JP4493097B2 - Continuous blood filtration device - Google Patents

Description

  The present invention relates to a continuous blood filtration device. More specifically, the present invention relates to an apparatus used for continuous hemofiltration therapy, which continuously flows blood through a hemofilter and continuously obtains filtrate.

  As blood purification devices, many systems based on separation / purification technology using filtration membranes or dialysis membranes have already been used. Generally used as a separation membrane including a filtration membrane or a dialysis membrane is a hollow fiber-like porous membrane. In addition to an artificial kidney that purifies blood by dialysis, a plasma filtration membrane that separates plasma and blood cell components In this combination, attempts have been made to remove high molecular weight proteins and lipids in plasma or viruses.

The continuous blood filtration device (CHF) has the ability to remove endogenous humoral mediators containing various cytokines, which are regarded as factors that induce organ damage during multiple organ failure, etc. Attempts have been made to treat it. Compared to continuous hemodiafiltration (CHDF), CHF does not require dialysate and does not require a dialysate pump, so the device itself is simple and can be easily implemented. In addition, application in general wards is also being tried.
Although CHF has the advantages as described above, it has a drawback that its solute removal performance is lower than that of CHDF, and therefore, as a blood purification therapy, CHDF is often the first choice. .

  A method generally adopted as a guide for improving the solute removal performance of CHF is control of the microstructure of the porous membrane. It is governed by the idea that the separation structure of the solute components to be permeated, that is, the various low molecular weight substances and the high molecular weight substances to be blocked, is the fine structure of the separation membrane, particularly the uniformity of the pore diameter that determines the filtration performance. It was. Therefore, various conditions in the film forming process, that is, the type of polymer material, the molecular weight or distribution thereof, the type of additive, the composition, the type of solvent, the concentration, the film forming temperature, the discharge rate during spinning, the spinning speed A lot of parameters such as the size of the nozzle, the air gap, and the cooling time have been intensively studied, and the control of the molecular weight cut off and the accuracy thereof have been required. However, it is difficult to realize the uniformity of the pore diameter above a certain level, and the improvement of the separation accuracy by controlling the structure of the membrane has been almost dealt with at present.

  On the other hand, it is necessary to pay attention to the change in filtration performance with time. Initially, excellent treatment capacity, permeation performance, and blocking performance were manifested by the accumulation of solute molecules on the surface of the separation membrane or the change in filtration performance due to changes in the micro physical structure of the separation membrane itself. There are often occasions when porous membranes gradually degrade performance. Along with the development of non-degrading separation membranes, attempts have also been made to design systems that prevent degradation or restore degraded performance.

  There is a concept of reverse filtration. When various components in the blood aggregate on the membrane surface, or when the permeate flow rate decreases due to clogging of the pores of the membrane, or when the removal rate of substances with a specific molecular weight decreases, As a means of approaching, the treatment liquid is made to flow in the direction opposite to the normal filtration direction, and the components aggregated on the membrane surface and the components blocking the pores are desorbed to the raw material liquid side to attempt to restore the flow path. To do.

Patent Document 1 discloses a technique for increasing separation efficiency in a dialysis membrane by pulsating flow. In the text of the specification, there is a description that “a reduction in filtration efficiency due to adhesion of proteins and platelets can be effectively prevented”.
Patent Document 2 also discloses the concept of reverse filtration as a means for recovering the filtration flow rate. Non-Patent Document 1 describes the concept of dialysis including reverse filtration called the Push & Pull method. Patent Documents 3 and 4 also describe a blood purification device including reverse filtration. However, these are all based on dialysis. The dialysate side of the hollow fiber membrane or plate type dialysis membrane is constantly supplied with fresh dialysate, and during reverse filtration, this dialysate flows into the blood and serves as a replacement fluid. . Since replenishment is performed simultaneously with reverse filtration, the amount of filtration at the time of reverse filtration, that is, the amount of replenishment, is premised on controlling the amount of filtration at the time of normal filtration performed alternately with it, that is, the same amount as the amount of water removal.
Patent Documents 5 and 6 show examples in which the concept of reverse filtration is applied to the purification of ascites. Similarly, after clogging occurs, it is used as a means to recover it.
As described above, the technique called reverse filtration has an effect of temporarily recovering a decrease in the filtration flow rate due to clogging, and there are several application examples. However, none of them are considered to build a system that maintains stable filtration flow rate and separation accuracy, so the recovered filtration flow rate decays in a short time and does not necessarily guarantee stable performance for a long time. .

