WO2012057185A1 - 血液成分吸着用担体及び血液成分吸着カラム - Google Patents
血液成分吸着用担体及び血液成分吸着カラム Download PDFInfo
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- WO2012057185A1 WO2012057185A1 PCT/JP2011/074629 JP2011074629W WO2012057185A1 WO 2012057185 A1 WO2012057185 A1 WO 2012057185A1 JP 2011074629 W JP2011074629 W JP 2011074629W WO 2012057185 A1 WO2012057185 A1 WO 2012057185A1
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- blood component
- group
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- nonwoven fabric
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28016—Particle form
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
- B01J20/28004—Sorbent size or size distribution, e.g. particle size
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28023—Fibres or filaments
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28033—Membrane, sheet, cloth, pad, lamellar or mat
- B01J20/28038—Membranes or mats made from fibers or filaments
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
- B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
- B01J20/3248—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
- B01J20/3251—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3285—Coating or impregnation layers comprising different type of functional groups or interactions, e.g. different ligands in various parts of the sorbent, mixed mode, dual zone, bimodal, multimodal, ionic or hydrophobic, cationic or anionic, hydrophilic or hydrophobic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0439—White blood cells; Leucocytes
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2913—Rod, strand, filament or fiber
- Y10T428/298—Physical dimension
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Definitions
- the present invention relates to a blood component adsorption carrier and a blood component adsorption column.
- Humoral factors such as inflammatory cytokines are deeply involved in the pathogenesis of inflammatory diseases such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, ulcerative colitis, and Crohn's disease. Attempts have been made to treat inflammatory diseases by inactivating these humoral factors in biologics. However, these humoral factors do not act on the site of inflammation alone, but multiple humoral factors act synergistically to develop and progress inflammatory diseases. Attention has been focused on leukocyte removal therapy that removes the activated leukocytes themselves from the living body.
- Leukocyte removal therapy is a method of purifying blood, removing blood from the veins outside the body, removing activated white blood cells with a column filled with an adsorption carrier, etc., and returning the purified blood to the opposite vein It is.
- Leukocytes are roughly divided into three types: granulocytes, monocytes and lymphocytes. Since leukocytes directly involved in inflammation of inflammatory diseases are considered to be granulocytes and monocytes, granulocytes are selected.
- Patent Document 1 has been developed (Patent Document 1) and a carrier that selectively adsorbs both activated granulocytes and monocytes, and also adsorbs inflammatory cytokines simultaneously (Patent Documents 2 and 3). Yes.
- lymphocytes are also known to be indirectly involved in inflammation of inflammatory diseases.
- the carrier (patent documents 4 and 5) which can adsorb
- the existing carrier capable of adsorbing all three types of white blood cells, granulocytes, monocytes and lymphocytes is made of a nonwoven fabric with a high bulk density made from ultrafine fibers, and most blood components other than red blood cells. Therefore, safety problems such as suspension of circulation and blood leakage due to pressure loss during blood circulation have been pointed out.
- a strong leukocyte removal carrier capable of adsorbing all three types of leukocytes and also capable of adsorbing inflammatory cytokines has been sought, but from the difficulty of overcoming the above problems, There are no reports of completed examples yet.
- the present invention is a blood component capable of adsorbing and removing leukocytes of granulocytes, monocytes and lymphocytes while suppressing the occurrence of pressure loss during blood circulation and simultaneously adsorbing and removing inflammatory cytokines.
- An object is to provide an adsorption carrier.
- the present inventors have a small pressure loss due to clogging, and can adsorb and remove inflammatory cytokines in addition to granulocytes, monocytes and lymphocytes with high efficiency.
- the present inventors have found a blood component-adsorbing carrier capable of achieving the above and have completed the present invention.
- the present invention provides the blood component adsorption carrier and the blood component adsorption column described in the following (1) to (7).
- a functional group having an acidic functional group selected from the group consisting of a sulfate group, a sulfite group and a sulfonic group and an amino group is introduced on the surface of a water-insoluble carrier comprising fibers or particles, and the fiber The carrier for adsorbing blood components, wherein the fiber diameter or the particle diameter of the particles is 0.5 to 20 ⁇ m.
- the carrier for adsorbing blood components of the present invention all three types of white blood cells, granulocytes, monocytes and lymphocytes, can be adsorbed and removed from the blood of patients with inflammatory diseases with high efficiency. It can be removed by adsorption at the same time.
- the blood component adsorption column packed with the blood component adsorption carrier of the present invention can be used for leukocyte removal therapy, and can be suitably used in the treatment of severe inflammatory diseases.
- the blood component adsorption carrier of the present invention has an acidic functional group selected from the group consisting of a sulfate group, a sulfite group and a sulfonate group on the surface of a water-insoluble carrier composed of fibers or particles, and a functional group having an amino group.
- the fiber diameter of the fibers or the particle diameter of the particles is 0.5 to 20 ⁇ m.
- Bood component adsorption carrier refers to a material capable of adsorbing and removing blood components from blood.
- a blood component refers to a component that constitutes blood, for example, a blood cell component such as red blood cells, white blood cells, or platelets or a humoral factor such as inflammatory cytokines, but for the purpose of treating inflammatory diseases. It is preferable that leukocytes and inflammatory cytokines are removed by adsorption.
