JP2013081771A - Hollow fiber binding means and purification column - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hollow fiber biding means for improving purification treatment efficiency or the like in a purification column in which ends of hollow fibers are not adhesively fixed to an end of a cylindrical casing by a barrier wall such as potting, and a purification column using the same.SOLUTION: The hollow fiber binding means separates the cylindrical casing containing hollow fibers into two different spaces of a hollow fiber filling portion 4 that is a space densely filled with the hollow fibers and a cavity portion 3 in which the hollow fibers are sparse by fixing the hollow fibers at the end of the casing. (a) The hollow fiber filling portion is spaced from the inner periphery of the casing and the cavity portion is located between the inner periphery of the casing and the hollow fiber filling portion. (b) The total surface area of the hollow fiber filling portion is 50% or more of the surface area of the end surface of the casing. (c) The hollow yarns are not fixed to any of the means and the casing with bond.

Description

  The present invention relates to a purification column containing a hollow fiber used for blood purification or the like.

  Conventionally, a hollow fiber column that has been generally used is filled with a hollow fiber bundle in a cylindrical casing, and both ends of the hollow fiber bundle are fixed to the inner surface of the casing with partition walls made of a resin composition. Cap members each having a connection port serving as a supply port or a discharge port for a liquid to be treated are attached to both ends, and connection ports serving as an inflow port and an outflow port for a treatment liquid are provided near both ends of the outer periphery of the casing. When the liquid to be treated was supplied and passed through the inside of each hollow fiber membrane, it was an apparatus for performing a purification treatment with a treatment liquid on the outside thereof. The process of fixing both ends of the hollow fiber bundle with the resin composition is called a potting process.For example, both ends of the casing loaded with the hollow fiber bundle are covered with caps and closed in this state. A resin liquid such as polyurethane is injected from the inlet and outlet of the processing liquid projecting in the vicinity of both ends of the casing on the outer periphery of the casing, and the resin liquid is allowed to flow and cure to the end of the casing by centrifugal force. The end of the hollow fiber bundle is fixed to the end of the casing by removing the unnecessary part and removing both the ends of the hollow fiber membrane. However, in the method using potting, there is a concern that the process becomes complicated and the cost is increased when creating a column. In addition, since the treatment liquid cannot be introduced to the outside of the hollow fiber, the outer surface of the hollow fiber hardly contributes to adsorption and removal, and there is a disadvantage that the removal efficiency is low.

  On the other hand, there is an example in which both ends of the purification column are sealed with a mesh or the like without being fixed by potting (Patent Documents 1, 2, and 3). In this method, it is possible to simultaneously introduce the treatment liquid into and out of the hollow fiber, but it is difficult to control the flow ratio between the inside of the hollow fiber and the outside of the hollow fiber, and the flow inside the column is part of the casing. There is concern about being biased toward Moreover, there may be unevenness in the density of the hollow fiber filled in the casing.

  In addition, there is an example in which a hole penetrating the potting portion is provided in the plate thickness direction in the potting portions at both ends of the casing so that the processing liquid can be uniformly dispersed on both the inside and outside of the hollow fiber ( Patent Documents 4, 5, 6, and 7). However, in these inventions, since one end of the hollow fiber is closed, there is a concern about an increase in the pressure loss of the processing liquid and an increase in the pressure of the column due to clogging.

JP 2009-254695 A Japanese Unexamined Patent Publication No. 2011-156022 International Publication No. 2009/128564 JP-A-5-161831 JP-A-5-161832 JP-A-6-343836 JP 2007-90309 A

  In the purification column in which the end of the hollow fiber is not bonded and fixed to the end of the cylindrical casing by a partition wall such as potting, a drift occurs due to non-uniform distribution of the processing liquid in the column, resulting in a decrease in processing efficiency. It is an object of the present invention to provide a hollow fiber restraint means and a purification column using the hollow fiber restraint means that can improve the purification treatment efficiency and the like.

  In order to solve the above problems, the present invention adopts the following configuration.

The hollow fiber filling portion and the hollow fiber, which are spaces in which the hollow fiber is tightly filled, are fixed by fixing the hollow fiber at the end of the cylindrical casing in which the hollow fiber is incorporated, which satisfies the following items: Hollow fiber restraint means that separates into two different spaces of a sparse void.
(A) The hollow fiber filling portion is disposed apart from the inner peripheral surface of the casing, and the gap portion exists between the casing inner peripheral surface and the hollow fiber filling portion (b) of the hollow fiber filling portion. The total surface area is 50% or more of the surface area of the casing end surface. (C) The hollow fiber is not fixed to either the means or the casing by adhesion.

