JPS61193668A - Serum treatment apparatus - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention relates to a plasma processing device that can be systematized by connecting a patch-type centrifugal separator and a transient membrane module. This system can efficiently remove pathogen-related substances and harmful substances such as immune complexes, immunoglobulin aggregates, and nucleic acids contained in the blood.0 (Conventional technology and its problems) An abnormal increase in high molecular weight substances is associated with rheumatism, autoimmune diseases such as 8LE, myasthenia gravis, Guttpasser chair syndrome, idiopathic thrombocytopenic purpura, and metabolic disorders such as multiple myeloma and macroglobulinemia. It has become clear that these substances are closely related to the onset and pathology of various diseases such as high-molecular-weight substances and hyperviscosity syndrome. The method involves first separating blood into plasma components and blood cell components, removing harmful high molecular weight substances from the separated plasma components, and returning the processed plasma components and previously separated blood cell components to the microorganism. Conventional methods for separating blood into plasma components and blood cell components include a membrane separation method using a transient 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 plasma separation membrane, plasma components containing harmful substances are removed, and an amount of new blood equivalent to the plasma components is removed. Method of mixing plasma with blood cell components and returning it to the body 0 (2) After separating blood into plasma and blood cell components through a plasma separation membrane, plasma components containing harmful substances are brought into contact with an adsorbent to remove harmful substances. A method in which substances are adsorbed and removed, and then the plasma components are mixed with blood cell components again and returned 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 Alponic, and high-molecular weight substances, using a plasma processing membrane, to remove harmful substances. A method for returning purified plasma from which high molecular weight substances have been removed, mixing it with blood cell components and returning it to the body (Japanese Patent Application Laid-open No. 56-7416
No. 4, No. 56-145860, etc.).

-) 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 including harmful substances, and this gel is removed with a temporary membrane. A method is known in which only low molecular weight substances that have passed through a membrane are mixed with blood cell components and returned to the body (Japanese Patent Application Laid-Open No. 57-31869).On the other hand, plasma processing methods using centrifugation include (1)
A method in which blood is separated into blood cell and plasma components using a centrifugal separator, the plasma components containing harmful substances are removed, and new plasma in an amount equivalent to the blood cell components is mixed with the blood cells and components and returned 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 transient membrane module, and purified plasma from which only high molecular weight substances have been removed is produced. Method of returning blood cells to the body along with blood cell components (
JP-A-571-64058, JP-A No. 59-8967).

It has been known.

Among the plasma processing methods mentioned above, in plasma exchange therapy, in which separated plasma is exchanged with new plasma, there are problems in securing plasma from healthy individuals to be transfused to patients. Because of the side effects of infection with new pathogens and serum sickness, it is considered desirable to purify one's own plasma and transfuse it later. Among them, the method of separating blood into blood cell components and plasma components using a centrifugal separator and then processing the separated plasma components using a filtration membrane module is an extremely safe and excellent method because there is no need to worry about decreases in separation efficiency or hemolysis. It's a method.

However, at present, there are almost no plasma processing methods in which plasma is processed using a combination of a centrifugal separator and a transient membrane module. The reason for this is that conventional centrifugal separators and transient membrane modules are connected through a dedicated closed circuit, and the control system of the centrifugal separator controls pumps and other equipment connected to the transient membrane module. This is thought to be because it was difficult to connect the centrifugal separator with the existing centrifugal separator, as it required modifying the control circuit of the centrifugal separator when connecting the transient membrane module.

(Means for Solving the Problems) Accordingly, an object of the present invention is to separate the control system of the plasma processing device from the control system of the centrifugal separator and perform the control separately, and to continuously connect the control system with the centrifugal separator. The object of the present invention is to provide a plasma processing device that can be used for various purposes.

