JPH0359706B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a blood processing device in which a centrifugal separator and a membrane module are connected and integrated.

(Conventional techniques and their problems) In recent years, an abnormal increase in high molecular weight substances in the blood has been associated with rheumatoid arthritis, SLE, myasthenia gravis, Guttopastier syndrome, and idiopathic thrombocytopenia purpura disease. It has become clear that these high molecular weight substances are closely related to the onset and pathology of various diseases such as immune diseases, multiple myeloma, metabolic abnormalities such as macroglobulinemia, and hyperviscosity syndrome, and it has become necessary to remove these high molecular weight substances. Plasma separation methods have become widely used for this purpose. In this plasma separation method, blood is first separated into plasma components and blood cell components, harmful high molecular weight substances are removed from the separated plasma components, and the thus treated plasma components and previously separated blood cell components are injected into the body. This is a method of returning the money to the

Conventional methods for separating blood into plasma components and blood cell components include a membrane separation method using a membrane module and a centrifugation method using a centrifugal separator. The plasma separation method using the membrane separation method described above is as follows: (1) After separating blood into plasma components and blood cell components through a membrane, plasma components containing harmful substances are removed and new plasma in an amount equivalent to the plasma components is separated into blood cells. A method of mixing with ingredients and returning it to the body.

(2) After separating blood into blood cell components (plasma components) through a plasma separation membrane, the plasma components containing harmful substances are brought into contact with an adsorbent to adsorb and remove the harmful substances, and then the plasma components are recombined with blood cell components. How to mix and return to the body.

(3) After separating blood into plasma components and blood cell components through a plasma separation membrane, the plasma components are further separated into low molecular weight substances including albumin and high molecular weight substances using a plasma processing membrane, and high molecular weight substances including harmful substances are separated. A method of returning purified plasma from which molecular weight substances have been removed by mixing it with blood cell count components and returning it to the body (Japanese Unexamined Patent Publication No. 74164/1983, No. 56
−145860, etc.).

(4) After separating blood into plasma components and blood cell components through a plasma separation membrane, the plasma components are cooled to gel high molecular weight substances containing harmful substances, and this gel is removed with a membrane membrane. A method in which only the low molecular weight substances that have passed through the membrane are mixed with blood cell components and returned to the body (Japanese Patent Laid-Open No. 57-31869).

It has been known.

On the other hand, plasma processing methods using centrifugation include (1) After separating blood into blood cell components and plasma components using a centrifugal separator, plasma components containing harmful substances are removed, and new plasma is produced in an amount equivalent to the plasma components. A method of mixing it with blood cell components and returning it to the body.

(2) After separating blood into plasma components and blood cell components using a centrifugal separator, the plasma components are separated into high molecular weight substances and low molecular weight substances using a membrane module, and the purified plasma from which only the high molecular weight substances have been removed is separated into blood cells. Method for returning ingredients to the body (Japanese Patent Application Laid-open No. 57-64058
No. 59-8967).

It has been known.

Among the above plasma processing methods, plasma exchange therapy, in which separated plasma is exchanged with new plasma, has problems in securing plasma from healthy people who will be transfused to patients.
In addition, since transfusion of plasma from a healthy person can cause side effects such as infection with new pathogens and incidence of serum sickness, it is considered desirable to purify the patient's own plasma before transfusion. Among these, there is a method in which blood is separated into blood cell components and plasma components using a centrifugal separator, and then the separated plasma components are processed using a membrane module.
This is an excellent and extremely safe method as there is no concern about reduction in separation efficiency or hemolysis. However, at present, there are almost no blood processing methods in which plasma is processed using a combination of a centrifugal separator and a membrane module. The reason for this is that there are two types of existing centrifugal separators: batch processing and continuous processing, and it is extremely difficult to connect and integrate them with the membrane module, and the centrifuge and membrane module have limited processing capacity. Because of the difference, it may be difficult to balance the flow rates by controlling only the membrane module independently of the control system of the centrifugal separator. Therefore, the conventional centrifugal separator and membrane module are connected through a dedicated closed circuit.
In addition, the pumps and other equipment connected to the membrane module are controlled by the control system of the centrifugal separator, and when connecting an existing centrifugal separator and membrane module, it is necessary to modify the control circuit of the centrifuge. It was hot. Moreover, such a device is extremely expensive because it is a device exclusively for blood processing.

