JP2017104852A - Porous fiber and phosphorus adsorption column - Google Patents

Abstract

PROBLEM TO BE SOLVED: To develop an adsorbent body that can directly remove phosphorus in blood and a phosphorus adsorption column using the adsorbent body, and to enable a novel high-phosphorus plasma treatment technique that efficiently reduces the phosphorus concentration in blood.SOLUTION: Provided is a porous fiber having a phosphorus adsorbent supported therein. After the fiber is stirred in physiological saline for 4 hours, the saline shows a pH change of -1 or more and +1 or less.SELECTED DRAWING: None

Description

  The present invention relates to a porous fiber that adsorbs phosphorus and a phosphorus adsorption column incorporating the same.

  Patients with impaired renal function often suffer from hyperphosphatemia due to decreased phosphorus excretion. Hyperphosphatemia causes serious abnormalities in calcium and phosphorus metabolism, and lowers serum calcium, promotes parathyroid hormone (PTH) production and secretion, ectopic calcification, and renal bone dystrophy due to inhibition of vitamin D activation Cause symptoms. Even if it shifts to dialysis therapy due to renal failure, the above-mentioned pathological condition persists unless phosphorus homeostasis is maintained. Therefore, hyperphosphatemia treatment is indispensable for renal failure dialysis patients and renal failure non-dialysis patients. Currently, dietary therapy and a method using an oral phosphorus adsorbent are known as methods for treating hyperphosphatemia. In the treatment of hyperphosphatemia in renal failure dialysis patients and renal failure non-dialysis patients, diet therapy is insufficient, and a method using an oral phosphorus adsorbent is required.

  As the oral phosphorus adsorbent, inorganic and organic ones are known.

  Conventionally, aluminum salts or calcium salts have been widely used as inorganic oral phosphorus adsorbents. Ingested aluminum and calcium combine with intestinal phosphate to form an insoluble phosphate, which inhibits phosphorus absorption. However, the administration of aluminum salts has a problem in that it causes accumulation of aluminum in the body and can cause brain diseases, osteomalacia and the like. In addition, absorption of calcium can cause hypercalcemia, and it is a problem that the death stage of a patient can be accelerated by calcification in the aorta and ectopic calcification.

  Therefore, lanthanum carbonate is known as an inorganic oral phosphorus adsorbent that does not increase the calcium concentration. However, intestinal absorption of lanthanum and bone accumulation are recognized, and there are concerns about long-term safety (Non-patent Document 1).

  Patent Document 1 discloses a lanthanoid carbonate as an inorganic oral phosphorus adsorbent. However, lanthanoid carbonate, like lanthanum carbonate, can easily release metal ions in a strong acid atmosphere such as gastric acid even if its water solubility is low under neutral conditions. Therefore, there has been a problem that accumulation of lanthanoids in bones can occur after long-term use.

  On the other hand, as an organic oral phosphorus adsorbent, sevelamer hydrochloride, which is a kind of polyallylamine, is known. Sevelamer hydrochloride is widely used in the treatment of hyperphosphatemia because it does not cause side effects from the inorganic salts. However, since a high dose is required to significantly reduce phosphate absorption, the dose of sevelamer hydrochloride is usually set at 3 to 6 g / day and a maximum of 9 g / day. Since sevelamer hydrochloride absorbs water in the gastrointestinal tract and swells, it causes problems such as constipation, abdominal pain, and abdominal distension, and there are reports of serious side effects such as intestinal perforation and intestinal obstruction ( Non-patent document 2). Furthermore, since absorption of fat-soluble vitamins (vitamin D, vitamin E, vitamin K) and folate is inhibited, it is necessary to replenish them for long-term administration.

  Moreover, considering that oral phosphate adsorbents must be taken continuously with lifelong dialysis treatment, depending on the type of oral agent used, as described above, Having side effects such as constipation and abdominal distension is not desirable in view of the patient's quality of life (QOL).

  Therefore, the development of a new form of treatment for hyperphosphatemia that is completely different from oral medications is significant.

  Patent Document 1 describes that a phosphorus adsorbent is supported on a porous carrier for the purpose of extracorporeal circulation to form a molded body. The molded body can be formed into a granular, thread-like, hollow-fiber-like, or other usage method. It is described that any suitable shape can be selected. As the phosphorus adsorbent, hydrated oxides of rare earth elements are disclosed. Specifically, an example is disclosed in which cerium hydroxide is added to polyethylene-vinyl alcohol, formed into granules, packed in a column, and evaluated for phosphorus adsorption performance.

  Patent Document 2 describes the combined use of a phosphorus adsorption column and a dialyzer. This patent document discloses a polycationic polymer having a specific structure as a phosphorus adsorbent.

  Patent Document 3 discloses a method in which a phosphorus adsorbent is dispersed on the dialysate side and supported on the inner and outer surfaces of the hollow fiber.

Takashi Shigematsu et al., “Bone biopsy test”, Bayer Yakuhin internal data, 2009 Kazuhiko Ishikiriyama et al., JOURNAL OF COLLOID AND INTERFACE SCIENCE, 1995, 171 volumes, p. 103-111

JP 61-004529 A JP 2002-102335 A International Publication No. 2011/125758

  However, the rare earth element hydrated oxide, which is a phosphorus adsorbent supported on a porous carrier in Patent Document 1, has a problem of large pH change and greatly disturbs the living environment, so it is supported inside the porous fiber. It is not preferable to use them.

  In addition, in the phosphorus adsorption column described in Patent Document 2, the polycationic polymer having a specific structure used as a phosphorus adsorbent has a large pH change in order to adsorb phosphorus in exchange for hydrochloric acid, so that the blood pH balance, There was a risk of disturbing the environment.

  Moreover, in the usage form of the phosphorus adsorbent described in Patent Document 3, in order to uniformly disperse the particles throughout the dialysate, it is necessary to devise a method such as adding a rotor to the dialysate. It is not good even from the aspect. Furthermore, since the amount of phosphorus adsorbent that can be supported is limited, there is a concern that phosphorus removal is insufficient.

  In view of the above situation, the present invention provides a phosphorus adsorbent used for phosphorus adsorption in extracorporeal circulation, which has a low risk of disturbing the living environment, and a porous material in which the phosphorus adsorbent is supported. It is an object of the present invention to provide a porous fiber which is a porous fiber and has a low possibility of disturbing the living environment, and a phosphorus adsorption column incorporating the porous fiber.

  In the present invention, as a result of diligent studies to solve the above problems, the following invention has been completed.

  In the porous fiber according to the present invention, a phosphorus adsorbent is supported inside the fiber, and the pH change after stirring for 4 hours in physiological saline is −1 or more and +1 or less. In addition, it is preferable that the pH change after 4 hours stirring in the physiological saline of phosphorus adsorption agent itself is also -1 or more and +1 or less.

  The phosphorus adsorbent of the present invention is a phosphorus adsorbent used for phosphorus adsorption in extracorporeal circulation and has a low risk of disturbing the living environment.

