JPH04200550A - Blood component separating system - Google Patents

Abstract

PURPOSE:To obtain the novel blood component separating system by connecting the fluid introducing port of a blood filter which captures only the leukocytes to a blood taking bag, connecting two sub-bags in parallel to the fluid outflow port of the blood filter device and connecting >=1 pieces of the further another sub-bags connected in series or parallel directly or at >=1 points of the connecting tubes connecting the blood filter device and the blood taking bag. CONSTITUTION:The blood taking bag 3 is connected via a blood taking tube 2 and is connected further at one end to a tube 4. This tube is branched at the other end by a Tee pipe 5. One thereof communicates with the filter device 7 for separating the leukocytes via a tube 6. Further, the filter device communicates with the bags 11, 13 for separating the blood components via tubes 10, 12 branched by a Tee pipe 9 from the tube 8 connected to the blood leading out port. The other side is communicated with the bag 17 for separating the blood components and the physiological soln. bag 19 housed therein with the physiological soln. for washing of the filter device 7 by tubes 14, 16, 18.

Description

[Detailed description of the invention] (Industrial application field) The present invention relates to a blood component separation system.

Specifically, the present invention relates to a blood component separation system comprising a bag and a leukocyte removal filter device for aseptically separating and storing blood obtained through blood donation or the like into each component.

(Prior Art) The form of blood transfusion has long since shifted from conventional whole blood transfusion to component transfusion, in which only the components required by the patient are transfused. Broad alloantibody sensitization occurs when existing immunocompetent cells such as white blood cells and platelets enter the body. Once antibody sensitization has occurred, if blood transfusions are continued, an antigen-antibody reaction will occur in the patient's body, resulting in chills and chills.
Not only does this cause side effects such as fever and convulsions, but the patient may also end up in a state where platelet transfusion is no longer possible and the actual value does not recover even if random platelet preparations are transfused.

In addition, an issue that has become increasingly important in recent years is GVHR (GVHR), where when a blood transfusion is given to an immunocompromised patient, the white blood cells of another person in the blood attack the patient themselves, leaving the patient with severe symptoms. Graft reaction, Graft Ver
Problems include sus Ho5t Reaction) and blood from a cytomegalovirus-positive donor present on the white blood cell membrane entering the body of a negative patient, causing the patient to develop serious symptoms such as interstitial pneumonia.

In addition, when concentrated red blood cell fluid has been stored for a long period of time, metabolites and physiologically active substances from white blood cells mixed in the concentrated red blood cell fluid are released, so these must be removed during blood transfusion. Since these substances also enter the patient's body, which is undesirable, it is necessary to remove white blood cells before these substances are produced in order to reduce the burden on the patient.

Therefore, in order to reduce such side effects after blood transfusion, it is necessary to reduce the number of white blood cells mixed in blood products as much as possible before transfusing them to patients, and various methods have been developed for this purpose. In particular, the filter method has attracted attention in recent years as a means for relatively efficiently separating leukocytes.

However, in the conventional filter method, after separating each blood cell component, an operation is performed to remove white blood cells and the like, so it is necessary to open the system once. For this reason, conventional methods cannot maintain completely sterile conditions, severely limit the expiration date, and pose a risk of infection.
The drawback was that it was necessary to use different filters for each formulation, making the operation complicated.

On the other hand, in platelet-rich plasma separated and collected using conventional methods, the platelets become pellets.
An operation to loosen this is essential, but this operation is time-consuming and may cause irreversible activation of platelets.

(Problems to be Solved by the Invention) Therefore, an object of the present invention is to provide a novel blood component separation system. The present invention also provides a blood component separation system that aseptically removes leukocytes before fractionating each blood component and is applicable to the non-pellet PC (Platelet Concentrate) method in which platelets are not pelleted. The purpose is to provide.

