JPH0112500B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a device used for collecting human plasma, which is used as a raw material for therapeutic infusions and plasma preparations.

Conventionally, plasma was collected from blood using a centrifuge, but recently plasma and formed components (red blood cells, red blood cells,
Membrane-type plasma separators that can separate white blood cells and platelets (white blood cells, platelets) have become available, and plasma collection using these devices has begun to be considered.

There is a presentation by the present inventors (Proceedings of the 20th Annual Conference of the Japanese Society for Artificial Organs, p. 123, 1982) regarding collection from a vein using a pump, and a method of perfusing blood using arterial pressure without using a pump. Regarding this, there is a presentation by Garland et al. (American Society for Artificial Organs, 29th Annual Conference Abstracts, p. 85, 1983).

The present inventors continued to study methods and devices for collecting plasma more safely using a pump, and arrived at the present invention.

FIGS. 1 and 2 are explanatory diagrams showing examples of basic embodiments of the plasma collection device of the present invention. Figure 1 shows how plasma is collected while collecting blood from a plasma donor.
FIG. 2 shows a mode in which plasma is collected while returning concentrated blood from the blood storage bag.

In the present invention, a puncture section 1, a blood conduit 2 having a pump pump, a plasma separator 3, a blood conduit 4, and a blood bag 5 are connected in this order, and the plasma conduit is connected to the plasma withdrawal port of the plasma separator. This plasma collection device is characterized in that it is equipped with a blood plasma bag 6, which is further equipped with a blood pump that is operated only when blood is collected, and configured such that the blood bag can be installed above the puncture section.

As a device similar to the device of the present invention, there may also be a device that reverses the blood pump even when returning blood and uses the blood pump to return blood. In this case, if some kind of error (delay in stopping the blood return pump) occurs at the end of blood return, there is no possibility that a serious accident such as air being injected into the plasma donor will occur. This is a problem with this method, which collects plasma by repeating this process over and over again. In other words, with the device of the present invention, if blood is returned by head without using a blood pump, the blood flow will automatically stop due to venous pressure, making it impossible to inject air into the plasma donor in the unlikely event of an accident. It disappears. This is one of the simple but important features of the device of the present invention.

The blood pump of the present invention, which operates only during blood collection, may be controlled manually, but for safety reasons, a controller is added to monitor the rotation speed of the blood pump and automatically stop it. It is preferable to do so. It can be adjusted according to the volume of the blood bag (usually 150 to 600 ml), but it stops when the set amount of blood, usually about 100 to 500 ml, preferably 200 to 400 ml, is delivered.

At this time, it is also preferable that at the same time as the blood pump is stopped, the rollers pressing the squeezing portion of the blood conduit are released and blood return begins automatically. Alternatively, a bypass conduit is provided at the strained part of the blood conduit,
It is also possible to close the bypass conduit when collecting blood and open it when returning blood.

Furthermore, instead of or in addition to the control based on the rotational speed of the blood pump, it is also preferable to use a control system that monitors the weight or liquid level of the blood bag and stops the blood pump.

In addition, in order to prevent the pump from suctioning too much blood from the donor's vein, a negative pressure detector (called a pillow in the blood circuit for artificial kidneys) is installed between the puncture site and the pump squeeze site. It is also preferable to add a control system that temporarily stops the blood pump or automatically reduces the rotation speed based on the signal.

When performing plasma collection, it is necessary to use an appropriate amount of blood anticoagulant. It goes without saying that if anticoagulant blood circuits and plasma separators are developed, they will be needed only for collected plasma. Any anticoagulant that can be used for extracorporeal blood perfusion may be used, such as heparin, citric acid (ACD, CPD, etc.), prostaglandin,
FOY, MD-805, FUT-175, etc. are used.
Depending on their properties, these can be administered to plasma donors by injection, or by creating a branch in the blood conduit at or after the puncture site, and administering them via a continuous dosing device (such as a heparin pump) or intravenous drip. It is also possible to administer.

As an example of using a citric acid anticoagulant, as shown in the explanatory diagram, an anticoagulant pump B linked to a blood pump is used to supply an anticoagulant 8 such as ACD or CPD using an anticoagulant circuit 7. Mix the optimal amount with blood. In this case, the mixing ratio is adjusted by controlling the rotational speed of blood pump A and anticoagulant pump B, or by changing the pipe diameter of the pump squeezing section.

The device of the present invention does not use a blood pump when returning blood, but returns blood using a drop, and the blood flow is automatically stopped due to venous pressure, thereby avoiding injecting air into the plasma donor in the unlikely event that the blood is returned. In this case, it is necessary to place the blood bag above the puncture site.

When blood is returned by head without using a pump, a part of the plasma is separated during blood collection and the blood stored in a blood bag has a high hematocrit value and becomes viscous, so-called concentrated blood, which causes plasma separation. It takes a long time for the blood to return through the vessel. In order to improve this, as shown in the explanatory diagram, an infusion pump C linked to a blood pump is used to infuse an infusion 10 such as Ringer's solution into a blood conduit 4 or a blood bag 5 using an infusion circuit 9 corresponding to the amount of collected plasma when blood is collected. It is preferable to infuse the amount in a range of 1/4 to 1/4 of the amount.

