TW202128233A - Ascites filtration concentrator - Google Patents

Abstract

The present invention provides an ascites filtration concentrator which can concentrate a large amount of ascitic fluid that contains high protein into a high-concentration protein solution with essential proteins and collect the solution, and reduce the collection rate of unnecessary proteins in the ascitic fluid.

The ascites filtration concentrator 1 of the present invention comprises: a storage container 10; a filtration filter 11; a cellulose-based hollow-fiber-membrane-type concentration filter 12 with an ultrafiltration performance ranging from 85mL/min/200mmHg to 300mL/min/200mmHg; a collection vessel 13 for collecting the protein solution concentrated by the concentration filter 12; the first flow path 14, where the first end connects the storage container 10 and the second end connects the inlet of the filtration filter 11; the second flow path 15, where the first end connects the outlet on the filtration-side of the filtration filter 11 and the second end connects the inlet of the concentration filter 12; the third flow path 16, where the first end connects the outlet of the concentration filter 12 and the second end connects the collection vessel 13; and the fourth flow path 17, which connects the outlet on the discharge-side of the concentration filter 12.

Description

Ascites filtration and concentration device

The invention relates to a device for filtering and concentrating ascites.

In recent years, the use of ascites filtration and concentration and then intravenous injection (Cell-free and Concentrated Ascites Reinfusion Therapy) treatment for patients with liver cirrhosis and cancer is increasing. Ascites filtration and concentration followed by intravenous injection method is to take ascites from the patient, filter the ascites and remove the cell components such as cancer cells and bacteria in the protein solution of the ascites, then concentrate and recover the protein solution containing necessary proteins such as albumin , And then inject the treatment into the patient's body.

Such a treatment method usually uses an ascites filtration and concentration device; the ascites filtration and concentration device, for example, has the following configuration: a storage container for storing ascites, a filter for filtration, a filter for concentration, and a recovery container are connected in series in sequence (see Patent Literature 1). Generally, a hollow fiber membrane type filter is used for a filter for filtration and a filter for concentration.

【Prior Technical Literature】

【Patent Literature】

[Patent Document 1] Japanese Invention Patent No. 5856821

However, the above-mentioned ascites filtration and concentration device needs to concentrate a large amount of high-protein ascites into a high-concentration protein solution containing necessary proteins such as albumin and recover it. However, in this case, the filter for concentration is easy to be clogged. In particular, cancerous ascites in cancer patients is highly viscous due to its high protein content. Therefore, it is easy to be clogged with a filter for concentration, and it is difficult to concentrate a large amount of ascites to a high concentration.

In addition, ascites contains useless proteins such as cytokines that may have an adverse effect on the patient's physical condition. The concentration filter of the ascites filtration and concentration device is ideal to remove this useless protein as much as possible to reduce the recovery rate of the useless protein to the recovery container. However, in the case of using the conventionally known polymeric hollow fiber membrane type concentrating filter to process high-protein and large amounts of ascites, the recovered liquid will also contain a large amount of useless protein.

The present invention was completed in view of this situation. One of its objectives is to provide an ascites filtration and concentration device that can concentrate a large amount of high-protein ascites into a high-concentration protein solution containing necessary proteins and recover it, and can reduce the uselessness of ascites. The recovery rate of the protein.

The present inventors found that the above-mentioned problems can be solved by using a cellulose hollow fiber membrane type concentrating filter with an ultrafiltration performance of 85 mL/min/200 mmHg or more and 300 mL/min/200 mmHg or less, thereby completing the present invention.

That is, the present invention includes the following aspects.

(1) A device for filtering and concentrating ascites, which is characterized by:

Storage container, which stores ascites;

The hollow fiber membrane filter is used to separate the cell components in the protein solution of the ascites fluid in the storage container;

The cellulose hollow fiber membrane type concentrating filter can concentrate the protein solution filtered by the filtering filter, and the ultrafiltration performance is 85mL/min/200mmHg or more and 300mL/min/200mmHg or less;

The recovery container is to recover the protein solution concentrated by the concentration filter;

The first channel is connected to the storage container at the first end, and connected to the inlet of the filtering filter at the second end;

The second channel is the first end connected to the outlet of the filtering side of the filter, and the second end is connected to the inlet of the concentrating filter;

The third channel is connected to the outlet of the concentrating filter at the first end, and connected to the recovery container at the second end; and

The fourth channel is connected to the outlet on the drain side of the thickening filter.

(2) The ascites filtration and concentration device according to (1), wherein the concentration filter is configured such that the linear velocity of the hollow fiber membrane is 2.8 m/hr or less when the protein solution is concentrated 5 times at 50 mL/min.

