JP2834534B2 - Permselective hollow fiber - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a permselective hollow fiber suitable for use in a body fluid treatment device such as an artificial kidney or a plasma separator. More specifically, the present invention relates to a hollow fiber in which the zeta potential on the inner surface of the hollow fiber is negative, and the zeta potential on the inner layer side of each part of the hollow fiber wall membrane is more negative than the outer layer side. More specifically, the present invention provides a hollow fiber having a wall membrane formed by joining a plurality of layers having different zeta potentials.

[Prior Art] The following are known as composite hollow fibers in which two or more layers are joined.

That is, JP-A-49-62380 discloses a sheath-core type composite hollow fiber-like semipermeable membrane in which the material for forming the sheath has a dense structure, and the material for forming the core has a porous structure, and the thickness of the sheath layer is large. A method is described for producing a core having a thickness of 1/5 or less of the thickness of the core layer.

JP-A-59-160506 discloses a composite hollow fiber separation membrane in which a polymer thin film is coated on the inner surface of a microporous hollow fiber.
The polymer thin film is formed on the inner surface so as not to substantially penetrate into the inner surface pores of the microporous hollow fiber.The average thickness of the polymer thin film is 100 to 20000 °, and the standard deviation σ of x is Is described as a ratio σ / ≦ 0.25.

Japanese Patent Application Laid-Open No. 60-139815 discloses a composite hollow fiber, which is composed of different or the same kind of thermoplastic polymer compound, and is bonded to at least two or more layers having micropores of different sizes. The micropores in each layer and between the layers communicate with each other to form micropores connected from one surface to the other surface, and the layer of large micropores is thicker than the layer of small micropores. There is a description.

However, these inventions only relate to the size of the micropores in each layer of the composite hollow fiber and the thickness of the layer. The hollow fibers disclosed in these prior arts have a function of separating substances only by the size of the perforations of the membrane.

[Problems to be Solved by the Invention] Hollow fiber separation membranes are used as materials for dialysers for artificial kidneys, but in recent years, long-term dialysis patients have suffered bone disorders due to abnormal metabolism of inorganic phosphorus in blood. It is said that this comes mainly from secondary hyperparathyroidism due to hyperphosphatemia due to the accumulation of phosphorus present as phosphate ions in the blood. In the current situation where the use of a phosphorus adsorbent containing Al is hesitant, P removal by dialysis is an important corrective measure for hyperpemia.

Since phosphate ions have a negative charge, it is easily analogized that a membrane used for separation is preferably charged on the positive side in view of the ease of phosphoric acid in solution. Has also been confirmed. On the other hand, when blood comes into contact with a positively charged membrane, such as in hemodialysis, the adhesion of negatively charged protein blood cells in the blood is promoted, and blood coagulation on the membrane surface is likely to occur. It is known to be. Therefore, when a hollow fiber is used as a material for an artificial organ such as an artificial kidney or plasma, a composite hollow fiber for efficiently separating and removing a substance having a negative charge such as an inorganic phosphorus with a low blood coagulation property is used. Had not yet been obtained.

[Means for Solving the Problems] The present inventors have reduced the coagulability of blood and increased the separation efficiency of substances having a negative charge such as inorganic phosphorus for hollow fibers as materials for artificial organs such as artificial kidneys. After extensive research with the aim of finding that, it was found that a hollow fiber in which the zeta potential on the inner surface of the hollow part on the blood contact side was made negative and the zeta potential was changed in the positive direction toward the outer surface was effective. Have reached the present invention.

That is, the present invention is a hollow fiber comprising a permselective wall membrane composed of an organic polymer compound, wherein the zeta potential of the hollow fiber wall membrane is negative on the inner surface of the hollow portion and toward the outer surface of the hollow fiber. Another object of the present invention is to provide a permselective hollow fiber characterized by changing to a more positive side.

The present invention includes a permselective hollow fiber having a plurality of hollow fiber wall membranes.

The present invention also includes a permselective hollow fiber in which the organic polymer compound constituting each layer forming the hollow fiber wall membrane is the same or different.

 Hereinafter, the present invention will be described in more detail.

That is, the hollow fiber of the present invention has a negative zeta potential on the inner surface of the hollow portion, and the zeta potential on the inner surface side of the hollow portion is more negative than the zeta potential on the outer surface side of the hollow fiber. It is. Regarding the magnitude of the different zeta potential as the object of the present invention, for example, in the case of a two-layer composite hollow fiber, it is preferable that the outer layer has 0 or positive charge and the inner layer has a negative charge, but both have a negative charge. And the outer layer may be closer to 0, that is, on the more positive side.