As an application example in blood purification, there is no example in which the concept of reverse filtration has been attempted in a blood purification device that does not include dialysis, that is, a blood filtration device, particularly a continuous blood filtration device. Excess water removed from the blood by filtration or unnecessary components are present as they are on the filtrate side. When reverse filtration is performed to temporarily recover the filtration flow rate, these unnecessary substances once removed from the blood are returned to the blood, and the blood purification process itself is reversed.
In addition, an operation called backwashing or backfiltration is performed for the purpose of discharging the eluted components accumulated or blocked by the flow of liquid from the reverse direction to the raw material liquid side. Therefore, in order to peel off the protein adhering to the surface of the porous membrane, a reverse membrane differential pressure of a certain level or more is applied, or a reverse filtration flow rate of a certain level or more is secured to obtain a shearing force. It has been done in dialysis. If the same thing is done with CHF, a large amount of unnecessary liquid components separated by filtration will be returned to the blood again. It is common knowledge in this field that reverse filtration is incompatible with CHF.

  However, when having the idea of constructing a system for maintaining separation accuracy, there may be a completely different technical idea using reverse filtration. In order to improve the separation accuracy of various medium molecular weight substances including cytokines and maintain the filtration performance for a long time, a new system not only controls the fine structure of the membrane but also introduces the concept of reverse filtration Construction is necessary.

To make the concept of reverse filtration, which temporarily reverses the time, work effectively on the overall device efficiency. Requires special equipment development.
JP-A-11-9985 JP 7-503641 gazette Japanese Patent Laid-Open No. 2005-6980 JP 2005-118506 A JP-A-53-117286 JP-A-53-117287 Medical Instrumentation Vol. 64, no. 3, (1994)

  The present invention is used for emergency medical care, intensive care, or management of water balance in the blood by extracorporeal circulation in the general ward, maintaining acid / base balance, correcting electrolytes, securing infusion space, removing substances in the body, etc. It is an object of the present invention to provide a blood purification apparatus having a high performance of removing medium molecular weight substances including cytokines.

As a result of intensive studies to solve the above-mentioned problems, the present inventors can achieve the above-mentioned object by performing reverse filtration under certain special conditions, and surprisingly succeeded in increasing the removal performance of medium molecular weight substances, The present invention has been obtained.
(1) an arterial line for introducing blood into the blood inlet side of the hollow fiber membrane blood filter;
A blood pump for delivering blood on the arterial line;
Hollow fiber membrane blood filter,
A venous line connected to the blood outlet side of the hollow fiber membrane blood filter and returning blood to the patient;
A filtrate line connected to the filtrate side of the hollow fiber membrane blood filter and leading to the filtrate,
And a continuous blood filtration device having at least a filtrate pump for feeding the filtrate on the filtrate line,
The filtrate effective filtration area 1 m ² per 0.5~20ml hollow fiber membrane type blood filter for each yield the filtrate effective filtration area 1 m ² per 2~500ml hollow fiber membrane type blood filter by the pump and the filtrate A continuous blood filtration device comprising backflow means for backflowing a filtrate having a volume of 0.1 to 50%.
(2) a fluid replacement line connected to the vein line for introducing fluid replacement;
And a replacement fluid pump for supplying the replacement fluid on the replacement fluid line,
(1) The continuous blood filtration device according to (1), wherein the hollow fiber membrane incorporated in the hollow fiber membrane blood purifier comprises:
The continuous blood filtration device according to (1) or (2), wherein the hydrophobic polymer is a hollow fiber membrane comprising a hydrophobic polymer and a hydrophilic polymer,
The continuous blood filtration device according to (3), wherein the polysulfone polymer and the hydrophilic polymer are polyvinyl pyrrolidone and / or polyalkylene glycol

  The present invention is a continuous blood filtration device that can effectively remove medium molecular weight substances, and is a continuous blood filtration device that is effective in removing medium molecular weight substances including cytokines.