  By installing the hollow fiber restraint means of the present invention at the end of the cylindrical casing and fixing the hollow fiber to form a purification column, the flow in the column is made more nearly uniform, the purification efficiency of the column, etc. Can be improved.

It is a schematic end view which shows the state which the hollow fiber restraint means which concerns on 1 aspect of this invention has restrained the hollow fiber in the casing edge part of the purification | cleaning column. It is a circuit diagram at the time of clearance measurement.

  The present invention relates to the flow of the processing liquid in the column by concentrating the hollow fiber at the end on the side where the processing liquid is introduced or discharged on the column containing the hollow fiber in the vicinity of the center in the cross section of the casing. Is provided with a hollow fiber restraint means capable of appropriately distributing the above, and a purification column with improved adsorption removal efficiency of unnecessary substances in the treatment liquid is provided.

  The hollow fiber restraining means in the present invention has a function of separating the hollow fiber into two different spaces in the casing by fixing the hollow fiber at the end of the casing in which the hollow fiber is incorporated, and is separated by the means. The space to be formed is a hollow fiber filling portion in which the hollow fibers are densely filled and a void portion in which the hollow fibers are sparse.

  The hollow fiber filling portion separated by the hollow fiber restraining device is arranged to be separated from the inner peripheral surface of the casing, and the gap portion exists between the casing inner peripheral surface and the hollow fiber filling portion. That is, by concentrating the hollow fiber in the vicinity of the central portion in the cross section of the casing, a gap is formed between the casing and the hollow fiber bundle, and the flow of the treatment liquid can be suppressed from being biased near the central portion in the cross section of the casing. The treatment liquid mainly flows inside the hollow fiber near the center of the casing cross section, and mainly flows outside the hollow fiber near the periphery. By appropriately adjusting the flow rate of the treatment liquid flowing through both of them, unnecessary substances in the treatment liquid can be efficiently adsorbed and removed inside and outside the hollow fiber.

  In this way, by introducing the liquid to be treated not only inside the hollow fiber but also outside the hollow fiber, the contact area between the liquid to be treated and the hollow fiber is dramatically increased, and the substance to be adsorbed can be made more efficient. It can be removed by adsorption. Further, when the hollow fiber film thickness part has pores, the diffusibility of the adsorbed substance to the film thickness part pores is improved by introducing the treatment liquid from both sides of the film thickness part.

  The hollow fiber restraining means used in the present invention is preferably an instrument made of plastic or metal. 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. The instrument used as the restraining means may be fixed in advance in the casing, or may be inserted into the casing in a state where the instrument is previously attached to the hollow fiber and the two are combined.

  An example of a specific aspect of the present invention will be described with reference to FIG. On the casing end face, 1 is a casing, 2 is a hollow fiber restraint device, 3 is a gap portion, and 4 is a hollow fiber filling portion. However, the purification column in the present invention is not limited to such a specific example, and the hollow fiber is placed in a container having an inlet and an outlet for the liquid and provided with a device for preventing the purification column from flowing out of the container. Any material may be used as long as it is filled. The hollow fiber restraint device 2 has a ring-shaped portion having a diameter slightly smaller than the casing diameter in a cylindrical casing, and a connection portion with the casing around the ring-shaped portion. The diameter of the ring-shaped portion may be variable, and the hollow fiber can be restrained by changing the size according to the size of the hollow fiber bundle. In FIG. 1, the hollow fiber restraint portion is ring-shaped, but the present invention is not limited to this, and it is preferable that the hollow fiber restraint portion includes a portion that surrounds and restrains the hollow fiber and a connection portion with the casing.

  Moreover, it is desirable that the hollow fiber filling part separated by the hollow fiber restraint device is one continuous space in the cross section. This means that the hollow fibers are bundled without fractionating the bundle of hollow fibers in the hollow fiber restraining means, and there may be minute gaps between the hollow fibers. By making the yarn bundle filling part one continuous space, the yarn bundle can be easily inserted into the casing, and the concern such as deformation of the hollow fiber is reduced. Specifically, a mode in which a bundle of about 10,000 hollow fibers is arranged in the axial direction of the cylindrical casing in the longitudinal direction can be mentioned.