- Inflammatory cytokines are proteins secreted from cells that transmit information to specific cells, such as interleukins, tumor necrosis factor- ⁇ , transforming growth factor beta, interferon- ⁇ (hereinafter referred to as “interferon-gamma”). INF- ⁇ ), angiogenic growth factors and immunosuppressive acidic proteins.
- Interleukins are cytokines that are secreted by leukocytes and function to regulate the immune system.
- Interleukins are cytokines that are secreted by leukocytes and function to regulate the immune system.
- interleukin-1 interleukin-6, interleukin-8 (hereinafter IL-8), interleukin- 10, interleukin-17 (hereinafter referred to as IL-17).
- IL-8 interleukin-8
- IL-17 interleukin-17
- Adsorption refers to the state where blood components adhere to the blood component adsorption carrier and do not easily peel off.
- Examples of the material of the “water-insoluble carrier comprising fibers or particles” include, for example, polyolefins such as polyethylene or polypropylene, polyesters such as polyethylene terephthalate or polybutylene terephthalate, fluorinated polymers such as Teflon (registered trademark), and poly (p-phenylene).
- Polysulfone polymers such as ethersulfone), polyetherimide, polyimide, polyamide, polyether, polyphenylene sulfide, polystyrene or acrylic polymer, or blended and alloyed of these polymer compounds.
- Polystyrene is preferred to facilitate the introduction of functional groups into the polymer, and polypropylene or polypropylene-polyethylene copolymer is preferred from the viewpoint of heat resistance or shape retention during processing.
- a functional group having an acidic functional group selected from the group consisting of a sulfuric acid group, a sulfite group and a sulfonic acid group and an amino group means at least one sulfate group in a part of the chemical structure of the functional group, A functional group containing an acidic functional group and an amino group selected from the group consisting of a sulfite group and a sulfonic acid group.
- the sulfuric acid group (—OSO 2 OH), the sulfite group (—O (SO) OH) and the sulfonic acid group (—SO 2 OH) have chemical structures similar to each other, and all have acidic hydroxyl groups. Therefore, it shows the common property of strong acidity and negative.
- the acidic functional group is located at the end of the functional group so that the interaction between the acidic functional group and the blood component becomes easier.
- the amino group is preferably a secondary amino group, and more preferably a tertiary amino group.
- a chemical structure existing between an acidic functional group and an amino group that is, a chemical structure (hereinafter referred to as a spacer) connecting the acidic functional group and the amino group is a hydrogen atom.
- the number of atoms which comprise a spacer is 200 or less.
- a “functional group having an acidic functional group selected from the group consisting of a sulfate group, a sulfite group and a sulfonic acid group and an amino group” onto the surface of the water-insoluble carrier, the water-insoluble carrier and the functional group described above
- the reactive functional group that mediates the bonding with halomethyl group active halogen group such as halomethyl group, haloacetyl group, haloacetamidomethyl group or halogenated alkyl group, epoxide group, carboxyl group, isocyanate group, thioisocyanate group
- an acid anhydride group may be mentioned, but an active halogen group is preferable and a haloacetamidomethyl group is more preferable from the viewpoint of appropriate reactivity.
- the above functional group in which the acidic functional group is located at the terminal and the spacer is an alkyl chain is, for example, a commercially available reagent that can be easily obtained by reacting an aminoalkylsulfonic acid with a haloacetamidomethyl group. Can be obtained.
- the above functional group in which the spacer is an alkyl chain having 3 or less carbon atoms is aminoethylsulfonic acid (hereinafter taurine), 3-aminopropiosulfonic acid (hereinafter homotaurine) or N-methylaminoethylsulfonic acid ( Hereinafter, it can be obtained by reacting N-methyltaurine) or 1,3-propane sultone (hereinafter referred to as propane sultone) with a haloacetamidomethyl group.
- taurine aminoethylsulfonic acid
- homotaurine 3-aminopropiosulfonic acid
- N-methylaminoethylsulfonic acid N-methylaminoethylsulfonic acid
- propane sultone 1,3-propane sultone
- “Fiber fiber diameter” and “particle particle diameter” of the “water-insoluble carrier composed of fibers or particles” need to be “0.5 to 20 ⁇ m” in order to exert the phagocytic ability of leukocytes. In order to exhibit the performance more stably, it is preferably 4 to 20 ⁇ m, more preferably 4 to 10 ⁇ m.
- a preferred value for the lower limit is 0.5 ⁇ m, more preferably 4 ⁇ m.
- a preferable value of the upper limit value is 20 ⁇ m, more preferably 10 ⁇ m. Any preferred lower limit can be combined with any preferred upper limit.
- the phagocytic ability of leukocytes refers to the property that granulocytes and monocytes capture microorganisms and bacteria that have entered the body such as humans and try to eat them.
- Fiber diameter of fiber refers to 10 small fiber samples taken at random and taken 2000 times using a scanning electron microscope, and 10 fibers (100 in total) for each photo. The average value of the measured values of the diameter.
- particle size of particle means that 10 small particle samples are randomly collected and 2000 times magnified photographs are taken using a scanning electron microscope. ) Is the average of the measured values of the diameter of the particles.
- a fiber having a larger diameter may be mixed from the viewpoint of securing the strength of the blood component adsorption carrier.
- the fiber diameter of such a fiber having a larger diameter is 10 ⁇ 50 ⁇ m is preferred.
- Examples of the shape of the water-insoluble carrier made of fibers include woven fabric, non-woven fabric, cotton fabric or hollow fiber.
