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JP-7855641-B2 - Hollow fiber membrane with improved biocompatibility and reduced elution of hydrophilic polymers

JP7855641B2JP 7855641 B2JP7855641 B2JP 7855641B2JP-7855641-B2

Inventors

  • パウル ミヒャエル
  • フィスラーゲ ライナー
  • ハンゼル ディートマー

Assignees

  • フレゼニウス メディカル ケア ドイッチェランド ゲゼルシャフト ミット ベシュレンクテル ハフツング

Dates

Publication Date
20260508
Application Date
20240613
Priority Date
20170201

Claims (14)

  1. A hollow fiber membrane having a membrane material containing polysulfone, polyvinylpyrrolidone, and at least one water-insoluble antioxidant, The polyvinylpyrrolidone content in the near-surface layer of the inner lumen of the membrane, as measured by XPS, is 22% by mass or more. The hollow fiber membrane is characterized in that the elution of polyvinylpyrrolidone after storage at 80°C and a relative humidity of less than 5% for 30 days is less than 4000 * 10⁻⁷ mg per individual fiber.
  2. The hollow fiber membrane according to claim 1, characterized in that it contains at least one water-insoluble antioxidant in an amount of 0.005 to 0.25% by mass relative to the total mass of the hollow fiber membrane.
  3. The hollow fiber membrane according to claim 1 or 2, characterized in that the zeta potential of the inner lumen-side surface of the hollow fiber membrane is -1 mV or more and less than -7 mV.
  4. A hollow fiber membrane according to any one of claims 1 to 3, characterized in that the peak height ratio of CNO- to SO2- in the surface layer of the inner lumen of the membrane, as measured by TOF-SIMS, is 4.5 or more.
  5. A hollow fiber membrane according to any one of claims 1 to 4, characterized in that the polyvinylpyrrolidone content of the hollow fiber membrane is 3 to 5% (w/w).
  6. A hollow fiber membrane according to any one of claims 1 to 5, characterized in that the mass-average molecular weight (Mw) of polyvinylpyrrolidone (PVP) on the inner lumen surface of the membrane is higher than the mass-average molecular weight (Mw) of PVP in the volume of the membrane.
  7. The hollow fiber membrane according to claim 6, wherein the mass-average molecular weight (Mw) of PVP on the surface of the inner lumen of the membrane is greater than 1,000,000 g/mol, and the mass-average molecular weight (Mw) of PVP in the volume of the membrane is less than 1,000,000 g/mol.
  8. The hollow fiber membrane according to claim 6 or 7, wherein the ratio of the mass-average molecular weight of PVP in the coagulant to the mass-average molecular weight of PVP in the spindle is at least 1.2.
  9. The hollow fiber membrane according to any one of claims 1 to 8, wherein the ratio of the albumin sieving coefficient measured after 5 minutes by the measurement method specified herein to the sieving coefficient measured after 30 minutes is less than 7, and the measurement of the albumin sieving coefficient is performed on the finished hollow fiber membrane filter using human plasma in accordance with DIN EN ISO 8637:2014 .
  10. The hollow fiber membrane according to any one of claims 1 to 9, wherein the ratio of the albumin sieving coefficient measured after 5 minutes by the measurement method specified herein to the sieving coefficient measured after 10 minutes is less than 3, and the measurement of the albumin sieving coefficient is performed on the finished hollow fiber membrane filter using human plasma in accordance with DIN EN ISO 8637:2014 .
  11. A hollow fiber membrane according to any one of claims 1 to 10, characterized in that the contact angle with water on the inner lumen surface, as measured by the "contact angle θ measurement" method, is less than 57°.
  12. A hollow fiber membrane according to any one of claims 1 to 11, characterized in that the platelet loss measured by the "platelet loss measurement" method is less than 50%.
  13. A hollow fiber membrane filter comprising a plurality of hollow fiber membranes according to any one of claims 1 to 12.
  14. The hollow fiber membrane filter according to claim 13, wherein the hollow fiber membrane filter is a dialyzer for hemodialysis.

