JP3353466B2 - Dialysis fluid management device for hemodialysis machine - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a dialysate management device for a hemodialysis apparatus, and more particularly, to transferring unnecessary components in blood into a circulating dialysate and removing the transferred unnecessary components. And a device capable of circulating and using the dialysate in a satisfactory manner.

[0002]

2. Description of the Related Art Among toxic substances dissolved in blood, many organic compounds exist in a state of being adsorbed to plasma proteins. For example,
Albumin, which is a plasma protein, adsorbs metabolites such as bilirubin. It is considered that these adsorption states are phenomena in which molecules that hardly form a bond with water molecules in an aqueous solution or atomic groups in the molecules aggregate with affinity. This phenomenon is called, for example, a hydrophobic bond.

In such a bound state, unnecessary components such as metabolites adsorbed on plasma proteins are difficult to separate and remove with a general hemodialysis apparatus. Therefore, a hemodialysis apparatus for solving this problem has been proposed in Japanese Patent Application Laid-Open No. 49-42189. In this hemodialysis apparatus, for example, albumin is contained in the dialysate, and metabolites adsorbed on albumin in the blood are adsorbed and separated on albumin of the dialysate via the semipermeable membrane of the dialyzer. ing.

[0004] Hemodialysis apparatuses include a so-called one-pass (single-pass) system and a batch system. The one-pass method is to prepare a dialysate while continuously diluting a concentrated stock solution for dialysate with water, and to discard the dialysate that has passed through the dialyzer. Therefore, in the one-pass system,
It is necessary to prepare a large amount of dialysate, which is close to 300 liters. On the other hand, in the batch system, the dialysate prepared in advance is circulated and passed through a dialyzer. In the batch system, about 70 liters of the dialysate need only be prepared. However, the batch system requires a smaller amount of dialysate and a lower dialysis cost than the one-pass system, but the one-pass system, which is superior in terms of treatment efficiency, is more widely used.

However, in the conventional hemodialysis apparatus disclosed in Japanese Patent Application Laid-Open No. 49-42189, the dialysate that has passed through the dialyzer is not mentioned at all, and is considered to be discarded as it is. That is, the above-mentioned conventional hemodialysis apparatus is considered to be a one-pass type, but this is not preferable because the dialysis cost increases. Therefore, a new apparatus in which the above-mentioned conventional hemodialysis apparatus is improved to a batch system has been demanded.

[0006] It is an object of the present invention to provide a dialysate management device for a hemodialysis apparatus which can solve the above problems.

[0007]

In order to achieve the above object, the present invention is characterized in that a dialysate flow is brought into contact with a blood flow through a semipermeable membrane of a dialyzer. An apparatus for adsorbing and separating unnecessary components adsorbed on plasma proteins into adsorbed components in a dialysate, comprising a dialysate circuit that passes through a dialyzer while the dialysate circulates.
A dialysate tank for storing the dialysate, (2) a circulation pump for circulating the dialysate, and (3) an adsorption separation device for adsorbing and separating unnecessary components adsorbed on the adsorbed components in the dialysate. And (4) an upstream / downstream flow rate adjusting device for adjusting the flow rates respectively on the upstream side and the downstream side of the dialyzer; and (5) the concentration of the adsorbed component in the dialysate provided in the dialysate tank. (6) a replenishing device for replenishing the dialysate tank with an adsorbed component when the sensor detects the sensor.

[0008] Each of the flow control devices may be a circulation pump.

[0009]

In blood dialysis, blood from the patient is passed through the dialyzer and returned to the patient. On the other hand, in the dialysate circuit,
The dialysate is circulated by the upstream and downstream circulation pumps. That is, the dialysate in the dialysate tank is returned to the dialysate tank after passing through the dialyzer and the adsorption separator.

[0010] As described above, when the dialysate is circulated in the dialysate circuit, the dialysate flow contacts the patient's blood flow through the semipermeable membrane. At this time, since the dialysate contains an adsorbed component, unnecessary components adsorbed on plasma proteins in the blood are:
After passing through the semipermeable membrane, it rapidly binds to the adsorbed component in the dialysate and is adsorbed and separated. Unnecessary components adsorbed on the adsorbed components of the dialysate are adsorbed and separated by the adsorbent of the adsorption / separation device.