Therefore, it is an object of the present invention to separate the control system of the membrane module from the control system of the centrifugal separator and perform it separately, and to continuously connect and integrate the control system with both of the two types of existing centrifugal separators. The purpose of the present invention is to provide a processing device.

(Means for solving the problem) The present invention continuously connects a centrifugal separator and a membrane module provided in an extracorporeal circulation circuit,
Plasma components separated by a centrifugal separator are separated into high molecular weight substances and low molecular weight substances by a membrane module.
In a blood processing device that returns purified plasma and blood cell components from which high molecular weight substances have been removed into the body, a plasma storage bag is provided in a plasma supply circuit that connects a centrifugal separator and a membrane module in the extracorporeal circulation circuit, and a plasma storage bag is provided. A plasma supply pump is provided that can adjust the flow rate so that the liquid level is within a set range by interlocking control with a means for detecting the liquid level in the bag, and the membrane module removes high molecular weight substances. A purified plasma storage bag is included in the purified plasma return circuit that returns plasma to the body, and the ratio between the amount of plasma introduced into the membrane module and the amount of purified plasma taken out is set to a predetermined value by interlocking control with the plasma supply pump. This is a blood processing device characterized by being equipped with a purified plasma delivery pump.

In the centrifugal separator connected to the membrane module in the present invention, blood is supplied into the centrifuge bowl from one side, only plasma components are continuously taken out from the bowl from the other side, blood cell components are accumulated in the bowl, and blood cells are collected. A batch-type centrifugal separator (manufactured by Haemonetics) that immediately stops blood collection and extracts the blood cell components accumulated in the bowl from the blood cell supply port when the blood cell detector detects that the components have overflowed the bowl and flowed into the plasma extraction tube. V-50 type device, PEX type device, etc.), and a continuous type centrifugal device (IBM Inc. 2997 type device and Fenwal CS-3000
There is a type device).

As the membrane module, a module having a built-in flat membrane or hollow fiber membrane can be used. In particular, it is preferable to use a module containing a hollow fiber membrane because it is easy to manufacture and can be miniaturized. The membrane used in the membrane module selectively separates plasma components into high molecular weight substances and low molecular weight substances, and the molecular weight cutoff can be set arbitrarily depending on the purpose. For example, in the case of autoimmune disease, which is one of the main target diseases for treatment using the device of the present invention, the molecular weight cutoff can be set at 100,000. This is because the causative substances of autoimmune diseases often exist in a form bound to γ-globulin, which has a molecular weight of about 160,000, so this removes substances with larger molecular weights and removes substances with lower molecular weights that are incompatible with living organisms. It is desirable to reflux especially useful albumin, which has a molecular weight of 67,000. Therefore, if the molecular weight cutoff is 100,000,
The above-mentioned γ-globulin and albumin can be sharply fractionated. The molecular weight cutoff of the membrane should be set according to the molecular weight of the target pathogenic substance. Set between 200,000. As such a membrane, any membrane may be used as long as it can fractionate and separate plasma components under pressure, and in this sense, membranes having ultrafiltration membranes can be widely used. Therefore, the membrane structure is not particularly limited, and homogeneous microporous membranes and asymmetric membranes can be used. Materials for such membranes include polyvinyl alcohol (PVA), ethylene-vinyl alcohol (EVA) copolymers, cellulose derivatives such as cellulose acetate, polyolefins, polyacrylonitrile, polyamides, polyesters,
Polysulfone or the like is used. Among these, it is desirable to use PVA type, EVA type, cellulose derivatives, polysulfone, etc., which have excellent biocompatibility.

(Function) The blood processing device of the present invention includes a plasma storage bag in the plasma supply circuit that connects the centrifugal separator and the membrane module, and a purified plasma return circuit that returns plasma purified by the membrane module to the body. By providing a purified plasma storage bag and interlockingly controlling the liquid level detection means of the plasma storage bag and the plasma supply pump, the control system of the centrifugal separator of the membrane module can be separated and operated independently. Therefore, it is possible to connect the membrane module continuously to either of the two types of centrifugal separators, and to process blood continuously as if the centrifugal separator and the membrane module were controlled by one control system. can.

