JP2023154449A - Body cavity fluid treatment device and concentrator - Google Patents

Abstract

To provide an ascites treatment device which, when filtered ascites is concentrated, is capable of suppressing increase in a transmembrane pressure difference of a hollow fiber membrane and recovering proteins in the ascites at a high recovery rate.SOLUTION: A concentrator 12 of an ascites treatment device 1 is configured to concentrate filtered ascites through a hollow fiber membrane consisting of a plurality of hollow fibers, where the hollow fiber membrane has a membrane area of 1.6 m2 or more and 2.9 m2 or less. When the ascites is concentrated under the conditions of an inlet-side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5±2 g/dL, a linear velocity of each hollow fiber is 2.2 m/hr or more and 3.8 m/hr or less, and when 6 L of the ascites is treated under the forementioned conditions, the transmembrane pressure difference of the hollow fiber membrane is maintained at 500 mmHg or less, and the recovery rate of proteins is 85% or more.SELECTED DRAWING: Figure 1

Description

The present invention relates to a body cavity fluid treatment device and a concentrator.

In recent years, treatment using Cell-free and Concentrated Ascites Reinfusion Therapy has been increasing for patients with liver cirrhosis and cancer. In the ascites filtration concentration re-infusion method, ascites is collected from a patient, filtered to remove cellular components such as cancer cells and bacteria present in the ascites, and then removed from the ascites, such as albumin, present in the ascites. The treatment involves concentrating the necessary proteins, collecting them, and then reinjecting them into the patient's body.

For such treatment, an ascites treatment device is usually used, and the ascites treatment device includes, for example, a storage container for storing ascites, a filtration filter (filter), a concentration filter (concentrator), and a collection container in this order. It has a configuration in which it is connected in series (see Patent Document 1). Filters using hollow fiber membranes are generally used for filters and concentrators.

Patent No. 5856821

By the way, in the above-mentioned ascites treatment apparatus, so-called high-speed processing is required in which a large amount of ascites can be filtered, concentrated, and recovered in a short period of time. However, ascites is high in protein and highly viscous. For this reason, in the conventional ascites treatment apparatus, when the processing flow rate for concentration is increased in the concentrator, the intermembrane pressure difference of the hollow fiber membrane increases immediately after the start of the treatment, reaches the upper limit pressure, and the treatment stops. Furthermore, it becomes difficult to recover the necessary proteins in ascites with a high recovery rate.

The present application has been made in view of these points, and is capable of suppressing an increase in the intermembrane pressure difference of a hollow fiber membrane when concentrating body cavity fluid such as filtered ascites, and which is The object of the present invention is to provide a body cavity fluid processing device and a concentrator that can recover proteins with a high recovery rate.

