Bioartificial liver system

Abstract

The utility model relates to the technical field of bioartificial livers, and provides a bioartificial liver system which comprises a plasma separator, an oxygenator and a hollow fiber bioreactor which are sequentially communicated through a plasma purification pipe, the plasma outlet end of the plasma separator is communicated with the plasma purification pipe; the outlet end of the bioreactor is also respectively communicated with a plasma return pipe and a plasma circulating pipe, the plasma return pipe is communicated with the blood return pipe, the plasma circulating pipe is communicated with the plasma inlet end of the plasma separator, a circulating pump is arranged on the plasma circulating pipe, and an ultrafiltration pump is arranged on the plasma purifying pipe. Treated plasma flows back to the plasma separator again through the circulating pump, and the ultrafiltration capacity of the ultrafiltration pump is increased under the condition that the flow of blood led out of the blood pump is not changed, so that the circulating flow of the plasma is increased, and the oxygen carrying capacity of the plasma is correspondingly improved. The plasma separation ratio of the blood newly led out by the blood pump is increased, and the treatment efficiency of the bioartificial liver system is improved.

Description

Technical Field

[0001] The utility model belongs to the technical field of bioartificial liver, and in particular relates to a bioartificial liver system. Background Art

[0002] The bioartificial liver support system mainly uses a cell group with liver metabolic function to purify the blood of patients with liver failure, realize the function of extracorporeal liver support, and buy precious time for liver regeneration or waiting for liver transplantation, which has important clinical application value. The existing bioartificial liver system structures are similar. The bioartificial liver reactor is the core part of the whole system, providing sufficient oxygen, appropriate nutrients and a suitable pH environment for the cell group, so that the cells can maximize their biological activity and provide a guarantee for achieving efficient liver function expression levels.

[0003] At present, the bioartificial liver support system used in clinical trials or treatment mainly includes three parts: plasma separator (or ultrafilter), oxygenator and bioreactor. After the patient's blood (or whole blood) is extracted from the body, the plasma and blood cells are first separated by the plasma separator; the separated plasma is loaded with enough oxygen by the oxygenator and then enters the bioreactor; in the bioreactor, the cell group uses the plasma as the basic nutrition for material metabolism and exchange; the plasma after removing the biotoxins is then mixed with the blood cells separated by the plasma separator and returned to the patient's body to achieve the function of in vitro artificial liver support.

[0004] The hollow fiber type is the most commonly used structural form of bioreactor, and the bioreactors used in existing bioartificial liver support systems are mostly hollow fiber bioreactors. Artificially cultured hepatocytes are inoculated in the hollow fiber outer cavity of the bioreactor, and the patient's plasma flows through the hollow fiber inner cavity of the bioreactor. The two exchange substances through the hollow fiber semipermeable membrane to purify the patient's plasma. However, compared with other bioreactors, the hollow fiber bioreactor has immune barrier properties due to the presence of the hollow fiber semipermeable membrane, which will affect the semipermeable membrane material exchange efficiency, plasma oxygen carrying capacity, and the flow rate of perfused plasma to a certain extent, ultimately affecting the treatment efficiency of the bioartificial liver system. Utility Model Content

[0005] The utility model aims to overcome the problem of low material exchange efficiency of the hollow fiber bioreactor of the existing bioartificial liver system, and provides a bioartificial liver system, comprising a plasma separator, an oxygenator and a hollow fiber bioreactor which are connected in sequence through a plasma purification tube; the plasma inlet end of the plasma separator is connected with a blood input tube, the blood input tube is provided with a blood pump, the blood outlet end of the plasma separator is connected with a blood return tube, and the plasma outlet end of the plasma separator is connected with the plasma purification tube; the outlet end of the bioreactor is also connected with a plasma return tube and a plasma circulation tube respectively, the plasma return tube is connected with the blood return tube, the plasma circulation tube is connected with the plasma inlet end of the plasma separator, the plasma circulation tube is provided with a circulation pump, the plasma purification tube is provided with an ultrafiltration pump, and the ultrafiltration pump is located between the plasma separator and the oxygenator.

