JPS6330026B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to an artificial liver device that uses cells that have a detoxifying effect, such as animal hepatocytes, in place of the liver.

Prior Art There is a conventional artificial liver device in which a column is filled with activated carbon.This device can remove some of the medium-molecular organic substances and low-molecular organic substances in the blood, and is particularly effective against liver diseases, such as acute hepatitis and Effective for some drug addictions. However, this device is almost unable to detoxify medium to high polymers, etc., and can only take over a portion of the liver, so it should rather be called an auxiliary device for the liver.

Problems with the Prior Art For this reason, artificial liver devices are being developed in which animal hepatocytes are transformed into floating cells using a certain type of enzyme, and these cells are made to have the same functions as the liver.
For example, hepatocytes are attached to the filter of a dialysis diffuser for plasma separation, and the hepatocytes metabolize toxic substances that pass through the filter. Since this substance is processed by dialysis, low molecular weight substances can be passed through, but medium and high molecular weight substances are difficult to dialysis because they are difficult to diffuse. Moreover, because the liver cells are densely arranged,
When detoxification residues accumulate, they are difficult to remove and have an adverse effect on the metabolic efficiency and survival of hepatocytes.

Purpose of the invention The present invention has been made in view of the above circumstances, and
The aim is to effectively carry out metabolism by floating cells, to enable detoxification of medium and high molecular organic substances, and to obtain an artificial liver device that is similar to the liver of the human body.

That is, the present invention provides a first filter for plasma separation, which is provided with an extracorporeal circulation circuit formed by a blood inflow pipe and a blood cell outflow pipe, and a plasma outflow pipe, a tank containing floating cells for detoxification, and a tank for separating filtrate. each comprising a dialyzer and a second filter for separating floating cells, which is provided with a plasma inflow pipe, a plasma outflow pipe, and a floating cell return pipe,
Connecting the plasma outflow pipe of the first filter to the plasma inflow pipe of the second filter via the tank and the dialyzer,
The artificial liver apparatus is constructed by connecting the plasma outflow pipe of the second superorganism to the extracorporeal circulation circuit and connecting the floating cell return pipe of the second superorganism to the tank.

Further, it is an object of the present invention to provide a specific invention characterized by an artificial liver device comprising a blood cell return tube for returning blood cells to the blood inflow tube, which is connected between the blood inflow tube and the blood cell outflow tube of the first organ. It is in.

Another object of the present invention is to provide a specific invention characterized by an artificial liver device in which the first filter includes a membrane filter with a pore size of 0.1 to 0.8 μ.

In addition, the first filter has a molecular weight cut-off of 50,000 to 1 million.
An object of the present invention is to provide a specific invention characterized by an artificial liver device equipped with a MW ultrafiltration membrane.

Another object of the present invention is to provide a specific invention characterized by an artificial liver device in which the second filter includes a membrane filter with a pore size of 0.1 to 0.8 μ.

In addition, the second filter has a molecular weight cut-off of 50,000 to 1,000,000.
An object of the present invention is to provide a specific invention characterized by an artificial liver device equipped with a MW ultrafiltration membrane.

Another object of the present invention is to provide a specific invention characterized by an artificial liver device in which the dialyzer is equipped with an ultrafiltration membrane having a molecular weight cut-off of 5,000 to 50,000 MW.

Another object of the present invention is to provide a specific invention characterized by an artificial liver device in which the dialyzer is equipped with a membrane filter having a pore size of 0.1 to 0.8 μ.

Specific description of the invention The present invention will be explained in detail below with reference to the drawings.

The drawing is an explanatory view of an artificial liver device showing an embodiment of the present invention, and this device is provided with a first strainer 1, a tank 2 containing suspended cells, a dialyzer 3, and a second strainer 4.

The first blood cell 1 includes an extracorporeal circulation circuit composed of a blood inflow tube 5 attached to the artery side of the human body M, a blood cell outflow tube 6 attached to the venous side of the human body M through which concentrated blood cell fluid flows, and a plasma A plasma outflow tube 7 through which components flow is provided, and blood flowing in from the blood inflow tube 5 is separated into concentrated blood cell fluid (hereinafter referred to as blood cell component) and plasma component by the action of a membrane 8. The above-mentioned membrane 8 may be a membrane filter having a plasma component separation effect, for example, a membrane filter with a pore size of 0.1 to 0.8μ, or a membrane filter with a molecular weight cut-off of 50,000 to 1,000,000.
MW ultrafiltration membrane is good. Further, the blood inflow pipe 5 is provided with a pump 9 and an air chamber 10,
Further, a pressure regulating valve 11 is attached to the blood cell outflow tube 6. Further, a blood cell return tube 12 for returning blood cell components to the blood inflow tube 5 side is connected between the blood inflow tube 5 and the blood cell outflow tube 6, and the pump 1 is connected to this return tube 12.
3 is provided. Further, the plasma outflow pipe 7 is connected to the tank 2 via a liquid level regulator 14,
Pumps 15 and 16 are provided on the plasma component inflow and outflow sides of the regulator, respectively.