  Moreover, the porous fiber of the present invention is a porous fiber in which a phosphorus adsorbent is supported, and has a low risk of disturbing the living environment.

  The phosphorus adsorption column of the present invention is a phosphorus adsorption column incorporating the porous fiber of the present invention.

  The phosphorus adsorbent, porous fiber and phosphorus adsorption column of the present invention will be specifically described below.

<Phosphorus adsorbent>
The phosphorus adsorbent of the present invention preferably contains a rare earth element carbonate or a Group 4 oxide, and is preferably a granular material having a solubility in 100 g of water at 20 ° C. of 10 mg or less, Used for phosphorus adsorption in extracorporeal circulation.

  In the present invention, the phosphorus adsorbent is a compound having phosphorus adsorption performance, that is, a decrease in the phosphorus concentration from the phosphorus start solution in the measurement of phosphorus adsorption performance described later. Moreover, a granular material means a particle | grain with an average particle diameter of 1 nm or more and 10 mm or less.

  The phosphorus adsorbent of the present invention preferably contains a rare earth element carbonate or a Group 4 oxide. Rare earth element carbonates have high phosphorus adsorption properties, low solubility in water, and small changes in pH in physiological saline. Therefore, even when phosphorus adsorbents and blood come into contact with inorganic ions, It is difficult to release and is suitable for extracorporeal circulation.

  Of the Group 4 oxides, titanium oxide is particularly preferable. Titanium oxide is suitable for extracorporeal circulation because it has high phosphorus adsorption performance similar to rare earth element carbonates, has low solubility in water, and has little pH change.

  Here, extracorporeal circulation in the present invention refers to inducing blood in a living body outside the body, removing a predetermined substance (the object in the present invention is a phosphorus compound), and then returning it to the body again.

  The phosphorus adsorbent of the present invention preferably contains a rare earth element carbonate. When the phosphorus adsorbent contains a rare earth carbonate, the pH change in physiological saline tends to be smaller.

  Here, the rare earth element means two elements of scadium (Sc) of atomic number 21 and yttrium (Y) of atomic number 39 and lutetium of 71 from atomic number 57 lanthanum (La) at the position of the periodic table. It is a total of 17 elements including La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and 15 elements up to (Lu).

  In the phosphorus adsorbent of the present invention, the rare earth element is preferably selected from the group consisting of lanthanum, cerium, samarium, praseodymium and neodymium. In this case, the rare earth element carbonates are lanthanum carbonate, cerium carbonate, samarium carbonate, praseodymium carbonate and neodymium carbonate. These rare earth element carbonates are preferred because of their low solubility in water and small changes in pH in vivo as described later. More preferred is samarium carbonate, and particularly preferred are cerium carbonate and neodymium carbonate, which have high phosphorus adsorption performance.

  In the phosphorus adsorbent of the present invention, the granular material may contain a rare earth oxide, a rare earth hydrated oxide, or the like as a component other than the rare earth element carbonate or the Group 4 oxide.

  These phosphorus adsorbents may be used alone or as a mixture of two or more.

  The phosphorus adsorbent of the present invention is preferably a granular material having a solubility in 100 g of water at 20 ° C. of 10 mg or less. The solubility is preferably 5 mg or less, more preferably 2 mg or less, and particularly preferably 1 mg or less. The solubility of the phosphorus adsorbent according to the present invention is measured by the method described later.

  The phosphorus adsorbent of the present invention has a phosphorus adsorption performance of 3.0 mg / g or more. And it is preferable that phosphorus adsorption | suction performance is 4.0 mg / g or more. The phosphorus adsorption performance is more preferably 4.5 mg / g or more, still more preferably 5.0 mg / g or more, even more preferably 15.0 mg / g or more, and more preferably 70.0 mg / g or more. It is preferable that it is 100.0 mg / g or more. When the phosphorus adsorption performance of the phosphorus adsorbent is within the above range, for example, when the phosphorus adsorbent is supported inside the porous fiber and used, the phosphorus adsorbent is contained in the final form of the extracorporeal circulation column. Even if it is not filled with a lot of porous fibers carried on the surface, a sufficient effect of removing and adsorbing phosphorus can be easily obtained. Therefore, as a result, the amount of blood taken out of the body for sufficient phosphorus removal can be easily reduced. Moreover, preferable adsorption performance is 1000.0 mg / g or less, More preferably, it is 800.0 mg / g or less, More preferably, it is 500.0 mg / g or less. When the phosphorus adsorption performance is within the above range, for example, hypophosphatemia that may occur due to increased removal of phosphorus can be easily prevented. The method for measuring the phosphorus adsorption performance of the phosphorus adsorbent in the present invention is as described below.

  The phosphorus adsorbent of the present invention is preferably a granular material having an average particle size of more than 100 nm and not more than 100 μm. The average particle diameter is preferably 100 μm or less, more preferably 80 μm or less, and particularly preferably 50 μm or less because the phosphorus adsorbent is preferably as small as possible. When the average particle size is 100 μm or less, for example, when a phosphorus adsorbent is supported and used inside the porous fiber, it is preferable that the spinneret is not clogged during spinning and the spinning performance is not easily lowered. In addition, the smaller the average particle size, the larger the specific surface area, and the higher the phosphorus adsorption efficiency. However, if the average particle size is smaller than the pores of the porous fiber, the phosphorus adsorbent may pass through the pores and elute into the liquid to be treated, such as blood. It can be said that it is preferable to exceed 100 nm. However, when the powder is an aggregate of primary particles, the primary particles are not limited to this.

  In the present invention, the particle size can be measured by a laser diffraction / scattering method using a fine particle counter, a particle size distribution meter, or the like. Set the particle shape as non-spherical and plot the horizontal axis diameter and vertical axis frequency (%) to obtain values such as volume average (MV), number average (MN), and area average (MA) as the particle diameter. However, in the present invention, the number average is used to obtain the average particle diameter.

  In addition, as a form in which the phosphorus adsorbent is not brought into direct contact with blood circulating in the extracorporeal blood circuit in dialysis treatment, such a phosphorus adsorbent may be dispersed in a dialysis solution and used in addition to the method of kneading into porous fibers. Alternatively, it may be used by filling the outside of the hollow fiber dialysis membrane.

  In addition, as a processing method when processing a polymer mixed with such a phosphorus adsorbent into a fiber shape, there are a dry spinning method, a wet spinning method, or a dry and wet spinning method in which dry and wet are combined. is not. The shape of the fiber formed by coagulation is determined by the shape of the cap used, and the main shape includes a hollow fiber shape and a solid yarn shape.

<PH>
In general, the pH balance in the ecology is very important, and when the balance is disturbed, it leads to various diseases. The phosphorous adsorbent according to the present invention has little influence on the pH of body fluids such as blood because the change in pH of physiological blood is small when in contact with blood. Here, in this invention, it is set as the parameter | index of whether it is excellent in the ecological pH balance with the pH change in the physiological saline. Specifically, assuming a 4-hour circulation in dialysis, the pH change before and after the phosphorus adsorbent is placed in physiological saline and stirred at 200 rpm for 4 hours is measured. The phosphorus adsorbent of the present invention has a pH change of −1.0 or more and +1.0 or less (within ± 1.0), preferably within ± 0.8, more preferably within ± 0.6, Most preferred is little pH change, ie within ± 0.1.