The present inventors solved the above problem by optimizing the membrane area of the hollow fiber membrane of the concentrator and the linear velocity of the hollow fiber, thereby suppressing the increase in the intermembrane pressure difference of the hollow fiber membrane and increasing the protein content in the body cavity fluid. It was discovered that it could be recovered at a good recovery rate, and the present invention was completed.
That is, aspects of the present invention include the following.
(1) A body cavity fluid processing device, which includes a first storage section that stores body cavity fluid, a filter that filters body cavity fluid, a concentrator that concentrates filtered body cavity fluid, and a body cavity fluid that collects concentrated body cavity fluid. a second storage section that stores the body cavity fluid, a first line that supplies the body cavity fluid in the first storage section to the filter, and a second line that supplies the body cavity fluid filtered by the filter to the concentrator. a third line that supplies the body cavity fluid concentrated by the concentrator to the second storage section, and a fourth line that discharges the separated fluid separated from the body cavity fluid by the concentrator. The concentrator is for concentrating the filtered body cavity fluid through a hollow fiber membrane consisting of a plurality of hollow fibers, and the hollow fiber membrane has a membrane area of 1.6 m ² or more and 2.9 m ² or less. , when the body cavity fluid is concentrated under the conditions that the inlet flow rate is 100 mL/min, the concentration ratio is 5 times, and the protein concentration is 5 ± 2 g/dL, the linear velocity of each of the hollow fibers is 2.2 m/hr or more 3.8 m/hr or less, and when 6 L of the body cavity fluid is processed under the above conditions, the intermembrane pressure difference of the hollow fiber membrane is maintained at 500 mmHg or less, and the protein recovery rate is 85% or more. A body cavity fluid treatment device consisting of:
(2) When the transmembrane pressure difference when processing 1L of body cavity fluid is A, the transmembrane pressure difference when processing 3L is B, and the transmembrane pressure difference when processing 6L is C, the concentrator The body cavity fluid treatment device according to (1), wherein B/A≦1.5 and C/A≦1.5 are satisfied.
(3) The body cavity fluid treatment device according to (1) or (2), wherein the hollow fiber membrane has 10,000 or more hollow fibers and has a length of 400 mm or less.
(4) The hollow fiber membrane is any one of polysulfone-based polymers, cellulose-based polymers, polyacrylic acid-based polymers, and polymethacrylic acid-based polymers, according to any one of (1) to (3). The body cavity fluid treatment device described in .
(5) A concentrator for concentrating filtered body cavity fluid through a hollow fiber membrane consisting of a plurality of hollow fibers, wherein the hollow fiber membrane has a membrane area of 1.6 m ² or more and 2.9 m ² or less, and the inlet 3. When the body cavity fluid is concentrated under the conditions of a side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5±2 g/dL, the linear velocity of each of the hollow fibers is 2.2 m/hr or more.3. 8 m/hr or less, and when 6 L of the body cavity fluid is processed under the conditions, the intermembrane pressure difference of the hollow fiber membrane is maintained at 500 mmHg or less, and the protein recovery rate is 85% or more. ing,
Concentrator.

According to the present invention, it is possible to suppress an increase in the intermembrane pressure difference of a hollow fiber membrane when concentrating filtered body cavity fluid, and it is also possible to recover proteins in body cavity fluid with a high recovery rate. It is possible to provide a body cavity fluid processing device and a concentrator that can perform the following.

It is an explanatory view showing an outline of an example of composition of an ascites treatment device. FIG. 2 is a schematic vertical cross-sectional view showing an example of a filter. It is a table showing experimental results of Examples.

Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings. Note that the positional relationships such as the top, bottom, left, and right of the drawings are based on the positional relationships shown in the drawings, unless otherwise specified. The dimensional ratios in the drawings are not limited to the illustrated ratios. Furthermore, the following embodiments are illustrative for explaining the present invention, and the present invention is not intended to be limited only to the embodiments. Further, the present invention can be modified in various ways without departing from the gist thereof.

FIG. 1 is an explanatory diagram schematically showing the configuration of an ascites treatment device 1 as a body cavity fluid treatment device according to the present embodiment.

As shown in FIG. 1, the ascites treatment device 1 includes, for example, a first container 10 as a first storage section, a filter 11, a concentrator 12, and a second container 13 as a second storage section. , a first line 14, a second line 15, a third line 16, a fourth line 17, a fifth line 18, a control device 19, etc.

The first container 10 is a container made of a soft resin such as polyvinyl chloride, and can contain ascites collected from a patient. The first container 10 has a capacity of, for example, 1 L or more, preferably 3 L or more, and more preferably 6 L or more.

The filter 11 is, for example, a hollow fiber membrane type filter. For example, the filter 11 has a cylindrical container 20, and inside the cylindrical container 20, a hollow fiber membrane 22 consisting of a large number of hollow fibers 21 is arranged along its longitudinal direction. The hollow fiber membrane 22 can separate cellular components such as cancer cells and bacteria from the protein solution of ascites. The upper and lower parts of the cylindrical container 20 are provided with entrances and exits 23 and 24 that communicate with the inner space of the hollow fiber membrane 22, and the side surfaces of the cylindrical container 20 are provided with two ports that communicate with the outer space of the hollow fiber membrane 22. Entrances and exits 25 and 26 are provided. The entrance/exit 26 communicates with the second line 15, and the entrance/exit 25 is closed. The inlet/outlet 24 communicates with the first line 14 and the inlet/outlet 23 communicates with the fifth line 18 . Note that "upper" and "lower" in this embodiment are based on the installation example of the ascites treatment apparatus 1 shown in FIG.