At the time of hemodialysis, while visually checking the dialysate volume in the dialysate tank, the rotation speed of the downstream circulation pump is set to be smaller than the rotation speed of the upstream circulation pump, and the transmembrane pressure is adjusted. : TMP
Say ) Is adjusted to an appropriate value so that the dialysate volume in the dialysate tank is substantially constant.

[0012]

An embodiment of the present invention will be described below with reference to the drawings. 1 and 2 show a continuous hemodialysis apparatus having a blood circuit 2 and a dialysate circuit 3 which pass through a dialyzer 1 respectively.

[0013] A continuous hemodialysis device is used as a continuous albumin purification system.
System: CAPS), a device for removing toxic substances in blood, and a device for purifying blood. Also, continuous dialysis is
It refers to dialysis in which the flow rate of the blood flow is about 30 ml / min and the dialysis is performed slowly over about 24 hours.

As shown in FIG. 3, the dialyzer 1 is a hollow fiber of a large area type. The dialyzer 1 is composed of a cylindrical case 6 having both open ends and a number of hollow fibers 7A exemplified as a semipermeable membrane. And a pair of upper and lower headers 8 and 9 that are externally fitted and fixed to the respective ends of the case 6.

The case 6 has a pair of upper and lower dialysate ports 10 and 11 for allowing the dialysate to pass outside the hollow fiber 7A.
Is provided.

The material of the hollow fiber 7A is preferably polyamide, polyacrylonitrile, cellulose triacetate, polysulfone, etc., but polymethyl methacrylate, which is somewhat less efficient, can also be used. The hollow fiber 7A used for ordinary hemodialysis has an average pore diameter of 20 to 30 °, but in the present invention, the hollow fiber 7A has an average pore diameter of 20 to 100 °,
In particular, a hyper-form type of 50 to 100 ° is preferable. The thickness of the hollow fiber 7A is 15 to 60 μm, preferably 15 to 50 μm. Each end of the hollow fiber bundle 7 is fixed to the inner surface of each end of the case 6 with an adhesive 12.

The headers 8, 9 are provided with blood ports 13, 14, respectively, for guiding blood into the hollow fiber 7A. Reference numeral 15 denotes an O-ring.

The blood circuit 2 dialyzes blood from a patient.
Through which the blood flows back to the patient. The arterial line 1 connects the artery of the patient to the upper blood port 13 of the dialyzer 1.
6 and a venous line 17 connecting the lower blood port 14 of the dialyzer 1 to a patient's vein. In the arterial line 16, a blood pump 18 such as a series of roller pumps for pumping arterial blood of the patient and an arterial chamber 19 for temporarily storing the pumped arterial blood are provided in the blood flow direction (arrow direction). And the arterial chamber 19 is
The stored arterial blood is supplied to the dialyzer 1. IV line 1
7 has a vein side chamber 20 for temporarily storing the blood dialyzed (purified) in the dialyzer 1.
Causes the pooled blood to return to the patient's vein. The devices of the arterial line 16 and the venous line 17 are respectively
They are connected by elastic tubes 16A and 17A.

In the vein line 17, an additional circuit 22 is often connected downstream of the vein side chamber 20 via a pair of bypass flow paths 23 and 24 indicated by phantom lines, but is not connected. Sometimes. The additional circuit 22 includes continuous hemodialysis (CH).
D) Circuit, Continuous Hemofiltratio
n: CHF) circuit or continuous simultaneous hemofiltration (Continuou
s Hemodiafiltraion (CHDF) circuit is used.
When the attachment circuit 22 is connected, the vein line 17
, The flow path 25 between the two bypass flow paths 23 and 24 is shut off.

The dialysate circuit 3 allows the dialysate to pass through the dialyzer 1 while circulating the dialysate, and constitutes a single unit system. The system is a closed system (Closed System). ). The dialysate circuit 3 includes a dialysate tank 27, a dialysate supply line 28 connecting the dialysate tank 27 and the lower dialysate port 11 of the dialyzer 1, an upper dialysate port 10 of the dialyser 1, and a dialysate tank. Dialysate reflux line 2 connecting the
9 is provided.