  The phosphorus adsorbent of the present invention is preferably used by being supported inside the porous fiber of the present invention described later.

<Porous fiber>
The porous fiber of the present invention is a porous fiber in which a phosphorus adsorbent is supported, and the pH change after stirring for 4 hours in physiological saline is −1.0 or more and +1.0 or less.

  In the present invention, the state in which the phosphorus adsorbent is supported inside means that the phosphorus adsorbent is physically mixed with the porous fiber so that its function is not impaired, and adheres to the inside of the porous fiber. Mainly refers to the state maintained. However, it is not necessarily limited to the state physically mixed with the porous fiber, and chemically bonded to the constituent molecules inside the porous fiber as long as the function of the phosphorus adsorbent is not impaired. It can also be said that the phosphorus adsorbent is supported inside.

  The porous fiber of the present invention has a pH change of -1.0 or more and +1.0 or less after stirring for 4 hours in physiological saline. The pH change is preferably −0.8 or more and +0.8 or less (within ± 0.8), more preferably within ± 0.6, and most preferably there is almost no pH change, ie within ± 0.1. It is. As described above, generally, the pH balance in the living body is very important, and if the balance is disturbed, it leads to various diseases. The porous fiber of the present invention has little influence on the pH of body fluids such as blood because the change in pH of physiological blood is small when it comes into contact with blood. Here, in this invention, it is set as the parameter | index of whether it is excellent in the in-vivo pH balance with the pH change in the physiological saline. Specifically, assuming a 4-hour circulation in dialysis, the change in pH before and after the porous fiber carrying the phosphorus adsorbent inside is put into physiological saline and stirred at 200 rpm for 4 hours. The method for measuring the pH of the porous fiber in the present invention is as described later.

  The porous fiber of the present invention preferably has a phosphorus adsorption performance of 3.0 mg / g or more. More preferable phosphorus adsorption performance is 3.5 mg / g or more, and further preferable phosphorus adsorption performance is 4.0 mg / g or more. Among them, 7.0 mg / g or more is preferable, and 15.0 mg / g or more is preferable. This is particularly preferable. When the porous fiber has a phosphorus adsorption performance of 3.0 mg / g or more, when it is used as an extracorporeal circulation column in the final form, a sufficient phosphorus adsorption removal effect can be obtained without filling a lot of porous fibers. It becomes easy. Therefore, as a result, the amount of blood taken out of the body for sufficient phosphorus removal can be easily reduced. The measuring method of the phosphorus adsorption | suction performance of the porous fiber in this invention is as mentioning later.

  The porous fiber of the present invention is preferably such that the phosphorus adsorbent is a granular material, and the solubility of the granular material in a state supported by the porous fiber in 100 g of water at 20 ° C. is 10 mg or less. . It is preferable that the phosphorus adsorbent is a granular material because it is easily supported uniformly in the porous fiber and the processing operation becomes easy. Further, since the solubility of the granular material in the state of being supported on the porous fiber in 100 g of water at 20 ° C. is 10 mg or less, the amount of elution of metal ions is reduced when coming into contact with blood. be able to. Here, the solubility in 100 g of water at 20 ° C. of the granular material supported by the porous fiber is measured by the method described later.

  In the porous fiber of the present invention, it is preferable that the phosphorus adsorbent is a powder and the average particle diameter is more than 100 nm and not more than 100 μm. The average particle size is preferably 100 μm or less, more preferably 80 μm or less, and particularly preferably 50 μm or less because the phosphorus adsorbent is preferably a powder particle as small as possible. When the average particle size is 100 μm or less, the spinneret is less likely to be clogged during spinning, and the spinning performance is less likely to deteriorate. In addition, the smaller the average particle size, the larger the specific surface area, and the higher the phosphorus adsorption efficiency. However, if the average particle size is smaller than the pores of the porous fiber, the phosphorus adsorbent may pass through the pores and elute into the liquid to be treated, such as blood. It can be said that it is preferable to exceed 100 nm. However, when the powder is an aggregate of primary particles, the primary particles are not limited to this.

  The phosphorus adsorbent carried inside the porous fiber of the present invention can specifically adsorb phosphate ions, particularly phosphate ions present in biological fluids, and inorganic particles are mainly used.

  In the porous fiber of the present invention, the phosphorus adsorbent preferably contains a rare earth element salt or a Group 4 oxide. Rare earth element salts are preferred because of their low solubility in water and high phosphorus adsorption capacity. Group 4 oxides are preferable in that they have low solubility in water and a small pH change.

  Among the rare earth element salts, carbonates of rare earth elements are more preferable. Rare earth element carbonates have high phosphorus adsorption properties, low solubility, and small pH change, so that inorganic ions are not easily released when contacted with blood, and are suitable for extracorporeal circulation.

  In the porous fiber of the present invention, the phosphorus adsorbent preferably contains a rare earth element carbonate, and the rare earth element is preferably selected from the group consisting of lanthanum, cerium, samarium, praseodymium and neodymium. In this case, the rare earth element carbonates are lanthanum carbonate, cerium carbonate, samarium carbonate, praseodymium carbonate and neodymium carbonate. These are preferable because of their low solubility in water and little change in pH in the living body. More preferred is samarium carbonate, and more preferred are neodymium carbonate and cerium carbonate, which have high phosphorus adsorption performance.

  The phosphorus adsorbent supported inside the porous fiber of the present invention is not limited to the compounds described above, and may be used as long as the above pH change is small and within the range according to the present invention.

  The phosphorus adsorbent supported inside the porous fiber of the present invention is preferably the above-described phosphorus adsorbent of the present invention.

The porous fiber of the present invention is preferably in the form of a fiber in which a phosphorus adsorbent is mixed with a biocompatible polymer and the phosphorus adsorbent is kneaded. In this case, the phosphorus adsorbent addition rate is preferably 5% by mass or more, more preferably 20% by mass or more, still more preferably 40% by mass or more, and the upper limit is 80% by mass or less with respect to the polymer to be mixed. Preferably, 70 mass% or less is more preferable, and 60 mass% or less is further more preferable. When the addition rate of the phosphorus adsorbent is less than 5% by mass, the amount of porous fibers required for sufficient phosphorus adsorption when the column is formed increases, so the column volume increases and the amount of blood taken out of the body. There is a concern that may increase. On the other hand, when the addition rate of the phosphorus adsorbent is more than 80% by mass, there is a concern that the fiber strength is lowered and the spinnability may be deteriorated. The addition rate of the phosphorus adsorbent can be calculated by the following formula 1.
Formula 1: addition rate%: [added phosphorus adsorbent mass] / (added phosphorus adsorbent mass + raw polymer weight) × 100
The porous fiber of the present invention preferably has a surface pore radius of 0.5 to 100 nm and a specific surface area of pores of 10 m ² / g or more. The lower limit of the average pore radius (hereinafter also referred to as pore diameter or pore diameter) is preferably 0.5 nm or more, more preferably 1.5 nm or more, particularly preferably 2.0 nm or more, while the upper limit is The thickness is preferably 100 nm or less, more preferably 40 nm or less, and particularly preferably 25 nm or less. When the lower limit of the uniform pore radius is as described above, the substance to be adsorbed easily enters the pores, so that the adsorption efficiency is hardly lowered. On the other hand, if the upper limit of the pore diameter is as described above, the adsorbed substance is easily adsorbed in the void portion, and thus the adsorption efficiency may be improved. Within the above pore diameter range, there is an optimum pore diameter depending on the size of the adsorbed substance to be removed.