This method reduces the viscosity of the blood stored in the blood bag, shortens the blood return time, and
The amount of plasma separated during blood return is greatly increased and the time required for plasma collection is shortened. In other words, the rate of plasma collection from collected blood has greatly increased, and anticoagulants (heparin, ACD,
The rate of return of plasma (CPD, etc.) to plasma donors is greatly reduced, making it safer. In addition, when the final blood is returned at the end of plasma collection, the blood can be returned while being pushed out with an infusion, making it possible to return the blood more completely. Furthermore, it is also possible to clean and fill the circuit and plasma separator with physiological saline, Ringer's solution, etc. through an infusion tube in preparation for plasma collection.

Embodiments of the device of the present invention will be described in detail.

Blood introduced from a blood collection needle (puncture point) punctured into the vein of a plasma donor (donor) is guided by a blood pump A to a blood bag 5 through a plasma separator 3. By placing the plasma bag 6 connected to the plasma extraction port of the plasma separator at the same height as the blood bag or below it, a pressure difference is created between the blood side and the plasma side of the plasma separation membrane to separate the plasma. Collect. Blood in which a portion of plasma is separated and blood cell components are concentrated (concentrated blood) is stored in a blood bag.

In order to obtain a sufficient plasma separation rate, the height difference between the blood bag and the plasma bag is about 20 cm to 150 cm, preferably about 40 cm to 120 cm. Increase the altitude difference,
For example, if the distance is 150 cm or more, the initial separation speed will increase, but its change over time will increase, and in some cases, hemolysis due to destruction of red blood cells will occur, which is undesirable. The differential pressure (overpressure, transmembrane pressure) suitable for plasma separation differs depending on the type of separation membrane, but generally a range of 0 to 150 mmHg, preferably 5 to 50 mmHg is appropriate, and therefore the above-mentioned The difference in altitude is adjusted.

Predetermined amount of blood (usually 100-400ml) into blood bag
When the blood is stored, blood begins to be returned.

By manually or automatically opening the straining part of blood pump A, the pooled blood is returned to the plasma donor from the puncture part through the plasma separator. At this time, a portion of the plasma is separated again and collected into a plasma bag.

In order to obtain a sufficient blood return rate and plasma separation rate, as described above, it is preferable to dilute the concentrated blood in the plasma bag with an infusion solution such as Ringer's solution at the time of blood collection or before and after blood collection. The amount of infusion fluid used ranges from the equivalent amount of plasma collected during blood collection to about 1/4 of that amount.
The amount is preferably about 2/3 to 1/3, and adjusted depending on the amount of anticoagulant used. When using citric acid-based ACD or CPD as an anticoagulant, a considerable rate of blood return can be obtained without using infusion fluids. When using citric acid-based anticoagulants, care must be taken, such as using an infusion solution that does not contain calcium ions. Furthermore, it is also a preferable method to dilute the anticoagulant with physiological saline or the like in an amount equivalent to an infusion solution and continuously inject it.

As mentioned above, the blood return speed and plasma separation speed during blood return vary depending on the amount of transfusion and anticoagulant used, but the positions of the blood bag and plasma bag are shown based on the puncture site. The blood bag should be 50~ above the puncture site.
120cm (H ₁ = 50-120cm in the illustration), preferably 60
~100cm, and the plasma bag is above the puncture site.
Between 40cm and 80cm below (H ₂ = -40 to 80 in the explanatory diagram)
cm), preferably around 0 to 40 cm below.

Normally, H ₁ is fixed between 60 and 100 cm, and H ₂ is fixed between 0 and 40 cm, and plasma collection can be performed without moving the blood bag or plasma bag during blood collection or blood return.

This blood collection and blood return process is repeated until a predetermined amount (generally 80~
Collect 1000 ml (usually 400-600 ml) of plasma into a plasma bag.

The puncture needle (blood collection needle) used in the puncture part of this device is the one used for normal blood donation and extracorporeal circulation14
A puncture needle of ~18 gauge is used. For blood conduits, plasma conduits, anticoagulant circuits, and infusion circuits, the inner diameter is 2 mm to 5 mm (the inner diameter of the strained part is 1.5 mm), which is used for normal blood collection and blood circuits for artificial kidneys.
A blood circuit tube made of vinyl chloride, silicone, etc., with a diameter of about 8 mm) is used.

As the blood bag, a bag with a content capacity of 150 to 600 ml, preferably 200 to 400 ml, which is made of vinyl chloride, silicone, polyolefin, etc. and is used for blood donation or blood fraction preparations and has good blood compatibility is used. As a plasma bag, the content is 80 to 1000.
Similar bags of 200-800 ml are used. In addition to bags, glass or plastic containers can also be used for blood bags and plasma bags.

