JP2007307463A - Oxidation-resistant hydrophilized polysulphone-based hollow-fiber membrane and its manufacturing method - Google Patents
Oxidation-resistant hydrophilized polysulphone-based hollow-fiber membrane and its manufacturing method Download PDFInfo
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- 238000004519 manufacturing process Methods 0.000 title claims description 10
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Abstract
Description
本発明は、強酸化剤による殺菌処理が必要な抗体・酵素などの各種医薬品の分離・精製用分離膜として優れたポリスルホン系中空糸膜に関するものである。 The present invention relates to a polysulfone-based hollow fiber membrane that is excellent as a separation membrane for separation and purification of various pharmaceuticals such as antibodies and enzymes that require sterilization treatment with a strong oxidizing agent.
ポリスルホン系ポリマーからなる分離膜は、その耐熱性、耐薬品性及び耐γ線性などの点より、滅菌操作が必要となる各種医薬品の精製工程などに用いられてきた。ところが、ポリスルホン系ポリマーは疎水性である為に疎水性物質による汚染が起きやすく、各種医薬品の精製工程において有用物質の回収率の低下を引き起こすことがあった。 Separation membranes made of polysulfone-based polymers have been used in the purification process of various pharmaceuticals that require sterilization operations because of their heat resistance, chemical resistance, and γ-ray resistance. However, since the polysulfone-based polymer is hydrophobic, it is likely to be contaminated with a hydrophobic substance, resulting in a decrease in the recovery rate of useful substances in various pharmaceutical purification processes.
有用物質がタンパク質の場合には、一般的に分子量が大きいほど、その疎水性が強くなるため、例えば分子量が約16万である抗体などは特に膜へ吸着しやすい。その為、抗体に代表されるようなタンパク質のポリスルホン系膜への吸着を抑制する手段として、ポリスルホン系ポリマー膜に親水性を付与する、いわゆる親水化技術に関して様々な方法がこれまで提案されてきた。例えば、親水性ポリマーであるポリビニルピロリドンを適正量含有させることにより、ポリスルホン系膜へ親水性を与え、それにより膜の汚れを抑制する方法が特公平2−18695号公報(特許文献1)、特開昭61−238834号公報(特許文献2)、特開昭63−99325号公報(特許文献3)、特開平6−296686号公報に(特許文献4)等に開示されている。また、親水性ポリマーセグメントと疎水性ポリマーセグメントからなるグラフトまたはブロックコポリマーをブレンドすることによりポリスルホン系膜の汚れを抑制する方法が特開昭62−201603号公報(特許文献5)、特開昭63−77941号公報(特許文献6)、特開昭63−258603号公報(特許文献7)、特開平2−2862号公報(特許文献8)、及び特開平2−160026号公報に(特許文献9)が開示されている。さらに、特許文献9には、ポリスルホンにスルホン化ポリスルホンをブレンドすることによりポリスルホン系膜の汚れを抑制する方法についても記載されている。 In the case where the useful substance is a protein, since the hydrophobicity generally increases as the molecular weight increases, for example, an antibody having a molecular weight of about 160,000 is particularly easily adsorbed to the membrane. For this reason, various methods have been proposed so-called hydrophilization techniques for imparting hydrophilicity to polysulfone-based polymer membranes as means for suppressing the adsorption of proteins such as antibodies to polysulfone-based membranes. . For example, Japanese Patent Publication No. 2-18695 (Patent Document 1) discloses a method for imparting hydrophilicity to a polysulfone-based membrane by containing an appropriate amount of a polyvinyl pyrrolidone that is a hydrophilic polymer, thereby suppressing membrane contamination. Japanese Patent Laid-Open No. 61-238834 (Patent Document 2), Japanese Patent Laid-Open No. 63-99325 (Patent Document 3), Japanese Patent Laid-Open No. 6-296686 (Patent Document 4) and the like. Japanese Patent Application Laid-Open No. 62-201603 (Patent Document 5) and Japanese Patent Application Laid-Open No. 63 (1994) disclose a method for suppressing contamination of a polysulfone-based membrane by blending a graft or block copolymer comprising a hydrophilic polymer segment and a hydrophobic polymer segment. JP-A-77941 (Patent Document 6), JP-A-63-258603 (Patent Document 7), JP-A-2-2862 (Patent Document 8), and JP-A-2-160026 (Patent Document 9). ) Is disclosed. Furthermore, Patent Document 9 also describes a method for suppressing contamination of a polysulfone-based membrane by blending sulfonated polysulfone with polysulfone.
しかし、従来の親水化技術では、酸化剤などによる薬品洗浄を施すことによって親水性ポリマーが分解されやすいという問題があった。例えば、一般に抗体や酵素等の医薬品の分離膜による精製工程では、雑菌の繁殖を防ぐために、分離膜の殺菌処理が必須となる。殺菌処理には通常、膜面付着物の分解・洗浄効果の高い次亜塩素酸ソーダ、塩素、過酸化水素等の酸化性殺菌剤が用いられる。そのため、従来の親水化技術を用いて製造されたポリスルホン系中空糸膜では、殺菌処理によって親水性ポリマーが分解され、タンパク質の吸着抑制能力が失われることがあった。 However, the conventional hydrophilization technique has a problem that the hydrophilic polymer is easily decomposed by chemical cleaning with an oxidizing agent or the like. For example, in general, in a purification process using a separation membrane for drugs such as antibodies and enzymes, a sterilization treatment of the separation membrane is essential in order to prevent the growth of various bacteria. For the sterilization treatment, an oxidizing sterilizer such as sodium hypochlorite, chlorine, hydrogen peroxide or the like, which has a high effect of decomposing and cleaning the film surface deposit, is usually used. For this reason, in a polysulfone-based hollow fiber membrane produced using a conventional hydrophilization technique, the hydrophilic polymer may be decomposed by the sterilization treatment, and the protein adsorption inhibiting ability may be lost.
一方、分離膜として用いられる中空糸膜には適度な機械的強度が必要とされるところ、親水性ポリマーの量が多いと、機械的強度が低下する傾向がある。
本発明は、上記従来技術に鑑みて、強酸化剤で酸化処理等を行った後も、タンパク質の吸着を抑制できる十分な親水性を保持し、且つ機械的強度にも優れたポリスルホン系中空糸膜を提供することを目的とする。 In view of the above prior art, the present invention is a polysulfone-based hollow fiber that retains sufficient hydrophilicity to suppress protein adsorption and is excellent in mechanical strength even after being subjected to oxidation treatment or the like with a strong oxidizing agent. The object is to provide a membrane.
本発明者らは、上記の目的を達成すべく鋭意研究を行った結果、強酸化剤による酸化処理を行った後の親水性ポリマーの残存量を所定の範囲とすれば、親水性が十分に保持され、且つ機械的強度にも優れたポリスルホン系中空糸膜が得られること、また、かかるポリスルホン系中空糸膜は、材料となるポリスルホン系ポリマーと親水性ポリマーの重量平均分子量の比、及び製膜溶液中における重量の比を所定の範囲とし、製膜溶液を吐出するノズル直下の空走部分の中心温度を製膜溶液の凝固点に対して所定の範囲内とすることによって得られることを見出し、本発明を完成するに至った。 As a result of diligent research to achieve the above object, the inventors of the present invention have sufficient hydrophilicity if the remaining amount of the hydrophilic polymer after the oxidation treatment with a strong oxidizing agent is within a predetermined range. A polysulfone-based hollow fiber membrane that is retained and excellent in mechanical strength can be obtained, and such a polysulfone-based hollow fiber membrane has a weight-average molecular weight ratio between a polysulfone-based polymer and a hydrophilic polymer as a material, and is manufactured. It is found that the ratio of the weight in the membrane solution is set within a predetermined range, and the center temperature of the idle portion directly under the nozzle for discharging the film forming solution is set within the predetermined range with respect to the freezing point of the film forming solution. The present invention has been completed.