The dialysate is also called a perfusion solution.
Contains appropriate adsorbent components. The adsorbed component is a component that adsorbs and separates unnecessary components (sometimes referred to as organic compounds, toxic substances, and toxic substances) adsorbed on plasma proteins in blood. For example, plasma proteins such as albumin and various globulins, or A polymer, a high molecular compound, or the like having the same effect is used, but albumin is used in the examples. When plasma protein is used as the adsorption component, the concentration of plasma protein in the dialysate may be higher than that in blood. When albumin was used as a plasma protein, the albumin concentration (content) in the dialysate was 25%.
~ 50 g / liter is preferred. Albumin concentration 25
When the amount is less than g / liter, the amount of the adsorbed and separated unnecessary components is reduced. When the amount is more than 50 g / liter, a large amount of expensive albumin is used, which causes an economic problem that the dialysis cost becomes too high.

The following organic compounds are unnecessary components that are adsorbed to plasma proteins in blood. That is, examples of the organic compound adsorbed on albumin in blood include metabolites such as bilirubin and bazoflavin, physiologically active substances such as chloromycetin and barbisealic acid, and pigments such as indocyanine green and bromosulfophthalene. In view of the mode of existence in blood, bilirubin includes free, conjugated and unconjugated bilirubin that weakly binds to albumin, and δ (delta) bilirubin that strongly binds to albumin. Organic compounds adsorbed on various globulins in blood include vitamins A, D, E,
K and the like. Other organic compounds that adsorb to plasma proteins include toxic substances that induce hepatic coma at the end of liver failure,
There are toxic substances that appear at the end of renal failure.

The dialysate tank 27 (sometimes called a stock tank or a storage tank) stores dialysate, and is made transparent or translucent so that the stored amount can be visually checked. In the dialysate in the dialysate tank 27,
The end of the dialysate supply line 28 is inserted, but the end of the dialysate reflux line 29 may or may not be inserted into the dialysate. Further, the dialysate tank 27 is provided with an albumin sensor 31 for detecting that the albumin concentration in the dialysate has fallen below the set concentration, and an albumin replenishing device 32 for replenishing the dialysate tank 27 with albumin. It is attached.

In the dialysate supply line 28, an upstream heating device 34 and an upstream circulation pump 35 are arranged in the above-described order in the dialysate circulation direction (the direction of the arrow). The dialysate reflux line 29 includes a downstream circulation pump 37,
The downstream-side heating device 38 and the adsorption / separation device 39 are arranged in the above-mentioned order in the dialysate circulation direction. The respective devices of the dialysate supply line 28 and the dialysate reflux line 29 are connected by elastic tubes 28A and 29A, respectively.

The upstream heating device 34 heats the dialysate supplied to the dialyzer 1 to a physiological temperature (body temperature) of about 37 ° C., and the downstream heating device 38 adsorbs and separates the dialysate. Device 3
9 can promote the adsorptive separation effect (for example, about 3
The temperature is 7 to 38 ° C, but may be higher or lower than this. ). Each heating device 34, 38
As shown in FIG. 4, a main body 41, a lid 42 provided on the main body 41 so as to be openable and closable, and a heating bag 4 removably provided on the main body 41 and sandwiched between the main body 41 and the lid 42.
And 3. The main body 41 and the lid 42 are each provided with a panel heater, and the lid 42 is fixed in a closed state by fixtures 44A and 44B. The heating bag 43 is formed with a flow passage 45 through which the dialysate flows vertically while meandering left and right. The upstream and downstream heating devices 34 and 38 may be integrated.

