinneret at a temperature of 50 ° C., and a solution consisting of 60 parts of dimethylacetamide and 40 parts of water is discharged as a core liquid from a double slit tube having an outer diameter of 0.35 mm and an inner diameter of 0.25 mm. After the formation, humidity was adjusted at a temperature of 30 ° C. and a dew point of 28 ° C., and after passing through a 250 mm dry zone atmosphere to which a dry mist of 10 microns or less was added, a temperature of 40 ° C. consisting of 20% by weight of dimethylacetamide and 80% by weight of water It was passed through a coagulation bath and passed through a water washing step at 80 ° C. for 15 minutes to obtain a wound bundle. The inner diameter of the hollow fiber is 200 μm and the film thickness is 40 μm. The bundle was washed with water at 100 ° C. for 2 hours, dried at 100 ° C. for 2 hours, further treated in a heat treatment step at 170 ° C. for 3.5 hours, and filled into a case so that the film area was 1.6 m 2 . Potting was performed, and both ends were opened, thereby obtaining a blood purification module. Thereafter, in a dry state, γ-ray irradiation (25 KGy) was performed and sterilized to obtain the membrane of Example 1.
得られたモジュールから膜を切り出し、５０本束ね、中空糸中空部を閉塞しないようにエポキシ系ポッティング剤で両末端をガラス管モジュールケースに固定し、ミニモジュールを作成した。該ミニモジュールの直径は約７mm、長さは約１２cmである。 Membranes were cut out from the obtained module, bundled 50, and both ends were fixed to a glass tube module case with an epoxy-based potting agent so as not to block the hollow portion of the hollow fiber, thereby producing a mini module. The minimodule has a diameter of about 7 mm and a length of about 12 cm.
また、実施例１の中空糸膜の透水性能は2050ml/hr・kPa・m2であり、表面官能基量は、酸性基66.3μmol/ｇ、塩基性基33.3μmol/ｇであった。中空糸膜表面の赤外分光解析で、カルボキシル基およびアミノ基の存在を確認した。最大孔径は内表面側で、０．０６ミクロンであった。
（実施例２）
ポリスルホン（アモコ社 Ｕｄｅｌ−Ｐ３５００）8部、（アモコ社 Ｕｄｅｌ−Ｐ１７００）8部、ポリビニルピロリドン（インターナショナルスペシャルプロダクツ社；以下ＩＳＰ社と略す） Ｋ３０ ４部、ポリビニルピロリドン（ＩＳＰ社Ｋ９０）２部をジメチルアセトアミド７７部、水１部を加熱溶解し、製膜原液とした。
Further, the water permeability of the hollow fiber membrane of Example 1 was 2050 ml / hr · kPa · m 2 , and the surface functional group amount was 66.3 μmol / g of acidic groups and 33.3 μmol / g of basic groups. The presence of carboxyl groups and amino groups was confirmed by infrared spectroscopic analysis of the hollow fiber membrane surface. The maximum pore size was 0.06 microns on the inner surface side.
(Example 2)
Polysulfone (Amoco Corporation Udel-P3500) 8 parts, (Amoco Corporation Udel-P1700) 8 parts, Polyvinylpyrrolidone (International Special Products Co .; hereinafter abbreviated as ISP) K30 4 parts, Polyvinylpyrrolidone (ISP K90) 2 parts 77 parts of acetamide and 1 part of water were dissolved by heating to obtain a stock solution.