- a skeleton material fiber such as polypropylene is added to maintain the shape. Is also preferable.
- the blood component adsorption carrier of the present invention is not intended to remove blood components by the principle of filtration.
- granulocytes and monocytes its phagocytic ability is used.
- lymphocytes and inflammatory cytokines “sulfate group” is used. Each of these is adsorbed and removed using the interaction between an acidic functional group selected from the group consisting of a sulfite group and a sulfonic acid group and a functional group having an amino group. Therefore, when the blood component adsorption carrier of the present invention is filled in a container such as a column, the void ratio can be increased as compared with the prior art, and the pressure loss can be greatly suppressed.
- the porosity of the water-insoluble carrier is preferably 85 to 98%, and preferably 90 to 95%. Is more preferable.
- a preferred value for the lower limit is 85%, more preferably 90%.
- a preferable value of the upper limit is 98%, more preferably 95%. Any preferred lower limit can be combined with any preferred upper limit.
- the acidic functional group included in the “functional group having an acidic functional group selected from the group consisting of a sulfate group, a sulfite group and a sulfonic acid group and an amino group” greatly contributes to the adsorption of lymphocytes. Is done.
- the density of acidic functional groups is too large, competitive adsorption between lymphocytes and positively charged proteins occurs, and it is assumed that the adsorption rate of lymphocytes decreases.
- the density of the acidic functional group can be expressed by a negative charge amount, but the negative charge amount of the blood component adsorption carrier of the present invention is 1.5 ⁇ 10 ⁇ 5 to 1.5 ⁇ 10 ⁇ 3 eq / g.
- the lower limit is preferably 1.5 ⁇ 10 ⁇ 5 eq / g, more preferably 1.0 ⁇ 10 ⁇ 4 eq / g.
- a preferable value of the upper limit is 1.5 ⁇ 10 ⁇ 3 eq / g, and more preferably 1.0 ⁇ 10 ⁇ 3 eq / g. Any preferred lower limit can be combined with any preferred upper limit.
- a negative charge amount of 1 eq / g means that 1 g of adsorption carrier can adsorb 1 mol of proton.
- the acidic functional group included in the “functional group having an acidic functional group selected from the group consisting of a sulfuric acid group, a sulfurous acid group and a sulfonic acid group and an amino group” contributes to the adsorption of inflammatory cytokines to some extent. It is guessed. In other words, the inflammatory cytokine is a protein of about 1 to several tens of kDa, and contains many kinds of ionic amino acids. Therefore, the positively charged site in the protein molecule interacts with the negative acidic functional group. It is presumed that
- the container shape of the blood component adsorption column of the present invention packed with the above-described blood component adsorption carrier may be any container having an inlet and an outlet for blood.
- Examples include prismatic containers such as columnar and octagonal cylinders.
- Containers that can be filled with a blood component adsorption carrier in a stacked form containers that can be filled with a blood component adsorption carrier wound in a cylindrical shape, or blood from the outer periphery of the cylinder.
- a container that flows inwardly and exits the container is preferred.
- wt% means weight%
- PP non-woven fabric After producing a nonwoven fabric composed of 85 wt% of this fiber and 15 wt% of polypropylene fiber having a diameter of 20 ⁇ m, a sheet-like polypropylene net (thickness 0.5 mm, single yarn diameter 0.3 mm, opening 2 mm) between the two nonwoven fabrics.
- a non-woven fabric having a three-layer structure (hereinafter referred to as PP non-woven fabric) was obtained by needle punching.
- PSt + PP non-woven fabric A non-woven fabric (PSt + PP non-woven fabric) having a core-sheath fiber diameter of 5 ⁇ m and a bulk density of 0.02 g / cm 3 by treating a non-woven fabric made of PP with a 3 wt% sodium hydroxide aqueous solution at 95 ° C.
- nonwoven fabric A was produced.
- Nitrobenzene 46 wt%, sulfuric acid 46 wt%, paraformaldehyde 1 wt%, N-methylol- ⁇ -chloroacetamide (hereinafter referred to as NMCA) 7 wt% were mixed, stirred and dissolved at 10 ° C. or less to prepare an NMCA reaction solution.
- the NMCA reaction solution was brought to 5 ° C., and to 1 g of non-woven fabric A, the NMCA reaction solution was added at a solid-liquid ratio of about 40 mL, and reacted for 2 hours while maintaining the reaction solution at 5 ° C. in a water bath.
- non-woven fabric B a chloroacetamidomethylated non-woven fabric
- non-woven fabric D (Preparation of sulfoethane aminated nonwoven fabric) 13 g of taurine was added to 500 mL of DMSO, and triethylamine was added thereto and mixed so that the concentration was 473 mM, and 10 g of non-woven fabric B was immersed therein and reacted at 70 ° C. for 6 hours.
- the non-woven fabric after the reaction was washed with DMSO and methanol, and further washed with water to obtain a sulfoethane-aminated non-woven fabric (hereinafter referred to as non-woven fabric D).
- Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric D.
- non-woven fabric E (Preparation of sulfopropane aminated nonwoven fabric) 13 g of homotaurine was added to 500 mL of DMSO, and triethylamine was added thereto and mixed so that the concentration was 473 mM, and 10 g of non-woven fabric B was immersed therein and reacted at 70 ° C. for 6 hours. The non-woven fabric after the reaction was washed with DMSO and methanol, and further washed with water to obtain a sulfopropane aminated non-woven fabric (hereinafter referred to as non-woven fabric E). Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric E.
