JPH0359708B2 - - Google Patents

Description

[Detailed Description of the Invention] <Industrial Application Field> The present invention provides cryoprecivitate (hereinafter abbreviated as CPPT) containing a large amount of blood coagulation factor, which is used for the treatment of hemophilia patients with bleeding tendency. ), specifically the above-mentioned separation system.
This device continuously collects CPPT-enriched plasma from plasma that contains a large amount of CPPT, that is, plasma that is continuously separated from donor blood.

<Conventional technology> Conventionally, CPPT-enriched plasma was obtained by centrifuging 200 ml of whole blood collected from a donor using a batch system, and dividing the resulting plasma for two donors by -20 mL. The frozen storage at a temperature between ℃ and -40℃ is thawed to a low temperature, and the CPPT as a precipitate in the low-temperature liquid plasma is collected in about 20 ml along with some plasma.
It was collected as CPPT plasma.

Furthermore, the present inventors have developed a highly efficient CPPT-enriched plasma separation device in order to meet the recent increase in demand for CPPT-enriched plasma. The device continuously collects plasma in extracorporeal blood circulation by membrane separation of anticoagulated blood from a donor, and enriches the collected plasma by continuous membrane filtration at low temperature.
CPPT plasma was collected as a component that does not pass through the membrane.

<Problems to be solved by the invention> Since the centrifugation method for collecting CPPT-enriched plasma is based on a batch system, continuous separation is not possible, and therefore high separation efficiency cannot be obtained. Unable to meet the increasing demand for CPPT plasma. Although the membrane filtration method described above to overcome this drawback enables highly efficient continuous separation, it has been observed that the filtration performance deteriorates over time due to clogging of the membrane.

<Means for solving the problem> First invention [Invention of Claim 1]
In extracorporeal circulation of anticoagulated donor blood via a plasma separator equipped with a plasma separation membrane, the plasma that has passed through the plasma separation membrane is heated to a temperature of 6°C to -10°C.
The centrifugal separator is continuously supplied to a centrifuge at a temperature of It consists of a cylindrical rotor communicated through a large number of small-diameter communication holes, and a stator that surrounds this rotor and is arranged concentrically with the rotor, and this stator introduces the plasma between it and the rotor. The rotor includes a plasma inlet port arranged at the top, a cryoprecipitate-rich plasma outlet port arranged at the lower side, and a cryoprecipitate-poor plasma outlet port arranged at the bottom. A derivation path is provided between the derivation port and the depletion path for guiding deficient cryoprecipitate in the rotor to the deficient cryoprecipitate plasma derivation port.

Furthermore, in the second invention [the invention set forth in claim 2], in the same configuration, the inner and outer surfaces of the periphery are communicated with each other through a large number of communication holes, and small-diameter pores are provided on the inner or outer surface. It is constructed using a cylindrical rotor covered with a membrane.

<Operation> According to the first invention, the plasma introduced between the rotor and the stator through the plasma introduction port is transferred to the inside of the stator by the centrifugal force generated by the rotation of the rotor. It is transported to the wall and separated into CPPT-rich and CPPT-poor plasma,
On the one hand, the separated CPPT-enriched plasma flows out from the CPPT-enriched plasma outlet port of the stator;
On the other hand, the separated CPPT-poor plasma flows to the inner surface of the rotor through the small-diameter communication hole, and the CPPT-poor plasma that reaches the bottom surface of the rotor flows through the outlet path.
Derived from the CPPT plasma outlet.

According to the second invention, in the same separation action as in the first invention, the separated CPPT-poor plasma is flowed out to the inner surface of the rotor through the pores of the membrane in the communication hole portion.

<Example> Hereinafter, an example of the present invention will be described first with reference to FIG. FIG. 1 shows the flow path system of this embodiment, in which blood from a blood vessel of a donor 1 passes through a blood supply line 3 equipped with a blood pump 2, and is provided with a plasma separation membrane by the operation of the blood pump 2. The plasma is then supplied to a plasma separator 4. During this time, an anticoagulant is continuously added to the blood at a prescribed rate from an anticoagulant container 6 by operation of an anticoagulant pump 5, so that the blood is anticoagulated. The anticoagulated blood supplied to the plasma separator 4 is separated into plasma, which passes through the plasma separation membrane, and red blood cell concentrate, which does not pass through the plasma separation membrane. This red blood cell concentrate is returned to the donor 1 from the separator 4 via a blood return line 7 connected to the blood vessel of the donor 1, and plasma is continuously separated by this extracorporeal circulation. This separated plasma is continuously supplied to a centrifuge 9 via a plasma line 8, during which time the plasma is
6°C to -10°C depending on the cooler 10 installed at
cooled to ℃.