The tank 2 allows plasma components to metabolize floating cells, and these floating cells are cells that have a detoxifying effect, such as animal liver cells, made into floating cells using an enzyme. As a method for converting cells into floating cells, for example, cells such as hepatocytes are preperfused with an appropriate perfusate to completely wash away blood, etc., and then
One method is to add collagenase, and then, when the liver tissue becomes considerably soft due to the action of this enzyme, the liver is removed, minced, filtered through a nylon mesh, and the cells are separated by gentle centrifugation. The inside of this tank 2 is maintained at a temperature suitable for the survival of floating cells (for example, 37° C.). Further, the tank 2 is connected to the dialyzer 3 by a plasma outflow pipe 17. This dialyzer 3 removes fluid by dialysis, and the dialysate used here is a fluid suitable for the survival of floating cells. Dialysis membrane 1 of dialyzer 3
8 is effective for removing medium and low molecular weight organic substances, for example, those with a molecular weight cutoff of 5000 to 50000MW;
In some cases, a membrane filter with a pore size of 0.1 to 0.8 μm may be incorporated. The outflow side of this dialyzer 3 is connected to the second filter 4.

This second filter device 4 is provided with a plasma inflow pipe 19 connected to the dialyzer 3, a plasma outflow pipe 20, and a floating cell return pipe 21, and the floating cells flowing in together with plasma components through a membrane 22 are removed. It is something that separates. The membrane filter 22 may be a membrane filter with a pore size of 0.1 to 0.8μ or a membrane filter with a molecular weight cut-off of 50,000 to 100, similar to the membrane 8 of the first filter 1.
A 10,000 MW ultrafiltration membrane is good. The plasma inflow pipe 19 is provided with a pump 23, and the suspended cell return pipe 21 is connected to the tank 2, with a pressure regulating valve 24 installed midway. The plasma outflow tube 20 is connected to the blood cell outflow tube 6 of the first excess device 1 via an excess level regulator 25.
Pumps 26 and 27 are provided on the plasma inflow side and plasma outflow side of the regulator 25, respectively.
An air chamber 28 is also installed at the connection point with the blood cell outflow tube 6. Note that 29 in the figure represents an air filter provided in each of the overlevel regulators 14 and 25.

Specific effects of the invention In the artificial liver device configured as described above,
When blood enters the first filter 1 from the human body M through the blood inflow pipe 5, it is separated into blood cell components and plasma components, and the blood cell components flow into the blood cell outflow pipe 6. Here, a part of the blood cell components flowing through the blood cell outflow tube 6 is returned to the blood inflow tube 5 by the action of the pump 9. The reason for doing this is that if the flow rate of blood flowing into the first superconductor 1 is small, for example, if the blood flow is performed without securing a shunt, the necessary excess amount cannot be obtained. The required blood flow rate can be ensured by returning the blood cell components, and the necessary excess amount can be obtained. In this case, the return amount is preferably about 50 to 700 per 100 blood flow from the human body M, and usually the total flow into the first blood vessel 1 is 100 to 700.
Make it 500ml/min.

In addition, a shunt is ensured for the return of blood cell components.
There is no particular need when there is sufficient blood flow.

On the other hand, the separated plasma components enter the tank 2 by the action of pumps 15 and 16, where they are metabolized by floating cells, and medium-high molecular weight organic substances and toxic substances are converted into non-toxic low-molecular substances. Also, low molecular weight toxic substances such as ammonia are synthesized into non-toxic substances such as urea. Plasma containing such metabolites is introduced into a dialyzer 3 together with floating cells, where unnecessary metabolites and low-molecular-weight poisons for the human body are removed by dialysis. Further, the dialyzer 3 can also play a role suitable for the survival of hepatocytes by adjusting the electrolyte and acid-base balance of plasma. In this case, it is generally better to use a dialysis membrane with a molecular weight cutoff of 5,000 to 50,000 MW.
Dialysis is suitable because it can be performed effectively, but for example, if the plasma contains protein binding matter that has proteins and toxic substances attached to it and needs to be removed, dialysis can be performed using a membrane filter with a pore size of 0.1 to 0.8μ. Preferably, it is removed. The plasma components after dialysis flow together with the floating cells into the second filter 4 by the action of the pump 23, where they are separated into floating cells and plasma components. The floating cells are returned to tank 2 through return pipe 21. On the other hand, the separated plasma components pass through the plasma outflow tube 20 by the action of the pumps 26 and 27 and enter the blood cell outflow tube 6, which constitutes a part of the extracorporeal circulation circuit, and enter the blood cell outflow tube 6 of the human body M together with the blood cell components flowing therethrough. be returned.