The present invention is continuously connected to a batch type centrifugal separator provided in an extracorporeal circulation circuit, and plasma components separated by the centrifugal separator are converted into high molecular weight substances and low molecular weight substances including albumin using a transient membrane module. In a plasma processing device in which purified plasma from which high molecular weight substances have been removed and separated blood cell components are returned to the body from a blood introduction circuit to a centrifugal separator, a centrifugal separator and a filtration membrane in the extracorporeal circulation circuit are provided. A plasma supply circuit connecting the Mosier is provided, a plasma storage bag is provided in the circuit, and a means for sensing the liquid level in the nuclear bag is provided, or the liquid level is controlled in conjunction with the liquid level sensing means. A plasma supply pump that can adjust the flow rate so that the surface level is within a set range is installed, and a circuit is installed to return purified plasma containing albumin from which high molecular weight substances have been removed by the cough membrane module to the body. In addition to providing a purified plasma storage tank, a purified plasma delivery pump is provided which is set so that the flow rate ratio between the amount of plasma introduced into the membrane module and the amount of purified plasma taken out is a predetermined value by interlocking control with the plasma supply pump; Furthermore, a concentrated plasma discharge pump set so that the discharge amount of high molecular weight substances is a predetermined value is installed in the concentrated plasma discharge circuit of the F:ii membrane module, and plasma is supplied through the purified plasma return circuit via a flow path switching means. The plasma storage bag is connected to the circuit, and the plasma storage bag and the purified plasma storage tank are connected by a communication circuit having one end opening into the upper space of the plasma storage bag and the other end opening into the purified plasma storage tank. It is a processing device.

The plasma processing device of the present invention is used in a continuous system with a centrifugal separator, and the plasma components separated by the separator are separated into high molecular weight substances and low molecular weight substances including albumin using a transient membrane module. The present invention relates to a plasma processing device that returns purified plasma from which high molecular weight substances have been removed to the body.

The patch-type centrifugal separator connected to the plasma section embedding device of the present invention supplies blood into a centrifugal bowl on one side, continuously extracts only plasma components from the bowl on the other hand, and removes blood cell components from the bowl. When the blood cell detector detects that blood cell components have overflowed the bowl and flowed into the plasma outlet tube, blood collection is immediately finished and the blood cell components accumulated in the bowl are removed from the blood supply port. Equipment (Haamone
As a transient membrane module for separating plasma in a zero plasma processing apparatus such as V-50 type device and PEX type device manufactured by tics, 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 from the viewpoint of ease of production and miniaturization. The filtration membrane used in the above filtration 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, treatment using the device of the present invention can be performed. In the case of autoimmune diseases as one of the main target diseases, the molecular weight cutoff can be set at 100,000. This is because the pathogenic substances of autoimmune diseases often exist in a form bound to γ-globulin, which has a molecular weight of approximately 160,000, so substances with a larger molecular weight are removed, and substances with a lower molecular weight and a lower molecular weight are removed. It is desirable that albumin, which has a molecular weight of 6,700 G and is useful for living organisms, be refluxed. Therefore, if the molecular weight cutoff is 100,000, the above-mentioned T-globulin and albumin can be sharply fractionated. The molecular weight cutoff of the transient membrane should be set depending on the molecular weight of the target pathogenic substance. It is set between 200,000. As such a transient membrane, any membrane may be used as long as it can fractionate and separate plasma components under pressure, and in this sense, transient membranes having ultra-P permeability can be widely used. Therefore, the structure of the membrane is not particularly limited, and a homogeneous microporous membrane or an asymmetric membrane can be used. The material of such a temporary film is polyvinyl alcohol (PVA).
Ethylene-vinyl alcohol (EVA) copolymers, cellulose derivatives such as cellulose acetate, polyolefins, polyacrylonitrile, polyamides, polyesters, polysulfones, and the like are used.

Among these, PVA type and EVA type which have excellent biocompatibility
It is preferable to use materials such as cellulose derivatives, cellulose derivatives, polysulfone, etc.