即ち、本発明に係る耐酸化性親水化ポリスルホン系中空糸膜は、ポリスルホン系ポリマー及び親水性ポリマーを主成分とし、強酸化剤により酸化処理を行った後の親水性ポリマーの残存量が、ポリマー全量の0.8〜9.8重量%であることを特徴とする。ここで、ポリマー全量とは、ポリスルホン系ポリマーと親水性ポリマーの合計の量を意味する。 That is, the oxidation-resistant hydrophilic polysulfone-based hollow fiber membrane according to the present invention has a polysulfone-based polymer and a hydrophilic polymer as main components, and the remaining amount of the hydrophilic polymer after the oxidation treatment with a strong oxidizing agent is a polymer. It is characterized by 0.8 to 9.8% by weight of the total amount. Here, the total amount of the polymer means the total amount of the polysulfone polymer and the hydrophilic polymer.
強酸化剤による酸化処理の後の親水性ポリマーの残存量が0.8〜9.8重量%の範囲であれば、十分なタンパク質吸着抑制効果を得られるとともに、機械的強度にも優れた耐酸化性親水化ポリスルホン系中空糸膜となる。 If the remaining amount of the hydrophilic polymer after the oxidation treatment with a strong oxidizing agent is in the range of 0.8 to 9.8% by weight, a sufficient protein adsorption suppressing effect can be obtained and the acid resistance is excellent in mechanical strength. Hydrophilic polysulfone-based hollow fiber membrane.
このような耐酸化性親水化ポリスルホン系中空糸膜は、ポリスルホン系ポリマー及び親水性ポリマーを含む製膜原液をチューブインオリフィス型ノズルより内部凝固液とともに空走部分に吐出した後、凝固液中に導いて中空糸状の分離膜を形成する乾湿式法による製膜工程を含み、前記ポリスルホン系ポリマー及び親水性ポリマーの重量平均分子量をそれぞれMw1、Mw2としたとき、Mw1/Mw2の値が0.6〜6.0の範囲にあり、前記製膜溶液が、前記ポリスルホン系ポリマー、前記親水性ポリマー、及び共通溶媒からなり、該ポリスルホン系ポリマー及び該親水性ポリマーの重量をそれぞれW1、W2としたとき、W2/W1の値が、1.2〜2.2の範囲であり、前記製膜溶液の凝固点をTc、前記ノズル直下の空走部分の中心温度をTagとしたとき、+50℃>Tag−Tc>−20℃の範囲にあることを特徴とする、製造方法によって製造することができる。 Such an oxidation-resistant hydrophilized polysulfone-based hollow fiber membrane is formed by discharging a membrane-forming stock solution containing a polysulfone-based polymer and a hydrophilic polymer from a tube-in-orifice nozzle together with an internal coagulating liquid into an idle running portion and then into the coagulating liquid. Including a membrane forming step by a dry and wet method for forming a hollow fiber-like separation membrane, where the weight average molecular weights of the polysulfone polymer and the hydrophilic polymer are Mw1 and Mw2, respectively, the value of Mw1 / Mw2 is 0.6. When the film-forming solution is comprised of the polysulfone polymer, the hydrophilic polymer, and a common solvent, and the weights of the polysulfone polymer and the hydrophilic polymer are W1 and W2, respectively. , W2 / W1 is in the range of 1.2 to 2.2, the freezing point of the film-forming solution is Tc, and the free running portion directly under the nozzle When the temperature was Tag, which lies in the range of + 50 ℃> Tag-Tc> -20 ℃, it can be manufactured by the method.
本発明によれば、強酸化剤による処理を行っても十分な親水性を保持し、タンパク質等の疎水性物質に対する吸着抑制効果も維持される耐酸化性親水化ポリスルホン系中空糸膜を得ることができる。 According to the present invention, it is possible to obtain an oxidation-resistant hydrophilized polysulfone-based hollow fiber membrane that retains sufficient hydrophilicity even when treated with a strong oxidizing agent and that also maintains the effect of suppressing adsorption to hydrophobic substances such as proteins. Can do.
以下、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明で云うポリスルホン系ポリマーとは、スルホン結合を有する高分子化合物の総称であり特に制限されるものではないが、例えば、下記式(1)〜式(5)のいずれかで示されるポリスルホン系ポリマーが広く市販されており、これらを本発明に用いることができる。特に、式(1)で示す化学構造を持つポリスルホン系ポリマーは、例えばSolvay Advanced Polymers社より「UDEL」の商品名で市販されており、重合度等によって幾つかの種類が存在するが、いずれを用いることもできる。 The polysulfone polymer referred to in the present invention is a general term for polymer compounds having a sulfone bond and is not particularly limited. For example, the polysulfone polymer represented by any one of the following formulas (1) to (5) Polymers are widely available and can be used in the present invention. In particular, a polysulfone-based polymer having a chemical structure represented by the formula (1) is commercially available, for example, from Solvay Advanced Polymers under the trade name “UDEL”, and there are several types depending on the degree of polymerization. It can also be used.
本発明に係る耐酸化性親水化ポリスルホン系中空糸膜は、強酸化剤により酸化処理を行った後も、親水性ポリマーが、ポリマー全量に対して、0.8〜9.8重量%残存する。ここで、強酸化剤による酸化処理としては、例えば、殺菌を目的とした酸化処理が挙げられ、強酸化剤としては、次亜塩素酸ソーダ、塩素、過酸化水素、オゾン等の殺菌剤が一般的であり特に限定されない。尚、殺菌を目的とした酸化処理においては、安全性の高い過酸化水素が好ましい。過酸化水素は強い酸化力がある上、カタラーゼや二酸化マンガンなどの触媒により容易に水と酸素というヒトには全く無害な物質に分解される。 In the oxidation-resistant hydrophilic polysulfone-based hollow fiber membrane according to the present invention, the hydrophilic polymer remains in an amount of 0.8 to 9.8% by weight based on the total amount of the polymer even after the oxidation treatment with a strong oxidizing agent. . Here, the oxidation treatment with a strong oxidizing agent includes, for example, an oxidation treatment for the purpose of sterilization. As the strong oxidizing agent, bactericides such as sodium hypochlorite, chlorine, hydrogen peroxide, and ozone are generally used. And not particularly limited. In the oxidation treatment for the purpose of sterilization, hydrogen peroxide having high safety is preferable. Hydrogen peroxide has a strong oxidizing power and is easily decomposed by water and oxygen into substances that are completely harmless to humans by catalysts such as catalase and manganese dioxide.
強酸化剤による処理時間の条件は強酸が0.01%〜1.00%の範囲では20℃〜30℃で6時間〜12時間である。酸化処理後の親水性ポリマーの残存量が多いほどタンパク吸着抑制効果が高くなるが、その反面中空糸膜の機械的強度が低下してしまう。逆に、0.8%未満になると十分なタンパク質吸着抑制が発揮できない。 The conditions for the treatment time with the strong oxidizing agent are 20 ° C. to 30 ° C. and 6 hours to 12 hours when the strong acid is in the range of 0.01% to 1.00%. As the residual amount of the hydrophilic polymer after the oxidation treatment increases, the protein adsorption suppressing effect increases, but on the other hand, the mechanical strength of the hollow fiber membrane decreases. On the other hand, if it is less than 0.8%, sufficient protein adsorption suppression cannot be exhibited.