  In the hollow fiber restraining means in the present invention, it is important to control the ratio of the surface area of the hollow fiber filling part and the gap part separated by the means. That is, when the ratio of the hollow fiber filling portion is too large, the flow rate ratio of the treatment liquid to the void portion is small. Further, it is difficult to fix the restraint in the casing. On the other hand, when the gap is too large, the flow rate ratio of the treatment liquid to the gap is increased, and a sufficient amount of the treatment liquid cannot be supplied to the hollow fiber filling portion. Therefore, in the cross section of the hollow fiber restraint means, the lower limit of the total surface area occupied by the hollow fiber filling portion on the casing end surface is 50% or more of the surface area of the end surface, more preferably 70% or more, and further preferably 75% or more. is there. Moreover, as an upper limit, it is 95% or less, More preferably, it is 90% or less, More preferably, it is 85% or less. Here, the total surface area of the hollow fiber filling portion is an area surrounded by the inner peripheral surface of the hollow fiber restraint tool 2.

  In the present invention, it is also important to control the filling rate of the hollow fiber in the hollow fiber filling part in order to appropriately distribute the treatment liquid to the hollow fiber filling part and the void part. That is, when the filling rate is too low, the flow rate of the hollow fiber filling portion increases, and when the filling rate is too high, the flow of the hollow fiber filling portion becomes small. Therefore, the filling rate of the hollow fiber in the hollow fiber filling part is preferably 47% or more and 75% or less, and more preferably 55% or more and 66% or less.

  Further, as described above, it is preferable that all the hollow fibers are present in the packed portion. However, for example, when vibration is applied during transportation of the purification column, some of the yarns are removed from the hollow fiber packed portion of the restraining device. There is a possibility of moving to the department. In order to achieve uniform distribution to the hollow fiber filling portion and the void portion, which is the gist of the present invention, it is preferable that the hollow fiber filled in the hollow fiber filling portion is 90% or more of the hollow fibers in the entire column. .

  Similarly, the present hollow fiber restraint means does not fix the hollow fiber and the means, or the hollow fiber and the casing by bonding, in order to achieve the purpose of introducing the treatment liquid to the part other than the opening part of the hollow fiber. . Thereby, the effort and cost which adhere and fix a hollow fiber and a casing can be saved significantly.

  The hollow fiber restraining means in the present invention is preferably used only on either the treatment liquid introduction side or the discharge side. By limiting to one of them, the possibility that the processing liquid short-passes the vicinity of the outer peripheral portion of the casing can be eliminated.

  An advantage of using the hollow fiber restraint means only on the side where the processing liquid is introduced is that the contact efficiency of the processing liquid to the entire hollow fiber in the column is increased.

  On the other hand, as a merit of using the hollow fiber restraint means only on the side of discharging the processing liquid, it is possible to reduce the pressure loss in the column and the possibility of the retention of the processing liquid.

  The hollow fiber referred to in the present invention is a cylindrical thread membrane having a hollow hole serving as a flow path for the liquid to be treated, and is a thread body in which the end of the hollow hole is opened without being sealed. .

  The material of the hollow fiber packed in the column using the hollow fiber restraining means of the present invention includes polymethyl methacrylate (hereinafter referred to as PMMA), polyacrylonitrile (hereinafter referred to as PAN), polysulfone, polyether sulfone, and polyaryl ether sulfone. Polypropylene, polycarbonate, cellulose, cellulose triacetate and the like are used. Among them, it is preferable to include a material having a property capable of adsorbing protein, and examples thereof include PMMA and PAN.

  The hollow fiber used in the present invention preferably has a dense layer on the inner surface and outer surface of the hollow fiber, and more preferably has a substantially uniform structure in the thickness direction of the film thickness portion. Thereby, an adsorption area can be increased.

  In the present invention, when the hollow fiber membrane is too thin, the strength of the hollow fiber membrane is weakened, the hollow fiber membrane is weakened by the impact during transportation and operation, and the hollow fiber is broken and broken. There is a concern that leaks will occur. On the other hand, if the film thickness is too large, the central part of the film thickness having a large distance from the inner and outer surfaces is not sufficiently utilized for adsorption and becomes excessive. Also, in terms of production, the progress speed of phase separation differs greatly between the inner surface and the outer surface, which is disadvantageous. Therefore, the film thickness of the hollow fiber membrane is preferably 20 μm or more, more preferably 25 μm or more, while 100 μm or less is preferable, and more preferably 75 μm or less.