(Means for Solving the Problems) In the above aspects, the fluid inlet of a blood filter device that captures only white blood cells is connected to a blood collection bag, and two child bags are connected in parallel to the fluid outlet of the blood filter device. and connected directly to one or more series or parallel connected child bags or blood collection bags, or at least one connection to a connecting tube between the blood filter device and the blood collection bag. This is achieved by a blood component separation system featuring:

The present invention also provides that either one of the child bags connected to the fluid outlet of the blood filter device is a bag for separating concentrated platelet fluid, is made of a material that does not reduce platelet function, and has platelet function contained therein. 1 shows a blood component separation system containing a drug for maintenance purposes. The present invention also provides a blood component separation system in which either one of the child bags connected to the fluid outlet of the blood filter device is a concentrated red blood cell fluid separation bag, and the red blood cell preservation solution is contained therein. The invention further provides a blood component separation system in which one of said separate child bags contains a red blood cell preservation solution or a platelet preservation solution. The present invention further includes:
Figure 3 shows a blood component separation system in which one of the further child bags contains a physiological solution for recovering platelets or red blood cells remaining in the filter device.

(Function) In the blood component separation system according to the present invention, the fluid inlet of the blood filter device that captures only white blood cells is connected to a blood collection bag, and the fluid outlet of the blood filter device functions as two blood component separation bags. one or more serially or parallelly connected subbags functioning as blood component separation bags or physiological solution bags are connected directly to the blood collection bag or to the blood filter. It is connected at one or more points to a connecting tube connecting the blood collection bag and the blood collection bag. In other words, since the leukocyte removal filter device is connected via a tube between the blood collection bag and the series of blood component separation bags, each blood cell component can be separated aseptically with a single centrifugation operation. Each blood cell component obtained in this manner has leukocytes removed.

Hereinafter, the present invention will be explained in more detail based on embodiments.

FIG. 1 is a plan view showing one embodiment of the blood component separation system of the present invention.

As shown in FIG. 1, in the blood component separation system of this embodiment, a blood collection needle 1 is connected to a blood collection bag 3 for storing collected blood via a blood collection tube 2. On the other hand, it is further connected to a tube 4, which is branched at the other end by a T-tube 5,
One of them communicates via a tube 6 with a filter device 7 for separating leukocytes. Furthermore, the filter device 7 has a tube 10 branched from a tube 8 connected to the blood outlet of the filter device 7 by a T-shaped tube 9.
．． 12 to blood component separation bags 11 and 13 which respectively contain separated blood components. on the other hand,
The other end of the tube 4 connected to the blood collection bag 3, which is branched by the T-tube 5, is connected to a blood component separation bag 17 and a filter device 7, which accommodate separated blood components through tubes 14.16 and 14.18, respectively. Physiological solution bag 19 containing a physiological solution for washing
are communicating.

Here, the detailed description of the blood component separation operation using the blood component separation system is as follows.

That is, blood from a healthy person is collected from a blood collection needle 1, and the collected blood is introduced into a blood collection bag 3 containing an anticoagulant such as CPD liquid through a blood collection tube 2. Next, this system was placed in a separation container (not shown) of a centrifuge with the side of the blood collection bag 3 with the blood collection tube facing upward, and after centrifugation at approximately 3,520 x g for 5 minutes, The blood collection bag 3 is removed from the container and set on a separation stand (not shown). Fluid valves on the tube 4 side and tube 14 side of the T-shaped tube 5, and the tube 14 side and the tube 16 of the T-shaped tube 15
The side fluid valve is opened, and while the blood collection bag 3 is gently pressurized, platelet-poor plasma (P P P) is transferred to the blood component separation bag 17 . Next, the proximal end of the tube 16 is sealed, and the blood component separation bag 17 is cut.

After this, the remaining PPP and buffy coat (
After opening the fluid valves on the tube 6 side of the T-tube 5 and the fluid valves on the tube 8 and tube 10 sides of the T-tube 9, the blood collection bag 3 is gently pressurized. The blood is transferred to a blood component separation bag 11 via a filter device 7.