(3) The ascites fluid filtering and concentrating device according to (1) or (2), wherein the hollow fiber membrane of the concentrating filter has a thickness of 45 μm or less.

(4) The ascites filtering and concentrating device according to (1) or (2), wherein the hollow fiber membrane of the concentrating filter has a thickness of 30 μm or less.

(5) The ascites filtration and concentration device according to any one of (1) to (4), wherein the effective membrane area of the hollow fiber membrane of the filter for concentration is 0.3 m ² or more.

(6) The ascites filtration and concentration device according to any one of (1) to (5), wherein the ultrafiltration performance of the filter for concentration is 95mL/min/200mmHg or more and 300mL/min/200mmHg or less.

(7) The ascites filtration and concentration device according to any one of (1) to (5), wherein the ultrafiltration performance of the concentration filter is 110 mL/min/200 mmHg or more and 300 mL/min/200 mmHg or less.

According to the present invention, a large amount of high-protein ascites can be concentrated into a high-concentration protein solution containing necessary proteins and recovered, and the recovery rate of useless proteins in the ascites can be reduced.

1: Ascites filtration and concentration device

10: Storage container

11: Filter for filtration

12: Filter for concentration

13: recycling container

14: Channel 1

14a: The first end of the first channel

14b: The second end of the first channel

15: Channel 2

15a: The first end of the second channel

15b: The second end of the second channel

16: Channel 3

16a: The first end of the third channel

16b: The second end of the third channel

17: Channel 4

17a: The first end of the 4th channel

17b: The 2nd end of the 4th channel

18: Channel 5

18a: The first end of the 5th channel

18b: The 2nd end of the 5th channel

19: Control device

20, 50: cylindrical container

21, 51: Hollow fiber membrane

22, 23, 52, 53: the entrance and exit to the inner space of the hollow fiber membrane

24, 25, 54, 55: the entrance and exit to the outer space of the hollow fiber membrane

30: hose pump

[Fig. 1] is an explanatory diagram showing an example of the configuration of the ascites fluid filtration and concentration device.

[Figure 2] is a schematic diagram showing the dimensions of the hollow fiber membrane.

[Figure 3] is a table showing the experimental results of the examples.

Hereinafter, the ideal implementation mode of the present invention will be described with reference to the drawings. In addition, the positional relationship of the top, bottom, left, and right of the diagram shall be based on the position relationship shown in the diagram as long as it is not declared in advance. Of schema The size ratio is not limited to the ratio shown in the figure. Furthermore, the following implementation type is used to illustrate the example of the present invention, and its purpose is not only to limit the present invention to this implementation type. In addition, the present invention can be variously modified as long as it does not deviate from its gist.

FIG. 1 is an explanatory diagram showing an example of the configuration of the ascites filtration and concentration device 1 of the present embodiment. The ascites filtration and concentration device 1 includes, for example, a storage container 10, a filtering filter 11, a concentration filter 12, a recovery container 13, a first channel 14, a second channel 15, a third channel 16, and a fourth channel 17, The fifth channel 18, and the control device 19, etc.

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

The filter 11 for filtration is, for example, a hollow fiber membrane filter. For example, the filter 11 for filtration has a cylindrical container 20, and inside the cylindrical container 20, many hollow fiber membranes 21 are arrange|positioned along the longitudinal direction. The hollow fiber membrane 21 can separate cell 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 inlets 22 and 23 leading to the inner space of the hollow fiber membrane 21; the side part of the cylindrical container 20 is provided with two outer spaces leading to the hollow fiber membrane 21 Entrance and exit 24, 25. The entrance 22 leads to the fifth passage 18, and the entrance 23 leads to the first passage 14. The port 24 leads to the second passage 15, and the port 25 is closed.

The first channel 14 is, for example, a flexible tube such as polyvinyl chloride. The first end 14a of the first channel 14 is connected to the storage container 10, and the second end 14b is connected to the filter 11 for filtration. In this embodiment, the second end 14b is connected to the inlet and outlet 23 of the inner space of the hollow fiber membrane 21 at the lower part of the filter 11 for filtration. The first passage 14 is provided with, for example, a hose pump 30, and the ascites in the storage container 10 can be sent to the recovery container 13 through the filter 11 for filtration and the filter 12 for concentration. Also, it may not be in the first The channel 14 is provided with a hose pump 30, and the ascites of the storage container 10 is supplied to the filter 11 for filtration by gravity falling.