  Moreover, when the hollow fiber membrane has an inner diameter that is too small, for example, when used in blood purification applications, there is a concern that the pressure loss of blood will increase, and the amount of filtration due to clogging may be reduced. On the other hand, if it is too large, the amount of the filling liquid in the blood purifier becomes large when used for blood purification, and it is considered that the patient is burdened during extracorporeal circulation. Therefore, the inner diameter of the hollow fiber membrane is preferably 120 to 260 μm.

  Also, when assembling the thread bundle into the casing, adjust the thread bundle to be longer than the effective length, and then cut both ends of the thread bundle after incorporation. This is more efficient for manufacturing. By installing the restraining device according to the present invention before cutting both ends of this yarn bundle, it is possible to restrain the movement of the yarn at the time of cutting, so that excessive stress is hardly applied and the yarn collapse of the hollow fiber is greatly suppressed. it can. The “collapsed yarn” that has been crushed refers to a yarn having a minor axis of the hollow fiber outer diameter of 50% or less of the major axis of the hollow fiber outer diameter. When the yarn is crushed, the pressure loss at the time of introducing the treatment liquid into the hollow fiber increases, and as a result, the removal performance of the removal target substance of the column tends to decrease. In addition, a phenomenon that the treatment liquid remains inside the hollow fiber even after the treatment liquid passes through the column tends to occur. If the presence of the restraint device in the casing is not preferable after the cutting step, the restraint device of the present invention is arranged at both ends of the casing before the cutting, and after the cutting, the restraint device on either the treatment liquid introduction side or the discharge side is temporarily attached. You may take the method of removing. By doing in this way, there are few crushing thread | yarns in a both-sides end surface of a casing, and it can flow a process liquid more uniformly in a casing at the time of process liquid introduction.

  The column using the hollow fiber restraint means of the present invention has a wide variety of uses and can be used as a blood purifier. The treatment method includes a method in which whole blood is directly perfused and a method in which plasma is separated from blood and then the plasma is passed through a column. The purification column of the present invention can be used in any method.

  Moreover, when using as a blood purifier, the method of carrying out adsorption removal on-line by incorporating in an extracorporeal circuit is preferable from the viewpoint of one-time processing amount and ease of operation. In this case, the purification column of the present invention may be used alone or may be used in series with an artificial kidney during dialysis. By using such a technique, 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 large molecular weight substances that are difficult to remove with an artificial kidney using a purification column.

  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 not easily affected by dialysis by the artificial kidney, so that the original performance of the purification 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 the adsorption removal efficiency can be expected to increase.

  An example of creating a column using the hollow fiber restraint means of the present invention will be described below.

  A spinning dope prepared by dissolving the polymer in a solvent is prepared. At this time, a polymer having a negatively charged group can be simultaneously dissolved. The higher the negative charge and the lower the stock solution concentration (concentration of the substance excluding the solvent in the stock solution), the higher the void ratio of the hollow fiber membrane. By appropriately setting the negative charge group and stock solution concentration, It is possible to control the porosity. From this point of view, the preferred stock solution concentration in the present invention is 30% by weight or less, more preferably 27% by weight or less, and still more preferably 24% by weight or less. The hollow fiber membrane uses a double tube annular slit type hollow fiber membrane die that can flow a liquid or gas for forming a hollow portion in the inner tube and a spinning stock solution in the outer tube. Is passed through a dry air part of a certain distance and then discharged into a coagulation bath. Examples of the liquid to be injected into the inner tube include a solvent in which the above-mentioned spinning solution can be dissolved, a coagulant such as water and alcohol, a mixture thereof, or a non-solvent of a polymer soluble in these or a mixture thereof. Some hydrophobic liquids such as n-octane, aliphatic hydrocarbons such as liquid paraffin, and fatty acid esters such as isopropyl myristate can also be used. In addition, when the discharged yarn is gelled by a temperature change in the air or quickly forms a strong structure by solidification, an inert gas such as nitrogen gas or air can be used by self-suction or press-fitting. . Such a gas injection method is a very advantageous method from the viewpoint of the process. In the case of an undiluted solution system in which gelation is caused by temperature change, gelation can be promoted by blowing cold air in the dry part. In general, the hollow fiber membrane is controlled by controlling the amount of spinning solution discharged and the inner diameter by the amount of injected liquid or gas.

