EP1600533B1 - Fibre poreuse, structure fibreuse poreuse et procede de production correspondant - Google Patents

Fibre poreuse, structure fibreuse poreuse et procede de production correspondant Download PDF

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Publication number
EP1600533B1
EP1600533B1 EP04710522A EP04710522A EP1600533B1 EP 1600533 B1 EP1600533 B1 EP 1600533B1 EP 04710522 A EP04710522 A EP 04710522A EP 04710522 A EP04710522 A EP 04710522A EP 1600533 B1 EP1600533 B1 EP 1600533B1
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Prior art keywords
fiber
fiber structure
fibers
porous
hydrophobic solvent
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German (de)
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EP1600533A1 (fr
EP1600533A4 (fr
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Takanori c/o Teijin Ltd MIYOSHI
Shinya c/o Teijin Ltd. KOMURA
Hiroyoshi c/o Teijin Ltd. MINEMATSU
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Teijin Ltd
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Teijin Ltd
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    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0015—Electro-spinning characterised by the initial state of the material
    • D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • D01D5/0038—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion the fibre formed by solvent evaporation, i.e. dry electro-spinning
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/24—Formation of filaments, threads, or the like with a hollow structure; Spinnerette packs therefor
    • D01D5/247—Discontinuous hollow structure or microporous structure
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
    • D01F6/44—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds as major constituent with other polymers or low-molecular-weight compounds
    • D01F6/56—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds as major constituent with other polymers or low-molecular-weight compounds of polymers of cyclic compounds with one carbon-to-carbon double bond in the side chain
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F6/00—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof
    • D01F6/88—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds
    • D01F6/92—Monocomponent artificial filaments or the like of synthetic polymers; Manufacture thereof from mixtures of polycondensation products as major constituent with other polymers or low-molecular-weight compounds of polyesters
    • 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