Furthermore, the fluid valve on the tube 18 side of the T-tube 15 is opened, the physiological solution bag 9 containing the physiological solution is set on a separation stand (not shown), and the physiological solution is gently pressurized and filtered. After washing the platelets remaining in the device 7, the proximal end of the tube 10 is sealed and the blood component separation bag 11 is cut. Next, after clamping the tube 14 and opening the fluid valve on the tube 12 side of the T-tube 9, the concentrated red blood cell fluid (CRC) remaining in the blood collection bag 3 is collected.
is gently pressurized and transferred to the blood component separation bag 13 via the filter device 7. Furthermore, the clamp on the tube 14 was released, the physiological solution bag 19 containing the physiological solution was set on the separation stand, and the physiological solution was gently pressurized to wash away the red blood cells remaining in the filter device 7. After that, the proximal end of the tube 12 is sealed and the blood component separation bag 13 is cut.

In this way, platelet-poor plasma is collected in the blood component separation bag 17, leukocyte-depleted concentrated platelet fluid is collected in the blood component separation bag 11, and leukocyte-depleted red blood cell preparation is collected in the blood component separation bag 13 in a sterile manner. can.

In the blood collection bag used in the present invention, the blood collection needle is connected to the blood collection tube, and the inside of the bag contains ACD as an anticoagulant.
liquid, CPD liquid, heparin, etc. In addition, the material for the blood collection bag of the present invention includes polyolefins such as polyvinyl chloride, ethylene-vinyl acetate copolymer (EVA), ethylene-6 monofluorinated propylene copolymer (FEP), and polyester. Can be mentioned.

Moreover, the blood collection tube of the present invention does not matter where it is connected to the blood collection bag. That is, the blood collection tube may be connected to a position opposite to the connection tube of the blood filter device.

The physiological solution for filter cleaning used in the present invention is:
There is no particular restriction as long as it does not affect blood cell components, and specific examples include physiological saline, phosphate buffer, Linkel's solution, and the like.

Materials for the blood component separation bag and the physiological solution bag used in the present invention include polyvinyl chloride, ethylene-vinyl acetate copolymer (EVA), and ethylene-6 monofluorinated propylene copolymer (FEP). ) and polyesters, preferably polyolefins from which plasticizers do not elute are used. In particular, it is desirable to use materials for blood component separation bags used for storing platelet concentrates that are transparent, flexible, have high oxygen permeability, are sterilizable, and do not reduce platelet function. Specifically, bags made of polyolefin elastomer and bags using phthalate ester as a plasticizer are mentioned.

Further, it is preferable that the bag contains a medicine such as a preservation solution for maintaining platelet function.

As this storage solution, a solution prepared by dissolving a predetermined amount of sodium chloride, sodium acetate, potassium chloride, magnesium chloride, or glucose sodium in water can be used. Further, it is preferable that a blood component separation bag used for storing concentrated red blood cell fluid contains a red blood cell preservation solution in the bag. Optisol, SAGM
, Adsol (Backstar), MAP, etc.

Furthermore, the solutions contained in the physiological solution bag may include physiological saline, red blood cell preservation solution, platelet preservation solution, and the like. If the solution in the physiological solution bag is a red blood cell preservation solution or platelet preservation solution, place these preservation solutions in a blood component separation bag used for preservation of concentrated red blood cell fluid or concentrated platelet fluid, respectively. There is no need to use a separate preservation solution to wash out the red blood cells and platelets remaining in the filter and place them in each blood component separation bag. You can also adjust the amount.

FIG. 2 is a sectional view showing an example of the configuration of the filter device 7 used in the blood component separation system of the present invention.

The filter device 7 shown in FIG. 2 captures white blood cells in blood, and includes a blood inlet 20 and a blood outlet 28.
A leukocyte removal filter 2 is contained within the housing.
5 and two pre-filters 23 and 24 arranged upstream of the removal filter.

