JPH0263469A - Blood treating device - Google Patents

Abstract

PURPOSE:To high-efficiently separate and sample concentrated albumin by a method wherein a low molecular weight blood plasma component consisting mainly of albumin by penetration of it through a first blood plasma separator is sampled, by the passage of it through a second blood separator, electrolyte and water are removed, albumin is concentrated, and concentrated albumin containing no AIDS virus is sampled for separation. CONSTITUTION:A blood 13 produced in a way that a resistive coagulant 12 is added in a blood 11 sampled from a blood donor 1 is penetrated by means of a first blood separator 3 to produce a low molecular weight blood plasma component 15, which is fed to a second blood separator 4. Albumin liquid 16 passing the second blood separator 4 is stored as concentrated albumin liquid in a storage bag 6. A fine blood plasma component 17 fed to a blood bag 5 is joined and mixed with a remaining blood component 14, and is returned as a mixed blood 18 to the donor 1. The blood 13 is fed to the first blood separator 3 through drive of a third pump 7c to separate it into the low molecular weight blood plasma component 15 consisting mainly of albumin and the remaining blood component 14 consisting of a high molecular weight blood plasma component and a blood cell.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a blood processing device, and more specifically, the present invention relates to a blood processing device that efficiently separates albumin from donor blood, condenses the albumin, collects it as concentrated albumin, and collects it as concentrated albumin for use in patients. It relates to a blood processing device that subjects the remaining blood components to the blood donor and returns the remaining blood components to the donor.

[Prior art] Albumin is a type of protein fractionated from plasma.
It is the most widely used drug among plasma derivatives, and is used for treatment of injuries, bleeding, burns, etc., treatment of hypoproteinemia before and after surgery, acute liver disease, etc. It is widely used for the treatment of insufficiency and acute atrophy.

Traditionally, albumin has been produced using plasma extracted from donor blood using HIK, fractionated and separated using formulation technology, but plasma for plasma fraction preparations is supplied in Japan by large amounts of imported plasma. However, there is a risk that the AIDS virus etc. may enter the albumin, and a solution to this problem has been desired.

[Problem to be solved by the invention]

In order to meet these demands, the present inventors have developed a blood processing device that efficiently separates and collects albumin, which is free from AIDS virus, hepatitis B virus, and non-A, non-B viruses, from donor blood. We developed this technology and arrived at the present invention.

[Means for Solving the Problems] That is, the present invention includes a collection part for collecting blood, and a part for separating blood into a low molecular weight plasma component mainly composed of albumin, a residual blood component consisting of a high molecular weight plasma component and a blood cell component. 1
a blood separator, a second blood separator for separating minute plasma components not containing albumin from the low molecular weight plasma components separated by the first blood separator, and concentrated albumin passed through the second blood separator. a container for storing a liquid, a reservoir for storing mixed blood obtained by combining and mixing residual blood components separated by a first blood separator and minute plasma components separated by a second blood divider, and the mixed blood. This is a blood processing device that returns blood to the body.

Further, in the present invention, the first blood separator has an average pore diameter of 0.02 to 0.
05μ, film thickness 10-60μ, effective film area 0.2-1.5
m! It is preferable that the blood processing device is composed of a module incorporating a large number of hollow fiber porous membranes.

Furthermore, the present invention provides that the second blood separator has an average pore diameter of 0.005 to 0.
．． 01μ, film thickness 5-30μ, effective film area 0.5-2.5
Preferably, the blood processing device is composed of a module incorporating a large number of m2 hollow fiber porous membranes.

Furthermore, the present invention is preferably a blood processing device in which these hollow fiber porous membranes are made of cellulose acetate, and the present invention preferably provides a blood processing device in which blood is collected from the body and mixed blood is returned to the body through continuous circulation using two needles. Preferably, it is a blood processing device comprising:

Furthermore, the present invention is preferably a blood processing device in which blood is collected from the body and mixed blood is returned to the body intermittently through a single needle.

The present invention also provides concentrated albumin from the second blood separator/&
, blood that is provided with a flow rate control unit in the outflow tube? Preferably, it is a fl blood processing device.

(Function) The present invention first permeates donor blood in a first blood separator to collect a low molecular weight plasma component mainly composed of albumin, and then transfers the low molecular weight plasma component to a second blood separator. to remove electrolytes, water, etc., and concentrate albumin.
This method collects and separates 'a11 albumin, which does not contain the AIDS virus. Since the present invention is a closed-circuit blood processing device that returns the remaining blood components to the donor, the donor's blood is definitely returned to the donor through an extracorporeal circulation mechanism.