- nonwoven fabric F (Production of methylsulfoethane aminated nonwoven fabric) 4.2 g of N-methyltaurine and 5 g of potassium iodide were added to 500 mL of DMSO, and triethylamine was added thereto so as to have a concentration of 473 mM. Reacted for hours. The nonwoven fabric after the reaction was washed with DMSO and methanol, and further washed with water to obtain a methylsulfoethane aminated nonwoven fabric (hereinafter, nonwoven fabric F). Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric E.
- nonwoven fabric H (Production of dimethylsulfopropane aminated nonwoven fabric) 10 g of non-woven fabric G was immersed in a solution obtained by adding 9.77 mL of propane sultone to 465 mL of THF and mixed, and reacted at 50 ° C. for 6 hours. The nonwoven fabric after the reaction was washed with THF and methanol, and further washed with water to obtain a dimethylsulfopropane aminated nonwoven fabric (hereinafter, nonwoven fabric H). Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric H.
- non-woven fabric I (Production of mercaptoethane aminated nonwoven fabric) 11.6 g of aminoethanethiol hydrochloride was added to 500 mL of DMSO, and triethylamine was added thereto and mixed so that the concentration was 473 mM, and 10 g of non-woven fabric B was immersed therein and reacted at 70 ° C. for 6 hours. The non-woven fabric after the reaction was washed with DMSO and methanol, and further washed with water to obtain a mercaptoethane aminated non-woven fabric (hereinafter referred to as non-woven fabric I). Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric I.
- tetraethylenepentaminated polysulfone nonwoven fabric After immersing 0.1 g of the nonwoven fabric A in a solution obtained by dissolving the recovered tetraethylenepentamated polysulfone again in 20 mL of DMF, the tetraethylenepentamined polysulfone nonwoven fabric (hereinafter, referred to as “tetraethylenepentaminated polysulfone nonwoven fabric”) is pulled up immediately and further immersed in methanol.
- Nonwoven fabric K was obtained. Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric I.
- nonwoven fabric L After immersing 0.1 g of the nonwoven fabric A in a solution obtained by re-dissolving the recovered sulfoethane aminated polysulfone in 20 mL of DMF, the nonwoven fabric is immediately pulled up and further immersed in methanol to thereby prepare a sulfoethane aminated polysulfone nonwoven fabric (hereinafter referred to as nonwoven fabric L). ) Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric L.
- nonwoven fabric M After immersing 0.1 g of the nonwoven fabric A in a solution obtained by re-dissolving the recovered sulfopropaneaminated polysulfone in 20 mL of DMF, the nonwoven fabric is immediately pulled up and further immersed in methanol to thereby prepare a sulfopropaneaminated polysulfone nonwoven fabric (hereinafter referred to as nonwoven fabric M). ) Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric M.
- nonwoven fabric N After immersing 0.1 g of the nonwoven fabric A in a solution obtained by dissolving the recovered mercaptoethane-aminated polysulfone in 20 mL of DMF again, it is immediately pulled up and further immersed in methanol to obtain a mercaptoethane-aminated polysulfone nonwoven fabric (hereinafter, nonwoven fabric N). ) Table 1 shows the structural formulas of the functional groups introduced into the nonwoven fabric N.
- Example 1 The nonwoven fabric D was cut out into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 1. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the following formulas 2 to 4. The results are shown in Table 2.
- Nonwoven fabric E was cut into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Example 3 The nonwoven fabric F was cut out into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Example 4 Nonwoven fabric H was cut out into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Example 5 The nonwoven fabric L was cut out into a disk shape having a diameter of 8 mm, and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Example 6 The nonwoven fabric M was cut out into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Nonwoven fabric C was cut into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- the non-woven fabric G was cut into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Nonwoven fabric I was cut into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Nonwoven fabric J was cut into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- Nonwoven fabric K was cut into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- the nonwoven fabric N was cut out into a disk shape having a diameter of 8 mm and placed in a polypropylene container. 1 mL of human blood (heparin concentration 30 U / mL) was added to this container, and the mixture was inverted and mixed in a 37 ° C. incubator for 20 minutes, and then the adsorption rate of each blood component was calculated. The results are shown in Table 2. The number of each blood component was measured using a multi-item automatic blood cell analyzer XT-1800i (Sysmex Corporation). The adsorption rate of each blood component was calculated by the above formulas 2-4. The results are shown in Table 2.
- the blood component adsorption carrier of the present invention in which a functional group having an acidic functional group was introduced on the surface of a water-insoluble carrier was compared with a carrier in which the functional group on the surface of the water-insoluble carrier had no acidic functional group.
- the adsorption rate of lymphocytes was significantly improved while maintaining the adsorption rate of granulocytes and monocytes.
- Example 7 Two pieces of non-woven fabric D were cut out into a disk shape having a diameter of 8 mm and placed in a polypropylene container. To this container, 0.8 mL of fetal bovine serum (hereinafter referred to as FBS) prepared so that the concentrations of IL-8, IL-17, and IFN- ⁇ were all 500 pg / mL was added and placed in a 37 ° C. incubator. Mix by inverting for 1 hour, and then measure the residual concentrations of IL-8, IL-17, and IFN- ⁇ by ELISA, respectively, and the IL-8, IL-17, and IFN- ⁇ adsorption rates according to the following formulas 5-7 was calculated. The results are shown in Table 3.