The average pore radius of the porous fiber is determined by measuring the degree of freezing point by capillary aggregation of water in the pores by differential scanning calorimetry (DSC) measurement using a differential scanning calorimeter (DSC). Calculated as radius. The adsorbent material was rapidly cooled to −55 ° C., heated to 0.3 ° C./min up to 5 ° C., and the peak top temperature of the obtained curve was taken as the melting point. Calculate the hole radius.
Formula 2: Primary average pore radius [nm] = (33.30-0.3181 × melting point drop [° C.]) / Melting point drop [° C.]
For the measurement / calculation method, the description of Non-Patent Document 2 described above is referred to.

The porous fiber of the present invention can improve the adsorption performance by increasing the specific surface area of the pores in order to adsorb the substance to be adsorbed. Therefore, the lower limit of the pore specific surface area is preferably 10 m ² / g, more preferably 20 m ² / g, still more preferably 30 m ² / g, particularly preferably 40 m ² / g, and more preferably 50 m ^2. / G. On the other hand, if the pore specific surface area is too large, the mechanical strength is insufficient. Therefore, the upper limit of the pore specific surface area is preferably 1000 m ² / g, more preferably 800 m ² / g, still more preferably 650 m ^2. / G, particularly preferably 500 m ² / g.

  The measurement of the pore specific surface area is performed using DSC in the same manner as the method for measuring the average pore radius. The calculation method of the specific surface area of the pore is as described in Non-Patent Document 2 (p104).

  The porous fiber of the present invention preferably supports the phosphorus adsorbent not only on the surface but also in the interior in order to increase the phosphorus adsorption efficiency. In extracorporeal circulation, the volume of blood taken from the patient should be reduced as much as possible to prevent the patient's risk of lowering blood pressure. For this purpose, it is necessary to increase the phosphorus adsorption performance per fiber volume. By supporting the phosphorus adsorbent not only on the surface of the porous fiber but also inside, the phosphorus adsorbent efficiently contacts the blood containing the target phosphorus, so the phosphorus adsorption performance per unit volume is large. Is preferred. It is possible to easily remove phosphorus contained in blood efficiently. Accordingly, it is preferable that the phosphorus adsorbent is carried inside the porous fiber, in other words, the adsorbent is kneaded inside the fiber. That is, the phosphorus adsorbent is preferably present in the porous fiber with good dispersibility.

  As the method, there is a method in which a phosphorus adsorbent is added to a fiber raw material polymer solution prepared at a predetermined concentration and mixed at a constant rotational speed. Alternatively, a method in which a polymer raw material, a phosphorus adsorbent, and a solvent for dissolving the polymer raw material are put in the same container from the beginning and mixed while rotating the rotor. Alternatively, a method of adding a phosphorus adsorbent while spraying a polymer solution already prepared to a predetermined concentration can be mentioned. The method is not limited to the above as long as the phosphorus adsorbent can be uniformly dispersed in the polymer. In the case of a polymer that gels at room temperature, it is preferable to heat in order to increase the dissolution efficiency of the polymer.

<Material of porous fiber>
The material for the porous fiber in the present invention is not particularly limited, but an organic material is preferably used from the viewpoint of easiness of molding and cost. More specifically, polymethyl methacrylate (hereinafter referred to as PMMA), polyacrylonitrile (hereinafter referred to as PAN), polysulfone, polyethersulfone, polyarylethersulfone, polypropylene, polystyrene, polycarbonate, cellulose, cellulose triacetate, ethylene-vinyl alcohol A copolymer or the like is preferably used. Among them, it is preferable to include a material that is an amorphous polymer and has a property of adsorbing protein, and examples thereof include PMMA and PAN. PMMA and PAN are also representative examples of fibers having a uniform structure in the thickness direction, and are preferable because a structure having a uniform structure and a sharp pore size distribution can be easily obtained. In particular, PMMA is preferable because it is excellent in molding processability and cost, and has high transparency, so that the internal state of the porous fiber is relatively easy to observe and the fouling state is easily evaluated.

<Thread shape of porous fiber>
Furthermore, if the thread shape of the porous fiber is hollow fiber or solid thread, it is easy to secure a sufficient adsorption area by making the film thickness part and the form inside the thread suitable for adsorption, respectively. It becomes easy to efficiently adsorb and remove the adsorption target substance contained in the blood. Of these, solid yarn is particularly preferable. In the case of hollow fibers, when the pressure loss differs between the inside and outside of the hollow fiber, there is a concern that the flow rate of the liquid to be treated will differ between inside and outside the hollow fiber, resulting in a decrease in the adsorption efficiency of the column. Because. Further, in order to equalize the pressure loss between the inside and outside of the hollow fiber, there are significant restrictions on the inner diameter of the hollow fiber and the column packing rate. Furthermore, when blood flows through a column filled with hollow fibers, the hollow portion of the hollow fibers is a closed environment that is fixed as compared to the environment outside the hollow fibers in the column (the gap outside the hollow fibers is There is a concern that thrombi and the like that are deformed by the movement of the thread in the column are likely to form.

  In the case of a solid yarn, the cross section of the yarn is not necessarily limited to a perfect circle, and other elliptical holes, rectangles, triangles, or those having a modified cross-sectional shape can be suitably used depending on the case. .

<Measurement method of fiber diameter>
The porous fiber of the present invention preferably has a fiber diameter of 50 to 1000 μm. The fiber diameter is preferably 50 μm or more, more preferably 100 μm or more, and still more preferably 150 μm or more. The fiber diameter is preferably 1000 μm or less, more preferably 800 μm or less, and still more preferably 500 μm or less. When the fiber diameter is 50 μm or more, more preferably 100 μm or more, and even more preferably 150 μm or more, even if the particle addition rate is increased, the fiber strength is hardly lowered and the productivity is easily improved. On the other hand, when the fiber diameter is 1000 μm or less, more preferably 800 μm or less, and even more preferably 500 μm or less, the packing rate of the adsorbing fibers packed in the column tends to increase, and the adsorption performance tends to improve.