(Example) Next, an example of the apparatus of the present invention will be described with reference to the drawings. Figure 1 is a system diagram of a device that combines a continuous centrifugal separator and a membrane module. To explain its configuration according to the flow of blood, blood first flows from the patient into the blood introduction section 1 (shunt, injection The blood is transported from a part (such as a needle that can be connected to an ordinary blood collector or a blood reservoir) through a blood introduction circuit 20 to a centrifugal separator 3 by a pump 2 such as a roller pump, if necessary. Blood introduced into the centrifugal separator 3 is separated into plasma components and blood cell components by centrifugal force, and the separated plasma components are connected to the membrane module 6 by a roller pump (not shown) built into the centrifuge. plasma supply circuit 21
The air contained in the plasma is separated and stored in the plasma storage bag 4, which is easily inflated by the pressure provided in the plasma supply circuit, and is stored in the upper part of the plasma storage bag. On the other hand, the separated blood cells are introduced from the blood cell supply circuit 23 to a mixer 9 such as a Y-shaped connector. The plasma storage bag 4 is provided with means 10 for detecting the liquid level in the bag. Once supplied to the plasma storage bag, the bag inflates and the separated air collects at the top. When a certain amount of plasma has accumulated in the plasma storage bag, the plasma supply pump 5, such as a roller pump whose motion is controlled by the liquid level detection means, is activated to take out the plasma from the plasma storage bag and transfer it to the membrane. Send to module 6. A drip chamber (not shown) to which a pressure gauge is connected is attached to the plasma supply circuit 21, and the membrane module 6
We are monitoring abnormal pressure due to clogging or other factors. The plasma sent to the membrane module 6 is separated into high molecular weight substances and low molecular weight substances in this module. The purified plasma consisting of low molecular weight substances separated by the membrane module 6 is sent to the purified plasma storage bag 8 provided in the purified plasma return circuit 22 by the purified plasma delivery pump 7 which is continuously controlled with the plasma supply pump 5. , I am saved by this bag. The purified plasma drawn out from the purified plasma storage bag 8 is mixed with blood cell components in a mixer 9 provided in the purified plasma return circuit 22, and then sent to the purified blood drawing unit 1.
8 (the part that can connect to the shunt, IV set, etc.) is infused to the patient. On the other hand, the concentrated plasma containing high molecular weight substances separated by the membrane module 6 is discharged by the concentrated plasma discharge pump 15 provided in the concentrated plasma discharge circuit 24. The flow rate of the concentrated plasma discharge pump 15 is normally set to 1/5 to 1/10 of the flow rate of the plasma supply pump 5. Alternatively, the concentrated plasma discharge pump 15 may be controlled in conjunction with the plasma supply pump 5 so that the flow rate ratio between the amount of plasma supplied to the membrane module and the amount of concentrated plasma derived from the module is normally a predetermined value. good. In this case, when the flow rate of the plasma supply pump 5 is set to 30c.c./min, the flow rate of the concentrated plasma discharge pump 15 is 1/5 to 1/5 of the flow rate of the plasma supply pump 5.
It is automatically adjusted to 1/10 or less, that is, 6 c.c./min to 3 c.c./min or less. Further, the purified plasma delivery pump 7 adjusts the flow rate ratio between the amount of plasma delivered to the membrane module 6 and the amount of purified plasma delivered from the membrane module to a predetermined value by interlocking control with the plasma supply pump 5. It is something that
For example, if the flow rate of the plasma supply pump 5 is set to 30 c.c./min, the purified plasma delivery pump will flow at 24 to 30 c.c./min.
It will be controlled by min. When the entire amount of plasma is passed through the membrane module, the flow rates of the plasma supply pump and purified plasma delivery pump are set to be equal. The concentrated plasma evacuation pump may then be stopped or removed from the device. In that case, it is necessary to close the concentrated plasma outlet of the membrane module.

When the entire amount of plasma is passed through, in order to prevent clogging of the membrane, as shown in FIG. A valve 17 may be provided which is opened and closed by interlocking control. In this case, when the membrane is clogged and the plasma supply pressure reaches a predetermined pressure, the valve 17 is temporarily opened and flushed. For example, the valve can be set so that when the plasma supply pressure becomes 400 mmHg or more, the valve remains open until the pressure decreases to 400 mmHg or less.