In the system disclosed in the present invention, blood is introduced into the blood inlet of a hollow fiber membrane blood filter by a blood pump from an arterial line through which blood is introduced, and filtration with the hollow fiber is performed in the filter. Is derived from the filtrate line, and the purified blood is led to a venous line connected to the blood outlet of the filter.
The continuous blood filtration device according to the present invention includes means for repeating normal filtration and reverse filtration and its control device.

The following considerations are necessary for setting the filtration amount for forward filtration and reverse filtration. After the filtration amount of the normal filtration reaches a certain amount, reverse filtration is performed, and after the filtration amount of the reverse filtration reaches a certain amount, the filtration is returned to the normal filtration. The continuous blood filtration of the present invention is performed by repeating this cycle a plurality of times, with the process of performing the normal filtration and the reverse filtration once each as one cycle.
The amount of the filtrate for forward filtration is preferably ^{2 to} 500 mL, more preferably 5 to 200 mL, and further preferably 5 to 50 mL per 1 m ^{2 of} membrane area. If the filtration amount of the normal filtration is ² mL or less per 1 m ^{2 of} membrane area, it is difficult to ensure the absolute amount of the treatment amount, which is not preferable. In addition, if the filtration amount of the normal filtration is 500 mL or more per 1 m ^{2 of} membrane area, the high molecular weight substance penetrates into the inside of the membrane structure, and there is no recovery of filtration performance due to improved separation accuracy or elimination of clogged substances even if reverse filtration is performed. This is not preferable because it is sufficient.
The filtration amount of reverse filtration is preferably 0.5 to ²⁰ mL, more preferably 0.5 to 10 mL, and further preferably 1 to ⁵ mL per 1 m ^{2 of} membrane area. If the filtration amount of reverse filtration is 0.5 mL or less per 1 m ^{2 of} membrane area, it is not preferable because the high molecular weight substance can be effectively returned to the raw material liquid side and clogging cannot be effectively recovered. Moreover, when the filtration amount of reverse filtration is 20 mL or more per 1 m ^{2 of} membrane area, it is difficult to ensure the absolute amount of the treatment amount, which is not preferable.

In order to proceed with the filtration treatment, it is essential that the filtration amount of the normal filtration is larger than the filtration amount of the reverse filtration in one cycle operation, but in order to obtain practical filtration efficiency, the filtration amount of the normal filtration The ratio of the filtration amount of the reverse filtration with respect to is required to be 0.1 to 50%. A more preferable range is 1 to 40%, and further preferably 5 to 30%. If the ratio of the filtration amount of the reverse filtration to the filtration amount of the normal filtration is 0.1% or less, the recovery of the filtration performance by the reverse filtration becomes insufficient, which is not preferable. Further, if the ratio of the filtration amount of the reverse filtration to the filtration amount of the normal filtration is 50% or more, it is difficult to ensure the absolute amount of the treatment amount, which is not preferable.
In addition, it is preferable that a replacement fluid line for introducing a replacement fluid is connected to the vein line of the continuous blood filtration apparatus in the present invention, and a replacement fluid pump for feeding the replacement fluid is installed. Since the reverse filtration is performed in a small range compared to the processing amount by the normal filtration, the replacement fluid is not introduced as a reverse filtration solution at the time of reverse filtration but is provided by providing an independent replacement fluid line.

The porous membrane material used under the above conditions can be used as long as it does not elute harmful substances when in contact with blood or cause specific harmful degeneration in blood components.
For example, in addition to polysulfone, which has a proven track record for medical use, polyolefin resins such as polyethylene, ethylene / vinyl alcohol copolymer, polypropylene, poly-4-methyl-2-pentene, polyvinylidene fluoride resin, ethylene / tetrafluoroethylene resin , Fluorine resins such as polychlorotrifluoroethylene resin, polystyrene, acrylic resin, nylon, polyester, polycarbonate, polyacrylamide, polyurethane, and other various synthetic polymers, agarose, cellulose, cellulose acetate, chitin, chitosan, alginate Natural polymers such as hydroxyapatite, glass, alumina, titania, and metals such as stainless steel, titanium, and aluminum.