Further, the form of the leukocyte removal filter incorporated into the filter device used in the present invention is not particularly limited as long as it can effectively capture leukocyte components. Specifically, examples include a porous body, a nonwoven fabric, a woven fabric, a knitted fabric, or a form filled with fibers as is.

In particular, a porous material has excellent trapping efficiency and is therefore preferable.

Here, the porous body includes a membrane shape such as a flat membrane shape and a hollow fiber shape, and a block shape such as a sponge shape. When this leukocyte removal filter is porous, its average pore diameter is 1 to 80 μm, preferably 8 to 10 μm, and the thickness is 0°1 to 10 mm, preferably 1 to 1 μm.
．． It is 5mm.

Note that the average pore diameter is calculated by cutting a porous short body with a three-dimensional continuous structure from any direction, photographing the cross-sectional image with a scanning electron microscope, observing at least 1000 pores, and calculating the pore diameter and appearance. This refers to the pore diameter that appears most frequently when examining the relationship with the frequency. Further, as the material for the leukocyte removal filter used in the present invention, fibrous substances, porous substances, particulate substances, and those that have been physically, chemically, or immunologically modified can be considered. In addition, various polymers can be used to form the porous material used as the leukocyte removal filter, and specific examples include polyurethane, polyvinylidene fluoride, polysulfone, polyester, poly(meth)
Examples include acrylate, butadiene-acrylonitrile copolymer, polyamide, polyether polyamide block polymer, polyvinyl acetal, ethylene-vinyl alcohol copolymer, and the like.

Further, the form of the pre-filter to be incorporated into the filter device used in the present invention as needed is not particularly limited, but specific examples include porous material, bead-like, fibrous material, etc. . In particular, a porous material has excellent trapping efficiency and is therefore preferable. Here, the porous body includes a membrane shape such as a flat membrane shape and a hollow fiber shape, and a block shape such as a sponge shape. When this pre-filter is porous, its average pore diameter is 10 to 1
00 μm1 is preferably 20 to 50 μm, and the thickness is 0.5 to 3 mm, preferably 1 to 1.5 mm. Further, the material of the prefilter used in the present invention is not particularly limited, and specifically, polyurethane or the like is used.

FIG. 3 is a plan view showing another embodiment of the blood component separation system of the present invention.

As shown in FIG. 3, in the blood component separation system of this embodiment, a blood collection needle 1 is connected to a blood collection bag 3 for storing collected blood via a blood collection tube 2. It is connected on the one hand to a tube 4, which is branched at the other end by a T-tube 5, one of which communicates with the blood inlet of a filter device 7 for separating leukocytes. Furthermore, the filter device 7 is connected to a blood component separation bag 11.13 containing the separated blood components via tubes 10.12 branched by a T-tube 9 from a tube connected to the blood outlet of the filter device 7. It's communicating.

Furthermore, the physiological solution bag 19 containing the physiological solution for cleaning the filter device 7 is connected to the other branched by the T-shaped tube 5 disposed in the middle of the tube 4 connecting the blood collection bag 3 and the filter device 7. It is connected via a tube 18 and communicates with the blood collection bag 3 and the filter device 7 .

Here, the detailed description of the blood component separation operation using the blood component separation system is as follows.

That is, blood from a healthy person is collected from a blood collection needle 1, and the collected blood is introduced into a blood collection bag 3 containing an anticoagulant such as CPD liquid through a blood collection tube 2. Next, this system is placed in a separation container (not shown) of a centrifuge with the side of the blood collection bag 3 with the blood collection tube facing upward, and after centrifugation at approximately 3,520 x g for 15 minutes, it is removed from the container. , set the blood collection bag 3 on a separation stand (not shown). Tube 4 side of T-tube 5 and filter device 7
Side fluid valve, T′￥: Open the fluid valves on the filter device 7 side of the tube 9 and the tube 10 side, and gently pressurize the blood collection bag 3. (CRC) is transferred to the blood component separation bag 13. Next, open the fluid valve on the tube 18 side of the T-shaped tube 5,
Stop the tube 4 with a clamp, set the physiological solution bag 19 containing the physiological solution on a separation stand (not shown), and gently pressurize the physiological solution to remove red blood cells remaining in the filter device 7. After cleaning, the proximal end of the tube 10 is sealed, the blood component separation bag 13 is cut, and at the same time, the tube 18 is stopped with a clamp. In this way, a leukocyte-depleted red blood cell preparation is obtained in the blood component separation bag 13 in a sterile manner.