その為、酸化処理後の親水性ポリマーの残存量は強酸化剤による酸化処理後の中空糸膜のポリマー全量(ポリスルホン系ポリマー+親水性ポリマー)の0.8重量%〜9.8重量%の範囲である必要があり、好ましくは1.2重量%〜8.8重量%、更に好ましくは1.5重量%〜6.8重量%の範囲である。 Therefore, the residual amount of the hydrophilic polymer after the oxidation treatment is 0.8% to 9.8% by weight of the total amount of the hollow fiber membrane polymer (polysulfone polymer + hydrophilic polymer) after the oxidation treatment with the strong oxidizing agent. It is necessary to be in the range, preferably 1.2% to 8.8% by weight, more preferably 1.5% to 6.8% by weight.
次に、本発明の耐酸化性親水化ポリスルホン系中空糸膜の製造方法について説明する。 Next, the manufacturing method of the oxidation-resistant hydrophilic polysulfone-based hollow fiber membrane of the present invention will be described.
本発明に係る対酸化性親水化ポリスルホン系中空糸膜の製造方法は、ポリスルホン系ポリマー及び親水性ポリマーを含む製膜溶液をチューブインオリフィス型ノズルより内部凝固液とともに空走部分に吐出した後、凝固液中に導いて中空糸膜を形成する乾湿式法による製膜工程を含む。 The method for producing the oxidizable hydrophilic polysulfone-based hollow fiber membrane according to the present invention, after discharging the membrane-forming solution containing the polysulfone-based polymer and the hydrophilic polymer from the tube-in-orifice nozzle together with the internal coagulating liquid to the idle running portion, It includes a film-forming process by a dry-wet method that leads to a coagulating liquid to form a hollow fiber membrane.
本発明で用いられる製膜溶液の溶媒は、ポリスルホン系ポリマー及び親水性ポリマーを溶解するものであり、ジメチルホルムアミド、ジメチルアセトアミド、N−メチル−2−ピロリドン、ジメチルスルホキシド、スルホラン、ジオキサン等の多種の溶媒、あるいは上記2種類以上の混合液からなる溶媒が用いられるが、特にジメチルアセトアミドあるいはN−メチル−2−ピロリドンが好ましく用いられる。更に、該溶媒に無機塩、例えば塩化リチウム、塩化ナトリウム、硝酸ナトリウム、硝酸カリウム、硫酸ナトリウム、塩化亜鉛等の無機酸の塩;酢酸ナトリウム、ギ酸ナトリウム等の有機酸の塩を1〜8重量%程度の少量を添加しても良い。 The solvent of the film-forming solution used in the present invention dissolves polysulfone-based polymers and hydrophilic polymers, and various solvents such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, sulfolane, dioxane and the like. A solvent or a solvent composed of the above two or more mixed solutions is used, and dimethylacetamide or N-methyl-2-pyrrolidone is particularly preferably used. Further, the solvent contains an inorganic salt such as a salt of an inorganic acid such as lithium chloride, sodium chloride, sodium nitrate, potassium nitrate, sodium sulfate, or zinc chloride; a salt of an organic acid such as sodium acetate or sodium formate. A small amount of may be added.
本発明に係る製造方法では、乾湿式法による製膜工程の後、洗浄する工程を行ってもよい。ここでいう洗浄工程とは、該乾湿式法による製膜工程によって得られた中空糸膜を洗浄する洗浄工程であって、乾湿式法による製膜工程と連続して、あるいは一旦中空糸膜を巻き取った後、行われる。洗浄工程では、例えば、膜中に残存する共通溶媒及び過剰の親水性高分子が、水洗または40〜90℃の温水洗によって抽出除去される。また、過剰な親水性高分子を短時間でより効率よく除去するために、アルコール水溶液や、酸性過マンガン酸カリウム水溶液、過酸化水素水、次亜塩素酸ナトリウム溶液等の酸化剤又は加水分解剤を用いて洗浄してもよい。 In the manufacturing method according to the present invention, a cleaning step may be performed after the film forming step by the dry and wet method. The washing step here refers to a washing step for washing the hollow fiber membrane obtained by the dry-wet film forming step, which is continuous with the dry-wet film-forming step or once the hollow fiber membrane is removed. This is done after winding. In the washing step, for example, the common solvent and excess hydrophilic polymer remaining in the membrane are extracted and removed by washing with water or washing with warm water at 40 to 90 ° C. In addition, in order to remove excess hydrophilic polymer more efficiently in a short time, an oxidizing agent or a hydrolyzing agent such as an alcohol aqueous solution, an acidic potassium permanganate aqueous solution, a hydrogen peroxide solution, or a sodium hypochlorite solution. You may wash using.
本発明において、製膜溶液中に含まれるポリスルホン系ポリマーの濃度は、目的用途に適合した特性を有する中空繊維膜の製造を可能とする濃度範囲であればよく、通常10〜25重量%、好ましくは15〜20重量%である。10重量%未満では中空糸膜としての十分な強度を得ることができず、また実用的な中空糸膜が形成できなくなる。また25重量%を越えると貫通孔が減少し膜の透過性能や透析性能の低下を引き起こすため実用的でない。 In the present invention, the concentration of the polysulfone-based polymer contained in the membrane-forming solution may be in a concentration range that enables the production of a hollow fiber membrane having characteristics suitable for the intended use, and is usually 10 to 25% by weight, preferably Is 15 to 20% by weight. If it is less than 10% by weight, sufficient strength as a hollow fiber membrane cannot be obtained, and a practical hollow fiber membrane cannot be formed. On the other hand, if it exceeds 25% by weight, the number of through-holes decreases, which causes a decrease in membrane permeation performance and dialysis performance, which is not practical.
本発明の耐酸化性親水化ポリスルホン系中空糸膜を得るには、ポリスルホン系ポリマーと親水性ポリマーの重量平均分子量の比、及び製膜溶液における重量比、また内部凝固液に添加するグリコール類の分子量及び添加量、更に空走部分の中心温度が極めて重要となる。 In order to obtain the oxidation-resistant hydrophilic polysulfone-based hollow fiber membrane of the present invention, the ratio of the weight average molecular weight of the polysulfone-based polymer and the hydrophilic polymer, the weight ratio in the membrane-forming solution, and the glycols added to the internal coagulation liquid The molecular weight and addition amount, and the center temperature of the free running portion are extremely important.
まず第一にポリスルホン系ポリマーの重量平均分子量をMw1、親水性ポリマーの重量平均分子量をMw2とした時の、Mw1/Mw2の値は0.60〜6.00の範囲とし、好ましくは1.20〜4.80、更に好ましくは1.60〜3.80とする。Mw1/Mw2の値が0.60を下回ると、製膜後膜の内外表面に親水性ポリマーによる散漫層が形成され、ゲル膨潤により濾過量及び分離性能が低下する傾向にある。また、強酸化処理を施した後の親水性ポリマーの残存量が9.8を上回ってしまい、中空糸膜の機械的強度が低下する。また、Mw1/Mw2の値が6.0を上回ると、強酸化剤処理を施した後の親水性ポリマーの残存量がポリマー全量の0.8未満となり、タンパク質吸着を抑制するために必要な親水性の効果が得られない。 First, when the weight average molecular weight of the polysulfone polymer is Mw1 and the weight average molecular weight of the hydrophilic polymer is Mw2, the value of Mw1 / Mw2 is in the range of 0.60 to 6.00, preferably 1.20. To 4.80, more preferably 1.60 to 3.80. When the value of Mw1 / Mw2 is less than 0.60, a diffuse layer made of a hydrophilic polymer is formed on the inner and outer surfaces of the membrane after film formation, and the amount of filtration and separation performance tend to decrease due to gel swelling. Further, the residual amount of the hydrophilic polymer after the strong oxidation treatment exceeds 9.8, and the mechanical strength of the hollow fiber membrane is lowered. Further, if the value of Mw1 / Mw2 exceeds 6.0, the remaining amount of the hydrophilic polymer after the strong oxidant treatment is less than 0.8 of the total amount of the polymer, and the hydrophilicity necessary for suppressing protein adsorption. Sexual effect cannot be obtained.