Definitions

  • the present invention relates to a porous fiber produced without needing a coagulating solution, a fiber structure made of the porous fibers, and a method for producing the fiber structure.
  • the present invention relates to a porous fiber mainly comprising a hydrophobic solvent-soluble polymer and an organic compound containing a plurality of hydroxyl groups, a fiber structure made of the porous fibers, and a method for producing the fiber structure.
  • porous structure In tissue engineering fields, a porous structure is sometimes used as a matrix (scaffold) when cells are cultured.
  • a freeze dried product of a bioabsorbable organic material, a foamed, and a fiber structure are known (see, for example, non-patent literature 1).
  • These porous structures must have affinity to cells, biodegradability, safety, and so on.
  • Polyglycolic acid which is used for a surgical suture etc., has excellent biocompatibility, biodegradability, and safety, and a fiber structure made of polyglycolic acid is being studied for using as the matrix (see, for example, non-patent literature 1).
  • fiber diameters obtained by using conventional methods are too large, and surface areas on which cells can be adhered are not sufficient.
  • fiber structures having finer fibers are desired.
  • electrospinning As a manufacturing process for a fiber structure having finer fibers, electrospinning is known (see, for example, patent literature 1 and 2).
  • the process for electrospinning comprises steps introducing a liquid, for example, a solution of a material which form a fibrous structure, into an electric field, drawing the solution toward an electrode by means of the electric force, and forming a fibrous material.
  • the fibrous material is hardened during the solution is drawn.
  • the hardening is performed, for example, by means of cooling (e.g., in cases where the solution to be spun is solid at room temperature), chemical hardening (e.g., a treatment with a hardening vapor), solvent vaporization, and so on.
  • the obtained fibrous material is collected on an adequately placed collector from which it can be removed if necessary. Furthermore, electrospinning can obtain a non-woven fibrous material directly, and thereby the operation of the process is simple and easy, that is, there is no need to form fibers once and then to form a fiber structure further.
  • the fiber structures obtained by using electrospinning are apt to take a dense structure having short distances between fibers since the fibers have fine diameters.
  • the fiber structure is used as a cell culture matrix, proliferated cells accumulate on the surfaces of fibers that form the fiber structure, the surfaces of the fiber structure are covered by the cells with progressing culture, and the surfaces are completely covered thick finally. Resultingly, it becomes difficult for a solution containing nutrients etc. to move sufficiently into inner parts of the fiber structure, and this causes a problem in which only sections near the surface can afford to curry out cell culture.
  • Patent literature 1 JP-A 63-145465 (JP-A means Japanese unexamined patent publication).
  • Patent literature 2 JP-A 2002-249966 .
  • Patent literature 3 The pamphlet of International Publication No. 02/16680, [Non-patent literature 1] Tissue Engineering, page 258, the translation was supervised by the team represented by Noriya Oono and Masuo Aizawa, NTS INC., January 31, 2002 .
  • Non-patent literature 2 Joel D.
  • the fiber structure expresses a three-dimensional structure that are formed with heaping, weaving, knitting, or another method from single or a plurality of obtained porous fibers.
  • Concrete forms of the fiber structure include, for example, nonwoven fabrics.
  • tubes, meshes, and the like that are obtained by processing the above mentioned fiber structure can be preferably used in the field of tissue engineering.
  • Porous fibers and fiber structures of the present invention contain polymers soluble in hydrophobic solvents.
  • the hydrophobic solvent of the present invention expresses an organic substance that can not dissolve water of 5% or more in concentration at room temperature (for example, 27°C) and is liquid at the temperature.
  • halogen element-containing hydrocarbons are preferable because they can dissolve polymers well.
  • Examples of more preferable hydrophobic solvents are methylene chloride, chloroform, dichloroethane, tetrachloroethane, trichloroethane, dibromomethane, bromoform, and the like, and methylene chloride is especially preferable.
  • volatile solvents are preferably used.
  • the volatile solvent expresses an organic substance that has a boiling point not higher than 200°C at atmospheric pressure and is liquid at room temperature (for example, 27°C).
  • “Soluble” in the present invention means that a solution containing a polymer of 1 wt.% can exist stably at room temperature (for example, at 27°C) without forming precipitates.