As shown in an enlarged view in FIG. 2, this centrifugal separator 9 includes a cylindrical rotor 31 whose surrounding inner and outer surfaces communicate with each other through a large number of small-diameter communication holes, and which surrounds this rotor 31. It consists of a stator 32 arranged concentrically with this rotor 31. The rotor 31 described above is made of a porous cylindrical body made of glass, ceramic, foamed plastic, etc., and a large number of holes formed integrally during molding constitute a small diameter communication hole, and the diameter of the communication hole is The thickness is set to 1μ or less to prevent precipitate from passing through. Also,
A pipe 40 that communicates with the inside of the rotor 31 is integrally provided at the center of the bottom surface of the rotor 31 and protrudes downward, and the lower end of this pipe 40 is connected to a poor cryoprecipitate plasma outlet port 35 of the stator 32, which will be described later. Watertight and rotatably inserted. This pipe 40 constitutes an outlet path for guiding the poor cryoprecipitate in the rotor 31 to the poor cryoprecipitate plasma outlet port 35.

This stator 32 has an upper plasma introduction port 33 for introducing the plasma between it and the rotor 31.
and CPPT-rich plasma introduction port 34 located on the lower side.
and a poor CPPT plasma outlet port 35 arranged on the bottom. Plasma from the plasma separator 4 to be supplied to the centrifuge 9 is introduced into the upper part between the rotor 31 and the stator 32 through the plasma introduction port 33 and is stored therein. Since the CPPT generated in the stored liquid plasma at a temperature of 6°C to -10°C has a relatively high specific gravity, the rotor 31
The centrifugal force generated by the rotation of the stator 32 causes separation by movement towards the inner wall of the stator 32. This separated CPPT is transferred to the stator 32 as the plasma is continuously supplied to the centrifuge 9.
The CPPT rich plasma outlet port 34 of FIG.
The CPPT plasma flows into the CPPT-enriched plasma container 12 via the CPPT plasma derivation line 11 . The CPPT-enriched plasma container is preferably in the form of a blood bag so that subsequent processing can be carried out advantageously.

In the above, the temperature during centrifugation was set at 6°C to prevent the decomposition of CPPT and form CPPT in liquid plasma.
℃ to -10℃, and the separated CPPT-rich plasma must be stored at 6℃ or below to prevent decomposition. The portion leading to the CPPT-enriched plasma container 12 is maintained at the required temperature by being housed in a cooling chamber such as an electronic cooling device or an electric refrigerator, or by being cooled by a suitable type of cooler such as a heat exchanger. In the cooling, the plasma line 8 and the CPPT-rich plasma derivation line 11 within the cooling range can be coiled to improve the cooling effect.

The above centrifugation process is carried out under a relative negative pressure condition inside the rotor 31. Therefore, the CPPT-poor plasma in the low density band from which most of the CPPT has been separated and removed as described above is inside the rotor 31. Since the pressure is lower than the external pressure, the rotor 31 passes through the communication hole.
It flows out onto the inner surface of the tube and flows downward along the inner surface.
The depleted CPPT that has reached the bottom surface of the rotor 31 is led to the CPPT plasma derivation port 35 via the pipe 40, further passes through the depleted CPPT plasma derivation line 13, and is stored in the depleted CPPT plasma container 14. this scarcity
CPPT plasma is used for the preparation of plasma preparations or as shown by the dot-dashed line in Figure 1.
The plasma is heated to a required temperature and returned to the donor 1 through a plasma return line 18 equipped with a warmer 18 without being stored in the CPPT plasma container 14.

In the above centrifugation process, the enriched CPPT
plasma line 11 and poor CPPT plasma line 13
The desired CPPT of the CPPT-enriched plasma can be adjusted by providing flow regulating means 15, 16, such as valves or locks, respectively, and adjusting the means 15, 16 to control the respective flow rates of the CPPT-rich and CPPT-poor plasma. Enrichment or yield can be obtained. For example, by restricting the flow rate of the CPPT-rich plasma line 11 and relatively opening the CPPT-poor plasma line 13, highly concentrated but low yield CPPT-rich plasma can be obtained.

Note that the holes in the rotor through which the CPPT-depleted plasma flows into the rotor are formed by forming a rotor with a large diameter communication hole made of a hard plastic molded product, and using a small diameter filtration membrane stretched on the inner or outer surface of the rotor. It is also possible to use pores with a diameter of 1μ or less.

In the case of this membrane, the pore size can be made smaller,
The effect of better preventing the contamination of CPPT into CPPT-poor plasma during centrifugation can be obtained.

Note that numerals 20 and 21 in the figure are air traps equipped with pressure gauges P1 and P2 that display the pressure in the related lines, respectively, and P3 is a pressure gauge that indicates the separation pressure.

In this embodiment, the rotation speed of the rotor 31 when the diameter of the rotor 31 is 30 to 200 mm is:
If the rotor does not include the membrane, 100 to 5000 rpm is effective for effective centrifugation;
When the membrane is provided, it is necessary to slightly lower the rotational speed to prevent poor CPPT plasma from passing through the membrane due to clogging of the membrane.