  Among these, materials that are preferably employed in the present invention are materials having a stable physical structure. For example, in the case of a porous film formed only from a hydrophilic material, the physical structure itself may change over time due to water absorption or solute adhesion. It is preferable that the skeleton of the porous membrane is formed of a hydrophobic material, and the portion in contact with blood has a hydrophilic structure. Hydrophobic porous membranes whose surface is made hydrophilic by coating or graft polymerization are preferably employed, but in particular, as blood treatment materials such as dialysis membranes and membranes for extracorporeal circulation, A film formed by dissolving a polysulfone and a hydrophilic polymer in a solvent by a film forming method called dry-wet spinning is preferably used.

The shape of the porous membrane is preferably a hollow fiber shape as a shape that can efficiently secure a large membrane area in a small volume.
As the structure of the porous membrane, a structure similar to a commonly used dialysis membrane is preferably employed. When a hollow fiber is used as the porous membrane, a structure in which a dense layer called a skin layer having a thickness of about 10 μm exists on the inner surface of the hollow fiber and filtration separation is performed by the skin layer is preferable. In the case of such a structure, a body fluid containing plasma is caused to flow in the hollow part of the hollow fiber, and a liquid component containing a low molecular weight component is filtered outside the hollow fiber through the hollow fiber.

  A preferred embodiment will be described with reference to FIGS. 1 to 5 by taking a hollow fiber-like porous membrane having a skin layer on the inner surface as an example. Blood is filtered from the inside of the hollow fiber to the outside.

  An example of a module filled with a hollow fiber-like porous membrane is shown in FIG. A hollow fiber-like porous membrane 1 is fixed in a blood filter case 3 by an adhesive part 2, and a hollow part 5 of the hollow fiber penetrates the adhesive part 2 and is in the blood filter inner space 6 outside the adhesive part. Leads to. In the present invention, while the bodily fluid containing plasma flows through the hollow portion 5 of the hollow fiber from the inlet 7 (8) to the outlet 8 (7), the hollow liquid-like porous membrane 1 is filtered, and the filtered liquid component Is discharged from the blood filter internal space 4 outside the hollow fiber through the outlet 10 (9).

In the blood filtration apparatus shown in FIG. 2, blood is supplied from the arterial line 12, and the blood passes through the chamber 19 by the blood pump 14 and flows into the blood filter 11 from the blood filter inlet 21. A part of the liquid component including unnecessary components in the blood filter 11 is filtered through the porous membrane by the filtrate pump 15 and guided into the drain bag 18 from the filtrate line 33, and the blood from which unnecessary components are filtered and separated is the venous line 13. Returned to the patient more. A liquid equivalent to the amount of water removed by filtration is supplied from the replacement fluid bag 17 by the replacement fluid pump 16. The above is a normal blood filtration operation mode. The filtrate pump 15 performs reverse rotation every predetermined time, and reverse filtration is performed. That is, the liquid removed from the drain bag 18 is allowed to flow back into the blood through the porous membrane in the hollow fiber membrane blood filter 11. The amount of liquid returned to the blood by reverse filtration is 50% or less of the amount of liquid filtered during normal filtration. FIG. 2 shows a case where a balancer 30 and a device for monitoring the weight of the replacement fluid bag 17 and the drain bag 18 are provided. It is preferable that such a balancer is provided in order to ensure the balance between the water removal by the filtrate pump 15 and the replacement fluid pump 16 and the flow rate of the replacement fluid. That is, the filtrate pump 15 and the replacement fluid pump 16 are driven while realizing a state in which the total amount of the replacement fluid in the replacement fluid bag 17 and the amount of water removal in the drain bag 18 are substantially equal. At the time of normal filtration, the filtrate pump 15 is rotated in the forward direction to allow the filtrate to flow into the drain bag, and an equal amount of replacement fluid is performed by the replacement fluid pump 16, so that the amount of fluid in the replacement fluid bag and the amount of fluid in the drain bag Is kept constant. After a predetermined time, the replacement fluid pump 16 is stopped and reverse filtration by the filtrate pump 15 is performed. The total amount of fluid in the replacement fluid bag and the drain bag is reduced by the amount returned to the blood by reverse filtration. Subsequently, while the replacement fluid pump 16 is stopped, the flow is shifted to the normal filtration mode, and the normal filtration is performed by the filtrate pump 15, and the fluid replacement pump 16 is driven when the amount of liquid in the drain bag 18 reduced by the reverse filtration is recovered. Then, a replacement fluid equivalent to the water removal amount is started. Repeat the above cycle. When the replacement fluid in the replacement fluid bag 17 is exhausted, the replacement fluid bag is replaced with a new one, and at the same time, the drain in the drain bag 18 is discharged by opening the valve 31.
It is also possible to put a certain amount of diluent in the drain bag 18 in advance. When the filtrate that flows in at the time of normal filtration is returned at the time of reverse filtration, the liquid to be back-filtered is diluted to a certain degree, the concentration of unnecessary components once filtered is reduced, and the dissolved low molecular weight substance Since the concentration is low, the viscosity is low, and the resistance during reverse filtration can be reduced. Such dilution is different from that intended for dialysis. It is not necessary to constantly supply a large amount of diluent into the blood purifier. As the amount of the diluent to be put in the drain bag in advance, 50 mL to 2000 mL, preferably 100 mL to 500 mL is suitably employed. A method of replacing the drain bag containing the diluent at the same time as replacing the replacement fluid bag 17 is preferably employed.