  • polymers soluble in the hydrophobic solvent are polylactic acid, polylactic acid-polyglycolic acid copolymers, aliphatic polyesters such as polycaprolactone, polycarbonates, polystyrene, polyarylates, polymethylmethacrylate, polyethylmethacrylate, cellulose diacetate, cellulose triacetate, polyvinyl acetate, polyvinyl methyl ether, poly(N-vinylpyrrolidone), polybutylene succinate, and polyethylene succinate, and copolymers of these polymers and the like.
  • polylactic acid polycaprolactone
  • polycarbonates polystyrene, and polyarylates are preferable.
  • Porous fibers and fiber structures of the present invention may contain one kind, or two or more kinds of polymers soluble in the hydrophobic solvent.
  • Porous fibers and fiber structures of the present invention contain an organic compound having a plurality of hydroxyl groups and a number-average molecular weight of not less than 62 nor more than 300.
  • an organic compound that does not have a plurality of hydroxyl groups is used, the objective porous fibers can not be obtained, further a fiber structure comprising the porous fibers can not be produced stably, and furthermore, the cell culture using the fiber structure becomes difficult in some cases; and thereby such an organic compound is not preferable.
  • the organic compound has a number-average molecular weight of more than 300, the forming of porous fibers becomes difficult.
  • an example of the organic compound having a molecular weight of 62 and a plurality of hydroxyl groups is ethylene glycol, and an organic compound having a molecular weight of less than 62 and a plurality of hydroxyl groups does not exist actually. More preferable number-average molecular weights of the organic compound are not less than 62 nor more than 250.
  • organic compounds having a plurality of hydroxyl groups include ethylene glycol, propylene glycol (1,2-propanediol), 1,3-propanediol, diethylene glycol, triethylene glycol, glycerin, pentaerythritol, polyethylene glycol, polypropylene glycol, polyethylene glycol-polypropylene glycol block polymers, and the like.
  • polymers or compounds other than hydrophobic solvent-soluble polymers and organic compounds having a plurality of hydroxyl groups can be combinedly used (for example, copolymers of polymers, polymer blends, or compound mixtures) in a range where the purposes are not impaired.
  • Porous fibers and fiber structures of the present invention have an average fiber diameter of 0.1-20 ⁇ m.
  • the average fiber diameter of less than 0.1 ⁇ m is not preferable because such porous fibers and fiber structures decompose too quickly in vivo when they are used as cell culture matrices for tissue engineering.
  • the average fiber diameter of larger than 20 ⁇ m is not preferable because the area on which cells can adhere becomes small.
  • a more preferable average fiber diameter is 0.2-15 ⁇ m, and an especially preferable average fiber diameter is 0.2-10 ⁇ m.
  • the fiber diameter expresses the diameter of a fiber cross-section when the cross-section is circler. However, sometimes the shape of a fiber cross-section is oval.
  • the fiber diameter of this case expresses the value calculated by averaging the lengths of the major axis and the minor axis of the oval. Further, when the cross-section of the fiber is not circular nor oval, it is approximated to a circle or an oval, and the cross-section is calculated.
  • porous fibers of the present invention it is preferable for porous fibers of the present invention to have fiber lengths of 20 ⁇ m or more. When the fiber lengths are less than 20 ⁇ m, the mechanical strengths of the fiber structure obtained from the fibers are insufficient.
  • the fiber lengths are preferably 40 ⁇ m or more, and more preferably 1 mm or more.
  • Porous fibers of the present invention express fibers having isolated holes and/or continuous holes on surfaces and in inner parts of fibers.
  • the isolated holes and the continuous holes of the inner parts may form empty bodies so that the fibers may be hollow fibers as a whole.
  • Fiber structures of the present invention comprise porous fibers having a void percentage of 5% at least.
  • the void percentage of 5% means that, on a fiber cross-section formed by cutting at an arbitrary position, the sum of the areas of the isolated holes and the continuous holes that reach to the fiber surface, and the areas of the isolated holes and the continuous holes existing in the inner parts of the fiber, that is, the sum of the space areas where fiber forming substances (hydrophobic solvent-soluble polymers, organic compounds having a plurality of hydroxyl groups, and other necessary polymers and compounds) are absent, occupies at least 5% of the whole area of the fiber cross-section including the space areas.
  • a void percentage of less than 5% is not preferable since a solution that contains nutrients and the like does not penetrate sufficiently into the inner parts of the matrix during cell culture.
  • the void percentage is preferably 10% or more.