(Example) Next, an example of the blood processing apparatus of the present invention will be described based on the drawings.

FIG. 1 is a schematic diagram of a blood processing apparatus in which blood is collected from the body and mixed blood is returned to the body intermittently using a single needle.

In the figure, 1 is a blood donor, 2 is a hanger containing an anticoagulant, 3 is a first blood separator, 4 is a second blood separator, and 5 is mixed blood from the first blood separator and the second blood separator. 6 is a storage bag for concentrated albumin liquid concentrated in the second blood separator.

11 is blood of a donor, 12 is an anticoagulant, 13 is blood containing an anticoagulant, 14 is a residual blood component consisting of a high molecular weight plasma component and a blood cell component that has passed through the first blood separator, 1
5 is a low molecular weight plasma component mainly composed of albumin that has passed through the first blood separator, 16 is a concentrated albumin liquid that has passed through the second blood separator, and 17 is passed through the hollow fiber porous membrane of the second blood separator M. The minute plasma component 18 is a mixed blood of the residual blood component 14 and the minute plasma component I7, and is the blood to be returned to the donor.

78 to 7d are the first to fourth pumps (among them, the first pump 7a is a pump that can send blood in both forward and reverse directions), and 88 to 8b are the pumps that open and close the channels through which the respective fluids flow. The first and second clamps to be performed, and 9, are flow control units that adjust the concentration of the 4-thick albumin liquid concentrated in the second blood separator.

The main operation of the embodiment of the present invention having such a configuration is that blood 13 obtained by adding an anticoagulant 12 to blood 11 collected from a blood donor 1 is separated into a low molecular weight plasma component 1 by a first blood separator 3.
5 and supplied to the second blood separator 4. On the other hand, the first
Residual blood components 14 consisting of high molecular weight plasma components and blood cell components that have passed through the blood separator 3 are stored in a blood bag 5. Next, the low molecular weight plasma component 15 that has passed through the first blood separator 3 passes through a minute plasma component 17 such as β2-microglobulin in the second blood separator 4, and is stored in the blood bag 5.

On the other hand, the albumin liquid 16 that has passed through the second blood separator 4 is stored in the storage bag 6 as a concentrated albumin liquid. The micro plasma component 17 supplied to the blood bung 5 is mixed with the remaining blood component 14, and the blood is returned to the donor 1 as mixed blood 18.

When collecting blood from the blood donor 1 through a needle, the first clamp 8
open the first pump 7 and close the second clamp 8b.
a and second pump 7b are driven to mix blood 11 from donor 1 and anticoagulant 12 to form blood 13.

This blood 13 is supplied to the first blood separator 3 by driving the third pump 7c and separated into a low molecular weight plasma component 15 mainly composed of albumin and a residual blood component 14 consisting of a high molecular weight plasma component and blood cell components. do.

The first blood separator 3 consists of a module incorporating a large number of hollow fiber porous membranes. Hollow fiber porous ILLS consists of a membrane with a microstructure with an average pore diameter of 0.02 to 0.05μ, and its thickness is 10 to 60μ, preferably 20 to 45μ.
μ, and the effective membrane area is 0.2 to 1.5 m”, preferably 0.5 to 1.0 m2.The membrane material is polyvinyl alcohol, polyolefin, polysulfone, ethylene/vinyl alcohol copolymer, polyvinyl alcohol, etc. It consists of acrylonitrile, polyamide, polyester, cellulose acetate, etc., and cellulose derivatives such as cellulose acetate are particularly preferred.

While the blood 13 supplied to the first blood separator 3 passes through the hollow fiber porous membrane, low molecular weight plasma components 15 such as albumin, myoglobulin, β2-microglobulin, electrolytes, and water are removed through the hollow fibers. The fourth pump 7d passes through the porous membrane.
The blood is then sent to the second blood separator 4. Preferably, the amount of albumin in low molecular weight plasma component 15 is at least 4%.

The blood that passes through the hollow fiber porous membrane without passing through it is composed of high molecular weight plasma components such as γ-globulin, fibrinogen, hepatitis virus, and AIDS virus, and blood cell components such as red blood cells, white blood cells, and platelets. This residual blood component 14 is stored in the blood bag 5.

Next, the second blood separator 4 also consists of a module incorporating a large number of hollow fiber porous membranes. The hollow fiber porous membrane is composed of a membrane with an average pore diameter of 0.005 to 0.01μ, a membrane thickness of 5 to 50μ, preferably 10 to 30μ, and an effective membrane area of 0.
．． 5-2.5 m”, preferably 0.8-1.5 m2
It is. The membrane material is made of polyvinyl alcohol, polyolefin, polysulfone, ethylene/vinyl alcohol copolymer, polyacrylonitrile, polyamide, polyester, cellulose acetate, etc., and cellulose derivatives such as cellulose derivatives are particularly preferred.