The method for measuring the fiber diameter is as follows. That is, 50 yarns (fibers) filled in the column are arbitrarily extracted and washed. After washing, the washing solution is completely replaced with pure water. Put between the slide glass and the cover glass. Using a projector (for example, Nikon V-10A), the outer diameter (outermost diameter) of the yarn is measured arbitrarily at two locations for the same yarn. Take the average of the two outer diameters and round off to the first decimal place. When the number of filled yarns is less than 50, all the yarns are measured and the average value is similarly taken. If the thread cross section of the porous fiber is other than a perfect circle, the diameter of the circle inscribed in the shape of the thread cross section is a, the diameter of the circumscribed circle is b, and (a × b) ^0.5 is the thread. The diameter of

<Phosphorus adsorption column>
Another aspect of the phosphorus adsorption column of the present invention is one in which the porous fiber of the present invention is incorporated.

  An example of producing a phosphorus adsorption column of the present invention (hereinafter sometimes simply referred to as a column) using a solid thread as the thread shape is shown below, but the present invention is limited to this. is not.

<Spinning method>
A polymer as a raw material for the porous fiber is dissolved in an appropriate solvent, and then a predetermined amount of the selected phosphorus adsorbent particles are added to prepare a spinning dope. The solvent is appropriately selected according to the polymer to be dissolved, but dimethylformamide, dimethyl sulfoxide, hexanone, xylene, tetralin, cyclohexanone, carbon tetrachloride, etc. are generally used. For example, when PMMA is used as the polymer, dimethyl sulfoxide (DMSO) is preferably used.

  If the spinning stock viscosity is too low, the stock solution may be highly fluid and difficult to maintain its intended shape. Therefore, the lower limit of the stock solution viscosity at the temperature of the spinneret is preferably 10 poise, more preferably 90 poise, still more preferably 400 poise, and particularly preferably 800 poise. On the other hand, when the viscosity of the spinning solution is too high, the discharge stability tends to decrease due to an increase in pressure loss during discharging the stock solution, and mixing of the stock solution may be difficult. Therefore, the upper limit of the stock solution viscosity at the temperature of the spinneret is 100000 poise, more preferably 50000 poise.

  The spinning dope is discharged from a die having a circular stock solution discharge port, or in the case of spinning a modified cross-section fiber, from a die having a stock solution discharge port having a shape matched to the cross-sectional shape, and is solid in a coagulation bath. To solidify. The coagulation bath usually comprises a coagulant such as water or alcohol, or a mixture of a solvent and a coagulant constituting the spinning dope. Further, the porosity of the porous fiber can be changed by controlling the temperature of the coagulation bath. Since the porosity can be affected by the type of spinning dope, etc., the temperature of the coagulation bath is also appropriately selected. In general, the porosity can be increased by increasing the coagulation bath temperature. Although this mechanism is not exactly clear, it is thought that the solvent reaction in the high temperature bath is fast and the solvent is solidified and fixed before shrinkage due to the competitive reaction between the solvent removal from the stock solution and the solidification shrinkage. However, if the coagulation bath temperature becomes too high, the pore diameter becomes excessive. For example, the solidification bath temperature is preferably 39 ° C. or higher when a solid yarn containing PMMA is used as the base material and gas is put into the inner tube. 42 ° C. or higher is more preferable. On the other hand, the coagulation bath temperature is preferably 50 ° C. or lower, more preferably 46 ° C. or lower.

  Next, a step of washing the solvent adhering to the solidified solid yarn is passed. The means for washing the solid yarn is not particularly limited, but a method of allowing the solid yarn to pass through a multi-staged water bath (referred to as a washing bath) is preferably used. What is necessary is just to determine the temperature of the water in a water-washing bath according to the property of the polymer which comprises a thread | yarn. For example, in the case of a yarn containing PMMA, 30 to 50 ° C. is used.

  Moreover, in order to maintain the pore diameter in the solid yarn after passing through the washing bath, a step of applying a moisturizing component may be added. The term “moisturizing component” as used herein refers to a component capable of maintaining the humidity of the solid yarn or a component capable of preventing a decrease in the humidity of the solid yarn in the air. Typical examples of moisturizing ingredients include glycerin and its aqueous solutions.

  After washing with water and applying moisturizing ingredients, it is possible to pass through a bath (called heat treatment bath) filled with an aqueous solution of heated moisturizing ingredients in order to improve the dimensional stability of solid yarn with high shrinkage. is there. The heat treatment bath is filled with an aqueous solution of heated moisturizing ingredients, and when the solid yarn passes through this heat treatment bath, it shrinks due to the thermal action and becomes difficult to shrink in the subsequent process, and the yarn structure Can be stabilized. The heat treatment temperature at this time varies depending on the material of the porous fiber, but in the case of a yarn containing PMMA, 75 ° C. or higher is preferable, and 82 ° C. or higher is more preferable. Moreover, 90 degrees C or less is preferable and 86 degrees C or less is set as a more preferable temperature.

<Case shape>
The solid yarn manufactured in this way is built in a casing to form a phosphorus adsorption column. As the shape of the casing, both ends are open ends, and examples thereof include a rectangular cylinder and a cylindrical body such as a square cylindrical body and a hexagonal cylindrical body. Among these, a cylindrical body, particularly a cylindrical body having a perfect circular section is preferable. This is because the casing does not have corners, which makes it easy to suppress the retention of the liquid to be processed at the corners. Moreover, by making both sides open ends, the flow of the liquid to be treated is less likely to be turbulent, and pressure loss can be easily minimized.

  Moreover, it is preferable that a casing is an instrument comprised with a plastic, a metal, etc. In the former case, it is manufactured by injection molding using a mold or by cutting a material. In the latter case, the instrument is manufactured by cutting the material. Among these, plastic is preferably used from the viewpoints of cost, moldability, weight, and blood compatibility.

  In the case of plastic, for example, a thermoplastic resin excellent in mechanical strength and thermal stability is used. Specific examples of such thermoplastic resins include polycarbonate resins, polyvinyl alcohol resins, cellulose resins, polyester resins, polyarylate resins, polyimide resins, cyclic polyolefin resins, polysulfone resins, polyether sulfones. Resin, polyolefin resin, polystyrene resin, polyvinyl alcohol resin, and mixtures thereof. Among these, polystyrene, polycarbonate, and derivatives thereof are preferable in terms of moldability, transparency, and radiation resistance required for the casing. This is because a resin with excellent transparency is convenient for ensuring safety because the internal state can be confirmed during blood perfusion, and a resin with excellent radiation resistance is preferable when radiated during sterilization. In the former case, it is manufactured by injection molding using a mold or by cutting a material, and in the latter case, an instrument is manufactured by cutting the material. Among these, plastic is preferably used from the viewpoints of cost, moldability, weight, and blood compatibility.