FIG. 1 is a system diagram of a system that combines a patch-type centrifugal separator and the plasma processing apparatus of the present invention. Sterile air flows into and out of the bowl during the blood collection and blood return process in a batch-type centrifugal separator. 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 sterile air causes the blood cell components accumulated in the bowl to flow into the bowl. K is expected to be kicked out. Therefore, care must be taken to prevent plasma components containing high molecular weight substances from being mixed into the sterile air flowing into the bowl during the blood return process. FIG. 1 shows an example of a system in which the plasma processing device 60 of the present invention is combined with a batch-type centrifugal separator 50, and its configuration will be explained according to the flow of blood.
In the blood collection process, the switching valve 47 is closed, the switching valve 48 is opened, and blood is introduced from the blood introduction section 1 into the centrifugal separator 50. Blood is first passed through the blood introduction circuit 10 from the blood introduction part 1 (a part that can be connected to a normal blood collection device or blood storage device such as a shunt or a syringe needle), and then, if necessary, to the centrifugal separator 50 using a pump such as a roller pump. transported into bowl 3. Then, the sterile air filled in the centrifugal bowl is expelled by the blood supplied under pressure by pump 2.
First, sterile air is supplied, and then the separated plasma components are supplied to the plasma storage bag 4 through the plasma supply circuit 16 from the inlet 80.
transported to. On the other hand, the separated blood cell components are accumulated in the centrifuge bowl as they are. When the blood cell detector 43 detects that the blood cell components accumulated in the centrifugal bowl overflow from the centrifugal bowl and flow into the plasma supply circuit, the device is stopped and the blood collection process is completed, followed by a blood return process. Move to. At the time of blood collection, the separated plasma is processed by the plasma processing device of the present invention. That is, the plasma components separated by the centrifugal separator 50 are led out from the plasma inlet 80 to the plasma supply circuit 16 by the cooler pump 14, which is self-attached to the centrifugal separator, and are stored in the plasma storage bag 4 provided in the circuit. The plasma storage bag 4 is provided with means 21 for sensing the liquid level in the bag. When more than a certain amount of plasma accumulates in the plasma storage bag, a plasma supply pump 5 such as a low 2'' pump that is controlled in conjunction with the liquid level sensing means is activated to remove the plasma from the bag and filter it through the filter membrane. Send to module 6. The plasma supply circuit 16 is provided with a drip chamber 22 connected to a pressure gauge 23 to monitor abnormal pressure caused by clogging of the transient membrane module 6 or other factors.

The plasma sent to the filtration membrane module 6 is separated into high molecular weight substances and low molecular weight substances including albumin. The purified plasma consisting of low molecular weight substances separated by the transient membrane module 6 is sent to a purified plasma storage tank 8 in a purified plasma return circuit 17 by a purified plasma delivery pump 7 which is controlled in conjunction with the plasma supply pump 5. , and are accumulated in the tank.

On the other hand, the concentrated plasma containing high molecular weight substances separated by the transient membrane module 6 is discharged to the drain tank 28 by the concentrated plasma discharge pump 26 provided in the concentrated plasma discharge circuit 27. The flow rate of this pump 26 is normally 11 times the flow rate of the plasma supply pump 5.
It is set to 5 to 1/10 or less. Also, the above pump 2
6 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 filtration membrane module and the amount of concentrated plasma derived from the module is always a predetermined value. In this case, when the flow rate of the plasma supply pump 5 is set to 3 Q e, e/min, the flow rate of the concentrated plasma discharge pump is 115 to 1/10 or less, that is, 5 cc/min to 3
It is automatically adjusted to below cc/min. In addition, the purified plasma delivery pump 7 is controlled in conjunction with the plasma supply pump 5 to determine a flow rate ratio between the amount of plasma delivered to the modienil filtration membrane 6 and the amount of purified plasma delivered from the transient membrane module. It is adjusted to the value. For example, when the flow rate of the plasma supply pump 5 is set to 39 ec/ml, the purified plasma delivery pump is controlled to 24 to 30 ca/ml. When plasma is passed through the membrane by Joule, the flow rates of the plasma supply pump and purified plasma delivery pump are set to be equal, and the concentrated plasma discharge pump is stopped.