Upstream / downstream circulation pumps 35 and 37
Has a pump function of circulating the dialysate, the upstream circulation pump 35 is provided at the upstream side of the dialyzer 1, and the downstream circulation pump 37 is provided at the downstream side of the dialyzer 1. It also has a function as a flow control device for adjusting the pressure. In the embodiment, each of the circulation pumps 35 and 37 is a series of roller pumps, and has guide surfaces 53 and 54 that are curved and concave, and rotating bodies 55 and 56 that are driven to rotate.
And a pair of rollers 57, 58 provided at both ends of the rotating bodies 55, 56.
9, 60 are configured. And dialysate supply line 2
8. The pumping action is performed by the elastic tubes 28A, 29A constituting each part of the dialysate reflux line 29 being along the guide surfaces 53, 54 and being squeezed by the rollers 57, 58.

The adsorbing / separating device 39 (sometimes referred to as an adsorbing cylinder) is provided with an adsorbent for purifying dialysate, and the adsorbent removes unnecessary components adsorbed on albumin (adsorbing component) in the dialysate. Is adsorbed and separated. As the adsorbent, for example, as disclosed in JP-B-56-7737, a single polymer composed of 2% by weight or more and less than 100% by weight of a crosslinkable polymerizable monomer and less than 98% by weight of a monovinyl monomer is used. The polymer mixture is copolymerized, and a porous copolymer having an average pore size of 300 to 9000 ° (preferably 600 to 8000 °) is used. As the crosslinkable polymerizable monomer, for example, divinylbenzene, divinyltoluene and the like are used, and as the monovinyl monomer, for example, styrene, alkyl-substituted styrene and the like are used.

For the purpose other than the adsorption / separation device 39, another adsorption device is provided in the dialysate reflux line 29 in series or parallel with the adsorption / separation device 39, or
Another adsorbent may be mixed with the adsorbent in the adsorption separation device 39. Adsorbents installed in the above other adsorption devices,
As the other adsorbent to be mixed, various activated carbons (for example, fibrous activated carbon and the like) commonly used as the adsorbent are used, and in addition, a mixture of activated carbon and alumina may be used. These adsorbents well adsorb metabolites having a molecular weight of 2000 or less, such as creatine, vitamin B12, and uric acid, which are not strongly adsorbed to plasma proteins, and in particular, a mixture of activated carbon and alumina adsorbs inorganic phosphorus compounds. However, the adsorbent hardly adsorbs large molecules such as proteins and therefore does not adsorb metabolites bound to albumin, for example, bilirubin. Therefore, the above adsorbent is not suitable as an adsorbent for the adsorption separation device 39.

According to the embodiment configured as described above, at the time of hemodialysis (blood purification, removal of toxic substances in blood), the arterial blood from the patient's artery is supplied to the blood pump 18 and the arterial chamber in the blood circuit 2. After passing through the inside of the hollow fiber 7A of the dialyzer 1 through the
Reflux to the patient's vein via 0. Before the reflux, the blood is passed through the attachment circuit 22 to further purify the blood and remove the water from the blood, or to supply the blood with a water replacement fluid such as a physiological saline solution. Sometimes they do.

On the other hand, in the dialysate circuit 3, the dialysate is circulated by the upstream and downstream circulation pumps 35 and 37.
That is, the dialysate in the dialysate tank 27 is sent to the upstream-side heating device 34 and heated to a physiological temperature of about 37 ° C., and then passes through the outside of the hollow fiber 7A of the dialyzer 1. Then, the dialysate passed through the dialyzer 1 is converted into a downstream heating device 38.
After being heated again to a temperature at which the adsorption / separation action of the adsorption / separation device 39 can be promoted, it is passed through the adsorption / separation device 39 and refluxed into the dialysate tank 27.

As described above, the dialysate is circulated on the upstream and downstream sides of the dialyzer 1 by the upstream / downstream circulation pumps 35 and 37. Can be circulated satisfactorily throughout.

As described above, when the dialysate is circulated in the dialysate circuit 3, the dialysate flow becomes the hollow fiber 7 which is a semipermeable membrane.
Via A, it comes into contact with the blood stream of the patient. At this time, since the dialysate contains albumin as an adsorption component,
Unnecessary components adsorbed on albumin in blood, such as metabolites such as bilirubin and bazoflavin, physiologically active substances such as chloromycetin and barbisealic acid, pigments such as indocyanine green and bromosulfophthalene, in particular, bilirubin is a hollow fiber After passing through 7A, it rapidly binds to albumin in the dialysate and is adsorbed and separated.

