JPH0780058A - Bag connector and method for separating and transporting component - Google Patents

Abstract

PURPOSE:To enable sepn. to four components and to rapidly make the bag connector aseptic by providing the bag connector with a tube communicating at one end with the top end of a firs bag and at the other end with a second bag, a tube communicating at one end with the bottom end of the first bag and at the other end with a third bag and a tube communicating at one end with a fourth bag and at the other end with the first bag. CONSTITUTION:This bag connector is quadrumple bags formed by connecting a blood taking bag 10, a plasma bag 40, a red cell bag 30 and a small-sized bag 50 by the respectively prescribed tubes. The upper part of the bag body 11 of the plasma bag 10 is provided with a discharge port 15 for blood transfusion and a connecting member 17 for connection to the plasma bag 40. The left side of the tube 40 in the upper tube 19 of the bag body 11 is provided with a connecting member 24 for connection to the red cell bag 30. One end of the tube 28 having flexibility is so connected to the center in the upper part of the bag body 50 of the small-sized bag 50 so as to communicate with a buffy coat housing part 53 and the other end of the tube 28 is connected to the branching end of a branching connector 26.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bag connecting body in which a plurality of bags are connected by a tube, and in particular, a body fluid such as blood or bone marrow fluid contained in a bag is separated into a plurality of components,
The present invention relates to a bag connected body used when transferring and collecting the separated component to another bag, and a method of separating and transferring the component using the connected body.

[0002]

2. Description of the Related Art Currently, when performing blood transfusion, in order to effectively use the blood and reduce the burden on the blood transfuse, the blood obtained from the blood donor is separated into each component by centrifugal separation, etc. A system is in place to transfuse only the ingredients. The introduction of this component transfusion has enabled effective use of blood compared to the conventional whole blood transfusion.

In such component blood transfusion, a bag connecting body (multiple bags) in which a plurality of bags including a blood collecting bag are connected by a tube is used. Of these multiple bags, the triple bag is a blood collection bag, a plasma storage bag (hereinafter referred to as a plasma bag), and a buffy coat storage bag (hereinafter referred to as a buffy coat bag).
And are respectively connected by tubes, and red blood cells are obtained by centrifuging the blood collected in the blood collecting bag.
After separating the buffy coat and the plasma into three layers, the upper layer plasma and the intermediate layer buffy coat are sequentially transferred to the plasma bag and the buffy coat bag through the respective tubes, and the lower layer red blood cells are left in the blood collection bag.

Also, as a blood collection bag, Japanese Patent Publication No. 63-2
A bag having a structure in which a tube for discharging plasma is connected to the upper end of a blood collecting bag of the type shown in No. 0144 and a tube for discharging red blood cells is connected to the lower end of the blood collecting bag is known. When such a bag is applied to a triple blood collection bag, a tube connected to the upper end and a tube connected to the lower end of the blood collection bag are connected to a plasma bag and a red blood cell storage bag (hereinafter referred to as a red blood cell bag), respectively. The blood collected in the blood collecting bag is centrifuged to separate it into three layers of red blood cells, buffy coat and plasma, and then the red blood cells in the lower layer and the plasma in the upper layer are passed through the respective tubes to the red blood cell bag and the plasma bag. And buffy coat in the middle layer is left in the blood collection bag.

By the way, the buffy coat remaining in the blood collection bag mainly contains platelets and leukocytes. When the platelets are separated and collected from the buffy coat, the blood collection bag is centrifuged again, The buffy coat is separated into upper layer platelets and lower layer white blood cells. In this case, since the blood collection bag has a volume capable of storing a predetermined blood collection amount (200 ml or 400 ml in Japan), it is necessary to centrifuge buffy coat of about 1/4 of the blood collection amount. The volume is too large, centrifugation is not performed sufficiently, or the blood collection bag is not expanded so much that the interface between platelets and leukocytes is easily disturbed after the separation, and the platelet yield (removal rate of leukocytes) decreases. There is a problem.

The buffy coat remaining in the blood collection bag is discharged from, for example, the discharge port provided in the blood collection bag,
It is also possible to transfer it to another small bag, centrifuge in this bag, and separate it into platelets and white blood cells,
This method has a drawback that it is difficult to aseptically perform the operation of transferring the buffy coat from the blood collection bag to another small bag, and there is a possibility of contamination due to invasion of bacteria.

[0007]

The object of the present invention is to rapidly and aseptically separate into four components, and to obtain a recovery rate or a removal rate of the separated components which is equal to or higher than conventional ones. It is an object to provide a bag connecting body and a method for separating and transferring components.

[0008]

Such an object is achieved by the present invention described in (1) and (18) below. Also,
The following (2) to (17) and (19) to (22) are preferable.

(1) A first bag, a second bag, a third bag, one end of which communicates with the upper end of the first bag and the other end of which communicates with the second bag. 1 tube, one end communicates with the lower end of the first bag,
A second tube having the other end communicating with the third bag;
A bag having a fourth bag having a smaller volume than the first bag, and a third tube having one end communicating with the fourth bag and the other end communicating with the first bag. Connected body.

(2) The first bag has a band-shaped partition portion extending from the upper end portion toward the lower end portion for partitioning the inside thereof into at least two spaces, and each space partitioned by the partition portion is , The one portion of the first tube communicates with one another in the vicinity of the lower end portion of the partition portion, and one end of the second tube communicates with one space partitioned by the partition portion during liquid circulation. The bag connecting body according to (1) above, which communicates with another space partitioned by the partition part during distribution.

(3) The lower end of the partition has a curved shape, and when the radius of curvature is R and the width of the partition is H, the relationship of 0.75H≤R is satisfied (2). The bag connected body according to.

(4) At the lower end of the partition, a circular
The bag connection body according to (2) or (3) above, which has an oval or drop-shaped land portion.

(5) At least one of the spaces partitioned by the partition section is in the form of a band, and the bag connecting body according to any one of (2) to (4) above.

(6) The bag connecting body according to (5), wherein the band-shaped space is formed along a side portion of the bag body.

(7) The minimum value of the width of the band-shaped space is 7
The bag connection body according to (5) or (6) above, which has a size of 13 mm.

