JPH0359707B2 - - Google Patents

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to an apparatus for separating cryoprecipitate from plasma in blood, and more specifically, a device for separating cryoprecipitate from plasma in blood using a membrane filter. This invention relates to an apparatus for separating cryoprecipitate whose main component is cryoprecipitate.

[Conventional technology]

Hemophilia, a bleeding disorder, is caused by a deficiency in one of the blood clotting factors. Hemophilia patients in particular are deficient in the factor involved in blood coagulation, and for many years now, when bleeding occurs during surgery, etc., blood coagulation factor has been injected in the form of fresh frozen plasma. This is a method that has been used for some time.

However, fresh frozen plasma requires separation from blood and freezing in a short period of time, and unnecessary plasma components are also administered into the blood, which puts a strain on the circulatory system. It is said that the use of cryoprecipitate, which is enriched with blood coagulation factors, places less burden on the heart and has a greater therapeutic effect.

Conventionally, cryoprecipitate is obtained by centrifuging blood, storing the frozen plasma at a temperature of -20°C to -40°C, thawing it at a temperature of 4°C to 6°C, and then centrifuging it. Therefore, it was collected as a precipitate in liquid plasma.

[Problem to be solved by the invention]

However, the method of centrifuging thawed frozen plasma to obtain cryoprecipitate takes a long time, and when separating with a membrane filtration membrane, cryoprecipitate precipitates clog the micropores of the filtration membrane. It has the disadvantage that cryoprecipitate cannot be obtained in a high yield due to a decrease in separation efficiency.

An object of the present invention is to provide an apparatus for obtaining cryoprecipitate with high efficiency in a continuous manner from plasma separated from blood.

A further object of the present invention is to provide an apparatus for obtaining cryoprecipitate with a reduced amount of fibrinogen.

[Means to solve the problem]

That is, the present invention provides a plasma container containing plasma separated from blood, and a plasma line provided in a plasma line from which the plasma is drawn from the container.
It is equipped with a cooler whose temperature is adjusted to 6°C and a large number of hollow fiber membranes having a pore size of 0.1 to 1.0μ to separate the plasma from the cooler into rich cryoprecipitate and cryoprecipitate-poor cryoprecipitate. A cryoprecipitate separation device characterized by comprising a filter and a cryoprecipitate-rich storage container maintained at 6° C. or lower and containing the rich cryoprecipitate that has passed through the filter.

[Effect]

The plasma extracted from the plasma storage container is stored in a cooler.
After being cooled to a temperature of 10℃~4℃, the pore size is 0.1~
It is fed into a filter loaded with a 1.0μ membrane.

The plasma cooled in this way contains cryoprecipitate in a suspended state, and is separated into cryoprecipitate-rich and cryoprecipitate-poor cryoprecipitate by the shearing force of the membrane with minute pores. .

The rich cryoprecipitate passed through the filter is 6
The temperature is maintained below ℃ to prevent decomposition of cryoprecipitate.

In addition, most of the fibrinogen in the plasma obtained by passing blood through a membrane-type plasma separator is blocked by the separator, so the filter membrane does not become clogged and long-term operation is possible. A high quality rich cryoprecipitate with low fibrinogen content is obtained.

〔Example〕

In the present invention, plasma cooled to a temperature of -10 to 6°C in a cooler is separated into rich cryoprecipitate and poor cryoprecipitate in a filter having a membrane with a pore size of 0.1 to 1.0 μ. Wealth Cryoprecipitate 6
It is to be stored in a container at a temperature below ℃.

Cryoprecipitate-enriched here refers to plasma that contains a large amount of coagulation factors such as blood coagulation factor and fibrinogen, and plasma that contains 1 unit or more of blood coagulation factor (hereinafter expressed as 1U/ml). means. Poor cryoprecipitate refers to plasma that does not contain or hardly contains coagulation factors such as plasma coagulation factor and fibrinogen.
0.1 units of blood coagulation factor in plasma (0.1U/ml)
The following refers to the plasma contained.

1U/ml here refers to "clinical blood transfusion science" (1976).
1 unit of titer shown on page 73 (Published by Igaku Shoin Co., Ltd. on January 15, 2015) is the average value of the activity contained in 1 ml of healthy individuals.

Next, one embodiment of the present invention will be described based on the drawings. FIG. 1 and FIG. 2 are explanatory diagrams showing flow path systems of different embodiments, respectively.