- FBS fetal bovine serum
- IL-8 adsorption rate (%) ⁇ (IL-8 concentration before inversion mixing) ⁇ (IL-8 concentration after inversion mixing) ⁇ / (IL-8 concentration before inversion mixing) ⁇ 100 ⁇
- Formula 5 IL-17 adsorption rate (%) ⁇ (IL-17 concentration before inversion mixing) ⁇ (IL-17 concentration after inversion mixing) ⁇ / (IL-17 concentration before inversion mixing) ⁇ 100 ⁇
- Formula 6 IFN- ⁇ adsorption rate (%) ⁇ (IFN- ⁇ concentration before inversion mixing) ⁇ (IFN- ⁇ concentration after inversion mixing) ⁇ / (IFN- ⁇ concentration before inversion mixing) ⁇ 100 ⁇ Formula 7
- Example 8 Two pieces of non-woven fabric E were cut into a disk shape having a diameter of 8 mm and placed in a polypropylene container. To this container, 0.8 mL of FBS prepared so that the concentrations of IL-8, IL-17, and IFN- ⁇ are all 500 pg / mL were added, and mixed by inverting for 1 hour in a 37 ° C. incubator. The residual concentrations of IL-8, IL-17, and IFN- ⁇ were measured by ELISA, and the IL-8, IL-17, and IFN- ⁇ adsorption rates were calculated according to the above formulas 5-7. The results are shown in Table 3.
- Example 6 Two pieces of the nonwoven fabric F were cut out into a disk shape having a diameter of 8 mm, and placed in a polypropylene container. To this container, 0.8 mL of FBS prepared so that the concentrations of IL-8, IL-17, and IFN- ⁇ are all 500 pg / mL were added, and mixed by inverting for 1 hour in a 37 ° C. incubator. The residual concentrations of IL-8, IL-17, and IFN- ⁇ were measured by ELISA, and the IL-8, IL-17, and IFN- ⁇ adsorption rates were calculated according to the above formulas 5-7. The results are shown in Table 3.
- Example 7 Two pieces of the nonwoven fabric H were cut out into a disk shape having a diameter of 8 mm, and placed in a polypropylene container. To this container, 0.8 mL of FBS prepared so that the concentrations of IL-8, IL-17, and IFN- ⁇ are all 500 pg / mL were added, and mixed by inverting for 1 hour in a 37 ° C. incubator. The residual concentrations of IL-8, IL-17, and IFN- ⁇ were measured by ELISA, and the IL-8, IL-17, and IFN- ⁇ adsorption rates were calculated according to the above formulas 5-7. The results are shown in Table 3.
- Example 8 Two pieces of the nonwoven fabric L were cut out into a disk shape having a diameter of 8 mm and placed in a polypropylene container. To this container, 0.8 mL of FBS prepared so that the concentrations of IL-8, IL-17, and IFN- ⁇ are all 500 pg / mL were added, and mixed by inverting for 1 hour in a 37 ° C. incubator. The residual concentrations of IL-8, IL-17, and IFN- ⁇ were measured by ELISA, and the IL-8, IL-17, and IFN- ⁇ adsorption rates were calculated according to the above formulas 5-7. The results are shown in Table 3.
- Example 9 Two pieces of the nonwoven fabric M were cut out into a disk shape having a diameter of 8 mm, and placed in a polypropylene container. To this container, 0.8 mL of FBS prepared so that the concentrations of IL-8, IL-17, and IFN- ⁇ are all 500 pg / mL were added, and mixed by inverting for 1 hour in a 37 ° C. incubator. The residual concentrations of IL-8, IL-17, and IFN- ⁇ were measured by ELISA, and the IL-8, IL-17, and IFN- ⁇ adsorption rates were calculated according to the above formulas 5-7. The results are shown in Table 3.
- the blood component adsorption carrier of the present invention in which a functional group having an acidic functional group was introduced on the surface of a water-insoluble carrier was compared with a carrier in which the functional group on the surface of the water-insoluble carrier had no acidic functional group. In some cases, it was revealed that the adsorption rate of IL-8, IL-17 and IFN- ⁇ was high.
- the present invention can be used as a blood component adsorption column in the medical field.