The concentration filter 12 is, for example, a cellulose-based hollow fiber membrane filter. For example, the filter 12 for concentration has a cylindrical container 50, and inside the cylindrical container 50, many hollow fiber membranes 51 are arrange|positioned along the longitudinal direction. The upper and lower parts of the cylindrical container 50 are provided with inlets 52 and 53 leading to the inner space of the hollow fiber membrane 51; the side part of the cylindrical container 50 is provided with two outer spaces leading to the hollow fiber membrane 51 Entrance and exit 54, 55. The entrance 52 leads to the third passage 16, and the entrance 53 leads to the second passage 15. The port 54 leads to the fourth passage 17, and the port 55 is closed.

The hollow fiber membrane 51 is composed of a cellulose-based material. The material of the hollow fiber membrane 51 is, for example, cellulose acetate, regenerated cellulose, surface modified cellulose, and cellulose acetate such as cellulose triacetate and cellulose diacetate.

The concentration filter 12 (hollow fiber membrane 51) has an ultrafiltration performance of 85 mL/min/200 mmHg or more and 300 mL/min/200 mmHg or less. The ultrafiltration performance of the concentration filter 12 is desirably 95mL/min/200mmHg or more and 200mL/min/200mmH or less; more desirably 110mL/min/200mmHg or more and 200mL/min/200mmHg or less. If the ultrafiltration performance of the concentration filter 12 is 85mL/min/200mmHg or more and 300mL/min/200mmHg or less, it is possible to concentrate 5L or more of high-concentration ascites by 5 times. If the ultrafiltration performance of the concentration filter 12 is 95mL/min/200mmHg or more, even if the concentration rate is further increased, high concentration ascites can be treated. If the ultrafiltration performance of the concentration filter 12 is 200mL/min/200mmHg or less, the pore size of the protein does not leak out, and it is within the linear velocity range that can prevent protein from accumulating on the inner surface of the hollow fiber membrane. Carry out product design, and the protein concentration of the recovered liquid can be concentrated Shrink to more than 10g/dL. In addition, the ultrafiltration performance of the concentration filter 12 can also be 85mL/min/200mmHg or more, 200mL/min/200mmHg or less, 95mL/min/200mmHg or more, 300mL/min/200mmHg or less, 110mL/min/200mmHg or more, 300mL/min /200mmHg or less.

The ultrafiltration performance is specified by the test shown below. Prepare bovine plasma whose protein concentration is adjusted to 6g/dL, and use a roller pump to deliver the solution to the concentration filter at a constant rate of 200 mL per minute. At this time, the outlet (port 54 in this embodiment) of the drain side (the side where the removed dewatering liquid is discharged) of the filter for concentration is in an open state. Compress the circuit connected to the outlet (inlet 52 of this embodiment) connected to the recovery liquid discharge side of the concentration filter (the side where the recovered liquid is discharged) to adjust, so that it is applied to the concentration filter as shown in the figure The pressure difference between the inner space R1 and the outer space R2 of the hollow fiber membrane 51 shown in 2 (hereinafter also referred to as "TMP") is 200 mmHg. At this time, measure the volume per unit time of the dewatering liquid discharged from the outlet on the drain side. The calculation method of TMP is as follows.

TMP=(the inlet side of the filter (inlet and outlet 53 of this embodiment) pressure + the outlet side of the filter (inlet and outlet 52 of this embodiment) pressure)/2-the pressure on the drainage side (the inlet and outlet 54 of this embodiment)

As shown in Figure 2, when the concentration filter 12 concentrates the protein solution 5 times at 50 mL/min, the linear velocity V of the hollow fiber membrane 51 is 2.8 m/hr or less, preferably 2.5 m/hr or less, and more preferably 1.0 It is composed of m/hr or more and 2.5 m/hr or less. The linear velocity V is calculated by the following formula.

^{Linear velocity V (m/hr) = (flow rate (m 3} /hr) from the inlet of the filter (the inlet and outlet 53 of this embodiment) to the outlet (the inlet and outlet 52 of this embodiment) (m 3 /hr))/(opening area ( m ² ))

Opening area (m ² )=(hollow fiber inner diameter/2)^2×π×number of hollow fiber

When the speed V is 2.8 m/hr or less, the adsorbability of the protein to the hollow fiber membrane 51 is improved, and the recovery rate of useless protein can be reduced. In addition, it is possible to prevent the TMP of the hollow fiber membrane 51 from increasing due to the influence of the flow velocity. When the linear velocity V is 1.0 m/hr or more, the increase in the amount of protein deposited on the inner wall of the hollow fiber membrane 51 can be suppressed, and the clogging of the hollow fiber membrane 51 caused by the clogging of the pores can be suppressed.