The first line 14 is a flexible tube made of polyvinyl chloride, for example. A first end 14a of the first line 14 is connected to the first container 10, and a second end 14b is connected to the filter 11. In this embodiment, the second end 14b is connected to an inlet/outlet 24 that communicates with the inner space of the hollow fiber membrane 22 at the lower side of the filter 11. The first line 14 is provided with, for example, a tube pump 30, and the tube pump 30 can send the ascites in the first container 10 to the filter 11. Note that the ascites in the first container 10 may be supplied to the filter 11 by falling by gravity without providing the tube pump 30 in the first line 14.

The concentrator 12 is a hollow fiber membrane type filter. For example, the concentrator 12 has a cylindrical container 50, and inside the cylindrical container 50, a hollow fiber membrane 52 consisting of a large number of hollow fibers 51 is arranged along its longitudinal direction. The upper and lower parts of the cylindrical container 50 are provided with ports 53 and 54 that communicate with the inner space of the hollow fiber membrane 52, and the side surfaces of the cylindrical container 50 are provided with two ports that communicate with the outer space of the hollow fiber membrane 52. Entrances and exits 55 and 56 are provided. The inlet/outlet 53 communicates with the second line 15 and the inlet/outlet 54 communicates with the third line 16. The entrance/exit 55 communicates with the fourth line 17, and the entrance/exit 56 is closed.

FIG. 2 is a schematic vertical cross-sectional view showing an example of the configuration of the concentrator 12. The hollow fiber membranes 52 are arranged in a cylindrical bundle at the center inside the cylindrical container 50. Both upper and lower ends of the hollow fiber membrane 52 are fixed to the inner wall surface of the cylindrical container 50 with a potting material 60 made of curable resin. For example, the inside of the cylindrical container 50 has an upstream space R1 facing the opening end 51a of the hollow fiber 51 of the hollow fiber membrane 52 and the entrance/exit 53, and an upstream space R1 facing the opening end 51b of the hollow fiber 51 of the hollow fiber membrane 52 and the entrance/exit 54. It has a facing downstream space R2, an intratubular space R3 inside the hollow fibers 51 of the hollow fiber membrane 52, and an extratubular space R4 outside the hollow fibers 51 of the hollow fiber membrane 52. The extravascular space R4 is formed around the outer periphery of the hollow fiber membrane 52 and communicates with the entrances and exits 55 and 56. The extravascular space R4, the upper space R1, and the lower space R2 are partitioned by a potting material 60.

The concentrator 12 uses an optimal hollow fiber membrane 52 to suppress an increase in the pressure difference between the hollow fiber membranes 52 when concentrating ascites and to recover proteins in ascites at a high recovery rate. It has an area and a linear velocity of the hollow fiber 51. The hollow fiber membrane 52 has an (effective) membrane area of 1.6 m ² or more and 2.9 m ² or less. The concentrator 12 has a linear velocity of each hollow fiber 51 of 2.2 m when ascites is concentrated under conditions 1: the inlet flow rate is 100 mL/min, the concentration ratio is 5 times, and the protein concentration is 5 ± 2 g/dL. /hr or more and 3.8m/hr or less, and when 6L of ascites is treated under the same conditions 1, the intermembrane pressure difference of the hollow fiber membrane 52 is maintained at 500 mmHg or less, and the protein recovery rate is 85% or more. It is configured as follows. Note that the inlet side flow rate is the flow rate of ascites at the inlet (inlet/outlet 53) of the concentrator 12.

The membrane area S of the hollow fiber membrane 52 is calculated by the following formula.
Membrane area S = (inner diameter d x π of hollow fiber 51) x (distance L1 between open ends 51a and 51b of hollow fiber 51) x (number of hollow fibers 51)

The linear velocity V of each hollow fiber 51 is calculated by the following formula.
Linear velocity V (m/hr) = (processing flow rate (m ³ /hr)) / (opening area (m ² ))
Opening area (m ² ) = ((inner diameter d/2 of hollow fiber 51)^2×π)×(number of hollow fibers 51)
Here, the processing flow rate is the rate of ascites flowing within the hollow fiber membrane 52.