(8) When the distance between the center line of the bag body and the end of the strip-shaped space opposite to the partition is f, the minimum value a of the width of the strip-shaped space is 0. 05 ≦
The bag connection body according to any one of the above (5) to (7), which satisfies the relationship of a / f ≦ 0.30.

(9) The bag connection according to any one of the above (5) to (8), wherein the width of the strip-shaped space gradually increases toward the end of the partition near the other end of the partition. body.

(10) When the minimum value of the width of the band-shaped space is a and the width of the band-shaped space near the other end of the partition is b, 1.25 ≦ b / a ≦ 2. The bag connecting body according to (9), which satisfies the relationship.

(11) The width H of the partition portion is 1 to 15
The bag connection body according to any one of the above (2) to (10), which has a size of mm.

(12) The bag connecting body according to any one of (2) to (11), wherein the partition portion is obtained by adhering or fusing a sheet material constituting a bag body.

(13) One end of the first tube is connected to the upper end of the first bag, and one end of the second tube is connected to the lower end of the first bag. ) The bag connected body according to [4].

(14) The connected bag according to any one of (1) to (13), wherein the other end of the third tube is connected in the middle of the first tube or the second tube. .

(15) The fourth bag according to any one of (1) to (14) above, wherein the ratio of the horizontal length to the vertical length of the storage space is 1: 1 to 1: 2. The bag connection body described.

(16) The bag connection body according to any one of (1) to (15), wherein the capacity of the fourth bag is 15 to 50% of the capacity of the first bag.

[0025]

(17) The sum of the volumes of the second bag, the third bag and the fourth bag is the first bag.
The bag connected body according to any one of (1) to (16), which has a capacity of 130 to 260% of the bag capacity.

(18) A method for separating and transferring a body fluid component by using the bag connecting body according to (1) above, wherein the body fluid contained in the first bag is at least an upper layer. A step of transferring the components of the upper layer to the second bag via the first tube after separating the components of the intermediate layer and the lower layer, and the components of the intermediate layer via the third tube. And the step of transferring the lower layer component to the third bag through the second tube in any order, and then the fourth bag. A method for separating and transferring components, characterized in that the components inside are further separated into a plurality of components.

(19) A method for separating and transferring a body fluid component by using the bag connecting body according to any one of (2) to (17), which comprises: Separating the stored body fluid into at least three components of an upper layer, an intermediate layer and a lower layer, and then transferring the components of the upper layer to the second bag via the first tube,
Transferring the components of the intermediate layer to the fourth bag via the third tube, and transferring the components of the lower layer to the third bag via the second tube, A method for separating and transferring components, which is carried out in an arbitrary order and then further separates the components in the fourth bag into a plurality of components.

(20) A step of transferring the components of the upper layer to the second bag through the first tube, and the components of the intermediate layer to the fourth bag through the third tube. The above (18) or (19), wherein any two steps of the step of transferring and the step of transferring the component of the lower layer to the third bag through the second tube are performed in parallel. Method of separating and transferring the components of.

(21) The separation of the body fluid contained in the first bag is performed by subjecting the first bag to centrifugation to separate the components according to any one of (18) to (20) above. , Transfer method.

(22) The method for separating and transferring the components according to any one of (18) to (21) above, wherein the components in the fourth bag are separated by subjecting the fourth bag to centrifugation. .

[0032]

BEST MODE FOR CARRYING OUT THE INVENTION A bag connecting body and a method for separating and transferring components according to the present invention will be described below in detail with reference to the preferred embodiments shown in the accompanying drawings. FIG. 1 is a plan view showing a configuration example of a bag connecting body of the present invention. As shown in the figure, the bag connecting body 1 includes a blood collecting bag (first bag) 10, a plasma bag (second bag) 40, a red blood cell bag (third bag) 30, and a small bag (first bag). 4 bags 50) are each connected by a predetermined tube to form a four-strip bag.

The blood-collecting bag 10 is formed into a bag shape by stacking resin-made flexible sheet materials, which will be described later, and fusing (heat-fusing, high-frequency fusing, etc.) or adhering them at the peripheral seal portion 12. It has a bag body 11 which is made.

The interior of the bag body 11 is partitioned into two spaces 14A and 14B by a strip-shaped partition portion 13. The space 14A is a space occupying most of the internal space of the bag body 11, and the space 14B is a band-shaped space formed along the side portion of the bag body 11. As will be described later, the space 14B functions as a flow path for discharging the lower layer red blood cells obtained by centrifuging blood to the outside of the bag body 11, and the space 14B has a band shape (a thin columnar shape when expanded). ), When the red blood cells flow in the space 14B from the lower (bottom) side to the upper side of the bag body 11, the flow becomes smooth and backflow is less likely to occur.

As shown in FIG. 1, both spaces 14A and 14B have a lower end portion (end portion 131) of the partition portion 13.
The vicinity, that is, near the bottom of the bag body 11 (the communication portion 14
It communicates with 1). The end portion 13 of the partition portion 13
1 has a curved shape, particularly a rounded shape.

The upper end of the partition portion 13 is connected to the seal portion 12. The partition portion 13 is preferably formed simultaneously with the seal portion 12 by fusing (heat fusion, high-frequency fusion, etc.) or adhering the sheet material forming the bag body 11. If formed by such a method, the partition portion 13 can be easily manufactured without increasing the number of manufacturing steps.

The width of the partition portion 13 is not particularly limited, but in the case of forming the sheet material by fusing or adhering, considering the peeling strength thereof, it is about 1 to 15 mm on average, and particularly about 2 to 10 mm on average. Preferably.

FIG. 2 is a plan view showing another configuration example of the blood collection bag. The blood collection bag 10 shown in FIG.
When the end 131 of 3 has a curved shape, the radius of curvature thereof is R, and the width of the partition 13 (the average value of widths other than the end 131) is H, it is preferable that 0.75H ≦ R. Is satisfied, and more preferably the relationship of H ≦ R is satisfied. When the internal pressure of the blood collection bag 10 increases due to centrifugal separation or the like, stress tends to concentrate on the end 131 of the partition portion 13, but by satisfying the above relationship,
A crack is prevented from being generated at the end 131 of the partition portion 13, and the bag body 11 is prevented from being damaged by the crack at the end 131.