  FIG. 3 is a diagram in which the backflow pump 25 is installed at the branch of the filtrate line 33 in order to realize forward filtration and reverse filtration. With the filtrate pump 15, it is possible to realize alternating operation of forward filtration and reverse filtration while maintaining a constant water removal amount. In this case, at the time of normal filtration, both the filtrate pump 15 and the backflow pump 25 are rotated in the forward direction to perform filtration, and at the time of backfiltration, the filtrate pump 15 is stopped, the backflow pump 25 is reversed, and the storage bag 26 is placed. A method of back-filtering the stored filtrate, or at the time of normal filtration, when filtration is performed only by forward rotation of the backflow pump 25, and when the amount corresponding to the filtration amount at the time of back-filtration is stored in the storage bag 26 The reverse flow pump 25 is stopped, water removal by the filtrate pump 15 is started, and after a predetermined time, the filtrate pump 15 is stopped and reverse filtration is performed by reverse rotation of the reverse flow pump 25. Furthermore, a constant flow rate by the filtrate pump 15 is set. Any of the methods of repeating forward filtration and reverse filtration by the backflow pump 25 while continuing water removal can be suitably employed. The balancer which monitors the total weight of the replacement fluid bag 17 and the drain bag 18 similarly to FIG. 2 is illustrated. In FIG. 3, when the water removal by the filtrate pump 15 and the replacement fluid by the replacement fluid pump 16 are performed at a constant flow rate, the pump flow rate is set so that the sum of the fluid amount in the replacement fluid bag and the fluid amount in the drain bag can always be kept constant. By controlling, water removal and the amount of replenisher can be controlled. The method of putting the diluent in the storage bag 26 can be suitably employed as in the case of FIG.

  FIG. 4 is an apparatus that performs reverse filtration by the backflow pump 25 instead of performing reverse filtration by reverse rotation of the filtrate pump 15 in the apparatus shown in FIG. 2. The operation method of the apparatus is the same except that the filtrate pump 15 is stopped and the reverse flow pump 25 is started instead of the reverse rotation of the filtrate pump 15 in FIG. In addition, the operation | movement by operating the filtrate pump 15 by fixed rotation speed and changing the rotation speed of the backflow pump 25 at the time of forward filtration and back filtration is also employable. That is, if the flow rate by the backflow pump 25 is less than the flow rate by the filtrate pump 15, normal filtration is performed, and if it is greater, reverse filtration is performed. By controlling the flow rate of the replacement fluid by the replacement fluid pump 16 according to the flow rate fluctuations by the filtrate pump 15 and the backflow pump 25 so that the weight is kept constant by the balancer 30, the amount of water removal and replacement fluid can be controlled.

  FIG. 5 is a device that realizes reverse filtration by the flow rate balance of the filtrate pump 15 and the reverse flow pump 25 instead of reverse filtration by reverse rotation of the reverse flow pump 25 in FIG. At the time of forward filtration by the filtrate pump 15, first, the valve 28 is closed and the valve 27 is opened. After the liquid amount corresponding to the filtration amount at the time of reverse filtration is stored in the storage bag 26, the valve 27 is closed and the valve 28 is closed. open. The normal filtration by the filtrate pump 15 is continued, and after a predetermined time, the filtrate pump 15 is stopped and the reverse filtration by the backflow pump 25 is performed. Only when the filtrate flows into the drain bag 18, an amount of replacement fluid equal to the amount of water removed is supplied from the replacement fluid bag 17 by the replacement fluid pump 16. In the balancer 30, the flow rates of the filtrate pump 15 and the backflow pump 25 are controlled so that the liquid amount in the replacement fluid bag and the liquid amount in the drain bag can be kept constant.