The transmembrane pressure difference (TMP) of the hollow fiber membrane 52 is the difference between the pressure in the inner tube space R3 of the hollow fiber membrane 52 and the pressure in the outer tube space R4 of the hollow fiber membrane 52. The transmembrane pressure difference (TMP) of the hollow fiber membrane 52 is calculated by the following formula.
Transmembrane pressure difference (TMP) = ((Pressure on the inlet side of the concentrator 12) + (Pressure on the outlet side of the concentrator 12))/2 - (Pressure on the drainage side)

In the concentrator 12, under condition 1, when the transmembrane pressure difference when treating 1 L of ascites is A, the transmembrane pressure difference when treating 3 L is B, and the transmembrane pressure difference when treating 6 L is C. It is configured to satisfy the following formula.
B/A≦1.5, C/A≦1.5
Note that C/A≦1.3 may be satisfied.

For example, the number of hollow fibers 51 in the hollow fiber membrane 52 is 10,000 or more, or 13,000 or more. The effective length L1 of the hollow fibers 51 is 400 mm or less, preferably 300 mm or less. The inner diameter of the hollow fiber 51 is 100 μm or more, preferably 185 μm or more, and more preferably 185 μm or more and 300 μm or less. By setting the inner diameter of the hollow fibers 51 to 100 μm or more, it is possible to prevent the number of hollow fibers 51 from increasing too much in order to secure the membrane area, and also to reduce the amount of ascites that remains in the hollow fibers 51 at the end of the treatment and cannot be recovered. can be reduced. Since the inner diameter of the hollow fibers 51 is 300 μm or less, the hollow fibers 52 can be stably manufactured. The overall outer diameter (diameter) D1 (shown in FIG. 2) of the hollow fiber membrane 52 is 30 mm or more, and the ratio (D1/L1) of the overall outer diameter D1 to the effective length L1 is 0.10 or more. be.

For example, as the material for the hollow fiber membrane 52, any one of polysulfone-based polymers, cellulose-based polymers, polyacrylic acid-based polymers, and polymethacrylic acid-based polymers is used.

For example, the hollow fibers 51 of the concentrator 12 have a pore diameter (wall pore diameter) such that the sieving coefficient of polyvinylpyrrolidone (PVP) of the hollow fibers 51 (hereinafter referred to as "PVP-K30 sieving coefficient") is 30% to 50%. have PVP-K30 indicates that a product with a molecular weight of K30 was used. The PVP-K30 sieving coefficient is calculated by dissolving PVP-K30 in 1/15M phosphate buffer (pH 7.0) to a concentration of 3% and flowing it inside the hollow fiber membrane to obtain the transmembrane pressure (TMP). This is the sieving coefficient after 20 minutes of filtering while applying 200 [mmHg]. The PVP-K30 sieving coefficient was measured at absorbance at 280 [nm].
The PVP-K30 sieving coefficient is calculated by the following formula.
PVP-K30 sieving coefficient = (absorbance of separated liquid after passing through the hollow fiber) / (absorbance of ascites before passing through the hollow fiber (wavelength 280 nm)) x 100 (%)

For example, the concentrator 12 (hollow fiber membrane 52) has an ultrafiltration performance of 85 mL/min/200 mmHg or more and 200 mL/min/200 mmHg or less.

Ultrafiltration performance is defined by tests such as those shown below. Bovine plasma with a protein concentration adjusted to 6 g/dL is prepared and fed to a concentrator at a constant rate of 200 mL/min using a roller pump. At this time, the outlet (the inlet/outlet 55 in this embodiment) on the drainage side (the side from which the separated liquid is discharged) of the concentrator is left open. Pressure is applied to the circuit connected to the outlet (inlet/outlet 54 in this embodiment) of the recovered liquid discharge side of the concentrator (the side from which the separated recovered liquid is discharged), and The transmembrane pressure difference (TMP) between the inner tube space R3 and the extra tube space R4 of the hollow fiber membrane is adjusted to 200 mmHg. At this time, the volume per unit time of the separated liquid discharged from the outlet on the drainage side is measured, and that value is defined as the critical filtration performance.