Abstract
Description
(1) 繊維又は粒子からなる水不溶性担体の表面に、硫酸基、亜硫酸基及びスルホン酸基からなる群から選ばれる酸性官能基と、アミノ基とを有する官能基が導入されてなり、上記繊維の繊維径又は上記粒子の粒子径は、0.5~20μmである、血液成分吸着用担体。
(2) 上記水不溶性担体の空隙率は、85~98%である、上記(1)に記載の血液成分吸着用担体。
(3) 上記水不溶性担体の陰性荷電量は、1.5×10-5~1.5×10-3eq/gである、(1)又は(2)に記載の血液成分吸着用担体。
(4) 上記水不溶性担体は、繊維径が4~10μmの繊維である、上記(1)~(3)のいずれかに記載の血液成分吸着用担体。
(5) 上記酸性官能基と上記アミノ基とは、アルキル鎖で結合されている、上記(1)~(4)のいずれかに記載の血液成分吸着用担体。
(6) 上記アルキル鎖は、炭素数3以下のアルキル鎖である、上記(5)に記載の血液成分吸着用担体。
(7) 上記(1)~(6)のいずれかに記載の血液成分吸着用担体が充填された、血液成分吸着カラム。
空隙率(%)={(b-a)/b}×100 ・・・・・・式1
a : 水不溶性担体で占められている部分の面積
b : 血液成分吸着担体の断面の全面積
36島の海島複合繊維であって、島が更に芯鞘複合によりなるものを次の成分を用いて、紡糸速度800m/分、延伸倍率3倍の製糸条件で得た。
島の芯成分: ポリプロピレン
島の鞘成分: ポリスチレン90wt%、ポリプロピレン10wt%
海成分: エチレンテレフタレート単位を主たる繰り返し単位とし、共重合成分として5-ナトリウムスルホイソフタル酸を3wt%含む共重合ポリエステル
複合比率(重量比率): 芯:鞘:海=45:40:15
PP製不織布を95℃、3wt%の水酸化ナトリウム水溶液で処理し、海成分を溶解することによって、芯鞘繊維の直径が5μmで、嵩密度が0.02g/cm3の不織布(PSt+PP製不織布、以下、不織布A)を作製した。
ニトロベンゼン46wt%、硫酸46wt%、パラホルムアルデヒド1wt%、N-メチロール-α-クロルアセトアミド(以下、NMCA)7wt%を10℃以下で混合、撹拌、溶解しNMCA化反応液を調製した。このNMCA化反応液を5℃にし、1gの不織布Aに対し、約40mLの固液比でNMCA化反応液を加え、水浴中で反応液を5℃に保ったまま2時間反応させた。その後、反応液から不織布を取り出し、NMCA反応液と同量のニトロベンゼンに浸漬し洗浄した。続いて不織布を取り出し、メタノールに浸漬し洗浄を行い、クロロアセトアミドメチル化不織布(以下、不織布B)を得た。
テトラエチレンペンタミン(以下、TEPA)の濃度が20mM、トリエチルアミンの濃度が473mMとなるようにそれぞれを500mLのジメチルスルホキシド(以下、DMSO)に溶解した液に、10gの不織布Bを浸して40℃で3時間反応させた。反応後の不織布をDMSO及びメタノールで洗浄し、さらに水洗することによって、TEPA化不織布(以下、不織布C)を得た。不織布Cに導入された官能基の構造式を、表1に示す。
13gのタウリンを500mLのDMSOに加え、そこへ濃度が473mMとなるようにトリエチルアミンを加えて混合した液に、10gの不織布Bを浸して70℃で6時間反応させた。反応後の不織布をDMSO及びメタノールで洗浄し、さらに水洗することによって、スルホエタンアミノ化不織布(以下、不織布D)を得た。不織布Dに導入された官能基の構造式を、表1に示す。
13gのホモタウリンを500mLのDMSOに加え、そこへ濃度が473mMとなるようにトリエチルアミンを加えて混合した液に、10gの不織布Bを浸して70℃で6時間反応させた。反応後の不織布をDMSO及びメタノールで洗浄し、さらに水洗することによって、スルホプロパンアミノ化不織布(以下、不織布E)を得た。不織布Eに導入された官能基の構造式を、表1に示す。
4.2gのN-メチルタウリン及び5gのヨウ化カリウムを500mLのDMSOに加え、そこへ濃度が473mMとなるようにトリエチルアミンを加えて混合した液に、10gの不織布Bを浸して60℃で6時間反応させた。反応後の不織布をDMSO及びメタノールで洗浄し、さらに水洗することによって、メチルスルホエタンアミノ化不織布(以下、不織布F)を得た。不織布Eに導入された官能基の構造式を、表1に示す。
2.5gのジメチルアミン及び5gのヨウ化カリウムを500mLのDMSOに加え、そこへ濃度が473mMとなるようにトリエチルアミンを加えて混合した液に、10gの不織布Bを浸して50℃で8時間反応させた。反応後の不織布をDMSO及びメタノールで洗浄し、さらに水洗することによって、ジメチルアミノ化不織布(以下、不織布G)を得た。不織布Fに導入された官能基の構造式を、表1に示す。
9.77mLのプロパンスルトンを465mLのTHFに加えて混合した液に、10gの不織布Gを浸して50℃で6時間反応させた。反応後の不織布をTHF及びメタノールで洗浄し、さらに水洗することによって、ジメチルスルホプロパンアミノ化不織布(以下、不織布H)を得た。不織布Hに導入された官能基の構造式を、表1に示す。
11.6gのアミノエタンチオール塩酸塩を500mLのDMSOに加え、そこへ濃度が473mMとなるようにトリエチルアミンを加えて混合した液に、10gの不織布Bを浸して70℃で6時間反応させた。反応後の不織布をDMSO及びメタノールで洗浄し、さらに水洗することによって、メルカプトエタンアミノ化不織布(以下、不織布I)を得た。不織布Iに導入された官能基の構造式を、表1に示す。
4.2gのジメチルアミノエタンチオール塩酸塩及び5gのヨウ化カリウムを500mLのDMSOに加え、そこへ濃度が473mMとなるようにトリエチルアミンを加えて混合した液に、10gの不織布Bを浸して60℃で6時間反応させた。反応後の不織布をDMSO及びメタノールで洗浄し、さらに水洗することによって、ジメチルメルカプトエタンアミノ化不織布(以下、不織布J)を得た。不織布Jに導入された官能基の構造式を、表1に示す。
32mLの5wt%ポリスルホン/ニトロベンゼン溶液に、0℃で調製した2mLの2wt%NMCA/硫酸溶液を加え、1時間撹拌した。ここに氷冷した800mLのメタノールを加えることでクロロアセトアミドメチル化ポリスルホンを析出させ、回収した。回収したクロロアセトアミドメチル化ポリスルホンを20mLのジメチルホルムアミド(以下、DMF)に溶解した液に、再度氷冷した400mLのメタノールを加えることで、クロロアセトアミドメチル化ポリスルホンを得た。
1gのクロロアセトアミドメチル化ポリスルホンを30mLのDMFに溶解し、そこへ濃度が20mMとなるようにテトラエチレンペンタミンを加えて17時間撹拌した後、ここに氷冷した600mLのメタノールを加えることでテトラエチレンペンタミン化ポリスルホンを析出させ、回収した。回収したテトラエチレンペンタミン化ポリスルホンを20mLのDMFに再度溶解した液に、0.1gの不織布Aを浸した後、直ぐに引き上げてさらにメタノールに浸すことによって、テトラエチレンペンタミン化ポリスルホン不織布(以下、不織布K)を得た。不織布Iに導入された官能基の構造式を、表1に示す。