第二に、製膜溶液中でのポリスルホン系ポリマーの重量をW1とし、親水性ポリマーの重量をW2とした時の、W2/W1の値は1.2〜2.2とし、好ましくは1.8〜2.2とする。W2/W1が1.2を下回ると、強酸化剤処理を行った後の親水性ポリマー残量が0.8重量%を下回る傾向にあり、十分な親水性が得られない。また、W2/W1が2.2を上回ると、製膜溶液の溶液粘度が上昇し製膜が困難になるだけでなく、得られた中空糸膜の強酸化剤処理を施した後の親水性ポリマーの残存量がポリマー全量の9.8重量%を上回る傾向にあり、結果として中空糸膜の機械的強度が低下する。 Second, when the weight of the polysulfone polymer in the membrane forming solution is W1 and the weight of the hydrophilic polymer is W2, the value of W2 / W1 is 1.2 to 2.2, preferably 1. 8 to 2.2. When W2 / W1 is less than 1.2, the remaining amount of the hydrophilic polymer after the strong oxidant treatment tends to be less than 0.8% by weight, and sufficient hydrophilicity cannot be obtained. Moreover, when W2 / W1 exceeds 2.2, not only the solution viscosity of the membrane-forming solution increases and the membrane formation becomes difficult, but the hydrophilicity after the obtained hollow fiber membrane is treated with a strong oxidizing agent. The residual amount of the polymer tends to exceed 9.8% by weight of the total amount of the polymer, resulting in a decrease in the mechanical strength of the hollow fiber membrane.
次に、内部凝固液に添加するグリコール類の重量平均分子量は6,000以下である必要があり、より好ましくは1,000以下、より好ましくは600以下である。内部凝固液に添加するグリコール類の重量平均分子量が6,000を上回ると製膜後の特に中空糸膜の内表面に親水性ポリマーによる散漫層が形成され、ゲル膨潤により濾過量及び分離性能が低下する傾向がある。内部凝固液に添加するグリコール類の添加濃度は特に限定されず、孔径や分画分子量に応じて適宜変更可能である。 Next, the weight average molecular weight of the glycols added to the internal coagulation liquid needs to be 6,000 or less, more preferably 1,000 or less, and more preferably 600 or less. When the weight average molecular weight of glycols added to the internal coagulation liquid exceeds 6,000, a diffused layer is formed by a hydrophilic polymer on the inner surface of the hollow fiber membrane after film formation, and the filtration amount and separation performance are improved by gel swelling. There is a tendency to decrease. The addition concentration of glycols added to the internal coagulation liquid is not particularly limited, and can be appropriately changed according to the pore size and the molecular weight cut off.
最後に、空走部分の中心温度をTag、製膜溶液の凝固点をTcとしたとき、+50℃>Tag−Tc>−20℃の範囲とし、好ましくは、+30℃>Tag−Tc>−20℃、更に好ましくは+20℃>Tag−Tc>−20℃とする。本発明において空走部分の中心温度とは、図1に示したようにノズル先端から凝固液水面までの距離をLとした時にノズルからの距離が0.5Lの平面内にあり、且つ、ノズル中心から凝固液水面に向けて鉛直に下ろした直線から半径約2cm以内の雰囲気温度をいう。(Tag−Tc)が+50℃を上回ると、親水性ポリマーの残存量が低下する。反対に、(Tag−Tc)が−20℃を下回ると、ノズルより製膜溶液が吐出された後、空走部で製膜溶液の凝固点以下に過冷却された状態となり、親水性高分子の残存量が必要以上に高くなるため、透水性能が大幅に低下し、機械的強度が低下する傾向がある。 Finally, when the center temperature of the free running portion is Tag and the freezing point of the film forming solution is Tc, the range is + 50 ° C.> Tag−Tc> −20 ° C., preferably + 30 ° C.> Tag−Tc> −20 ° C. More preferably, + 20 ° C.> Tag−Tc> −20 ° C. In the present invention, the center temperature of the idle portion is within a plane having a distance of 0.5 L from the nozzle when the distance from the nozzle tip to the solidified liquid water surface is L as shown in FIG. An ambient temperature within a radius of about 2 cm from a straight line drawn vertically from the center toward the water surface of the coagulation liquid. When (Tag-Tc) exceeds + 50 ° C., the remaining amount of the hydrophilic polymer decreases. On the other hand, when (Tag-Tc) falls below -20 ° C., after the film-forming solution is discharged from the nozzle, it becomes supercooled below the freezing point of the film-forming solution in the idle running portion, and the hydrophilic polymer Since the residual amount becomes higher than necessary, the water permeability performance is greatly lowered and the mechanical strength tends to be lowered.
本発明に係る耐酸化性親水化ポリスルホン系中空糸膜のその他の製造工程は、従来公知の乾湿式法による製膜工程と洗浄工程を用いることが出来る。例えば、ポリスルホン系ポリマー及び親水性ポリマーを極性溶剤に溶解して製膜溶液を製造し、これを中空糸状の成形ノズルを経て常法に従って紡糸し、得られた糸を凝固液中に浸漬して中空糸膜を製造すれば良い。また、凝固液としては、ポリスルホン系樹脂の非溶剤を用いることができ、極性溶剤と混じり易い液体、例えば水、食塩水、界面活性剤水溶液等を挙げることができるが、水の使用が一般的である。また、凝固液の温度は、目的とする孔径によって、随時設定可能であるが、例えば水を使用した場合は5〜95℃であり、好ましくは30〜70℃である。 The other manufacturing process of the oxidation-resistant hydrophilic polysulfone-based hollow fiber membrane according to the present invention can use a conventionally known dry-wet film forming process and washing process. For example, a polysulfone-based polymer and a hydrophilic polymer are dissolved in a polar solvent to produce a film-forming solution, which is spun according to a conventional method through a hollow fiber-shaped molding nozzle, and the obtained yarn is immersed in a coagulation liquid. A hollow fiber membrane may be manufactured. Further, as the coagulating liquid, a non-solvent of polysulfone resin can be used, and examples thereof include liquids that are easily mixed with polar solvents, such as water, saline, and aqueous surfactant solutions. It is. Further, the temperature of the coagulation liquid can be set as needed depending on the intended pore diameter. For example, when water is used, it is 5 to 95 ° C, and preferably 30 to 70 ° C.