The second line 15 shown in FIG. 1 is a flexible tube, such as polyvinyl chloride. The first end 15a of the second line 15 is connected to an inlet/outlet 26 communicating with the extraluminal space of the hollow fiber membrane 22 in the upper part of the filter 11. The second end 15b of the second line 15 is connected to an inlet/outlet 53 communicating with the pipe interior space R3 of the hollow fiber membrane 52 in the upper part of the concentrator 12. The second line 15 is provided with, for example, a tube pump 80 , and the tube pump 80 can send the filtered ascites from the second line 15 to the concentrator 12 . Note that the ascites in the second line 15 may be supplied to the concentrator 12 by falling by gravity without providing the tube pump 80 in the second line 15.

The second container (recovery container) 13 is a container made of a soft resin such as polyvinyl chloride, and stores the protein solution (recovery liquid) containing the necessary protein concentrated in the concentrator 12. I can do it.

The third line 16 is a flexible tube, such as polyvinyl chloride. The first end 16a of the third line 16 is connected to an inlet/outlet 54 that communicates with the inner tube space R3 of the hollow fiber membrane 52 in the lower part of the concentrator 12. The second end 16b of the third line 16 is connected to the second container 13.

The fourth line 17 is a flexible tube made of polyvinyl chloride, for example. The first end 17a of the fourth line 17 is connected to an inlet/outlet 55 of the hollow fiber membrane 52 at the lower side of the concentrator 12, which communicates with the extravascular space R4. The second end of the fourth line 17 is connected to a waste liquid section (not shown) of the liquid separated from ascites.

The fifth line 18 is a flexible tube, such as polyvinyl chloride. The first end 18a of the fifth line 18 is connected to an inlet/outlet 23 that communicates with the pipe interior space of the hollow fiber membrane 22 at the upper side of the filter 11. The second end of the fifth line 18 is connected to a waste fluid section (not shown) for waste fluid containing cellular components separated from ascites fluid.

The control device 19 is, for example, a computer, and controls the operation of the tube pumps 30 and 80 by, for example, executing a program recorded in a recording unit on a CPU, and adjusts the ascites treatment flow rate, ascites concentration ratio, etc. can do. Note that when ascites is treated using a head, the ascites treatment device 1 does not need to include the control device 19.

Next, a method of operating the ascites treatment device 1 and a method of treating ascites will be explained.

First, the first container 10 containing, for example, 6 L or more of ascites collected from a patient is connected to the first line 14. For example, ascites is cancerous ascites collected from cancer patients, and is a highly concentrated protein solution containing cellular components such as cancer cells and bacteria. Ascites contains necessary proteins such as albumin and unnecessary proteins such as cytokines. Ascites includes those having protein concentrations of 0.5 g/dL or more, 1.0 g/dL or more, 2.0 g/dL or more, and 2.5 g/dL or more.

Next, the tube pumps 30 and 80 are activated, and the ascites contained in the first container 10 is supplied to the intraluminal space of the hollow fiber membrane 22 from the inlet/outlet 24 of the filter 11 through the first line 14. . Ascites flows from the intraluminal space of the hollow fiber membrane 22 to the extraluminal space through the hollow fiber membrane 22, and at this time, cellular components such as cancer cells and bacteria present in the ascites are separated. Ascitic fluid (filtered ascites) that has passed through the hollow fiber membrane 22 flows out from the inlet/outlet 26 of the filter 11 , passes through the second line 15 , and enters the tube space of the hollow fiber membrane 52 from the inlet/outlet 53 of the concentrator 12 . Supplied to R3.

When filtered ascites flows into the tube space R3 of the hollow fiber membrane 52 of the concentrator 12, water containing unnecessary proteins such as cytokines passes through the hollow fiber membrane 52 and is separated from the ascites. It flows out into the outside space R4. The water and proteins (separated liquid) that have flowed out into the extravascular space R4 of the hollow fiber membrane 52 flow out from the inlet/outlet 55 of the concentrator 12, and are discharged through the fourth line 17 to the waste liquid section. For example, this concentration process is performed at a high flow rate such that the inlet side flow rate in the concentrator 12 is 50 mL/min or more, 100 mL/min or more, 150 mL/min or more, or 200 mL/min or more. Further, the concentration process is performed at a high concentration ratio of 5 times or more.