  • a preferable mode of the present invention is porous fibers comprising a hydrophobic solvent-soluble polymer and an organic compound having a plurality of hydroxyl groups, and having an average fiber diameter of 0.1-20 ⁇ m and a void percentage of at least 5%, and fiber structures made therefrom. It is preferable to use an aliphatic polyester, a polycarbonate, polystyrene, or a polyarylate as the hydrophobic solvent-soluble polymer.
  • a solution prepared by dissolving a hydrophobic solvent-soluble polymer and an organic compound having a plurality of hydroxyl groups in a hydrophobic solvent is discharged into an electrostatic field generated between electrodes, the solution is drawn toward an electrode, and the formed fibrous material is accumulated on a collector, and thereby a fiber structure can be obtained. That is, when the fibrous material is accumulated, porous fibers of the present invention are already formed.
  • the fibrous material expresses not only a material having a state of porous fibers and fiber structures in which the solvent of the solution is already evaporated, but also a material having a state in which the solvent of the solution is contained.
  • the electrode to be used in the present invention may be arbitrarily selected from metals, inorganic materials, and organic materials as long as it exhibits conductivity. Further, it may be a body formed by placing a thin film of a metal, an inorganic substance, or an organic substance that shows electroconductivity on an insulator.
  • the electrostatic field of the present invention is formed between a pair of electrodes or among a plurality of electrodes, and a high voltage can be applied on any electrode. This includes the case where three electrodes in total consisting of two electrodes of different high voltages (for example, 15 kV and 10 kV) and an electrode connected to a ground are used, and the case where more than three electrodes are used is also included.
  • a solution is produced by dissolving a hydrophobic solvent-soluble polymer and an organic compound having a plurality of hydroxyl groups in a hydrophobic solvent.
  • the concentration of the hydrophobic solvent-soluble polymer is preferably 1-30 wt.%.
  • the concentration of the hydrophobic solvent-soluble polymer of less than 1 wt.% is not preferable because the formation of fiber structures becomes difficult due to extremely low concentration. Further, the concentration of more than 30 wt.% is not preferable because fiber diameters of the obtained fiber structure become large.
  • the concentration of the hydrophobic solvent-soluble polymer is more preferably 2-20 wt.%.
  • the concentration of the organic compound having a plurality of hydroxyl groups in the solution of the present invention is 2-50 wt.%. It is not preferable that the concentration of the organic compound having a plurality of hydroxyl groups is less than 2 wt.% since the total areas of the recessed parts and the void parts on fiber cross-sections become small. Further, the concentration of more than 50 wt.% is not preferable since the formation of fiber structures becomes difficult.
  • the concentration of the organic compound having a plurality of hydroxyl groups is more preferably 4-30 wt.%.
  • the boiling point of the organic compound having a plurality of hydroxyl groups of the present invention is low, a part of the compound sometimes evaporates together with a solvent during spinning by means of electrospinning.
  • the concentration of the organic compound in the fiber structure is more preferably 5-60 wt.%, and further preferably, 10-60 wt.%.
  • the hydrophobic solvent can be used alone, or a plurality of the hydrophobic solvents can be used in combination. Further, the hydrophobic solvent can be used in combination with another kind of solvent in a range where the purpose of the present invention is not missed.
  • the concrete examples of the hydrophobic solvent are already shown above.
  • the solution (2 in Figure 1 ) is supplied to the nozzle, the solution is placed at a proper position in the electrostatic force, the solution is drawn from the nozzle by means of the electrostatic field, and thereby fibers are formed from the solution.
  • an appropriate apparatus can be used.
  • an appropriate means e.g., an injection needle-shaped solution ejection nozzle (1 in Figure 1 ) on which voltage is applied by using a high voltage generator (6 in Figure 1 )
  • a cylindrical solution-holding tank (3 in Figure 1 ) of a syringe is placed at the tip of a cylindrical solution-holding tank (3 in Figure 1 ) of a syringe, and the solution is guided to the tip.
  • the tip of the ejection nozzle (1 in Figure 1 ) is placed at an appropriate distance from a grounded fibrous material-collection electrode (5 in Figure 1 ), and when the solution (2 in Figure 1 ) comes out from the tip of the ejection nozzle (1 in Figure 1 ), a fibrous material is formed between the tip and the fibrous material-collection electrode (5 in Figure 1 ).
  • fine drops of the solution can be introduced into the electric field with a method known by those in the art, and one preferable mode of the method will be explained by using Figure 2 .