In the figure, 1 is a filter, 2 is a plasma supply line, 3 is a rich cryoprecipitate transport line, 5 and 10
is a pump, 6 is a cooler, 7 is a rich cryoprecipitate storage container, and 9 is a pressure regulating valve.

In FIG. 1, plasma from one or more plasma containers 11 containing pre-separated plasma is transferred to a cooler by operating a plasma pump 5 that communicates with a plasma supply line 2 and is disposed in the line. When using a plurality of plasma containers 11, a clamp 12 is placed in the line from each plasma container 11 to the plasma supply line 2, and the empty plasma is Container 11 can be replaced with plasma containers filled with plasma in sequence to enable continuous plasma supply.

The plasma container 11 referred to here is preferably a bag-type one made of plastic because it is easy to handle, and the filter 1 may be a flat plate containing a flat membrane, but it is preferable to use a bag-type one made of plastic. is compact and preferable.

Membrane materials include cellulose acetate, cellulose, cellulose acetate, polyvinyl alcohol,
Polyolefin etc. are used.

The cooler 6 is arranged in the form of a heat exchanger or the like in the plasma supply line 11 from the plasma container 11 to the filter 1, and the plasma drawn out from the plasma container 11 is kept at -10°C.
Cooled to ~6°C.

The plasma cooled to a low temperature is then supplied to a filter 1, where it is separated into cryoprecipitate-rich and cryoprecipitate-poor cryoprecipitate. Filter 1 has a pore diameter of 0.1~
It is loaded with a 1.0μ membrane. If the pore size is larger than 1.0μ, migration of cryoprecipitate to the filtrate side will be excessive, and if it is smaller than 0.1μ, the filtration efficiency tends to decrease significantly.

In the plasma supplied to the filter 1, the poor cryoprecipitate permeates through the small pores of the membrane, and the rich cryoprecipitate passes through the filter 1 and is transferred from the rich cryoprecipitate transport line to the rich cryoprecipitate storage. It is housed in a container 7. The rich cryoprecipitate storage container 7 is preferably in the form of a plastic bag. On the other hand, the cryoprecipitate-poor cryoprecipitate that has permeated through the membrane passes through the discharge line 4, preferably into a filtered plasma container 8 of the same type as the cryoprecipitate-rich storage container 7.
and stored for reuse.

The rich cryoprecipitate is stored in a rich cryoprecipitate storage container 7 maintained at 6° C. or lower to prevent decomposition of the cryoprecipitate.

Alternatively, the line and equipment enclosed by the chain line from the cooler 6 to the rich cryoprecipitate storage container 7 via the filter 1 can be housed and cooled in a cooling chamber such as an electronic cooling device or an electric refrigerator.

A pressure regulating valve 9 provided in the cryoprecipitate-rich transport line 3 is used to adjust the flow rate of the rich cryoprecipitate and to adjust the filtration pressure within the filter 1. Higher filtration pressures increase the cryoprecipitate content of rich cryoprecipitate, and lower filtration pressures decrease the cryoprecipitate content.

FIG. 2 is an explanatory diagram showing a flow rate system of a different embodiment, in which rich cryoprecipitate is decomposed from plasma obtained by separating fresh blood or stored blood immediately after blood collection.

The membrane type plasma separator 11 is composed of a flat membrane or hollow fiber porous membrane with a pore size of 0.1 to 1.0μ, and the membrane material includes cellulose acetate, cellulose,
Cellulose acetate, polyvinyl alcohol, polyolefin, etc. are used.

Blood contained in a bag-type blood container 21 is pumped by a blood pump 22 to a membrane-type plasma separator 23, and blood cell components in the blood pass through the separator 23 and are stored in a container 24 as a concentrated red blood cell solution. Ru. On the other hand, plasma, which is a filtrate component, which has passed through the membrane of the separator 23 flows into the plasma supply line 2. The plasma flowing into the plasma supply line 2 is cooled by a cooler 6 in the same way as shown in FIG. 1, and separated into rich cryoprecipitate and poor cryoprecipitate by a filter 1. The rich cryoprecipitate is transferred from the rich cryoprecipitate transport line 3 to the rich cryoprecipitate storage container 7 . On the other hand, the poor cryoprecipitate that has passed through the membrane of the filter 1 is stored in the filtrate plasma container 8.