例えば、γグロブリンを内圧ろ過で濃縮することを目的とし場合、中空糸膜の外表面に平均孔径0.1μm以上の孔を有し、かつ内表面に0.01μm以下の平均孔径をもった限外ろ過膜が好ましく、その場合は内部凝固液に添加するグリコール類の添加濃度を80%未満にし、かつ凝固浴の温度を80℃以上にすればよい。また、内圧ろ過でγグロブリンを90%以上透過させることを目的とした場合は、中空糸膜の外表面に平均孔径0.1μm以上の孔を有し、かつ内表面に平均孔径0.01μm以上の孔を有する精密ろ過膜が好ましく、その場合は、内部凝固液に添加するグリコール類の添加濃度を80%以上にし、かつ凝固浴の温度を80℃以上にすればよい。 For example, when the purpose is to concentrate gamma globulin by internal pressure filtration, the hollow fiber membrane has a pore having an average pore diameter of 0.1 μm or more on the outer surface and an inner surface having an average pore diameter of 0.01 μm or less. An outer filtration membrane is preferable. In this case, the concentration of glycols added to the internal coagulation liquid may be less than 80%, and the temperature of the coagulation bath may be 80 ° C. or higher. Further, when the purpose is to allow γ globulin to permeate 90% or more by internal pressure filtration, the outer surface of the hollow fiber membrane has pores having an average pore diameter of 0.1 μm or more, and the inner surface has an average pore diameter of 0.01 μm or more. In this case, the concentration of glycols added to the internal coagulation liquid should be 80% or higher, and the temperature of the coagulation bath should be 80 ° C. or higher.
更に、γグロブリンを外圧ろ過で濃縮することを目的とし場合、中空糸膜の外表面に平均孔径0.01μm以下の孔を有し、かつ内表面に0.01μm以上の平均孔径をもった限外ろ過膜が好ましく、その場合は内部凝固液に添加するグリコール類の添加濃度を80%以上にし、かつ凝固浴の温度を80℃以下にすればよい。また、外圧ろ過でγグロブリンを90%以上透過させることを目的とした場合は、中空糸膜の外表面に平均孔径0.01〜80.0μmの孔を有し、かつ内表面に平均孔径0.1以上の孔を有する精密ろ過膜が好ましく、その場合は、内部凝固液に添加するグリコール類の添加濃度を80%以上にし、かつ凝固浴の温度を80℃以上にすればよい。 Furthermore, when the purpose is to concentrate γ globulin by external pressure filtration, the outer surface of the hollow fiber membrane has pores with an average pore diameter of 0.01 μm or less, and the inner surface has an average pore diameter of 0.01 μm or more. An outer filtration membrane is preferable. In this case, the concentration of glycols added to the internal coagulation liquid may be 80% or more, and the temperature of the coagulation bath may be 80 ° C. or less. When the purpose is to allow 90% or more permeation of gamma globulin by external pressure filtration, the hollow fiber membrane has pores with an average pore size of 0.01 to 80.0 μm on the outer surface and an average pore size of 0 on the inner surface. A microfiltration membrane having one or more pores is preferable, in which case the concentration of glycols added to the internal coagulation liquid may be 80% or more and the temperature of the coagulation bath may be 80 ° C. or more.
以下、実施例及び参考例を用いて本発明を詳細に説明するが、これらは本発明の範囲を制限するものでない。 EXAMPLES Hereinafter, although this invention is demonstrated in detail using an Example and a reference example, these do not restrict | limit the scope of the present invention.
初めに本実施例で用いられる評価法について記載する。
(1)ポリスルホン系ポリマーの重量平均分子量測定
SEC (Size Exclusion Chromatography)法により測定した。約0.06gのポリマーを10mlの塩化メチレンに溶解し試料とした。移動相に塩化メチレンを持ちて、SEC分析を行い、ポリスチレンを標準物質としたポリスチレン換算重量平均分子量を算出した。
(2)親水性ポリマーの重量平均分子量測定
SEC (Size Exclusion Chromatography)法により測定した。約0.01gのポリマーを100mlのKH2PO4(0.02mM)+Na2HPO4(0.02ml)pH6.9 の溶液に溶解し試料とした。移動相にKH2PO4(0.02mM)+Na2HPO4(0.02ml)pH6.9溶液を持ちて、SEC分析を行い、ポリエチレングリコールを標準物質としたポリエチレングリコール換算重量平均分子量を算出した。
(3)ポリマー溶液のTc測定
200mlの気密性のある蓋付きサンプル瓶にサンプルした製膜溶液150mlを50℃の恒温水槽中で1℃/時間の速度で温度を下げて行き凝固点を確認する。
(4)チューブインオリフィス型ノズル
チューブインオリフィス型ノズルは、例えば図2に示す構造を持つノズルである。図2(B)は、図2(A)のIIB-IIB線に沿った断面図である。図示されるように、中央に内部凝固液流路11が形成され、それを囲むように同心円状の製膜溶液流路12が形成されている。
(5)強酸化剤による酸化処理
0.1重量%の過酸化水素水に25℃で12時間、浸漬した後、流水中で24時間洗浄する。なお、過酸化水素水の量は中空糸膜5重量%に対し、95重量%になるように調整した。
(6)親水性ポリマー残存量測定
d-DMFを溶媒として用い40℃の加温状態で1H−NMR測定(日本電子社製Lamba400)を行い、親水性ポリマーのモノマーユニットのモル比を測定し、全ポリマー重量に対する親水性ポリマーの重量比を算出する。
(7)破断強度測定
破断強度測定は、株式会社島津製作所製のオートグラフAGS-5Dを使用し、試験長50mmの膜について、温度25℃、引張速度50mm/分の条件で引張試験を行い、膜が破断した時の強度を6回測定し、その平均値を破断強度とした。
First, the evaluation method used in this example will be described.
(1) Measurement of weight average molecular weight of polysulfone polymer
It was measured by the SEC (Size Exclusion Chromatography) method. About 0.06 g of polymer was dissolved in 10 ml of methylene chloride to prepare a sample. SEC analysis was carried out with methylene chloride as the mobile phase, and the polystyrene-converted weight average molecular weight was calculated using polystyrene as a standard substance.
(2) Weight average molecular weight measurement of hydrophilic polymer
It was measured by the SEC (Size Exclusion Chromatography) method. About 0.01 g of polymer was dissolved in 100 ml of a solution of KH 2 PO 4 (0.02 mM) + Na 2 HPO 4 (0.02 ml) pH 6.9 to prepare a sample. A mobile phase having KH 2 PO 4 (0.02 mM) + Na 2 HPO 4 (0.02 ml) pH 6.9 solution was subjected to SEC analysis, and the weight average molecular weight in terms of polyethylene glycol was calculated using polyethylene glycol as a standard substance.
(3) Tc measurement of polymer solution
150 ml of the film-forming solution sampled in a 200 ml airtight sample bottle with a lid is cooled at a rate of 1 ° C / hour in a constant temperature water bath at 50 ° C, and the freezing point is confirmed.
(4) Tube-in-orifice-type nozzle The tube-in-orifice-type nozzle is, for example, a nozzle having the structure shown in FIG. FIG. 2B is a cross-sectional view taken along the line IIB-IIB in FIG. As shown in the figure, an internal
(5) Oxidation treatment with strong oxidizing agent
After immersing in 0.1% by weight hydrogen peroxide solution at 25 ° C. for 12 hours, wash in running water for 24 hours. The amount of the hydrogen peroxide solution was adjusted to 95% by weight with respect to 5% by weight of the hollow fiber membrane.
(6) Measurement of remaining amount of hydrophilic polymer
1 -NMR measurement (Lamba400, manufactured by JEOL Ltd.) was performed using d-DMF as a solvent at 40 ° C, and the molar ratio of monomer units of the hydrophilic polymer was measured. Calculate the weight ratio.
(7) Break strength measurement The break strength measurement is performed using Shimadzu Corporation Autograph AGS-5D, and a tensile test is performed on a film with a test length of 50 mm at a temperature of 25 ° C and a tensile speed of 50 mm / min. The strength when the membrane broke was measured 6 times, and the average value was taken as the breaking strength.