原液粘度は５０℃で1．2Pa・secであった。この原液を温度５０℃の紡糸口金部へ送り、外径０．３５ｍｍ、内径０．２５ｍｍの２重スリット管から芯液としてジメチルアセトアミド６０部、水４０部からなる溶液を吐出させ、中空糸状を形成させた後、温度３０℃、露点２８℃で調湿し、１０ミクロン以下のドライミストを加えた２５０ｍｍのドライゾーン雰囲気を経て、ジメチルアセトアミド２０重量％、水８０重量％からなる温度４０℃の凝固浴を通過させ、８０℃15分の水洗工程を通過させ、巻き取り束とした。中空糸内径は200μｍ、膜厚40μｍである。この束を100℃で2時間水洗した後、１００℃で２時間乾燥後、１７０℃の熱処理工程でさらに３．５時間処理し、実施例２の膜を得た。得られた膜の表面官能基密度を測定した。また中空糸を５０本束ね、中空糸中空部を閉塞しないようにエポキシ系ポッティング剤で両末端をガラス管モジュールケースに固定し、ミニモジュールを作成した。該ミニモジュールの直径は約７mm、長さは約１２cmである。中空糸の透水性能は2230ml/hr・kPa・m2であり、酸性基64.3μmol/ｇ、塩基性基33.3μmol/ｇであった。中空糸膜表面の赤外分光解析で、カルボキシル基およびアミノ基の存在を確認した。 最大孔径は内表面側で、０．０７ミクロンであった。
（実施例３）
ポリスルホン（アモコ社 Ｕｄｅｌ/Ｐ３５００）8部、（アモコ社 Ｕｄｅｌ/Ｐ１７００）8部、ポリビニルピロリドン（インターナショナルスペシャルプロダクツ社；以下ＩＳＰ社と略す） Ｋ３０ ４部、ポリビニルピロリドン（ＩＳＰ社Ｋ９０）２部をジメチルアセトアミド７７部、水１部を加熱溶解し、製膜原液とした。
The viscosity of the stock solution was 1.2 Pa · sec at 50 ° C. This stock solution is sent to a spinneret at a temperature of 50 ° C., and a solution consisting of 60 parts of dimethylacetamide and 40 parts of water is discharged as a core liquid from a double slit tube having an outer diameter of 0.35 mm and an inner diameter of 0.25 mm. After the formation, humidity was adjusted at a temperature of 30 ° C. and a dew point of 28 ° C., and after passing through a 250 mm dry zone atmosphere to which a dry mist of 10 microns or less was added, a temperature of 40 ° C. consisting of 20% by weight of dimethylacetamide and 80% by weight of water It was passed through a coagulation bath and passed through a water washing step at 80 ° C. for 15 minutes to obtain a wound bundle. The inner diameter of the hollow fiber is 200 μm and the film thickness is 40 μm. The bundle was washed with water at 100 ° C. for 2 hours, dried at 100 ° C. for 2 hours, and further treated in a heat treatment step at 170 ° C. for 3.5 hours to obtain the film of Example 2. The surface functional group density of the obtained film was measured. Further, 50 hollow fibers were bundled, and both ends were fixed to a glass tube module case with an epoxy-based potting agent so as not to block the hollow portion of the hollow fiber, thereby producing a mini module. The minimodule has a diameter of about 7 mm and a length of about 12 cm. The water permeability of the hollow fiber was 2230 ml / hr · kPa · m 2 , and the acid group was 64.3 μmol / g and the basic group was 33.3 μmol / g. The presence of carboxyl groups and amino groups was confirmed by infrared spectroscopic analysis of the hollow fiber membrane surface. The maximum pore size was 0.07 microns on the inner surface side.
(Example 3)
Polysulfone (Amoco Corporation Udel / P3500) 8 parts, (Amoco Corporation Udel / P1700) 8 parts, Polyvinylpyrrolidone (International Special Products Co .; hereinafter abbreviated as ISP) K30 4 parts, Polyvinylpyrrolidone (ISP K90) 2 parts 77 parts of acetamide and 1 part of water were dissolved by heating to obtain a stock solution.
原液粘度は５０℃で1．2Pa・secであった。この原液を温度５０℃の紡糸口金部へ送り、外径０．３５ｍｍ、内径０．２５ｍｍの２重スリット管から芯液としてジメチルアセトアミド６０部、水４０部からなる溶液を吐出させ、中空糸状を形成させた後、温度３０℃、露点２８℃で調湿し、１０ミクロン以下のドライミストを加えた２５０ｍｍのドライゾーン雰囲気を経て、ジメチルアセトアミド２０重量％、水８０重量％からなる温度４０℃の凝固浴を通過させ、８０℃1分の水洗工程を通過させ、巻き取り束とした。中空糸内径は200μｍ、膜厚40μｍである。この束を１００℃で２時間乾燥後、膜面積１．６ｍ2になるように、ケースに充填し、ポッティングし、端部を両面開口させて、血液浄化モジュールとした。この後乾燥状態で、γ線照射（２５ＫＧｙ）を行ない滅菌し、実施例３の膜を得た。得られた膜を切り出し、５０本束ね、中空糸中空部を閉塞しないようにエポキシ系ポッティング剤で両末端をガラス管モジュールケースに固定し、ミニモジュールを作成した。該ミニモジュールの直径は約７mm、長さは約１２cmである。中空糸の透水性能は1680ml/hr・kPa・m2であり、酸性基8.3μmol/ｇ、塩基性基4.5μmol/ｇであった。中空糸膜表面の赤外分光解析で、カルボキシル基およびアミノ基の存在を確認した。最大孔径は、内表面側で、０．０５ミクロンであった。