1gのクロロアセトアミドメチル化ポリスルホンを30mLのDMFに溶解し、そこへ濃度が200mMとなるようにタウリンを加えて17時間撹拌した後、ここに氷冷した600mLのメタノールを加えることでスルホエタンアミノ化ポリスルホンを析出させ、回収した。回収したスルホエタンアミノ化ポリスルホンを20mLのDMFに再度溶解した液に、0.1gの不織布Aを浸した後、直ぐに引き上げてさらにメタノールに浸すことによって、スルホエタンアミノ化ポリスルホン不織布(以下、不織布L)を得た。不織布Lに導入された官能基の構造式を、表1に示す。
1gのクロロアセトアミドメチル化ポリスルホンを30mLのDMFに溶解し、そこへ濃度が200mMとなるようにホモタウリンを加えて17時間撹拌した後、ここに氷冷した600mLのメタノールを加えることでスルホプロパンアミノ化ポリスルホンを析出させ、回収した。回収したスルホプロパンアミノ化ポリスルホンを20mLのDMFに再度溶解した液に、0.1gの不織布Aを浸した後、直ぐに引き上げてさらにメタノールに浸すことによって、スルホプロパンアミノ化ポリスルホン不織布(以下、不織布M)を得た。不織布Mに導入された官能基の構造式を、表1に示す。
1gのクロロアセトアミドメチル化ポリスルホンを30mLのDMFに溶解し、そこへ濃度が200mMとなるようにアミノエタンチオール塩酸塩を加えて17時間撹拌した後、ここに氷冷した600mLのメタノールを加えることでメルカプトエタンアミノ化ポリスルホンを析出させ、回収した。回収したメルカプトエタンアミノ化ポリスルホンを20mLのDMFに再度溶解した液に、0.1gの不織布Aを浸した後、直ぐに引き上げてさらにメタノールに浸すことによって、メルカプトエタンアミノ化ポリスルホン不織布(以下、不織布N)を得た。不織布Nに導入された官能基の構造式を、表1に示す。
不織布Dを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表1に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、以下の式2~4により算出した。結果を表2に示す。
顆粒球吸着率(%)={(循環前血液中の顆粒球数)-(循環後血液中の顆粒球数)}/(循環前血液中の顆粒球数)×100 ・・・・・・式2
単球吸着率(%)={(循環前血液中の単球数)-(循環後血液液中の単球数)}/(循環前血液中の単球数)×100 ・・・・・・式3
リンパ球吸着率(%)={(循環前血液中のリンパ球数)-(循環後血液液中のリンパ球数)}/(循環前血液中のリンパ球数)×100 ・・・・・・式4
不織布Eを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Fを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Hを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Lを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Mを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Cを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Gを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Iを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Jを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Kを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Nを直径8mmの円板状に切り抜き、ポリプロピレン製の容器に入れた。この容器に、ヒト血液(ヘパリン濃度30U/mL)を1mL添加し、37℃のインキュベータ内で20分間転倒混和してから各血液成分の吸着率を算出した。結果を表2に示す。なお、各血液成分数の測定は、多項目自動血球分析装置XT-1800i(シスメックス株式会社)を用いて行った。各血液成分の吸着率は、上記の式2~4により算出した。結果を表2に示す。
不織布Dを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したウシ胎児血清(以下、FBS)を0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、以下の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
IL-8吸着率(%)={(転倒混和前のIL-8濃度)-(転倒混和後のIL-8濃度)}/(転倒混和前のIL-8濃度)×100 ・・・・・・式5
IL-17吸着率(%)={(転倒混和前のIL-17濃度)-(転倒混和後のIL-17濃度)}/(転倒混和前のIL-17濃度)×100 ・・・・・・式6
IFN-γ吸着率(%)={(転倒混和前のIFN-γ濃度)-(転倒混和後のIFN-γ濃度)}/(転倒混和前のIFN-γ濃度)×100 ・・・・・・式7
不織布Eを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Fを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Hを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Lを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Mを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Cを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Gを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8の濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8の残濃度を測定し、上記の式5によりIL-8吸着率を算出した。結果を表3に示す。
不織布Iを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Jを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Kを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