本実施例では、破断強度が3MPa以上であれば機械的強度は十分であると考え、合格とした。
(8)タンパク質溶液の透水保持率の測定
リン酸緩衝液(pH7.0)をもちいて250mg/1000mlのBSA(bovine serum albumin)溶液を作成した。有効長20cmの中空糸膜モジュールを作成し平均操作圧力50kPa、線速度1m/sec、溶液温度25℃でクロスフローろ過を行う。なお、クロスフローろ過において平均操作圧力とは、モジュールの入口側(供給液)圧力と出口側(濃縮液)圧力の和の1/2の圧力である。また線速度とは、供給液流量を処理装置の有効断面積で割ったものを一般に線速度と呼ぶが、中空糸膜を内圧濾過法で用いる場合は、供給液の平均流量を中空糸膜の内径から計算される円の面積で割った値となる。ろ過開始直後の透過量をF0(g/min)、90分後の透過量をF(g/min)とし、以下の式から透水保持率を算出する。
In this example, it was considered that the mechanical strength was sufficient if the breaking strength was 3 MPa or more, and it was determined as acceptable.
(8) Measurement of water permeability of protein solution A 250 mg / 1000 ml BSA (bovine serum albumin) solution was prepared using a phosphate buffer (pH 7.0). A hollow fiber membrane module having an effective length of 20 cm is prepared and subjected to cross flow filtration at an average operating pressure of 50 kPa, a linear velocity of 1 m / sec, and a solution temperature of 25 ° C. In the cross-flow filtration, the average operating pressure is a pressure that is half the sum of the inlet side (supply liquid) pressure and the outlet side (concentrated liquid) pressure of the module. The linear velocity is generally the linear velocity obtained by dividing the supply liquid flow rate by the effective cross-sectional area of the processing apparatus. However, when the hollow fiber membrane is used in the internal pressure filtration method, the average flow rate of the supply liquid is determined by the hollow fiber membrane. It is the value divided by the area of the circle calculated from the inner diameter. The permeation rate immediately after the start of filtration is F 0 (g / min), the permeation amount after 90 minutes is F (g / min), and the water permeability is calculated from the following equation.
透水保持率(%)=(F/F0)×100
本実施例では、透水保持率が55%以上であればタンパク質吸着抑制能は十分であると考え、合格とした。
Permeability retention rate (%) = (F / F 0 ) x 100
In this example, if the water permeability retention rate was 55% or more, it was considered that the protein adsorption inhibiting ability was sufficient, and it was determined as acceptable.
〔実施例1〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化ポリマーとして重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)36重量部を、溶媒であるN-メチル-2-ピロリドン46重量部に70℃で溶解し製膜溶液を得た。なお本溶液は37.5℃で凝固した。本溶液をチューブインオリフィス型ノズルを用いて、内部凝固液として60%ポリエチレングリコール(和光純薬PEG600、重量平均分子量600)水溶液を用い、空中走行距離40cm、凝固液は40℃の温水を用いて紡糸速度10m/minで乾湿式法より紡糸した。なお、凝固液の液面から20cmの高さの温度が65℃になるように空走部分の空気温度を制御した。得られた中空糸を脱溶剤及び熱収縮させる目的で80℃の温水で約4時間洗浄した後、121℃のオートクレーブ滅菌処理(高圧蒸気滅菌処理)を1時間行った。得られた膜の諸物性を表1に示す。
表1に示されるように、酸化処理後のポリエチレングリコール(PEG)残存量は4.7重量%となり、BSA透水保持率は62%であり、酸化処理後も、タンパク質吸着抑制能が十分に保持されることが確認された。また、破断強度も3.25MPaと高く、十分な機械的強度が得られることも確認された。
[Example 1]
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udelpolysulfone P-3500) and 36 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilic polymer are used as a solvent. A film-forming solution was obtained by dissolving at 46 ° C. in 46 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 37.5 ° C. Using a tube-in-orifice nozzle for this solution, a 60% polyethylene glycol (Wako Pure Chemical Industries, Ltd. PEG600, weight average molecular weight 600) aqueous solution was used as the internal coagulation liquid, air travel distance was 40 cm, and the coagulation liquid was 40 ° C hot water. Spinning was performed by a dry and wet method at a spinning speed of 10 m / min. Note that the air temperature in the idling portion was controlled so that the
As shown in Table 1, the residual amount of polyethylene glycol (PEG) after the oxidation treatment is 4.7% by weight, the BSA water permeability retention rate is 62%, and the protein adsorption inhibiting ability is sufficiently retained even after the oxidation treatment. It was confirmed. In addition, the breaking strength was as high as 3.25 MPa, and it was confirmed that sufficient mechanical strength was obtained.
〔実施例2〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量20,000のポリエチレングリコール(Merck社 PEG20,000)21重量部を、溶媒であるN-メチル-2-ピロリドン61重量部に70℃で溶解し製膜溶液を得た。なお本溶液は36.5℃で凝固した。本溶液をチューブインオリフィス型ノズルを用いて、内部凝固液として60%ポリエチレングリコール(和光純薬PEG600、重量平均分子量600)水溶液を用い、空中走行距離40cm、凝固液は40℃の温水を用いて10m/minで乾湿式法より紡糸した。なお、凝固液の液面から20cmの高さの温度が85℃になるように空走部分の空気温度を制御した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表1に示す。
表1に示されるように、酸化処理後のPEG残存量は0.8%重量となり、BSA透水保持率は58%であり、酸化処理後も、タンパク質吸着抑制能が十分に保持されることが確認された。また、破断強度も3.67MPaと高く、十分な機械的強度が得られることも確認された。
[Example 2]
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udel Polysulfone P-3500) and 21 parts by weight of polyethylene glycol having a weight average molecular weight of 20,000 (Merck PEG20,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 61 ° C. in 61 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 36.5 ° C. Using a tube-in-orifice nozzle for this solution, a 60% polyethylene glycol (Wako Pure Chemical Industries, Ltd. PEG600, weight average molecular weight 600) aqueous solution was used as the internal coagulation liquid, air travel distance was 40 cm, and the coagulation liquid was 40 ° C hot water. Spinning was performed at 10 m / min by a dry and wet method. The air temperature of the idle running portion was controlled so that the
As shown in Table 1, the residual amount of PEG after the oxidation treatment was 0.8% weight, the BSA water permeability retention rate was 58%, and it was confirmed that the protein adsorption inhibiting ability was sufficiently retained even after the oxidation treatment. It was. In addition, the breaking strength was as high as 3.67 MPa, and it was confirmed that sufficient mechanical strength was obtained.
〔実施例3〕
重量平均分子量66,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-1700)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)39重量部を、溶媒であるN-メチル-2-ピロリドン43重量部に70℃で溶解し製膜溶液を得た。なお本溶液は40.5℃で凝固した。本溶液をチューブインオリフィス型ノズルを用いて、内部凝固液として60%ポリエチレングリコール(和光純薬PEG600、重量平均分子量600)水溶液を用い、空中走行距離40cm、凝固液は40℃の温水を用いて10m/minで乾湿式法より紡糸した。なお、凝固液の液面から20cmの高さの温度が22℃になるように空走部分の空気温度を制御した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表1に示す。
表1に示されるように、酸化処理後のPEG残存量は9.8重量%となり、BSA透水保持率は85%であり、酸化処理後も、タンパク質吸着抑制能が十分に保持されることが確認された。また、破断強度も3.02MPaと高く、十分な機械的強度が得られることも確認された。
Example 3
18 parts by weight of polysulfone having a weight average molecular weight of 66,000 (Solvay Advanced Polymers, Udelpolysulfone P-1700) and 39 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 as a hydrophilizing agent (Clariant PEG35,000) are solvents. A film-forming solution was obtained by dissolving at 43 ° C. in 43 parts by weight of N-methyl-2-pyrrolidone. The solution solidified at 40.5 ° C. Using a tube-in-orifice nozzle for this solution, a 60% polyethylene glycol (Wako Pure Chemical Industries, Ltd. PEG600, weight average molecular weight 600) aqueous solution was used as the internal coagulation liquid, air travel distance was 40 cm, and the coagulation liquid was 40 ° C hot water. Spinning was performed at 10 m / min by a dry and wet method. The air temperature in the idle running portion was controlled so that the
As shown in Table 1, the residual amount of PEG after the oxidation treatment was 9.8% by weight, the BSA water permeability retention rate was 85%, and it was confirmed that the protein adsorption inhibiting ability was sufficiently retained even after the oxidation treatment. It was. In addition, the breaking strength was as high as 3.02 MPa, and it was confirmed that sufficient mechanical strength was obtained.