  • the only requirement in this mode is that a droplet is held in the electrostatic field apart from the fibrous material-collection electrode (5 in Figure 2 ) at a distance in which fibers can be formed.
  • an electrode (4 in Figure 2 ) which directly opposes the fibrous material-collection electrode may be directly inserted into the solution (2 in Figure 2 ) in a solution-holding tank (3 in Figure 2 ) having a nozzle (1 in Figure 2 ).
  • a plurality of nozzles can be used so that the production rate of the fibrous material increases.
  • the distance between the electrodes depends on an electrostatic charge level, the size of a nozzle, the flow and the concentration of the solution to be spun, and the like, but the distance of 5-20 cm was appropriate with approximately 10 kV.
  • an impressed electrostatic voltage is generally 3-100 kV, preferably 5-50 kV, and more preferably 5-30 kV.
  • the desired electrostatic voltage can be generated by using an appropriate method arbitrarily selected out of known technology.
  • a collector can be additionally placed between electrodes so that a fiber structure is collected on it.
  • a belt-shaped material is placed between electrodes, and by using the material as the collector, a fiber structure can be produced continuously.
  • the solvent normally evaporates completely before the fibrous material is collected on the collector at ordinary room temperature and atmospheric pressure; however, if the evaporation of the solvent is not sufficient, the solution may be drawn under reduced pressure.
  • porous fibers of the present invention are formed.
  • the temperature for spinning fibers depends on the evaporation behavior of the solvent and the viscosity of the solution to be spun; however, it is usually 0-50°C.
  • the porous fibers are further accumulated over themselves on the collector, and thereby a fiber structure of the present invention is formed.
  • a preferable mode of fabrication methods of the present invention includes a step in which a solution is produced by dissolving a hydrophobic solvent-soluble polymer and an organic compound having a plurality of hydroxyl groups in a hydrophobic solvent, a step in which the solution is spun by using electrospinning, and a step in which a fiber structure accumulated on a collector is obtained; and the fiber structure comprising porous fibers having an average fiber diameter of 0.1-20 ⁇ m and a void percentage of at least 5% is obtained in the preferable mode.
  • hydrophobic solvent-soluble polymer an aliphatic polyester, a polycarbonate, polystyrene, or a polyarylate is used, and yet it is preferable to use a volatile solvent as the hydrophobic solvent.
  • a fiber structure obtained in the present invention can be used alone; however, it may be used in combination with another member with due regard to handleability and other requirements.
  • a nonwoven fabric, a woven fabric, a film, or the like that can serve as a supporting material is used as the collector, and a fiber structure is formed on it; and thereby a member in which a supporting material and the fiber structure are combined can be obtained.
  • fiber structures obtained in the present invention are not limited to cell culture matrices for tissue engineering, but they can be used as various materials such as all sorts of filters, catalyst supporting materials, or the like in which special features of the present invention, that is, dent parts and voids, are used practically.
  • the whole part of the fiber cross-section was cut out from the photograph paper of the cross-section photograph image, and its weight was measured. Subsequently, the void parts of the fiber were cut out from the photograph paper, and their weights were measured. The void percentage of a fiber was calculated from these weights. This process was repeated five times, and the average value was calculated.
  • the solution was discharged over 5 minutes toward a collector electrode by using an apparatus shown in Figure 2 .
  • the inside diameter of the nozzle was 0.8 mm, the voltage was 12 kV, and the distance from the nozzle to the collector electrode was 10 cm.
  • the obtained fiber structure was examined by using a scanning electron microscope (S-2400, manufactured by Hitachi). The average fiber diameter was 3 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 40%, and the ethylene glycol content in the fiber structure was 18.0 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 3 and Figure 4 .
  • Example 2 Except that 1 pt. wt. of diethylene glycol (special grade chemical, manufactured by Wako Pure Chemical Industries, Ltd.) was used in stead of the ethylene glycol, the same operations as Example 1 were curried out.
  • the average fiber diameter was 4 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 15%, and the diethylene glycol content in the fiber structure was 47.9 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 5 and Figure 6 .
  • Example 2 Except that 1 pt. wt. of triethylene glycol (special grade chemical, manufactured by Wako Pure Chemical Industries, Ltd.) was used in stead of the ethylene glycol, the same operations as Example 1 were curried out.