After this, remove the clamp from the tube 4, and insert the buffy coat remaining in the blood collection bag 3 into the T-shaped tube 9.
After opening the fluid valve on the tube 12 side of the blood collection bag 3
is gently pressurized and transferred to the blood component separation bag 11 via the filter device 7. Furthermore, the drain on the tube 18 is removed, and the physiological solution bag 1 containing the physiological solution is removed.
9 is set on a separation stand, and after washing platelets remaining in the filter device 7 by gently pressurizing the physiological solution, the proximal end of the tube 12 is sealed, and the blood component separation bag 11 is cut. do. In this way, leukocyte-removed concentrated platelet fluid (PC) is collected in the blood component separation bag 11 in a sterile manner.

Next, after sealing the proximal ends of the tube 4 and blood collection tube 2, the blood collection bag 3 contains platelet-poor plasma (
PPP) can be collected aseptically.

As a result, platelet-poor plasma can be collected in the blood collection bag 3, leukocyte-depleted red blood cell preparation can be collected in the blood component separation bag 13, and leukocyte-depleted concentrated platelet fluid can be collected in the blood component separation bag 11 in a sterile manner.

(Example) Hereinafter, the present invention will be explained more specifically using examples.

Example 1 Using 400 ml of blood, an experiment was conducted based on the embodiment shown in FIG. 1 above.

As a result, no bag breakage or filter damage was observed after centrifuging the system at 3,520xg.

Furthermore, after washing the inside of the filter device 7 with 20 ml of physiological saline in the physiological solution bag 19, the number of remaining white blood cells in the concentrated platelet fluid collected in the blood component separation bag 11 is 0.01 compared to the original blood. %, the yield of platelets was 70%, and the percentage of contaminated red blood cells was 0.15%.

In addition, 200 ml of platelet-poor plasma was collected in the blood component separation bag 17.

On the other hand, the hematocrit value of the red blood cell preparation collected in the blood component separation bag 13 is 5% in the physiological solution bag 19.
When the inside of the filter device 7 was washed with 0 ml of physiological saline, it was 40%, the number of residual white blood cells was 0.1% of the original blood, and the rate of platelet contamination was 10%.

The filter device 7 uses a polyurethane porous sheet with an average pore diameter of 10 μm and a thickness of 1.0 mm as a leukocyte removal filter, and a polyurethane porous sheet with an average pore diameter of 30 to 40 μm and a thickness of 1°0 mm as a pre-filter 23. , and a pre-filter 24, each set of polyurethane porous sheets with an average pore diameter of 20 to 30 μm and a thickness of 1.5 mm were used. The effective area of the leukocyte removal filter was 104C♂, and the weight was 3.5 g. In addition, CPD liquid is put in the blood collection bag 3 as an anticoagulant, and the material of the blood component separation bag 11 is a sheet made of a material that uses phthalate ester as a plasticizer. A system was used in which Optisol was placed in the separation bag 13 as a red blood cell preservation solution, and physiological saline was placed in one physiological solution bag.

Example 2 An experiment was conducted based on the embodiment shown in FIG. 3 above using 400 ml of blood collected.

As a result, no bag breakage or filter damage was observed after centrifuging the system at 3.520xg.