When the blood sampling process is completed, the switching valve 48 closes, and the switching valve 47 closes.
When the valve is opened, the cooler pump 2 for introducing blood into the bowl rotates in the opposite direction to proceed to the blood return process. First, the pump 2 rotates in the reverse direction, and the blood cells in the centrifugal bowl 3 are sucked by the four-ra pump 2 and returned to the body through the blood introduction section 1 provided in the blood introduction circuit 10. When the blood cells start to flow out of the bowl, the inside of the bowl becomes negative pressure, so that purified plasma in an amount equal to the flowed out blood cells is sucked into the bowl from the purified plasma return circuit 17, mixed with blood cell components, and returned to the body. Purified plasma storage tank-9 Once all the purified plasma has been sucked into the bowl,
The sterile air collected in the upper part of the plasma storage tank 4 is connected to the communication circuit 4.
When the purified blood in the bowl is completely replaced with sterile air and the sterile air flows out from the bowl. , the bubble detector 42 provided in the blood introduction circuit 10 is activated to complete the blood return process. The above blood collection process and blood return process are repeated as many times as necessary. In this device, in order to suck the sterile air expelled into the plasma storage bag during blood collection into the centrifugal bowl during the blood return process and replace it with purified blood, there is a communication circuit that transfers the sterile air from the plasma storage bag to the purified plasma storage tank. 49 is absolutely necessary. The opening of this communication circuit to the plasma storage bag must be opened into the upper space of the plasma storage bag so that plasma components are not sucked into the bowl together with sterile air. Further, in place of the above-mentioned communication circuit, intake/exhaust holes with sterilizing filters may be provided above the plasma storage bag and the purified plasma storage tank.

A circuit 1 for replenishing purified plasma with a replacement fluid such as albumin or human tetraxyethyl starch (HES) from a replacement fluid bag 12 in order to supplement the concentrated plasma removed by the transient membrane module 6.
3 may be connected to the upstream side of the purified plasma delivery pump of the purified plasma return circuit 17.

In this case, the flow rate of the purified plasma delivery pump is adjusted so that the amount of plasma supplied to the transient membrane module 6 is equal to the amount of purified plasma, which is obtained by adding replacement fluid to the purified plasma sent from the transient membrane module 6. When set, when a replacement fluid equivalent to the amount of concentrated plasma discharged by the concentrated plasma discharge pump 26 is injected into the purified plasma storage tank 8, the value becomes K.

The means 2 for detecting the liquid level in the plasma storage bag 4 is preferably a method of constantly monitoring the liquid level or changing the setting of the liquid level. As this liquid level detection means, a method using a pressure sensor that detects the liquid level by pressure, a method of sensing the liquid level by weight, a method of directly detecting the liquid level by ultrasonic waves, etc. can be used. .

FIG. 2 shows an example in which a pressure sensor is used as the liquid level sensing means 21. A tube 31 with an inner diameter of 1 mm or less, usually 0.8 mm, is inserted into the pressure detection hole 30 provided at the bottom of the plasma storage bag 4.
is connected, and a pressure sensor 21 is attached to the end thereof. A diaphragm pressure transducer is usually used as the pressure sensor. When plasma is supplied into the plasma storage bag and the liquid level changes, head pressure is applied to the air sealed in the thin tube, and this air pressure gives displacement to the diaphragm. This minute displacement of the diaphragm is detected by a metal wire strain gauge, a semiconductor strain gauge, etc., and the detection signal is transmitted to a control device 32 that controls the drive of each pump. The signal transmitted from the pressure sensor is amplified by an amplification circuit 33 and sent to a comparison circuit 34. In the comparison circuit, setting circuit 35
The signal is sent to the drive circuit 36 to control the rotation of the pump 5.7.26.

This liquid level detection means 21 senses the amount of plasma stored in the plasma storage bag 4, and also automatically changes the number of revolutions of the plasma supply pump 50 or automatically switches the rotation speed of the plasma supply pump 50 by interlocking control with this detection means. By turning it ON-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 a set level, the rotation speed of the plasma supply pump 5 may be slowed down or temporarily stagnated.

The means for controlling the flow rate of each of the pumps 5, 7, and 26 described above may be a method of electrically controlling the rotational speed of the pumps. Alternatively, a dual or twin 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 flexible bag of 50 to 3000 cc;
For example, a commercially available blood bag can be used. In addition, a flexible bag of 200 to 3000 e (!) is usually used as the purified plasma storage tank. In addition to the above device, there is a plasma warmer that warms the cooled plasma during extracorporeal circulation, and a device that removes formed components in the plasma. A pre-filter may be provided upstream of the filtration membrane module.