The thickness D of the hollow fiber membrane 51 of the concentration filter 12 is set to 45 μm or less, preferably 30 μm or less, and more preferably 10 μm or more and 25 μm or less. When the thickness D of the hollow fiber membrane 51 is 45 μm or less, the TMP of the hollow fiber membrane 51 becomes smaller, and the leakage of necessary protein through the hollow fiber membrane 51 can be reduced. In addition, if the membrane thickness D of the hollow fiber membrane 51 is 45 μm or less, when the membrane area is increased to improve the ultrafiltration performance, the container size can be controlled within the allowable range. When the thickness D of the hollow fiber membrane 51 is 10 μm or more, the strength of the hollow fiber membrane 51 can be maintained, and the hollow fiber membrane 51 can be manufactured stably.

Filter and concentrated in effective membrane area of 12 E-based hollow fiber membranes 51 is set to 0.3M of ² or more, desirably 1.0m ² or more, more preferably ² or more is ² or less 1.5m 3.0m. The effective membrane area E of the hollow fiber membrane 51 is calculated by the formula of the inner circumference of the hollow fiber membrane 51 (the inner diameter of the hollow fiber membrane 51 d×π)×the distance between the opening end faces L×the number of hollow fiber membranes. When the effective membrane area E of the hollow fiber membrane 51 is 0.3 m ² or more, a design to maintain a small pore size of the hollow fiber membrane 51 can be performed, and as a result, the leakage of necessary protein can be reduced. In addition, when the effective membrane area E of the hollow fiber membrane 51 is 3.0 m ² or less, the linear velocity V that does not cause congestion can be maintained.

Furthermore, the inner diameter of the hollow fiber membrane 51 is set to 100 μm or more, desirably 185 μm or more, and more desirably 185 μm or more and 300 μm or less. When the inner diameter of the hollow fiber membrane 51 is 100 μm or more and 300 μm or less, concentration can be performed within the ideal linear velocity V range. this In addition, if the inner diameter of the hollow fiber membrane 51 is 300 μm or less, the hollow fiber membrane 51 can be manufactured stably.

The effective length (total length L) of the hollow fiber membrane 51 is set to 10 cm or more, desirably 15 cm or more, and more desirably 15 cm or more and 28 cm or less. If the effective length of the hollow fiber membrane 51 is 10 cm or more, it can be manufactured with a head capacity that is not prone to local flow with the number of hollow fibers used to obtain the necessary ultrafiltration performance. In addition, if the effective length of the hollow fiber membrane 51 is 10 cm or more and 28 cm or less, an ideal linear velocity in the hollow fiber membrane can be obtained.

The hollow fiber membrane 51 is preferably given a wrinkle structure. Wrinkle refers to the wavy shape given to the hollow fiber membrane. In the case where the hollow fiber membrane 51 has a wrinkle structure, the wrinkle amplitude (the size of the swing in the direction perpendicular to the longitudinal direction) is set to, for example, 0.1 mm or more and 1.0 mm or less, and ideally 0.4 mm or more and 0.6 mm or less. If the amplitude of the wrinkles is 0.1 mm or more, the contact between the hollow fiber membranes 51 can be reduced, and the wrinkles can be imparted stably in manufacturing. If the wrinkle amplitude is 1.0 mm or less, the hollow fiber membrane 51 collapses during manufacturing can be reduced, and the insertability when the fiber bundle is inserted into the cylindrical container 50 can be maintained well, so that the concentration filter 12 can be manufactured stably .

The wavelength of the wrinkles (the repetitive width in the longitudinal direction) is set to, for example, 3.0 mm or more and 16 mm or less, preferably 6.0 mm or more. If the wave length of the wrinkles is above 3.0 mm and below 16 mm, the contact between the hollow fiber membranes 51 can be reduced to improve the performance of the hollow fiber membranes 51. If the wrinkle wavelength is 3.0 mm or more, the hollow fiber membrane 51 can be prevented from collapsing during manufacturing, and the hollow fiber membrane 51 can be manufactured stably.

The filling rate of the hollow fiber membrane 51 is set to, for example, 30% or more and 95% or less, and desirably 50% or more and 70% or less. If the filling rate of the hollow fiber membrane 51 is 30% or more and 95% or less, then It is possible to prevent the hollow fiber membranes 51 from contacting each other and hinder the flow, and it is possible to exert the necessary filtering ability.

The second channel 15 shown in FIG. 1 is, for example, a flexible tube such as polyvinyl chloride. The first end 15a of the second passage 15 is connected to the inlet and outlet 24 of the outer space of the hollow fiber membrane 21 on the upper side of the side of the filter 11 for filtering. The second end 15b of the second channel 15 is connected to the inlet and outlet 53 of the inner space R1 of the hollow fiber membrane 51 at the lower part of the concentration filter 12.