The low molecular weight plasma component 15 supplied from the first blood separator 3 to the second blood separator 4 by the fourth pump 7d contains myoglobin, β2-microglobulin, electrolyte and water while passing through the hollow fiber porous membrane. The minute plasma components 17 such as the above permeate the hollow fiber porous membrane and are sent to the blood bag 5. In the blood bag 5, the minute plasma component 17 is mixed with the remaining blood component 14 supplied from the first blood separator 3 to form mixed blood 18, which is returned to the blood donor 1. Mixed blood 18 is donor 1
When blood is to be returned, the first clamp 8a is closed, the second clamp 8b is opened, and the second pump is stopped.

Then, the first pump 7a is rotated in the opposite direction to pump the mixed blood 1.
8 is returned to donor 1. This series of operations is smoothly performed by a computer-driven controller incorporating an automatic programming control mechanism.

On the other hand, in the low molecular weight plasma component 15 passing through the hollow fiber porous membrane of the second blood separator 4, albumin is concentrated by the minute plasma component 17 passing through the hollow fiber porous membrane and stored as a concentrated albumin liquid 16. Stored in hang 6. The albumin concentration of the concentrated albumin l& varies depending on the flow rate of the flow rate regulator 9 provided in the flow path from the second blood separator 4 to the storage bag 6, but is at least 15%.

As the flow rate adjustment section 9, for example, a so-called auto-cleaner is used in which the opening degree of a tube, which is a flow path for concentrated albumin liquid, is changed steplessly by driving a motor.

Examples 1 to 3 A cellulose triacetate membrane having the following configuration was used as the hollow fiber porous membrane of the first blood separator 3, fresh blood was supplied for 40 minutes according to FIG. 1, and low molecular weight plasma components were separated. Cellulose triacetate hollow fiber porous membrane has an average pore diameter of 0.02μ, an inner diameter of 275μ, a membrane thickness of 40μ, and an effective length of 2.
20mm, effective area 1.0m2, blood volume 100m1
It is.

Table 1 shows the protein components in the low molecular weight plasma components obtained by the blood flow rate supplied to the first blood separator.

As is clear from Table 1, as blood/JiI increases, the yield of albumin in low molecular weight plasma components increases, but the albumin concentration (g/ml) tends to decrease.

Examples 4 to 6 The low molecular weight plasma component obtained in Example 1 was supplied to the second blood separator at a flow rate of 200 ml/min for 40 minutes to obtain a concentrated albumen.

The hollow fiber porous membrane of the second blood component M is a cellulose triacetate membrane, with an average pore diameter of 0.008μ, a membrane thickness of 15μ, an effective membrane area of 1.1 m'', and an effective length of 2001.

The 'a thickness' obtained by adjusting the flow rate of the concentrated albumin solution by changing the opening degree of the flow rate adjustment section, that is, the autocleaning tube, provided in the flow path of the 4-thickness albumin solution flowing out from the second blood separator. The concentration of albumin in the albumin solution shown in Table 2 indicates that it was not detected in the analysis.

As is clear from Table 2, the albumin concentration in the concentrated albumin solution increases by increasing the amount of distribution.

Note that the distribution amount in the table refers to the ratio of the amount of concentrated albumin liquid coming out of the second blood separator to the amount of low molecular weight plasma component supplied to the second blood separator.

Next, a blood processing apparatus using the two-needle method shown in FIG. 2, which is another embodiment of the present invention, will be described.

FIG. 2 is an explanatory diagram of a blood processing apparatus for obtaining concentrated albumin solution by continuously circulating blood collected from the body and the treated mixed blood returned to the body using two needles. The symbols in the figure are the same as in FIG. In the figure, 78 and 7b indicate the first pump and the second pump. The first pump is a roller pump that simultaneously supplies an anticoagulant and blood in which the anticoagulant has been added to blood from the donor, and the inner diameter of the tube for delivering the anticoagulant and the blood to which the anticoagulant has been added is The supply amount can be determined by adjusting the ratio. Usually, the inner diameter of the tube for the blood 113 containing the anticoagulant is 2.5 to 5 times the inner diameter of the tube for the anticoagulant 12.

The main operation of another embodiment of the present invention having such a configuration is to add the anticoagulant 12 from the anticoagulant hasog 2 to the blood 11 collected from the blood donor 1 by driving the first pump 7a; Let it be blood 13. The blood 13 is then supplied to the first blood separator 3 by the first pump 7a. Blood 13 is the first
It passes through the hollow fiber porous membrane of the blood separator 3 to become a low molecular weight plasma component 15, which is supplied to the second blood separator 4 by driving the second pump 7b.