As the plasma separator, any membrane type plasma separator that has a high plasma separation rate and good plasma protein permeability can be used. Hollow fiber separators, which have been recently developed, are preferably used because they have a small amount of blood filling. As the membrane material, any material that is safe for the living body can be used, such as polymethyl methacrylate, cellulose acetate, polyvinyl alcohol, polyethylene, polypropylene, polycarbonate, and polyvinyl chloride.

The present invention will be explained below with reference to Examples.

Example: Toray Industries, Inc. “Plasmatux” as a plasma separator
PS-02 (polymethyl methacrylate hollow fiber membrane, blood capacity 20 ml, membrane area 0.15 m ² ), blood conduit, vinyl chloride tube (Clinical Supply Co., Ltd. for artificial kidney blood circuit, inner diameter 3.7 mm) as a blood conduit and plasma conduit, the straining part of the blood conduit A vinyl chloride tube with an inner diameter of 6.3 mm is used, a tube with an inner diameter of 2.1 mm is used for the squeezing part of the anticoagulant circuit and the infusion circuit, and a blood bag for blood collection (Terumo Corporation "Telfrex" capacity 350 ml) is used as the blood bag and plasma bag. A device was fabricated as shown in FIG. Blood pump A, anticoagulant pump B, and infusion pump C were controlled to rotate in conjunction with each other, and when a negative pressure detector attached to the blood conduit indicated negative pressure, the pumps were stopped with an alarm.

As an anticoagulant, CPD solution (sodium citrate 2.63g, citric acid 0.327g, sodium phosphate 0.251g, glucose 2.32g in 100ml) is used, and as an infusion solution for diluting concentrated blood, Midori Jujisha Fidiosol 2 is used. No. was used.

Blood bag is 80cm above the puncture site (H ₁ = 80cm)
The plasma bag is placed 20cm below the puncture site (H ₂ = 20cm).
It was installed in

The left femoral vein of a mixed dog weighing 29 kg was secured under Nembutal anesthesia, and a plastic puncture needle (14G, Nipro) was used as the puncture site.

Connect the puncture needle and blood conduit, and pump the blood every minute.
Blood was collected by rotating with 65 ml. In conjunction with this, the anticoagulant pump and infusion pump rotate at the same rotational speed, every minute.
Anticoagulant and intravenous fluid were injected at 7.2 ml. Until the blood from the puncture site reached the blood bag, the blood conduit was disconnected from the blood bag, the filled saline was discarded, and plasma collection was started.

4 minutes and 30 seconds after the start, 230 ml of blood was collected in the blood bag, and about 90 ml of plasma was collected in the plasma bag. Then, the pump was stopped, and the blood pump roller was moved away from the squeezing part to return blood using a drop. Blood return from the blood bag was completed in 4 minutes and 20 seconds, and about 155 ml of plasma was collected in the plasma bag. These blood collection and blood return procedures were repeated, and approximately 18
Approximately 290 ml of plasma was collected in minutes.

During the final blood return, only the infusion pump was operated to push out the blood with approximately 50 ml of Fidiosol No. 2 solution, resulting in almost complete blood return.

The total protein concentration of the collected plasma was compared to that of the plasma collected from the dog at the end of the blood collection and centrifuged.
It was 78%. Furthermore, the hematocrit value of the dog's blood at the start of this experiment was 45%, and approximately 520 ml of blood was taken out of the body, which calculated that 79% of the plasma contained therein was collected, and the anticoagulant used was Approximately 12ml (21%) of the 58ml (CPD fluid) is returned to the dog's body.

According to the device of the present invention, since no air injection occurs during blood return, it is possible to safely collect plasma. In addition, by infusing blood at the time of blood return, plasma can be obtained at a high yield, and a relatively small amount of anticoagulant can be injected into the plasma donor.

[Brief explanation of drawings]

FIG. 1 is a schematic explanatory diagram showing an example of a basic embodiment of the plasma collection device of the present invention at the time of blood collection. FIG. 2 is a schematic explanatory diagram showing an embodiment in which the rotation of the pump shown in FIG. 1 is stopped and the roller of the blood pump A is separated from the straining part of the blood conduit to return blood by a drop. DESCRIPTION OF SYMBOLS 1...Puncture part, 2...Blood conduit having a pump squeezing part, 3...Plasma separator, 4...Blood conduit, 5...Blood bag, 6...Plasma bag, 7...Anticoagulant circuit, 8
... Anticoagulant, 9... Infusion circuit, 10... Infusion, A... Blood pump, B... Anticoagulant pump, C... Infusion pump, H ₁ ... Distance from the puncture site to the blood bag upward, H ₂ ... Distance from the puncture site to the plasma bag in a downward direction.

Claims (1)

[Claims] 1. A puncture section 1, a blood conduit 2 having a pump squeezing section, a plasma separator 3, a blood conduit 4, and a blood bag 5 are connected in this order, and connected to the plasma extraction port of the plasma separator by a plasma conduit. plasma bag 6
What is claimed is: 1. A plasma collection device comprising: a blood pump configured to operate only during blood collection, and configured such that the blood bag can be installed above the puncture portion.