The recovery container 13 is, for example, a container made of soft resin such as polyvinyl chloride, and can contain the protein solution (recovered liquid) containing the necessary protein concentrated by the concentration filter 12. The recovery container 13 has a capacity smaller than that of the storage container 10, for example.

The third channel 16 is, for example, a flexible tube such as polyvinyl chloride. The first end 16a of the third channel 16 is connected to the inlet 52 of the upper part of the concentration filter 12 leading to the inner space R1 of the hollow fiber membrane 51. The second end 16b of the third channel 16 is connected to the recovery container 13.

The fourth channel 17 is, for example, a flexible tube such as polyvinyl chloride. The first end 17a of the fourth passage 17 is connected to the inlet and outlet 54 of the upper side surface of the concentration filter 12 leading to the outer tube space R2 of the hollow fiber membrane 51. The second end 17b of the fourth channel 17 is connected to the waste liquid part (not shown) of the dewatering liquid for dewatering from the protein solution.

The fifth channel 18 is, for example, a flexible tube such as polyvinyl chloride. The first end 18a of the fifth channel 18 is connected to the inlet 22 of the upper part of the filtering filter 11 leading to the inner space of the hollow fiber membrane 21. The second end 18b of the fifth channel 18 is connected to a waste liquid part (not shown) containing a waste liquid of cell components separated from the protein solution.

The control device 19, for example, a computer, can control the operation of the hose pump 30 by executing a program recorded in the recording section with a CPU, so as to adjust the protein solution of the filter 11 for filtration. The flow rate and the flow rate of the protein solution in the concentration filter 12, etc.

Next, the operation method of the above-mentioned ascites filtering and concentrating device 1 will be described.

First, a storage container 10 containing ascites taken from a patient, for example, 3L or more is connected to the first channel 14. Ascites, for example, is cancerous ascites taken from cancer patients, and is a high-concentration protein solution containing cell components such as cancer cells and bacteria. The protein solution contains essential proteins such as albumin and useless proteins such as cytokines. Ascites, for example, has 1.0mPa. Viscosity above s, even 1.5mPa. Stickiness above s.

Next, the hose pump 30 is operated, and the ascites of the storage container 10 is supplied to the inner space of the hollow fiber membrane 21 from the inlet and outlet 23 of the filter 11 through the first channel 14. Ascites fluid flows from the inner space of the hollow fiber membrane 21 into the outer space through the hollow fiber membrane 21. At this time, cell components such as cancer cells and bacteria present in the protein solution are separated. The protein solution (filtrate) filtered through the hollow fiber membrane 21 flows out from the inlet and outlet 24 of the filtration filter 11, and is supplied to the tube of the hollow fiber membrane 51 from the inlet and outlet 53 of the concentration filter 12 through the second channel 15内空间 R1.

When the protein solution flows into the inner space R1 of the hollow fiber membrane 51 of the filter 12 for concentration, the moisture of the protein solution flows out through the hollow fiber membrane 51 to the outer space R2 of the hollow fiber membrane 51. At this time, some useless proteins such as cytokines can flow out together with water. A part of the useless protein can be adsorbed by the hollow fiber membrane 51. The water and protein (dehydration liquid) flowing out into the outer space R2 of the hollow fiber membrane 51 flows out from the inlet and outlet 54 of the concentration filter 12 and is discharged to the waste liquid part through the fourth channel 17.

The protein solution (recovered liquid) in which moisture and a part of the useless protein are removed in the tube inner space R1 of the hollow fiber membrane 51 of the concentration filter 12, flows out from the inlet and outlet 52 of the concentration filter 12, and is recovered through the third channel 16 To the recovery container 13. This protein solution contains A large amount of necessary protein such as albumin.

According to this embodiment, by using the cellulose hollow fiber membrane type concentrating filter 12 with an ultrafiltration performance of 85mL~300mL/min/200mmHg, the filtering capacity of the concentrating filter 12 is improved, and the high protein content can be reduced. A large amount of ascites is concentrated into a high-concentration protein solution containing essential proteins such as albumin and recovered. In addition, the cellulose-based material has the property of adsorbing protein, so the absolute amount of useless protein in the recovered liquid can be reduced. By this, it is possible to suppress side effects such as fever and kidney damage, which are considered to be caused by useless protein.