FIGS. 6 and 7 show a system in which the function of the backflow pump 25 of FIGS. When the piston is pulled, forward filtration is performed, and when the piston is pushed, reverse filtration is performed, and the filtration amount and the amount of the replacement fluid are controlled by the pumps 15 and 16 and the balancer 30 as in the case of FIGS.
EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited by the following Example.

[Example 1]
A hollow fiber membrane made of polysulfone and polyvinylpyrrolidone was formed by the following method. 18% by weight of polysulfone (P-3500, manufactured by Solvay, USA), 6% by weight of polyvinylpyrrolidone (K90, manufactured by ISP), dimethylacetamide (manufactured by Wako Pure Chemical Industries) 76 Dissolved in weight% to make a uniform solution. This film-forming stock solution was kept at 65 ° C., discharged together with an internal solution composed of a mixture of 15% dimethylacetamide and 85% water from a spinning nozzle (slit width 70 μm), and immersed in a water coagulation bath. The wound yarn bundle was cut, washed with a 40% by weight dimethylacetamide aqueous solution at 85 ° C., and further washed with water to remove the residual solvent in the film.
The hollow fiber membrane had an inner diameter of 198 μm and a film thickness of 41 μm. 6000 hollow fiber membranes were filled in a module case and adhered to a container with urethane resin to obtain a blood filter shown in FIG. The effective hollow fiber length was 14 cm.

In the experiment, bovine plasma added with prolactin as a standard for medium molecular weight substances was used. As an anticoagulant, 12.3 mL of CPD was added to 100 mL of blood. The composition of CPD was obtained by dissolving 30 g of trisodium citrate dihydrate, 23.2 g of glucose, 3.58 g of citric acid monohydrate, and 2.51 g of sodium dihydrogen phosphate dihydrate in 1 L of water for injection. It is a thing. All reagents used were manufactured by Wako Pure Chemical Industries. The blood was centrifuged at 3500 rpm for 15 minutes, and plasma was collected.
Experiments were performed using the apparatus shown in FIG. That is, the filtrate was also returned to the raw material plasma in the container 18, and filtration was continued by circulation, and the permeability of prolactin, albumin, and α1MG (α1-microglobulin) was measured.
Circulating plasma volume was 500 mL, prolactin was added at 50 μg / L, and α1MG was added at 1 mg / L.
The plasma circulation flow rate by the blood pump 14 was 100 mL / min, the filtration flow rate by the filtrate pump 15 was 10 mL / min for both normal filtration and reverse filtration, and the normal filtration time 50 seconds and the reverse filtration time 10 seconds were repeated for 3 hours. Membrane area 0.52 m ^2, positive filtered while 16 mL / m ^2, the reverse filtration time of 3.2 mL / m ^2, both the ratio is 20% for. The results are shown in Table 1.

[Comparative Example 1]
Evaluation was performed under the same conditions as in Example 1 except that reverse filtration was not performed. The results are shown in Table 1.

In the examples, while the albumin permeability was maintained at 1% or less, prolactin, which is a medium molecular weight substance, was able to achieve about 1.5 times the removal performance improvement of the comparative example.

Industrial applicability

  According to the present invention, it is possible to provide a continuous blood filtration system having a high separation accuracy with a high removal rate of medium molecular weight cytokines and the like, and a small loss of useful proteins such as albumin. It can be suitably used in fields that require rapid blood purification, including the emergency medical field.