FIG. 3 is an internal transparent front view of another embodiment of the centrifugal separator 9. In FIG. 3, the reference numeral 42 is a stator corresponding to the stator 32 shown in FIG. 2, and the other configurations are the same as in FIG. 2.
The same reference numerals as those in FIG. 2 are used. The stator 42 has a downwardly expanding tapered shape, which increases the radius of centrifugation toward the bottom, thereby increasing the separation radius.
This allows CPPT plasma to accumulate at the lower end corner of this stator 42, and this accumulated CPPT-enriched plasma
The CPPT plasma is discharged from the plasma discharge port 34, and the other functions are the same as in the case of FIG.

<Effects of the Invention> In the present invention, plasma separation is continuously performed using a membrane-type plasma separator during extracorporeal circulation of anticoagulated donor blood, and the separated plasma is enriched and enriched by centrifugal force at low temperatures. Since the cryoprecipitate-poor cryoprecipitate is continuously separated, it is a highly efficient rich CPPT.
Plasma can be collected, and in plasma separation by membrane separation, the transfer of fibrinogen from the blood into the plasma is greatly restricted, resulting in high-quality enrichment.
CPPT plasma can be obtained. Furthermore, since the rotor of the centrifugal separator used in the present invention has a rotor in which the inner and outer surfaces of the periphery communicate with each other through a large number of communication holes, it is suitable for continuous centrifugation, and is compatible with conventional membrane methods. In comparison, there is no risk of deterioration in separation performance due to membrane clogging.

[Brief explanation of drawings]

FIG. 1 is a flow path system diagram of an embodiment of the present invention, and FIGS. 2 and 3 each include a partially cutaway cross section of another embodiment of a centrifugal separator installed in the flow path system of FIG. 1. 1 is a transparent front view of the inside, 1 is a donor, 4 is a plasma separator, 9 is a centrifugal separator, 10 is a cooler, 12 is a rich
CPPT plasma container, 31 is rotor, 32, 42 is stator, 33 is plasma introduction port, 34 is rich CPPT
Plasma derivation port, 35 is poor CPPT plasma derivation port.

Claims (1)

[Claims] 1. In extracorporeal circulation of anticoagulated donor blood via a plasma separator equipped with a plasma separation membrane, the plasma that has passed through the plasma separation membrane is heated to a temperature of 6°C to -10°C.
An apparatus for separating cryoprecipitate-rich plasma in a high specific gravity range and cryoprecipitate-poor plasma in a low specific gravity range by being continuously supplied to a centrifuge at a temperature of It consists of a cylindrical rotor whose surrounding inner and outer surfaces communicate with each other through a large number of small-diameter communication holes, and a stator that surrounds this rotor and is arranged concentrically with the rotor. a plasma inlet port arranged at the top for introducing the plasma into the rotor, a cryoprecipitate-rich plasma outlet port arranged at the lower side, and a cryoprecipitate-poor plasma outlet port arranged at the bottom; A derivation path is provided between the depleted cryoprecipitate plasma derivation port and the depleted cryoprecipitate in the rotor to guide the depleted cryoprecipitate plasma derivation port, and the depleted cryoprecipitate is introduced from the plasma introduction port. The plasma is separated into rich and cryoprecipitate-poor plasma by centrifugal force generated by the rotation of the rotor, and the separated rich and cryoprecipitate-poor plasma are separated from the rich and cryoprecipitate-poor plasma, respectively. A continuous cryoprecipitate separation device characterized in that cryoprecipitate is extracted from a plasma outlet port. 2. In extracorporeal circulation of anticoagulated donor blood via a plasma separator equipped with a plasma separation membrane, the plasma that has passed through the plasma separation membrane is continuously fed into a centrifuge at a temperature of 6° to -10°C. A device that separates cryoprecipitate-rich plasma in a high specific gravity range and cryoprecipitate-poor plasma in a low specific gravity range, the centrifugal separator having a large number of communicating holes between the inner and outer surfaces of the periphery. The rotor is composed of a cylindrical rotor, which is connected to the rotor by a cylindrical rotor, and a membrane having small diameter pores is stretched on the inner or outer surface of the rotor, and a stator that surrounds this rotor and is arranged concentrically with the rotor. The stator includes an upper plasma introduction port for introducing the plasma between the stator and the rotor, a cryoprecipitate-rich plasma outlet port located at the lower side, and a cryoprecipitate-poor plasma outlet port located at the bottom. , an outlet path is provided between the bottom surface of the rotor and the cryoprecipitate-poor plasma outlet port to guide the cryoprecipitate-poor cryoprecipitate in the rotor to the cryoprecipitate-poor cryoprecipitate outlet port, and the The plasma introduced from the plasma introduction port is separated into rich and cryoprecipitate-poor plasma by centrifugal force generated by the rotation of the rotor, and the separated rich and cryoprecipitate-poor plasma are separated into cryoprecipitate-rich and cryoprecipitate-poor plasma. A cryoprecipitate continuous separation device characterized in that cryoprecipitate is extracted from the rich and poor cryoprecipitate plasma extraction boats, respectively.