The purified plasma delivery pump of the purified plasma return circuit 22 of the fluid replacement circuit 25 replenishes the purified plasma with replacement fluids such as albumin and hydroxyethyl starch (HES) from the fluid replacement bag 11 to supplement the concentrated plasma removed by the membrane module 6. It may be connected to the upstream side. In this case, the flow rate of the purified plasma delivery pump 7 is set so that the amount of plasma supplied to the membrane module 6 and the amount of purified plasma, which is the amount of purified plasma to which replacement fluid is added, delivered from the membrane module are equal. Then, a replacement fluid equivalent to the amount of concentrated plasma discharged by the concentrated plasma discharge pump 15 is injected into the purified plasma storage bag 8. A bypass circuit 12 that bypasses the purified plasma delivery pump when a fluid replacement circuit is provided.
It is preferable to provide This bypass circuit opens the valve 13 and transfers replacement fluid to the purified plasma storage bag 8 when a problem occurs that requires replacing the membrane module due to clogging of the membrane module 6, and all pumps of the membrane module are stopped. It is transported by bypass. When the trouble is resolved, the valve 13 can be closed and normal operation can be resumed. Therefore, even when the device is stopped, continuous infusion can be performed without interruption to the patient, resulting in higher safety.

Preferably, the means 10 for detecting the liquid level in the plasma storage bag 4 constantly monitors the liquid level because the setting of the liquid level can be easily changed. As the liquid level detection means, a method using a pressure sensor that detects the liquid level by pressure, a method of detecting the liquid level by weight, a method of directly detecting the liquid level by ultrasonic waves, etc. can be used. The plasma storage bag 4 is detected by this liquid level detection means 10.
In addition to detecting the amount of plasma stored in the plasma, the number of rotations of the plasma supply pump 5 is automatically changed or the switch is automatically turned on by interlocking control with this detection means.
By turning it ON and OFF, the liquid level in the plasma storage bag can be controlled to be within the set range. For example, if the liquid level falls below the set level, the rotation speed of the plasma supply pump 5 is slowed down,
Alternatively, it is better to temporarily stop it. In particular, in a system where the plasma supply pump is automatically turned on and off, if the flow rate of the plasma supply pump is set higher than the plasma flow rate derived from the centrifugal separator, a large amount of plasma will accumulate in the plasma storage bag 4. Plasma can be processed quickly without any problems.

The means for controlling the flow rate of each of the pumps 5, 7, and 15 may be a method of electrically controlling the rotational speed of the pumps. Alternatively, a double or triple roller pump may be used. In this case, the flow rate of liquid flowing through each circuit can be adjusted by changing the diameter of each tube. The plasma storage bag 4 is a plastic bag that easily expands under pressure, and a blood bag of 50 to 3000 c.c. is usually used. The purified plasma storage bag 8 is normally a plastic flexible plasma bag with a capacity of 200 to 3000 c.c., similar to the plasma storage bag described above, but when purified plasma is returned to the body using a purified plasma delivery pump,
A non-flexible container of ~50 c.c., such as a drip chamber, may also be used. The mixer 9 is for mixing purified plasma and blood cell components, and it is preferable to mix it by stirring, etc.
Sufficient mixing can also be achieved by combining two fluids. The above device may further be provided with a plasma warmer for warming the plasma cooled during extracorporeal circulation and a prefilter for removing formed components in the plasma on the upstream side of the membrane module.

FIG. 3 is a system diagram of an apparatus that combines a batch type centrifugal separator and a membrane module. In a batch-type centrifugal separator, sterile air flows into or out of the centrifugal bowl during the blood collection and blood return steps. In other words, the sterile air initially filled in the centrifuge bowl is expelled by the blood introduced into the bowl during blood collection, but when blood is returned, the blood cell components accumulated in the bowl flow into the bowl. Bacteria are being driven out by the air. In addition, in the batch-type centrifugal separator, in addition to the two-arm method in which blood is collected and returned (or returned plasma) using separate needles, purified plasma and blood cell components are mixed in a centrifuge bowl and the blood is returned from the blood inlet. There is an arm method. Fig. 3 shows an example of a device using the two-arm method, and its configuration will be explained according to the blood flow. The blood is transported from the part that can be connected to a blood reservoir or the like through the blood introduction circuit 20 into the bowl of the centrifugal separator 3 by a pump 2, such as a roller pump, if necessary. Then, the sterile air filled in the centrifugal bowl is expelled by the blood supplied by the pump 2, and first the sterile air and then the separated plasma components are transported to the plasma storage bag 4 via the plasma supply circuit 21. . On the other hand, the separated blood cell components are accumulated as they are in the centrifuge bowl. When a blood cell detector (not shown) detects that the blood cell components accumulated in the centrifugal bowl overflow from the centrifugal bowl and flow into the plasma supply circuit, the drive of the centrifugal separator is stopped and the blood collection process is completed; Move on to the blood return process. Plasma separated by a centrifugal separator during blood collection is processed by a membrane module 6. That is, the plasma components separated by the centrifugal separator are led to the plasma supply circuit 21 by a roller pump (not shown) built into the centrifugal separator, and stored in the plasma storage bag 4 provided in the above-mentioned path. Plasma components stored in the plasma storage bag 4 are separated into high molecular weight substances and low molecular weight substances by the membrane module 6 in the same way as shown in FIG. 1, and the separated purified plasma is transferred to the purified plasma storage bag by the purified plasma delivery pump 7. Sent to 8. The purified plasma drawn out from the purified plasma storage bag 8 is infused into the patient from the purified plasma return circuit 22 through the purified plasma delivery section 18 (a section that can be connected to a shunt, drip set, etc.).