That is, the zeta potential on the inner surface of the hollow portion is negative, and a range of −20 mV or more is preferable.
Particularly, a range of −5 mV or more is preferable. The zeta potential on the outer surface of the hollow fiber is preferably −4 mV to +20 mV, and particularly preferably −2 mV.
The range from mV to +10 mV is preferred.

By giving a difference in charge between the inside and the outside of the hollow fiber, that is, a difference in zeta potential, the permeability of negative ions such as P in blood is improved, and the hollow fiber has compatibility with blood. Can be something.

As for the zeta potential, a potential (streaming potential) is generated between electrodes placed at both ends of a tube when a liquid is flushed through a capillary tube or a capillary system filled with powder. If the viscosity coefficient of the fluid at this time is η, the specific conductivity of the liquid is λ, ε is the dielectric constant of the fluid, P is the pressure difference at both ends of the tube, and E is the flow potential between the electrodes at both ends, the zeta potential ζ becomes Can be obtained by the Helmholtz-Smoluchowski equation.

ζ = 4πηλE / εP A more preferred form of the hollow fiber of the present invention is a hollow fiber composite membrane in which the hollow fiber wall is composed of two or more layers. In this case, the innermost layer has a negative zeta potential, and the zeta potential of the inner layer is more negative than the zeta potential of the outer layer between the layers. The number of layers is preferably from 2 to 5, particularly preferably 2 or 3 layers, because it is easy to manufacture and the desired effect can be obtained. It is preferable that these layers are bonded to each other so that they are not easily separated from each other, because part of the film during use can be prevented.

As the inner diameter of the hollow fiber, 50 to 500μ is practical,
For example, in the case of a hollow fiber for hemodialysis, 150 to 300 μm is preferable. The film thickness is preferably from 5 to 100 μm for practical use, and particularly preferably from 15 to 50 μm is advantageous for enhancing the material permeation.
In the case of a multilayer, it means that the sum of the film thicknesses of the respective layers is within such a range.

In the case of a multilayer composite hollow fiber, for example, in the case of a two-layer composite hollow fiber, the size of the micropores (pores) in the outer layer and the inner layer, and the thickness of each layer are not particularly specified, but for the purpose described above, As a desirable state, the pores of the inner layer are of the order that the blood cell proteins in the blood cannot pass therethrough, and pores of several tens to several hundreds of mm are preferable.
It can be said that the degree is desirable. On the other hand, there is no particular problem with the outer layer as long as it has the permeability of the target substance to be separated, but generally it can be said that it is desirable that the inner layer is denser than the outer layer.

For example in the case of a blood dialyzer hollow fiber, water permeation rate from the hollow fiber to the outside side 3ml / m ² · hr · mmHg or higher, as more preferably a 5ml / m ² · hr · mmHg or more, film It is desirable to have a film structure including the thickness.

Further, by providing a protrusion extending in the longitudinal direction on the outer surface of the hollow fiber, or by imparting a crimp to the entire hollow fiber, adhesion between the hollow fibers is prevented to further increase the efficiency of mass transfer. Is practically preferable.

Examples of the organic polymer compound that can be employed in the present invention include, for example, cellulose, cellulose ester, polymethyl methacrylate, polyacrylonitrile, polyamide, polycarbonate, polyethylene, polypropylene, polyethylene terephthalate, polysulfone, polyvinyl alcohol-ethylene copolymer, or these. Copolymer as component, chemical derivative for imparting electric charge,
Alternatively, it may contain additives and plasticizers.

The method for producing the hollow fiber of the present invention includes, for example, a method of spinning a multi-layer composite hollow fiber using an organic polymer compound having a negative zeta potential on the inner surface side of the hollow fiber, and a method of spinning a different kind or the same type of organic polymer. After spinning a hollow fiber made of a molecular compound, there is a method in which the inner layer side is made to have a more negative zeta potential by a chemical treatment or the like.

That is, regarding the method for producing a hollow fiber, using a hollow fiber production nozzle having two or more annular discharge ports concentrically arranged, each discharge port is made of a different or the same kind of polymer having a different zeta potential at each discharge port. A hollow fiber having at least two or more layers constituted is obtained, and the hollow fiber is used as it is or further subjected to a chemical treatment as necessary so that the zeta potential of the outer layer is more positive than that of the inner layer. Is obtained by

Further, the hollow fiber of the present invention can be made to have a difference in zeta potential between the inner layer and the outer layer by a chemical treatment, for example, after producing a hollow fiber composed of the same kind of polymer.