In addition, the hematocrit value of the red blood cell preparation collected in the blood component separation hang 13 is 50 in the physiological solution bag 19.
When the inside of the filter device 7 was washed with ml of physiological saline, the residual white blood cell count was 42% and 0 compared to the original blood.
．． 1%, and the platelet contamination rate was 8%.

On the other hand, after washing the inside of the filter device 7 with 201111 physiological saline in the physiological solution bag 19, the number of remaining white blood cells in the concentrated platelet fluid collected in the blood component separation bag 11 was 0.601% of the original blood. Furthermore, the yield of platelets was 71%, and the percentage of contaminated red blood cells was 0.3%. In addition, the blood collection bag 3 contains 180a of platelet-poor plasma.
+1 was taken.

Note that the filter device 7 used was the same as that used in Example 1. In addition, a CPD solution is put in the blood collection bag 3 as an anticoagulant, and the blood component separation bag 1 is made of a sheet made of a material that uses phthalate ester as a plasticizer. SAGM is put into the separation bag 13 as a red blood cell preservation solution,
A system was used in which a physiological solution bag 19 contained physiological saline.

(Effects of the Invention) As described above, in the present invention, the fluid inlet of a blood filter device that captures only white blood cells is connected to a blood collection bag, and two child bags are connected in parallel to the fluid outlet of the blood filter device. and one or more series or parallel connected child bags are connected directly to the blood collection bag or at one or more points to a connecting tube connecting the blood filter device and the blood collection bag. Because this blood component separation system is characterized by the following, plasma, leukocyte-depleted red blood cell preparations, and leukocyte-depleted concentrated platelet fluid can be separated and manufactured in a sterile manner from blood collected from blood donors in a single centrifugation operation. It is something. Furthermore, in the blood component separation system of the present invention, during centrifugation,
There was no damage to the bag or filter, and unlike conventional production methods, the platelet concentrate that is obtained does not require the operation of loosening pelleted platelets, and the processing time can be shortened. Furthermore, the preparation obtained by the blood component separation system of the present invention does not contain physiologically active substances derived from white blood cells, such as histamine and white blood cell aggregates present in neutrophils, and therefore, compared to current preparations. This has the advantage that the effect on living organisms is reduced.

[Brief explanation of the drawing]

FIG. 1 is a plan view showing an embodiment of the blood component separation system of the present invention, FIG. 2 is a sectional view showing an example of the configuration of a leukocyte removal filter device, and FIG. 3 is a plan view showing an embodiment of the blood component separation system of the present invention. FIG. 4 is a plan view of another embodiment of the system. 1... Blood collection needle, 3... Blood collection bag, 7... Filter device, 11.13.17... Blood component separation bag, 19.
...Physiological solution bag, 20...Blood inlet, 23.
24... Prefilter-1 25... Leukocyte removal filter, 28... Blood outflow port. Figure 2 Figure 3

Claims (5)

[Claims] (1) The fluid inlet of the blood filter device that captures only white blood cells is connected to the blood collection bag, and the fluid outlet of the blood filter device is connected to two child bags in parallel, and one or more series or A blood component separation system characterized in that another child bag connected in parallel is connected directly to the blood collection bag or at one or more points to a connecting pipe connecting the blood filter device and the blood collection bag. (2) One of the child bags connected to the fluid outlet of the blood filter device is a concentrated platelet fluid separation bag, which is made of a material that does not reduce platelet function, and which maintains platelet function. The blood component separation system according to claim 1, which contains the target drug. (3) The blood component separation system according to claim 1 or 2, wherein either one of the child bags connected to the fluid outlet of the blood filter device is a bag for separating concentrated red blood cell fluid, and contains a red blood cell preservation solution therein. (4) The blood component separation system according to any one of claims 1 to 3, wherein one of the separate child bags contains a red blood cell preservation solution or a platelet preservation solution. (5) Blood component separation according to any one of claims 1 to 4, wherein one of the separate child bags contains a physiological solution for recovering platelets or red blood cells remaining in the filter device. system.