Incidentally, if you want to treat all large amounts of ascites at a high rate, you need to improve the ultrafiltration performance. The method to improve the ultrafiltration performance is to increase the number of hollow fiber membranes or increase the pore size of the hollow fiber membranes. In the case of using a polymer-based hollow fiber membrane, the thickness of the membrane will increase. Therefore, if the number of hollow fiber membranes is increased, the filter container will become larger and the possibility of uneven flow will increase. In addition, if it is desired to reduce the size of the container and increase the filling rate, the hollow fibers contact each other, and the filtering ability cannot be exerted. If the pore size of the hollow fiber membrane is increased, the leakage to the filter side will increase and the recovery rate of necessary protein will decrease. In addition, if a filter is used to increase the number of hollow fiber membranes while maintaining the pore size to improve the ultrafiltration performance, a large amount of useless protein will also be recovered. According to this embodiment, by using the cellulose-based hollow fiber membrane type concentrating filter 12, the membrane thickness is thinner than that of the polymer-based hollow fiber membrane. Therefore, even if the number of hollow fiber membranes is increased, the The container can also be designed to be smaller than that of the waste. As a result, the ultrafiltration performance can be improved by increasing the number of hollow fiber membranes.

The ascites filtering and concentrating device 1 of this embodiment is particularly effective when concentrating cancerous ascites. In the clinical data of the inventors, the concentration of TP (total protein) in hepatic and cancerous ascites, the TP concentration in hepatic ascites is about 1g/dL (Max 2.5g/dL) on average, and the TP concentration in cancerous ascites The average is about 3 g/dL (Max 9 g/dL). Generally, cancerous ascites has a higher TP concentration than hepatic ascites, and concentration becomes difficult. Here, the inventors found that, by making the ultrafiltration performance of 85 mL/min/200 mmHg or more as in the present embodiment, even cancerous ascites can be concentrated and treated with 3L of ascites by 5 times. In addition, compared with hepatic ascites, cancerous ascites not only has a higher concentration of TP, but also has a higher content (absolute amount) of useless protein. Here, the inventors found that by using a cellulose membrane with protein adsorption properties as a filter for concentration of cancerous ascites, the absolute amount of useless protein in the recovered liquid can be reduced. In other words, in the case of hepatic ascites, the cellulose membrane has been disliked due to the decrease in the amount of protein recovered. However, the inventors found that by using the cellulose membrane as a filter for concentration for cancerous ascites, the recovery of protein The influence of the amount is in a small range, and it can reduce the absolute amount of the useless protein in the cancerous ascites compared with the hepatic ascites.

The filter 12 for concentration is preferably configured such that the linear velocity of the hollow fiber membrane 51 is 2.8 m/hr or less when the protein solution is concentrated 5 times at 50 mL/min. Thereby, the adsorption amount of unnecessary proteins such as cytokines to the hollow fiber membrane 51 can be increased, and the recovery rate of the useless proteins can be reduced.

The thickness D of the hollow fiber membrane 51 of the filter 12 for concentration is preferably 45 μm or less. Thereby, the TMP of the hollow fiber membrane 51 becomes smaller, and the leakage of necessary protein through the hollow fiber membrane 51 can be reduced.

The effective membrane area E of the hollow fiber membrane 51 of the filter 12 for concentration is ^{preferably 0.3 m 2} or more. Thereby, even if the ultrafiltration performance of 85mL~300mL/min/200mmHg is obtained, the pore size of the hollow fiber membrane 51 can be maintained small. As a result, the leakage of necessary protein through the hollow fiber membrane 51 can be reduced.

Above, suitable implementation forms of the present invention have been described with reference to the accompanying drawings, but the present invention is not limited to such an example. Those who have general knowledge in the technical field to which the present invention belongs can obviously apply for Considering various alterations or amendments within the scope of the thoughts recorded in the scope of the patent, it should be understood that they naturally also belong to the technical scope of the present invention.

For example, the structure of the ascites filtering and concentrating device 1 of the above-mentioned embodiment may not be limited to this but may have another structure. For example, the pump may be provided not only in the first channel 14, but also in other channels such as the second channel 15. In addition, the pump may not be provided in the first channel 14 but in the second channel 15. The fourth channel 17 may also be provided with a negative pressure generating device. Furthermore, when the protein solution is sent from the storage container 10 to the recovery container 13, it is also possible to use a drop pressure without using a pump. The filtration method of the ascites filtration and concentration device 1 can also use the external pressure filtration method. For example, the first channel 14 may be connected to the inlet and outlet 24 of the filtration filter 11, and the second channel 15 may be connected to the inlet and outlet 23 of the filtration filter 11, so that ascites can pass from the outside of the hollow fiber membrane 21 to the inside. The concentrating filter 12 can also be used by connecting multiple units in parallel or in series. In addition, the manufacturing method of the ascites fluid filtering and concentrating device 1 and the concentrating filter 12, etc., is appropriately selected using a conventional wet and dry membrane forming technique, and is not particularly limited.

[Examples]

The following shows the experimental results confirming that the present invention can concentrate a large amount of high-protein ascites to a high concentration and recover it, and can reduce the recovery rate of useless protein in the ascites.