[0006] Furthermore, the outlet end of the bioreactor is also connected to a cell filter, and the cell filter has a first plasma outlet end, a second plasma outlet end and a third plasma outlet end, the first plasma outlet end is connected to the plasma circulation tube; the second plasma outlet end is connected to a plasma shunt tube, the plasma shunt tube is connected to the plasma purification tube between the ultrafiltration pump and the plasma separator, and a flow regulating valve is provided on the plasma shunt tube; the plasma reflux tube is connected to the third plasma outlet end.

[0007] Since the hollow fiber lumen of the bioreactor circulates plasma, and the outer lumen of the hollow fiber is the cultured cells injected for material exchange with plasma, there are cells and cell fragments that may fall off in the outer lumen of the bioreactor, and these cell fragments may penetrate the hollow fiber semipermeable membrane into the hollow fiber lumen, and flow back to the human body with the plasma, causing harm to the patient. By connecting the cell filter at the outlet end of the bioreactor, the cell filter is used to filter the cell fragments in the bioreactor to prevent the fragments from entering the human body. In addition, the cell filter adopts a hollow fiber structure, which increases the filtration area and effectively reduces the pressure drop of the cell filter under high flow conditions. Through the action of the plasma shunt tube, the cell filter is flushed to avoid the cell filter being blocked by cell fragments, and the service life and filtration effect of the cell filter are extended. Through the action of the flow control valve, the plasma flow of the plasma shunt tube is adjusted, and then the plasma flow of the plasma reflux tube is adjusted, and the pipeline pressure of the plasma purification tube can be balanced to avoid the problem of membrane rupture of the hollow fiber semipermeable membrane of the bioreactor.

[0008] Furthermore, the cell filter also has a flushing port and a waste liquid port, the flushing port is connected to a physiological saline flushing tube, the waste liquid port is connected to a waste liquid tube, and the waste liquid tube is connected to a waste liquid bag.

[0009] By providing a physiological saline flushing tube connected to the flushing port and a waste liquid tube connected to the waste liquid port, the cell filter is flushed with physiological saline, and the cell fragments in the cell filter are flushed into the waste liquid bag to ensure the filtering effect of the cell filter.

[0010] Furthermore, the ultrafiltration volume of the ultrafiltration pump is equal to the sum of the circulation flow of the circulation pump, the flow of the plasma shunt tube and the flow of the plasma return tube.

[0011] Furthermore, the flow rate of the plasma shunt tube is 5-10 ml / min.

[0012] Furthermore, the blood input tube is connected to an arterial pot, and the plasma circulation tube is connected to the arterial pot; the blood return tube is connected to a venous pot, and the plasma return tube is connected to the venous pot.

[0013] Furthermore, the oxygenator is connected to a constant temperature water tank.

[0014] The beneficial effects of the utility model are as follows: by setting a plasma circulation tube connected between the bioreactor and the plasma separator, and setting a circulation pump on the plasma circulation tube, and setting an ultrafiltration pump on the plasma purification tube, the treated plasma is refluxed to the plasma separator again by the circulation pump, and the ultrafiltration volume of the ultrafiltration pump is increased while the blood flow rate drawn out by the blood pump remains unchanged, thereby increasing the plasma circulation flow rate, and correspondingly increasing the oxygen carrying capacity of the plasma. At the same time, the plasma separation ratio of the blood newly drawn out by the blood pump is also increased, thereby improving the treatment efficiency of the bioartificial liver system. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 It is a schematic structural diagram of the bioartificial liver system of the utility model.

[0016] In the figure, 1-plasma purification tube; 2-plasma separator; 3-oxygenator; 4-bioreactor; 5-blood input tube; 6-blood pump; 7-blood return tube; 8-plasma return tube; 9-plasma circulation tube; 10-circulation pump; 11-plasma shunt tube; 12-cell filter; 13-flow regulating valve; 14-ultrafiltration pump; 15-arterial pot; 16-venous pot; 17-constant temperature water tank. DETAILED DESCRIPTION

[0017] The present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0018] like Figure 1As shown, the bioartificial liver system proposed by the utility model comprises a plasma separator 2, an oxygenator 3 and a hollow fiber bioreactor 4 which are connected in sequence through a plasma purification tube 1; the plasma inlet end of the plasma separator 2 is connected with a blood input tube 5, on which a blood pump 6 is arranged, the blood outlet end of the plasma separator 2 is connected with a blood return tube 7, and the plasma outlet end of the plasma separator 2 is connected with the plasma purification tube 1; the outlet end of the bioreactor 4 is also connected with a plasma return tube 8 and a plasma circulation tube 9 respectively, the plasma return tube 8 is connected with the blood return tube 7, the plasma circulation tube 9 is connected with the plasma inlet end of the plasma separator 2, a circulation pump 10 is arranged on the plasma circulation tube 9, and an ultrafiltration pump 14 is arranged on the plasma purification tube 1, and the ultrafiltration pump 14 is located between the plasma separator 2 and the oxygenator 3.