On the other hand, residual blood components 14 consisting of high molecular weight plasma components and blood cell components that have passed through the first blood separator 3 are stored in the blood trap 5. The low molecular weight plasma component 15 supplied to the second blood separator 4 passes through the hollow fiber porous membrane and becomes a minute plasma component 17 such as β2-microglobulin in the blood trap 5.
and is mixed with the residual blood component 14 sent from the first blood separator 3. On the other hand, the albumin liquid 16 that has passed through the second blood separator 4 is stored in the storage bag 6 as a concentrated albumin liquid.

The minute plasma component 17 and the residual blood component 14 mixed in the blood trap 5 are returned to the blood donor 1 as mixed blood 18. This series of operations is performed in continuous circulation, and the blood collection system uses extracorporeal circulation to ensure that the donor's blood returns to the donor.

Example 7 Using the first blood separator and second blood separator M used in the previous example, blood flow It 60 according to FIG.
Fresh blood was supplied at a rate of ml/n+in, and the relationship between the collection time and the amount of albumin in the albumin solution was investigated. The results are shown in Table 3.

” As is clear from Table 3, the albumin yield increases with the passage of collection time, but the albumin concentration remains at 40%.
It remains almost constant after a minute passes.

(Effects) The blood processing device of the present invention is a safe and efficient extracorporeal blood processing device that collects a concentrated albumin solution from the donor's blood and returns other blood components to the donor.

The collected A-thick albumin fluid does not contain viruses such as AIDS virus, hepatitis B virus, and non-A non-B viruses, and unlike conventional albumin fluid,
There is no need for sterilization operations such as heat treatment for 10 hours.

In addition, since the blood processing device of the present invention is a closed system, a series of operations are performed by circulating continuously or intermittently, so that the donor's blood is definitely returned to the donor, and the blood of others is not returned. You can rest assured that there will be no fear.

The albumin concentration in the obtained concentrated albumin solution is 15 to 25%, which is 95% or more based on the total protein, and is albumin with high purity.

[Brief explanation of the drawing]

FIG. 1 is an explanatory diagram of a blood processing apparatus using the single needle method of the present invention, and FIG. 2 is an explanatory diagram of a blood processing apparatus using the two needle method of the present invention. In the figure, 1 is a blood donor, 3 is a first blood separator, 4 is a second blood separator, 5 is a blood reservoir, 6 is a concentrated albumin liquid reservoir, 12 is an anticoagulant, 14 is a residual blood component, 15 is a low molecular weight plasma component, 16 is a concentrated γ albumin solution, 17 is a minute plasma component, and 18 is a mixed blood.

Claims (8)

[Claims] (1) A sampling section for collecting blood, a first blood separator for separating blood into a low molecular weight plasma component mainly composed of albumin, a residual blood component consisting of a high molecular weight plasma component and a blood cell component, and the first blood separation device. a second blood separator that separates minute plasma components that do not contain albumin from the low molecular weight plasma components separated by the second blood separator; a container that stores the concentrated albumin liquid that has passed through the second blood separator; Blood characterized by comprising: a reservoir for storing mixed blood in which the separated residual blood components and minute plasma components separated by a second blood separator are combined and mixed, and the mixed blood is returned to the body. Processing equipment. (2) The first blood separator has an average pore diameter of 0.02 to 0.05μ
, film thickness 10~60μ, effective membrane area 0.2~1.5m^2
The blood processing device according to claim 1, comprising a module incorporating a large number of hollow fiber porous membranes. (3) The second blood separator has an average pore diameter of 0.005 to 0.01
μ, film thickness 5-30μ, effective film area 0.5-2.5m^2
The blood processing apparatus according to claim 1 or 2, comprising a module incorporating a large number of hollow fiber porous membranes. (4) The blood processing device according to claim 2 or 3, wherein the hollow fiber porous membrane is made of cellulose acetate. (5) The blood processing apparatus according to any one of claims 1 to 4, wherein the reservoir comprises a blood bag or a blood trap. (6) The blood processing device according to any one of claims 1 to 5, wherein blood is collected from the body and mixed blood is returned to the body through continuous circulation using two needles. (7) The blood processing device according to any one of claims 1 to 5, wherein the blood is collected from the body and the mixed blood is returned to the body through intermittent circulation using a single needle. (8) The blood processing apparatus according to any one of claims 1 to 7, wherein a flow rate control section is provided in the concentrated albumin liquid outflow pipe from the second blood separator.