不織布Nを直径8mmの円板状に2枚切り抜き、ポリプロピレン製の容器に入れた。この容器に、IL-8、IL-17及びIFN-γの濃度がいずれも500pg/mLになるように調製したFBSを0.8mL添加し、37℃のインキュベータ内で1時間転倒混和してからELISA法にてIL-8、IL-17及びIFN-γの残濃度をそれぞれ測定し、上記の式5~7によりIL-8、IL-17及びIFN-γ吸着率を算出した。結果を表3に示す。
Claims (7)
- 繊維又は粒子からなる水不溶性担体の表面に、硫酸基、亜硫酸基及びスルホン酸基からなる群から選ばれる酸性官能基と、アミノ基とを有する官能基が導入されてなり、
前記繊維の繊維径又は前記粒子の粒子径は、0.5~20μmである、血液成分吸着用担体。 - 前記水不溶性担体の空隙率は、85~98%である、請求項1記載の血液成分吸着用担体。
- 前記水不溶性担体の陰性荷電量は、1.5×10-5~1.5×10-3eq/gである、請求項1又は2記載の血液成分吸着用担体。
- 前記水不溶性担体は、繊維径が4~10μmの繊維である、請求項1~3のいずれか一項記載の血液成分吸着用担体。
- 前記酸性官能基と前記アミノ基とは、アルキル鎖で結合されている、請求項1~4のいずれか一項記載の血液成分吸着用担体。
- 前記アルキル鎖は、炭素数3以下のアルキル鎖である、請求項5記載の血液成分吸着用担体。
- 請求項1~6のいずれか一項記載の血液成分吸着用担体が充填された、血液成分吸着カラム。
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- 2011-10-26 CA CA2814942A patent/CA2814942C/en active Active
- 2011-10-26 TW TW100138768A patent/TWI590844B/zh not_active IP Right Cessation
- 2011-10-26 AU AU2011321457A patent/AU2011321457B2/en not_active Ceased
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CN108136112A (zh) * | 2015-10-22 | 2018-06-08 | 西托索尔本茨公司 | 用于从生物流体中去除基于蛋白质的毒素和钾的多功能血液相容性多孔聚合物珠吸着剂 |
JP2019500917A (ja) * | 2015-10-22 | 2019-01-17 | サイトソーベンツ・コーポレーション | 生体液よりタンパク質ベースの毒素とカリウムを除去するための多機能性の血液適合性多孔性ポリマービーズ吸着剤 |
US11723916B2 (en) | 2015-10-22 | 2023-08-15 | Cytosorbents Corporation | Multi-functional hemocompatible porous polymer bead sorbent for removing protein based toxins and potassium from biological fluids |
US10646850B2 (en) | 2016-09-09 | 2020-05-12 | Toray Industries, Inc. | Material for blood purification |
WO2018225764A1 (ja) * | 2017-06-06 | 2018-12-13 | 東レ株式会社 | 活性化白血球-活性化血小板複合体の除去材料 |
JPWO2018225764A1 (ja) * | 2017-06-06 | 2020-02-27 | 東レ株式会社 | 活性化白血球−活性化血小板複合体の除去材料 |
US10888840B2 (en) | 2017-06-06 | 2021-01-12 | Toray Industries, Inc. | Material for removing activated leukocyte-activated platelet complex |
US11660383B2 (en) | 2017-06-06 | 2023-05-30 | Toray Industries, Inc. | Material for removing activated leukocyte-activated platelet complex |
JPWO2019049962A1 (ja) * | 2017-09-08 | 2020-08-27 | 東レ株式会社 | 免疫抑制性白血球吸着材料及び吸着カラム |
JP7193085B2 (ja) | 2017-09-08 | 2022-12-20 | 東レ株式会社 | 免疫抑制性白血球吸着材料及び吸着カラム |
JP7347288B2 (ja) | 2019-03-29 | 2023-09-20 | 東レ株式会社 | ホモセリン誘導体の吸着材料 |
WO2022039112A1 (ja) * | 2020-08-20 | 2022-02-24 | 昭和電工マテリアルズ株式会社 | 吸着剤粒子、基材粒子、充填カラム、及び希土類元素を回収する方法 |
Also Published As
Publication number | Publication date |
---|---|
ES2724199T3 (es) | 2019-09-09 |
AU2011321457A1 (en) | 2013-03-28 |
JPWO2012057185A1 (ja) | 2014-05-12 |
EP2633872A1 (en) | 2013-09-04 |
TWI590844B (zh) | 2017-07-11 |
JP5929197B2 (ja) | 2016-06-01 |
KR20130056313A (ko) | 2013-05-29 |
EP2633872A4 (en) | 2014-04-30 |
CN103167886B (zh) | 2016-05-18 |
SG189405A1 (en) | 2013-05-31 |
CA2814942A1 (en) | 2012-05-03 |
CA2814942C (en) | 2014-12-16 |
EP2633872B1 (en) | 2019-04-24 |
US9802178B2 (en) | 2017-10-31 |
AU2011321457B2 (en) | 2014-06-05 |
TW201221162A (en) | 2012-06-01 |
US20130220912A1 (en) | 2013-08-29 |
CN103167886A (zh) | 2013-06-19 |
KR101483469B1 (ko) | 2015-01-26 |
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