For such a treatment, the treatment can be performed in the state of an endless hollow fiber, or once assembled into a hemodialyzer or the like, and a chemical treatment causes a difference in zeta potential between the inner layer and the outer layer of the hollow fiber. It can also be done.

As a chemical treatment to make the zeta charge of the inner layer more negative than the outer layer, a reactive substance having a positive potential is flowed or filled in the outer layer and reacted with the hollow fiber inner surface layer, or a negative charge is formed in the inner layer side. There is a method of flowing or filling a reactive substance having the following formula to react with the outer surface layer. Examples of the group having a positive charge include a tertiary amine group, a quaternary ammonium group or a derivative thereof.
Examples include a sulfonic acid group, a carbonyl group, a phosphoric acid group, and a carbonic acid group.

Further, as a method for producing the hollow fiber of the present invention, there is a method for producing a composite hollow fiber by mixing a compound having the above group in the inner layer and / or the outer layer.

[Effect of the Invention] When the hollow fiber is used as a material for an artificial organ such as an artificial kidney and plasma, the composite hollow fiber according to the present invention has good blood coagulability and has a negative charge such as inorganic phosphorus. It is intended to provide a hollow fiber for efficiently separating and removing substances.

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples.

Examples and Comparative Examples Using a hollow fiber manufacturing nozzle having two concentrically arranged annular discharge ports, 50% by weight of polyethylene glycol as a plasticizer was mixed with cellulose diacetate from the outer discharge port. And a mixture of polymethyl methacrylate and 50% by weight of N-methylpyrrolidone and 50% by weight of polyethylene glycol discharged from the inner discharge port at a discharge temperature of 210 ° C. and wound at a winding speed of 200 m / min. Was. The dimensions of the obtained two-layer composite hollow fiber were as follows:
μ, and the thicknesses of the inner layer and the outer layer were 12 μ and 18 μ, respectively.

Separately, as a comparative example, one layer of hollow fiber was spun using a mixture of diacetate and 50% by weight of polyethylene glycol, and separately, 50% by weight of polymethyl methacrylate, 50% by weight of N-methylpyrrolidone and 50% by weight of polyethylene glycol. , A layer of hollow fiber was spun and wound up. In these two types of hollow fibers, the yarn diameter is 205
μ, and the film thickness was 30 μ.

These three types of hollow fiber raw yarns were dried with hot water at 60 ° C. to extract a spinning plasticizer and the like in the hollow fiber raw yarns, adhere glycerin thereto, and dry. The zeta potential of this hollow fiber was measured, and the three types of dried hollow fibers obtained in this manner were bundled, respectively, and assembled into a dialyzer having an effective area of 1 m ^2.
The dialysis performance of inorganic phosphorus in the itro (dialysis) and porcine blood were circulated for 30 minutes, and then, after returning blood with water, the amount of blood remaining in the dialyzer (residual blood) was measured. In addition, the measurement method of the dialysance of inorganic phosphorus was measured based on the performance evaluation standard of the Japanese Society for Artificial Organs. Table 1 shows the results.

It can be seen that when the composite hollow fiber according to the present invention is used, a blood treatment device having good dialysis performance of inorganic phosphorus and low blood coagulation (residual blood) can be obtained.

──────────────────────────────────────────────────続 き Continuing on the front page (51) Int.Cl. ⁶ Identification symbol FI D01F 2/28 D01F 2/28 A (72) Inventor Kuroda Toshimasa 3-4-1, Amihara, Ibaraki-shi, Osaka Teijin Research Institute of Osaka, Ltd. Inside the center (56) References JP-A-59-26116 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) B01D 69/08 D01D 5/24 B01D 71/16 B01D 71/40 D01F 2/28 A61M 1/18 500

Claims (3)

(57) [Claims] 1. A hollow fiber comprising a permselective wall membrane composed of an organic polymer compound, wherein the zeta potential of the hollow fiber wall membrane is negative on the inner surface of the hollow portion and toward the outer surface of the hollow fiber. A permselective hollow fiber characterized by being changed to a more positive side. 2. The permselective hollow fiber according to claim 1, wherein said hollow fiber wall membrane forms a plurality of layers. 3. The permselective hollow fiber according to claim 2, wherein the organic polymer compound constituting each layer forming the hollow fiber wall membrane is the same or different.