The ascites (recovered fluid) from which water and unnecessary proteins have been removed in the tube space R3 of the hollow fiber membrane 52 of the concentrator 12 flows out from the inlet/outlet 54 of the concentrator 12 and flows through the third line 16 to the second container 13. will be collected. This recovered solution contains many necessary proteins such as albumin.

According to this embodiment, the concentrator 12 has a hollow fiber membrane 52 with a membrane area of 1.6 m ² or more and 2.9 m ² or less, an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein When ascites was concentrated under condition 1 with a concentration of 5±2 g/dL, the linear velocity of each hollow fiber 51 was 2.2 m/hr or more and 3.8 m/hr or less, and 6 L of ascites was treated under condition 1. Sometimes, the pressure difference between the hollow fiber membranes 52 is maintained at 500 mmHg or less, and the protein recovery rate is 85% or more. According to the inventor's findings, in order to increase the flow rate in the hollow fiber membrane 52 of the concentrator 12, it is possible to increase the membrane area, but it is not enough to simply increase the membrane area. If the membrane area is increased too much, the amount of ascites remaining in the hollow fibers 51 after the treatment is completed increases, and the recovery rate decreases. Then, in order to design the optimum amount of increase in membrane area for the target flow rate in the hollow fiber membrane 52, we realized that the linear velocity functions as a parameter. According to the concentrator 12 having such a configuration, by increasing the membrane area of the hollow fiber membrane 52 and adjusting the linear velocity of the hollow fiber 51 to an optimal range, the hollow fiber membrane 52 can be increased when concentrating filtered ascites. It is possible to suppress an increase in the transmembrane pressure difference, and to recover proteins in ascites at a high recovery rate. As a result, so-called high-speed processing, in which ascites can be filtered, concentrated, and recovered in a short period of time, can be realized.

When the transmembrane pressure difference when 1L of ascites is processed is A, the transmembrane pressure difference when 3L is processed is B, and the transmembrane pressure difference when 6L is processed is C, the concentrator 12 has B/A≦. 1.5, and C/A≦1.5. Since the concentrator 12 can sufficiently suppress the increase in the pressure difference between the hollow fiber membranes 52, a large amount of ascites can be treated in a short time.

The hollow fiber membrane 52 has 10,000 or more hollow fibers 51 and has a length L1 of 400 mm or less. Thereby, the membrane area of the hollow fiber membrane 52 and the linear velocity of the hollow fiber 51 in the concentrator 12 can be suitably adjusted.

Although preferred embodiments of the present invention have been described above with reference to the accompanying drawings, the present invention is not limited to such examples. It is clear that those skilled in the art can come up with various changes or modifications within the scope of the idea described in the claims, and these naturally fall within the technical scope of the present invention. It is understood that

For example, the configuration of the ascites treatment apparatus 1 in the above embodiment is not limited to this, and may have other configurations. For example, the pump may be provided not only in the first line 14 and the second line 15 but also in other channels such as the third line 16. Further, the pump may be provided only in the first line 14, only in the second line 15, or only in the third line 16. The fourth line 17 may be provided with a negative pressure generator. Furthermore, when sending ascites from the first container 10 to the second container 13, the head pressure may be used instead of using a pump. In FIG. 1, the first line 14 is connected to the inlet/outlet 23 of the filter 11, the second line 15 is connected to the inlet/outlet 25 of the filter 11, and the fifth line 18 is connected to the inlet/outlet 24 of the filter 11. You can leave it there. The filtration method of the ascites treatment device 1 may be an external pressure filtration method or an internal pressure filtration method. In the case of the external pressure filtration method, for example, the first line 14 is connected to the inlet/outlet 25 of the filter 11, the second line 15 is connected to the inlet/outlet 23 of the filter 11, and ascites is passed from the inside of the hollow fiber membrane 22 to the outside. It may be allowed to pass. The present invention is not limited to the treatment of ascites fluid, but can also be applied to the treatment of other body cavity fluids such as pleural effusion and pericardial fluid.