<Filter for concentration>

The ultrafiltration performance of the concentration filter is achieved by controlling the membrane area (hollow fiber membrane bundle, effective length) or pore size (manufacturing conditions: the concentration and temperature of the original liquid and inner liquid extruded from the double spinning nozzle), and Manufacturing and adjustment. The linear velocity is adjusted by manufacturing by controlling the membrane area (hollow fiber membrane bundle) or the inner diameter of the hollow fiber (manufacturing conditions: internal liquid conveying pressure, etc.).

<Experimental method>

Prepare 5L of simulated ascites with protein concentration adjusted to 3g/dL, and use it as a cytokine indicator, add 1mg/L of protein α1-MG (α1-microglobulin) in the same low molecular weight region. This simulated ascites can be regarded as having passed through the filter and has no cellular components, so it is implemented by omitting the filter for filtration. The flow rate of the pump was adjusted to 5L of simulated ascites and 50 mL per minute was introduced into the concentration filter, and the recovered liquid was recovered to the recovery container at 10 mL per minute (the dewatering liquid was dewatered at 40 mL per minute), and the simulated ascites was concentrated 5 times. Measure the protein concentration of the recovered liquid recovered to the recovery container (recovered liquid TP concentration), the recovery rate of the protein (α1-MG) in the same low molecular weight region as the cytokine in the recovered liquid (protein in the ascites of the storage container (α1-MG) ), the ratio of the protein (α1-MG) recovered to the recovery container) and the protein concentration of the dewatering solution (the TP concentration of the dewatering solution). The various conditions and results of the experiment are shown in the table in Figure 3.

(Example 1)

Use a cellulose triacetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 100mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a linear velocity of 2m/hr when the protein solution is concentrated 5 times at 50mL/min, a membrane thickness of 15μm, and an effective membrane area of 1.5m ² .

(Example 2)

Use a cellulose triacetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 100mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a linear velocity of 3 m/hr when the protein solution is concentrated 5 times at 50 mL/min. The membrane thickness and effective membrane area of the hollow fiber membrane are the same as in Example 1.

(Example 3)

Using ultrafiltration performance of 86mL/min/200mmHg tri-cellulose acetate (CTA) hollow Fiber membrane type concentrating filter. The hollow fiber membrane of the filter for concentration uses a linear velocity of 3m/hr and a membrane thickness of 50μm when the protein solution is concentrated 5 times at 50mL/min. The effective membrane area of the hollow fiber membrane is the same as in Example 1.

(Example 4)

Use a cellulose triacetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 86mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a membrane with a thickness of 50μm. The linear velocity and effective membrane area of the hollow fiber membrane are the same as in Example 1.

(Example 5)

Use a cellulose triacetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 100mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a linear velocity of 3m/hr when the protein solution is concentrated 5 times at 50mL/min, a membrane thickness of 50μm, and an effective membrane area of 0.2m ² .

(Example 6)

Use a cellulose triacetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 100mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses an effective membrane area of 0.2m ² . The linear velocity and film thickness of the hollow fiber membrane are the same as in Example 1.

(Example 7)

Use a tri-cellulose acetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 125mL/min/200mmHg. The effective membrane area, line speed and membrane thickness of the hollow fiber membrane of the filter for concentration are the same as in Example 1.

(Comparative example 1)

The use of a polyfloc (PSF) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 107mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a linear velocity of 2m/hr when the protein solution is concentrated 5 times at 50mL/min, a membrane thickness of 45μm, and an effective membrane area of 1.5m ² .

(Comparative example 2)

The use of a polyfloc (PSF) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 350mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a linear velocity of 1.1 m/hr when the protein solution is concentrated 5 times at 50 mL/min, a membrane thickness of 43 μm, and an effective membrane area of 2.6 m ² .

(Comparative example 3)

Use a cellulose triacetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 40mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a linear velocity of 5m/hr when the protein solution is concentrated 5 times at 50mL/min, a membrane thickness of 15μm, and an effective membrane area of 0.7m ² .

(Comparative Example 4)

Use a tri-cellulose acetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 330mL/min/200mmHg. The hollow fiber membrane of the filter for concentration uses a linear velocity of 1.0 m/hr when the protein solution is concentrated 5 times at 50 mL/min, a membrane thickness of 15 μm, and an effective membrane area of 3.0 m ² .

For example, it can be confirmed from Examples 1 to 7 and Comparative Examples 1 to 4 that if a cellulose triacetate (CTA) hollow fiber membrane type concentrating filter with an ultrafiltration performance of 100 mL/min/200 mmHg is used, it can be used in the middle of the process. In the case of obstruction, treat 5L or more of high-protein simulated ascites with a protein concentration of 3g/dL. The protein solution of the recovered liquid can be concentrated to a high concentration of 5g/dL or more with a single concentration process, and the cytokine molecule area can be reduced. The recovery rate of α1-MG is less than 30%.