  The casing length of the phosphorus adsorption column of the present invention is preferably 1 cm or more and 500 cm or less, more preferably 3 cm or more and 50 cm or less. Here, the casing length is the axial length of the cylindrical casing before a partition is provided or a cap is attached. When the casing length of the column is 500 cm or less, more preferably 50 cm or less, the insertability of the porous fibers into the column tends to be good, and the handling during actual use as a phosphorus adsorption column tends to be easy. Conceivable. Moreover, when it is 1 cm or more, more preferably 3 cm or more, it is easy to be advantageous, for example, when forming a partition part etc., and the handleability at the time of columning tends to be good. The shape of the porous fiber when incorporated in the column is preferably a straight shape, and it is preferable to incorporate the straight fiber by inserting it in parallel to the longitudinal direction of the column case. Since the straight porous fiber easily secures the flow path of the liquid to be treated, it is easy to distribute the liquid to be treated evenly in the column, and it is easy to suppress the resistance of the flow path. This is also advantageous for an increase in pressure loss due to adhesion of water. Therefore, even when highly viscous blood is used as the liquid to be treated, it is easy to suppress the risk of coagulation in the casing. The porous fiber can be processed as a knitted fabric, a woven fabric, a non-woven fabric, or the like. However, since a large tension is applied to the yarn during processing, there is a restriction that the porosity of the porous fiber cannot be increased. Furthermore, processing the porous fiber may cause an increase in the number of steps and an increase in cost.

  The number of porous fibers incorporated in the phosphorus adsorption column of the present invention is preferably about 1,000 to 500,000.

<Filling rate>
The upper limit of the packing rate of the adsorbent in the column casing is preferably 70%, and more preferably 63% or less. The lower limit of the filling rate of the adsorbent is preferably 13%, more preferably 30%, and particularly preferably 45%. By setting the filling rate of the adsorbent to 13% or more, the amount of blood necessary for blood purification is reduced, so that the burden on the patient can be easily reduced. In addition, when the filling rate of the adsorbent is 70% or less, the air release property tends to be good. Furthermore, since the adsorbent is easily filled, the working efficiency is easily improved. The filling rate here is the ratio of the adsorbent volume in the casing volume provided with the inlet part into which the blood flow before purification flows and the outlet part from which the blood flow after purification is discharged, Does not include the header part.

The filling rate is a ratio of the casing volume (Vc) calculated from the cross-sectional area and length of the casing to the fiber cross-sectional area, casing length, and fiber volume (Vf) calculated from the number of fibers, and is obtained as follows. .
Vc = Cross sectional area of casing body × Effective length Vf = Fiber cross sectional area × Number of fibers × Effective length filling factor = Vf / Vc × 100 (%)
In addition, about the cross-sectional area of a casing trunk | drum, when a casing has a taper, it is set as the cross-sectional area in a casing center.

Here, Vc does not include the volume of a member that does not contain a fiber, for example, a member that serves as an inlet / outlet port of a liquid to be treated, such as a header or header cap. Further, regarding Vf, when a spacer fiber or the like for preventing adhesion between fibers in the case is used, the volume is also included. The effective length of the fiber refers to the length obtained by subtracting the length of the partition wall from the casing length, but the upper limit of the effective length of the fiber is that the fiber is difficult to bend. From the viewpoint of facilitating reduction, the thickness is preferably 5000 mm, more preferably 500 mm, and particularly preferably 210 mm. In addition, as the lower limit of the effective length of the fiber, it is possible to reduce the amount of yarn discarded when cutting excess yarn that has jumped out of the column in order to align the length of the yarn, making it easier to improve productivity, From the viewpoint of easy handling of the fiber bundle, 5 mm is preferable, more preferably 20 mm, and particularly preferably 30 mm. As a method for measuring the effective length of the fiber, in the case of a crimped yarn such as crimp, the yarn length is measured in a straight shape with both ends of the yarn extended. Specifically, one piece of fiber taken out from the column is fixed with tape or the like and lowered vertically, and the other piece is given a weight of 8 g per cross-sectional area (mm ² ) of the yarn, so that the fiber becomes linear. Measure the total length of This measurement is performed on 30 fibers arbitrarily selected in a column or the like, the average value of 30 fibers is calculated in mm, and the first decimal place is rounded off.

<Sterilization method>
Moreover, when using for a medical device etc., it is preferable to sterilize or sterilize and use. Examples of sterilization and sterilization methods include various sterilization and sterilization methods such as high-pressure steam sterilization, gamma ray sterilization, ethylene oxide gas sterilization, chemical sterilization, and ultraviolet sterilization. Among these methods, gamma ray sterilization, high-pressure steam sterilization, and ethylene oxide gas sterilization are preferable because they have little effect on sterilization efficiency and materials.

<Column Phosphorus Adsorption Performance>
Phosphorus adsorption performance can also be measured for the column produced as described above. Detailed measurement methods will be described later in Examples. The phosphorus adsorption performance of the column is preferably 3.0 mg / g or more, more preferably 4.0 mg / g, even more preferably 5.0 mg / g or more, preferably 10.0 mg / g or more, particularly preferably 15 0.0 mg / g or more.

<Usage pattern>
The usage of the phosphorus adsorption column in the present invention is various and can be used for water treatment, purification, blood purification and the like. In the case of blood purification applications, there are two methods of treatment: direct perfusion of whole blood and separation of plasma from blood followed by passage of plasma through the column. The phosphorus adsorption column of the present invention should be used for both methods. Can do.

  Moreover, when using as a blood purifier, the method of carrying out adsorption removal on-line by incorporating in an extracorporeal circuit from a viewpoint of the processing amount of one time, the simplicity of operation, etc. is preferable. In this case, the phosphorus adsorption column of the present invention may be used alone, or may be used in series with an artificial kidney during dialysis or the like. By using such a method, it is possible to remove substances that are insufficiently removed only by an artificial kidney simultaneously with dialysis. In particular, the function of the artificial kidney can be complemented by adsorbing and removing phosphorus, which is insufficiently removed by the artificial kidney, using the phosphorus adsorption column of the present invention.

  Moreover, when using together with an artificial kidney, it may be connected before the artificial kidney or after the artificial kidney in the circuit. The merit of connecting in front of the artificial kidney is that it is difficult to be affected by dialysis by the artificial kidney, so that the original performance of the phosphorus adsorption column is easily exhibited. On the other hand, the merit of connecting after the artificial kidney is that the blood after the water removal by the artificial kidney is processed, so that the solute concentration is high, and an increase in the adsorption and removal efficiency of phosphorus can be expected.

[Measurement Examples 1 to 9]
(1) Phosphorus adsorption performance evaluation Plasma was obtained by centrifugation from bovine blood to which disodium ethylenediaminetetraacetate was added. The bovine plasma was adjusted so that the total protein amount (TP) was 6.5 ± 0.5 g / dL. The bovine plasma used was within 5 days after blood collection.

3400 mg of sodium monohydrogen phosphate (Na ₂ HPO ₄ ) and 13.8 mg of potassium dihydrogen phosphate (KH ₂ PO ₄ ) were dissolved per 400 mL of the bovine plasma to obtain a phosphorus start solution. The phosphorus concentration of this phosphorus start solution is Cs (mg / dL).