  The spinning dope discharged from the double tube annular slit hollow fiber membrane die is solidified into a hollow yarn shape in a coagulation bath. The coagulation bath usually consists of a mixture with a coagulant such as water or alcohol, or a solvent constituting the spinning dope. Usually, water can be used. In the present invention, a solution having a functional group having the negative charge described above can be added to the coagulation bath. Further, the porosity 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 membrane pore diameter becomes excessive. For example, the coagulation bath temperature when the hollow fiber membrane is a membrane containing PMMA and gas is put into the inner tube is preferably 39 ° C. or higher. 42 degreeC or more is more preferable. On the other hand, 50 degrees C or less is preferable, More preferably, it is 46 degrees C or less. At this time, as described above, it is possible to improve blood compatibility by adding a solution having a negatively charged functional group to the coagulation bath.

  Next, a step of washing the solvent adhering to the solidified hollow fiber membrane is passed. The means for washing the hollow fiber membrane is not particularly limited, but a method of allowing the hollow fiber membrane 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 washing bath according to the property of the polymer which comprises a film | membrane. For example, in the case of a film containing PMMA, 30 to 50 ° C. is used.

  Further, the hollow fiber membrane may be provided with a step of applying a moisturizing component in order to maintain the pore size after the washing bath. The term “moisturizing component” as used herein refers to a component capable of maintaining the humidity of the hollow fiber membrane or a component capable of preventing a decrease in the humidity of the hollow fiber membrane in the air. Typical examples of moisturizing ingredients include glycerin and its aqueous solutions.

  After washing with water and applying moisturizing components, it is possible to pass through a process of a bath (called heat treatment bath) filled with a heated aqueous solution of moisturizing components in order to enhance the dimensional stability of the highly shrinkable hollow fiber membrane. is there. The heat treatment bath is filled with an aqueous solution of a heated moisturizing component, and when the hollow fiber membrane passes through this heat treatment bath, it undergoes thermal action and shrinks, making it difficult to shrink in subsequent steps. The structure can be stabilized. The heat treatment temperature at this time varies depending on the film material, but in the case of a film 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.

  An example of means for producing a purification column equipped with the hollow fiber restraint means of the present invention using the obtained hollow fiber membrane is as follows.

  First, the hollow fiber membrane is cut into a required length, bundled in a necessary number, and then put into a plastic case that becomes a cylindrical portion of the purification column. At this time, by attaching an instrument for restraining the yarn bundle to the plastic case and inserting the hollow fiber bundle into the hollow fiber filling portion, the hollow fibers can be concentrated at the center of the end portion. Thereafter, both ends of the hollow fiber bundle may be cut with a cutter or the like so that the hollow fiber membrane fits in the casing, and a mesh or the like for fixing the yarn bundle may be applied to the end portion. Finally, a purification column can be obtained by attaching an inlet port and an outlet port of a processing solution called a header cap.

  Moreover, since it is necessary to sterilize when using for a medical device etc., a radiation is irradiated to the said blood purification column.

Example 1
31.7 parts by weight of syn-PMMA having a weight average molecular weight of 400,000, 31.7 parts by weight of syn-PMMA having a weight average molecular weight of 1.4 million, and 16.7 parts by weight of iso-PMMA having a weight average molecular weight of 500,000 Then, 20 parts by weight of PMMA copolymer having a molecular weight of 300,000 containing 1.5 mol% of parastyrene sulfonic acid soda was mixed with 376 parts by weight of dimethyl sulfoxide, 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. The obtained spinning dope is kept in air at a rate of 2.5 g / min from a double tube hollow fiber membrane die having an outer diameter / inner diameter = 2.1 / 1.95 mmφ of an annular slit portion kept at 93 ° C. Was discharged. Here, nitrogen gas was simultaneously injected into the inner tube portion of the double tube, and the air portion was allowed to travel 50 cm before being led to the coagulation bath. A hollow fiber membrane was obtained by setting the water temperature (coagulation bath temperature) used in the coagulation bath to 42 ° C. After washing each hollow fiber membrane with water and applying glycerin as a 63 wt% aqueous solution as a moisturizing agent, the heat treatment bath temperature was set to 86 ° C. After removing excess glycerin, the spacer yarn was wound and wound at 60 m / min. . The obtained hollow fiber membrane had an inner diameter / film thickness of 200/30 μm.