[0019] A plasma circulation tube 9 is provided between the bioreactor 4 and the plasma separator 2, and a circulation pump 10 is provided on the plasma circulation tube 9, and an ultrafiltration pump 14 is provided on the plasma purification tube 1. The processed plasma is refluxed to the plasma separator 2 again by the circulation pump 10, and the ultrafiltration volume of the ultrafiltration pump 14 is increased while the blood flow rate drawn by the blood pump 6 remains unchanged, thereby increasing the plasma circulation flow rate and correspondingly increasing the oxygen carrying capacity of the plasma. At the same time, the plasma separation ratio of the newly drawn blood by the blood pump 6 is also increased, thereby improving the treatment efficiency of the bioartificial liver system.

[0020] The outlet of the bioreactor 4 is also connected to a cell filter 12, which also adopts a hollow fiber filter. The cell filter 12 has a first plasma outlet, a second plasma outlet and a third plasma outlet, the first plasma outlet is connected to the plasma circulation tube 9; the second plasma outlet is connected to a plasma shunt tube 11, the plasma shunt tube 11 is connected to the plasma purification tube 1 between the ultrafiltration pump 14 and the plasma separator 2, and a flow regulating valve 13 is provided on the plasma shunt tube 11; the plasma reflux tube 8 is connected to the third plasma outlet. Since the hollow fiber lumen of the bioreactor 4 circulates plasma, and the hollow fiber outer cavity is the cultured cells injected for material exchange with plasma, there are cells and cell fragments that may fall off in the outer cavity of the bioreactor 4, and these cell fragments may penetrate the hollow fiber semipermeable membrane into the hollow fiber lumen, and flow back to the human body with the plasma, causing harm to the patient. By connecting the cell filter 12 at the outlet of the bioreactor 4, the cell fragments in the bioreactor 4 are filtered by the cell filter 12 to prevent the fragments from entering the human body. In addition, the cell filter 12 adopts a hollow fiber structure, which increases the filtration area and effectively reduces the pressure drop of the cell filter 12 under high flow conditions. Through the action of the plasma shunt tube 11, the inner cavity of the cell filter 12 is flushed, dead-end filtration is avoided, the cell filter 12 is prevented from being blocked by cell debris, and the service life and filtration effect of the cell filter 12 are extended. By adjusting the opening of the flow control valve 13, the plasma flow of the plasma shunt tube 11 is adjusted (bypass shunt principle), and then the plasma flow of the plasma reflux tube 8 is adjusted, and the pipeline pressure of the plasma purification tube 1 can be balanced to avoid the problem of broken membrane of the hollow fiber semipermeable membrane of the bioreactor 4.

[0021] In order to remove the cell debris that may exist in the system, the cell filter 12 also has a flushing port and a waste liquid port, the flushing port is connected to a physiological saline flushing tube, the waste liquid port is connected to a waste liquid tube, and the waste liquid tube is connected to a waste liquid bag. By providing a physiological saline flushing tube connected to the flushing port and a waste liquid tube connected to the waste liquid port, the cell filter 12 is flushed with physiological saline, and the cell debris in the cell filter 12 is flushed into the waste liquid bag, thereby ensuring the filtering effect of the cell filter 12.

[0022] The ultrafiltration volume of the ultrafiltration pump 14 is equal to the sum of the circulation flow of the circulation pump 10, the flow of the plasma shunt tube 11 and the flow of the plasma return tube 8. The flow of the plasma shunt tube 11 is 5-10 ml / min.