  • the average fiber diameter was 3 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 15%, and the triethylene glycol content in the fiber structure was 46.2 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 7 and Figure 8 .
  • Example 2 Except that 1 pt. wt. of polyethylene glycol (average molecular weight of 200, first class chemical, manufactured by Wako Pure Chemical Industries, Ltd.) was used in stead of the ethylene glycol, the same operations as Example 1 were curried out.
  • the average fiber diameter was 2 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 15%, and the polyethylene glycol content in the fiber structure was 50.0 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 9 and Figure 10 .
  • Example 2 Except that 1 pt. wt. of propylene glycol (1,2-propanediol) (special grade chemical, manufactured by Wako Pure Chemical Industries, Ltd.) was used in stead of the ethylene glycol, the same operations as Example 1 were curried out.
  • the average fiber diameter was 4 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 15%, and the 1,2-propanediol content in the fiber structure was 15.3 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 11 and Figure 12 .
  • Example 2 Except that 1 pt. wt. of polycaprolactone (average molecular weight of 70,000-100,000, manufactured by Wako Pure Chemical Industries, Ltd.) was used in stead of the polylactic acid, the same operations as Example 1 were curried out.
  • the average fiber diameter was 4 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 15%, and the ethylene glycol content in the fiber structure was 16.7 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 13 and Figure 14 .
  • Example 2 Except that 1 pt. wt. of polycarbonate (trade mark of "Panlite L1250", manufactured by Teijin Chemicals Ltd.) was used in stead of the polylactic acid, the same operations as Example 1 were curried out.
  • the average fiber diameter was 3 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 35%, and the ethylene glycol content in the fiber structure was 12.3 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 15 and Figure 16 .
  • Example 2 Except that 1 pt. wt. of polystyrene (average molecular weight of 250,000, manufactured by Kanto Chemicals Ltd.) was used in stead of the polylactic acid, the same operations as Example 1 were curried out.
  • the average fiber diameter was 6 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 35%, and the ethylene glycol content in the fiber structure was 11.2 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 17 and Figure 18 .
  • Example 2 Except that 1 pt. wt. of polyarylate (trade mark of "U-polymer U-100", manufactured by Yunitika) was used in stead of the polylactic acid, the same operations as Example 1 were curried out.
  • the average fiber diameter was 3 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected.
  • the void percentage was approximately 35%, and the ethylene glycol content in the fiber structure was 12.5 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 19 and Figure 20 .
  • Example 2 Except that 1 pt. wt. of methylene chloride was used in stead of the ethylene glycol, the same operations as Example 1 were curried out.
  • the average fiber diameter was 2 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected. Dent parts and void parts were not observed in fiber cross-sections, and hence the void percentage was 0%, and the content of the hydroxyl-containing organic compound in the fiber structure was 0 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 21 and Figure 22 .
  • Example 2 Except that 1 pt. wt. of polyethylene glycol (average molecular weight of 400, first class chemical, manufactured by Wako Pure Chemical Industries, Ltd.) was used in stead of the ethylene glycol, the same operations as Example 1 were curried out.
  • the average fiber diameter was 3 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than 20 ⁇ m were not detected. Dent parts and void parts were not observed in fiber cross-sections, and hence the void percentage was 0%, and the content of polyethylene glycol in the fiber structure was 50.0 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 23 and Figure 24 .
  • Example 2 Except that 1 pt. wt. of polyethylene glycol (average molecular weight of 600, first class chemical, manufactured by Wako Pure Chemical Industries, Ltd.) was used in stead of the ethylene glycol, the same operations as Example 1 were curried out.
  • the average fiber diameter was 3 ⁇ m, and fibers having a fiber diameter of more than 20 ⁇ m were not detected. Further, fibers having a fiber length of less than ⁇ m were not detected. Dent parts and void parts were not observed in fiber cross-sections, and hence the void percentage was 0%, and the content of polyethylene glycol in the fiber structure was 50.0 wt.%. Scanning electron micrographs of a surface and a fiber cross section of the fiber structure are shown in Figure 25 and Figure 26 .