FIG. 3 is a perspective view of a part of the monitor constituting the plasma processing apparatus of the present invention. A plasma supply circuit 16 and a purified plasma supply circuit 17 are attached. Further, a pipe 31 that leads the head pressure of the plasma storage bag 4 to a pressure sensor is connected to the connector 61, and a pipe that leads the pressure inside the drip chamber 22 provided in the plasma supply circuit to a pressure gauge is connected to the connector 62. 63 is a digital liquid level gauge that displays the liquid level of the plasma storage bag, and displays the head pressure (liquid level) in a per graph. Reference numeral 76 is a switch for setting the plasma level, and the plasma level can be set arbitrarily by this switch. 64 is a pressure gauge that displays the pressure on the inlet side of the filtration membrane module.

Reference numeral 71 is a knob for setting the flow rate of the plasma supply pump 5. The instantaneous flow rate of this pump is digitally displayed on the flow meter 67. The total amount of plasma supplied to the membrane module by the pump is displayed on the totalizer 70.

72 is a main switch. 73 is a changeover switch between automatic operation and manual operation. During automatic operation, when the plasma level in the plasma storage bag is above the set value, the lamp 74 lights up and the pump rotates.

When the plasma level falls below the set value, the above lamp will turn off.
The pump will stop. 75 is an integration button.

The monitor is provided with a lamp that indicates an abnormality when it occurs. 65 is a pressure alarm 2 lamp that lights up when the pressure on the inlet side of the filtration membrane module exceeds the upper and lower limit alarm settings, 66 is a lamp that lights up when the cover of the pump 68 is opened, and 67 is a plasma storage bag light. This is a 2-lamp that lights up when more plasma has accumulated than the allowable amount.

The entire control system of the plasma processing apparatus of the present invention is housed in a part of the monitor. Therefore, when the apparatus of the present invention and the centrifugal separator are connected in series to form a system, the control of the centrifugal separator and the apparatus of the present invention can be performed completely separately.

(Effects) As described above, the device of the present invention is equipped with a plasma storage bag and a purified plasma storage tank, and by interlockingly controlling the liquid level detection means of the plasma storage bag, the plasma supply pump, and the purified plasma delivery pump, We can provide a blood processing system that is continuously connected to a continuous centrifugal separator. This system can efficiently and safely remove harmful substances from the blood without damage or loss of red blood cells or platelets, and without loss of serum proteins. Can be removed.

[Brief explanation of drawings]

The drawing shows one embodiment of the plasma processing apparatus of the present invention, and shows the first embodiment of the plasma processing apparatus of the present invention.
The figure is a system diagram of a system that combines a continuous centrifugal separator and the plasma processing device of the present invention], FIG. 2 is an electric circuit diagram of the liquid level detection means of the plasma storage bag, and FIG. FIG. 1 is a perspective view of a plasma processing device of the present invention.

Claims (1)

[Claims] 1. Continuously connected to a patch-type centrifugal separator installed in the extracorporeal circulation circuit, plasma components separated by the centrifugal separator are separated into high molecular weight substances and low molecular weight substances including albumin using a transient membrane module. In a plasma processing device in which purified plasma from which high molecular weight substances have been removed and separated blood cell components are returned to the body from a blood introduction circuit to a centrifugal separator, a centrifugal separator and a transient membrane in the extracorporeal circulation circuit are used. A plasma supply circuit connecting the modules is provided, a plasma storage bag is provided in the circuit, and a means for sensing the liquid level in the bag is provided, and the liquid level is controlled by interlocking control with the liquid level sensing means. A plasma supply pump is provided that can adjust the flow rate so that the flow rate is within a set range, and a circuit is provided to return purified plasma containing albumin from which high molecular weight substances have been removed by the filtration membrane module to the body, and the purified plasma is stored in this circuit. In addition to providing a tank, a purified plasma delivery pump is provided which is set so that the flow rate ratio between the amount of plasma introduced into the filtration membrane module and the amount of purified plasma taken out is a predetermined value by interlocking control with the plasma supply pump. The module's concentrated plasma discharge circuit is provided with a concentrated plasma discharge pump that is set so that the discharge amount of high molecular weight substances is a predetermined value, and the purified plasma return circuit is connected to the plasma supply circuit via a flow path switching means. A plasma processing device, characterized in that a plasma storage bag and a purified plasma storage tank are connected by a communication circuit having one end opening into the upper space of the plasma storage bag and the other end opening into the purified plasma storage tank.