Description

This invention relates to a method for producing a hollow fiber membrane, and to a membrane material comprising a hydrophobic polymer and a hydrophilic polymer, and to a type of processed hollow fiber membrane having improved biocompatibility properties, particularly improved properties with respect to C5a activation and "platelet loss." Hollow fiber membranes are widely used in liquid filtration. In particular, hollow fiber membranes are used in medical applications to purify blood during dialysis treatment for patients with kidney disease. Hollow fiber membranes are formed into bundles within filter modules used for extracorporeal blood treatment. This type of filter module for blood purification, so-called dialyzers, is mass-produced. Hollow fiber membranes used in blood purification are often composed of hydrophobic and hydrophilic polymers, particularly polysulfones and polyvinylpyrrolidones, because these materials have been demonstrated to be particularly blood-compatible and are therefore medically suitable for blood treatment, especially hemodialysis. In the context of this application, "polysulfone" refers to polymers having sulfone groups in the polymer back chain or side chains. Typical examples of polysulfones include bisphenol A (PSU), polyethersulfone (PES), polyphenylsulfone, and polysulfones based on copolymers containing sulfone groups. Further examples of polysulfone polymers are known in the prior art and are suitable for producing the blood treatment membranes defined in this invention. "Polyvinylpyrrolidone" refers to polymers produced using vinylpyrrolidone monomers or their derivatives. Further suitable hydrophobic polymers include polyamides, polyacrylonitriles, and regenerated cellulose and cellulose derivatives. Polyethylene glycol is yet another suitable hydrophilic polymer. The basic principles for generating hollow fiber membranes, as well as the products thereof, are described in the following prior art. - Marcel Mulder, "Principles of Membrane Technology," Kluwer Academic Publisher, 1996, Chapter III, Preparation of synthetic membranes.・EP 0 168 783 These methods described in the prior art for producing hollow fiber membranes prepare a spinning solution containing a polysulfone-based hydrophobic polymer and a vinylpyrrolidone-based hydrophilic polymer, particularly polyvinylpyrrolidone, and one or more solvents and any additives that may be required. Polar aproton solvents, particularly dimethylacetamide (DMAc), N-methylpyrrolidone (NMP), dimethylformamide (DMF), or dimethyl sulfoxide (DMSO), are commonly used as solvents. The term "solvent" thereby refers to the solubility of the solvent for the polymers used, particularly polysulfone and polyvinylpyrrolidone. The spinning solution may also contain small amounts of additives, such as polar proton solvents like water, at low percentages. Mixtures of solvents are also known in the prior art. The spindle is spun through the circular concentric annular gap of the spinneret. The spinneret further has a bore through which a coagulant is guided. The coagulant is usually composed of a mixture of an aproton polar solvent, such as DMAc, and a proton liquid, such as water. The spindle and coagulant are processed by passing the coagulant through the annular gap and bore of the spinneret into the strand, whose lumen contains the coagulant. The strand is then guided through a void, usually through which the spindle of the strand begins to solidify and form a two-phase system of gel and sol phases. Next, the strand is introduced into a precipitation bath containing a precipitant. When the strand is introduced into the precipitation bath, a hollow fibrous membrane structure is formed. Water or a mixture of proton and aproton solvents, in particular water and dimethylacetamide, N-methylpyrrolidone, dimethylformamide, or dimethyl sulfoxide, usually serve as precipitants. The resulting hollow fiber membrane is then passed through a rinsing bath, dried, and wound onto a winding machine. The hollow fiber membrane can be removed from the winding machine in the form of a hollow fiber bundle. To constitute a hollow fiber membrane filter, such a bundle is placed in a housing, preferably a cylindrical housing. The ends of the hollow fiber membrane bundle are embedded in a cast compound, while the open ends of the hollow fibers are exposed. The cast compound forms a sealed region between the interior of the hollow fiber membrane, the housing, and the area surrounding the hollow fiber membrane. This forms the inlet and outlet regions of the ends of the hollow fiber membrane bundle, as well as a first chamber within the finished hollow fiber membrane filter surrounding the interior of the hollow fiber membrane. A second chamber is correspondingly formed from the areas between the hollow fiber membranes and the space between the housing wall and the hollow fiber membranes. Fluid ports on the housing of the hollow fiber membrane filter allow liquids and f