The obtained hollow fiber membranes are bundled by a known method, and an effective length of about 13,000 hollow fiber membranes is provided in a plastic case which is a cylindrical portion of a purification column having an inner diameter of 40 mm so that an effective membrane area is 1.6 m ² . It loaded so that it might become 5 cm. In addition, on the treatment liquid introduction side of the plastic case, a polycarbonate hollow fiber restraint having a shape shown in FIG. 1 and having a total surface area of the hollow fiber filling portion of 79% of the surface area of the end surface is installed in advance. Were filled in the hollow fiber filling portion 4 in FIG. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did.
Thereafter, a mesh of 40 mm in diameter and 0.5 mm in thickness (fiber diameter: 200 μm, opening: 435 μm) made of polyethylene terephthalate for fixing the yarn bundle to both ends was applied. Finally, a purification column was created by attaching blood inlet and outlet ports called headers. The obtained purification column was washed inside with RO water, and then each port was sealed with a cap, packaged with a film, and γ-irradiated.
About the obtained purification | cleaning column, the clearance measurement of (beta) _2- MG was performed by the method shown below. (1) Measuring method of clearance of β ₂ -MG As a performance evaluation of the adsorption column, the clearance of β ₂ -MG was measured. β ₂ -MG is known to be a causative protein of dialysis amyloidosis, which is a long-term dialysis complication. The clearance of β ₂ -MG was measured as follows.
1. To the bovine plasma obtained by centrifuging anticoagulated bovine blood using ACD-A solution, β ₂ -MG was added to 1 mg / L, and the protein concentration was 6.5 ± 0.5 g / dL. Prepare bovine plasma solution. The bovine plasma was divided into 2 L for circulation and 1.5 L for clearance measurement.
2. The circuit was set as shown in FIG.
3. The Bi circuit inlet is placed in a beaker for circulation containing 2 L (37 ° C.) of bovine blood adjusted as described above, the Bi pump is started at a flow rate of 200 mL / min, and the liquid discharged from the Bo circuit outlet is for 90 seconds. Immediately after the disposal, the Bo circuit outlet was inserted into the circulation beaker to circulate.
4). After 1 hour of circulation, the pump was stopped.
5. The Bi circuit inlet was placed in the clearance-measured bovine blood adjusted as described above, and the Bo circuit outlet was placed in a waste beaker.
6). 2 L of bovine plasma solution is circulated under the conditions of a blood side (inside the hollow fiber membrane) flow rate (QBin) of 200 mL / min and a filtrate flow rate of 10 mL / min / m ² using the closed circulation circuit of FIG.
7). Circulation was stopped, the blood side supply solution was replaced with a fresh bovine plasma solution, and the blood side (inside the hollow fiber membrane) was flowed at a flow rate (QBin) of 200 mL / min using a single pass circuit.
8). Between 4 and 5 minutes after the start of single-pass liquid feeding, 10 ml of blood inlet side liquid and blood outlet side liquid are sampled and used as a sample for measuring β ₂ -MG clearance.
9.4. The β ₂ -MG concentration in each sample is measured using a latex agglutination immunoassay (medical and testing equipment / reagents 26 (2) 127-134, 2003 are available as references). β ₂ -MG clearance is calculated by the following equation. β ₂ -MG clearance = (QBin × CBin−QBout × CBout) / CBin
CBin: concentration of β ₂ -MG on the blood inlet side (mg / L)
CBout: β ₂ -MG concentration on the blood outlet side (mg / L)
QBin: Blood side inlet flow rate (mL / min)
QBout: Blood side outlet flow rate (mL / min)
Example 2
About 13,000 hollow fiber membranes obtained in Example 1 are bundled by a known method so that the effective membrane area of the hollow fiber inner portion is 1.6 m ² and the effective membrane area of the hollow fiber outer portion is 2.0 m ^2. Then, it was loaded into a plastic case which is a cylindrical portion of a blood purifier module having an inner diameter of 40 mm so as to have an effective length of 19.5 cm. In addition, on the treatment liquid introduction side of the plastic case, a polycarbonate hollow fiber restraint having a shape shown in FIG. 1 and having a total surface area of the hollow fiber filling portion of 65% of the surface area of the end surface is installed in advance. Were filled in the hollow fiber filling portion 4 in FIG. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did. Thereafter, a mesh made of polyethylene terephthalate (fiber diameter: 200 μm, opening: 435 μm) having a diameter of 40 mm and a thickness of 0.5 mm for fixing the yarn bundle to both ends was applied. Subsequent steps were in accordance with Example 1.