In the blood return process, the roller pump 2 that introduces blood into the centrifugal bowl is rotated in the opposite direction. Then, the blood cell components accumulated in the bowl are sucked into the blood introduction circuit 20 and returned to the body from the blood introduction section 1 through the circuit. This blood return operation is performed using a centrifugal separator. When the blood cell components in the bowl are taken out, the inside of the bowl becomes negative pressure, so that the sterilized air accumulated in the upper part of the plasma storage bag 4 is sucked into the bowl from the plasma supply circuit 21. When the blood cell components in the bowl are completely replaced with sterile air and this sterile air is further sucked by the roller pump 2 and flows out into the blood introduction circuit 20, an air bubble detector (not shown) provided in the blood introduction circuit is activated. The pump 2 is then stopped, and the blood return process is thus completed. The above two steps of blood collection and blood return are considered as one cycle, and this is repeated as many times as necessary.

In FIGS. 2 and 3, the same parts as in FIG. 1 are given the same numbers, and their explanations are omitted.

(Effects of the Invention) As described above, the device of the present invention includes a plasma storage bag in the plasma supply circuit that connects the centrifugal separator and the membrane module, and a purification system that returns plasma purified by the membrane module to the body. By providing a purified plasma storage bag in the plasma return circuit, plasma separated by the centrifugal separator is temporarily stored in the plasma storage bag, and purified plasma processed by the membrane module is also temporarily stored in the purified plasma storage bag. ,
The permembrane module corrects the imbalance between the plasma flow rate separated by the centrifuge and the plasma flow rate processed by the permembrane module, the plasma flow rate processed by the permembrane module, and the purified plasma returned to the patient. can be connected continuously with either of two types of centrifugal separators. Furthermore, in the device of the present invention, by interlockingly controlling the liquid level detection means provided in the plasma storage bag and the plasma supply pump, the control system of the centrifugal separator of the membrane module can be separated and operated independently. Blood can be continuously processed as if the centrifugal separator and membrane module were controlled by one control system.

With the device of the present invention, harmful substances in the blood can be removed efficiently and safely without damage or loss of red blood cells or platelets or loss of serum proteins.

[Brief explanation of drawings]

The drawings show one embodiment of the blood processing device of the present invention, and FIGS. 1 and 2 are system diagrams of a blood processing device that combines a continuous centrifugal separator and a membrane module, and FIG. 1 is a system diagram of an apparatus that combines a type centrifugal separator and a membrane module. 1...Blood introduction port, 3...Centrifugal separator, 4...
...Plasma storage bag, 5...Plasma supply pump, 6...
...Membrane module, 7...Purified plasma delivery pump, 8...Purified plasma storage bag, 18...Blood outlet.

Claims (1)

[Claims] 1 A centrifugal separator and a membrane module installed in the extracorporeal circulation circuit are connected continuously, and the plasma components separated by the centrifugal separator are separated into high molecular weight substances and low molecular weight substances by the membrane module. In a blood processing device that returns purified plasma and blood cell components from which molecular weight substances have been removed into the body, a plasma storage bag is provided in a plasma supply circuit that connects a centrifugal separator and a membrane module in the extracorporeal circulation circuit; A plasma supply pump is provided that can adjust the flow rate so that the liquid level is within a set range by interlocking control with a means for detecting the liquid level in the membrane, and the purified plasma from which high molecular weight substances have been removed by the membrane module is provided. A purified plasma storage bag is installed in the purified plasma return circuit that returns the purified plasma to the body, and the ratio between the amount of plasma introduced into the membrane module and the amount of purified plasma taken out is set to a predetermined value by interlocking control with the plasma supply pump. A blood processing device characterized by being provided with a plasma delivery pump.