In order to satisfy the above relationship, it is preferable to form a land portion having, for example, a circular shape, an elliptical shape, a drop shape, or a combination thereof in the end portion 131, as shown in the figure. When the radius of curvature R is not constant, such as when the contour shape of the land is elliptical, the radius of curvature R
It is preferable that the minimum value of satisfies the above relationship.

FIG. 3 is a plan view showing the position of the end of the partition 13 in the blood collection bag 10. The end portion 131 of the partition portion 13 may be located at any of the positions X, Y and Z in FIG. 2 or may be located at an intermediate position therebetween.

In this case, the position X in FIG. 3 indicates the lower layer (red blood cell layer) and the intermediate layer (buffy coat layer) when the blood contained in the bag body 11 of the blood collection bag 10 is centrifuged. The position is below the boundary. The Z position is the lowest position, that is, near the center of the bottom of the bag body 11.

In particular, it is preferable to set the position of the end portion 131 of the partition portion 13 to any position from X to Y. This makes it easier to store the blood collection bag 10 in the centrifuge cup, further reduces damage to the bag during the centrifugation operation due to the influence of the end 131, and the amount of leukocytes and the like mixed into the separated red blood cell layer. Is significantly reduced, and the recovery rate of red blood cells is improved.

When the space 14B is formed in a strip shape as shown in the drawing, the minimum value a of the width of the space 14B is 2c <a <5c when the inner diameter of the tube 25 is c (see FIGS. 2 and 3).
It is preferable to satisfy the following relation. Specifically, a is 7
It is preferably about 13 mm. When the minimum value a of the width of the space 14B is less than 7 mm, the space 14B is easily closed due to the deformation of the side portion of the bag main body in the expanded state of the bag main body 11 after centrifugation, and such closure is not generated. Even so, the width of the space 14B is too narrow, and the discharge speed of red blood cells from the bag body 11 becomes slow. If a exceeds 13 mm, the red blood cell recovery rate (removal rate of white blood cells from red blood cells) decreases.

For the same reason as above, when the distance between the center line 110 of the bag body 11 and the boundary line between the space 14B and the seal portion 12 is f (see FIG. 3), the space 14
The minimum value a of the width of B preferably satisfies the relationship of 0.05 ≦ a / f ≦ 0.30, and 0.1 ≦ a / f ≦ 0.2.
It is more preferable to satisfy the relationship of 3.

The width of the space 14B does not necessarily have to be constant over the entire length thereof, and the width of the space 14B may be gradually reduced or gradually increased from the upper portion to the lower portion of the bag body 11. That is, the blood collection bag 10 shown in FIG.
The width of the space 14B continuously increases from the middle of the partition 13 to the end 131 of the partition 13. With such a configuration, the recovery rate of red blood cells and the leukocyte removal rate from red blood cells are further improved.

In the case of such a configuration, the minimum value a and the maximum value (width of the space 14B at the end 131) b of the space 14B satisfy the relationship of 1.25 ≦ b / a ≦ 2. Is preferred. In such a range, the recovery rate of red blood cells and the leukocyte removal rate from red blood cells are improved.

In the blood collection bag 10 as described above, the volume ratio of the spaces 14A and 14B is not particularly limited, but the volume of the space 14B is less than 5% of the total volume of the bag body 11, particularly 0.6 to 4.0. It is preferable to set it to about%.

On the upper part of the bag body 11, a blood transfusion outlet 15 that is openably sealed by a peel tab and a connecting member (sealing member) 17 for connecting to the plasma bag 40.
Are provided, and one end of a flexible tube 19 for introducing blood collection blood is connected. The discharge port 15, the connecting member 17, and the tube 19 are
Both communicate with the space 14A.

One end of a flexible tube 18 is connected to the connecting member 17. The other end of the tube 18
It is connected to one end of a tube 27 via a tee-shaped branch connector 26. The other end of the tube 27 is connected to the upper portion of a plasma bag 40 described later. The tubes 18 and 27 form a first tube.

A blood collection needle 21 is attached to the other end of the tube 19 via a hub 20. A cap 22 that encloses the blood collection needle 21 is attached to the hub 20.

The tube 1 above the bag body 11
A connection member (sealing member) 24 similar to the connection member 17 for connecting to the red blood cell bag 30 is provided on the left side of FIG. The connecting member 24 communicates with the space 14B. Further, one end of a flexible tube (second tube) 25 is connected to the connecting member 24. The other end of the tube 25 has an erythrocyte bag 30 described later.
Attached to the top of.

As the connecting members 17 and 24, it is preferable to use sealing members whose flow paths are closed before breakage, but the flow paths are opened when they break, and a structural example thereof will be described later in detail.

Incidentally, such connecting members 17 and 24
Respectively project to the outside of the bag body 2 and do not project into the spaces 14A and 14B, so that the vibration of the opening (liquid flow) causes the boundary surface of each component layer separated by centrifugal separation in the bag. It does not disturb and contributes to the improvement of the yield of the separated components.

Further, in the present invention, such a connecting member 1
7 and 24 are not provided, but tubes 18 and 2 can be
5 may be appropriately closed or released.

In the blood collecting bag 10 having the above structure,
Since the connection of the tubes 18, 19, 25 and the like can be concentrated on the upper end side of the bag body 11, it is possible to prevent the bag from being mistakenly put in the centrifuge cup during centrifugation. The bags of the bag connecting body 1 have a good bundling property, are easy to handle, and the dead space generated in the centrifuge cup is reduced, so that the bag is prevented from being damaged by the pressure during centrifugation.

Red blood cell bag 30 located on the left side in FIG.
Is a flexible resin sheet described below,
At the peripheral seal portion 32, there is a bag-shaped bag body 31 which is fused (heat fusion, high frequency fusion, etc.) or adhered to form a bag.

An erythrocyte storage portion 33 for storing the concentrated erythrocytes separated from the blood in the blood collection bag 10 is formed in an inner portion surrounded by the seal portion 32 of the bag body 31.

At the top of the bag body 31, there are two drainage ports 34 for transfusion, which are openably sealed by peel tabs.
34 is formed, and the red blood cell storage 3 is formed on the side thereof.
The end of the tube 25 is connected so as to communicate with the tube 3. As a result, when the flow path of the connecting member 24 is opened, the space 14B of the blood collection bag 10 and the red blood cell storage portion 33 of the red blood cell bag 30 communicate with each other via the tube 25.