About the obtained purification column, the clearance measurement of (beta) _2- MG was performed by the method similar to Example 1. FIG.
Example 3
About 13,000 hollow fiber membranes obtained in Example 1 are bundled by a known method so that the effective membrane area of the hollow fiber inner portion is 1.6 m ² and the effective membrane area of the hollow fiber outer portion is 2.0 m ^2. Then, it was loaded into a plastic case which is a cylindrical portion of a blood purifier module having an inner diameter of 40 mm so as to have an effective length of 19.5 cm. In addition, on the treatment liquid introduction side of the plastic case, a hollow fiber restraint made of polycarbonate having a total surface area of the hollow fiber filling portion of 55% of the surface area of the end face is installed in advance as shown in FIG. Were filled in the hollow fiber filling portion 4 in FIG. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did. Thereafter, a mesh made of polyethylene terephthalate (fiber diameter: 200 μm, opening: 435 μm) having a diameter of 40 mm and a thickness of 0.5 mm for fixing the yarn bundle to both ends was applied. Subsequent steps were in accordance with Example 1.

About the obtained purification column, the clearance measurement of (beta) _2- MG was performed by the method similar to Example 1. FIG.
Example 4
About 13,000 hollow fiber membranes obtained in Example 1 are bundled by a known method so that the effective membrane area of the hollow fiber inner portion is 1.6 m ² and the effective membrane area of the hollow fiber outer portion is 2.0 m ^2. Then, it was loaded into a plastic case which is a cylindrical portion of a blood purifier module having an inner diameter of 40 mm so as to have an effective length of 19.5 cm. In addition, on both the treatment liquid introduction side and the discharge side of the plastic case, a polycarbonate hollow fiber restraint having the shape shown in FIG. 1 and having a total surface area of the hollow fiber filling portion of 65% of the surface area of the end surface is previously installed. The hollow fiber bundles were all filled in the hollow fiber filling part 4 in FIG. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did. Thereafter, a mesh made of polyethylene terephthalate (fiber diameter: 200 μm, opening: 435 μm) having a diameter of 40 mm and a thickness of 0.5 mm for fixing the yarn bundle to both ends was applied. Subsequent steps were in accordance with Example 1.

About the obtained purification column, the clearance measurement of (beta) _2- MG was performed by the method similar to Example 1. FIG.
Comparative Example 1
About 13,000 hollow fiber membranes obtained in Example 1 are bundled by a known method so that the effective membrane area of the hollow fiber inner portion is 1.6 m ² and the effective membrane area of the hollow fiber outer portion is 2.0 m ^2. Then, it was loaded into a plastic case which is a cylindrical portion of a blood purifier module having an inner diameter of 40 mm so as to have an effective length of 19.5 cm. At this time, no hollow fiber restraint device was applied to the plastic case. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did. Thereafter, a mesh made of polyethylene terephthalate (fiber diameter: 200 μm, opening: 435 μm) having a diameter of 40 mm and a thickness of 0.5 mm for fixing the yarn bundle to both ends was applied. Subsequent steps were in accordance with Example 1.

About the obtained purification column, the clearance measurement of (beta) _2- MG was performed by the method similar to Example 1. FIG.
Comparative Example 2
About 13,000 hollow fiber membranes obtained in Example 1 are bundled by a known method, and an effective length of 19 is attached to a plastic case which is a cylindrical portion of a blood purifier module having an inner diameter of 40 mm so that an effective membrane area is 1.6 m ^2. It was loaded to be 5 cm. At this time, no hollow fiber restraint device was applied to the plastic case. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did. Thereafter, a mesh of 40 mm in diameter and 0.5 mm in thickness (fiber diameter: 200 μm, opening: 435 μm) made of polyethylene terephthalate for fixing the yarn bundle to both ends was applied. Further, a polyethylene terephthalate film having a diameter of 10 mm and a thickness of 0.3 mm was disposed at the center of the mesh. Subsequent steps were in accordance with Example 1.