Below, an experiment was conducted to confirm that the present invention suppresses an increase in the intermembrane pressure difference of a hollow fiber membrane during concentration of ascites and achieves a high protein recovery rate.

<Experimental method>
6 L of simulated ascites was prepared with the protein concentration adjusted to 5 g/dL and the albumin concentration adjusted to 2.7 g/dL. The simulated ascites was adjusted as follows. We created simulated ascites using bovine blood. First, bovine blood to which heparin sodium injection (10,000 units/1 L of bovine blood) has been added as an anticoagulant is centrifuged to obtain plasma layer, red blood cell layer, and buffy coat layer solutions, which are collected separately. Plasma was obtained by this. Next, the plasma was filtered through a filter (ascites filter AHF-MO-W, manufactured by Asahi Kasei Medical Corporation), and then mixed with physiological saline to achieve a protein concentration of 5 (g/dL) and an albumin concentration of 2. 7 (g/dL), and 6 L of the original solution, which is pseudo ascites, was prepared. Since this simulated ascites can be regarded as having no cellular components that have passed through the filter, the method was performed without using a filter. The flow rate of the pump was adjusted so that 6 L of simulated ascites was introduced into the concentrator at a rate of 100 mL per minute, and the collected liquid was collected into the collection container at a rate of 20 mL per minute (water removal liquid was removed at a rate of 80 mL per minute). , the simulated ascites was concentrated five times. The transmembrane pressure difference when 1L of the original solution was processed was designated as A, the transmembrane pressure difference when 3L was processed was designated as B, and the transmembrane pressure difference when 6L was processed was designated as C. The protein concentration of the recovery liquid collected in the recovery container (recovery liquid TP concentration) was measured, and the protein recovery rate was calculated.
Protein recovery rate = (amount of protein in the recovered solution) / (amount of protein in the original solution) x 100 (%)
The various conditions and results of the experiment are shown in the table of FIG.

(Example 1)
When the membrane area of the hollow fiber membrane of the concentrator is 2.6 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 2.48 m/hr. When 6 L of ascites was treated, the transmembrane pressure of the hollow fiber membrane was 141 mmHg, and the protein recovery rate was 91%. In addition, in the table of FIG. 3, the case where the transmembrane pressure difference of the hollow fiber membrane reaches the upper limit pressure of 500 mmHg before completing the treatment of 6L of ascites is indicated by "×", and the case where the transmembrane pressure difference of the hollow fiber membrane reaches the upper limit pressure of 500 mmHg is indicated by A case where treatment of 6 L of ascites was completed before reaching the upper limit pressure of 500 mmHg was indicated as "○". In addition, those whose protein recovery rate was less than 85% were indicated as "×".

(Example 2)
When the membrane area of the hollow fiber membrane of the concentrator is 2.2 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 2.92 m/hr. When 6 L of ascites was treated, the transmembrane pressure of the hollow fiber membrane was 210 mmHg, and the protein recovery rate was 89%.

(Example 3)
When the membrane area of the hollow fiber membrane of the concentrator is 1.8 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 3.60 m/hr. When 6 L of ascites was treated, the transmembrane pressure of the hollow fiber membrane was 373 mmHg, and the protein recovery rate was 86%.

(Example 4)
When the membrane area of the hollow fiber membrane of the concentrator is 2.6 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 2.91 m/hr. When 6 L of ascites was treated, the transmembrane pressure of the hollow fiber membrane was 215 mmHg, and the protein recovery rate was 85%.

(Comparative example 1)
When the membrane area of the hollow fiber membrane of the concentrator is 1.5 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 4.20 m/hr. The transmembrane pressure of the hollow fiber membrane when treating 1 L of ascites was 400 mmHg, and the treatment was stopped when the upper limit pressure of 500 mmHg was reached before treating 6 L of ascites.