50 mL of the above phosphorus start solution was added to 0.01 g of various particulate phosphorus adsorbents shown in Table 1, and the mixture was shaken at 37 ° C. for 4 hours to be reacted. After the reaction for 4 hours, the reaction solution was centrifuged at 9000 rpm for 5 minutes, and the supernatant was collected. The supernatant was sent to Nagahama Life Science Laboratory of Oriental Yeast Co., Ltd. The phosphorus concentration in the supernatant was measured and used as the final concentration Ce (mg / dL). The phosphorus start solution was also sent to the Nagahama Life Science Laboratory for measurement. Thereafter, the phosphorus adsorption performance per 1 g of the adsorbent was calculated by the following formula 3. In addition, the phosphorus adsorption | suction performance calculated | required from this type | formula becomes a value when adsorption | suction is not saturated.
Formula 3: Phosphorus adsorption performance [mg / g] = [(Cs-Ce) × 0.5 (dL)] / 0.01 (g)
The method for measuring the phosphorus adsorption performance of the porous fiber is the same as that described above except that 0.02 g of the porous fiber carrying the phosphorus adsorbent is used instead of 0.01 g of the phosphorus adsorbent. It carried out like the case of adsorption | suction performance. In calculating the phosphorus adsorption performance, the following formula 4 was used.
Formula 4: Phosphorus adsorption performance of porous fiber [mg / g] = [(Cs (mg / dL) -Ce (mg / dL)) × 0.5 (dL)] / porous fiber mass (g)
(2) Average particle size of phosphorus adsorbent The particle size was measured by a laser diffraction / scattering method using MT3300 manufactured by NIKKISO. The particle shape was set to a non-spherical shape, the horizontal axis diameter and the vertical axis frequency (%) were plotted, and the number average was used as the average particle diameter.

(3) pH measurement As a pH measurement method, the glass electrode method, which is the most commonly used measurement method, is used. This is a method of measuring the pH of a target solution by using two electrodes, a glass electrode and a reference electrode, and knowing the voltage (potential difference) generated between the two electrodes. Specifically, a compact pH meter LAQUATwin manufactured by HORIBA, Ltd. can be used.

  The pH of the phosphorus adsorbent was measured with a compact pH meter LAQUATwin manufactured by Horiba. First, the pH scale is calibrated using known standard buffers (pH 4.01 and 6.86). The pH of the physiological saline is measured and set as pH (start). Phosphorus adsorbent 0.1 g was weighed and added to 10 mL of physiological saline and stirred at room temperature for 4 hours. After stirring, 1 mL of physiological saline solution added with the phosphorus adsorbent was sampled and centrifuged at 9000 rpm for 5 minutes. 500 μL of the supernatant was added to the measurement chamber and the pH was measured to obtain pH (4H). The change in pH was determined by Equation 5.

When directly measuring the pH of the porous fiber, the measurement was performed in the same manner as in the case of measuring the phosphorus adsorbent except that 0.2 g of the porous fiber was weighed as a sample.
Formula 5: pH change = pH (4H) -pH (start)
4) Solubility (water solubility) measurement of adsorbent 100 g of water and a rotor brought to 20 ° C. in a thermostatic bath and a rotor were placed in a flask, and 100 mg of phosphorus adsorbent was added and stirred for 4 hours or more. Subsequently, the phosphorus adsorbent particles and the solution were separated by centrifugation at 12,000 rpm for 20 minutes. The supernatant was sampled and the particle ion concentration of the dissolved phosphorus adsorbent was measured. When the adsorbent was a powder, it was measured by inductively coupled plasma-mass spectrometry (ICP-MS). The particle mass was calculated from the measured ion concentration, and the dissolved particle mass per 100 g of the supernatant was defined as the water solubility.

  In the case of porous fibers, the same evaluation as described above was conducted except that 200 mg of porous fibers were added to 100 g of water.

[Example 1]
First, a 21% by mass PMMA stock solution was prepared. 31.7 parts by weight of syndiotactic-PMMA (syn-PMMA, manufactured by Mitsubishi Rayon, “Dynar” BR-85) having a mass average molecular weight of 400,000, and syn-PMMA having a mass average molecular weight of 1,400,000 (manufactured by Sumitomo Chemical) , "SUMIPEX" AK-150), 31.7 parts by mass, 16.7 parts by mass of isotactic-PMMA (iso-PMMA, manufactured by Toray) porous fiber having a mass average molecular weight of 500,000, and sodium parastyrene sulfonate Was mixed with 376 parts by mass of dimethyl sulfoxide (DMSO) with a molecular weight of 300,000 PMMA copolymer (manufactured by Toray) containing 1.5 mol% and stirred at 110 ° C. for 8 hours to prepare a spinning dope. The obtained spinning dope had a viscosity at 110 ° C. of 1240 poise.

  Next, 1 g of titanium oxide particles (Measurement Example 6) as a phosphorus adsorbent was added to 50 g of the obtained spinning dope to prepare a titanium oxide / PMMA stock solution. While heating at 100 ° C., the mixture was stirred at 100 rpm and mixed uniformly. The stock solution was added to a 10 mL syringe, and discharged into a coagulation liquid maintained at a temperature of 45 ° C. at a discharge linear speed of 6 m / min using a syringe pump, and then automatically wound at 100 rpm. The formed fiber was thoroughly washed with pure water. A solid porous fiber having a phosphorus adsorbent content of 8.7% by mass and a cross-sectional outer diameter of 200 μm was obtained.

  The phosphorus adsorption performance of the phosphorus adsorption fiber obtained in Example 1 was evaluated. 1 g of porous fiber (inner phosphorus adsorbent is 0.087 g) is added to 50 mL of phosphorus start solution prepared in (1) phosphorus adsorption performance evaluation described above in the measurement example, and adsorbed for 4 hours while shaking at 37 ° C. Reaction was performed. During shaking, the reaction solution was sampled every predetermined time, the sampled solution was centrifuged at 9000 rpm for 5 minutes, the supernatant was recovered, and the phosphorus concentration was quantified. On the other hand, the fiber that had been reacted for 4 hours was washed with physiological saline, further washed with water, dried in an oven at 50 ° C. overnight, confirmed that there was no mass change, and reweighed. The mass of the porous fiber was used. The phosphorus adsorption performance of the porous fiber was calculated by the above formula 4. The results are shown in Table 2.

[Example 2]
4 g of titanium oxide particles (Measurement Example 6) as a phosphorus adsorbent were added to 50 g of the 21 mass% PMMA stock solution prepared in Example 1 to prepare a titanium oxide / PMMA stock solution. Thereafter, spinning was performed in the same manner as in Example 1. A solid-shaped porous fiber containing 27.6% by mass of a phosphorus adsorbent and having a cross-sectional outer diameter of 350 μm was obtained.
The phosphorus adsorption performance of the porous fiber was evaluated. As in Example 1, 1 g of porous fiber (inner phosphorus adsorbent is 0.275 g) was added to 50 mL of the phosphorus start solution prepared in the measurement example (1) Phosphorus adsorption performance evaluation. The phosphorus concentration and the porous fiber mass were quantified in the same manner as in 1, and the phosphorus adsorption performance of the porous fiber was calculated according to Equation 4. The results are shown in Table 2.