About the obtained purification column, the clearance measurement of (beta) _2- MG was performed by the method similar to Example 1. FIG.
Comparative Example 3
About 13,000 hollow fiber membranes obtained in Example 1 are bundled by a known method, and an effective length of 19 is attached to a plastic case which is a cylindrical portion of a blood purifier module having an inner diameter of 40 mm so that an effective membrane area is 1.6 m ^2. It was loaded to be 5 cm. At this time, no hollow fiber restraint device was applied to the plastic case. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did. Thereafter, a mesh of 40 mm in diameter and 0.5 mm in thickness (fiber diameter: 200 μm, opening: 435 μm) made of polyethylene terephthalate for fixing the yarn bundle to both ends was applied. Furthermore, a 10 mm diameter, 0.5 mm thick polyethylene terephthalate 40 mm diameter, 0.5 mm thick mesh (fiber diameter: 200 μm, opening: 435 μm) was applied to the center of the mesh. Subsequent steps were in accordance with Example 1.

About the obtained purification column, the clearance measurement of (beta) _2- MG was performed by the method similar to Example 1. FIG.
Comparative Example 4
About 13,000 hollow fiber membranes obtained in Example 1 are bundled by a known method so that the effective membrane area of the hollow fiber inner portion is 1.6 m ² and the effective membrane area of the hollow fiber outer portion is 2.0 m ^2. Then, it was loaded into a plastic case which is a cylindrical portion of a blood purifier module having an inner diameter of 40 mm so as to have an effective length of 19.5 cm. In addition, on the treatment liquid introduction side of the plastic case, a polycarbonate hollow fiber restraint having a total surface area of the hollow fiber filling portion of 45% of the surface area of the end face is installed in advance as shown in FIG. Were filled in the hollow fiber filling portion 4 in FIG. After cutting both ends of the hollow fiber bundle with a cutter or the like so that the hollow fiber membrane fits in the casing, arbitrarily observe 200 of the column end surface hollow fibers with an optical microscope, and calculate the number of crushed yarns contained therein. did. Thereafter, a mesh made of polyethylene terephthalate (fiber diameter: 200 μm, opening: 435 μm) having a diameter of 40 mm and a thickness of 0.5 mm for fixing the yarn bundle to both ends was applied. Subsequent steps were in accordance with Example 1.

About the obtained purification column, the clearance measurement of (beta) _2- MG was performed by the method similar to Example 1. FIG.

  The results are shown in Table 1.

From the results of Examples 1 to 3 in Table 1, the β ₂ -MG removal performance of the column was increased by applying a hollow fiber restraint device to the end on the side where the treatment liquid was introduced. In addition, when a hollow fiber restraint device in which the total surface area of the hollow fiber packed portion was 45% of the surface area of the end face was installed, the performance was greatly reduced as compared to the column having 55% or more.

  Moreover, from Table 1, the number of crushed yarns could be significantly reduced by using a hollow fiber restraint tool.

DESCRIPTION OF SYMBOLS 1 Casing 2 Hollow fiber restraint device 3 Cavity part 4 Hollow fiber filling part 5 Purification column 6 Bi pump 7 Disposal container 8 Blood for circulation 9 Blood for clearance measurement 10 Bi circuit 11 Bo circuit 12 Di circuit

Claims (5)

The hollow fiber filling portion and the hollow fiber, which are spaces in which the hollow fiber is tightly filled, are fixed by fixing the hollow fiber at the end of the cylindrical casing in which the hollow fiber is incorporated, which satisfies the following items: Hollow fiber restraint means that separates into two different spaces of a sparse void.
(A) The hollow fiber filling portion is disposed apart from the inner peripheral surface of the casing, and the gap portion exists between the casing inner peripheral surface and the hollow fiber filling portion (b) of the hollow fiber filling portion. The total surface area is 50% or more of the surface area of the casing end surface. (C) The hollow fiber is not fixed to either the means or the casing by adhesion.   The hollow fiber restraint means according to claim 1, wherein the hollow fiber filling portion separated by the hollow fiber restraint means is one continuous space in its cross section.   A purification column having a cylindrical casing, in which a hollow fiber is built in the casing, and the hollow fiber restraining means according to claim 1 or 2 provided on only one end face of the casing.   The purification column according to claim 3, wherein an end surface of the casing provided with the hollow fiber restraining means is an end surface on the introduction side of the processing liquid.   The purification column according to claim 3 or 4, which is used as a blood purifier.

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