For example, it can be confirmed from Example 1 and Example 2 that if the linear velocity of the hollow fiber membrane is less than 2.8 m/hr when the protein solution is concentrated 5 times at 50 mL/min, the protein solution in the recovered liquid is concentrated to 5 g/hr. At the high concentration above dL, the recovery rate of α1-MG in the cytokine molecule area decreases.

For example, it can be confirmed from Example 1 and Example 4 that if the thickness D of the hollow fiber membrane is 45 μm or less, the recovery rate of α1-MG in the cytokine molecule region is 30% or less, and the protein solution of the recovered liquid The concentration is increased. In addition, it can be confirmed that the protein concentration of the dewatering liquid has decreased. That is, it can be confirmed that the leakage of essential proteins through the hollow fiber membrane is inhibited, and the adsorption of α1-MG in the cytokine molecule region to the hollow fiber membrane is promoted.

For example, it can be confirmed from Example 1 and Example 6 that if the membrane area is 0.3m ² or more, the protein solution of the recovered liquid is concentrated to a high concentration of 5g/dL or more, and the α1-MG in the cytokine molecule region While the recovery rate is less than 30%, the protein concentration of the dewatering liquid is less than 0.20g/dL. That is, it can be confirmed that the leakage of necessary proteins through the hollow fiber membrane is inhibited, and the adsorption of α1-MG to the hollow fiber membrane in the cytokine molecule region is promoted.

【Industrial Utilization】

The present invention is useful in providing an ascites filtration and concentration device that can concentrate a large amount of high-protein ascites into a high-concentration protein solution containing essential proteins and recover it, and can reduce the recovery rate of useless proteins in the ascites.

1: Ascites filtration and concentration device

10: Storage container

11: Filter for filtration

12: Filter for concentration

13: recycling container

14: Channel 1

14a: The first end of the first channel

14b: The second end of the first channel

15: Channel 2

15a: The first end of the second channel

15b: The second end of the second channel

16: Channel 3

16a: The first end of the third channel

16b: The second end of the third channel

17: Channel 4

17a: The first end of the 4th channel

17b: The 2nd end of the 4th channel

18: Channel 5

18a: The first end of the 5th channel

18b: The 2nd end of the 5th channel

19: Control device

20, 50: cylindrical container

21, 51: Hollow fiber membrane

22, 23, 52, 53: the entrance and exit to the inner space of the hollow fiber membrane

24, 25, 54, 55: the entrance and exit to the outer space of the hollow fiber membrane

30: hose pump

Claims (7)

A device for filtering and concentrating ascites, which is characterized by: Storage container, which stores ascites; The hollow fiber membrane filter is used to separate the cell components in the protein solution of the ascites fluid in the storage container; The cellulose hollow fiber membrane type concentrating filter can concentrate the protein solution filtered by the filtering filter, and the ultrafiltration performance is 85mL/min/200mmHg or more and 300mL/min/200mmHg or less; The recovery container is to recover the protein solution concentrated by the concentration filter; The first channel is connected to the storage container at the first end, and connected to the inlet of the filtering filter at the second end; The second channel is the first end connected to the outlet of the filtering side of the filter, and the second end is connected to the inlet of the concentrating filter; The third channel is connected to the outlet of the concentrating filter at the first end, and connected to the recovery container at the second end; and The fourth channel is connected to the outlet on the drain side of the thickening filter. The ascites filtration and concentration device according to claim 1, wherein the filter for concentration is configured such that the linear velocity of the hollow fiber membrane is 2.8 m/hr or less when the protein solution is concentrated 5 times at 50 mL/min. The ascites filtering and concentrating device according to claim 1 or 2, wherein the hollow fiber membrane of the concentrating filter has a thickness of 45 μm or less. The ascites filtering and concentrating device according to claim 1 or 2, wherein the concentrating filter The thickness of the hollow fiber membrane in the device is 30 μm or less. The ascites filtering and concentrating device according to any one of claims 1 to 4, wherein the effective membrane area of the hollow fiber membrane of the concentrating filter is 0.3 m ² or more. The ascites filtration and concentration device according to any one of claims 1 to 5, wherein the ultrafiltration performance of the filter for concentration is 95mL/min/200mmHg or more and 300mL/min/200mmHg or less. The ascites filtration and concentration device according to any one of claims 1 to 5, wherein the ultrafiltration performance of the concentration filter is 110 mL/min/200 mmHg or more and 300 mL/min/200 mmHg or less.

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