Specific Effects of the Invention According to this device, floating cells with a detoxifying effect decompose toxic substances through metabolism, making it possible to detoxify substances with high and medium molecules. Can be applied to diseases. In addition, small and medium molecule organic substances are generated due to the metabolism of floating cells, but this is removed by the dialyzer 3, so there is no burden on the human body M, and the floating cells are not adversely affected by these small and medium molecule organic substances. Provides conditions suitable for survival.

Furthermore, even when a sufficient flow rate of blood from the human body M is not ensured, by providing the return pipe 12 and the pump 13, the flow rate of blood flowing into the first filter 1 can be ensured, and as a result, the necessary amount of plasma components can be efficiently obtained. Can be separated.

Furthermore, by specifying the type of floating cells or the dialysis membrane of the dialyzer 3, it is also possible to detoxify poisonous substances (protein binding matter) attached to proteins.

Note that the pumps 15 and 26 provided in the above embodiment
is not necessarily required, and the pressure regulating valves 11 and 24 are not necessarily required depending on the overcapacity and overload principle of the first overloader 1 and the second overloader 4, and the properties of the overflow membrane used.

As described above, the artificial liver device according to the present invention includes:
Because it has a function similar to that of the human liver, it is effective not only for acute hepatitis and drug poisoning, but also for liver diseases that require detoxification of medium- and high-molecular organic substances. Furthermore, by changing the overcharacteristics of the first and second filters, the dialysis characteristics of the dialyzer, and the dialysate composition, it is possible to make the device suitable for various liver diseases. Furthermore, by returning the blood cells, the necessary amount of plasma components can be separated without having to secure a shunt, which widens the scope of application.

[Brief explanation of the drawing]

The drawing is an explanatory diagram of an artificial liver device showing one embodiment of the present invention. 1... First filter, 2... Tank, 3... Dialyzer,
4... Second filter, 5... Blood inflow tube, 6... Blood cell outflow tube, 7... Plasma outflow tube, 12... Blood cell return tube, 19
...Plasma inflow pipe, 20...Plasma outflow pipe, 21...Floating cell return pipe.

Claims (1)

[Scope of Claims] 1. A first filtration device for plasma separation equipped with an extracorporeal circulation circuit formed by a blood inflow pipe and a blood cell outflow pipe and a plasma outflow pipe, a tank containing floating cells for detoxification, and a filtrate. A dialyzer for separation and a second strainer for separating suspended cells each having a plasma inflow tube, a plasma outflow tube, and a suspended cell return tube are provided, and the plasma outflow tube of the first strainer is connected to a tank and a dialyzer. and connect the plasma inflow tube of the second strainer to the plasma inflow tube of the second strainer, connect the plasma outflow tube of the second strainer to the extracorporeal circulation circuit, and connect the floating cell return tube of the second strainer to the tank. An artificial liver device. 2. The artificial liver device according to claim 1, wherein a blood cell return tube for returning blood cells to the blood inflow tube is connected between the blood inflow tube and the blood cell outflow tube of the first organ. 3. The artificial liver device according to claim 1 or 2, wherein the first filter comprises a membrane filter with a pore size of 0.1 to 0.8 μ. 4 The first filter has a molecular weight cut-off of 50,000 to 1,000,000 MW.
The artificial liver device according to claim 1 or 2, comprising an ultrafiltration membrane. 5. The artificial liver device according to claim 1 or 2, wherein the second filter comprises a membrane filter with a pore size of 0.1 to 0.8 μ. 6 The second filter has a molecular weight cutoff of 50,000 to 1,000,000 MW.
The artificial liver device according to claim 1 or 2, comprising an ultrafiltration membrane. 7. The artificial liver device according to claim 1 or 2, wherein the dialyzer is equipped with an ultrafiltration membrane having a molecular weight cut-off of 5,000 to 50,000 MW. 8. The artificial liver device according to claim 1 or 2, wherein the dialyzer is equipped with a membrane filter having a pore size of 0.1 to 0.8 μ.