(Comparative example 2)
When the membrane area of the hollow fiber membrane of the concentrator is 3.0 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 2.12 m/hr. When 6 L of ascites was treated, the transmembrane pressure of the hollow fiber membrane was 102 mmHg, but the protein recovery rate was 83%.

(Comparative example 3)
When the membrane area of the hollow fiber membrane of the concentrator is 2.6 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 3.83 m/hr. The transmembrane pressure of the hollow fiber membrane when treating 3 L of ascites was 430 mmHg, and the treatment was stopped when the upper limit pressure of 500 mmHg was reached before treating 6 L of ascites.

(Comparative example 4)
When the membrane area of the hollow fiber membrane of the concentrator is 3.0 m ² and ascites is concentrated under the conditions of an inlet side flow rate of 100 mL/min, a concentration ratio of 5 times, and a protein concentration of 5 ± 2 g/dL, Each hollow fiber had a linear velocity of 2.64 m/hr. The transmembrane pressure of the hollow fiber membrane when 1 L of ascites was treated was 440 mmHg, and the treatment was stopped when the upper limit pressure of 500 mmHg was reached before 6 L of ascites was treated.

The present invention provides a body cavity that can suppress an increase in the intermembrane pressure difference of a hollow fiber membrane when concentrating filtered body cavity fluid, and can recover proteins in body cavity fluid with a high recovery rate. It is useful in providing liquid processing devices and concentrators.

1 Ascites treatment device 10 First container 11 Filter 12 Concentrator 51 Hollow fiber 52 Hollow fiber membrane 13 Second container 14 First line 15 Second line 16 Third line 17 Fourth line

Claims (5)

A body cavity fluid treatment device, comprising:
a first storage section that stores body cavity fluid;
a filter that filters body cavity fluid;
a concentrator for concentrating the filtered body cavity fluid;
a second storage section that stores concentrated body cavity fluid;
a first line that supplies body cavity fluid in the first reservoir to the filter;
a second line that supplies the body cavity fluid filtered by the filter to the concentrator;
a third line that supplies the body cavity fluid concentrated in the concentrator to the second storage section;
a fourth line for discharging the separated liquid separated from the body cavity fluid by the concentrator,
The concentrator includes:
The filtered body cavity fluid is concentrated through a hollow fiber membrane consisting of multiple hollow fibers,
The hollow fiber membrane has a membrane area of 1.6 m ² or more and 2.9 m ² or less, the inlet side flow rate is 100 mL/min, the concentration ratio is 5 times, and the protein concentration is 5 ± 2 g/dL. When concentrating, the linear velocity of each of the hollow fibers becomes 2.2 m/hr or more and 3.8 m/hr or less, and when 6 L of the body cavity fluid is treated under the above conditions, the intermembrane The pressure difference is maintained at 500 mmHg or less, and the protein recovery rate is 85% or more.
Body cavity fluid processing device. When the transmembrane pressure difference when 1L of body cavity fluid is processed is A, the transmembrane pressure difference when 3L is processed is B, and the transmembrane pressure difference when 6L is processed is C,
The body cavity fluid treatment device according to claim 1, wherein the concentrator is configured so that B/A≦1.5 and C/A≦1.5. The body cavity fluid treatment device according to claim 1 or 2, wherein the hollow fiber membrane has 10,000 or more hollow fibers and has a length of 400 mm or less. The body cavity fluid treatment device according to claim 1 or 2, wherein the hollow fiber membrane is any one of a polysulfone polymer, a cellulose polymer, a polyacrylic acid polymer, and a polymethacrylic acid polymer. A concentrator that concentrates filtered body cavity fluid through a hollow fiber membrane consisting of a plurality of hollow fibers,
The hollow fiber membrane has a membrane area of 1.6 m ² or more and 2.9 m ² or less, the inlet side flow rate is 100 mL/min, the concentration ratio is 5 times, and the protein concentration is 5 ± 2 g/dL. When concentrating, the linear velocity of each of the hollow fibers becomes 2.2 m/hr or more and 3.8 m/hr or less, and when 6 L of the body cavity fluid is treated under the above conditions, the intermembrane The pressure difference is maintained at 500 mmHg or less, and the protein recovery rate is 85% or more.
Concentrator.

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