Although the reason for the above-mentioned adsorption separation has not been elucidated, it is considered to be due to agglutination. For example,
Albumin serves as an aggregation source, bilirubin serves as an agglutinin, and bilirubin acts as a bridge between albumin in the blood and albumin in the dialysate to form aggregates, and the affinity between bilirubin and albumin in the dialysate, It is presumed to overcome the affinity between bilirubin and albumin in the blood. In addition, based on the above presumption, as in the example, the average pore diameter of the hollow fiber 7A was set to 50 to 1
00 and a thickness of 15 to 60 μm (preferably 15 to 6 μm).
0 μm), suitable results were obtained.

As described above, the dialysate passing through the dialyzer 1 comes into contact with the blood flow of the patient.
As a result, the dialysate is heated to a physiological temperature of about 37 ° C., so that the patient's body temperature does not decrease and there is no fear that the patient will be adversely affected.

As described above, the albumin of the dialysate that has passed through the dialyzer 1 adsorbs unnecessary components such as bilirubin. Only unnecessary components are adsorbed and separated, and are returned to the dialysate tank 27. Therefore, the dialysate is reused,
Can be reperfused.

Before the above adsorption separation by the adsorbent,
Since the dialysate is heated again by the downstream heating device 38 to a temperature at which the adsorption / separation action can be promoted, the adsorption / separation action by the adsorbent can be promoted, and the adsorption / separation efficiency can be improved.

During the dialysis, the amount of water removed from the blood is determined by the TMP, which is the difference between the blood pressure in the dialyzer 1 and the dialysate pressure, and the TMP is controlled by the blood pump 18 and the upstream circulation pump 35. The rotation speed of the downstream-side circulation pump 37 is determined by the osmotic pressure difference between blood and dialysate. If the TMP is not an appropriate value and is high, a large amount of water is removed from the blood (water removal), a large amount of water is transferred from the blood to the dialysate, and the albumin concentration of the dialysate is significantly reduced. Problems arise.

The upstream and downstream circulation pumps 35, 3
Even if the rotation speed of the pump 7 is the same, if the TMP is high, the water moves from the blood to the dialysate, and the flow rate of the downstream circulation pump 37 becomes larger than that of the upstream circulation pump 35. The flow rate difference of 37 is exclusively absorbed by the elastic deformation of the elastic tube 29A of the dialysate reflux line 29.

Therefore, in the present invention, the following treatment is performed, focusing on the fact that the amount of dialysate in the dialysate tank 27 increases when water moves from the blood to the dialysate. That is, at the time of dialysis, while visually checking the dialysate volume in the dialysate tank 27, the rotational speed of the downstream circulation pump 37 is made smaller than that of the upstream circulation pump 35, and the TMP is adjusted to an appropriate value. The amount of dialysate in 27 is made substantially constant. This can prevent a large amount of water removal from the blood,
A large amount of water from the blood can be prevented from being transferred to the dialysate, and the albumin concentration of the dialysate can be prevented from being significantly reduced.

When the albumin concentration of the dialysate drops below the set value due to the water that migrates from the blood to the dialysate, this drop in concentration is detected by the albumin sensor 31 of the dialysate tank 27, Albumin is replenished into the liquid tank 27 by the albumin replenishing device 32 in an amount corresponding to the concentration decrease.

In the embodiment, the present invention is applied to an artificial kidney. However, the present invention is also applicable to an artificial liver, a toxic poisoning treatment apparatus, and the like.

Next, in order to confirm the effectiveness of the apparatus shown in the above embodiment, the following test was conducted.

In the apparatus shown in the above embodiment, a cellulose triacetate fiber (outer diameter: about 250 μm, inner diameter: about 200 μm, molecular weight cut off: about 10,000) was used as the hollow fiber of the dialyzer.
0, length 20 cm), and 15,000 of these fibers were bundled to form a hollow fiber bundle. The total dialysis effective area of the hollow fiber bundle was 1.5 m ² .