（実施例４）
ポリスルホン（アモコ社 Ｕｄｅｌ/Ｐ１７００）１４部、ポリビニルピロリドン（Ｋ９０）７部、水２部をジメチルアセトアミド７７部に加熱溶解し、外径1.0mm、内径0.7mmの環状オリフィスからなる口金孔内から注入液としてジメチルスルホキシド／水＝９５／５を注入しつつ、吐出させ、口金面から１．０cm下方に設置した８０℃に保温した水を有する凝固浴に通過させ、水洗後カセにまき取り、内径３００μｍ、外径４６０μｍの中空糸条膜を得た。口金は６０℃に保温した。得られた中空糸膜を100℃で２時間水洗浄した後、100℃で２時間乾燥後、空気中150℃で5時間処理を施し実施例４の膜を得た。得られた膜を５０本束ね、中空糸中空部を閉塞しないようにエポキシ系ポッティング剤で両末端をガラス管モジュールケースに固定し、ミニモジュールを作成した。該ミニモジュールの直径は約７mm、長さは約１２cmである。透水性は224ml/hr・Pa・m2であり酸性基の密度は52.3μmol/ｇ、塩基性基は26.3μmol/ｇであった。アルブミン透過率は９８％であった。中空糸膜表面の赤外分光解析で、カルボキシル基およびアミノ基の存在を確認した。最大孔径は内表面側で、１．８ミクロンであった。
（比較例１）
ポリスルホン（アモコ社 Ｕｄｅｌ/Ｐ１７００）１４部、ポリビニルピロリドン（Ｋ９０）７部、水２部をジメチルアセトアミド７７部に加熱溶解し、外径1.0mm、内径0.7mmの環状オリフィスからなる口金孔内から注入液としてジメチルスルホキシド／水＝９５／５を注入しつつ、吐出させ、口金面から１．０cm下方に設置した８０℃に保温した水を有する凝固浴に通過させ、水洗後カセにまき取り、内径３００μｍ、外径４６０μｍの中空糸条膜を得た。口金は６０℃に保温した。得られた中空糸膜を100℃で２時間水洗浄した後、100℃で２時間乾燥した。得られた膜を５０本束ね、中空糸中空部を閉塞しないようにエポキシ系ポッティング剤で両末端をガラス管モジュールケースに固定し、ミニモジュールを作成した。該ミニモジュールの直径は約７mm、長さは約１２cmである。透水性は12540ml/hr・kPa・m2であり酸性基の密度は10.2μmol/ｇ、塩基性基は２μmol/ｇ以下であり、塩基性基は実質測定誤差に埋まり、検出できなかった。アルブミン透過率は９８％であった。中空糸膜表面の赤外分光解析で、カルボキシル基の存在を確認した。最大孔径は内表面側で、１．８ミクロンであった。
（実施例５、比較例２）
実施例４，比較例１の膜を使用して作成した５０本入り中空糸膜ミニモジュールに免疫沈殿が可能なヒトインターロイキンＩＬ−６の抗体を水溶性カルボジイミドを用いて水溶液系で１０００pg/mlの濃度で膜内表面側に灌流しながら反応させた。１０mlのウサギ血漿に５００pg/mlのヒトインターロイキンＩＬ−６を溶かして、膜面積（内表面換算）１ｍ2当たり100ml/minの流速で中空糸内腔側へ６０min灌流した。灌流後のウサギ血漿中のヒトインターロイキンＩＬ−６の濃度を測定したところ、実施例４の膜では５pg/ml、比較例１の膜では125pg/mlとなった。明らかに実施例４で効率的に抗体結合が起こっていることがわかる。
The viscosity of the stock solution was 1.2 Pa · sec at 50 ° C. This stock solution is sent to a spinneret at a temperature of 50 ° C., and a solution consisting of 60 parts of dimethylacetamide and 40 parts of water is discharged as a core liquid from a double slit tube having an outer diameter of 0.35 mm and an inner diameter of 0.25 mm. After the formation, humidity was adjusted at a temperature of 30 ° C. and a dew point of 28 ° C., and after passing through a 250 mm dry zone atmosphere to which a dry mist of 10 microns or less was added, a temperature of 40 ° C. consisting of 20% by weight of dimethylacetamide and 80% by weight of water It was passed through a coagulation bath and passed through a water washing step at 80 ° C. for 1 minute to obtain a wound bundle. The inner diameter of the hollow fiber is 200 μm and the film thickness is 40 μm. The bundle was dried at 100 ° C. for 2 hours, filled in a case so as to have a membrane area of 1.6 m 2 , potted, and opened at both ends to form a blood purification module. Thereafter, in a dry state, γ-ray irradiation (25 KGy) was performed and sterilized to obtain a membrane of Example 3. The obtained membrane was cut out, bundled 50, and both ends were fixed to the glass tube module case with an epoxy-based potting agent so as not to block the hollow portion of the hollow fiber, and a mini module was prepared. The minimodule has a diameter of about 7 mm and a length of about 12 cm. The water permeability of the hollow fiber was 1680 ml / hr · kPa · m 2 , with an acidic group of 8.3 μmol / g and a basic group of 4.5 μmol / g. The presence of carboxyl groups and amino groups was confirmed by infrared spectroscopic analysis of the hollow fiber membrane surface. The maximum pore size was 0.05 microns on the inner surface side.