[Example 3]
26.19 g of DMSO was added to 23.81 g of the 21 mass% PMMA stock solution prepared in Example 1, to obtain 50 g of a polymer solution containing 10 mass% of PMMA. 5 g of titanium oxide particles (Measurement Example 6) as a phosphorus adsorbent are added to 50 g of the 10 mass% PMMA stock solution, heated to 100 ° C. and uniformly mixed with stirring at a rotation speed of 100 rpm, and the titanium oxide / PMMA stock solution Was prepared. Thereafter, spinning was performed in the same manner as in Example 1. A solid porous fiber having a phosphorus adsorbent content of 50% by mass and an outer cross-sectional diameter of φ250 μm was obtained.

  50 mL of the phosphorus start solution prepared in the above (1) evaluation of phosphorus adsorption performance was added to 0.1 g of the porous fiber obtained above (inner phosphorus adsorbent was 0.05 g), and the phosphorus concentration was the same as in Example 1. The porous fiber mass was quantified, and the phosphorus adsorption performance of the porous fiber was calculated by Equation 4.

[Example 4]
26.19 g of DMSO was added to 23.81 g of the 21 mass% PMMA stock solution prepared in Example 1 to obtain 50 g of a polymer solution having a PMMA concentration of 10 mass%. 5 g of lanthanum carbonate particles (Measurement Example 3) as a phosphorus adsorbent are added to 50 g of the 10 mass% PMMA stock solution, heated to 100 ° C. and uniformly mixed with stirring at a rotation speed of 100 rpm, and lanthanum carbonate / PMMA stock solution Was prepared. Thereafter, spinning was performed in the same manner as in Example 1. A solid porous fiber having a phosphorus adsorbent content of 50% by mass and an outer diameter of 170 μm in cross section was obtained.

  50 mL of the phosphorus start solution prepared in the above (1) evaluation of phosphorus adsorption performance was added to 0.1 g of the porous fiber obtained above (inner phosphorus adsorbent was 0.05 g), and the phosphorus concentration was the same as in Example 1. The porous fiber mass was quantified, and the phosphorus adsorption performance of the porous fiber was calculated by Equation 4.

[Example 5]
A neodymium carbonate / PMMA stock solution was prepared in the same manner as in Example 4. Thereafter, spinning was performed in the same manner as in Example 1. A solid porous fiber having a phosphorus adsorbent content of 50% by mass and an outer diameter of 170 μm in cross section was obtained.

  50 mL of the phosphorus start solution prepared in the above (1) evaluation of phosphorus adsorption performance was added to 0.1 g of the above porous fiber (inner phosphorus adsorbent was 0.05 g). The mass was quantified, and the phosphorus adsorption performance of the porous fiber was calculated according to Equation 4.

[Comparative Example 1]
Spinning was performed in the same manner as in Example 1 except that no particles were added, and solid yarn-shaped PMMA fibers having a cross-sectional outer diameter of 138 μm were obtained. About the obtained PMMA fiber, the phosphorus adsorption | suction performance was evaluated by the method similar to Example 1. FIG.

[Examples 6 to 7]
<Production of column>
The plurality of porous fibers obtained in Example 3 or Example 4 were arranged in a polycarbonate cylindrical casing having an inner diameter of 10 mm and an axial length of 12.2 mm. Inserted in a straight shape parallel to the direction.

  More specifically, in Example 6, a total of 540 pieces of the yarn having a diameter of 270 μm cut in Example 3 and cut to 11 mm in length are packed to obtain a column having a packing rate of 35.5%. It was. On the other hand, in Example 7, a total of 760 pieces of the yarn having a diameter of 170 μm obtained in Example 4 which were also cut to a length of 11 mm were packed to obtain a column having a packing rate of 19.8%.

  Next, a polypropylene mesh filter having an aperture equivalent diameter of 84 μm and an aperture ratio of 36%, which was cut to a diameter equivalent to the casing inner diameter, was attached to the outlet of the liquid to be treated on both side end faces of these columns. Finally, a cap called a header having an inlet and an outlet for the liquid to be treated was attached to the casing end.

<Measurement of column phosphorus adsorption performance>
As the adsorption performance evaluation, the phosphorus adsorption performance of the column was measured. Bovine plasma was obtained in the same manner as in (1) phosphorus adsorption performance evaluation in Examples 1 to 5 and Comparative Examples 1 to 3. The bovine plasma was prepared so that the total protein was 6.5 ± 0.5 g / dL. The bovine plasma used was within 5 days after blood collection. Next, 7.85 mg sodium monohydrogen phosphate (Na ₂ HPO ₄ ) and 3.45 mg potassium dihydrogen phosphate (KH ₂ PO ₄ ) are dissolved per 100 mL of the bovine plasma to mimic high phosphorus plasma. The liquid to be processed was prepared.

  Silicone tubes were attached to the inlet and outlet of the column, and both the inlet and outlet were immersed in the liquid to be treated to form a circulation system. The liquid to be treated was flowed at a flow rate of 1 mL / min, and after passing through the column from the column inlet, the purified liquid was returned to the liquid to be treated from the outlet. The liquid to be treated and the purified liquid at the outlet were sampled, and the phosphorus concentration in the sample was measured. Further, after circulation, the yarn was washed with physiological saline and water and then dried overnight in an oven at 60 ° C., and it was confirmed that there was no mass change, and the dry mass was obtained.

Claims (9)

A porous fiber in which a phosphorus adsorbent is supported inside the fiber,
The fiber is a porous fiber whose pH change after stirring for 4 hours in physiological saline is −1 or more and +1 or less.   The porous fiber of Claim 1 whose phosphorus adsorption | suction performance is 3 mg / g or more. The phosphorus adsorbent is a granular material,
The porous fiber of Claim 1 or 2 whose solubility in 100 g of water of 20 degreeC of the said granular material in the state carry | supported by the said porous fiber is 10 mg or less.   The porous fiber according to any one of claims 1 to 3, wherein the phosphorus adsorbent is a powder and has an average particle size of 100 µm or less.   The porous fiber as described in any one of Claims 1-4 whose fiber diameter is 50-1000 micrometers. The porous fiber according to any one of claims 1 to 5, wherein the average pore radius is 0.5 to 100 nm, and the specific surface area of the pores is 10 m ² / g or more.   The porous fiber according to any one of claims 1 to 6, wherein the phosphorus adsorbent contains a rare earth element salt or a Group 4 oxide. The phosphorus adsorbent contains a rare earth carbonate;
The porous fiber according to claim 7, wherein the rare earth element is one selected from lanthanum, cerium, praseodymium, samarium, and neodymium.   A phosphorus adsorption column in which the porous fiber according to any one of claims 1 to 8 is incorporated.