In FIG. 2, the filtration pressure adjustment means of the filter 1 is controlled by adjusting the filtrate flow rate in accordance with the rotational speed of the filtrate pump 10. Fibrinogen in the blood plasma obtained by separating it from blood in the membrane-type plasma separator 23 is partially blocked by the membrane of the separator, so that the plasma supplied to the filter 1 contains less fibrinogen. Therefore, there is less clogging of the membrane of the filter 1, and long-time operation is possible. The obtained rich cryoprecipitate contains 80 to 180 mg/dl of fibrinogen in plasma, and is cryoprecipitate with a small amount of fibrinogen.

Example 1 In Figure 1, the inner diameter is 270μ, the wall thickness is 80μ, and the hole diameter is
Using a filter 1 loaded with a cellulose triacetate hollow fiber porous membrane with a diameter of 0.4μ and an effective membrane area of ^0.25m2 ,
The stored plasma was cooled to 0°C and fed to the filter at 20 ml/min. 2~ while changing the filtration pressure with the pressure regulating valve 9.
It was possible to continuously obtain 8 ml/min. of rich cryoprecipitate. The blood coagulation factor concentration of this rich cryoprecipitate varies depending on the flow rate of the rich cryoprecipitate. Flow rate is 2ml/min.
At this time, the amount of blood coagulation factor in plasma is 9U/ml,
Fibrinogen amount is 230 mg/dl, flow rate is 8 ml/dl.
At min., the amount of blood coagulation factor was 2.25 U/ml and the amount of fibrinogen was 195 mg/dl.

Example 2 In Figure 2, the inner diameter is 270μ, the wall thickness is 80μ, and the hole diameter is
Membrane-type plasma filter 23 containing a cellulose triacetate hollow fiber porous membrane with a diameter of 0.3 μ and an effective membrane area of 0.5 m ²
Using the filter 1 used in Example 1, blood was supplied from the blood container 21 to the membrane plasma filter 23 at a blood flow rate of 100 ml/min. to obtain plasma at a flow rate of 40 ml/min. The plasma was supplied to the filter 1 while being cooled to 0°C. While adjusting the rotational speed of the filtrate pump 10 and the filtration pressure of the filter 1, 6 to 12 ml/min. of rich cryoprecipitate was obtained. The concentration of this rich cryoprecipitate is when the flow rate is 6 ml/min.
The blood coagulation factor level was 6 U/ml, and the fibrinogen level was 120 mg/dl. When the flow rate was 12 ml/min., the amount of blood coagulation factor was 3 U/ml and the amount of fibrinogen was 105 mg/dl.

〔effect〕

Since the cryoprecipitate separation device of the present invention continuously obtains cryoprecipitate from plasma obtained by separating blood using the membrane of a filter, it can achieve a higher yield in a shorter time than a batch method. Cryoprecipitate can be obtained at

In addition, in plasma separated from blood using a membrane-type plasma separator, fibrinogen is partially blocked by the membrane of the separator, so the amount of fibrinogen in the plasma that has permeated through the membrane is lower than in plasma obtained by centrifugation. Since the enriched cryoprecipitate obtained by passing through the filter has a small amount of fibrinogen in the plasma, the cryoprecipitate obtained by the present invention can be used to reduce the amount of cryoprecipitate obtained by using a large amount of The problem of hyperfibrinogenemia is resolved.

[Brief explanation of drawings]

FIG. 1 and FIG. 2 are explanatory diagrams showing flow path systems of different embodiments, respectively. In the figure, 1 is a filter, 2 is a plasma supply line, 3 is a rich cryoprecipitate transport line, 5 and 10
is a pump, 6 is a cooler, 7 is a rich cryoprecipitate storage container, and 9 is a pressure regulating valve.

Claims (1)

[Claims] 1. A plasma container containing plasma separated from blood, a cooler provided in a plasma line from which plasma is drawn out from the container and adjusting the temperature of the plasma to -10°C to 6°C, and a cooler from the cooler. A filter equipped with a large number of hollow fiber membranes having a pore size of 0.1 to 1.0μ to separate blood plasma into rich cryoprecipitate and cryoprecipitate-poor cryoprecipitate, and a cryoprecipitate-rich cryoprecipitate passed through the filter. 1. A cryoprecipitate separation device comprising: a cryoprecipitate-enriched storage container maintained at 6° C. or lower containing tate;