Plasma bag 40 located on the right side in FIG.
Is a flexible resin sheet described below,
At the peripheral seal portion 42, a bag-shaped bag body 41 is formed by fusing (heat fusing, high-frequency fusing, etc.) or adhering.

A plasma storage portion 43 for storing the plasma separated from the blood in the blood collection bag 10 is formed inside the bag main body 41 surrounded by the seal portion 42.

On the upper part of the bag body 41, two blood transfusion outlets 44, which are openably sealed by peel tabs,
44 is formed, and the plasma storage portion 43 is further formed on the side thereof.
The end of the flexible tube 27 is connected so as to communicate with the. Thereby, when the flow path of the connecting member 17 is opened, the space 14A of the blood collection bag 10 and the plasma bag 40 are closed.
The plasma storage part 43 of the tube 18, the branch connector 2
6 and the tube 27.

Blood collection bag 10 and plasma bag 40 in FIG.
The small bag 50 positioned between the upper and lower sides is formed by stacking flexible sheet materials made of resin, which will be described later, and the seal portion 5 at the periphery thereof.
2 has a bag-shaped bag body 51 which is fused (heat fusion, high frequency fusion, etc.) or adhered to form a bag.

A buffy coat accommodating portion 53 for accommodating the buffy coat separated from the blood in the blood collecting bag 10 is formed in an inner portion surrounded by the seal portion 52 of the bag body 51.

One end of a flexible tube (third tube) 28 is connected to the center of the upper portion of the bag body 50 so as to communicate with the buffy coat accommodating portion 53, and the other end of the tube 28 is connected to the branch connector 26. Is connected to the branch end of. As a result, when the flow path of the connecting member 17 is opened, the space 14A of the blood collection bag 10 and the buffy coat storage portion 53 of the small bag 50 are connected to the tube 18 and the branch connector 26.
And through the tube 28.

Further, one end of a flexible tube 29 is connected to the upper portion of the small bag 50 so as to communicate with the buffy coat storage portion 53, and the other end of the tube 29 is sealed by, for example, fusion bonding. There is.

The ratio of the horizontal length W to the vertical length L of the buffy coat storage portion 53 is preferably W: L = 1: 1 to 1: 2, and W: L = 1: 1. More preferably, it is 3 to 1: 1.7. When the aspect ratio of the buffy coat storage portion 53 is within such a range, centrifugal force is appropriately applied when centrifuging the buffy coat stored in the small bag 50, which is advantageous and the centrifugal assist cup It has the advantages that it can be easily inserted into the container and that the components can be easily separated by a separation stand or the like after centrifugation.

In the bag connecting body 1 shown in FIG. 1, for example, soft polyvinyl chloride is preferably used as the constituent material of the sheet material that constitutes the bag body of each bag 10, 30, 40, 50.

Examples of the plasticizer in this soft polyvinyl chloride include di (ethylhexyl) phthalate (D
EHP), di- (n-decyl) phthalate (DnDP)
Etc. are used. The content of such a plasticizer is
The amount is preferably about 30 to 70 parts by weight with respect to 100 parts by weight of polyvinyl chloride.

As another constituent material of the sheet material of each bag 10, 30, 40, 50, a polyolefin, that is, a polymer obtained by polymerizing or copolymerizing an olefin or diolefin such as ethylene, propylene, butadiene, isoprene, or the like is used. It can be used, and examples thereof include polyethylene, polypropylene, ethylene-vinyl acetate copolymer (EVA), polymer blends of EVA and various thermoplastic elastomers, and any combination thereof. Furthermore, polyethylene terephthalate (PET), polybutylene terephthalate (PB)
T), polyester such as poly-1,4-cyclohexanedimethyl terephthalate (PCHT), or polyvinylidene chloride can also be used.

The thickness of the sheet material constituting each bag 10, 30, 40, 50 is determined and used in consideration of the gas permeability of oxygen gas, carbon dioxide gas, etc., the strength that can withstand the centrifugal separation operation, etc. Although it depends on the constituent material of the sheet material, the thickness of the sheet material of the blood collection bag 10 is usually about 0.2 to 1.0 mm, and preferably about 0.3 to 0.5 mm,
The sheet materials of the red blood cell bag 30 and the plasma bag 40 each have a thickness of about 0.2 to 0.7 mm, particularly 0.3.
The thickness of the sheet material of the small bag 50 is preferably about 0.2 to 1.0 mm, and more preferably about 0.5 to 0.5 mm.
It is preferably about 3 to 0.5 mm.

As the sheet material constituting the platelet storage bag described later, the same material as the sheet material such as the bag 10 described above can be used, but in order to improve the platelet storage property, gas permeation is improved. It is preferable that the above-mentioned polyolefin or DnDP plasticized polyvinyl chloride is used as the sheet material, or the sheet material is relatively thin (for example, 0.
The thickness is preferably about 1 to 0.5 mm, particularly about 0.1 to 0.3 mm).

Capacity of blood collection bag 10 (spaces 14A, 14
The total volume of B) is not particularly limited, but it is necessary to have a volume corresponding to the amount of blood collected. About 200 or 400 ml is used in Japan, and 350 to 400 is used overseas. It is preferably about 600 ml.

Capacity of red blood cell bag 30 (red blood cell storage 3
3) and the volume of the plasma bag 40 (the plasma storage unit 4
The volume of 3) is not particularly limited, but it is about 100 to 400 ml, particularly about 150 to 300 ml for use in Japan, and about 150 to 600 ml, particularly about 200 for use abroad. It is preferably about 450 ml.

The capacity of the small bag 50 (the capacity of the buffy coat storage portion 53) is less than the capacity of the blood collection bag 10, and is preferably smaller than both the capacity of the red blood cell bag 30 and the capacity of the plasma bag 40. Specifically, the capacity of the small bag 50 is 15 to 15 times the capacity of the blood collection bag 10.
It is preferably about 50%, particularly about 20 to 35%. If it is less than 15%, it is not possible to transfer and collect a sufficient amount of the separated components to the small bag 50, and if it exceeds 50%, the small bag 50 becomes large and handling at the time of centrifugal separation operation is difficult. In addition, the separation becomes insufficient when centrifuging the buffy coat, and the interface of the separated components is easily disturbed when recovering the separated components, and the platelet yield (leukocyte removal rate) Because it will decrease.