Example 4
14 parts of polysulfone (Amoco Udel / P1700), 7 parts of polyvinyl pyrrolidone (K90) and 2 parts of water are dissolved in 77 parts of dimethylacetamide by heating and injected from the inside of a mouthpiece hole consisting of an annular orifice with an outer diameter of 1.0 mm and an inner diameter of 0.7 mm. While injecting dimethyl sulfoxide / water = 95/5 as a liquid, the liquid was discharged, passed through a coagulation bath having water kept at 80 ° C. installed 1.0 cm below the base surface, rinsed with water, and taken up in a cake. A hollow fiber membrane having an outer diameter of 300 μm and an outer diameter of 460 μm was obtained. The base was kept at 60 ° C. The obtained hollow fiber membrane was washed with water at 100 ° C. for 2 hours, dried at 100 ° C. for 2 hours, and then treated in air at 150 ° C. for 5 hours to obtain a membrane of Example 4. 50 membranes obtained were bundled, and both ends were fixed to the glass tube module case with an epoxy-based potting agent so as not to block the hollow portion of the hollow fiber, thereby producing a mini module. The minimodule has a diameter of about 7 mm and a length of about 12 cm. The water permeability was 224 ml / hr · Pa · m 2 , the density of acidic groups was 52.3 μmol / g, and the basic groups were 26.3 μmol / g. The albumin permeability was 98%. The presence of carboxyl groups and amino groups was confirmed by infrared spectroscopic analysis of the hollow fiber membrane surface. The maximum pore size was 1.8 microns on the inner surface side.
(Comparative Example 1)
14 parts of polysulfone (Amoco Udel / P1700), 7 parts of polyvinyl pyrrolidone (K90) and 2 parts of water are dissolved in 77 parts of dimethylacetamide by heating and injected from the inside of a mouthpiece hole consisting of an annular orifice with an outer diameter of 1.0 mm and an inner diameter of 0.7 mm. While injecting dimethyl sulfoxide / water = 95/5 as a liquid, the liquid was discharged, passed through a coagulation bath having water kept at 80 ° C. installed 1.0 cm below the base surface, rinsed with water, and taken up in a cake. A hollow fiber membrane having an outer diameter of 300 μm and an outer diameter of 460 μm was obtained. The base was kept at 60 ° C. The obtained hollow fiber membrane was washed with water at 100 ° C. for 2 hours and then dried at 100 ° C. for 2 hours. 50 membranes obtained were bundled, and both ends were fixed to the glass tube module case with an epoxy-based potting agent so as not to block the hollow portion of the hollow fiber, thereby producing a mini module. The minimodule has a diameter of about 7 mm and a length of about 12 cm. The water permeability was 12540 ml / hr · kPa · m 2 , the density of acidic groups was 10.2 μmol / g, the basic groups were 2 μmol / g or less, and the basic groups were buried in substantial measurement errors and could not be detected. The albumin permeability was 98%. The presence of carboxyl groups was confirmed by infrared spectroscopic analysis of the hollow fiber membrane surface. The maximum pore size was 1.8 microns on the inner surface side.
(Example 5, Comparative Example 2)
Example 4 Human interleukin IL-6 antibody capable of immunoprecipitation was prepared at 1000 pg / ml in an aqueous system using water-soluble carbodiimide on 50 hollow fiber membrane minimodules prepared using the membrane of Comparative Example 1. The reaction was carried out while perfusing the inner surface of the membrane at a concentration of. 500 pg / ml human interleukin IL-6 was dissolved in 10 ml of rabbit plasma and perfused for 60 min toward the hollow fiber lumen side at a flow rate of 100 ml / min per 1 m 2 of membrane area (inner surface equivalent). When the concentration of human interleukin IL-6 in the rabbit plasma after perfusion was measured, it was 5 pg / ml for the membrane of Example 4 and 125 pg / ml for the membrane of Comparative Example 1. Clearly, antibody binding occurs efficiently in Example 4.
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| JP2009101346A (en) * | 2007-10-03 | 2009-05-14 | Toray Ind Inc | Membrane for humidification, and method for manufacturing the same |
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