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Dispersion Chemistry (AREA)
  • Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)
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Claims (8)

  1. Fibre poreuse comprenant un polymère soluble dans les solvants hydrophobes et un composé organique ayant une pluralité de groupes hydroxyle, et ayant un diamètre moyen de fibre de 0,1 à 20 µm et un pourcentage de vides d'au moins 5 %,
    dans laquelle la masse moléculaire moyenne en nombre du composé organique ayant une pluralité de groupes hydroxyle n'est pas inférieure à 62 ni supérieure à 300, et
    dans laquelle la fibre poreuse a des trous isolés et/ou continus dans des parties internes de la fibre.
  2. Fibre poreuse selon la revendication 1, dans laquelle le solvant hydrophobe est un hydrocarbure contenant un élément halogène.
  3. Fibre poreuse selon la revendication 2, dans laquelle l'hydrocarbure contenant un élément halogène est choisi dans le groupe constitué par le chlorure de méthylène, le chloroforme, le dichloroéthane, le tétrachloroéthane, le trichloroéthane, le dibromométhane et le bromoforme.
  4. Fibre poreuse selon la revendication 1, dans laquelle le polymère soluble dans les solvants hydrophobes est choisi dans le groupe constitué par l'acide polylactique, la polycaprolactone, les polycarbonates, le polystyrène et les polyarylates.
  5. Structure fibreuse comprenant des fibres poreuses selon l'une quelconque des revendications 1 à 4.
  6. Procédé de production d'une structure fibreuse comprenant des fibres poreuses ayant un diamètre moyen de fibre de 0,1 à 20 µm et un pourcentage de vides d'au moins 5 %, comprenant une étape dans laquelle une solution est produite en dissolvant un polymère soluble dans les solvants hydrophobes et un composé organique ayant une pluralité de groupes hydroxyle dans un solvant hydrophobe, une étape dans laquelle la solution est filée par électrofilature, et une étape dans laquelle une structure fibreuse accumulée sur un collecteur est obtenue,
    dans lequel la masse moléculaire moyenne en nombre du composé organique ayant une pluralité de groupes hydroxyle n'est pas inférieure à 62 ni supérieure à 300, et
    dans lequel la fibre poreuse a des trous isolés et/ou continus dans des parties internes de la fibre.
  7. Procédé de production de la structure fibreuse selon la revendication 6, dans lequel le solvant hydrophobe est un hydrocarbure contenant un élément halogène.
  8. Procédé de production de la structure fibreuse selon la revendication 7, dans lequel l'hydrocarbure contenant un élément halogène est choisi dans le groupe constitué par le chlorure de méthylène, le chloroforme, le dichloroéthane, le tétrachloroéthane, le trichloroéthane, le dibromométhane et le bromoforme.
EP04710522A 2003-02-13 2004-02-12 Fibre poreuse, structure fibreuse poreuse et procede de production correspondant Expired - Lifetime EP1600533B1 (fr)