〔実施例4〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)22重量部を、溶媒であるN-メチル-2-ピロリドン60重量部に70℃で溶解し製膜溶液を得た。なお本溶液は37.5℃で凝固した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表1に示す。
表1に示されるように、酸化処理後のPEG残存量は4.2重量%となり、BSA透水保持率は60%であり、酸化処理後も、タンパク質吸着抑制能が十分に保持されることが確認された。また、破断強度も3.45MPaと高く、十分な機械的強度が得られることも確認された。
Example 4
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udelpolysulfone P-3500) and 22 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 as a hydrophilizing agent (Clariant PEG35,000) are used as a solvent. A film-forming solution was obtained by dissolving at 60 ° C. in 60 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 37.5 ° C. The other conditions were the same as in Example 1. Table 1 shows various physical properties of the obtained film.
As shown in Table 1, the residual amount of PEG after the oxidation treatment was 4.2% by weight, the BSA water permeability retention rate was 60%, and it was confirmed that the protein adsorption inhibiting ability was sufficiently retained even after the oxidation treatment. It was. Moreover, the breaking strength was as high as 3.45 MPa, and it was confirmed that sufficient mechanical strength was obtained.
〔実施例5〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)40重量部を、溶媒であるN-メチル-2-ピロリドン60重量部に70℃で溶解し製膜溶液を得た。なお本溶液は43.0℃で凝固した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表1に示す。
表1に示されるように、酸化処理後のPEG残存量は6.9重量%となり、BSA透水保持率は68%であり、酸化処理後も、タンパク質吸着抑制能が十分に保持されることが確認された。また、破断強度も3.27MPaと高く、十分な機械的強度が得られることも確認された。
Example 5
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Eudelpolysulfone P-3500) and 40 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 60 ° C. in 60 parts by weight of N-methyl-2-pyrrolidone. The solution solidified at 43.0 ° C. The other conditions were the same as in Example 1. Table 1 shows various physical properties of the obtained film.
As shown in Table 1, the residual amount of PEG after the oxidation treatment was 6.9% by weight, the BSA water permeability retention rate was 68%, and it was confirmed that the protein adsorption inhibiting ability was sufficiently retained even after the oxidation treatment. It was. In addition, the breaking strength was as high as 3.27 MPa, and it was confirmed that sufficient mechanical strength was obtained.
〔実施例6〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)36重量部を、溶媒であるN-メチル-2-ピロリドン46重量部に70℃で溶解し製膜溶液を得た。なお本溶液は37.5℃で凝固した。なお、凝固液の液面から20cmの高さの温度が85.5℃になるように空走部分の空気温度を制御した以外の条件は実施例1と同様に行った。得られた膜の諸物性を表1に示す。
表1に示されるように、酸化処理後のPEG残存量は2.6重量%となり、BSA透水保持率は60%であり、酸化処理後も、タンパク質吸着抑制能が十分に保持されることが確認された。また、破断強度も3.45MPaと高く、十分な機械的強度が得られることも確認された。
Example 6
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udelpolysulfone P-3500) and 36 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 46 ° C. in 46 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 37.5 ° C. The conditions were the same as in Example 1 except that the air temperature in the idle running portion was controlled so that the
As shown in Table 1, the residual amount of PEG after the oxidation treatment was 2.6% by weight, the BSA water permeability retention rate was 60%, and it was confirmed that the protein adsorption inhibiting ability was sufficiently retained even after the oxidation treatment. It was. Moreover, the breaking strength was as high as 3.45 MPa, and it was confirmed that sufficient mechanical strength was obtained.
〔実施例7〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)36重量部を、溶媒であるN-メチル-2-ピロリドン46重量部に70℃で溶解し製膜溶液を得た。なお本溶液は37.5℃で凝固した。なお、凝固液の液面から20cmの高さの温度が20℃になるように空走部分の空気温度を制御した以外の条件は実施例1と同様に行った。得られた膜の諸物性を表1に示す。
表1に示されるように、酸化処理後のPEG残存量は7.2重量%となり、BSA透水保持率は68%であり、酸化処理後も、タンパク質吸着抑制能が十分に保持されることが確認された。また、破断強度も3.27MPaと高く、十分な機械的強度が得られることも確認された。
Example 7
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udelpolysulfone P-3500) and 36 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 46 ° C. in 46 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 37.5 ° C. The conditions were the same as in Example 1 except that the air temperature in the idle running portion was controlled so that the
As shown in Table 1, the residual amount of PEG after the oxidation treatment was 7.2% by weight, the BSA water permeability retention rate was 68%, and it was confirmed that the protein adsorption inhibiting ability was sufficiently retained even after the oxidation treatment. It was. In addition, the breaking strength was as high as 3.27 MPa, and it was confirmed that sufficient mechanical strength was obtained.
〔比較例1〕
重量平均分子量66,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-1700)18重量部及び親水化剤として重量平均分子量10,000のポリエチレングリコール(Merck社 PEG10,000)40重量部を、溶媒であるN-メチル-2-ピロリドン42重量部に70℃で溶解し製膜溶液を得た。なお本溶液は34.5℃で凝固した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表2に示す。
本例では、Mw1/Mw2が0.6〜6.0の範囲になく、その結果、PEG残存量は0.6重量%しかなかった。BSA溶液透水保持率も38%と低く、酸化処理によって、タンパク質吸着抑制能が低下したことが確認された。
[Comparative Example 1]
18 parts by weight of polysulfone having a weight average molecular weight of 66,000 (Solvay Advanced Polymers, Udelpolysulfone P-1700) and 40 parts by weight of polyethylene glycol having a weight average molecular weight of 10,000 (Merck PEG10,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 42 ° C. in 42 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 34.5 ° C. The other conditions were the same as in Example 1. Table 2 shows various physical properties of the obtained film.
In this example, Mw1 / Mw2 was not in the range of 0.6 to 6.0, and as a result, the residual amount of PEG was only 0.6% by weight. The BSA solution water permeability was also low at 38%, and it was confirmed that the protein adsorption inhibiting ability was reduced by the oxidation treatment.
〔比較例2〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量150,000のポリエチレングリコール(住友精化社 PEG150,000)20重量部を、溶媒であるN-メチル-2-ピロリドン62重量部に70℃で溶解し製膜溶液を得た。なお本溶液は41.5℃で凝固した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表2に示す。
本例では、Mw1/Mw2が0.6〜6.0の範囲になく、PEG残存量は10.2重量%に達した。その結果、破断強度が2.72MPaと低くなり、十分な機械的強度を得られなかった。
[Comparative Example 2]
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udel Polysulfone P-3500) and 20 parts by weight of polyethylene glycol having a weight average molecular weight of 150,000 as a hydrophilizing agent (PEG 150,000, Sumitomo Seika) Was dissolved in 62 parts by weight of N-methyl-2-pyrrolidone at 70 ° C. to obtain a film forming solution. The solution solidified at 41.5 ° C. The other conditions were the same as in Example 1. Table 2 shows various physical properties of the obtained film.