As an adsorbent for purifying the dialysate in the adsorption / separation apparatus, 350 g of BR-350, a styrene-di-vinylbenzene copolymer resin, manufactured by Asahi Medical Co., Ltd. was used. The amount of the adsorbent used for blood purification is generally 350 g or less.

Then, the following processing was performed. That is, while maintaining a temperature of 37 ° C. of plasma having a bilirubin concentration of 37 mg / deciliter (collected from the waste liquid of plasma exchange), 60 ml / dil is continuously introduced into the hollow fiber of the dialyzer.
Per minute and circulated.

On the other hand, the dialysate is a kindergarten AF-2 solution manufactured by Fuso Chemical Co., Ltd. in which sodium chloride, potassium chloride, sodium bicarbonate, glucose and the like are dissolved, and contains 42 g / liter of albumin.
The osmotic pressure was adjusted to 298 milliosmol. The dialysate was continuously circulated in the dialysate circuit at a flow rate of 30 ml / min while maintaining the temperature at 37 ° C.

The rotational speeds of the upstream circulation pump and the downstream circulation pump were adjusted so that the dialysate volume in the dialysate tank was substantially constant.

As a result of measuring the bilirubin concentration in the dialysate by the diazo method, the bilirubin concentration was reduced to 0.1 after 10 minutes.
6 mg / deciliter, 0.7 mg / deciliter after 40 minutes, 0.8 mg / deciliter after 60 minutes, 0.9 mg / deciliter after 90 minutes, 0.9 m after 120 minutes
g / deciliter. The bilirubin concentration in plasma became 22 mg / deciliter after 120 minutes.

From the above test results, it can be considered that about 5 g of bilirubin per liter of plasma migrated from the plasma to the dialysate, and most of the bilirubin was adsorbed by the adsorbent.

[0050]

As described in detail above, according to the present invention,
Unnecessary components adhering to plasma proteins in blood can be removed, and the dialysis solution can be circulated and used satisfactorily as a batch system, so that dialysis costs can be reduced. In addition, a large amount of water can be prevented from being removed from the blood during dialysis, and a large decrease in the concentration of the adsorbed component of the dialysate can be prevented.

[Brief description of the drawings]

FIG. 1 is a blood circuit diagram showing one embodiment of the present invention.

FIG. 2 is a dialysate circuit diagram showing one embodiment of the present invention.

FIG. 3 is a longitudinal sectional view of a dialyzer showing one embodiment of the present invention.

FIG. 4 is a perspective view of a heating device showing one embodiment of the present invention.

[Explanation of symbols]

Reference Signs List 1 dialyzer 2 blood circuit 3 dialysate circuit 6A hollow fiber (semi-permeable membrane) 27 dialysate tank 28 dialysate supply line 29 dialysate reflux line 35, 37 upstream / downstream circulation pump (flow rate control device) 39 adsorption Separation device

Claims (2)

(57) [Claims] 1. A method in which a dialysate flow is brought into contact with a blood flow via a semipermeable membrane of a dialyzer, and an unnecessary component adsorbed on plasma proteins in blood is adsorbed and separated into an adsorbed component in the dialysate. Wherein a dialysate circuit is provided for passing the dialysate while circulating the dialysate, wherein the dialysate circuit comprises: (1) a dialysate tank for storing the dialysate; and (2) a circulation pump for circulating the dialysate. (3) Unnecessary components adsorbed on the adsorbed components in the dialysate are
An adsorption / separation device for adsorbing and separating with the adsorbent; (4) an upstream / downstream flow rate adjusting device for adjusting the flow rate on the upstream side and the downstream side of the dialyzer, respectively; and (5) provided in the dialysate tank. A sensor for detecting that the concentration of the adsorbed component in the dialysate has fallen below a set value; and (6) a replenishing device for replenishing the dialysate tank with the adsorbed component upon detection of the sensor. A dialysate management device for a hemodialysis machine, characterized in that: 2. The dialysate management device for a hemodialysis apparatus according to claim 1, wherein each of the flow rate adjusting devices is a circulation pump.