For the same reason, the red blood cell bag 3 is used.
0, the total volume of the plasma bag 40 and the small bag 50 is preferably about 130 to 260%, particularly about 190 to 240% of the capacity of the blood collection bag 10. An example of the capacity of each bag is shown in Table 1 below.

[0076]

[Table 1]

In the bag connecting body 1 shown in FIG. 1, the constituent materials of the tubes 18, 19, 25, 27, 28 and 29 are, for example, polyvinyl chloride, polyethylene,
Examples thereof include polypropylene, polyesters such as PET and PBT, ethylene-vinyl acetate copolymers, polyurethanes, polyester elastomers, thermoplastic elastomers such as styrene-butadiene-styrene copolymers, and among them, polyvinyl chloride is particularly preferable. preferable. If each tube is made of polyvinyl chloride, sufficient flexibility and flexibility can be obtained, so that it is easy to handle and suitable for clogging by clenching, and each bag body 11, 3
This is because the bondability with 1, 41 and 51 is good. The type and content of the plasticizer used in each tube are not particularly limited.

It is preferable that the blood collection bag 10 contains an anticoagulant in advance. This anticoagulant is
Usually a liquid, for example, ACD-A liquid, CPD liquid, C
Examples thereof include PDA-1 solution and heparin sodium solution.
Appropriate use amounts of these anticoagulants are about 15 ml each of ACD-A solution and heparin sodium solution and about 14 ml of CPD solution and CPDA-1 solution per 100 ml of human whole blood.

The red blood cell bag 30 may contain a red blood cell preservation solution in advance. As this red blood cell preservation liquid, for example, S.A.G.M liquid (sodium chloride: 0.877 W / V%, adenine: 0.0169 W / V%, glucose:
0.818 W / V%, D-mannitol: an aqueous solution containing 0.525 W / V%), OPTISOL solution, ADSOL solution, MAP solution and the like.

The small-sized bag 50 may contain a platelet preservation solution in advance. Examples of the platelet preservation solution include physiological saline solution, GAC solution, PAS solution, P
Examples include SM-1 liquid and Synthetic Storage Medium liquid. In addition, such a platelet storage solution may be put in a platelet storage bag described later.

Next, the structure of the connecting member 17 will be described. FIG. 7 is a vertical cross-sectional view showing an enlarged configuration example of the connecting member 17. As shown in the figure, the connecting member 17 includes a short tube 170 made of a flexible resin such as soft polyvinyl chloride, and the short tube 17
And a cylindrical body 171 that is liquid-tightly fitted into the inside of the cylinder 0 and has one end closed by a solid columnar portion 172.

One end of the tube 18 is liquid-tightly connected to the upper end of the short tube 170 in FIG.
The lower end in FIG. 7 is the seal part 1 on the upper part of the bag body 11.
It is liquid-tightly adhered or fused to 2. A thin and fragile breaking portion 173 is formed on the outer periphery of the cylindrical body 171. From the outside of the short tube 170 with fingers or the like, the short tube 170
The flow path is opened by bending the solid columnar portion 172 to break the fractured portion 173 and separating the solid columnar portion 172.

As the constituent material of the cylindrical body 171, for example,
Hard materials such as hard polyvinyl chloride, polycarbonate and polyester can be used. The upper part of the solid columnar part 172 in the drawing has a wedge shape, and its upper end (top part) 1
74 has a dimension in the width direction smaller than the outer diameter of the cylindrical body 171,
The solid columnar section 172 has a size larger than the inner diameter of the tube 18 and is separated from the solid columnar section 172 by fracture.
It is preferable to have a structure that does not block the. further,
As shown in the figure, the upper end portion 174 of the solid columnar portion 172 has
A groove 175 may be provided to promote the flow of liquid. The connecting member 24 may have the same structure as that shown in FIG. 7.

FIG. 4 is a plan view showing another structural example of the bag connecting body of the present invention. The bag connecting body 2 shown in FIG.
The small bag 50 is the same as the bag connecting body 1 except that the connecting position of the tube 28 is different. That is, the branch connector 26 is installed in the middle of the blood collection tube 19, and one end of the tube 28 is connected to the branch end of the branch connector 26. As a result, the space 14A of the blood collection bag 10 and the buffy coat storage portion 5 of the small bag 50 are accommodated.
3 communicates with each other via the tube 19, the branch connector 26, and the tube 28.

In the bag connecting body 2 as described above, when the blood sample is introduced into the blood collecting bag 10 through the tube 19, the tube 28 is closed in the middle by using a clamp or the like.

FIG. 5 is a plan view showing another structural example of the bag connecting body of the present invention. The bag connecting body 3 shown in FIG.
The small bag 50 is the same as the bag connecting body 1 except that the connecting position of the tube 28 is further different. That is, the branch connector 26 is installed in the middle of the tube 25, and one end of the tube 28 is connected to the branch end of the branch connector 26. As a result, when the flow path of the connecting member 24 is opened, the space 14B of the blood collection bag 10 and the buffy coat storage portion 53 of the small bag 50 are separated from each other by the tube 25,
It communicates via the branch connector 26 and the tube 28.

When transferring the red blood cells in the blood collection bag 10 to the red blood cell bag 30 through the space 14B and the tube 25 in the bag connecting body 3 as described above,
The tube 28 is closed in the middle using a clamp or the like, and the blood collection bag 1 is inserted through the space 14B and the tubes 25 and 28.
When the buffy coat in 0 is transferred to the small bag 50, the tube 25 on the red blood cell bag 30 side of the branch connector 26 is closed using a clamp or the like.

The structure of the blood collection bag 10 according to the present invention is as follows.
The configuration is not limited to the configuration shown in each drawing, and for example, the inside of the bag body 11 may be divided into three spaces by two strip-shaped partition portions. These partition parts can be formed, for example, along both side parts of the bag body 11, and the partition parts are divided into second spaces in the belt-shaped spaces on both side parts of the bag body.
Tubes are connected.

FIG. 6 is a plan view showing another structural example of the bag connecting body of the present invention. The bag connecting body 4 shown in FIG.
The bag connecting body 1 except that the structure of the blood collecting bag is different.
Is the same as. That is, the blood collection bag 60 in the bag connecting body 4 is formed by stacking the above-mentioned flexible sheet materials made of resin, and fusing (heat fusing, high-frequency fusing, etc.) or bonding at the seal portion 62 at the periphery thereof. , And has a bag-shaped bag body 61. The seal portion 62 of the bag body 61
A blood storage portion 63 for storing the collected blood is formed in an inner portion surrounded by.

On the upper part of the bag body 61, the discharge port 15 and the connecting member 17 similar to the above are installed, and the end of the tube 19 is connected. Further, one end of the tube 25 is connected to the center of the lower part of the bag body. As a result, the blood container 63 of the blood collection bag 60 is
And the red blood cell storage portion 33 of the red blood cell bag 30 communicate with each other via the tube 25.

In this blood collection bag 60, of the separated blood components, the upper layer plasma is discharged from the connecting member 17 and transferred to the plasma bag 40 via the tubes 18 and 27, and the intermediate layer buffy coat is The red blood cells in the lower layer, which are discharged from the connecting member 17 and transferred to the small bag 50 through the tubes 18 and 28, are discharged from the lower portion (bottom) of the bag body 61 and transferred to the red blood cell bag 30 through the tube 25.

In the bag connecting body 4, the branch connector 26 may be provided in the middle of the tube 25, and one end of the tube 28 may be connected to the branch end.
Further, in the bag connected body 1 or 4, the branch connector 26 may not be provided, and the end of the tube 28 may be directly connected to the upper end of the blood collection bag 10 or 60.

Next, preferred examples of the method for separating and transferring the components of the present invention will be described. The method for separating and transferring the components of the present invention is carried out using the bag connecting body of the present invention. Hereinafter, a method for separating and transferring components using the above-described bag connecting body 1 will be described as a representative example.

[1] The blood collection needle 21 is punctured into the blood vessel, and the blood collection is introduced into the blood collection bag 10 through the tube 19. At this time, the collected blood is introduced into the space 14A of the blood collecting bag 10 through the tube 19 and the portion of the space 14A of the bag body 11 gradually swells. The swelling causes the bag body 11 to bend at the partition 13 as a boundary. Therefore, the communication part 1 of both spaces 14A and 14B is
Since the closed state of 41 is maintained, blood hardly enters the space 14B. Note that, for example, the space 14B
Even if blood invades inside, the space 14B is crushed by the centrifugal force on the inner surface of the cup of the centrifugal cup during centrifugal separation, which will be described later. Therefore, a small amount of blood remains in the space 14B, and most of the blood is red blood cells. In particular, the end 1 of the partition 13
When 31 has the shape having the land portion, it is advantageous for closing the communication portion 141.

Further, in order to more reliably close the communication portion 141, the sheet materials in the vicinity of the communication portion 141 may be previously blocked (bonded), or may be sealed by a clamp or the like. The blood sampling amount is, for example, 200 or 400 ml, or 450 to 500 ml.

[2] After completion of blood collection in the blood collection bag 10, the tube 19 is sealed by, for example, fusion bonding, and the sealed portion is cut to separate and remove the tube on the side of the blood collection needle 21.

[3] Next, the blood collection bag 10, the red blood cell bag 30, the plasma bag 40, and the small bag 50 are bundled, placed in a centrifuge cup of a centrifuge with the bottom of each bag facing downward, and subjected to centrifugation. As the centrifuge, for example, CR7B3 manufactured by Hitachi Ltd. can be used. In this case, the centrifugation conditions are, for example, 4670 G and 6 minutes (1.2 × 10 ⁶ g · sec). It should be noted that even during the centrifugation operation, blood does not enter the space 14B.

By such centrifugation, the blood in the space 14A is separated from the upper layer into three layers, that is, the plasma layer, the buffy coat layer and the red blood cell layer (not shown). The constituent components of the separated layers differ depending on the centrifugation conditions.

During the centrifugation operation, the bag body 11
Since the internal pressure in the lower part of the inside increases, the lower part of the bag body further expands accordingly, so that the end 131 of the partition part 13
Although stress tends to concentrate in the vicinity, when the end portion 131 has a rounded shape, particularly when the above-mentioned conditions are satisfied,
No peeling or cracking of the end portion 131 occurs, and as a result, damage to the bag body 11 is prevented.

[4] After centrifugation, the bag connecting body 1 is gently taken out from the centrifuge cup, and the blood collection bag 10 is set on a separation stand (not shown).

The separation stand may be either a manual type or an electric type. The manual type has, for example, a pair of pressing plates and a lever fixed to one of the pressing plates. With the blood collecting bag 10 set between the pressing plates, the lever is operated to rotate one pressing plate about one side thereof with respect to the other pressing plate, thereby collecting the blood collecting bag 1
It is possible to use a simple structure in which 0 is clamped or pressed.

Further, an automatic separating device provided with a bag compressing device (motorized separating stand), an optical sensor for detecting the interface of separated components, a control means (microcomputer), etc. may be used.

[5] The tube 28 is clamped in the middle by clamping with a clamp or the like to open the internal channel of the connecting member 17 as described above, and the blood collection bag 10 is gradually pressed by the separation stand. As a result, the upper layer plasma is discharged from the opened connecting member 17, and is transferred to the plasma storage portion 43 of the plasma bag 40 via the tube 18, the branch connector 26, and the tube 27.

[6] The tube 28 is unblocked, the tube 27 is clamped by clamping it in the middle of the tube 27, and the blood collection bag 10 is gradually pressed by the separation stand.
As a result, the intermediate layer buffy coat is discharged from the opened connecting member 17, and transferred to the buffy coat storage portion 53 of the small bag 50 via the tube 18, the branch connector 26 and the tube 28.

[7] The connecting member 24 as described above.
The internal flow path is opened, and the blood collection bag 10 is gradually pressed by the separation stand. As a result, the red blood cells (concentrated red blood cells) in the lower layer enter the space 14B via the communication portion 141, are discharged from the opened connecting member 24, and are transferred to the red blood cell storage portion 33 of the red blood cell bag 30 via the tube 25. .

The above steps [5], [6] and [7]
Can be performed in the following order, for example. The steps [5], [6], and [7] are performed in this order. The steps [5], [7], and [6] are performed in this order. The steps [7], [5], and [6] are performed in this order. Steps [5] and [7] are performed simultaneously, and then step [6] is performed. The step [5] is performed, and then the steps [6] and [7] are performed simultaneously.

Alternatively, the pattern shown in FIGS. 8 to 19 can be used. Of these, and somewhat, when two steps are performed in parallel as in each pattern shown in FIGS. 8 to 19, the components can be separated and transferred in a shorter time, and the separation can be performed. Since the fluctuation of the interface between the components is reduced, the yield of the separated components, especially the leukocyte (particularly lymphocyte) removal rate in the red blood cell preparation is increased, which is preferable.

Of the above, in the pattern of FIGS. 11 and 15, when performing the step [6],
In the middle of the tube 25, in the space 14B, or in the communication part 1
41 is clamped by a clamp or the like to close it, thereby preventing the buffy coat from flowing out to the red blood cell bag 30 side.

When discharging and transferring such separated components, the discharge flow rate can be adjusted by pressing the tube 18 or 25 in the middle with fingers or a device such as a roller clamp. Such adjustment can be performed in order not to disturb the interface between the separated components, which contributes to the improvement of the yield of the separated components.

When transferring the separated components to the bags 30, 40 and 50, the weight of each bag may be measured, and when the preset weight is reached, the liquid transfer may be stopped. . In the case of the small bag 50, the weight (set weight) of the buffy coat to be collected is 50 to 6
The amount is about 5 g (when the blood sampling amount is 400 ml). Alternatively, an optical sensor may be installed to detect the interface between the separated components, and the liquid transfer may be stopped when the interface reaches the upper end or the lower end of the space 14A of the blood collection bag 10.

[8] When each separated component in the blood collection bag 10 is transferred to a predetermined bag, the tube 25,
The middles of 27 and 28 are sealed by fusion, and these sealed portions are cut to separate the blood collection bag 10, the red blood cell bag 30, the plasma bag 40, and the small bag 50 from each other. As a result, the red blood cell bag 3 in which the red blood cells, plasma and buffy coat are stored in a sealed state, respectively.
0, plasma bag 40 and small bag 50 are obtained.

Before the tubes 27 and 28 are sealed, the plasma in the plasma bag 40 is transferred to the tubes 27 and 2.
There is also a case where a small amount is transferred into the small bag 50 via 8 in advance.

[9] A platelet storage bag (not shown) is prepared separately, and the tube 2 of the small bag 50 in which the tube connected to this bag and the buffy coat are stored
8 and 8 are connected by a tube connecting device, for example. As the tube connecting device and the connecting method, for example, the one (SCD) described in Japanese Patent Publication No. 61-30582 can be applied. In addition, such a small bag 5
0 and the platelet storage bag may be connected after the small bag 50 is centrifuged.

[10] As the small bag 50 and the platelet storage bag connected by a tube, a centrifugal cup of the same centrifugal separator as described above (having a size and shape corresponding to the size of the bag to be stored can be used. ) And centrifuge. In this case, the centrifugation conditions are, for example,
It takes about 6.5 minutes at 170 to 180G.

Due to such centrifugation, the small bag 5 is
The buffy coat in 0 is in a state of being separated into almost two layers of upper layer platelets (concentrated platelet plasma) and lower layer white blood cells (not shown). In this case, as described above, since the small bag 50 has an appropriately small capacity, the buffy coat can be sufficiently separated into platelets and leukocytes, and the platelet yield (leukocyte removal rate) can be kept high. it can.

[11] After centrifugation, the connected body of the small bag 50 and the platelet storage bag is gently removed from the centrifuge cup, the small bag 50 is set on the same separation stand as described above, and the small bag 50 is gradually compressed. . As a result, the upper layer platelets are transferred to the platelet storage bag via the tube 28 and the like, and the lower layer white blood cells remain in the small bag 50. In this case, as described above, since the capacity of the small bag 50 is appropriately small and the small bag 50 is compressed in a state of being inflated to some extent, channeling does not occur and the interface of the separated components is not disturbed, and the platelet The yield (removal rate of white blood cells) can be kept high.

[12] When the platelets in the small bag 50 are transferred to the platelet storage bag, the tube 28 and the like are sealed in the middle by fusion, and the sealing portion is cut to cut the small bag 50 and the platelet storage bag. And separate. This allows
A platelet storage bag and a small bag 50, in which platelets and white blood cells are respectively stored in a sealed state, are obtained. In addition, the platelet storage bag is subjected to shaking storage at room temperature, for example.

As described above, according to the present invention, the separation of blood into four components of plasma, red blood cells, white blood cells and platelets can be performed aseptically in a closed system (closed system). It is possible to prevent contamination due to.

Next, a method of separating and transferring the components using the above-described bag connecting body 3 will be described. In this method, the steps [5], [6] and [7] in the method for separating and transferring the components using the bag connecting body 1 described above respectively include the following steps [5 '], [6'] and [6 ']. 7 '] is replaced with the same as above.

[5 '] The blood collection bag 1 is opened by opening the internal flow path of the connecting member 17 and by the separation stand.
Gradually press 0. As a result, the plasma of the upper layer is discharged from the opened connecting member 17, and transferred to the plasma storage portion 43 of the plasma bag 40 via the tube 18.

[6 '] Release the blockage of the tube 28,
Tube 2 on the side of red blood cell bag 30 from the branch connector 26
The middle of 5 is clamped by clamping with a clamp or the like, and the blood collection bag 10 is gradually pressed by the separation stand. As a result, the buffy coat of the intermediate layer is formed into the opened connecting member 2
4, and is transferred to the buffy coat storage portion 53 of the small bag 50 via the tube 25, the branch connector 26 and the tube 28.

[7 '] The tube 28 is clamped and closed in the middle with a clamp or the like to open the internal flow path of the connecting member 24, and at the same time, the blood collection bag 10 is separated by the separation stand.
Gradually squeeze. As a result, the red blood cells (concentrated red blood cells) in the lower layer enter the space 14B via the communication part 141, and are discharged from the opened connecting member 24, and the tube 2
Then, it is transferred to the red blood cell storage section 33 of the red blood cell bag 30 via

The above steps [5 '], [6'] and [7 '] can be performed in the following order, for example. The steps [5 ′], [7 ′], and [6 ′] are performed in this order. The steps [7 ′], [5 ′], and [6 ′] are performed in this order. The steps [7 ′], [6 ′], and [5 ′] are performed in this order. Steps [5 ′] and [7 ′] are performed simultaneously, and then step [6 ′] is performed. Carrying out step [7 ′], then step [5 ′],
Perform [6 '] at the same time.

When two processes are carried out in parallel as in and, among these, the separation and transfer of the components can be carried out in a shorter time, and the fluctuation of the interface of the separated components is reduced. Therefore, the yield of the separated components, particularly the removal rate of white blood cells (particularly lymphocytes) in the red blood cell preparation is increased, which is preferable. In addition to the above, the same pattern as in FIGS. 8 to 19 may be used.

Although the bag connecting body of the four-strip bag has been described above, the present invention is not limited to this, and for example, the four-strip bag connecting body 1, 2 or 3 may be provided with a platelet storage bag. It may be an added 5-strip bag.

Further, the use of the present invention is not limited to the separation of the above blood components (particularly, the production of blood products from whole blood), and for example, concentration of bone marrow fluid (removal of peripheral blood), washing of red blood cells, etc. It can also be used.

[0127]

As described above, according to the bag connecting body of the present invention and the component separating and transferring method using the same,
For example, blood can be separated into four components aseptically, and a recovery rate or a removal rate of the separated components that is equal to or higher than the conventional one can be obtained.

In particular, when red blood cells and platelets are collected from blood, the removal rate of white blood cells (particularly lymphocytes) becomes high. Therefore, by using such red blood cell preparations and platelet preparations, infection of hepatitis, AIDS, GVHD, etc. Can be prevented with a higher probability.

When the first bag has a partition portion, it is easy to handle during centrifugation and a simple device such as a separation stand that has been used conventionally is used. The components can be transferred after centrifugation by a simple operation, the discharge speed of the separated components does not decrease, the recovery time is short, and the recovery rate or removal rate of the separated components is further improved.

In the method for separating and transferring the components of the present invention, when any two steps among the steps for transferring the separated components of the upper layer, the intermediate layer and the lower layer are performed in parallel, the separation and transfer operations are performed. Can be performed more rapidly, and the recovery rate or removal rate of the separated components is further improved.

[Brief description of drawings]

FIG. 1 is a plan view showing a configuration example when a bag connecting body of the present invention is applied to a bag connecting body for separating blood components.

FIG. 2 is a plan view showing another configuration example of the blood collection bag according to the present invention.

FIG. 3 is a plan view showing a position of an end portion of a partition portion in the blood collection bag.

FIG. 4 is a plan view showing another configuration example of the bag connecting body of the present invention.

FIG. 5 is a plan view showing another configuration example of the bag connecting body of the present invention.

FIG. 6 is a plan view showing another configuration example of the bag connecting body of the present invention.

FIG. 7 is a vertical cross-sectional view showing an enlarged configuration example of a connecting member in the present invention.

FIG. 8 is a graph showing an example of the transfer order of each separated component in the component separation and transfer method of the present invention.

FIG. 9 is a graph showing an example of the transfer sequence of each separated component in the component separation and transfer method of the present invention.

FIG. 10 is a graph showing an example of the transfer sequence of each separated component in the component separation and transfer method of the present invention.

FIG. 11 is a graph showing an example of the transfer sequence of each separated component in the component separation and transfer method of the present invention.

FIG. 12 is a graph showing an example of the transfer sequence of each separated component in the component separation / transfer method of the present invention.

FIG. 13 is a graph showing an example of the transfer sequence of each separated component in the component separation and transfer method of the present invention.

FIG. 14 is a graph showing an example of the transfer sequence of each separated component in the component separation and transfer method of the present invention.

FIG. 15 is a graph showing an example of the transfer sequence of each separated component in the component separation / transfer method of the present invention.

FIG. 16 is a graph showing an example of the transfer order of each separated component in the component separation / transfer method of the present invention.

FIG. 17 is a graph showing an example of the transfer sequence of each separated component in the component separation and transfer method of the present invention.

FIG. 18 is a graph showing an example of the transfer order of each separated component in the component separation / transfer method of the present invention.

FIG. 19 is a graph showing an example of the transfer sequence of each separated component in the component separation / transfer method of the present invention.

[Explanation of symbols]

 1, 2, 3, 4 Bag connected body 10 Blood collection bag 11 Bag body 110 Center line 12 Seal part 13 Partition part 131 End part (land part) 132 Upper curved part 14A, 14B Space 141 Communication part 15 Discharge port 17 Connecting member 170 Short tube 171 Cylindrical body 172 Solid columnar section 173 Broken section 174 Upper end section 175 Groove 18, 19 Tube 20 Hub 21 Blood collection needle 22 Cap 24 Connecting member 25 Tube 26 Branch connector 27, 28, 29 Tube 30 Red blood cell bag 31 Bag body 32 Seal part 33 Red blood cell storage part 34 Discharge port 40 Plasma bag 41 Bag body 42 Seal part 43 Plasma storage part 44 Discharge port 50 Small bag (buffy coat bag) 51 Bag body 52 Seal part 53 Buffy coat storage part 60 Blood sampling bag 61 bag Body 62 seal portion 63 blood containing portion X, Y, the position of the Z partition portion end

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Nobukazu Tanokura 818 Sanzodaira, Fujinomiya-shi, Shizuoka Terumo Co., Ltd.

Claims (2)

[Claims] 1. A first bag, a second bag, and a third bag.
A first tube having one end communicating with the upper end of the first bag and the other end communicating with the second bag, and one end communicating with the lower end of the first bag, and the like. A second tube having an end communicating with the third bag, a fourth bag having a smaller volume than the first bag, one end communicating with the fourth bag, and the other end having the first bag And a third tube communicating with the bag connecting body. 2. A method of separating and transferring a body fluid component by using the bag connecting body according to claim 1, wherein the body fluid contained in the first bag is at least an upper layer or an intermediate layer. After separating into three components of a layer and a lower layer, the component of the upper layer is passed through the first tube to the second component.
Transferring the components of the intermediate layer to the fourth bag via the third tube, and transferring the components of the lower layer to the third tube via the second tube. The step of transferring to a bag is performed in an arbitrary order, and thereafter, the components in the fourth bag are further separated into a plurality of components, the method for separating and transferring components.