[0023] The blood input tube is connected to an arterial pot 15 , and the plasma circulation tube 9 is connected to the arterial pot 15 ; the blood return tube 7 is connected to a venous pot 16 , and the plasma return tube 8 is connected to the venous pot 16 .

[0024] The oxygenator 3 is connected to a constant temperature water tank 17 .

[0025] The plasma separator 2 or ultrafilter in this embodiment separates 30% of the plasma from the blood or whole blood and enters the ultrafiltration pump 14 .

[0026] In this example, the circulating pump 10 is used to shunt and infuse the processed plasma into the blood circulation after the blood pump 6 and flow in parallel with the blood; when the blood flow rate drawn out by the blood pump 6 remains unchanged, the ultrafiltration volume of the ultrafiltration pump 14 increases, wherein the upper limit of the ultrafiltration volume = the blood flow rate of the blood pump 6 * (1-Hct) + the circulation flow rate of the circulating pump 10, wherein the circulation flow rate of the circulating pump 10 is the plasma flow rate of the plasma circulation tube 9, and the ultrafiltration volume increases the plasma circulation flow rate relative to the bioartificial liver system without a shunt return structure. At the same time, the plasma separation ratio of the newly drawn blood is increased, and the treatment efficiency of the bioartificial liver is improved. Among them, Hct is the hematocrit (Red blood cell specific volume), which refers to the percentage of red blood cells in a certain volume of whole blood. It is also called hematocrit (specific volume / hematocrit), and 1-Hct is the percentage of plasma in whole blood. The blood pump 6 generally uses a peristaltic pump. According to the characteristics of the peristaltic pump, the shunt return of plasma will not affect the patient.

[0027] The above are only preferred implementations of the utility model. The protection scope of the utility model is not limited to the above embodiments. All technical solutions under the idea of ​​the utility model belong to the protection scope of the utility model. It should be pointed out that for ordinary technicians in this technical field, some improvements and modifications without departing from the principle of the utility model should also be regarded as the protection scope of the utility model.

Claims

1. A bioartificial liver system, characterized in that: The invention comprises a plasma separator, an oxygenator and a hollow fiber bioreactor which are connected in sequence through a plasma purification tube; the plasma inlet end of the plasma separator is connected with a blood input tube, the blood input tube is provided with a blood pump, the blood outlet end of the plasma separator is connected with a blood return tube, and the plasma outlet end of the plasma separator is connected with the plasma purification tube; the outlet end of the bioreactor is also connected with a plasma return tube and a plasma circulation tube respectively, the plasma return tube is connected with the blood return tube, the plasma circulation tube is connected with the plasma inlet end of the plasma separator, the plasma circulation tube is provided with a circulation pump, the plasma purification tube is provided with an ultrafiltration pump, and the ultrafiltration pump is located between the plasma separator and the oxygenator.

2. A bioartificial liver system according to claim 1, characterized in that: The outlet end of the bioreactor is also connected to a cell filter, which has a first plasma outlet end, a second plasma outlet end and a third plasma outlet end, wherein the first plasma outlet end is connected to the plasma circulation tube; the second plasma outlet end is connected to a plasma shunt tube, which is connected to the plasma purification tube between the ultrafiltration pump and the plasma separator, and a flow regulating valve is provided on the plasma shunt tube; the plasma reflux tube is connected to the third plasma outlet end.

3. A bioartificial liver system according to claim 2, characterized in that: The cell filter also has a flushing port and a waste liquid port. The flushing port is connected to a physiological saline flushing tube, the waste liquid port is connected to a waste liquid tube, and the waste liquid tube is connected to a waste liquid bag.

4. A bioartificial liver system according to claim 2, characterized in that: The ultrafiltration volume of the ultrafiltration pump is equal to the sum of the circulation flow of the circulation pump, the flow of the plasma shunt tube and the flow of the plasma return tube.

5. A bioartificial liver system according to claim 2, characterized in that: The flow rate of the plasma shunt tube is 5-10 ml / min.

6. A bioartificial liver system according to claim 2, characterized in that: The blood input tube is connected to an arterial pot, and the plasma circulation tube is connected to the arterial pot; the blood return tube is connected to a venous pot, and the plasma return tube is connected to the venous pot.

7. A bioartificial liver system according to claim 2, characterized in that: The oxygenator is connected with a constant temperature water tank.

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