FIG. 1 is a schematic diagram showing an example of the structure of a module filled with a hollow fiber membrane used in the present invention. FIG. 2 is a schematic view showing an embodiment of a blood filtration device according to the present invention. FIG. 3 is a schematic view showing another embodiment of the blood filtration device according to the present invention. FIG. 4 is a schematic view showing still another embodiment of the blood filtration device according to the present invention. FIG. 5 is a schematic view showing still another embodiment of the blood filtration device according to the present invention. FIG. 6 is a schematic view showing still another embodiment of the blood filtration device according to the present invention. FIG. 7 is a schematic view showing still another embodiment of the blood filtration device according to the present invention. FIG. 8 is a schematic diagram showing an aspect of a system used in an evaluation experiment of a blood filtration device according to the present invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Porous membrane 2 Adhesive part 3 Blood filter case 4 Blood filter internal space outside hollow fiber 5 Hollow fiber hollow part 6 Blood filter internal space outside adhesive part 7 Inlet (outlet)
8 Exit (entrance)
9 Entrance (exit)
10 Exit (entrance)
DESCRIPTION OF SYMBOLS 11 Hollow fiber membrane type blood filter 12 Arterial line 13 Vein line 14 Blood pump 15 Filtrate pump 16 Fluid replacement pump 17 Fluid replacement bag 18 Drain bag 19 Defoaming chamber 20 Defoaming chamber 21 Blood inlet 22 Blood outlet 23 Filtrate outlet 24 Filtrate outlet 25 Liquid feed pump 26 Bag 27 Valve 28 Valve 29 Air filter 30 Balancer 31 Valve 32 Syringe 33 Filtrate line 34 Fluid replacement line

Claims (4)

An arterial line for introducing blood into the blood inlet side of the hollow fiber membrane blood filter,
A blood pump for delivering blood on the arterial line;
Hollow fiber membrane blood filter,
A venous line connected to the blood outlet side of the hollow fiber membrane blood filter and returning blood to the patient;
A filtrate line connected to the filtrate side of the hollow fiber membrane blood filter and leading to the filtrate,
And a continuous blood filtration device having at least a filtrate pump for feeding the filtrate on the filtrate line,
The hollow fiber membrane incorporated in the hollow fiber membrane blood filter is composed of a hydrophobic polymer and a hydrophilic polymer.
A hollow fiber membrane, wherein the hydrophobic polymer is a polysulfone polymer, and the hydrophilic polymer.
Is polyvinylpyrrolidone and / or polyalkylene glycol,
The filtrate effective filtration area 1 m ² per 0.5~20ml hollow fiber membrane type blood filter for each yield the filtrate effective filtration area 1 m ² per 2~500ml hollow fiber membrane type blood filter by the pump and the filtrate A continuous blood filtration device comprising backflow means for backflowing a filtrate having a volume of 0.1 to 50%. A fluid replacement line connected to the venous line to introduce fluid replacement;
And a replacement fluid pump for supplying the replacement fluid on the replacement fluid line,
The continuous blood filtration device according to claim 1, comprising: An arterial line for introducing blood into the blood inlet side of the hollow fiber membrane blood filter,
A blood pump for delivering blood on the arterial line;
Hollow fiber membrane blood filter,
A venous line for drawing blood from the blood outlet side of the hollow fiber membrane blood filter;
A filtrate line connected to the filtrate side of the hollow fiber membrane blood filter and leading to the filtrate,
And a method of operating a continuous blood filtration device having at least a filtrate pump for delivering filtrate on the filtrate line,
The hollow fiber membrane incorporated in the hollow fiber membrane blood filter is composed of a hydrophobic polymer and a hydrophilic polymer.
A hollow fiber membrane, wherein the hydrophobic polymer is a polysulfone polymer, and the hydrophilic polymer.
Is polyvinylpyrrolidone and / or polyalkylene glycol,
The operating method includes a normal filtration step of obtaining a filtrate of a hollow fiber membrane blood filter by the filtrate pump, and a reverse filtration step of flowing back the filtrate of the hollow fiber membrane blood filter,
The positive filtration step obtains 2-500 ml of filtrate per 1 m ^{2 of} effective filtration area,
In the reverse filtration step, the filtrate having a volume of 0.5 to ²⁰ ml per 1 m ^{2 of} effective filtration area and 0.1 to 50% of the amount of the filtrate is caused to flow backward,
After the forward filtration step reaches a certain amount of filtration, a control means for controlling to repeat one cycle of performing the reverse filtration step of backflowing the constant amount a plurality of times is operated. Method of operating a blood filtration device. A fluid replacement line connected to the venous line to introduce fluid replacement;
And a replacement fluid pump for supplying the replacement fluid on the replacement fluid line,
The operation method of the continuous blood filtration apparatus according to claim 3, wherein: