JPH0435670A - Blood separating device - Google Patents

Abstract

PURPOSE:To house not only an additive for preserving blood corpuscles but also blood platelets by forming a child bag to house an additive for preserving blood corpuscles beforehand with a polyolefine including no plastic agent, in a quadruple bags. CONSTITUTION:A blood separating device is composed of a parent bag 1 whose capacity is large enough to house the blood from a blood donor or to add additive 15 for preserving blood corpuscles to a dense blood corpuscle liquid in the blood, and housing an anticoagulative agent beforehand, the first child bag 2 whose capacity is large enough to house a middle phase of blood component obtained by separating centrifugally the blood in the parent bag 1, the second child bag 3 whose capacity is large enough to house a blood corpuscle preserving additive 15 beforehand, the third child bag 4 whose capacity is large enough to house a blood component mainly of the blood plasma of the supernatant fluid obtained by separating the blood in the bag 1 centrifugally, tubes 7 to 11 to link those bags, and a tube 6 to link a needle 5 and the parent bag 1. The second child bag 3 is formed to a polyolefine such as polyethylene and polypropylene.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a blood separation device, and more specifically, to a device for storing whole blood and efficiently storing each blood component obtained by separating the whole blood in each bag with high purity. The present invention relates to a blood separation device.

[Conventional technology]

Conventionally, blood from a donor is collected in a bag, and the blood is separated into blood components such as red blood cells, platelets, and plasma through operations such as centrifugation, and stored. Blood separation devices are widely used for returning blood to hospitals or storing blood for transfusion.

For example, Japanese Patent Application Laid-Open No. 60-174151 discloses that blood from a blood donor is stored in a parent bag containing an anticoagulant in advance;
Transfer the supernatant plasma obtained by centrifugation to the second child bag. Next, transfer the plasma substitute containing an oxygen release enhancer from the first child bag to the parent bag where the blood cell concentrate remains. Next, the plasma in the second child bag is centrifuged to separate the upper layer of plasma and the lower layer of platelets, and the upper plasma is transferred to the third child bag. A quadruple bag system is introduced.

[Problem to be solved by the invention]

However, the blood products in the parent bag used as blood for transfusion contain white blood cells, and by repeating blood transfusions to a patient, antibodies are produced in the patient's body against the antigen on the surface of the white blood cells, resulting in antigen-antibody antibodies. There is a problem that it can cause a reaction, causing fever, rash, etc. Furthermore, the first child bag into which the plasma substitute containing the oxygen release enhancer was transferred is not effectively utilized as it is discarded empty.

[Means to solve the problem]

In order to solve these problems, the present inventors conducted various studies and arrived at the present invention.

That is, the present invention contains whole blood containing an anticoagulant,
By centrifugation, the supernatant layer is separated into a supernatant layer mainly composed of plasma, an intermediate layer mainly composed of platelets and white blood cells, and a lower layer mainly composed of red blood cells, and the supernatant layer and the Nakazaki! A parent bag receives and mixes the red blood cell preservation additive liquid from the second child bag with the blood components remaining after transferring the blood components from the second child bag to each child bag, and the middle layer blood components separated by the parent bag are mixed. A first child bag, in which the upper layer of concentrated platelet plasma obtained by suspending platelets in the plasma by centrifugation is transferred to an empty second child bag, and an additive solution for preserving red blood cells is added in advance. After transferring the additive liquid to the parent bag in which only the blood components in the lower layer remain, a second child bag made of polyolefin that receives and stores the platelet-rich plasma from the first child bag, and This blood separation device consists of a third child bag that accommodates the blood components of the separated supernatant layer and a tube that connects the bags.

The present invention also provides the blood separation device in which the polyolefins include (a) 25 to 60% by weight of poly(ethylene butylene) polystyrene block copolymer, (b) 20 to 40% by weight of polypropylene, and (C) ethylene acrylate copolymer. A polymer mixture having a composition of 5 to 35% by weight of the copolymer, having at least two or more portions in which the polystyrene segments of the block copolymer of (a) are crystallized and aligned, and the above-mentioned (a) to (c) This blood separation device is a polymer alloy in which molecular chains of polymers are intertwined in a network.

[Effect]

Since the blood separation device of the present invention uses polyolefin that does not contain a plasticizer as the material for the second bag, the plasticizer does not ooze out into the red blood cell storage additive solution, and even when platelets are stored for a long period of time, the platelets remain intact. It has the property of not reducing functionality. Furthermore, all of the quadruple bags consisting of four bags are used effectively, and almost no white blood cells are present in the red blood cell concentrate remaining in the parent bag after centrifugation.

〔Example〕

FIG. 1 is a schematic diagram of a blood separation device showing one embodiment of the present invention, in which 1 is a parent bag, 2 is a first child bag, 3 is a second child bag, 4 is a third child bag, 5 is a syringe needle, 6-11
12 and 13 are bent rods, 14 is an anticoagulant, and 15 is an additive solution for preserving red blood cells.

The blood separator shown in FIG. 1 is a blood separator that contains blood from a blood donor, or a container that contains an anticoagulant 14 in advance and has a capacity large enough to add an additive liquid 15 for preserving red blood cells to the red blood cell concentrate in the blood. A bag 1, a first child bag 2 large enough to accommodate an intermediate phase blood component obtained by centrifuging the blood in the parent bag 1, and a first child bag 2 large enough to accommodate an additive liquid 15 for preserving red blood cells in advance. A second child bag 3 having the size of a barrel, and a third child bag 4 having the size of a barrel to accommodate blood components whose main component is plasma of the supernatant obtained by centrifuging the blood in the parent bag 1. and,
It consists of tubes 7 to 11 that connect these bags and a tube 6 that connects the injection needle 5 and the parent bag 1.

CPD liquid, ACD liquid, CPDA-1 liquid, and CPDA-2 are prepared in advance to prevent blood from the donor from coagulating in parent bag 1.
Blood is collected from the injection needle 5 while containing an anticoagulant 14 such as a liquid, the whole blood is stored in the main bag 1 through the tube 6, and the tube 6 is melt-sealed and cut.Then, the tube 7 is clipped (
(not shown) and centrifuge at high speed for example at 3500 rpm.
When centrifuged for 5 minutes, the whole blood in the parent bag 1 is separated into a supernatant layer of platelet-poor plasma, an intermediate layer consisting of plasma containing platelets and white blood cells, and a lower layer of concentrated red blood cells. Next, tubes 10 and 11 are sealed with clips, and bent rod 1
3 and transfer the platelet-poor plasma in the supernatant layer to the third bag.

Transfer of the separated blood components takes place, for example, by placing the bag between a vertical wall and a pressure plate and activating the pressure plate by means of a suitable drive. The plasma in the supernatant layer is then transferred from the parent bag 1 through tubes 7, 8 and 9 to the third child bag 4, and separated from the quadruple bag by sealingly cutting tube 9. The plasma in the third child bag 4 is stored as frozen plasma. In the blood separation device of the present invention, the amount of plasma stored in the third child bag 4 is 50 to 70% by volume of the whole blood collected in the parent bag. It is.

The material for the parent bag 1 and the third child bag is preferably polyvinyl chloride containing a plasticizer such as di(2-ethylhexyl) phthalate di(2-ethylhexyl) adipate. In Figure 1, the whole blood used is from a donor. Since blood is used, an anticoagulant is stored in the parent bag in advance, but stored blood containing an anticoagulant in advance may also be used.

Next, the tube 8 is sealed with a clip, and the intermediate layer consisting of plasma containing platelets and white blood cells from the parent bag 1 is passed from the parent bag 1 through tubes 7 and 10 to the first tube in a conventional manner.
Transfer to child bag 2. The capacity of the first child bag 2 is 20 to 30% by volume of the parent bag I, and the lengths of the tubes 7 and 10 are preferably short to prevent platelets from remaining in the tubes and being lost. 1st child bag 2
The amount of plasma containing platelets and white blood cells transferred to the sample is 10 to 20% by volume relative to the amount of whole blood collected in the parent bag 1. The material for the first child bag 2 is preferably polyvinyl chloride or polyolefin containing a plasticizer such as di(2-ethylhexyl) phthalate or di(2-ethylhexyl) adipate.

On the other hand, the second child bag 3 contains an additive solution for preserving red blood cells in advance.

Additives for preserving red blood cells include mannitol, adenine, inosine, phosphate, silyl sugar, glucose, lactose, sodium chloride, citrate, pyruvet, pyruvate salt,
A composition containing at least one compound selected from the group consisting of maltose, sorbitol, citrate, and maltitol, such as SAGM solution (composition of sodium chloride, glucose, mannitol, and adenine)
, PIPA solution (composition of adenine, inosine, sodium phosphate and pyruvate) or Japanese Patent Publication 61-5
02750, a composition of glucose, mannitol, potassium citrate, adenine and sodium chloride, and a composition of mannitol, adenine, glucose, sodium citrate, sodium phosphate and sodium chloride.

The additive solution for red blood cell preservation is stored in the second child bag 3, and by adding it to the concentrated red blood cell solution in the parent bag 1, the lifespan of the red blood cells is extended, the red blood cells are activated, and the storage period of the red blood cells is extended. Ru.

The second child bag 3 is made of a polyolefin of polyethylene, polypropylene, ethylene propylene copolymer, ethylene vinyl acetate copolymer, or a mixture thereof, particularly polypropylene, poly(ethylene butylene) polystyrene block copolymer, and ethylene acrylate copolymer. A polymer alloy (hereinafter referred to as polymer alloy) consisting of a mixture with a polymer is preferred.

The polymer alloy has a composition of (a) 25 to 60% by weight of poly(ethylene butylene) polystyrene block copolymer, (b) 20 to 40% by weight of polypropylene, and (C) 5 to 35% by weight of ethylene acrylate copolymer. A polymer mixture in which the polystyrene segments of the block copolymer (a) have at least two crystallized aligned portions, and the molecular chains of the polymers (a) to (c) have a network structure. It is a polymer intertwined with.

Poly(ethylene butylene) used in polymer alloys
The polystyrene block copolymer has a structure in which the hard segment is a styrene polymer such as polystyrene or polymethylstyrene, and the soft segment is a polyethylene butylene copolymer.

The molecular weight of the polystyrene polymer used as the hard segment is 5,000 to 120,000. Polyethylene butylene copolymer, which is a soft segment, is produced by reacting polybutadiene with a molecular weight of 10,000 to 250,000 with polystyrene to produce a poly(ethylene butylene polystyrene block copolymer), and then hydrogenating the block copolymer. Polyethylene butylene copolymer, which is a soft segment, has a composition ratio of ethylene and butylene of 40 to 60/60.
~40 mol%.

The range of the amount of block copolymer used is 25% in the polymer mixture.
~60% by weight, and if the amount used is less than 25% by weight, the flexibility of the bag tends to be poor;
If it exceeds % by weight, moldability tends to deteriorate. Polypropylene is polypropylene alone or a copolymer mainly composed of polypropylene. Copolymer components other than propylene include ethylene, butene-1, etc., and the proportion thereof is 10% by weight or less.

Polypropylene has the ability to improve the strength when molded into bags, and when mixed with other polymers in a specific ratio,
By forming a polymer alloy, the strength of the resulting bag is significantly improved.

The amount of such polypropylene used ranges from 20 to 40% by weight in the polymer mixture; if it is less than 20% by weight, the transparency and strength of the bag tend to deteriorate;
If it exceeds % by weight, flexibility tends to deteriorate. The ethylene acrylic ester copolymer functions to make the block copolymer and polypropylene compatibilizing and contributes to the formation of a polymer alloy.The acrylic esters used here include methyl acrylate, ethyl acrylate, butyl acrylate, etc. The proportion thereof in the copolymer component is 5 to 90 moles. When the amount of acrylic acid ester is less than 5 mol%, transparency tends to deteriorate, and when it exceeds 90 mol%, the elastic modulus in a high temperature region tends to decrease.Amount of the ethylene acrylic ester copolymer used The range is 5 to 35% by weight in the polymer mixture, and if the amount used is less than 5% by weight, the dispersion of the polymer will be poor, extrusion processability and transparency will be poor, and above all, the low temperature properties will tend to be poor. , also 35% by weight
If it exceeds , mechanical strength tends to decrease.

When the homogeneously mixed polymer mixture is melt-extruded and molded, two or more polystyrene segments, which are hard segments of the block copolymer, are gathered together to form a crystallized and aligned region, and this region is formed by at least a portion of the polymer mixture. A chemical in which the soft segment of the block copolymer, the hard segment of the block copolymer that is not crystallized, and the molecular chains of polypropylene and ethylene acrylate copolymer are entangled with each other in a network. Forms a structured polymer alloy.

A bent rod 12 is installed on the boat which is the outlet of the red blood cell storage additive contained in the second child bag 3, and when the quadruple bag is centrifuged, the red blood cell storage additive in the second child bag 3 is removed. is designed to prevent it from leaking out of the bag.

Next, seal the tube 10 with a clip, break the bendable rod 12, and transfer the red blood cell preservation additive solution in the second bag to the tube 1.
After steps 1.8 and 7, the red blood cell concentrate is transferred to the remaining parent bag 1 by centrifugation # and blood component transfer operation to prepare a red blood cell mixture. Then, the tube 7 is sealed and cut to separate the parent bag 1 from the quadruple bag. The red blood cell mixture in the parent bag 1 is stored at 4° C. and used for blood transfusion.

The plasma mainly composed of platelets and white blood cells transferred to the first child bag 2 and stored is, for example, 800 rpm.

The mixture is centrifuged for 3 minutes to sediment white blood cells and mixed red blood cells, and the upper layer is separated from platelet-enriched plasma in which platelets are suspended in plasma. At this time, the tube 10 is sealed with a clip and centrifuged. The platelet concentrate plasma separated in the upper layer of the first child bag 2 is transferred to the empty second child bag via the tubes 10 and 8 after the tube 10 is unclipped and stored.

When molding bags, plasticizers are added to the polymer.
Melt the mixture after homogeneous mixing in a blender or mixer, or in the case of no plasticizer, melt the polymer;
The medical bag is manufactured by melt extruding into a mold in the shape of a blood bag, blow molding, or extruding into a sheet and heat sealing the edges. The thickness of the sheet can be appropriately selected depending on its use, but for example, 20
It is 0 to 500μ.

Although the blood separation device of the present invention has been described above with reference to FIG. 1, the order of the child bags is not limited to the above description, and blood components in the intermediate layer accommodated in the first child bag are transferred to the second child bag 3. Alternatively, the third child bag 4 may contain a fresh red blood cell preservation solution containing an additive solution for red blood cell preservation.

Example 1 Di(2-ethylhexyl) phthalate (hereinafter referred to as 13El
) from a polyvinyl chloride sheet (thickness 350μ) containing 35% by weight of
, 150 m long blood bags were formed, and the parent bag 1 (capacity 450 m) and the first child bag 2 (capacity 150 m) in Fig. 1 were molded.
M1) and third child bag 4 (capacity 300+d).

The second child bag is made of poly(ethylene butylene) polystyrene block copolymer (Krayton G-16 manufactured by Shell Chemical Co., Ltd.
5040% by weight, polypropylene (manufactured by Sumitomo Chemical Co., Ltd. PL
-6711N) 30% by weight and 30% by weight of ethylene ethyl acrylate copolymer (ethyl acrylate amount: 15 mol%, Nippon Unicar Co., Ltd. DPDJ6182) were mixed in a mixer and melted at 200°C to form a polymer alloy into a sheet. It was extruded and molded.

(Sheet thickness: 250μ, capacity: 300m) Each bag is connected with a polyvinyl chloride tube.

The parent bag 1 contains the CPD liquid 56d in advance, and the second child bag 3 contains the SAGM liquid 90jd.

After 4007 blood samples are collected from the injection needle 5 and mixed with the CPN solution, the tube 6 is sealed and cut. Thereafter, the parent bag 1 was placed in a centrifuge and centrifuged at 3,500 rpm for 5 minutes. The blood in the parent bag consisted of a supernatant layer containing plasma as the main component and an intermediate layer containing platelets and white blood cells as the main components. and a lower layer consisting mainly of red blood cells.

Seal the tube 10 with a clip, fold the bending rod 13, set the parent bag 1 on a separation stand (Pro B55-1), press it with a push plate to push out the plasma in the supernatant layer, and remove the tubes 7, 8 and 9. After that, 260 Jd plasma was stored in the third child bag 4. The tube 9 is melt-sealed and cut to form the third child bag 4.
was separated from the quadruple bag and stored frozen.

After the tube 8 was sealed with a clip, the middle layer of plasma mainly composed of platelets and white blood cells in the parent bag 1 was compressed and extruded using a separation stand in the same manner as described above, and 70 M1 of the plasma was transferred to the first child bag 2.

Next, the bending rod 12 is broken, the tube 10 is sealed with a clip, and the red blood cell preservation additive solution in the second child bag 3 is transferred to the parent bag L, where it is mixed with the red blood cell concentrate that has settled and remained in the parent bag 1. did. Then, the tube 7 was sealed and cut to separate the parent bag 1 from the quadruple bag. The number of white blood cells in the red blood cell concentrate that had settled and remained in parent bag 1 was 2.3 compared to the number of white blood cells in the blood obtained from the donor.
%, and by centrifugation most of the white blood cells were removed from the red blood cell concentrate that settled in the parent bag and remained.

Next, the tube 10 is sealed with a clip, the first child bag 2 is placed in a centrifuge, and centrifuged at 800 rpm for 3 minutes. The red blood cells are separated into a layer in which they have precipitated, and the platelet-rich plasma in the supernatant layer is transferred to the empty second child bag 3 through tubes 10 and 8 for 50d. Then, the tube 11 is melt-sealed and cut, and the platelet-rich plasma is stored in the second bag.

Table 1 shows the platelet aggregation ability after the platelet-rich plasma was stored in the second bag for 120 hours.

Platelet aggregation ability is platelet-rich plasma 20 after 120 hours.
After adding 1 g of 4mM CaC to d^DP20a
It is measured by the maximum aggregation rate induced by adding M.

Comparative Example 1 Blood was centrifuged in the same manner as in Example 1 using the same polyvinyl chloride bag as the bag used for the third child bag in Example 1 as the second child bag in FIG. Blood components were transferred to Distribute the platelet concentrate plasma obtained in Example 1 to the second child bag, and distribute it to the second child bag.
Table 1 shows the platelet aggregation ability after storage for 20 hours.

Table 1 As is clear from Table 1, the blood separation device of Example 1 of the present invention, in which the material of the second child bag is polyolefin,
Compared to the blood separation device of Comparative Example 1 in which the child bag material is polyvinyl chloride, the decline in platelet function is small.

〔effect〕

The blood separation device of the present invention is a quadruple bag in which blood components obtained by centrifuging blood are transferred to and stored in each bag, and the material of the child bag that contains the additive solution for preserving red blood cells in advance does not contain any dirt. Being made of polyolefin, the bag can accommodate platelets as well as red blood cell storage additives, so that the separated blood components can be distributed to all the bags of the quadruple bag and all the bags can be used effectively. used.

In addition, white blood cells that cause fever and rash in patients during blood transfusions are separated and stored in the first child bag, so there are few white blood cells in the red blood cell concentrate in the parent bag, and it is safe to repeat blood transfusions.

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram of a blood separation device showing one embodiment of the present invention, in which 1 is a parent bag, 2 is a first child bag, 3 is a second child bag, 4 is a third child bag, 5 is a syringe needle, 6-11
12 and 13 are bent rods, 14 is an anticoagulant, and 15 is an additive for preserving red blood cells.

Claims (2)

[Claims] (1) Contains whole blood containing an anticoagulant and separates it by centrifugation into a supernatant layer consisting mainly of plasma, an intermediate layer consisting mainly of platelets and white blood cells, and a lower layer consisting mainly of red blood cells. a parent bag that receives and mixes the red blood cell preservation additive solution from the second child bag with the blood components remaining after the blood components in the supernatant layer and the intermediate layer are transferred to each child bag; A first child bag that transfers and accommodates the separated blood components in the middle layer, and transfers the platelet-rich plasma in the upper layer obtained by suspending platelets in the plasma by centrifugation to the empty second child bag. Then, after storing an additive solution for preserving red blood cells in advance and transferring the additive solution to the parent bag in which only the blood components in the lower layer remain, a polyolefin bag that receives and accommodates the platelet-rich plasma from the first child bag is used. A second child bag and a third bag contain the blood components of the supernatant layer separated in the parent bag.
A blood separation device consisting of a child bag and a tube that connects the bags. (2) The polyolefin is (a) 25 to 60% by weight of poly(ethylene butylene) polystyrene block copolymer, (
b) A polymer mixture consisting of 20 to 40% by weight of polypropylene and (c) 5 to 35% by weight of ethylene acrylate copolymer, wherein the polystyrene segments of the block copolymer of (a) have a crystallized alignment. 2. The blood separation device according to claim 1, which is a polymer alloy having at least two portions in which the molecular chains of the polymers (a) to (c) are intertwined in a network.