Applications Claiming Priority (5)

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JP2003034779 2003-02-13
JP2003034779 2003-02-13
JP2003094176 2003-03-31
JP2003094176 2003-03-31
PCT/JP2004/001453 WO2004072336A1 (fr) 2003-02-13 2004-02-12 Fibre poreuse, structure fibreuse poreuse et procede de production correspondant

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EP1600533A1 EP1600533A1 (fr) 2005-11-30
EP1600533A4 EP1600533A4 (fr) 2006-10-18
EP1600533B1 true EP1600533B1 (fr) 2010-04-14

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JP (1) JP4361529B2 (fr)
KR (1) KR101056982B1 (fr)
AT (1) ATE464408T1 (fr)
DE (1) DE602004026561D1 (fr)
ES (1) ES2340927T3 (fr)
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104603344A (zh) * 2012-06-26 2015-05-06 卡博特公司 柔性绝缘结构及其制造和使用方法

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4262695B2 (ja) * 2005-04-25 2009-05-13 独立行政法人海洋研究開発機構 膜状バイオデバイス及びバイオリアクター
US7901611B2 (en) * 2007-11-28 2011-03-08 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Method for predicting and optimizing system parameters for electrospinning system
US8263029B2 (en) * 2008-08-25 2012-09-11 Kent State University Method for preparing anisotropic particles and devices thereof
CA2780441A1 (fr) * 2009-11-11 2011-05-19 Teijin Limited Article a base de fibres moulees
CN101805940A (zh) * 2010-03-23 2010-08-18 浙江大学 聚合物静电纺丝纤维及其制备方法和应用
JP5846550B2 (ja) * 2011-05-02 2016-01-20 国立研究開発法人物質・材料研究機構 短繊維足場材料、短繊維−細胞複合凝集塊作製方法及び短繊維−細胞複合凝集塊
CN104271164B (zh) 2012-05-14 2017-11-17 帝人株式会社 片成形体和止血材料
CN102787444A (zh) * 2012-08-18 2012-11-21 东华大学 纳米纤维素/二氧化硅多孔网络结构纤维膜的制备方法
WO2014066297A1 (fr) * 2012-10-22 2014-05-01 North Carolina State University Matières fibreuses non tissées
CN107447296B (zh) * 2017-09-29 2019-08-23 上海沙驰服饰有限公司 一种感温感湿纺织纤维及制备方法
WO2019114575A1 (fr) * 2017-12-12 2019-06-20 中国科学院大连化学物理研究所 Matériau d'électrode à structure de fibres et sa préparation

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3177557A (en) * 1964-01-22 1965-04-13 Du Pont Process for producing bulk yarns from film strips
GB1527592A (en) * 1974-08-05 1978-10-04 Ici Ltd Wound dressing
EP0047795A3 (fr) * 1980-09-15 1983-08-17 Firma Carl Freudenberg Fibre en matière polymère filée par voie électrostatique
DE68919142T3 (de) * 1988-07-20 1998-03-26 Asahi Chemical Ind Hohlfasermembran.
JP2899352B2 (ja) * 1990-03-29 1999-06-02 株式会社クラレ 多孔性の中空糸膜
US5766455A (en) * 1996-04-30 1998-06-16 Zentox Corporation Fibrous matte support for the photopromoted catalyzed degradation of compounds in a fluid stream
US5993738A (en) * 1997-05-13 1999-11-30 Universal Air Technology Electrostatic photocatalytic air disinfection
US6596296B1 (en) * 1999-08-06 2003-07-22 Board Of Regents, The University Of Texas System Drug releasing biodegradable fiber implant
DE10040897B4 (de) * 2000-08-18 2006-04-13 TransMIT Gesellschaft für Technologietransfer mbH Nanoskalige poröse Fasern aus polymeren Materialien
US6645618B2 (en) * 2001-06-15 2003-11-11 3M Innovative Properties Company Aliphatic polyester microfibers, microfibrillated articles and use thereof
US6884399B2 (en) * 2001-07-30 2005-04-26 Carrier Corporation Modular photocatalytic air purifier
TWI241199B (en) * 2001-08-30 2005-10-11 Ind Tech Res Inst Method for manufacturing porous bioresorbable material having interconnected pores
US6673137B1 (en) * 2001-11-27 2004-01-06 Sheree H. Wen Apparatus and method for purifying air in a ventilation system

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104603344A (zh) * 2012-06-26 2015-05-06 卡博特公司 柔性绝缘结构及其制造和使用方法

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US20060204750A1 (en) 2006-09-14
TW200424385A (en) 2004-11-16
JP4361529B2 (ja) 2009-11-11
KR101056982B1 (ko) 2011-08-16
WO2004072336A1 (fr) 2004-08-26
ATE464408T1 (de) 2010-04-15
JPWO2004072336A1 (ja) 2006-06-01
EP1600533A4 (fr) 2006-10-18
ES2340927T3 (es) 2010-06-11
KR20050098861A (ko) 2005-10-12
DE602004026561D1 (de) 2010-05-27

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