In this example, Mw1 / Mw2 was not in the range of 0.6 to 6.0, and the residual amount of PEG reached 10.2% by weight. As a result, the breaking strength was as low as 2.72 MPa, and sufficient mechanical strength could not be obtained.
〔比較例3〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)16重量部を、溶媒であるN-メチル-2-ピロリドン66重量部に70℃で溶解し製膜溶液を得た。なお本溶液は34.5℃で凝固した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表2に示す。
本例では、W2/W1が1.2〜2.2の範囲になく、その結果、PEG残存量は0.7重量%しかなかった。BSA溶液透水保持率も38%と低く、酸化処理によって、タンパク質吸着抑制能が低下したことが確認された。
[Comparative Example 3]
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udelpolysulfone P-3500) and 16 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 66 ° C. in 66 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 34.5 ° C. The other conditions were the same as in Example 1. Table 2 shows various physical properties of the obtained film.
In this example, W2 / W1 was not in the range of 1.2 to 2.2, and as a result, the residual amount of PEG was only 0.7% by weight. The BSA solution water permeability was also low at 38%, and it was confirmed that the protein adsorption inhibiting ability was reduced by the oxidation treatment.
〔比較例4〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)43重量部を、溶媒であるN-メチル-2-ピロリドン61重量部に70℃で溶解し製膜溶液を得た。なお本溶液は43.0℃で凝固した。なお、それ以外の条件は実施例1と同様に行った。得られた膜の諸物性を表2に示す。
本例では、W2/W1が1.2〜2.2の範囲になく、PEG残存量は10.0重量%に達した。その結果、破断強度が2.88MPaと低くなり、十分な機械的強度を保持していないことが示された。
[Comparative Example 4]
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udel Polysulfone P-3500) and 43 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 61 ° C. in 61 parts by weight of N-methyl-2-pyrrolidone. The solution solidified at 43.0 ° C. The other conditions were the same as in Example 1. Table 2 shows various physical properties of the obtained film.
In this example, W2 / W1 was not in the range of 1.2 to 2.2, and the residual amount of PEG reached 10.0% by weight. As a result, the breaking strength was as low as 2.88 MPa, indicating that sufficient mechanical strength was not maintained.
〔比較例5〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)36重量部を、溶媒であるN-メチル-2-ピロリドン46重量部に70℃で溶解し製膜溶液を得た。なお本溶液は37.5℃で凝固した。なお、凝固液の液面から20cmの高さの温度が89.5℃になるように空走部分の空気温度を制御した以外の条件は実施例1と同様に行った。得られた膜の諸物性を表2に示す。
本例では、Tag及びTcが、+50℃>Tag-Tc>-20℃を満たさず、その結果、PEG残存量は0.7重量%しかなかった。BSA溶液透水保持率も39%と低く、酸化処理によって、タンパク質吸着抑制能が低下したことが確認された。
[Comparative Example 5]
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udelpolysulfone P-3500) and 36 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 46 ° C. in 46 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 37.5 ° C. The conditions were the same as in Example 1 except that the air temperature in the idle running portion was controlled so that the
In this example, Tag and Tc did not satisfy + 50 ° C.>Tag-Tc> −20 ° C. As a result, the residual amount of PEG was only 0.7% by weight. The BSA solution water permeability was also low at 39%, and it was confirmed that the protein adsorption inhibiting ability was reduced by the oxidation treatment.
〔比較例6〕
重量平均分子量75,000のポリスルホン(Solvay Advanced Polymers社製、ユーデルポリサルホンP-3500)18重量部及び親水化剤として重量平均分子量35,000のポリエチレングリコール(Clariant社 PEG35,000)36重量部を、溶媒であるN-メチル-2-ピロリドン46重量部に70℃で溶解し製膜溶液を得た。なお本溶液は37.5℃で凝固した。なお、凝固液の液面から20cmの高さの温度が15℃になるように空走部分の空気温度を制御した以外の条件は実施例1と同様に行った。得られた膜の諸物性を表2に示す。
本例では、Tag及びTcが、+50℃>Tag-Tc>-20℃を満たさず、PEG残存量は11.0重量%に達した。その結果、破断強度が2.68MPaと低くなり、十分な機械的強度を得られなかった。
[Comparative Example 6]
18 parts by weight of polysulfone having a weight average molecular weight of 75,000 (Solvay Advanced Polymers, Udelpolysulfone P-3500) and 36 parts by weight of polyethylene glycol having a weight average molecular weight of 35,000 (Clariant PEG35,000) as a hydrophilizing agent are used as a solvent. A film-forming solution was obtained by dissolving at 46 ° C. in 46 parts by weight of N-methyl-2-pyrrolidone. This solution solidified at 37.5 ° C. The conditions were the same as in Example 1 except that the air temperature in the idle running portion was controlled so that the
In this example, Tag and Tc did not satisfy + 50 ° C.>Tag-Tc> −20 ° C., and the residual amount of PEG reached 11.0% by weight. As a result, the breaking strength was as low as 2.68 MPa, and sufficient mechanical strength could not be obtained.
10…チューブインオリフィス型ノズル、11…内部凝固液流路、12…製膜溶液流路、20…空走部分の中心
DESCRIPTION OF
Claims (6)
ポリスルホン系ポリマー及び親水性ポリマーを含む製膜溶液をチューブインオリフィス型ノズルより内部凝固液とともに空走部分に吐出した後、凝固液中に導いて中空糸膜を形成する乾湿式法による製膜工程を含み、
前記ポリスルホン系ポリマー及び前記親水性ポリマーの重量平均分子量をそれぞれMw1、Mw2としたとき、Mw1/Mw2の値が0.6〜6.0の範囲にあり、
前記製膜溶液が、前記ポリスルホン系ポリマー、前記親水性ポリマー、及び共通溶媒からなり、該ポリスルホン系ポリマー及び該親水性ポリマーの重量をそれぞれW1、W2としたとき、W2/W1の値が1.2〜2.2の範囲にあり、
前記製膜溶液の凝固点をTc、前記ノズル直下の空走部分の中心温度をTagとしたとき、+50℃>Tag−Tc>−20℃の範囲にあることを特徴とする、製造方法。 A method for producing an oxidation-resistant hydrophilic polysulfone-based hollow fiber membrane according to any one of claims 1 to 3,
A film-forming process by a dry-wet method in which a film-forming solution containing a polysulfone-based polymer and a hydrophilic polymer is discharged from a tube-in-orifice nozzle together with an internal coagulating liquid to an idle running part and then guided into the coagulating liquid to form a hollow fiber film. Including
When the weight average molecular weights of the polysulfone polymer and the hydrophilic polymer are Mw1 and Mw2, respectively, the value of Mw1 / Mw2 is in the range of 0.6 to 6.0,
The film-forming solution is composed of the polysulfone-based polymer, the hydrophilic polymer, and a common solvent. When the weights of the polysulfone-based polymer and the hydrophilic polymer are W1 and W2, respectively, the value of W2 / W1 is 1. In the range of 2 to 2.2,
The manufacturing method, wherein Tc is a freezing point of the film-forming solution and Tag is a center temperature of a free running portion immediately below the nozzle, a range of + 50 ° C.>Tag−Tc> −20 ° C.
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